bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective quantification of sound sensory attributes in side-by-side vehicles using multiple linear regression models
Authors: Benghanem Abdelghani , Valentin Olivier , Gauthier Philippe-Aubert , Berry Alain
Published: October 2024

The evaluation of sound quality is a pivotal area of research within audio and acoustics. The sound quality evaluation methods commonly used include both objective and subjective, the latter being time-consuming and costly as they rely on listening tests. This research work aims to investigate the use of predictive sound quality models as a way to objectively assess the Desire-to-buy of side-by-side vehicles, in a more efficient, faster, and less costly way than conventional methods. Multiple linear regression algorithms were used to validate the objective models derived from objective physical metrics and perceptual psycho-physical metrics. The sensory profile objective models reported in this paper were constructed using parsimonious linear Lasso and Elastic-net algorithms. Our results show that linear objective models effectively account for each of the perceptual attributes of the sensory profiles and the Desire-to-buy, while only requiring a few physical and psychophysical metrics.
Case Report: Multidisciplinary management of a patient with indolent systemic mastocytosis and refractory symptoms
Authors: Hamilton Matthew J. , Greene Loren W. , Madigan Lauren M. , Wang Sa A. , Arana Yi Cecilia , Kuykendall Andrew , George Tracy I. , Castells Mariana C.
Published: October 2024

Systemic mastocytosis (SM) is a rare hematologic condition characterized by the proliferation and accumulation in tissue of clonal mast cells in multiple organ systems. The release of mast cell mediators in the indolent disease type and the predominant mast cell infiltration of tissues in advanced disease contribute to the heterogeneous clinical presentation. The disease driver in >90% of adult cases is an activating KIT mutation, with D816V being the most frequent. Here we describe a case of a young adult male presenting with osteoporosis with associated symptoms of reflux and a history of bee sting anaphylaxis. A multidisciplinary approach to the diagnosis and management was required to minimize morbidities and prevent complications. Current best supportive care was inadequate to control the patient's disease, and a selective KIT D816V inhibitor (avapritinib) was initiated. Conventional, and advanced therapies, including those in the treatment pipeline for SM are discussed.
Hydrodynamic exposure – on the quest to deriving quantitative metrics for mariculture sites
Authors: Lojek Oliver , Goseberg Nils , Føre Heidi Moe , Dewhurst Tobias , Bölker Thea , Heasman Kevin Gerald , Buck Bela H. , Fredriksson David W. , Rickerich Samuel
Published: October 2024

This work attempts to define metrics for hydrodynamic exposure, using known oceanographic variables to provide a universal site assessment method for mariculture structures. Understanding environmental conditions driving open-ocean mariculture siting is crucial in establishing consistent ocean governance, minimizing adverse environmental impacts, and facilitating economically sustainable farm operations. To provide a metric of oceanic conditions and associated requirements for structural design and operation of aquaculture systems, six Exposure Indices (EI) are proposed that consider physical energy levels related to hydrodynamic forces at a site. Four of the proposed indices consider only environmental conditions, while the other two also consider the dimensions of the gear that is exposed to the external loads. These indices are: Exposure Velocity (EV), Exposure Velocity at Reference Depth (EVRD), Specific Exposure Energy (SEE), Depth-integrated Energy Flux (DEF), Structure-centered Depth-integrated Energy (SDE), and a Structure-centered Drag-to-Buoyancy Ratio (SDBR). While these indices are derived with a focus on aquaculture structures, they may also have applications for estimating biological stressors and operational challenges. The proposed exposure indices were evaluated for a range of known aquaculture sites around the world. A sensitivity analysis was conducted that quantified the relationship between the exposure indices and storm event return period. At a regional scale, hindcast numerical data for the German Bight combined with calculations of 50-year extreme values were used to calculate and map each proposed index spatially. Resulting maps showed that exposure is not simply a function of distance from shore. The six indices show plausible performance regarding the objective assessment of aquaculture sites. The authors herein present the indices to the aquaculture and ocean engineering communities for discussion, application, and potential adoption of one or more of the proposed indices.
DCMA: faster protein backbone dihedral angle prediction using a dilated convolutional attention-based neural network
Authors: Zhang Buzhong , Zheng Meili , Zhang Yuzhou , Quan Lijun
Published: October 2024

