bluuebunny/crossref_metadata_2025 huggingface dataset:
Online model adaptation in Monte Carlo tree search planning
Authors: Zuccotto Maddalena , Fusa Edoardo , Castellini Alberto , Farinelli Alessandro
Published: June 2024

We propose a model-based reinforcement learning method using Monte Carlo Tree Search planning. The approach assumes a black-box approximated model of the environment developed by an expert using any kind of modeling framework and it improves the model as new information from the environment is collected. This is crucial in real-world applications, since having a complete knowledge of complex environments is impractical. The expert’s model is first translated into a neural network and then it is updated periodically using data, i.e., state-action-next-state triplets, collected from the real environment. We propose three different methods to integrate data acquired from the environment with prior knowledge provided by the expert and we evaluate our approach on a domain concerning air quality and thermal comfort control in smart buildings. We compare the three proposed versions with standard Monte Carlo Tree Search planning using the expert’s model (without adaptation), Proximal Policy Optimization (a popular model-free DRL approach) and Stochastic Lower Bounds Optimization (a popular model-based DRL approach). Results show that our approach achieves the best results, outperforming all analyzed competitors.
Exact solutions of the $$(2+1)$$-dimensional Zoomeron model arising in nonlinear optics via mapping method
Authors: Akgül Ali , Manzoor Saliha , Ashraf Farrah , Ashraf Romana
Published: June 2024

The Zoomeron model covers particular kinds of solitons with distinctive properties that appear in several physical scenarios, such as, fluid dynamics, nonlinear optics and laser physics. First time utilising the mapping method, we determine the analytical solution to the described model, including several novel dynamical behaviours. Through symbolic computation, we are able to derive the breather waves, kink waves, dark soliton, singular soliton, periodic soliton and bright soliton of this model. Additionally, we encounter single kink waves and single breather waves. We find novel hyperbolic trigonometric, rational and elliptic functions. Modelling our observations with MATLAB tools and producing many 3D graphs. The results obtained will be crucial for further research on complicated nonlinear models.
It’s About Time: The Inequitable Distribution of Time as a Resource for College, by Gender and Race/Ethnicity
Authors: Wladis Claire , Hachey Alyse C. , Conway Katherine
Published: June 2024

Existing qualitative research in higher education on students’ work and family commitments already suggests that time as a resource for college is likely not distributed equitably by race/ethnicity or gender. However, the relationship between race/ethnicity, gender, and time as a resource for college has yet to be quantitatively measured in large-scale higher education research. This study explored whether gender or race/ethnicity correlated with differences in time as a resource for college; and further, the extent to which differences in time as a resource for college may be explained by other factors such as age, number of children, and access to childcare. Retrospective survey responses (n = 41,579) on self-reported time use were merged with institutional data records from students at the City University of New York (CUNY), a large diverse public university in the U.S. Women, Black, and Hispanic students were all significantly more time poor than male, White, or Asian students. Age accounted for significant portions of these differences, perhaps because it correlates with increased work and family responsibilities. Having children as well as a student’s access to childcare also explained a significant portion of inequitable distributions of time as a resource for college.
Upscaling and Effective Behavior for Two-Phase Porous-Medium Flow Using a Diffuse Interface Model
Authors: Kelm Mathis , Bringedal Carina , Flemisch Bernd
Published: June 2024

We investigate two-phase flow in porous media and derive a two-scale model, which incorporates pore-scale phase distribution and surface tension into the effective behavior at the larger Darcy scale. The free-boundary problem at the pore scale is modeled using a diffuse interface approach in the form of a coupled Allen–Cahn Navier–Stokes system with an additional momentum flux due to surface tension forces. Using periodic homogenization and formal asymptotic expansions, a two-scale model with cell problems for phase evolution and velocity contributions is derived. We investigate the computed effective parameters and their relation to the saturation for different fluid distributions, in comparison to commonly used relative permeability saturation curves. The two-scale model yields non-monotone relations for relative permeability and saturation. The strong dependence on local fluid distribution and effects captured by the cell problems highlights the importance of incorporating pore-scale information into the macro-scale equations.
Unleashed: walking dogs off the lead greatly increases habitat disturbance in UK lowland heathlands
Authors: Thomas Rebecca L. , Papworth Sarah K. , Fellowes Mark D.E.
Published: June 2024

