bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposed standard guideline for managing information systems (ISs) in libraries in Africa
Authors: Ocloo Patience Emefa Dzandza , King  Lizette
Published: August 2023

Purpose

Libraries in Africa are adopting technology at a fast pace. However, literature has provided enough evidence of the many challenges libraries on the continent are facing in the use of the adopted information technology of which information systems (ISs) are major components. Literature also does not provide evidence of IS standard, policy or guideline at both national and international levels as a benchmark for the use of these systems. Therefore, this paper aims to propose an IS standard guideline as a guide for libraries in Africa to develop IS policies, standards or guidelines to help in effective use of IS in libraries.

Design/methodology/approach

The researchers based their proposed standard guideline on the findings from their earlier research works and evidence from other existing literature as has been reviewed in this paper.

Findings

Findings from the literature revealed that libraries in Africa face a number of challenges in the use of IS which can be categorised into four main areas, namely, financial challenges, technological and infrastructural challenges, human resource challenges and organizational challenges.

Originality/value

This paper proposed an IS standard guideline to serve as a guide for libraries in Africa to develop IS policies, standards or guidelines to help in effective use of IS in libraries.
The mediating role of planned behaviour in the religiosity and nascent entrepreneurship nexus
Authors: Onjewu Adah-Kole Emmanuel , Anosike Paschal , Godwin Eun Sun
Published: August 2023

Purpose

Increasingly, there is scholarly recognition that individuals' faith constitutes a background factor much like other antecedents conditioning entrepreneurial inclination. Yet, there is room to expand knowledge on how faith interrelates with psychological and social determinants of entrepreneurship, especially in under-researched contexts such as Nigeria.

Design/methodology/approach

This inquiry conceptualises associations between religiosity and (1) entrepreneurial self-efficacy, (2) entrepreneurial attitudes (3) and subjective norms as predictors of nascent entrepreneurship. For analysis, 1,259 observations of Nigerian students are assessed by structural equation modelling.

Findings

The path analysis showed that the religiosity–nascent entrepreneurship nexus is altogether mediated by entrepreneurial self-efficacy, entrepreneurial attitudes and subjective norms. Entrepreneurial self-efficacy is found to have the greatest impact on nascent entrepreneurship, followed by subjective norms and then entrepreneurial attitudes.

Originality/value

Theoretically, this study is one of the first to test all three dimensions of the theory of planned behaviour in the religiosity–nascent entrepreneurship nexus. It draws fresh attention to faith motivation and praxis, role-taking and attribution theory as explainers of the inherent correlations. Practically, the findings summon stakeholders to consider religious activity in the delivery of entrepreneurship programmes.
Multiobjective network security dynamic assessment method based on Bayesian network attack graph
Authors: Xie Jialiang , Zhang Shanli , Wang Honghui , Chen Mingzhi
Published: August 2023

Purpose

With the rapid development of Internet technology, cybersecurity threats such as security loopholes, data leaks, network fraud, and ransomware have become increasingly prominent, and organized and purposeful cyberattacks have increased, posing more challenges to cybersecurity protection. Therefore, reliable network risk assessment methods and effective network security protection schemes are urgently needed.

Design/methodology/approach

Based on the dynamic behavior patterns of attackers and defenders, a Bayesian network attack graph is constructed, and a multitarget risk dynamic assessment model is proposed based on network availability, network utilization impact and vulnerability attack possibility. Then, the self-organizing multiobjective evolutionary algorithm based on grey wolf optimization is proposed. And the authors use this algorithm to solve the multiobjective risk assessment model, and a variety of different attack strategies are obtained.

Findings

The experimental results demonstrate that the method yields 29 distinct attack strategies, and then attacker's preferences can be obtained according to these attack strategies. Furthermore, the method efficiently addresses the security assessment problem involving multiple decision variables, thereby providing constructive guidance for the construction of security network, security reinforcement and active defense.

Originality/value

A method for network risk assessment methods is given. And this study proposed a multiobjective risk dynamic assessment model based on network availability, network utilization impact and the possibility of vulnerability attacks. The example demonstrates the effectiveness of the method in addressing network security risks.
Digital quality’s role in US online higher education
Authors: Chakraborty Subhajit
Published: August 2023

Purpose

The emergence of internet-based business models has given rise to online higher education institutions (OHEIs) that offer their undergraduate and graduate degree programs exclusively online with minimal physical presence. Research on OHEIs discusses the need for external legitimacy and resource acquisition, often ignoring the role of quality among these institutions. Hence, this study aims to investigate the role of digital quality of education on OHEIs’ survival.

Design/methodology/approach

Guided by four different inter-disciplinary theories, a conceptual framework is offered based on a comprehensive literature review.

Findings

The role of digital quality of education in improving the survival and strategic competitiveness of institutions in the US online higher education industry is highlighted.