The dihedral angle of the protein backbone can describe the main structure of the protein, which is of great significance for determining the protein structure. Many computational methods have been proposed to predict this critically important protein structure, including deep learning. However, these heavyweight methods require more computational resources, and the training time becomes intolerable. In this article, we introduce a novel lightweight method, named dilated convolution and multi-head attention (DCMA), that predicts protein backbone torsion dihedral angles (ϕ,ψ). DCMA is stacked by five layers of two hybrid inception blocks and one multi-head attention block (I2A1) module. The hybrid inception blocks consisting of multi-scale convolutional neural networks and dilated convolutional neural networks are designed for capturing local and long-range sequence-based features. The multi-head attention block supplementally strengthens this operation. The proposed DCMA is validated on public critical assessment of protein structure prediction (CASP) benchmark datasets. Experimental results show that DCMA obtains better or comparable generalization performance. Compared to best-so-far methods, which are mostly ensemble models and constructed of recurrent neural networks, DCMA is an individual model that is more lightweight and has a shorter training time. The proposed model could be applied as an alternative method for predicting other protein structural features.
N-acetyl-L-cysteine reduces testis ROS in obese fathers but fails in protecting offspring from acquisition of epigenetic traits at cyp19a1 and IGF11/H19 ICR loci
Authors: Pastore Arianna , Badolati Nadia , Manfrevola Francesco , Sagliocchi Serena , Laurenzi Valentina , Musto Giorgia , Porreca Veronica , Murolo Melania , Chioccarelli Teresa , Ciampaglia Roberto , Vellecco Valentina , Bucci Mariarosaria , Dentice Monica , Cobellis Gilda , Stornaiuolo Mariano
Published: October 2024

Introduction

Paternal nutrition before conception has a marked impact on offspring’s risk of developing metabolic disorders during adulthood. Research on human cohorts and animal models has shown that paternal obesity alters sperm epigenetics (DNA methylation, protamine-to-histone replacement, and non-coding RNA content), leading to adverse health outcomes in the offspring. So far, the mechanistic events that translate paternal nutrition into sperm epigenetic changes remain unclear. High-fat diet (HFD)-driven paternal obesity increases gonadic Reactive Oxygen Species (ROS), which modulate enzymes involved in epigenetic modifications of DNA during spermatogenesis. Thus, the gonadic pool of ROS might be responsible for transducing paternal health status to the zygote through germ cells.

Methods

The involvement of ROS in paternal intergenerational transmission was assessed by modulating the gonadic ROS content in male mice. Testicular oxidative stress induced by HFD was counterbalanced by N-acetylcysteine (NAC), an antioxidant precursor of GSH. The sires were divided into four feeding groups: i) control diet; ii) HFD; iii) control diet in the presence of NAC; and iv) HFD in the presence of NAC. After 8 weeks, males were mated with females that were fed a control diet. Antioxidant treatment was then evaluated in terms of preventing the HFD-induced transmission of dysmetabolic traits from obese fathers to their offspring. The offspring were weaned onto a regular control diet until week 16 and then underwent metabolic evaluation. The methylation status of the genomic region IGFII/H19 and cyp19a1 in the offspring gDNA was also assessed using Sanger sequencing and methylation-dependent qPCR.

Results

Supplementation with NAC protected sires from HFD-induced weight gain, hyperinsulinemia, and glucose intolerance. NAC reduced oxidative stress in the gonads of obese fathers and improved sperm viability. However, NAC did not prevent the transmission of epigenetic modifications from father to offspring. Male offspring of HFD-fed fathers, regardless of NAC treatment, exhibited hyperinsulinemia, glucose intolerance, and hypoandrogenism. Additionally, they showed altered methylation at the epigenetically controlled loci IGFII/H19 and cy19a1.

Conclusion

Although NAC supplementation improved the health status and sperm quality of HFD-fed male mice, it did not prevent the epigenetic transmission of metabolic disorders to their offspring. Different NAC dosages and antioxidants other than NAC might represent alternatives to stop the intergenerational transmission of paternal dysmetabolic traits.
Single-stranded DNA oligonucleotides containing CpG motifs are non-stimulatory in vitro but offer protection in vivo against Burkholderia pseudomallei
Authors: Scott Andrew , Farrar Benjamin , Young Tom , Prior Joann , Stratilo Chad , Unterholzner Leonie , D’Elia Riccardo
Published: October 2024

