bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting host O-linked glycan biosynthesis affects Ebola virus replication efficiency and reveals differential GalNAc-T acceptor site preferences on the Ebola virus glycoprotein
Authors: Bagdonaite Ieva , Abdurahman Samir , Mirandola Mattia , Pasqual Denis , Frank Martin , Narimatsu Yoshiki , Joshi Hiren J. , Vakhrushev Sergey Y. , Salata Cristiano , Mirazimi Ali , Wandall Hans H.
Published: May 2024

Ebola virus glycoprotein (EBOV GP) is one of the most heavily O-glycosylated viral glycoproteins, yet we still lack a fundamental understanding of the structure of its large O-glycosylated mucin-like domain and to what degree the host O-glycosylation capacity influences EBOV replication. Using tandem mass spectrometry, we identified 47 O-glycosites on EBOV GP and found similar glycosylation signatures on virus-like particle- and cell lysate-derived GP. Furthermore, we performed quantitative differential O-glycoproteomics on proteins produced in wild-type HEK293 cells and cell lines ablated for the three key initiators of O-linked glycosylation, GalNAc-T1, -T2, and -T3. The data show that 12 out of the 47 O-glycosylated sites were regulated, predominantly by GalNAc-T1. Using the glycoengineered cell lines for authentic EBOV propagation, we demonstrate the importance of O-linked glycan initiation and elongation for the production of viral particles and the titers of progeny virus. The mapped O-glycan positions and structures allowed to generate molecular dynamics simulations probing the largely unknown spatial arrangements of the mucin-like domain. The data highlight targeting
GALNT1
or
C1GALT1C1
as a possible way to modulate O-glycan density on EBOV GP for novel vaccine designs and tailored intervention approaches.

IMPORTANCE

Ebola virus glycoprotein acquires its extensive glycan shield in the host cell, where it is decorated with N-linked glycans and mucin-type O-linked glycans. The latter is initiated by a family of polypeptide GalNAc-transferases that have different preferences for optimal peptide substrates resulting in a spectrum of both very selective and redundant substrates for each isoform. In this work, we map the exact locations of O-glycans on Ebola virus glycoprotein and identify subsets of sites preferentially initiated by one of the three key isoforms of GalNAc-Ts, demonstrating that each enzyme contributes to the glycan shield integrity. We further show that altering host O-glycosylation capacity has detrimental effects on Ebola virus replication, with both isoform-specific initiation and elongation playing a role. The combined structural and functional data highlight glycoengineered cell lines as useful tools for investigating molecular mechanisms imposed by specific glycans and for steering the immune responses in future vaccine designs.
Draft genome sequence of
Escherichia coli
MTR_GS_S1457 strain isolated from a soil sample of a vegetable garden in Gazipur, Bangladesh
Authors: Islam Md. Saiful , Pramanik Pritom Kumar , Rana Md. Liton , Ullah Md. Ashek , Neloy Fahim Haque , Ramasamy Srinivasan , Schreinemachers Pepijn , Oliva Ricardo , Rahman Md. Tanvir
Published: May 2024

We announce the sequence of the
Escherichia coli
MTR_GS_S1457 strain isolated from a soil sample of a vegetable gardening system for the first time in Bangladesh. With a length of 4,918,647 bp, this strain contained one plasmid, two CRISPR arrays, 54 predicted antibiotic resistance genes, and 81 predicted virulence factor genes.
Mammalian orthoreovirus capsid protein σ3 antagonizes RLR-mediated antiviral responses by degrading MAVS
Authors: Li Dianyu , Mo Rongqian , Li Xiaoyi , Cheng Rongrong , Xie Jingying , Li Hongshan , Yang Yanmei , Li Shasha , Li Huixia , Yan Zhenfang , Wei Suocheng , Idris Adi , Li Xiangrong , Feng Ruofei
Published: May 2024

Mammalian orthoreovirus (MRV) outer capsid protein σ3 is a multifunctional protein containing a double-stranded RNA-binding domain, which facilitates viral entry and assembly. We reasoned that σ3 has an innate immune evasion function. Here, we show that σ3 protein localizes in the mitochondria and interacts with mitochondrial antiviral signaling protein (MAVS) to activate the intrinsic mitochondria-mediated apoptotic pathway. Consequently, σ3 protein promotes the degradation of MAVS through the intrinsic caspase-9/caspase-3 apoptotic pathway. Moreover, σ3 protein can also inhibit the expression of the components of the RNA-sensing retinoic acid-inducible gene (RIG)-like receptor (RLR) signaling pathway to block antiviral type I interferon responses. Mechanistically, σ3 inhibits RIG-I and melanoma differentiation-associated gene 5 expression is independent of its inhibitory effect on MAVS. Overall, we demonstrate that the MRV σ3 protein plays a vital role in negatively regulating the RLR signaling pathway to inhibit antiviral responses. This enables MRV to evade host defenses to facilitate its own replication providing a target for the development of effective antiviral drugs against MRV.