Research limitations/implications

This conceptual paper highlights how the digital quality of education becomes increasingly important over the life cycle of OHEIs.

Practical implications

The proposed framework suggests that despite the competition provided by traditional and well-entrenched players, OHEIs can improve their survival and competitiveness if they invest strategically in the digital quality of education.

Originality/value

This study offers an overarching conceptual framework developed through an integration of multiple theoretical perspectives and grounded in the US online higher education industry.
The crowding‐out effects of innovation information disclosure on peers' innovation: Evidence from innovation‐driven M&As in China
Authors: Cao Zhangfan , Hua Chen , Tong Yan , Wang Xi
Published: August 2023

This study investigates the impact of rivals' announcements of innovation‐driven mergers and acquisitions (M&As) on focal firms' ex‐post corporate innovation performance. Exploiting a hand‐collected dataset of Chinese listed firms from 2011 to 2018, we find that focal firms file fewer patents after rivals' announcements of innovation‐driven M&As. Further analyses show that focal firms become more conservative and hold more cash when rivals intend to obtain innovation resources through M&As. We find that such crowding‐out effects are more pronounced for focal firms that are more financially constrained, those facing higher competition, those whose rivals are industry leaders, and those operating in traditional industries.
Defects of the spliceosomal gene SNRPB affect osteo‐ and chondro‐differentiation
Authors: Knill Chris , Henderson Ellie J. , Johnson Craig , Wah Vun Yee , Cheng Kevin , Forster Annie J. , Itasaki Nobue
Published: August 2023

Although gene splicing occurs throughout the body, the phenotype of spliceosomal defects is largely limited to specific tissues. Cerebro‐costo‐mandibular syndrome (CCMS) is one such spliceosomal disease, which presents as congenital skeletal dysmorphism and is caused by mutations of SNRPB gene encoding Small Nuclear Ribonucleoprotein Polypeptides B/B′ (SmB/B′). This study employed in vitro cell cultures to monitor osteo‐ and chondro‐differentiation and examined the role of SmB/B′ in the differentiation process. We found that low levels of SmB/B′ by knockdown or mutations of SNRPB led to suppressed osteodifferentiation in Saos‐2 osteoprogenitor‐like cells, which was accompanied by affected splicing of Dlx5. On the other hand, low SmB/B′ led to promoted chondrogenesis in HEPM mesenchymal stem cells. Consistent with other reports, osteogenesis was promoted by the Wnt/β‐catenin pathway activator and suppressed by Wnt and BMP blockers, whereas chondrogenesis was promoted by Wnt inhibitors. Suppressed osteogenic markers by SNRPB knockdown were partly rescued by Wnt/β‐catenin pathway activation. Reporter analysis revealed that suppression of SNRPB results in attenuated Wnt pathway and/or enhanced BMP pathway activities. SNRPB knockdown altered splicing of TCF7L2 which impacts Wnt/β‐catenin pathway activities. This work helps unravel the mechanism underlying CCMS whereby reduced expression of spliceosomal proteins causes skeletal phenotypes.
Effect of antifungal compounds secreted by Lactiplantibacillus plantarum 124 against Aspergillus flavus and Penicillium sp. and its application in Kaeng‐Tai‐Pla‐Haeng to extend the shelf life
Authors: Kanjan Pochanart , Sakpetch Phat
Published: August 2023

Aspergillus flavus and Penicillium spp. are the most common spoilage fungi in the ready‐to‐eat, intermediate‐moisture Thai curry of Kaeng‐Tai‐Pla‐Haeng, which causes serious economic loss and public health concerns. The use of lactic acid bacteria (LAB) with antifungal activity has been a growing interest in food bio‐preservation. In this study, the antifungal efficacy of Lactiplantibacillus plantarum 124 (L. plantarum 124) against the spoilage fungi Aspergillus flavus and Penicillium sp. was evaluated. The cell‐free supernatants (CFSs) of L. plantarum 124 showed strong inhibition against A. flavus and Penicillium sp., with MIC ranging from 11.25 to 22.5 mg mL−1. The significant loss of antifungal activity was observed by pH neutralisation, whereas either heat or proteinase K treatment showed no influence. The major compounds present in CFSs were lactic acid (49.57%) and acetic acid (25.85%). Others, such as 2,3‐dimethyl‐5‐ethylpyrazine (6.07%), 2,5‐dimethyl‐3‐propylpyrazine (2.10%), Cyclo(D‐Leu‐L‐Pro) (2.30%), Ethyl 5‐oxopyrrolidine‐3‐carboxylate (1.84%), and palmitic acid (1.80%), were detected in low relative amounts. As observed by electron microscopy, the CFSs secreted by L. plantarum 124 caused severe damage to cell membranes and organelles of A. flavus and Penicillium sp. In addition, L. plantarum 124 supernatant demonstrated no cytotoxicity on Vero cells, and it could extend the food product's shelf life from 7 days to 21 days without any commercial preservatives. These results demonstrate that antifungal metabolites secreted by L. plantarum 124 are candidates for the development of bio‐preservative agents.
SiC modified self‐healing ytterbium disilicate materials for potential environmental barrier coating application
Authors: Du Jinping , Wang Yanfei , Wan Fan , Li Junsheng , Li Duan , Liu Rongjun
Published: August 2023

