bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral delivery of semaglutide and tirzepatide using milk-derived small extracellular vesicles
Authors: Zhang Yuefei , Han Jianyi , Wu Wei , Dang Bobo
Published: December 2024

Therapeutic proteins and peptides have revolutionized modern biomedicine. However, the large size and complex structure of these macromolecules preclude their oral administration, greatly limiting their applications in patient care. Biochemical degradation in the gastrointestinal tract, mucus, and cellular barrier are the major obstacles to oral development. Small extracellular vesicles (sEVs) are natural nano lipid vesicles serving as essential vehicles for intercellular communication. sEVs are resistant to biochemical degradation, permeable to mucus barriers, and can penetrate cellular barriers. sEVs are thus considered the next-generation vehicles with the potential for oral peptide/protein drug delivery. Herein, we report the use of milk-derived sEVs as delivery vehicles to achieve successful and highly efficient oral delivery of two therapeutic GLP-1 receptor agonists, semaglutide and tirzepatide. We showed that semaglutide and tirzepatide can be efficiently loaded onto sEVs in vitro, and oral gavage of semaglutide-loaded sEVs or tirzepatide-loaded sEVs can effectively lower blood glucose levels in db/db mouse models. This study demonstrates that sEVs is a platform technology for oral peptide drug delivery and opens a new avenue for oral peptide/protein therapeutics delivery.
Migrastatic Therapy as a Potential Game-Changer in Adaptive Cancer Treatment
Authors: Schneider Katharina , Spekking Louise , Azimi Sepinoud , Peltanová Barbora , Rösel Daniel , Brown Joel S. , Gatenby Robert A. , Brábek Jan , Staňková Kateřina
Published: December 2024

Adaptive therapy, which anticipates and counters the evolution of resistance in cancer cells, has gained significant traction, especially following the success of the Zhang et al.’s protocol in treating metastatic castrate-resistant prostate cancer. While several adaptive therapies have now advanced to clinical trials, none currently incorporates migrastatics, i.e. treatments designed to inhibit cancer cell metastasis.

In this study, we propose integrating migrastatics into adaptive therapy protocols and evaluate the potential benefits of using a game-theoretic spatial model. Our results demonstrate that combining adaptive therapy with migrastatics effectively delays the onset of metastasis and reduces both the number and size of metastases across most cancer scenarios analyzed. This approach not only extends the time to the first metastasis but also enhances the overall efficacy of adaptive therapies. Our findings suggest a promising new direction for cancer treatment, where adaptive therapy, in combination with migrastatic agents, can target both the evolution of resistance and the metastatic spread of cancer cells.
A Non-Pharmacological, Nociceutical Formulation Lessens Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients
Authors: Servitja Sonia , Castro-Henriques Maria , Álvarez-Busto Iñaki , Díez-Franco Carlota , Medina-Castillo Alba , Algarra-García Maria Asunción , López-Miranda Elena , Lario-Martínez Margaret , Luengo-Alcázar Maria Isabel , Borregón Miguel , Davó Ana , Gassull-Delgado Anna , Roque-García Sara , Gonzaga-López Ana , Poveda-Ferriols Jesus Manuel , Pascal Severine , Ferrándiz-Huertas Clotilde , Mitroi-Marinescu Ana María , García-Escolano Marta , Fernández-Carvajal Asia , Ferrer-Montiel Antonio
Published: December 2024

Purpose

Up to 80% of patients undergoing taxanes or platinum-based chemotherapy (CT) develop a disturbing peripheral polyneuropathy referred to as CIPN, that affects their treatment compliance to CT and long-term quality of life (QoL). Cumulative evidence shows that taxanes and platinum agents sensitize epidermal nociceptive terminals by potentiating the activity of nociceptor thermosensitive channels. Our aim was to evaluate the efficacy and safety of a non-pharmacological nociceutical formulation acting on epidermal nociceptive endings preventing, delaying and/or lessening CIPN sensory symptoms during CT.

Methods

We designed a proof-of-concept, double-blind, randomized, two-arms multicenter clinical study (NCT06733545). Participants started a daily topical application of the assigned formulation in hands (moisturizing or nociceutical). Upon appearance of neuropathic symptoms in hands and/or feet, they applied the creams twice daily in hands and feet. Diagnosis and follow up of CIPN grade and adverse effects were conducted by study investigators, as well as a QoL questionnaire.

Results

A cohort of 142 patients treated with taxanes and/or platinum agents were randomly assigned to the two groups. Withdrawals were similar in both arms (9 and 14), leading to a balanced number of patients per group (61 moisturizing vs 58 nociceutical). Overall, a similar number of participants developed a peripheral neuropathy in both arms (73% moisturizing vs 67% nociceutical, p=0.1). A lower CIPN incidence in hands was observed in the nociceutical arm (32% vs 13%, p=0.03). Furthermore, the nociceutical formulation delayed the appearance of neuropathic symptoms as compared to the moisturizing cream (6 vs 8 cycle, p=0.009). The Leonard scale questionnaire revealed that the nociceutical formulation attenuated the severity of patients’ neuropathic symptoms from extremely to hardly any (58% vs. 35%, p<0.0017), increasing patient QoL.