Therapies that modulate and appropriately direct the immune response are promising candidates for the treatment of infectious diseases. One such candidate therapeutic is DZ13, a short, synthetic, single-stranded DNA molecule. This molecule has enzymatic activity and can modulate the immune response by binding to and degrading the mRNA encoding a key immuno-regulatory molecule. Originally developed and entering clinical trials as an anti-cancer agent, DZ13 has also been evaluated as a treatment for viral infections, and has been shown to provide protection against infection with influenza virus in a mouse model of infection. In this work, we evaluated whether the immuno-modulatory properties of DZ13 could provide protection against the potential biothreat pathogen Burkholderia pseudomallei which causes the neglected tropical disease melioidosis. Treatment of mice infected with B. pseudomallei demonstrated that DZ13 did indeed provide excellent protection after only two post-exposure treatments. However, our data indicated that the enzymatic activity contained in DZ13 was not required for protection, with control oligonucleotide treatments lacking activity against the target mRNA equally as protective against B. pseudomallei. We have designed new sequences to study the mechanism of protection further. These novel sequences offer enhanced protection against infection, but are not directly anti-microbial and do not appear to be stimulating the immune system via TLR9 or other key innate immune sensors, despite containing CpG motifs. The molecular mechanism of these novel sequences remains to be elucidated, but the data highlights that these oligonucleotide-sensing pathways are attractive and relevant targets to modulate during bacterial and viral infections.
How large language model-powered conversational agents influence decision making in domestic medical triage contexts
Authors: Gomez Catalina , Yin Junjie , Huang Chien-Ming , Unberath Mathias
Published: October 2024

Introduction

Effective delivery of healthcare depends on timely and accurate triage decisions, directing patients to appropriate care pathways and reducing unnecessary visits. Artificial Intelligence (AI) solutions, particularly those based on Large Language Models (LLMs), may enable non-experts to make better triage decisions at home, thus easing the healthcare system's load. We investigate how LLM-powered conversational agents influence non-experts in making triage decisions, further studying different persona profiles embedded via prompting.

Methods

We designed a randomized experiment where participants first assessed patient symptom vignettes independently, then consulted one of the two agent profiles—rational or empathic—for advice, and finally revised their triage ratings. We used linear models to quantify the effect of the agent profile and confidence on the weight of advice. We examined changes in confidence and accuracy of triage decisions, along with participants' perceptions of the agents.

Results

In a study with 49 layperson participants, we found that persona profiles can be differentiated in LLM-powered conversational agents. However, these profiles did not significantly affect the weight of advice. Notably, less confident participants were more influenced by LLM advice, leading to larger adjustments to initial decisions. AI guidance improved alignment with correct triage levels and boosted confidence in participants' decisions.

Discussion

While LLM advice improves triage recommendations accuracy, confidence plays an important role in its adoption. Our findings raise design considerations for human-AI interfaces, highlighting two key aspects: encouraging appropriate alignment with LLMs' advice and ensuring that people are not easily swayed in situations of uncertainty.
Glucose-lowering medications and glucose levels as the major determinants of progression of carotid atherosclerosis in middle-aged adults and elders: a community-based prospective study
Authors: Chou Chao-Liang , Lu Shu-Xin , Cheng Chun-Fang , Wu Tzu-Wei , Wang Li-Yu
Published: October 2024

Background

Few prospective studies explored the incidence and determinant of carotid atherosclerosis (CA) progression (CAP). This community-based prospective study focused on the effects of diabetes mellitus (DM) treatments and glucose levels on CAP risks.

Methods

We followed up a group of 657 CA-positive middle-aged adults and elders for CAP. CAP was defined as an increase in the total number of carotid plaque and/or an increase in diameter stenosis by at least 10%.

Results

After 4.05 years of followed-up, CAP was detected in 364 (55.4%) subjects. The multivariable-adjusted hazard ratios (HRs) were 1.805 (95% confidence interval [CI]: 1.374-2.358) and 0.694 (95% CI: 0.510-0.944) for elevated fasting plasma glucose (eFPG; FPG≥100 mg/dL) and glucose-lowering medications (GLM), respectively. As compared to GLM-negative+eFPG-positive subjects, the multivariable-adjusted HRs were 0.497 (95% CI: 0.373-0.662), 0.537(95% CI: 0.306-0.942), and 0.586 (95% CI: 0.412-0.833) for GLM-negative+eFPG-negative, GLM-positive+eFPG-negative, and GLM-positive+ eFPG-positive subjects, respectively. The multivariable-adjusted risks of CAP were similar between GLM-negative+eFPG-negative and GLM-positive+ eFPG-positive subjects (p=0.77). Stratified analyses showed that the multivariable-adjusted HRs per 5.0 mg/dL increase in FPG were significantly increased among GLM-negative subjects (HR=1.131; 95% CI: 1.094-1.171) and non-significantly decreased among GLM-positive subjects (HR=0.985; 95% CI: 0.957-1.013).