Environmental barrier coatings (EBCs) are crucial to the reliability and durability of SiCf/SiC composite components seeking applications in hot sections of next‐generation advanced aero‐engines. The cracks initiated and developed in EBCs owing to various reasons during service greatly undermine their lifespans. To address this problem, in this work, silicon carbide (SiC) in the forms of particles and whiskers with various amounts have been introduced to ytterbium disilicate (Yb2Si2O7), the mainstream EBC topcoat materials, so as to gain some self‐healing potential. The results reveal that, the SiC inclusions in Yb2Si2O7 in the presence of ytterbium monosilicate (Yb2SiO5) can trigger the following reactions. Specifically, SiC self‐healing agents are oxidized to form viscous SiO2, which actively reacts with Yb2SiO5 upon encountering it, forming Yb2Si2O7. This has brought twofold beneficial effects including ① silicon supplementation of disilicate topcoat, whose silicon element tends to be “dragged out” by water vapor, leading to the deterioration of thermal mismatch; as well as ② crack self‐healing resulting from the volume expansion induced by the above reactions. Then the two aspects of self‐healing agents, namely the “promptness” and “sustainability,” have been discussed in detail. The former is unveiled to be more pertinent to the repairing of large cracks, whilst the latter is more relevant to the self‐healing of tiny cracks at initiation or early stage of propagation. The current work sheds some lights on the design and development of more durable and robust EBCs with self‐healing capability.
European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for appendiceal neuroendocrine tumours (aNET)
Authors: Kaltsas Gregory , Walter Thomas , Knigge Ulrich , Toumpanakis Christos , Santos Ana P. , Begum Nehara , Pape Ulrich F. , Volante Marco , Frilling Andrea , Couvelard Anne
Published: August 2023

The aim of the present guidance paper is to update the previous ENETS guidelines on well differentiated appendiceal neuroendocrine tumours (NET), providing practical guidance for the diagnosis and management of appendiceal NET (aNET); poorly differentiated neoplasms are dealt with in a separate guidance paper. This paper is structured on a question‐answer format in order to also address controversial issues and areas where uncertainty regarding the management and follow‐up of aNET exists. All recommendations are offered on the basis of the best available evidence, along with the authors' experiences in managing these neoplasms. Each recommendation for treatment will provide a level of evidence and grade of recommendation as per the GRADE system (adapted in Infectious Disease Society of United States Public Health Service grading system).
Expanding the genetic and clinical spectrum of SORD‐related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement
Authors: Li Lu , Xie Yongzhi , Zeng Sen , Li Xiaobo , Lin Zhiqiang , Huang Shunxiang , Zhao Huadong , Cao Wanqian , Liu Lei , Liu Jun , Rong Pengfei , Zhang Ruxu
Published: August 2023

Background and Aims

Biallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot–Marie–Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD‐related PN (SORD‐PN).

Methods

A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole‐exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD‐PN were collected and analyzed.

Results

Eleven (10.28%) of 107 patients were identified as SORD‐PN, including four with CMT2 and seven with dHMN. The SORD variant c.210 T > G;p.His70Gln in F‐d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD‐PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in one patient, and muscle edema in five patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88‐fold higher in SORD‐PN patients (9.69 ± 1.07 mg/L) than in healthy heterozygous subjects (0.11 ± 0.01 mg/L) and 138‐fold higher than in healthy controls (0.07 ± 0.02 mg/L).

Interpretation

The novel SORD variant c.210 T > G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD‐PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow‐up cohort study.
Endogenous choice of price or quantity contract with upstream advertising
Authors: Hu Qing , Li Dan , Mizuno Tomomichi
Published: August 2023

We investigate a supply chain comprising a manufacturer engaged in advertising and two retailers who compete with differentiated products. We examine the endogenous choice between competing on quantity or price for the retailers. Our analysis reveals that, depending on the level of product substitutability, the range of possible outcomes is varied and includes Cournot, Bertrand, and Cournot‐Bertrand under informative advertising. This result contradicts the established understanding that firms tend to engage in Cournot competition as their dominant strategy. Furthermore, we find that under persuasive advertising, Cournot or Bertrand outcomes may be optimal, but Cournot‐Bertrand never arises as an equilibrium.
Iron‐dependent regulation of leaf senescence: a key role for the H2B histone variant HTB4
Authors: Dubos Christian
Published: August 2023