Conclusion

This pilot study suggests that topical protection of nociceptive epidermal terminals with a topical nociceutical formulation reduced the incidence of CIPN in hands, delayed its onset and increased the QoL of patients. These findings provide solid evidence for a larger, confirmatory clinical study.
Influences on rural HPV vaccine hesitancy: A multi-level mixed methods study
Authors: Gorin Sherri Sheinfeld , Klugas Arturas , Stack Matthew , Chuisano Samantha , Knoll Hannah , Jamison Cornelius D. , McGrady Angela , Chen Dongru , Hyman Rebecca , DeJonckheere Melissa
Published: December 2024

Human Papillomavirus (HPV) is the most common sexually transmitted infection and the leading cause of cervical and oropharyngeal cancers. Vaccination can prevent over 90% of HPV- attributed cancers among those aged 9-26. Rural populations are less likely to receive the complete HPV protocol than urban. The purpose of this convergent mixed methods study was to explore in depth the perspectives that influence hesitancy for HPV vaccination among rural youth, caregivers, and primary care providers in rural Michigan. A mixed methods analysis was conducted to integrate quantitative (cross-sectional PCP survey) and qualitative data (youth, parent focus groups) in a joint display table. Youths and parents reported limited unbiased HPV vaccine information; yet, all responding physicians reported educating their patients about the HPV vaccine. Inductive descriptive analyses revealed that youth wanted a greater role in decision-making about the HPV vaccine, while parents were the PCPs primary focus.

Integrative analyses of both qualitative and quantitative data identified parental out-of-pocket costs as significant predictors of lower HPV vaccine uptake. Clinic structural supports were significantly associated with higher HPV vaccine uptake. Adapting evidence-based dissemination approaches to rural primary care physicians could decrease HPV vaccine hesitancy. Youths could be engaged as HPV vaccine champions. Accessing community resources could increase access.
Exploring Digital Health Solutions: Personalised Medicine and N-of-1 Trials in Ghana: A Scoping Review
Authors: Sackey Godsway , Owoyele Babajide , Baiden Frank , Konigorski Stefan
Published: December 2024

Background

Digital health solutions and personalised medicine are rapidly evolving fields that offer significant potential for enhancing healthcare delivery, particularly in low-resource settings. N-of-1 trials, a personalised experimental approach, hold particular promise for individualised patient care and empowerment. This scoping review aims to explore the current landscape of these innovations in the context of Ghana.

Objectives

This review seeks to map existing literature on digital health solutions, personalised medicine, and N-of-1 trials in Ghana. It also aims to identify key themes, trends, and gaps in the literature while discussing the current role and potential of N-of-1 trials in this context as an important knowledge base for future exploration of personalised medicine and digital N-of-1 trials in low resource settings like Ghana.

Methods

A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar; from year 2000 to April 2024, to identify relevant studies. Inclusion criteria were studies focusing on digital health, personalised medicine, and N-of-1 trials within Ghana or similar low-resource settings. Data were extracted and analysed to identify common themes, trends, and gaps in the existing literature.

Results

The scoping review included 40 publications, that is, only very few studies have been published in this field that fit our objectives. The studies revealed a predominant focus on digital health solutions in Ghana, particularly mobile health (mHealth) interventions, which account for 60% of the interventions reviewed. These solutions include mobile applications for clinical decision support, patient monitoring, and health education, and have been effective in enhancing healthcare delivery, especially in remote and underserved areas. Introducing electronic health records (EHRs) represent 24% of the interventions and have shown promise in improving data management and patient care coordination. However, challenges such as poor network infrastructure and resistance to change need to be addressed. Personalised medicine, though less represented in the reviewed literature (7.5%), shows promise in providing tailored treatments based on individual genetic profiles. The review did not identify any studies specifically focused on N-of-1 trials, highlighting the innovative potential for future research in this area.

Conclusion

The findings underscore the need for robust digital infrastructure, training for healthcare providers, and policy frameworks to support the adoption of digital health solutions, personalised medicine, and N-of-1 trials in Ghana. Addressing these gaps requires concerted efforts to enhance digital infrastructure, provider education, and supportive policies. N-of-1 trials offer substantial potential for personalised care but necessitate further exploration and integration into the healthcare system.
One-Year Outcomes in Acute Strokes with Hyperglycemia in Low Resource Settings (SHAPE): A Prospective Cohort Study Protocol
Authors: Rajbhandari Bibek , Shakya Yogendra Man , Maharjan Ramesh Kumar , Malla Dipak , Thapa Paras , Regmi Prakash , Shrestha Bikal , Shahi Sumit
Published: December 2024

Background

Stroke is a significant global health issue, serving as a leading cause of death and disability. The burden of this condition is especially severe in low- and middle-income countries, where the majority of stroke-related fatalities occur. Hyperglycemia, a common metabolic disturbance observed in acute stroke patients, is known to worsen clinical outcomes, contributing to higher rates of mortality and morbidity. This study aims to investigate the relationship between hyperglycemia, morbidity and mortality outcomes in patients with acute stroke, assessing how varying glycemic levels influence short-term (1 month), mid-term (3 months), and long-term (1 year) mortality rates.