Conclusion

We found that more than 50% of CA-positive subjects had CAP in 4 years and higher FPG significantly increased and GLM significantly decreased the risks of CAP. Additionally, GLM and FPG demonstrated an interactive effect on CAP risks. It seems possible that GLM may induce effects beyond lowering glucose levels and subsequently lowers CAP risks.
Pharmacological blockade of the mast cell MRGPRX2 receptor supports investigation of its relevance in skin disorders
Authors: Macphee Colin H. , Dong Xinzhong , Peng Qi , Paone Daniel V. , Skov Per Stahl , Baumann Katrine , Roethke Theresa , Goldspink Deborah A. , Pearson Samuel K. , Wu Zining
Published: October 2024

Introduction

Because MRGPRX2 is now recognized as the mast cell receptor for basic secretagogues, there is currently a tremendous interest in whether MRGRPX2 could play an important role in various pruritic dermatoses such as chronic spontaneous urticaria. Therefore, we sought to identify new potent and selective antagonists to pharmacologically characterize the biological role of MRGPRX2.

Methods

Various relevant in vitro, ex vivo, and in vivo model systems were used to investigate the role of MRGPRX2. This included the study of freshly isolated human skin mast cells and human basophils as well as an ex vivo human skin microdialysis preparation. The additivity of MRGPRX2 and FcεR1-mediated degranulation was also investigated. Human MRGPRX2 knock-in mice were generated to interrogate pharmacokinetic/pharmacodynamic relationships because both antagonists studied were shown to be human specific.

Results

Two novel and structurally distinct MRGPRX2 antagonists were identified with one, Compound B, being orally active and demonstrating high potency in blocking Substance P–mediated degranulation using freshly isolated human skin mast cells with half maximal inhibitory concentration (IC50) at 0.42 nM. Compound B also potently blocked Substance P–stimulated histamine release from resident mast cells in a human skin explant setup as well as blocking itch in an established behavioral scratching model using MRGPRX2 knock-in mice. Unlike human mast cells, Substance P failed to elicit a functional response in human basophils.

Conclusion

These data fully support the investigation of MRGPRX2 receptor antagonists in mast cell–driven allergic skin disorders such as chronic spontaneous urticaria.
The vacuolar anti-Pseudomonal activity of neutrophil primary granule peptidyl-arginine deiminase enzymes
Authors: Baird Rory , Yusuf Azeez , Forde Luke , Pohl Kerstin , Kavanagh Kevin , Fitzpatrick Fidelma , Gogoi Debananda , Reeves Emer P.
Published: October 2024

The role of neutrophils in host defense involves several cell processes including phagocytosis, degranulation of antimicrobial proteins, and the release of neutrophil extracellular traps (NETs). In turn, dysregulated cell activity is associated with the pathogenesis of airway and rheumatic diseases, in which neutrophil-derived enzymes including peptidyl-arginine deiminases (PADs) play a role. Known physiological functions of PADs in neutrophils are limited to the activity of PAD isotype 4 in histone citrullination in NET formation. The aim of this study was to extend our knowledge on the role of PADs in neutrophils and, specifically, bacterial killing within the confines of the phagocytic vacuole. Human neutrophils were fractionated by sucrose gradient ultracentrifuge and PADs localized in subcellular compartments by Western blot analysis. Direct interaction of PADs with Pseudomonas aeruginosa (P. aeruginosa) was assessed by flow cytometry and Western blot overlay. The participation of neutrophil PAD2 and PAD4 in killing of P. aeruginosa was assessed by inclusion of PAD-specific inhibitors. In vitro, bactericidal activity of recombinant human PAD2 or PAD4 enzymes against P. aeruginosa was determined by enumeration of colony-forming units (CFU). Together with neutrophil elastase (NE), PAD2 and PAD4 were localized to primary granules and, following activation with particulate stimuli, were degranulated in to the phagocytic vacuole. In vitro, PAD2 and PAD4 bound P. aeruginosa (p = 0.04) and significantly reduced bacterial survival to 49.1 ± 17.0 (p < 0.0001) and 48.5 ± 13.9% (p < 0.0001), respectively. Higher antibacterial activity was observed at neutral pH levels with the maximum toxicity at pH 6.5 and pH 7.5, comparable to the effects of neutrophil bactericidal permeability increasing protein. In phagosomal killing assays, inclusion of the PAD2 inhibitor, AFM-30a, or PAD4 inhibitor, GSK484, significantly increased survival of P. aeruginosa (AFM-30a, p = 0.05; and GSK484, p = 0.0079). Results indicate that PAD2 and PAD4 possess antimicrobial activity and are directly involved in the neutrophil antimicrobial processes. This study supports further research into the development of PAD-based antimicrobials.
Promoting resilience among medical students using the Wadi framework: a clinical teacher’s perspective
Authors: Shorbagi Ali Ibrahim
Published: October 2024