IMPORTANCE

Mammalian orthoreovirus (MRV) is an important zoonotic pathogen, but the regulatory role of its viral proteins in retinoic acid-inducible gene-like receptor (RLR)-mediated antiviral responses is still poorly understood. Herein, we show that MRV σ3 protein co-localizes with mitochondrial antiviral signaling protein (MAVS) in the mitochondria and promotes the mitochondria-mediated intrinsic apoptotic pathway to cleave and consequently degrade MAVS. Furthermore, tryptophan at position 133 of σ3 protein plays a key role in the degradation of MAVS. Importantly, we show that MRV outer capsid protein σ3 is a key factor in antagonizing RLR-mediated antiviral responses, providing evidence to better unravel the infection and transmission mechanisms of MRV.
Microbiome depletion and recovery in the sea anemone,
Exaiptasia diaphana
, following antibiotic exposure
Authors: MacVittie Sophie , Doroodian Saam , Alberto Aaron , Sogin Maggie
Published: May 2024

Microbial species that comprise host-associated microbiomes play an essential role in maintaining and mediating the health of plants and animals. While defining the role of individual or even complex communities is important toward quantifying the effect of the microbiome on host health, it is often challenging to develop causal studies that link microbial populations to changes in host fitness. Here, we investigated the impacts of reduced microbial load following antibiotic exposure on the fitness of the anemone,
Exaiptasia diaphana
and subsequent recovery of the host’s microbiome. Anemones were exposed to two different types of antibiotic solutions for 3 weeks and subsequently held in sterilized seawater for a 3-week recovery period. Our results revealed that both antibiotic treatments reduced the overall microbial load during and up to 1 week post-treatment. The observed reduction in microbial load was coupled with reduced anemone biomass, halted asexual reproduction rates, and for one of the antibiotic treatments, the partial removal of the anemone’s algal symbiont. Finally, our amplicon sequencing results of the 16S rRNA gene revealed that anemone bacterial composition only shifted in treated individuals during the recovery phase of the experiment, where we also observed a significant reduction in the overall diversity of the microbial community. Our work implies that the
E. diaphana’s
microbiome contributes to host fitness and that the recovery of the host’s microbiome following disturbance with antibiotics leads to a reduced, but stable microbial state.

IMPORTANCE

Exaiptasia diaphana
is an emerging model used to define the cellular and molecular mechanisms of coral-algal symbioses.
E. diaphana
also houses a diverse microbiome, consisting of hundreds of microbial partners with undefined function. Here, we applied antibiotics to quantify the impact of microbiome removal on host fitness as well as define trajectories in microbiome recovery following disturbance. We showed that reduction of the microbiome leads to negative impacts on host fitness, and that the microbiome does not recover to its original composition while held under aseptic conditions. Rather the microbiome becomes less diverse, but more consistent across individuals. Our work is important because it suggests that anemone microbiomes play a role in maintaining host fitness, that they are susceptible to disturbance events, and that it is possible to generate gnotobiotic individuals that can be leveraged in microbiome manipulation studies to investigate the role of individual species on host health.
Long-term follow-up of relapse and remission of CIDP in a Chinese cohort
Authors: Niu Jingwen , Zhang Lei , Hu Nan , Cui Liying , Liu Mingsheng
Published: May 2024

Objective

We aim to describe the long-term outcome of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) after immune treatment in a Chinese cohort.

Methods

Between March 2015 and March 2023, 89 patients fulfilling the criteria for CIDP were followed up for a median of 22 months after treatment. Nine had positive antibodies against nodal-paranodal cell-adhesion molecules. Patients were treated according to clinical requirements with prednisone, intravenous immunoglobulin (IVIg) and/or immunosuppressant.

Results

A total of 78/89 patients had decreased inflammatory neuropathy cause and treatment (INCAT) scores at the last follow-up. For CIDP patients treated with steroids, 35 were stable without relapse after cessation or with a small maintenance dose; 2 relapsed at a high dose (20 mg/day); 15 relapsed at a low dosage (<20 mg/day) and 11 did not respond. The INCAT before treatment was significantly lower in those without relapse (median INCAT 2 vs 3, p=0.030). IVIg was effective in 37/52 CIDP patients. 28 CIDP patients and 4 autoimmune nodopathy patients were treated with immunosuppressants. The average INCAT was 3.3±1.9 before and 1.9±1.3 after immunosuppressant treatment (p=0.001) in CIDP.

Conclusion

The long-term prognosis of CIDP patients was generally favourable. Nearly half of our patients treated with steroid were stable without relapse after cessation or with a small maintenance dose. The risk of relapse was higher in those with high INCAT. We recommend slowly tapering prednisone based on clinical judgement.
Dose–response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews
Authors: Lugo Alessandra , Bosetti Cristina , Peveri Giulia , Rota Matteo , Bagnardi Vincenzo , Gallus Silvano
Published: May 2024

Introduction

Only a limited number of meta-analyses providing risk curve functions of dose–response relationships between various smoking-related variables and cancer-specific risk are available.