Human population growth is associated with increased disturbance to wildlife. This effect is particularly acute in urban and periurban areas, where the area of effective disturbance extends beyond that of human presence by the roaming behaviour of pet dogs. Dogs are globally the dominant companion animal, with a population of ~ 12 million in the UK. As urban areas extend, dogs are exercised in green space close to housing. In southeast and southern England these areas include lowland heath, a habitat of high conservation value. To quantify disturbance caused by dog walkers and their dogs, we used GPS units to track the movement of people and their dogs across four lowland heath sites, used a questionnaire to ask about dog walking habits, and mapped potential areas of disturbance caused by dog walkers. Questionnaires were completed by 798 dog walkers and the walks of 162 owners and their 185 dogs were recorded. Mean (± SE) walk time was 56 ± 23 min, walk distance 3.75 ± 1.68 km and dogs were a median distance of 20 m from the owner during walks. Dogs were walked once (44%) or twice (56%) a day. Most (always: 85%; always or occasionally: 95%) dogs were walked off the lead even when signs were present requesting that dogs were kept on a lead. This resulted in up to a 21% increase in reserve area disturbed. In one reserve (Snelsmore Common), > 90% of the area was disturbed by dogs, greatly eroding its conservation value. This work highlights the importance of considering how dog ownership can exacerbate levels of disturbance in sensitive periurban habitats when housing developments are planned.
An update on non-aureus staphylococci and mammaliicocci in cow milk: unveiling the presence of Staphylococcus borealis and Staphylococcus rostri by MALDI-TOF MS
Authors: Penati Martina , Ulloa Fernando , Locatelli Clara , Monistero Valentina , Pavesi Laura Filippone , Santandrea Federica , Piccinini Renata , Moroni Paolo , Bronzo Valerio , Addis Maria Filippa
Published: June 2024

Non-aureus staphylococci and mammaliicocci (NASM) are the microorganisms most frequently isolated from milk. Given their numerosity and complexity, MALDI-TOF MS is one of the preferred species identification approaches. Nevertheless, reference mass spectra for the novel species Staphylococcus borealis were included only recently in the Bruker Biotyper System (MBT) library, and other species of veterinary interest such as S. rostri are still absent. This work provides an updated picture of the NASM species found in milk, gained by retrospectively analyzing the data relating to 21,864 milk samples, of which 6,278 from clinical mastitis (CM), 4,039 from subclinical mastitis (SCM), and 11,547 from herd survey (HS), with a spectrum library including both species. As a result, S. borealis was the second most frequently isolated NASM (17.07%) after S. chromogenes (39.38%) in all sample types, with a slightly higher percentage in CM (21.84%), followed by SCM (17.65%), and HS (14.38%). S. rostri was also present in all sample types (3.34%), reaching 8.43% of all NASM in SCM and showing a significant association (p < 0.01) with this condition. Based on our findings, the presence of S. borealis and S. rostri in milk and their potential association with mastitis might have been overlooked, possibly due to the difficulties in differentiating these species from other closely related NASM. Our results indicate that S. borealis could be a more frequent contributor to bovine udder infections than previously thought and that S. rostri should also not be underestimated considering its significant association with SCM.
Rapid Assessment of Bio-distribution and Antitumor Activity of the Photosensitizer Bremachlorin in a Murine PDAC Model: Detection of PDT-induced Tumor Necrosis by IRDye® 800CW Carboxylate, Using Whole-Body Fluorescent Imaging
Authors: McMorrow Roisin , de Bruijn Henriette S. , Que Ivo , Stuurman Debra C. , de Ridder Corrina M.A. , Doukas Michail , Robinson Dominic J. , Mezzanotte Laura , Lowik Clemens W.G.M.
Published: June 2024