This article is a Commentary on Yang et al. (2023), 240: 694–709.
Music as an Important Means of Foreign Policy
Authors: Zakharova Oksana
Published: August 2023

The article discusses the influence of music on the process of political socialization, analyzes the mechanisms of interaction between the musical and political spheres of society at different historical stages. The relevance of this article lies in the fact that at this historical stage the questions of studying the experience of establishing cooperation between states using the methods of cultural negotiations are most relevant in connection with the events taking place in world politics. The purpose of this study is to analyze musical art as an important element of international political relations, as well as to substantiate the effectiveness of the use of musical art in political negotiations. The article describes the cultural relations of allies during political negotiations at different historical stages using archival scientific materials. The principles of construction are considered, as well as the artistic features of concert programs at the Royal Albert Hall of Arts and Sciences. The methodological basis of the study is the work of cultural communication researchers. The main methods of cognition are theoretical analysis of scientific-journalistic literature, narrative analysis and historical method, comparative and typological method, generalization of theoretical and practical experience of influence of music on political processes in the world. The practical significance of the research on "Music as an important instrument of foreign policy" is that the data obtained in the scientific research can be used by specialists and teachers of higher educational institutions, as well as in the preparation of a methodological educational program in the field of "History" and "Political Science". The results of the ongoing research may be of scientific interest to students, specialists and teachers of history, political science and cultural studies in higher educational institutions and advanced training courses.
The Mediating Role of Reporting Tendencies of Environmental News in the Relationship Between Information Sources and Citizen’s Environmental Awareness via Southern Weekend
Authors: Ye He , Mahamed Mastura , Shari Sharil Nizam
Published: August 2023

This article takes China's Southern Weekend Green newspaper as an example, selects 235 articles in Southern Weekend Green from 2018 to 2020. Conduct relevant research on environmental news reported in newspapers and magazines. Most of the previous studies focus on the classification of content, and there is no relevant research on the information source and the audience's environmental awareness. Therefore, the purpose of this study was to investigate the mediating role of reporting bias between information sources and the audience's environmental awareness. The research method adopts the quantitative research method, adopts the random sampling method to conduct a questionnaire survey on the respondents, and distributes a total of 392 questionnaires. Correlation analysis was carried out on the influence of different information sources on reporting tendency and dissemination effect, and SPSS was used for correlation test.
“Lightbulb Moments”: The (Re)Conceptualization of Coach Development in Aotearoa, New Zealand
Authors: Fyall Glenn , Cowan Jackie , Bennett Blake , Hapeta Jeremy , Walters Simon
Published: August 2023

Systems thinking is used extensively in organizational research as a framework to understand individual and organizational learning, adaptation, and change. However, systems thinking has had limited application in sport coaching research. In this study, we draw on a systems thinking framework to investigate Sport New Zealand’s recently conceptualized and implemented coach development program known as Coach Developer Aotearoa. To do so, we employ an interpretive phenomenological analysis to analyze the semistructured interview data gathered from the original six-member, Coach Developer Aotearoa design team. Our initial deductive analysis revealed that the participants acquired a more sophisticated understanding of coach development as they interrogated their own personal, collective, and societal assumptions. Specifically, concepts of learner-centeredness, active learning, and reflection, and a greater emphasis on cultural sensitivities replaced traditional behaviorist perspectives of coaching development. In our discussion, informed by our further abductive analysis, we describe the challenges faced by Sport New Zealand when looking to promote their new vision across the New Zealand sport landscape. In doing so, we offer emergent understanding and raise awareness about the possibilities that an alternative definition of critical reflection could offer when seeking systemic change on such a large scale.
Reduced nitrite accumulation at the primary nitrite maximum in the cyclonic eddies in the western North Pacific subtropical gyre
Authors: Liu Li , Chen Mingming , Wan Xianhui S. , Du Chuanjun , Liu Zhiyu , Hu Zhendong , Jiang Zong-Pei , Zhou Kuanbo , Lin Hongyang , Shen Hui , Zhao Duo , Yuan Lanying , Hou Lei , Yang Jin-Yu T. , Li Xiaolin , Kao Shuh-Ji , Zakem Emily J. , Qin Wei , Dai Minhan , Zhang Yao
Published: August 2023

Nitrite, an intermediate product of the oxidation of ammonia to nitrate (nitrification), accumulates in upper oceans, forming the primary nitrite maximum (PNM). Nitrite concentrations in the PNM are relatively low in the western North Pacific subtropical gyre (wNPSG), where eddies are frequent and intense. To explain these low nitrite concentrations, we investigated nitrification in cyclonic eddies in the wNPSG. We detected relatively low half-saturation constants (i.e., high substrate affinities) for ammonia and nitrite oxidation at 150 to 200 meter water depth. Eddy-induced displacement of high-affinity nitrifiers and increased substrate supply enhanced ammonia and nitrite oxidation, depleting ambient substrate concentrations in the euphotic zone. Nitrite oxidation is more strongly enhanced by the cyclonic eddies than ammonia oxidation, reducing concentrations and accelerating the turnover of nitrite in the PNM. These findings demonstrate a spatial decoupling of the two steps of nitrification in response to mesoscale processes and provide insights into physical-ecological controls on the PNM.
Quantifying longline bycatch mortality for pelagic sharks in western Pacific shark sanctuaries
Authors: Shea Brendan D. , Gallagher Austin J. , Bomgardner Lindsay K. , Ferretti Francesco
Published: August 2023