Methods and analysis

To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose–response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose–response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose–response relationship framework.

Ethics and dissemination

Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking.

Trial registration number

This protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991).
The RELIEF feasibility trial: topical lidocaine patches in older adults with rib fractures
Authors: Clout Madeleine , Turner Nicholas , Clement Clare , Braude Philip , Benger Jonathan , Gagg James , Gendall Emma , Holloway Simon , Ingram Jenny , Kandiyali Rebecca , Lewis Amanda , Maskell Nick A , Shipway David , Smith Jason E , Taylor Jodi , Darweish Medniuk Alia , Carlton Edward
Published: May 2024

Background

Lidocaine patches, applied over rib fractures, may reduce pulmonary complications in older patients. Known barriers to recruiting older patients in emergency settings necessitate a feasibility trial. We aimed to establish whether a definitive randomised controlled trial (RCT) evaluating lidocaine patches in older patients with rib fracture(s) was feasible.

Methods

This was a multicentre, parallel-group, open-label, feasibility RCT in seven hospitals in England and Scotland. Patients aged ≥65 years, presenting to ED with traumatic rib fracture(s) requiring hospital admission were randomised to receive up to 3×700 mg lidocaine patches (Ralvo), first applied in ED and then once daily for 72 hours in addition to standard care, or standard care alone. Feasibility outcomes were recruitment, retention and adherence. Clinical end points (pulmonary complications, pain and frailty-specific outcomes) and patient questionnaires were collected to determine feasibility of data collection and inform health economic scoping. Interviews and focus groups with trial participants and clinicians/research staff explored the understanding and acceptability of trial processes.

Results

Between October 23, 2021 and October 7, 2022, 206 patients were eligible, of whom 100 (median age 83 years; IQR 74–88) were randomised; 48 to lidocaine patches and 52 to standard care. Pulmonary complications at 30 days were determined in 86% of participants and 83% of expected 30-day questionnaires were returned. Pulmonary complications occurred in 48% of the lidocaine group and 59% in standard care. Pain and some frailty-specific outcomes were not feasible to collect. Staff reported challenges in patient compliance, unfamiliarity with research measures and overwhelming the patients with research procedures.

Conclusion

Recruitment of older patients with rib fracture(s) in an emergency setting for the evaluation of lidocaine patches is feasible. Refinement of data collection, with a focus on the collection of pain, frailty-specific outcomes and intervention delivery are needed before progression to a definitive trial.

Trial registration number

ISRCTN14813929.
Agreement between audiometric hearing loss and self-reported hearing difficulty on the Revised Hearing Handicap Inventory differs by demographic factors
Authors: Dillard Lauren K , Matthews Lois J , Dubno Judy R
Published: May 2024

Background

New standardised measures of self-reported hearing difficulty can be validated against audiometric hearing loss. This study reports the influence of demographic factors (age, sex, race and socioeconomic position (SEP)) on the agreement between audiometric hearing loss and self-reported hearing difficulty.

Methods

Participants were 1558 adults (56.9% female; 20.0% racial minority; mean age 63.7 (SD 14.1) years) from the Medical University of South Carolina Longitudinal Cohort Study of Age-Related Hearing Loss (1988–current). Audiometric hearing loss was defined as the average of pure-tone thresholds at frequencies 0.5, 1.0, 2.0 and 4.0 kHz >25 dB HL in the worse ear. Self-reported hearing difficulty was defined as ≥6 points on the Revised Hearing Handicap Inventory (RHHI) or RHHI screening version (RHHI-S). We report agreement between audiometric hearing loss and the RHHI(-S), defined by sensitivity, specificity, accuracy, positive predictive value, negative predictive value and observedminuspredicted prevalence. Estimates were stratified to age group, sex, race and SEP proxy.

Results

The prevalence of audiometric hearing loss and self-reported hearing difficulty were 49.0% and 48.8%, respectively. Accuracy was highest among participants aged <60 (77.6%) versus 60–70 (71.4%) and 70+ (71.9%) years, for white (74.6%) versus minority (68.0%) participants and was similar by sex and SEP proxy. Generally, agreement of audiometric hearing loss and RHHI(-S) self-reported hearing difficulty differed by age, sex and race.