Methods

The SHAPE study is a prospective cohort study conducted at the Emergency Department of Tribhuvan University Teaching Hospital (TUTH). The study will enroll adults aged over 40 who present with BEFAST-positive symptoms of acute stroke, confirmed through CT/MRI imaging. Participants will be classified into two groups: those exhibiting hyperglycemia (exposed group) and those with normal glycemic levels (unexposed group). Sixty participants will be recruited (30 hyperglycemic and 30 normoglycemic) and followed for one year to assess mortality and functional outcomes using the modified Rankin Scale (mRS). Data collection will involve regular follow-ups through phone calls, clinic visits, and home visits at 1, 3, and 12 months post-stroke. The analysis will include bivariate comparisons for categorical and continuous variables, logistic regression to identify independent predictors of mortality and functional outcomes, and Kaplan-Meier analysis for assessing survival rates.

Ethical Considerations

The SHAPE Study was approved by the Ethics Review Committee of the Institute of Medicine (Ref no.. 6-11E2), and written informed consent will be obtained from all participants. Results will be disseminated via a peer-reviewed journal.

Trial registration number

ClinicalTrials.gov IDNCT06560983
Primary sensory neuron dysfunction underlying mechanical itch hypersensitivity in a Shank3 mouse model of autism
Authors: Huzard Damien , Marias Mélanie , Granat Chloé , Oliva Giulia , Soubeyre Vanessa , Grellier Gawain , Negm Ahmed , Devaux Jérôme , Bourinet Emmanuel , François Amaury
Published: December 2024

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by social deficits, repetitive behaviors, and atypical sensory perception. The link between ASD and skin abnormalities, inducing itchiness, has never been investigated in depth. This study explores mechanical itch sensitivity in the Shank3ΔC/ΔCmouse model. Key observations include heightened scratching in response to skin deformation and hypersensitivity to mechanical itch (i.e. alloknesis) in Shank3ΔC/ΔCmice. In Shank3ΔC/ΔCmice,ex vivoelectrophysiological experiments revealed that C-fiber low-threshold mechanoreceptors (C-LTMRs) were hyporesponsive, and transcriptomic analysis showed a downregulation of TAFA4, a protein secreted by C-LMTRs. Interestingly, pharmacologically inhibiting Aβ-LTMR, important in mechanical itch initiation, abolished the itch hypersensitivity. Also, TAFA4 injections reduced the spontaneous scratching response to skin deformation but failed to restore itch sensitivity. Our data suggest that somatosensory deficits in Shank3ΔC/ΔCmice lead to hypersensitivity to itchiness and indicate that two pathways might regulate mechanical itchiness, dependent on TAFA4.
Proteome Analysis of Soybean Root Apoplast Combined with AlphaFold Prediction RevealMacrophomina phaseolinaInfection Strategies and Potential Targets for Engineering Resistance
Authors: Veeraganti Naveen Prakash Chetan , Sivaramakrishnan Muthusaravanan , Goel Sakshi , Porwal Vasudha , Amrate Pawan Kumar , Shrivastava Manoj Kumar , Chandrasekar Balakumaran
Published: December 2024

Macrophomina phaseolina(Tassi) Goid. is a hemibiotrophic pathogen that causes charcoal rot (CR) disease in various legumes, including soybean. To date, no reliable resistance gene sources have been identified in soybean or other legumes to combatM. phaseolina. Therefore, the identification of mechanistic targets is crucial for improving resistance against the pathogen. The apoplast is a critical region where intense molecular cross-talk occurs between plants and pathogens, and the outcome of their interactions is determined in this compartment. Here, we employed label-free quantitative (LFQ) proteomics to investigate the dynamics of soybean root apoplast duringM. phaseolinainfection. We have detected several secreted proteins ofM. phaseolinaand differential regulation of soybean-secreted proteins in root apoplast during infections. Glycome analysis and callose deposition assays have revealed changes in soybean root cell wall compositions and potential polysaccharide targets ofM. phaseolina. AlphaFold 2 (AF2) analysis was instrumental in revealing several interesting sequence-unrelated structurally similar (SUSS) effectors and effectors with novel structural folds secreted byM. phaseolina. Structured-guided engineering of protease-inhibitor complexes is emerging as an important strategy to engineer resistance in plants against pathogens. AlphaFold Multimer (AFM) analysis of candidate-secreted proteins from soybean andM. phaseolinahas predicted cysteine and serine protease-inhibitor complexes with high confidence. We have validated these interactions using molecular dynamics (MD) and competitive activity-based protein profiling (ABPP) approaches. Therefore, our work provides insights into Soybean-M. phaseolinainteractions in the root apoplast and unveil potential candidates for engineering resistance.
Catestatin improves heart metabolic flexibility by promoting mitochondrial structure and function
Authors: Chirasani Venkat R. , Kal Satadeepa , Biswas Nilima , Mahata Sumana , Tang Kechun , Pasqua Teresa , Avolio Ennio , Jati Suborno , Bandyopadhyay Gautam , Head Brian P. , Patel Hemal H. , van den Bogaart Geert , Sahoo Debashis , Senapati Sanjib , Mahata Sushil K.
Published: December 2024