Marine protected areas are increasingly touted for their role in conserving large marine predators such as sharks, but their efficacy is debated. Seventeen “shark sanctuaries” have been established globally, but longline fishing continues within many such jurisdictions, leading to unknown levels of bycatch mortality levels. Using public data from Global Fishing Watch and Regional Fisheries Management Organizations, we quantified longline fishing within eight shark sanctuaries and estimated pelagic shark catch and mortality for seven pelagic shark species. Sanctuary mortality ranged from 600 individuals (Samoa) to 36,256 individuals (Federated States of Micronesia), equivalent to ~5% of hypothesized sustainable levels for blue sharks to ~40% for silky sharks, with high mortality levels in the Federated States of Micronesia, Palau, and the Marshall Islands. Unsustainable mortality rates were exceeded for silky sharks in two sanctuaries, highlighting a need for additional stock assessments and implementation of bycatch reduction measures. Big data integration workflows represent a transformative tool in fisheries management, particularly for data-poor species.
Discovery of enhanced lattice dynamics in a single-layered hybrid perovskite
Authors: Zhang Zhuquan , Zhang Jiahao , Liu Zi-Jie , Dahod Nabeel S. , Paritmongkol Watcharaphol , Brown Niamh , Stollmann Alexia , Lee Woo Seok , Chien Yu-Che , Dai Zhenbang , Nelson Keith A. , Tisdale William A. , Rappe Andrew M. , Baldini Edoardo
Published: August 2023

Layered hybrid perovskites exhibit emergent physical properties and exceptional functional performances, but the coexistence of lattice order and structural disorder severely hinders our understanding of these materials. One unsolved problem regards how the lattice dynamics are affected by the dimensional engineering of the inorganic frameworks and their interaction with the molecular moieties. Here, we address this question by using a combination of spontaneous Raman scattering, terahertz spectroscopy, and molecular dynamics simulations. This approach reveals the structural dynamics in and out of equilibrium and provides unexpected observables that differentiate single- and double-layered perovskites. While no distinct vibrational coherence is observed in double-layered perovskites, an off-resonant terahertz pulse can drive a long-lived coherent phonon mode in the single-layered system. This difference highlights the dramatic change in the lattice environment as the dimension is reduced, and the findings pave the way for ultrafast structural engineering and high-speed optical modulators based on layered perovskites.
Cross-species analysis identifies mitochondrial dysregulation as a functional consequence of the schizophrenia-associated 3q29 deletion
Authors: Purcell Ryan H. , Sefik Esra , Werner Erica , King Alexia T. , Mosley Trenell J. , Merritt-Garza Megan E. , Chopra Pankaj , McEachin Zachary T. , Karne Sridhar , Raj Nisha , Vaglio Brandon J. , Sullivan Dylan , Firestein Bonnie L. , Tilahun Kedamawit , Robinette Maxine I. , Warren Stephen T. , Wen Zhexing , Faundez Victor , Sloan Steven A. , Bassell Gary J. , Mulle Jennifer G.
Published: August 2023

The 1.6-megabase deletion at chromosome 3q29 (3q29Del) is the strongest identified genetic risk factor for schizophrenia, but the effects of this variant on neurodevelopment are not well understood. We interrogated the developing neural transcriptome in two experimental model systems with complementary advantages: isogenic human cortical organoids and isocortex from the 3q29Del mouse model. We profiled transcriptomes from isogenic cortical organoids that were aged for 2 and 12 months, as well as perinatal mouse isocortex, all at single-cell resolution. Systematic pathway analysis implicated dysregulation of mitochondrial function and energy metabolism. These molecular signatures were supported by analysis of oxidative phosphorylation protein complex expression in mouse brain and assays of mitochondrial function in engineered cell lines, which revealed a lack of metabolic flexibility and a contribution of the 3q29 gene
PAK2.
Together, these data indicate that metabolic disruption is associated with 3q29Del and is conserved across species.
Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import
Authors: Mann Jacob R. , McKenna Elizabeth D. , Mawrie Darilang , Papakis Vasileios , Alessandrini Francesco , Anderson Eric N. , Mayers Ryan , Ball Hannah E. , Kaspi Evan , Lubinski Katherine , Baron Desiree M. , Tellez Liana , Landers John E. , Pandey Udai B. , Kiskinis Evangelos
Published: August 2023