Conclusions

Relationships of audiometric hearing loss and self-reported hearing difficulty vary by demographic factors. These relationships were similar for the full (RHHI) and screening (RHHI-S) versions of this tool.
Nigrostriatal blood-brain barrier opening in Parkinson’s disease
Authors: Gasca-Salas Carmen , Pineda-Pardo José A , Del Álamo Marta , Jiménez Tamara , Trompeta Clara , Toltsis Gabriella , Garcia-Cañamaque Lina , Fernández-Rodríguez Beatriz , Matarazzo Michele , Plaza de las Heras Isabel , Natera-Villalba Elena , Martínez-Fernández Raúl , Duque Alicia , Ruiz de Aguiar Santiago , Blesa Javier , Rachmilevich Itay , Obeso José A
Published: May 2024

Background

The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson’s disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods

Three patients underwent MRgFUS for midbrain and putamen BBB-O. Patients were evaluated clinically and underwent brain MRI with gadolinium (baseline, 24 hours, 14 days and 3 months postprocedure). In two patients, BBB-O was repeated after 2–3 weeks, and 18F-Choline-PET was performed immediately after.

Results

The right SN and putamen were simultaneously opened unilaterally in 3 patients once and the left SN in 1 patient in a different session. No severe clinical or neuroimaging adverse events developed in any patient. 18F-Choline-PET uptake was enhanced in the targeted SN and putamen regions.

Conclusion

BBB-O of the nigrostriatal system is a feasible and well-tolerated approach in patients with PD. 18F-Choline-PET uptake indicates penetration into the parenchyma after BBB-O, which suggests that the opening is functionally effective. This minimally invasive technique could facilitate delivery of putative neurorestorative molecules to brain regions vulnerable to neurodegeneration.
Shifting ocean conditions influence temporal variation in the fecundity of California Current rockfishes (Sebastes spp.)
Authors: Beyer Sabrina G. , Sogard Susan M. , Stafford David M. , Kashef Neosha S , Rodriguez Abel , Alonzo Suzanne H. , Field John C.
Published: May 2024

Successful reproduction is critical to the growth and persistence of marine fish populations, yet how changes in the environment influence reproduction remains largely unknown. We explored how shifting ocean conditions influenced larval production in four species of long-lived, live-bearing rockfish ( Sebastes spp.) in the California Current. Brood fecundity, body size, and environmental information were analyzed from the mid-1980s through 2020. Interannual variation in brood fecundity was greater than 50% in the single-brooding yellowtail rockfish ( S. flavidus) and widow rockfish ( S. entomelas). Brood fecundity varied less in chilipepper ( S. goodei) and bocaccio ( S. paucispinis), two species capable of multiple broods per year. In these two species, interannual fecundity variability is more likely to depend on the number of broods produced than on brood size alone. In all four species, brood fecundity was positively correlated with maternal length and body condition. Variable ocean conditions influenced the strength of maternal size effects by year. These results provide evidence for reproductive plasticity and environmental effects on fecundity, with implications for changes in population reproductive potential with climate change.
Dynamics of graphene as an open quantum system
Authors: Mir Showkat Ahmad , Shah M. A.
Published: May 2024

We examine the imbalance thermodynamics of uncontaminated decoherence in graphene. In a uncontaminated decoherence process, no exchange of energy takes place directly between graphene and the surroundings. It is seen that due to decoherence heat dissolution takes place due to which energy of the environment cannot remain conserved. In this paper, we find out the energy eigenvalues and wave function in the graphene from the perturbed Hamiltonian to find out the density matrix and entropy of the system and their unique relation between the density matrix, momentum of the graphene and entropy where the graphene is taken as an open system. In graphene, the behavior of electrons is controlled by the massless Hamiltonian and ([Formula: see text]) Dirac equation.
Noether symmetry analysis for fourth-order modified gravity theory: Cosmological solution and evolution
Authors: Hembrom Shriton , Bhaumik Roshni , Chakraborty Subenoy
Published: May 2024

A modified fourth-order gravity theory namely the [Formula: see text] theory is considered in flat FLRW model to investigate both classical and quantum cosmology. The field equations are reduced to second-order differential equations by considering the technique of Lagrange multiplier. Noether symmetry analysis has been used both for obtaining classical solution and the wave function of the Universe in quantum cosmology. Finally the cosmological solutions are examined from observational view point.
Self-Labeling Learning Ensemble via Deep Recurrent Neural Network and Self-Representation for Speech Emotion Recognition
Authors: Cui Yan , Jiang Xiaoyan , Dai Yue
Published: May 2024

Speech emotion recognition (SER) methods rely on frames to analyze the speech data. However, the existing methods typically divide a speech sample into smaller speech frames and label them with a single emotional tag, which fails to consider the possibility of multiple emotion tags coexisting within a speech sample. To deal with this limitation, we present a novel approach called self-labeling learning ensemble via DRNN and self-representation (En-DRNN-SR) for SER. This method automatically segments speech sample into speech frames, and then the deep recurrent neural network (DRNN) is applied to learn the deep features, and next the self-representation is built to get a relational degree matrix, finally the speech frames is divided into three parts using a relational degree matrix: the key emotional frames, the compatible emotional frames and the noise frames. The emotion tags of the compatible emotional frames are adaptive cyclic learned based on the key emotion frames vias the relational degree matrix, while also checking the emotion tags associated with the key compatible frames. Additionally, we introduce a new self-labeling criterion based on fuzzy membership degree for SER. To evaluate the feasibility and effectiveness of the proposed En-DRNN-SR, we conducted extensive experiments on IEMOCAP, EMODB, and SAVEE database, the proposed En-DRNN-SR obtains 69.13%, 82.83%, and 52.31% results on IEMOCAP, EMODB, and SAVEE database, which outperformed all competing algorithms. The experimental results clearly demonstrate that the proposed approach outperforms state-of-the-art SER methods, achieving superior performance on feature learning and classification.
Holographic inflation, primordial black holes and early structure formation
Authors: Banks Tom , Fischler Willy
Published: May 2024