Hypertension, a major cause of cardiomyopathy, is one of the most critical risk factors for heart failure and mortality worldwide. Loss of metabolic flexibility of cardiomyocytes is one of the major causes of heart failure. Although Catestatin (CST) treatment is known to be both hypotensive and cardioprotective, its effect on cardiac metabolism is unknown. In this study, we undertook a transcriptomic approach to identify differentially expressed genes that were filtered using Boolean implication relationships to develop a model of gene regulation in saline or CST-supplemented CST knockout (CST-KO) mice. The analysis revealed a set of gene signatures (fibroblast, cardiomyocyte, and macrophage) rescued after CST supplemented CST-KO mice compared to wild-type. Furthermore, we independently validated these gene signature models using publicly available patient datasets. Since the gene signature includes genes related to glucose, fatty acid metabolism, and mitochondrial function, we assessed the glucose and fatty acid uptake after CST treatment. We found that CST treatment can restore the cardiac metabolic inflexibility in CST-KO heart due to the metabolic shift of glucose utilization to fatty acid as energy source. Binding studies after immunoprecipitation and mass spectrometry revealed CST binding with ATP synthase, supported by molecular simulation and computational modeling that predicted CST binding to α/β subunit of ATP synthase. Colocalization of CST with mitochondria and increased mitochondrial membrane potential and ATP production upon CST treatment in neonatal cardiomyocytes further exhibit CST as a key regulator of cardiac metabolism and mitochondrial function.
Protists as mediators of complex microbial and viral associations
Authors: Schulz Frederik , Yan Ying , Weiner Agnes K.M. , Ahsan Ragib , Katz Laura A. , Woyke Tanja
Published: December 2024

Microbial eukaryotes (aka protists) are known for their important roles in nutrient cycling across different ecosystems. However, the composition and function of protist-associated microbiomes remains largely elusive. Here, we employ cultivation-independent single-cell isolation and genome-resolved metagenomics to provide detailed insights into underexplored microbiomes and viromes of over 100 currently uncultivable ciliates and amoebae isolated from diverse environments. Our findings reveal unique microbiome compositions and hint at an intricate network of complex interactions and associations with bacterial symbionts and viruses. We observed stark differences between ciliates and amoebae in terms of microbiome and virome compositions, highlighting the specificity of protist-microbe interactions. Over 115 of the recovered microbial genomes were affiliated with known endosymbionts of eukaryotes, including diverse members of the Holosporales, Rickettsiales, Legionellales, Chlamydiae, Dependentiae, and more than 250 were affiliated with possible host-associated bacteria of the phylum Patescibacteria. We also identified more than 80 giant viruses belonging to diverse viral lineages, of which some were actively expressing genes in single cell transcriptomes, suggesting a possible association with the sampled protists. We also revealed a wide range of other viruses that were predicted to infect eukaryotes or host-associated bacteria. Our results provide further evidence that protists serve as mediators of complex microbial and viral associations, playing a critical role in ecological networks. The frequent co-occurrence of giant viruses and diverse microbial symbionts in our samples suggests multipartite associations, particularly among amoebae. Our study provides a preliminary assessment of the microbial diversity associated with lesser-known protist lineages and paves the way for a deeper understanding of protist ecology and their roles in environmental and human health.
Errors-in-variables and validation problems in reaction norm predictions for wild populations
Authors: Ergon Rolf
Published: December 2024

Studies of phenotypic responses in wild populations are often based on reaction norm models where the environmental drivers in many cases are related to climate change. Such input signals will never be exactly known, and there will always be measurement errors also in the recorded responses. In parameter estimation these errors give rise to errors-in-variables problems, especially in form of overfitting caused by errors in the input measurements. A second important feature of such phenotypic response problems is that the environmental inputs must be given appropriate but largely unknown reference values. A third problem is that it is difficult to find good validation methods for predicted responses. Essential aspects of these problems are here studied by use of a reaction norm model in its simplest univariate form, characterized by a mean intercept value and a mean plasticity slope value, and the overall conclusion is that validated disentanglement of plasticity and genetic adaptation based on realistically short data for wild populations is a difficult task. In a proposed validation method, the available input-output data is split into one part for modeling and one part for validation, and the feasibility of this approach is studied in simulations with use of a prediction error method, which is essentially a maximum likelihood method. It is also argued that validation of a chosen or estimated reference environment in practice is impossible when the data comes from the (unintended) anthropogenic global warming experiment, where no independent experimental data exists. When the evolution is slow because of small genetic variances, overlapping generations and long lifetimes, or because of near optimal adaptive plasticity, the best quantitative genetics option may be to assume a constant plasticity slope value, equal to the initial value. It turns out to be easy to estimate this value, but that should be done without setting other unknown parameter values to zero. This option is appealing also because it removes the dependence of a guessed or estimated reference environment.
Direct RNA Oxford Nanopore sequencing distinguishes between modifications in tRNA at the U34position
Authors: Kusmirek W. , Strozynska N. , Martin-Arroyo Cerpa P. , Dziergowska A , Leszczynska G. , Nowak R. , Adamczyk M.
Published: December 2024

The measurement of tRNA modifications with single transcript resolution has been feasible for only a few modifications due to the lack of available methods. This limitation does not allow to advance basic research studies on the dynamic nature of tRNA modification and its cellular function in time and space, neither to develop modern diagnostic tools for several already known tRNA-dependent human diseases. Nanopore is a well-established sequencing method that has proven to be efficient for the study of RNA. The analysis of tRNA modifications by Nanopore is still under development. We have investigated the efficacy of nanopore technology to discriminate between complex modifications of uridine 34 in tRNA, which affect the base-calling properties of neighbouring bases and are therefore difficult to accurately predict. We have developed new methods to chemically and enzymatically synthesise single modified tRNA molecules with modifications at the anticodon loop. Nanopore technology captures the features produced by uridine with and without a thiol group when present on synthetic tRNA molecules. Thus, Oxford Nanopore Technology (ONT) has great potential for developing strategies to accurately identify the modification status of the tRNA anticodon loop (ACL), which encompasses the most complex modifications on uridine-containing RNA motifs.