Loss-of-function variants in NIMA-related kinase 1 (NEK1) constitute a major genetic cause of amyotrophic lateral sclerosis (ALS), accounting for 2 to 3% of all cases. However, how
NEK1
mutations cause motor neuron (MN) dysfunction is unknown. Using mass spectrometry analyses for NEK1 interactors and NEK1-dependent expression changes, we find functional enrichment for proteins involved in the microtubule cytoskeleton and nucleocytoplasmic transport. We show that α-tubulin and importin-β1, two key proteins involved in these processes, are phosphorylated by NEK1 in vitro. NEK1 is essential for motor control and survival in
Drosophila
models in vivo, while using several induced pluripotent stem cell (iPSC)–MN models, including NEK1 knockdown, kinase inhibition, and a patient mutation, we find evidence for disruptions in microtubule homeostasis and nuclear import. Notably, stabilizing microtubules with two distinct classes of drugs restored NEK1-dependent deficits in both pathways. The capacity of NEK1 to modulate these processes that are critically involved in ALS pathophysiology renders this kinase a formidable therapeutic candidate.
Direct photocatalytic patterning of colloidal emissive nanomaterials
Authors: Maeng Seongkyu , Park Sun Jae , Lee Jaehwan , Lee Hyungdoh , Choi Jonghui , Kang Jeung Ku , Cho Himchan
Published: August 2023

We present a universal direct photocatalytic patterning method that can completely preserve the optical properties of perovskite nanocrystals (PeNCs) and other emissive nanomaterials. Solubility change of PeNCs is achieved mainly by a photoinduced thiol-ene click reaction between specially tailored surface ligands and a dual-role photocatalytic reagent, pentaerythritol tetrakis(3-mercaptopropionate) (PTMP), where the thiol-ene reaction is enabled at a low light intensity dose (~ 30 millijoules per square centimeter) by the strong photocatalytic activity of PeNCs. The photochemical reaction mechanism was investigated using various analyses at each patterning step. The PTMP also acts as a defect passivation agent for the PeNCs and even enhances their photoluminescence quantum yield (by ~5%) and photostability. Multicolor patterns of cesium lead halide (CsPbX
3
)PeNCs were fabricated with high resolution (<1 micrometer). Our method is widely applicable to other classes of nanomaterials including colloidal cadmium selenide–based and indium phosphide–based quantum dots and light-emitting polymers; this generality provides a nondestructive and simple way to pattern various functional materials and devices.
Osteopetrosis with Arnold Chiari malformation type I
Authors: Alagappan Alamelu , Satpathy Amit Kumar , Sahoo Biswajit , Nayak Manoj Kumar
Published: August 2023

Osteopetrosis is a rare genetic disorder resulting in increased bone density and decreased bone remodelling. Bone expansion results in the crowding of neural foramina causing cranial nerve compression. Here, we describe a female infant in her mid infancy presented with no eye contact since birth, and abdominal distension for 2 months. On CT evaluation, sclerotic bones with bilateral optic canal narrowing were present. A crowded posterior fossa with Arnold Chiari type I malformation was seen on MRI evaluation, suggesting a rare association of osteopetrosis with Arnold Chiari’s malformation.
Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study)
Authors: Hashimoto Tadayoshi , Tsukada Yuichiro , Ito Masaaki , Kanato Keisuke , Mizusawa Junki , Fukuda Haruhiko , Tsukamoto Shunsuke , Takashima Atsuo , Kanemitsu Yukihide
Published: August 2023

Introduction

In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076,NCT04288999).

Methods and analysis

JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue–agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points.

Ethics and dissemination

The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.
Multimodal molecular landscape of response to Y90-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma
Authors: Kaya Neslihan Arife , Tai David , Lim Xinru , Lim Jia Qi , Lau Mai Chan , Goh Denise , Phua Cheryl Zi Jin , Wee Felicia Yu Ting , Joseph Craig Ryan , Lim Jeffrey Chun Tatt , Neo Zhen Wei , Ye Jiangfeng , Cheung Lawrence , Lee Joycelyn , Loke Kelvin S H , Gogna Apoorva , Yao Fei , Lee May Yin , Shuen Timothy Wai Ho , Toh Han Chong , Hilmer Axel , Chan Yun Shen , Lim Tony Kiat-Hon , Tam Wai Leong , Choo Su Pin , Yeong Joe , Zhai Weiwei
Published: August 2023

Background

Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.

Methods

By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.

Results

We found that higher tumor mutation burden,NCOR1mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy.