Photodynamic therapy (PDT) is a light-based anticancer therapy that can induce tumor necrosis and/or apoptosis. Two important factors contributing to the efficacy of PDT are the concentration of the photosensitizer in the tumor tissue and its preferential accumulation in the tumor tissue compared to that in normal tissues. In this study, we investigated the use of optical imaging for monitoring whole-body bio-distribution of the fluorescent (660 nm) photosensitizer Bremachlorin in vivo, in a murine pancreatic ductal adenocarcinoma (PDAC) model. Moreover, we non-invasively, examined the induction of tumor necrosis after PDT treatment using near-infrared fluorescent imaging of the necrosis avid cyanine dye IRDye®-800CW Carboxylate. Using whole-body fluorescence imaging, we observed that Bremachlorin preferentially accumulated in pancreatic tumors. Furthermore, in a longitudinal study we showed that 3 hours after Bremachlorin administration, the fluorescent tumor signal reached its maximum. In addition, the tumor-to-background ratio at all-time points was approximately 1.4. Ex vivo, at 6 hours after Bremachlorin administration, the tumor-to-muscle or -normal pancreas ratio exhibited a greater difference than it did at 24 hours, suggesting that, in terms of efficacy, 6 hours after Bremachlorin administration was an effective time point for PDT treatment of PDAC. In vivo administration of the near infrared fluorescence agent IRDye®-800CW Carboxylate showed that PDT, 6 hours after administration of Bremachlorin, selectively induced necrosis in the tumor tissues, which was subsequently confirmed histologically. In conclusion, by using in vivo fluorescence imaging, we could non-invasively and longitudinally monitor, the whole-body distribution of Bremachlorin. Furthermore, we successfully used IRDye®-800CW Carboxylate, a near-infrared fluorescent necrosis avid agent, to image PDT-induced necrotic cell death as a measure of therapeutic efficacy. This study showed how fluorescence can be applied for optimizing, and assessing the efficacy of, PDT.
Agile model-driven re-engineering
Authors: Lano Kevin , Haughton Howard , Yuan Ziwen , Alfraihi Hessa
Published: June 2024

In this paper we describe an Agile model-driven engineering (MDE) approach, AMDRE, for the re-engineering of legacy systems. The objective is to support the reuse of business-critical functionality from such systems and the porting of legacy code to modernised platforms, together with technical debt reduction to improve the system maintainability and extend its useful life. AMDRE uses a lightweight MDE process which involves the automated abstraction of software systems to UML specifications and the interactive application of refactoring and rearchitecting transformations to remove quality flaws and architectural flaws. We demonstrate the approach on Visual Basic, COBOL and Python legacy codes, including a finance industry case. Significant quality improvements are achieved, and translation accuracy over 80% is demonstrated. In comparison to other MDE re-engineering approaches, AMDRE does not require high MDE skills and should be usable by mainstream software practitioners.
Mathematical Assessment of the Role of Intervention Programs for Malaria Control
Authors: Korsah Maame Akua , Johnston Stuart T. , Tiedje Kathryn E. , Day Karen P. , Flegg Jennifer A. , Walker Camelia R.
Published: June 2024

Malaria remains a global health problem despite the many attempts to control and eradicate it. There is an urgent need to understand the current transmission dynamics of malaria and to determine the interventions necessary to control malaria. In this paper, we seek to develop a fit-for-purpose mathematical model to assess the interventions needed to control malaria in an endemic setting. To achieve this, we formulate a malaria transmission model to analyse the spread of malaria in the presence of interventions. A sensitivity analysis of the model is performed to determine the relative impact of the model parameters on disease transmission. We explore how existing variations in the recruitment and management of intervention strategies affect malaria transmission. Results obtained from the study imply that the discontinuation of existing interventions has a significant effect on malaria prevalence. Thus, the maintenance of interventions is imperative for malaria elimination and eradication. In a scenario study aimed at assessing the impact of long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and localized individual measures, our findings indicate that increased LLINs utilization and extended IRS coverage (with longer-lasting insecticides) cause a more pronounced reduction in symptomatic malaria prevalence compared to a reduced LLINs utilization and shorter IRS coverage. Additionally, our study demonstrates the impact of localized preventive measures in mitigating the spread of malaria when compared to the absence of interventions.
Cardiac tamponade – a rare cause of sudden death in autoimmune polyglandular syndrome
Authors: Tan Luzern , Gilbert John D. , Byard Roger W.
Published: June 2024