Resilience is essential for medical students to navigate the challenges of their education and future careers. Defined as the ability to adapt well in the face of adversity, resilience can be learned and is critical for maintaining mental health. Medical educators play a pivotal role in fostering resilience by integrating it into both formal and informal curricula, including the hidden curriculum, which can significantly influence students’ coping strategies. Research highlights the importance of resilience training in reducing depression and anxiety among students, underscoring its necessity as a core component of medical education. This essay presents the Systematic Assessment for Resilience (SAR) framework, which provides a comprehensive approach to promoting resilience through four key constructs: self-control, management, engagement, and growth. Practical strategies for each construct are discussed, including assessment mapping, time management, and the use of formative assessments to enhance students’ preparedness and self-control. Engagement is fostered through collaborative assessments, open book exams, and regular formative feedback, while growth is encouraged via self-reflection and faculty development. Implementing the SAR framework has shown positive outcomes, with students reporting reduced anxiety and improved performance. However, further exploration and institutional support are needed to fully integrate these strategies into medical education. The SAR framework offers a feasible and effective method for cultivating resilience, contributing to students’ mental well-being and equipping them to face future challenges in their medical careers. Continued refinement and broader institutional adoption will be crucial to sustaining the impact of resilience training in medical education.
Phage therapy to treat cystic fibrosis Burkholderia cepacia complex lung infections: perspectives and challenges
Authors: Canning Jack S. , Laucirica Daniel R. , Ling Kak-Ming , Nicol Mark P. , Stick Stephen M. , Kicic Anthony
Published: October 2024

Burkholderia cepacia complex is a cause of serious lung infections in people with cystic fibrosis, exhibiting extremely high levels of antimicrobial resistance. These infections are difficult to treat and are associated with high morbidity and mortality. With a notable lack of new antibiotic classes currently in development, exploring alternative antimicrobial strategies for Burkholderia cepacia complex is crucial. One potential alternative seeing renewed interest is the use of bacteriophage (phage) therapy. This review summarises what is currently known about Burkholderia cepacia complex in cystic fibrosis, as well as challenges and insights for using phages to treat Burkholderia cepacia complex lung infections.
Gender differences in the use of an upper-extremity exoskeleton during physically and cognitively demanding tasks- a study protocol for a randomized experimental trial
Authors: Wollesen Bettina , Gräf Julia , Hansen Lasse , Gurevich Anna , Elprama Shirley A. , Argubi-Wollesen Andreas , De Pauw Kevin
Published: October 2024

Background

Upper limb exoskeletons are recommended to alleviate muscle fatigue, particularly in working conditions inducing musculoskeletal discomfort like overhead work. However, wearing an exoskeleton might introduce cognitive-motor interference, affecting performance. Understanding its neural impact and potential gender differences in design effects is crucial. Therefore, the aim of this study is to examine exoskeleton effects addressing cross-gender comparisons, and exploring the impact on cognitive and physical workload in real-world scenarios. The research questions address the impact of exoskeleton use on muscle synergies, upper body posture, cognitive resources, comfort/discomfort, acceptance and usability.

Methods

The cross-sectional study integrates a multifactorial mixed-measure design. Participants are grouped by gender (female vs. male) and working condition (with vs. without exoskeleton). Motor performance and underlying neuronal correlates (fNIRS) will be analyzed. Based on an a priori sample size calculation, 80 participants (40 female/40 male) will be recruited. Working performance will be assessed by 1. Physical Performance Task (PILE task) and 2. Precision Task (following the Fitts paradigm), while body postures will be monitored with an Xsens motion capture system. Brain activation will be captured with an fNIRS system comprising 32 active optodes. Postural comfort/discomfort, acceptance, and usability will be reported via standardized questionnaires.

Discussion

The study will gain insights into potential gender differences in exoskeleton use and will contribute to designing and optimizing the implementation of exoskeletons by considering muscle synergies, movement variability and cognitive resource allocation. Additionally, the study also highlights user discomfort, a crucial factor that could impede widespread adoption, particularly among females, in real-world scenarios.
A new variant of the electromagnetic field theory of consciousness: approaches to empirical confirmation
Authors: Strupp Wolfram
Published: October 2024