Abstract Figure
MicroRNA profiling identifies novel regulators of stem cell function in the adultDrosophilaintestine
Authors: Sreejith Perinthottathil , Yon Joshuah , Lapenta Kalina , Biteau Benoit
Published: December 2024

Precise control of stem cell activity is critical to maintain homeostasis and regenerative capacity of adult tissues and limit proliferative syndromes. Hence, stem cell-specific complex regulatory networks exist to exquisitely maintain gene expression and adapt it to tissue demand, controlling self-renewal, fate commitment and differentiation of developing and adults cell lineages. One of the essential and conserved regulatory components that fine-tune gene expression are microRNAs, which post-transcriptionally regulate stability and translation of messengers. microRNAs have been identified as critical stem cell regulators across stem cell populations and organisms. Here, we report the profiling of microRNAs expressed in stem cells and their immediate daughter cells in theDrosophilaadult intestine. Our analysis identifies over 60 miRs that can be reliably detected in these sorted progenitor cells; a few of these have been reported to control fly intestinal stem cells, but most have yet to be investigated in the adult intestinal lineage. To validate the relevance of our unbiased analysis, we chose to characterize the phenotypes associated with genetic manipulations of two of these microRNAs, miR-31a and miR-34, which are conserved in other organisms, but whose function has not been investigated in the Drosophila midgut. We found that miR-31a acts as anti-proliferation factor and is important for the re-entry of ISC into quiescence after tissue damage. Additionally, we demonstrate that miR-34 is essential for ISC proliferation, but its over-expression also prevents proliferation, highlighting the complexity of miR-mediated control of stem cell function. Altogether, our work establishes a new critical resource to investigate the detailed mechanisms that control stem cell proliferation and intestinal differentiation under homeostatic conditions, in response to tissue damage, or during epithelial transformation and aging.
Plasmodium falciparumexpresses fewervargenes at lower levels during asymptomatic dry season infections than clinical malaria cases
Authors: Ceesay Sukai , Kampmann Martin , Votborg-Novél Lasse , Hansson Helle Smedegaard , Jensen Rasmus Weisel , Carrasquilla Manuela , Cisse Hamidou , Turner Louise , Dabbas Usama , Ntalla Christina , Bandermann Silke , Doumbo Safiatou , Doumtabe Didier , Ongoiba Aissata , Kayentao Kassoum , Traore Boubacar , Crompton Peter D , Lavstsen Thomas , Portugal Silvia
Published: December 2024

In seasonal transmission areas, clinical malaria occurs during the wet season when mosquitoes are present, while in the dry season, malaria transmission is interrupted and clinical cases are rare. In Mali,Plasmodium falciparumcan persist in low parasitaemic asymptomatic individuals through the six-month dry season and shows reduced cytoadhesion of infected erythrocytes, evidenced by the circulation of further developed parasite stages compared to clinical malaria cases. How prolonged circulation of infected erythrocytes is achieved remains unknown. Here, we exploredvargene expression in subclinical infections and clinical malaria cases of Malian children, collected during the dry and wet seasons. We sequenced expressedvarDBLα-tags, used bioinformatic tools to predict their domain composition, binding phenotype and upstream sequence type; and determined their relationship to seasonality and clinical presentation. We found that parasites of asymptomatic infections expressed fewervargenes, with a larger proportion ofvartranscripts attributed to one or a fewvars. In contrast, clinical cases exhibited expression of manyvargenes at lower proportions. We found that parasites of asymptomatic carriers expressed a mixture of CD36- and EPCR-binding PfEMP1, which changed over time. We confirmed thatvarsencoding CD36-binding PfEMP1 dominated in non-severe malaria cases, and found no significant difference in expressedvartypes between dry and wet seasons. Asymptomatic carriers were older, had higher titers of anti-P. falciparumantibodies, and broader reactivity to PfEMP1, suggesting that host immunity was the main determinant limitingvartranscript variation in asymptomatic carriers. However, by RNAseq and qRT-PCR we also observed significantly higher totalvartranscript levels in malaria cases compared to asymptomatic carriers, suggesting that in addition to the parasite’s switching and the host’s immune selection of expressedvargenes, parasites able to sustain long-term infections may be poised for reduced PfEMP1 expression.
Shedding light on dark sectors with high-energy muons at the NA64 experiment at the CERN SPS
Authors: Andreev Yu. M. , Banerjee D. , Oberhauser B. Banto , Bernhard J. , Bisio P. , Charitonidis N. , Crivelli P. , Depero E. , Dermenev A. V. , Donskov S. V. , Dusaev R. R. , Enik T. , Frolov V. N. , Gardikiotis A. , Gertsenberger S. V. , Girod S. , Gninenko S. N. , Hösgen M. , Joosten R. , Kachanov V. A. , Kambar Y. , Karneyeu A. E. , Kasianova E. A. , Kekelidze G. , Ketzer B. , Kirpichnikov D. V. , Kirsanov M. M. , Kolosov V. N. , Kramarenko V. A. , Kravchuk L. V. , Krasnikov N. V. , Kuleshov S. V. , Lyubovitskij V. E. , Lysan V. , Matveev V. A. , Fredes R. Mena , Yanssen R. G. Mena , Bueno L. Molina , Mongillo M. , Peshekhonov D. V. , Polyakov V. A. , Radics B. , Salamatin K. M. , Samoylenko V. D. , Shchukin D. A. , Soto O. , Sieber H. , Tikhomirov V. O. , Tlisova I. V. , Toropin A. N. , Tuzi M. , Veit B. M. , Volkov P. V. , Volkov V. Yu. , Voronchikhin I. V. , Zamora-Saá J. , Zhevlakov A. S. ,   NA64 Collaboration
Published: December 2024