Conclusions

This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.
Personalized neoantigen viro-immunotherapy platform for triple-negative breast cancer
Authors: Brito Baleeiro Renato , Liu Peng , Chard Dunmall Louisa S , Di Gioia Carmela , Nagano Ai , Cutmore Lauren , Wang Jun , Chelala Claude , Nyambura Lydon Wainaina , Walden Peter , Lemoine Nicholas , Wang Yaohe
Published: August 2023

Background

Triple-negative breast cancer (TNBC) corresponds to approximately 20% of all breast tumors, with a high propensity for metastasis and a poor prognosis. Because TNBC displays a high mutational load compared with other breast cancer types, a neoantigen-based immunotherapy strategy could be effective. One major bottleneck in the development of a neoantigen-based vaccine for TNBC is the selection of the best targets, that is, tumor-specific neoantigens which are presented at the surface of tumor cells and capable of eliciting robust immune responses. In this study, we aimed to set up a platform for identification and delivery of immunogenic neoantigens in a vaccine regimen for TNBC using oncolytic vaccinia virus (VV).

Methods

We used bioinformatic tools and cell-based assays to identify immunogenic neoantigens in TNBC patients’ samples, human and murine cell lines. Immunogenicity of the neoantigens was tested in vitro (human) and ex vivo (murine) in T-cell assays. To assess the efficacy of our regimen, we used a preclinical model of TNBC where we treated tumor-bearing mice with neoantigens together with oncolytic VV and evaluated the effect on induction of neoantigen-specific CD8+T cells, tumor growth and survival.

Results

We successfully identified immunogenic neoantigens and generated neoantigen-specific CD8+T cells capable of recognizing a human TNBC cell line expressing the mutated gene. Using a preclinical model of TNBC, we showed that our tumor-specific oncolytic VV was able to change the tumor microenvironment, attracting and maintaining mature cross-presenting CD8α+dendritic cells and effector T-cells. Moreover, when delivered in a prime/boost regimen together with oncolytic VV, long peptides encompassing neoantigens were able to induce neoantigen-specific CD8+T cells, slow tumor growth and increase survival.

Conclusions

Our study provides a promising approach for the development of neoantigen-based immunotherapies for TNBC. By identifying immunogenic neoantigens and developing a delivery system through tumor-specific oncolytic VV, we have demonstrated that neoantigen-based vaccines could be effective in inducing neoantigen-specific CD8+T cells response with significant impact on tumor growth. Further studies are needed to determine the safety and efficacy of this approach in clinical trials.
Augmentation of flow diverter vessel wall apposition using the Comaneci device: case experience from a novel, off-label technique
Authors: Lin Li-Mei , Collard de Beaufort Jonathan , Wang Alice S , Campos Jessica K , Zarrin David A , Meyer Benjamen M , Colby Geoffrey P , Coon Alexander L
Published: August 2023

Background

Flow diversion (FD) embolization of intracranial cerebral aneurysms is an increasingly common modality where treatment success depends on adequate vessel wall apposition of the device. This study aimed to investigate off-label use of the Comaneci device for augmenting vessel wall apposition in post-deployed flow diversion stents (FDS).

Methods

Over a 20- month period, all FD cases for the treatment of internal carotid artery (ICA) aneurysms were reviewed. Cases in which the Comaneci device was used to augment vessel wall apposition were analyzed. Data including patient demographics, case characteristics, and procedural outcomes were collected and analyzed as counts.

Results

From a total of 74 ICA FD cases, the Comaneci device was used to improve vessel wall apposition in 22 cases (29.7%) . Of these cases, 91% were female with a mean patient age of 64.9±11.3 years, and an average aneurysm size of 4.5±2.5 mm. Comaneci device deployment and retrieval was successful in all (100%) cases, with an average fluoroscopy time of 27.3±7.8 min, an average contrast usage of 25.8±13.2 mL, and an average radiation exposure of 915.1±320.8 mGy. Only two cases (9%) required subsequent balloon angioplasty after Comaneci deployment to improve vessel wall apposition throughout the FDS.

Conclusion

Our experience with this technique demonstrates the feasibility of using the Comaneci device for augmentation of FDS vessel wall apposition with 100% success in the deployment and retrieval of the Comaneci device.
Planck length in classical and quantum Hamiltonian formulations of general relativity
Authors: Cremaschini Claudio
Published: August 2023

The physical meaning of the Planck length ($$\ell _{P}$$

ℓ
P

) is investigated in the framework of the unconstrained synchronous variational formulation of classical general relativity (GR). This theoretical setting permits the establishment of manifestly-covariant Lagrangian and Hamiltonian theories for the Einstein field equations of the continuum gravitational field. It is shown that such a formulation is distinguished by the existence of a novel variational contribution expressed by an infinite series summation of suitable 4-scalar terms in which the coupling coefficients are even powers of the Planck length. However, the requirement of realization of a classical GR Hamiltonian theory places stringent constraints on the admissible Planck-length power terms to be retained. In fact, excluding the trivial gauge constant, it is proved that only the $$O\left( \ell _{P}^{0}\right) $$