A 27-year-old male died suddenly due to cardiac tamponade arising from pericarditis complicating autoimmune polyglandular syndrome (APS) type 2. He had a history of primary Addison disease and autoimmune hypothyroidism which were corroborated at autopsy. In addition a florid fibrinous pericarditis was associated with 287 g of turbid fluid in the pericardial sac. Although pericarditis with tamponade is a potential complication of APS, it has rarely if ever, been reported as a cause of sudden death. Lethal mechanisms may involve both compressive and restrictive effects.
Asciminib in Patients With CML-CP Previously Treated With ≥ 2 Tyrosine Kinase Inhibitors: 96-Week Results From the Japanese Subgroup Analysis of the ASCEMBL Study
Authors: Minami Yosuke , Doki Noriko , Matsuoka Hiroshi , Yokota Takafumi , Tomita Akihiro , Takahashi Naoto , Kubo Kohmei , Goto Tatsunori , Kirito Keita , Maki Akio , Aoki Makoto , Dawson Meryem Ktiouet , Matsumura Itaru
Published: June 2024

Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.
Metabolite profiles of Paragliomastix luzulae (formerly named as Acremonium striatisporum) KMM 4401 and its co-cultures with Penicillium hispanicum KMM 4689
Authors: Starnovskaya Sofya S. , Nesterenko Liliana E. , Popov Roman S. , Kirichuk Natalya N. , Chausova Viktoria E. , Chingizova Ekaterina A. , Chingizov Artur R. , Isaeva Marina P. , Yurchenko Ekaterina A. , Yurchenko Anton N.
Published: June 2024

The marine holothurian-derived fungal strain KMM 4401 has been identified as Paragliomastix luzulae using 28S rDNA, ITS regions and the partial TEF1 gene sequences. The metabolite profile of the fungal culture was studied by UPLC-MS technique. The strain KMM 4401 is a source of various virescenoside-type isopimarane glycosides suggested as chemotaxonomic feature for this fungal species. Also Px. luzulae KMM 4401 was proposed as possible source of new bioactive secondary metabolites especially antimicrobials. Moreover, the co-cultures of Px. luzulae KMM 4401 with another marine fungus Penicillium hispanicum KMM 4689 inoculated simultaneously or after two weeks were investigated by same way. It was shown, that P. hispanicum KMM 4689 suppressed the production of most of Px. luzulae KMM 4401 metabolites. On the other hand, the co-cultivation of P. hispanicum KMM 4689 and Px. luzulae KMM 4401 resulted in increasing of production of main deoxyisoaustamide alkaloids of P. hispanicum KMM 4689 on 50–190%.

Graphical Abstract
Mapping the Apps: Ethical and Legal Issues with Crowdsourced Smartphone Data using mHealth Applications
Authors: Farag Nada , Noë Alycia , Patrinos Dimitri , Zawati Ma’n H.
Published: June 2024