A search for dark sectors is performed using the unique M2 beam line at the CERN Super Proton Synchrotron. New particles (X) could be produced in the bremsstrahlung-like reaction of high-energy 160 GeV positively charged muons impinging on an active target, μN→μNX, followed by their decays, X→invisible. The experimental signature would be a scattered single muon from the target, with about less than half of its initial energy and no activity in the subdetectors located downstream from the interaction point. The full sample of the 2022 run is analyzed through the missing-energy/momentum channel, with total statistics of (1.98±0.02)×1010 muons on target. We demonstrate that various muonphilic scenarios involving different types of mediators, such as scalar or vector particles, can be probed simultaneously with such a technique. For the vector case, besides a Lμ−Lτ Z′ vector boson, we also consider an invisibly decaying dark photon (A′→invisible). This search is complementary to NA64 running with electrons and positrons, thus opening the possibility to expand the exploration of the thermal light dark matter parameter space by combining the results obtained with the three beams.

Published by the American Physical Society
2024
Higgs boson production at
μ+μ+
colliders
Authors: Hamada Yu , Kitano Ryuichiro , Matsudo Ryutaro , Okawa Shohei , Takai Ryoto , Takaura Hiromasa , Treuer Lukas
Published: December 2024

We study Higgs boson production at μ+μ+ colliders at high energy. Since both initial-state particles are positively charged, there is no W boson fusion at the leading order, as it requires a W+W− pair. However, we find that the cross section of the higher-order, γ-and Z-mediated W boson fusion process is large at high center-of-mass energies s, growing as (logs)3. This is in contrast to the logs behavior of the leading-order W boson fusion. Thus, even though it is a higher-order process, the rate of Higgs boson production for 10 TeV energies at μ+μ+ colliders with polarized beams can be as high as about half of the one at μ+μ− colliders, assuming the same integrated luminosity. To calculate the cross section of this process accurately, we carefully treat the collinear emission of the photon in the intermediate state. The thereby obtained large cross section furthermore shows the significance of Higgs production with an extra W boson in the final state also at μ+μ− and e+e− colliders.

Published by the American Physical Society
2024
Azimuthal angular correlation of
J/ψ
plus jet production at the electron-ion collider
Authors: Maxia Luca , Yuan Feng
Published: December 2024

By investigating the soft gluon radiation in the J/ψ plus jet photoproduction at the electron-ion collider (EIC), we demonstrate that the azimuthal angular correlations between the leading jet and heavy quarkonium provide a unique probe to the production mechanism of the latter. In particular, a significant cos(ϕ) asymmetry is found for the color-singlet channel, whereas it vanishes or has an opposite sign for color-octet production, depending on the jet transverse momentum. Numerical results of cos(ϕ) and cos(2ϕ) asymmetries employing both the color-singlet model and the nonrelativistic QCD approach are presented for typical kinematics at the future EIC.

Published by the American Physical Society
2024
Spin-independent interactions of Dirac fermionic dark matter in the composite Higgs models
Authors: Belyakova M. G. , Nevzorov R.
Published: December 2024

According to recent measurements, the dark matter magnetic dipole moment is strongly constrained. In the composite Higgs models the magnetic dipole moment of the Dirac dark matter fermion and its mass can be suppressed by the approximate U(1) symmetry. We consider the E6 inspired composite Higgs model (E6CHM) with U(1) symmetry violating operators, which give rise to dark matter’s mass and coupling constant to Higgs boson. The dependence of the spin-independent dark matter-nucleon scattering cross section on the E6CHM parameters is explored. We argue that there are regions of the parameter space which are still safe from all current constraints and may lead to spectacular LHC signatures.

Published by the American Physical Society
2024
New insights into the analytic structure of correlation functions via kinetic theory
Authors: Brants Robbe
Published: December 2024

The way a relativistic system approaches fluid dynamical behavior can be understood physically through the signals that will contribute to its linear response to perturbations. What these signals are is captured in the analytic structure of the retarded correlation function. The nonanalyticities can be grouped into three types based on their dimension in the complex frequency plane. In this paper, we will use kinetic theory in the (momentum-dependent) relaxation time approximation to find how we can calculate their corresponding signals. In the most general case of a system with particles that have a continuum of thermalization rates, we find that a nonanalytic region appears. To calculate its signal, we introduce the “nonanalytic area density” that describes the properties of this region, and we construct a method to calculate it. Further, to take into account the ambiguity present in signal analysis, following from manipulations of the nonanalyticities, we will identify two specific choices called “pictures” with interesting analytic properties and compare in what scenarios each picture is most useful.