Evidence has accumulated that there are SuperMassive Black Holes (SMBHs) in the centers of most galaxies, and that these were formed in the very early universe by some as yet unknown process. In particular, there is evidence [J. Silk, M. C. Begelman, C. Norman, A. Nusser and R. F. G. Wyse, Astrophys. J. Lett. 961 (2024) L39, https://doi.org/10.3847/2041-8213/ad1bf0 , arXiv:2401.02482 [astroph. GA]; A. Bogdan et al., Nature Astron. 8 (2024) 126, https://doi.org/10.1038/s41550-023-02111-9 , arXiv:2305.15458 [astro-ph.GA]; S. Y. Guo, M. Khlopov, X. Liu, L. Wu, Y. Wu and B. Zhu, arXiv:2306.17022 [hep-ph]] that at least some galaxies formed as early as [Formula: see text] years after the big bang host SMBHs. We suggest that the holographic model of inflation, whose dark matter candidates are primordial black holes carrying a discrete gauge charge, which originated as a small subset of the inflationary horizon volumes in the very early universe, can provide the seeds for this early structure formation. Aspects of the model pointed out long ago suggested an early era of structure formation, with structures dominated by dark matter. The additional assumption that the dark matter consists of discretely charged black holes implies black hole dominance of early structures, which seems to be implied by JWST data.
Variational Principles of Nano Laminated Composite Plates with Flexoelectric Effect
Authors: Fan Tao
Published: May 2024

Flexoelectric effect is strengthened in dielectrics at nanoscale so that it could not be neglected. In this work, a laminated composite plate with flexoelectric core and two coverings of CNTRCs is modeled. The variational principles of the plate with generalized supporting conditions are derived considering both the flexoelectricity of the piezoelectric core and the reinforcement of the CNTRCs. According to it, the governing equation and boundary conditions with any supporting types are obtained. Then the analytical solutions to the displacements and resonant frequencies of the plate with two different boundary conditions for free vibration are given. The numerical results prove that the flexoelectric effect relies on the scale seriously. Moreover, the CNTRCs coverings can improve the bending stiffness of the whole plate. Therefore, the bending responses such as resonant frequency and bending deflection can be adjusted and optimized by changing the ratio of the CNTs to the matrix. It’s hopeful to provide the theoretical basis of numerical calculation of electronic devices with laminated structures at nanoscale.
Anisotropic stellar structures in energy–momentum squared theory with Tolman–Kuchowicz spacetime
Authors: Sharif M. , Zeeshan Gul M.
Published: May 2024

This paper examines the viable characteristics of anisotropic compact stars in [Formula: see text] theory ([Formula: see text] is the Ricci scalar and [Formula: see text]). In this perspective, we use Tolman–Kuchowicz solutions [Formula: see text] and [Formula: see text] to examine the configurations of static spherically symmetric structures. The unknown constants are found by the first fundamental form of Darmois junction conditions. We analyze the behavior of fluid parameters in the interior of 4U 1538-52, PSRJ 1614-220, EXO 1785-248 and SAXJ 1808.4-3658 compact stars correspond to different models of this theory. Furthermore, the stability of the proposed compact stellar objects is examined through sound speed and adiabatic index methods. The satisfaction of requisite conditions ensures that stable compact objects exist in this framework.
Computational Insights into the Resistance of the Gatekeeper Mutation V564F of FGFR2 Against Pemigatinib
Authors: Liu Jiayu , Jin Qi , Xia Jingying , Liu Ling , Liu Yuee , Jiang Lei
Published: May 2024