More than 5 billion people in the world own a smartphone. More than half of these have been used to collect and process health-related data. As such, the existing volume of potentially exploitable health data is unprecedentedly large and growing rapidly. Mobile health applications (apps) on smartphones are some of the worst offenders and are increasingly being used for gathering and exchanging significant amounts of personal health data from the public. This data is often utilized for health research purposes and for algorithm training. While there are advantages to utilizing this data for expanding health knowledge, there are associated risks for the users of these apps, such as privacy concerns and the protection of their data. Consequently, gaining a deeper comprehension of how apps collect and crowdsource data is crucial. To explore how apps are crowdsourcing data and to identify potential ethical, legal, and social issues (ELSI), we conducted an examination of the Apple App Store and the Google Play Store in North America and Europe to identify apps that could potentially gather health data through crowdsourcing. Subsequently, we analyzed their privacy policies, terms of use, and other related documentation to gain insights into the utilization of users’ data and the possibility of repurposing it for research or algorithm training purposes. More specifically, we reviewed privacy policies to identify clauses pertaining to the following key categories: research, data sharing, privacy/confidentiality, commercialization, and return of findings. Based on the results of these app search, we developed an App Atlas that presents apps which crowdsource data for research or algorithm training. We identified 46 apps available in the European and Canadian markets that either openly crowdsource health data for research or algorithm training or retain the legal or technical capability to do so. This app search showed an overall lack of consistency and transparency in privacy policies that poses challenges to user comprehensibility, trust, and informed consent. A significant proportion of applications presented contradictions or exhibited considerable ambiguity. For instance, the vast majority of privacy policies in the App Atlas contain ambiguous or contradictory language regarding the sharing of users’ data with third parties. This raises a number of ethico-legal concerns which will require further academic and policy attention to ensure a balance between protecting individual interests and maximizing the scientific utility of crowdsourced data. This article represents a key first step in better understanding these concerns and bringing attention to this important issue.
Urban air mobility (UAM) and ground transportation integration: A survey
Authors: Yan Yiping , Wang Kai , Qu Xiaobo
Published: June 2024

This study explores urban air mobility (UAM) as a strategy for mitigating escalating traffic congestion in major urban areas as a consequence of a static transportation supply versus dynamic demand growth. It offers an in-depth overview of UAM development, highlighting its present state and the challenges of integration with established urban transport systems. Key areas of focus include the technological advancements and obstacles in electric vertical take-off and landing (eVTOL) aircrafts, which are essential for UAM operation in urban environments. Furthermore, it explores the infrastructure requirements for UAM, including vertiport deployment and the creation of adept air traffic control (ATC) systems. These developments must be integrated into the urban landscape without exacerbating land-use challenges. This paper also examines the regulatory framework for UAM, including existing aviation regulations and the necessity for novel policies specifically designed for urban aerial transport. This study presents a comprehensive perspective for various stakeholders, from policymakers to urban planners, highlighting the need for a thorough understanding of UAM’s potential and effective assimilation into urban mobility frameworks.
Efficient identification and classification of apple leaf diseases using lightweight vision transformer (ViT)
Authors: Ullah Wasi , Javed Kashif , Khan Muhammad Attique , Alghayadh Faisal Yousef , Bhatt Mohammed Wasim , Al Naimi Imad Saud , Ofori Isaac
Published: June 2024

The timely diagnosis and identification of apple leaf diseases is essential to prevent the spread of diseases and ensure the sound development of the apple industry. Convolutional neural networks (CNNs) have achieved phenomenal success in the area of leaf disease detection, which can greatly benefit the agriculture industry. However, their large size and intricate design continue to pose a challenge when it comes to deploying these models on lightweight devices. Although several successful models (e.g., EfficientNets and MobileNets) have been designed to adapt to resource-constrained devices, these models have not been able to achieve significant results in leaf disease detection tasks and leave a performance gap behind. This research gap has motivated us to develop an apple leaf disease detection model that can not only be deployed on lightweight devices but also outperform existing models. In this work, we propose AppViT, a hybrid vision model, combining the features of convolution blocks and multi-head self-attention, to compete with the best-performing models. Specifically, we begin by introducing the convolution blocks that narrow down the size of the feature maps and help the model encode local features progressively. Then, we stack ViT blocks in combination with convolution blocks, allowing the network to capture non-local dependencies and spatial patterns. Embodied with these designs and a hierarchical structure, AppViT demonstrates excellent performance in apple leaf disease detection tasks. Specifically, it achieves 96.38% precision on Plant Pathology 2021—FGVC8 with about 1.3 million parameters, which is 11.3% and 4.3% more accurate than ResNet-50 and EfficientNet-B3. The precision, recall and F score of our proposed model on Plant Pathology 2021—FGVC8 are 0.967, 0.959, and 0.963 respectively.
Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance
Authors: McCarthy Nicholas , Gui Gege , Dumezy Florent , Roumier Christophe , Andrew Georgia , Green Sarah , Jenkins Madeleine , Adams Alexandra , Khan Naeem , Craddock Charles , Hourigan Christopher S. , Plesa Adriana , Freeman Sylvie
Published: June 2024