There are various electromagnetic (EM) field theories of consciousness. They postulate an epineural EM field which, due to its binding properties, unifies the different neuronal information differences originating from various sensory and cognitive processes. Only through a real physical integration in space within this field could phenomenal consciousness arise. This would solve the binding problem mentioned in the philosophy of mind. On closer inspection, the electromagnetic interaction not only provides an explanation for the integrative property of the EM field, but also for the necessary differentiating contrasts of information. This article will take a closer look at the physical properties of a postulated EM field. It will also show how the problem of qualia in connection with emergentism could be solved by a new variant of EM field theory. If it can be clearly demonstrated that the postulated epineural EM field plays a decisive role in the origin of consciousness in addition to neuronal “wired” information processing, this also leaves less room for metaphysical assumptions that attempt to solve the binding problem. In experiments to prove the postulated epineural EM field by means of external electromagnetic manipulations, it can never be ruled out that these also have a direct effect on the “wired” neuronal signal processing. Therefore, on the way to proving the EM field theory of consciousness, an experimental method is needed that must ensure that external manipulations only affect the extensions of the EM field without directly influencing the neuronal network. A method will be discussed here that works with the shielding of EM fields instead of external electromagnetic stimuli.
Evolving trends in oral cancer burden in Europe: a systematic review
Authors: Ghanem Amr Sayed , Memon Hafsa Aijaz , Nagy Attila Csaba
Published: October 2024

Introduction

Oral cavity cancer (OCC), primarily oral squamous cell carcinoma (OSCC), is a growing concern in Europe, particularly among younger populations. Preventable lifestyle factors and social determinants of health contribute significantly to the disease burden. Limited access to healthcare and delayed diagnoses further complicate treatment and reduce survival rates.

Methods

This systematic literature review adhered to PRISMA guidelines to explore trends in OSCC epidemiology, etiology, diagnosis, treatment, and survival across Europe. A comprehensive search strategy using PubMed, GLOBOCAN data, and the EUROCARE-5 study identified relevant articles focusing on human populations in Europe with a primary interest in OSCC epidemiology. Only peer-reviewed publications in English with full-text access were included.

Results

This study investigated the burden of OSCC across Europe, revealing variations in incidence, mortality, and prognosis. Eastern and Central Europe displayed the highest burden. Males exhibited a significantly higher risk compared to females. Age-related disparities existed in life expectancy and time to achieve favorable outcomes. HPV emerged as a growing risk factor for oropharyngeal cancer. Public health strategies should target modifiable risk factors and improve early detection.

Conclusion

This review reveals concerning disparities in European OSCC. Region, sex, and age all influence burden and prognosis. Future research should focus on controlling risk factors and personalized medicine to optimize treatment. This will lead to a Europe with reduced OSCC incidence and demonstrably better patient outcomes.
Breast conservation and oncoplastic surgery are associated with improved quality of life
Authors: Barbalho Daniel , Polidorio Natalia , Mori Lincon , Barros Alfredo , Sampaio Marcelo , Melo Sandro , Assis Amilcar , Bioni Pamela , Miziara Giovanna , Fraga Murilo , Andrade Felipe
Published: October 2024

Introduction

Local treatment can be distressful to breast cancer patients. We aimed to evaluate how different types of local treatment impact the quality of life of patients.

Methods

In this retrospective cohort study, one-year postoperative Breast-Q Satisfaction with Breasts scores were used as a surrogate for Quality of Life. Linear regression was used to estimate the impact of breast conservation, oncoplastic surgery, breast reconstruction, and radiation therapy on Breast-Q scores. All analyses were adjusted for multiple covariates.

Results

Of the 711 eligible patients, 349 female patients answered both the pre- and one-year postoperative questionnaires and were included in the final analysis. In total, 237 (68%) patients underwent breast-conserving surgeries and 112 (32%) underwent mastectomies. All mastectomy patients underwent breast reconstruction and 176 (74% of breast-conserving surgeries) underwent concomitant oncoplastic surgery. After multivariate analysis, mastectomy was associated with lower scores compared to breast-conserving surgery (-21.3; 95%CI: -36.2, -6.4, p=0.005), and oncoplastic surgery was associated with higher scores (9.2; 95%CI: 0.8, 17.6, p=0.032). There was a tendency for higher scores with the use of flaps in breast reconstruction and a tendency for lower scores with the use of radiation therapy, but the difference was not significant.

Conclusions

Breast-conserving surgery is associated with better quality of life than mastectomy. Additionally, oncoplastic surgery is associated with a better quality of life than standard breast-conserving surgery. Patients should be counseled whenever multiple options for surgery are possible, and efforts should be made to increase the availability of trained surgeons in oncoplastic techniques.
Trend and forecast analysis of the changing disease burden of pancreatic cancer attributable to high fasting glucose in China, 1990–2021
Authors: Song Lichen , Chen Ziyi , Li Yongjie , Ran Lirong , Liao Dongwei , Zhang Yuanyuan , Wang Guangming
Published: October 2024

Background

Pancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors.

Methods

PC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection.

Results

The number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73–1.52) and 1.00% (95% CI, 0.63–1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032.