The fibroblast growth factor receptor 2 (FGFR2), a transmembrane receptor tyrosine kinase, is implicated in a plethora of human cancers, including intrahepatic cholangiocarcinomas. The clinically relevant V564F gatekeeper mutation conferred resistance to the current FGFR2 drug−Pemigatinib. Here, we conducted integrated computational methods to compare the protein−ligand interactions between the FGFR2 kinase domain in the wild-type and V564F mutant states and Pemigatinib. Based on molecular docking, molecular dynamic simulations and hydrogen bond analysis, we revealed that the reduced hydrogen bonding interactions in the V564F mutant were the key factor to decrease the binding affinity of Pemigatinib to the FGFR2. The per-residue free energy decomposition analysis implemented by the molecular mechanics/generalized born surface area method revealed the reduced contributions from the key residues G488, F564 and A567 located at the kinase hinge domain were responsible for the decreased binding affinity in the V564F mutant. This study elucidated the molecular mechanism for the resistance of Pemigatinib in FGFR2 triggered by the V564F mutation and may provide insights for future drug development and optimization.
THE RELATIONSHIP BETWEEN FINANCIAL DEVELOPMENT AND SUSTAINABLE DEVELOPMENT GOALS — A BIBLIOMETRIC ANALYSIS
Authors: THEN WENDY WEE JIN
Published: May 2024

The Sustainable Development Goals (SDGs) serve as a common aim that brings many nations together, led by the United Nations with the purpose to achieve a set of 17 targets by 2030. One very important factor in achieving these aims is finance. The advancement in financial development all around the world will be able to speed up achieving SDGs where governments, policymakers, and people will be able to grow the economic development and infrastructure of the country, provide adequate job opportunities for many people, reduce poverty, as well as improve sustainability around the world. In opposition to that, some researchers see the advancement in financial development as an activity that will jeopardize achieving SDGs as financial development might lead to the production of carbon footprints at a faster rate. Using bibliometric analysis, this paper was able to discover that there is an increase in attention and interest in the field with the rise in publications in recent years, especially in 2022. Furthermore, this paper also identifies research hotspots within the field while also finding and analyzing the most impactful authors and publications on the topic. Ultimately, this paper hopes to provide a better definition for the relationship between financial development and SDGs with the use of bibliometric analysis, where data is collected from the Scopus database and analyzed using VOSviewer.
Do We Trust Artificially Intelligent Assistants at Work? An Experimental Study
Authors: Cvetkovic Anica , Savela Nina , Latikka Rita , Oksanen Atte
Published: May 2024

The fourth industrial revolution is bringing artificial intelligence (AI) into various workplaces, and many businesses worldwide are already capitalizing on AI assistants. Trust is essential for the successful integration of AI into organizations. We hypothesized that people have higher trust in human assistants than AI assistants and that people trust AI assistants more if they have more control over their activities. To test our hypotheses, we utilized a survey experiment with 828 participants from Finland. Results showed that participants would rather entrust their schedule to a person than to an AI assistant. Having control increased trust in both human and AI assistants. The results of this study imply that people in Finland still have higher trust in traditional workplaces where people, rather than smart machines, perform assisting work. The findings are of relevance for designing trustworthy AI assistants, and they should be considered when integrating AI technology into organizations.
Supplemental Table 5 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella
Published: May 2024

REC and nitro-PAH signatures in New England
Supplementary Figure 1 from The Impact of Improved Treatments on Survival of Adult U.S. Leukemia Patients: 1990–2018
Authors: Howlader Nadia , Sharon Elad , Bhattacharya Manami , Ehrlich Lori A. , Richardson Nicholas C. , Gormley Nicole J. , de Claro R. Angelo , Wood Amy E. , Mariotto Angela B. , Cronin Kathleen A.
Published: May 2024

Supplementary Figure 1: Trends in Mortality by Leukemia Subtypes and Race Ethnicity. Total US 1992-2018. Results are shown for mortality trends for CML (panel A), ALL (panel B), and CLL (panel C), 1992-2018. For each panel, we show age-adjusted mortality rates by five mutually exclusive race-ethnicity categories: non-Hispanic White, non-Hispanic Black, non-Hispanic Asian Pacific Islander, non-Hispanic American Indian/Alaskan Natives, and Hispanic.
Supplementary Figure 2 from Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: May 2024

Supplementary Figure 2: Visual mapping of mosaic chromosomal alterations
Supplemental Table 4 from Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies
Authors: Hathaway Cassandra A. , Conejo-Garcia Jose R. , Fridley Brooke L. , Rosner Bernard , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Hecht Jonathan L. , Sasamoto Naoko , Terry Kathryn L. , Tworoger Shelley S. , Townsend Mary K.
Published: May 2024

Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics
Supplementary Figure S8 from COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination
Authors: Salvatore Maxwell , Hu Miriam M. , Beesley Lauren J. , Mondul Alison M. , Pearce Celeste Leigh , Friese Christopher R. , Fritsche Lars G. , Mukherjee Bhramar
Published: May 2024