Published by the American Physical Society
2024
Probing
|Vcs|
and lepton flavor universality through
D→K0*(1430)ℓνℓ
decays
Authors: Yang Yin-Long , Tian Hai-Jiang , Wang Ya-Xiong , Fu Hai-Bing , Zhong Tao , Wang Sheng-Quan , Huang Dong
Published: December 2024

In this paper, we calculate the semileptonic decays D→K0*(1430)ℓνℓ with ℓ=(e,μ) induced by c→sℓνℓ transition. For the key component, D→K0*(1430) transition form factors (TFFs) f±(q2) are calculated within the framework of QCD light cone sum rule. Then, we consider two scenarios for K0*(1430)-meson twist-2 distribution amplitude. For the scenario 1 (S1), we take the truncated form based on Gegenbauer polynomial series. Meanwhile, we also consider the scenario 2 (S2) constructed by light cone harmonic oscillator model, where the model parameters are fixed by the K0*(1430)-meson twist-2 distribution amplitude tenth-order ξ moments calculated by using the background field theory. For the TFFs at a large recoil point, we have f+(S1)(0)=0.597−0.121+0.122 and f−(S1)(0)=−0.136−0.035+0.023, f+(S2)(0)=0.663−0.134+0.135, and f−(S2)(0)=−0.202−0.046+0.026. After extrapolating TFFs to the whole physical q2 region, we calculate the branching fractions of D0→K0*+(1430)ℓ−ν¯ℓ and D+→K0*0(1430)ℓ+νℓ, which at 10−4-order level for the S1 and S2 cases. Meanwhile, we predict the CKM matrix |Vcs|(S1)=0.973−0.183+0.259, |Vcs|(S2)=0.880−0.165+0.234, and lepton flavor universality RK0*(S1)=0.768−0.368+0.560, RK0*(S2)=0.764−0.365+0.555. Finally, we discuss the angular observables of forward-backward asymmetries, lepton polarization asymmetries, and q2-differential flat terms for this decay.

Published by the American Physical Society
2024
Unveiling van Hove singularity modulation and fluctuated charge order in kagome superconductor
CsV3Sb5
via time-resolved ARPES
Authors: Zhong Yigui , Suzuki Takeshi , Liu Hongxiong , Liu Kecheng , Nie Zhengwei , Shi Youguo , Meng Sheng , Lv Baiqing , Ding Hong , Kanai Teruto , Itatani Jiro , Shin Shik , Okazaki Kozo
Published: December 2024

Kagome superconductor CsV3Sb5, which exhibits intertwined unconventional charge-density wave (CDW) and superconductivity, has garnered significant attention recently. Despite extensive static studies, the nature of these exotic electronic orders remains elusive. In this study, we investigate the nonequilibrium electronic structure of CsV3Sb5 via time- and angle-resolved photoemission spectroscopy (ARPES). Our results reveal that upon laser excitation, the van Hove singularities immediately shift towards the Fermi level and subsequently oscillate in sync with a 1.3-THz coherent phonon mode. By analyzing the coherent intensity oscillations in the energy-momentum (-k) map, we find that this coherent phonon is strongly coupled with electronic bands from both Sb and V orbitals. While typically observable only in the CDW state, remarkably, we find that the 1.3-THz coherent phonon mode can be persistently excited at temperatures above TCDW, suggesting the potential existence of fluctuated CDW in CsV3Sb5. These findings enhance our understanding of the unconventional CDW in CsV3Sb5 and provide insights into the ultrafast control of kagome superconductivity.

Published by the American Physical Society
2024
Cross-national benchmarking and acceptance of pandemic mitigation policies: human value approach
Authors: Mandal Purnendu , Bagchi Kallol , Udo Godwin
Published: December 2024

Purpose

This study analyzes the reasons for satisfaction or dissatisfaction among people with public health mitigation policies, particularly with focus on human values. Recent studies reveal that the citizenry of various nations reacted to government policy measures differently when asked if they are satisfied with government handling of COVID-19. Human values such as openness-to-change and conservation might influence the acceptance of pandemic mitigation measures.

Design/methodology/approach

A structural equation model (SEM) is proposed, which incorporates mitigation strategies and human value variables. National health survey data of the COVID-19 pandemic in Great Britain and Italy is used to test several hypotheses.

Findings

The model analysis suggests that prioritizing public health, monitoring and tracking people, border closures and restricting people’s movement played important roles in the satisfaction of government handling of the COVID-19 pandemic. Individuals with a high conservation value are more likely to have a higher probability of dissatisfaction with the government’s handling of COVID-19 pandemic. During a pandemic, the citizens are more willing to trade a good economy for public health. They are also more willing to sacrifice privacy in the government’s efforts to track the spread.

Originality/value

This is a unique study which combines human value variables and mitigation policies in determining acceptance of government policies among citizenry during national health crisis. A SEM modeling framework is presented to analyze empirically several hypotheses.
BiGRU-CNN-AT: classifiying emotion on social media
Authors: Amriza Rona Nisa Sofia , Ngafidin Khairun Nisa Meiah
Published: December 2024

Purpose

This research aims to develop a robust deep-learning approach for classifying emotion in social media.

Design/methodology/approach

This study integrates three deep learning techniques: Bidirectional Gated Recurrent Units (BiGRU), convolutional neural networks (CNN) and an attention mechanism, resulting in the Bidirectional Gated Recurrent Units Convolution Attention (BiGRU-CNN-AT) model. The BiGRU captures potential semantic features, the CNN extracts local features and the attention mechanism identifies keywords critical for classification.