O

ℓ

P

0

contribution of the series is ultimately permitted, namely the unique one which is independent of $$\ell _{P}$$

ℓ
P

. Therefore, the Planck length is effectively not allowed to appear at the classical level for consistency with the Hamiltonian principle. This places important consequences on the mathematical establishment of the corresponding canonical quantum gravity theory, which is then found to be correct through $$O\left( \ell _{P}^{2}\right) $$

O

ℓ

P

2

. Additional implications concern the physical significance of related quantum momenta and their meaning in the semi-classical limit, as well as the role of the Planck length in the same quantum-gravity realm.
Spatio-temporal changes in racial segregation and diversity in large US cities from 1990 to 2020: a visual data analysis
Authors: Dmowska Anna , Stepinski Tomasz F.
Published: August 2023

Urban populations in large US cities exhibit racial and ethnic diversity, yet they remain residentially segregated. The examination of temporal trends in segregation and diversity is crucial for sociologists and urban planners. In this study, we investigate the spatio-temporal changes in segregation and diversity across 61 major US cities, utilizing data from four US Censuses conducted between 1990 and 2020. Unlike previous studies, our approach relies on visual data analysis, enabling us to capture the overarching changes in racial coresidence during this period. We employ four distinct perspectives – geographical, temporal, groups evolution, and desegregation scale limit – to visualize and analyze the data. Geographical analysis uncovers a decrease in regional disparities in urban diversity and segregation since 1990, as urban racial integration extends beyond West Coast and Southwestern cities to encompass the entire US. Through temporal analysis, we observe a general trend of rapidly increasing diversity and gradual reduction in segregation, albeit with varying rates across different cities. Groups evolution analysis reveals that cities grouped based on their diversity and segregation metrics in 1990 follow the overall trend toward larger diversity and smaller segregation while preserving group’s coherence but not their distinctiveness. Finally, the desegregation scale limit perspective suggests that, on average, over the 1990 to 2020 period, the desegregation scale has started to subceed the lower limit of the census block. By employing these diverse analytical perspectives, our study provides a comprehensive understanding of the changes in racial segregation and diversity within US cities over the past three decades.
Towards hypergraph cognitive networks as feature-rich models of knowledge
Authors: Citraro Salvatore , De Deyne Simon , Stella Massimo , Rossetti Giulio
Published: August 2023

Conceptual associations influence how human memory is structured: Cognitive research indicates that similar concepts tend to be recalled one after another. Semantic network accounts provide a useful tool to understand how related concepts are retrieved from memory. However, most current network approaches use pairwise links to represent memory recall patterns (e.g. reading “airplane” makes one think of “air” and “pollution”, and this is represented by links “airplane”-“air” and “airplane”-“pollution”). Pairwise connections neglect higher-order associations, i.e. relationships between more than two concepts at a time. These higher-order interactions might covariate with (and thus contain information about) how similar concepts are along psycholinguistic dimensions like arousal, valence, familiarity, gender and others. We overcome these limits by introducing feature-rich cognitive hypergraphs as quantitative models of human memory where: (i) concepts recalled together can all engage in hyperlinks involving also more than two concepts at once (cognitive hypergraph aspect), and (ii) each concept is endowed with a vector of psycholinguistic features (feature-rich aspect). We build hypergraphs from word association data and use evaluation methods from machine learning features to predict concept concreteness. Since concepts with similar concreteness tend to cluster together in human memory, we expect to be able to leverage this structure. Using word association data from the Small World of Words dataset, we compared a pairwise network and a hypergraph with $N= 3586$
N
=
3586
concepts/nodes. Interpretable artificial intelligence models trained on (1) psycholinguistic features only, (2) pairwise-based feature aggregations, and on (3) hypergraph-based aggregations show significant differences between pairwise and hypergraph links. Specifically, our results show that higher-order and feature-rich hypergraph models contain richer information than pairwise networks leading to improved prediction of word concreteness. The relation with previous studies about conceptual clustering and compartmentalisation in associative knowledge and human memory are discussed.
Data-driven Communicative Behaviour Generation: A Survey
Authors: Oralbayeva Nurziya , Aly Amir , Sandygulova Anara , Belpaeme Tony
Published: August 2023

The development of data-driven behaviour generating systems has recently become the focus of considerable attention in the fields of human–agent interaction and human–robot interaction. Although rule-based approaches were dominant for years, these proved inflexible and expensive to develop. The difficulty of developing production rules, as well as the need for manual configuration to generate artificial behaviours, places a limit on how complex and diverse rule-based behaviours can be. In contrast, actual human–human interaction data collected using tracking and recording devices makes humanlike multimodal co-speech behaviour generation possible using machine learning and specifically, in recent years, deep learning. This survey provides an overview of the state of the art of deep learning-based co-speech behaviour generation models and offers an outlook for future research in this area.