Measurable residual disease (MRD) surveillance in acute myeloid leukemia (AML) may identify patients destined for relapse and thus provide the option of pre-emptive therapy to improve their outcome. Whilst flow cytometric MRD (Flow-MRD) can be applied to high-risk AML/ myelodysplasia patients, its diagnostic performance for detecting impending relapse is unknown. We evaluated this in a cohort comprising 136 true positives (bone marrows preceding relapse by a median of 2.45 months) and 155 true negatives (bone marrows during sustained remission). At an optimal Flow-MRD threshold of 0.040%, clinical sensitivity and specificity for relapse was 74% and 87% respectively (51% and 98% for Flow-MRD ≥ 0.1%) by ‘different-from-normal’ analysis. Median relapse kinetics were 0.78 log10/month but significantly higher at 0.92 log10/month for FLT3-mutated AML. Computational (unsupervised) Flow-MRD (C-Flow-MRD) generated optimal MRD thresholds of 0.036% and 0.082% with equivalent clinical sensitivity to standard analysis. C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis.
Effectiveness of traditional band and loop space maintainer vs 3D-printed space maintainer following the loss of primary teeth: a randomized clinical trial
Authors: Thakur Bhagyashree , Bhardwaj Anuj , Luke Alexander Maniangat , Wahjuningrum Dian Agustin
Published: June 2024

This study evaluates the efficacy of 3D-printed band and loop space maintainers (3D-BLSMs) to mitigate concerns caused by early primary tooth loss in children when compared to their conventional equivalents. Over 9 months, 62 participants aged 6 to 12 years participated in a randomized clinical study. This study evaluated their failure rates (de-cementation, debonding, solder breakage, loop breakage, band breakage, and abutment tooth fracture), gingival health, and patient overall satisfaction. Random assignments were made to place the participants in two groups: traditional band and loop space maintainers or the 3D-BLSMs. The findings show that at 9 months, 3D-BLSMs provided significantly higher survival rates (77.4%) than conventional maintainers (51.6%, p < 0.01). Gum inflammation was mild in both groups, highlighting the need for good oral hygiene. In both groups, patient satisfaction exceeded 90%. Although there was some pain at first with 3D-BLSMs, this eventually subsided and aesthetic preferences disappeared. There were no negative consequences noted, and both groups needed ongoing dental treatment. In conclusion, with excellent patient satisfaction in both groups, 3D-printed space maintainers offer greater long-term durability in reducing dental concerns following early primary tooth loss.
A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis
Authors: Hemond Christopher C. , Deshpande Mugdha , Berrios-Morales Idanis , Zheng Shaokuan , Meyer Jerrold S. , Slavich George M. , Cole Steven W.
Published: June 2024

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these “silent” symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.
A digital intervention to support childhood cognition after the COVID-19 pandemic: a pilot trial
Authors: Kirk Hannah , Spencer-Smith Megan , Jobson Laura , Nicolaou Elizabeth , Cornish Kim , Melzak Ebony , Hrysanidis Caitlin , Moriarty Cassie , Davey Belinda , Whyman Theoni , Bird Laura , Bellgrove Mark A.
Published: June 2024