Conclusions

It was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country’s future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.
Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion
Authors: King Lisa A. , de Jong Milon , Veth Myrthe , Lutje Hulsik David , Yousefi Parsa , Iglesias-Guimarais Victoria , van Helden Pauline M. , de Gruijl Tanja D. , van der Vliet Hans J.
Published: October 2024

Background

Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

Methods

We evaluated whether bivalent single domain antibodies (VHHs) that link Vδ2-TCR specific VHHs with different affinities could support Vγ9Vδ2 T-cell expansion and could be incorporated in a bispecific engager format when additionally linked to a tumor antigen specific VHH.

Results

Bivalent VHHs that link a high and low affinity Vδ2-TCR specific VHH can support Vγ9Vδ2 T-cell expansion. The majority of Vγ9Vδ2 T-cells that expanded following exposure to these bivalent VHHs had an effector or central memory phenotype and expressed relatively low levels of PD-1. Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice.

Conclusion

By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells.
The DLPFC is centrally involved in resolving Stroop conflicts, suppressing distracting sensory input within the auditory and visual system
Authors: Ehlis Ann-Christine , Zarantonello Lisa , Haeussinger Florian B. , Rohe Tim , Rosenbaum David , Fallgatter Andreas J. , Maier Moritz J.
Published: October 2024

Introduction

Cognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear.

Methods

To further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based event-related potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory theta-burst stimulation—a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)—over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices.

Results

The results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials (“Gratton effect”) that was only accomplished with an intact DLPFC (i.e., following placebo stimulation).

Discussion

Because non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities.
Performance of self-performed SARS-CoV-2 rapid antigen test: a systematic review and meta-analysis
Authors: Cai Peiling , Wang Junren , Ye Peng , Zhang Yarong , Wang Mengping , Guo Ronglian , Zhao Hongying
Published: October 2024

Background

The aim of this study was to investigate the accuracy of self-tested SARS-CoV-2 rapid antigen tests.

Methods

Databases of Pubmed, Embase, and Cochrane Library were searched for original studies investigating accuracy of self-tested SARS-CoV-2 rapid antigen tests, with RT-PCR as “gold standard.”

Results

Forty-five eligible studies were found after database searching and screening using pre-defined criteria. The accuracy results from 50,897 suspected COVID-19 patients were pooled, and the overall sensitivity, specificity and diagnostic odds ratio were 0.77, 1.00, and 625.95, respectively. Subgroup analysis showed higher sensitivity of rapid antigen tests in subgroups of Abbott Panbio, self-collected nasal swab samples, and use of nasopharyngeal or oropharyngeal swab and lower Ct cutoff value in RT-PCR.

Conclusion

Fully self-performed SARS-CoV-2 rapid antigen tests showed overall high accuracy compared to “gold standard,” and are reliable surrogates for the standard test of COVID-19 using nasopharyngeal or oropharyngeal samples and RT-PCR.
Research on Global Nonsingular Fast Terminal Sliding Mode Control Strategy of Ball Screw Feed System Based on Improved Double Power Reaching Law
Authors: Wu Qin , Zhou Shunqian , Wang Xinglian
Published: October 2024

Aiming at the problems of low trajectory tracking accuracy, serious chattering and poor robust performance of ball screw feed systems in traditional sliding mode control (SMC), in this paper, a global nonsingular fast terminal sliding mode control (GNFTSMC) strategy based on improved double power reaching law (DPRL) and extended state observer (ESO) is proposed. Firstly, the system state variable is introduced into the power term of DPRL, so that the improved DPRL has the characteristics of variable speed reaching, which solves the contradiction between the reaching rate and the sliding mode chattering. Secondly, ESO is designed to observe the state of the system and match the external disturbance to improve the anti-interference performance of the system. Finally, GNFTSMC is designed for the ball screw feed system, and the global sliding mode factor is introduced to improve the trajectory tracking accuracy of the system. The results show that the proposed control strategy can effectively improve the tracking accuracy and anti-interference performance of the system.
Research on Energy-Saving Transformation of Rural Residential Building Envelope Structures and Heating Modes in Northeast China
Authors: Zhang Zhizheng , Hua Yunfeng , Peng Na , Liu Kailong
Published: October 2024