Findings

The BiGRU-CNN-AT model outperformed several state-of-the-art emotion classification algorithms. The model was compared against various baselines across multiple emotion datasets, with deep learning methods consistently surpassing traditional approaches. BiGRU and Bi-LSTM networks demonstrated superior performance, particularly when combined with attention mechanisms. Additionally, analysis of execution times indicated that the BiGRU model processed data more efficiently. They were configuring hyperparameters and integrating GloVe word embeddings, which significantly enhanced model performance, with the adam optimizer proving effective for optimization.

Originality/value

This paper contributes to the development of a novel framework, BiGRU-CNN-AT, which integrates bidirectional GRU, CNN and attention mechanisms for text-based emotion classification. By leveraging the strengths of each component, this framework significantly enhances accuracy in emotion classification tasks. Furthermore, the study offers comprehensive experimental analyses across multiple emotion datasets.
Microstructure and high temperature tribological properties of arc ion plated CrN and CrAlN coatings on AISI H13 steel
Authors: Zhang Long , Zhang Kaiwei , Kong Dejun
Published: December 2024

Purpose

The purpose of this study to investigate the high temperature tribological performances of CrN and CrAlN coatings on AISI H13 steel, which was beneficial to improve the wear resistance of hot work molds.

Design/methodology/approach

Arc ion plating was used to deposit the CrN and CrAlN coatings on AISI H13 steel, and the tribological performances of CrN and CrAlN coatings were evaluated using a ball-on-plate wear tester.

Findings

The average coefficients of friction and wear rate of CrAlN coating in the normal wear period are 0.33 and 5.34 × 10–9 mm3·N–1·mm–1, respectively, which are lower than those of CrN coating, exhibiting that the outstanding friction reduction. The formations of Cr and Al oxides during the wear process are the main factor in enhancing the tribological performance of CrAlN coating.

Originality/value

CrN and CrAlN coatings were applied for hot work molds, and their tribological performances were comparatively investigated.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-09-2024-0359/
Historic core of Sarajevo in the frame of Historic Urban Landscape (HUL) approach – review of the effects on the ground
Authors: Kudumovic Lana
Published: December 2024

Purpose

Recognisable urban fabric of Sarajevo was developed over different periods throughout history. The historic core called Bascarsija (Bašcaršija) was designated as protected area by the Regulatory plan in 1975. Establishing boundaries for the protection of the historic area triggered attitude, which expanded to embrace other architectural ensembles too and, with the decision’s final passage, even a wider area. Sarajevo is proclaimed as Historic Urban Landscape (HUL) in 2020 by the Decision of the Commission to preserve National Monuments of Bosnia and Herzegovina. This paper aims to evaluate effects of HUL approach applied on the case of Sarajevo, which is mostly limited to the new adjustments made to the governing of the protected areas.

Design/methodology/approach

Referring to the HUL Recommendation, the content of the current decision as well as its practical implications and the extent of stakeholder engagement was evaluated, and the summary of practical results, if any, three years (since 2020) after the adaptation.

Findings

HUL approach applied on case of Sarajevo is currently reflected only as a Decision with limited practical effects. This paper, therefore, defined the missing tools. Also, it was possible to distinguish positive and negative effects, and limitations of the applied HUL approach reflected in practice.

Originality/value

According to the international legislation, HUL is understood to be a comprehensive approach that covers a greater area in order to improve urban living sustainably and encourage the preservation of historic assets. Learning from the case of Sarajevo, from its consequences on the ground and limitations for successful application, this paper contributes to the understanding of the HUL approach.
Evaluation of amla and tomato pomace for polyphenol bioaccessibility and prebiotic effects by in vitro digestion and fermentation
Authors: Mall Urvashi P. , Patel V. H.
Published: December 2024

Purpose

This paper aims to determine the impact of in vitro gastrointestinal digestion (IVD) on the bioaccessibility of phenolic compounds derived from tomato pomace flour (TPF) and amla pomace flour (APF), and to evaluate their potential health benefits as prebiotics on gut microbiota.

Design/methodology/approach

The nutritional and functional properties and the bioaccessibility of phenolic compounds obtained from APF and TPF were measured using IVD model and the potential prebiotic effects were assessed during in vitro fermentation.

Findings

APF and TPF contained significant amounts of total dietary fibre (55.83% and 48.29%, respectively) and protein (2.1% and 14.37%, respectively). After IVD, a considerable amount of polyphenols from APF and TPF were released. In the intestinal phase, APF and TPF showed significant (p = 0.05) release of total phenolics (81% and 57%, respectively) and flavonoids (84% and 76%, respectively). Additionally, in comparison to the control samples, IVD increased antioxidant capacity. The proliferation of bacteria (L. acidophilus) and the production of short-chain fatty acids (SCFAs), including propionate and butyrate, were both increased during in vitro fermentation of APF and TPF. Both the flours showed a positive prebiotic activity with the value of <1.50.

Social implications

The study supports sustainable agriculture and global pollution reduction. Incorporating these by-products into diets might increase the availability of inexpensive, nutritious food choices, improve digestive health and create economic possibilities for food producers and farmers.

Originality/value

The research provides novel information on the bioaccessibility of polyphenols and antioxidants during digestion, and the prebiotic potential APF, which have not been previously documented.