Difficulties in executive functioning (EF) can result in impulsivity, forgetfulness, and inattention. Children living in remote/regional communities are particularly at risk of impairment in these cognitive skills due to reduced educational engagement and poorer access to interventions. This vulnerability has been exacerbated by the COVID-19 pandemic and strategies are needed to mitigate long-term negative impacts on EF. Here we propose a pilot trial investigating the benefits, feasibility, and acceptability of a school-based EF intervention for primary school students (6–8 years) living in regional, developmentally vulnerable, and socio-economically disadvantaged communities. Students were randomised to a digital intervention or teaching as usual, for 7 weeks. Children completed measures of EF and parents/educators completed ratings of everyday EF and social/emotional wellbeing at pre-intervention, post-intervention, and 3-month follow-up. Change in EFs (primary outcome), everyday EF, and social/emotional wellbeing (secondary outcomes) from pre- to post-intervention and pre-intervention to 3-month follow-up were examined. Feasibility and acceptability of the intervention was assessed through educator feedback and intervention adherence.

Protocol Registration: The stage 1 protocol for this Registered Report was accepted in principle on 20 April 2023. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/WT3S2. The approved Stage 1 protocol is available here: https://osf.io/kzfwn.
Optimized production and characterization of endo-β-mannanase by Aspergillus niger for generation of prebiotic mannooligosaccharides from guar gum
Authors: Nath Suresh , Kango Naveen
Published: June 2024

Optimized production of Aspergillus niger ATCC 26011 endo-β-mannanase (ManAn) on copra meal resulted in 2.46-fold increase (10,028 U/gds). Purified ManAn (47 kDa) showed high affinity towards guar gum (GG) as compared to konjac gum and locust bean gum with Km 2.67, 3.25 and 4.07 mg/mL, respectively. ManAn efficiently hydrolyzed GG and liberated mannooligosaccharides (MOS). Changes occurring in the rheological and compositional aspects of GG studied using Differential scanning calorimetry (DSC), Thermal gravimetric analysis (TGA) and X-ray diffraction (XRD) revealed increased thermal stability and crystallinity of the partially hydrolyzed guar gum (PHGG). Parametric optimization of the time and temperature dependent hydrolysis of GG (1% w/v) with 100 U/mL of ManAn at 60 °C and pH: 5.0 resulted in 12.126 mg/mL of mannotetraose (M4) in 5 min. Enhanced growth of probiotics Lactobacilli and production of short chain fatty acids (SCFA) that inhibited enteropathogens, confirmed the prebiotic potential of PHGG and M4.
The impact of spectral and temporal processing on speech recognition in children with cochlear implants
Authors: DeFreese Andrea , Camarata Stephen , Sunderhaus Linsey , Holder Jourdan , Berg Katelyn , Lighterink Mackenzie , Gifford René
Published: June 2024

While the relationships between spectral resolution, temporal resolution, and speech recognition are well defined in adults with cochlear implants (CIs), they are not well defined for prelingually deafened children with CIs, for whom language development is ongoing. This cross-sectional study aimed to better characterize these relationships in a large cohort of prelingually deafened children with CIs (N = 47; mean age = 8.33 years) by comprehensively measuring spectral resolution thresholds (measured via spectral modulation detection), temporal resolution thresholds (measured via sinusoidal amplitude modulation detection), and speech recognition (measured via monosyllabic word recognition, vowel recognition, and sentence recognition in noise via both fixed signal-to-noise ratio (SNR) and adaptively varied SNR). Results indicated that neither spectral or temporal resolution were significantly correlated with speech recognition in quiet or noise for children with CIs. Both age and CI experience had a moderate effect on spectral resolution, with significant effects for spectral modulation detection at a modulation rate of 0.5 cyc/oct, suggesting spectral resolution may improve with maturation. Thus, it is possible we may see an emerging relationship between spectral resolution and speech perception over time for children with CIs. While further investigation into this relationship is warranted, these findings demonstrate the need for new investigations to uncover ways of improving spectral resolution for children with CIs.
Molecular phylogeny reveals Varroa mites are not a separate family but a subfamily of Laelapidae
Authors: Oh Jaeseok , Lee Seunghyun , Kwon Woochan , Joharchi Omid , Kim Sora , Lee Seunghwan
Published: June 2024