Rural areas in Northeast China present a large demand for heating energy in winter, but there are problems in such areas with poor thermal performance of building envelopes and poor indoor thermal comfort. In addition, coal-fired boilers are still widely used. China’s “Dual-Carbon Goals” and “Clean Heating” policy call for the creation of a green and comfortable living environment for rural residential buildings. This paper considers the impact of the improvement of the thermal performance of envelope structures on the initial investment of the transformation program and the rated power of the ASHP and proposes an energy-saving transformation method to replace traditional coal-fired boilers with the ASHP on the basis of the improvement of the thermal performance of envelope structures. By establishing a typical rural residential building model in Northeast China, this energy-saving method is simulated based on TRNSYS. The results show that the payback period of investment of the transformation method of “envelope structure + heating system” is not superior to that of the transformation method of only improving the thermal performance of the envelope structure, but it has advantages in the comprehensive life-cycle benefits and it has great advantages in improving the satisfaction of rural residents in the use of heating systems.
Theoretical Investigation of Rate Coefficients and Dynamical Mechanisms for N + N + N Three-Body Recombination Based on Full-Dimensional Potential Energy Surfaces
Authors: Xu Chong , Wei Zhenxuan , Hu Huayu , Hu Xixi , Xie Daiqian
Published: October 2024

Three-body recombination reactions, in which two particles form a bound state while a third one bounces off after the collision, play significant roles in many fields, such as cold and ultracold chemistry, astrochemistry, atmospheric physics, and plasma physics. In this work, the dynamics of the recombination reaction for the N3 system over a wide temperature range (5000–20,000 K) are investigated in detail using the quasi-classical trajectory (QCT) method based on recently developed full-dimensional potential energy surfaces. The recombination products are N2(X) + N(4S) in the 14A″ state, N2(A) + N(4S) in the 24A″ state, and N2(X) + N(2D) in both the 12A″ and 22A″ states. A three-body collision recombination model involving two sets of relative translational energies and collision parameters and a time-delay parameter is adopted in the QCT calculations. The recombination process occurs after forming an intermediate with a certain lifetime, which has a great influence on the recombination probability. Recombination processes occurring through a one-step three-body collision mechanism and two distinct two-step binary collision mechanisms are found in each state. And the two-step exchange mechanism is more dominant than the two-step transfer mechanism at higher temperatures. N2(X) formed in all three related states is always the major recombination product in the temperature range from 5000 K to 20,000 K, with the relative abundance of N2(A) increasing as temperature decreases. After hyperthermal collisions, the formed N2(X/A) molecules are distributed in highly excited rotational and vibrational states, with internal energies mainly distributed near the dissociation threshold. Additionally, the rate coefficients for this three-body recombination reaction in each state are determined and exhibit a negative correlation with temperature. The dynamic insights presented in this work might be very useful to further simulate non-equilibrium dynamic processes in plasma physics involving N3 systems.
Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT2A Receptors
Authors: Cui Meng , Lu Yongcheng , Mezei Mihaly , Logothetis Diomedes E.
Published: October 2024

Recent breakthroughs in the determination of atomic resolution 3-D cryo-electron microscopy structures of membrane proteins present an unprecedented opportunity for drug discovery. Structure-based drug discovery utilizing in silico methods enables the study of dynamic connectivity of stable conformations induced by the drug in achieving its effect. With the ever-expanding computational power, simulations of this type reveal protein dynamics in the nano-, micro-, and even millisecond time scales. In the present study, aiming to characterize the protein dynamics of the 5HT2A receptor stimulated by ligands (agonist/antagonist), we performed 1 µs MD simulations on 5HT2A/DOI (agonist), 5HT2A/GSK215083 (antagonist), and 5HT2A (APO, no ligand) systems. The crystal structure of 5HT2A/zotepine (antagonist) (PDB: 6A94) was used to set up the simulation systems in a lipid bilayer environment. We found the monitoring of the ionic lock residue pair (R3.50-E6.30) of 5HT2A in MD simulations to be a good approximation of the effects of agonists (ionic lock breakage) or antagonists (ionic lock formation) on receptor activation. We further performed analyses of the MD trajectories, including Principal Component Analysis (PCA), hydrogen bond, salt bridge, and hydrophobic interaction network analyses, and correlation between residues to identify key elements of receptor activation. Our results suggest that in order to trigger receptor activation, DOI must interact with 5HT2A through residues V5.39, G5.42, S5.43, and S5.46 on TM5, inducing significant conformational changes in the backbone angles of G5.42 and S5.43. DOI also interacted with residues W6.48 (toggle switch) and F6.51 on TM6, causing major conformational shifts in the backbone angles of F6.44 and V6.45. These structural changes were transmitted to the intracellular ends of TM5, TM6, and ICL3, resulting in the breaking of the ionic lock and subsequent G protein activation. The studies could be helpful in future design of selective agonists/antagonists for various serotonin receptors (5HT1A, 5HT2A, 5HT2B, 5HT2C, and 5HT7) involved in detrimental disorders, such as addiction and schizophrenia.