Severe COVID-19 among recent cancer (within three years of positive COVID-19 test; n = 6,143) and non-cancer patients (n = 41,545) who tested positive and have non-missing covariates. The results were from the model logit P(YSevereCOVID = 1|X, Cancer, Covariate) = β0 + βXX + βCancerCancer + βIntX × Cancer + βCovCovariate, where Covariate = Age + Race/Ethnicity + Sex + Disadvantage Index (quartile) + Comorbidity Score. Reference groups were age: 18 to 35, sex: female, BMI: 18.5 to 25, race: white/non-Hispanic, smoking status: never. A unit change in the continuous age variable is 10 years. The comorbidity score ranges from 0 to 6 and is the sum of indicators for presence of six categories of preexisting conditions in the electronic health record.
Supplementary Figure S4 from COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination
Authors: Salvatore Maxwell , Hu Miriam M. , Beesley Lauren J. , Mondul Alison M. , Pearce Celeste Leigh , Friese Christopher R. , Fritsche Lars G. , Mukherjee Bhramar
Published: May 2024

An UpSet diagram showing the distribution of cancer treatment patterns among COVID-19 positive individuals with cancer (n = 13,752). Treatment-based analyses were performed using three mutually exclusive categories: chemotherapy (n = 2,910), radiation only (n = 690), and surgery only (n = 172). Treatment was defined according to Table S2.
Supplementary Table 4 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: May 2024

Supplemental Table 4 shows the associations of Visit 2 sMICA and sMICB levels (in quartiles) with CRC risk.
Supplementary Figure S2 from COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination
Authors: Salvatore Maxwell , Hu Miriam M. , Beesley Lauren J. , Mondul Alison M. , Pearce Celeste Leigh , Friese Christopher R. , Fritsche Lars G. , Mukherjee Bhramar
Published: May 2024

Flowcharts describing the definitions of outcomes (panel A) and vaccination status (panel B).
Adolescent Physical Activity and Breast Cancer Risk in Young Women: Findings From the ProF-SC Study
Authors: Kehm RD , Genkinger JM , MacInnis RJ , John EM , Knight JA , Kurian AW , Colonna SV , Chung WK , Phillips KA , Andrulis IL , Buys SS , Daly MB , Hopper JL , Terry MB
Published: May 2024

Study Purpose: The incidence of breast cancer (BC) in young women under age 40 years has increased substantially over time, underscoring the need for a better understanding of early life modifiers of risk. We examined the association of recreational physical activity (RPA) with BC risk before age 40 years, focusing on RPA during the adolescent window of susceptibility. Methods: We used data from the ProF-SC Study, which is enriched for young women at increased risk for BC. We conducted an ambidirectional cohort analysis that included women, aged ≤ 55 years at baseline, who were enrolled within 5 years of their first primary BC diagnosis or had no history of BC at baseline (n = 14,865). Women reported by baseline questionnaire their average levels of moderate and strenuous RPA during adolescence (12–17 years), which we converted to total metabolic equivalents per week (METs-per-week) and categorized into quartiles after adjusting for baseline age. We conducted attained age analyses until 40 years using multivariable Cox proportional hazards regression models adjusted for baseline sociodemographic and lifestyle factors. Follow-up started at age 18 years and ended at age at first invasive BC diagnosis, last follow-up, or 40 years, whichever came first. Results: There were 1,646 BC diagnoses before age 40 during 30,5594 person-years of follow-up. Being in the highest vs. lowest quartile of adolescent RPA was significantly associated with a 16% reduced risk of BC until age 40 before adjustment for baseline RPA (HR = 0.84, 95% CI = 0.73–0.97). This association was attenuated and no longer statistically significant after adjustment for baseline RPA (HR = 0.89, 95% CI = 0.77–1.04). We identified a statistically significant multiplicative interaction between adolescent and baseline RPA (interaction P value = 0.03). A one standard deviation increase in METs-per-week of baseline RPA was associated with a 5% reduced BC risk for women in the 10th percentile of adolescent RPA (HR = 0.95, 95% CI = 0.90–1.00) and an 11% reduced risk in the 90th percentile (HR = 0.89, 95% CI = 0.84–0.95). Conclusions: These findings suggest that adolescent physical activity might reduce breast cancer risk in young women and underscore the importance of maintain or increasing RPA levels across the lifecourse.
Association Between Clinical, Demographic Factors, and Substance Use Among Young Adult Survivors of Childhood Cancer
Authors: Kim Y , Huh J , Miller KA , Ritt-Olson A , Hoyt MA , Milam JE
Published: May 2024

Purpose of the study: Childhood cancer survivors are at risk for late effects related to their cancer treatment, but little is known about clinical, and demographic associated with substance use behaviors. The purpose of this study is to examine the associations between substance use behaviors (tobacco, marijuana, e-cigarette, and alcohol) and cancer-related follow-up care, treatment intensity, late effects, depressive symptoms, self-rated health, race/ethnicity, and neighborhood socioeconomic status (nSES). Methods: Participants were from the Project Forward cohort, a population-based study of young adult survivors of childhood cancer. Participants (N = 1,166, Mage = 25.1 years) were recruited through the Los Angeles Cancer Surveillance Program (Cancer Registry covering Los Angeles County, California). Multivariate path analyses were performed with substance use as the outcome variables and clinical and demographic factors as independent variables. Covariates included current age and sex. Results: Substance use was positively associated with being at risk for clinical depression, and inversely associated with cancer-related follow-up care, female sex, current age, Hispanic ethnicity, treatment intensity, and self-rated health. Neighborhood SES was inversely associated with tobacco use, while being positively associated with binge drinking and e-cigarette use. Conclusions: The results highlight the interrelationship among the clinical and demographic variables and their associations with different substance use. Findings support effective interventions targeting integrative care and health promotion efforts for polysubstance use behavior among CCS. This will help improve long-term outcomes and mitigate the risk for early morbidity.
Cancer-Related Fatigue Is Associated With Objective Measures of Physical Function in Survivors of Cancer
Authors: Marker RJ , Leach HJ
Published: May 2024

Purpose: Cancer-related fatigue (CRF) is a common and limiting symptom reported by survivors of cancer and may have a negative impact on functional activities. The purpose of this study was to investigate the relationships between CRF and objective measures of physical function in survivors. Methods: A retrospective analysis was performed on 428 survivors initiating a clinical exercise oncology program. A physical assessment was performed prior to program start and included a six-minute walk test (6MWT), handgrip strength assessment, and a 10 m walk test to measure both usual and fast gait speed. CRF was measured with the Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-Fatigue), a commonly used 13-item questionnaire, with scores ranging from 0–52. Lower scores indicate greater CRF. Participant demographics, cancer diagnosis, and treatment information were self-reported at program start. Four multiple linear regression analyses were performed, with 6MWT, handgrip strength, usual gait speed, and fast gait speed as the dependent variables. In each model, FACIT-Fatigue was entered as a predictor and covariates were age, gender, cancer diagnosis, and cancer treatment (currently receiving chemotherapy or radiation or not). Results: Participants were on average 55.2 (SD = 14.1) years old, majority women (64%) and breast cancer survivors (30.5%). Approximately half were currently receiving cancer treatment (48%). The means (SD) of measures of physical function were: 6MWT = 582 (120) m; grip strength = 32.7 (10.5) kg; usual gait speed = 1.36 (0.25) m/s; and fast gait speed = 1.9 (0.38) m/s. The mean (SD) FACIT-Fatigue score was 33.7 (10.8). All regression models were significant (P < 0.01). FACIT-Fatigue was significantly associated with 6MWT (Î2 = 3.39, P < 0.01), handgrip strength (Î2 = 0.13, P < 0.01), usual gait speed (Î2 = 0.005, P < 0.01), and fast gait speed (Î2 = 0.009, P < 0.01). Conclusions: Findings demonstrated that higher CRF was significantly associated with reduced performance on objective measures of physical function, providing insight on how CRF may contribute to limitations of functional day-to-day activities. Future studies should investigate whether reductions in CRF mediate the improvements in physical function seen after participation in exercise programs.
Epigenetic Aging Differs By Race, Subtype and Social Vulnerability Index in Breast Cancer Patients
Authors: Wu YN , Thompson CL , Schumacher FR
Published: May 2024

Purpose: Although breast cancer (BrCa) disparities by age of onset, subtype and mortality are well recognized between Black and White women, the underlying causes remain unknown. We were interested in the impact of methylation on racial disparities, BrCa subtypes and social vulnerability index (SVI). Methods: A whole-genome methylation array was used with DNA extracted from blood samples from women diagnosed with BrCa. After quality control, 158 BrCa patients were included. The biological age and epigenetic age acceleration, defined as the residual from regressing chronological and biological age, were computed using Horvath and GrimAge clocks. The association with aging for the independent factors of self-reported race, BrCa molecular subtypes (ER and HER2), and SVI were evaluated with Mann-Whitney tests and linear regression models. Statistical significance was defined as a P value <0.05. Results: Nearly one-third of our sample were self-reported Black women (28.8%) and the overall mean age at diagnosis was 57.8 years ±11.6. The proportion of women diagnosed with ER− and HER2+ BrCa was 43.6% (N = 68) and 14.7% (N = 23), respectively. Overall, the mean age acceleration is estimated as 2.41 years greater for Black women compared to White women by the GrimAge clock (P = 0.005), and 0.87 years for the Horvath clock (P = 0.52). Among ER- BrCa subtypes, Black women had an average biological age of 1.68 years greater than White women (P = 0.24). Similarly, among HER2+ BrCa, the biological age for Black women was 2.62 years older than White women (P = 0.14). In addition, the SVI median stratified analysis identified a 1.24-year increased age difference for Black women compared to White women in the upper SVI. In the lower SVI stratified analysis, the biological age for Black women was 0.67 years younger than White women. Conclusions: Our analysis identified statistically significant epigenetic age acceleration differences between self-reported Black and White BrCa patients. Both stratified analyses by BrCa subtype and SVI yielded biological age differences by self-reported race, however, directional effects differed based on strata. Although our sample size is limited, our stratified analysis revealed novel research directions to better understand racial disparities in BrCa.