Varroa mites, notorious for parasitizing honeybees, are generally classified as Varroidae. Their extremely modified morphologies and behaviors have led to debates regarding their phylogenetic position and classification as an independent family. In this study, two different datasets were employed to reconstruct the phylogenies of Varroa mites and related Laelapidae species: (1) 9257 bp from the whole 13 mitochondrial protein-coding genes of 24 taxa, (2) 3158 bp from 113 taxa using Sanger sequencing of four nuclear loci. Both mitochondrial and nuclear analyses consistently place Varroa mites within the Laelapidae. Here we propose to place Varroa mites in the subfamily Varroinae stat. nov., which represents a highly morphologically adapted group within the Laelapidae. Ancestral state reconstructions reveal that bee-associated lifestyles evolved independently at least three times within Laelapidae, with most phoretic traits originating from free-living ancestors. Our revised classification and evolutionary analyses will provide new insight into understanding the Varroa mites.
Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats
Authors: Luo Ang , Hao Rongrong , Zhou Xia , Jia Yangfan , Bao Changlei , Yang Lei , Zhou Lirong , Gu Chenxin , Desai Ankit A. , Tang Haiyang , Chu Ai-ai
Published: June 2024

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log2fold change) > log21.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.
Association between sleep state misperception and bedtime behavior in patients with chronic insomnia
Authors: Kudo Mizuki , Ayabe Naoko , Takeshima Masahiro , Ogasawara Masaya , Itoh Yu , Yoshizawa Kazuhisa , Kitamura Shingo , Mishima Kazuo
Published: June 2024

Previous studies on sleep state misperception have objectively evaluated sleep status in special environments using polysomnography. There is a paucity of data from studies that evaluated habitual sleep status in home environments. The present study aimed to investigate sleep state misperception in the home environment of patients with chronic insomnia using a lumbar-worn actigraphy to identify sleep habits associated with sleep state misperception severity. Thirty-one patients and 42 healthy volunteers were included in the insomnia and non-insomnia group, respectively. Participants recorded subjective assessments in sleep diaries, objective assessments with an actigraphy worn for 14 days, and self-assessments using questionnaires. Both groups had similar objective sleep ratings; however, insomnia group had significantly worse subjective ratings (total sleep time, wake after sleep onset, and sleep onset latency). A significant correlation was found between subjective and objective total sleep time scores in non-insomnia group but not in insomnia group. Insomnia group had earlier bedtimes, significantly longer bedtimes, and impaired daytime functioning (Sheehan Disability Scale score); additionally, they underestimated their total sleep time, particularly with earlier bedtimes and longer laying durations. Monitoring the sleep status and habits of individuals in home environments could be instrumental in identifying key points for targeted interventions on sleep hygiene and cognitive behavioral therapy for insomnia.
Preclinical and first-in-human safety studies on a novel magnetism-based haemofiltration method
Authors: Waalders Nicole , van Lier Dirk , Gerretsen Jelle , Moran Lucy , Stegmann Kerstin A. , Twigger Will , Blanco-Andujar Cristina , Frodsham George , Kox Matthijs , Pickkers Peter
Published: June 2024

Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the “IL-6-Sieve”, wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads—directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended—in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use.
A multi-population multi-stage adaptive weighted large-scale multi-objective optimization algorithm framework
Authors: Xiong Lixue , Chen Debao , Zou Feng , Ge Fangzhen , Liu Fuqiang
Published: June 2024

Weighted optimization framework (WOF) achieves variable dimensionality reduction by grouping variables and optimizing weights, playing an important role in large-scale multi-objective optimization problems. However, because of possible problems such as duplicate weight vectors in the selection process and loss of population diversity, the algorithm is susceptible to local optimization. Therefore, this paper develops an algorithm framework called multi-population multi-stage adaptive weighted optimization (MPSOF) to improve the performance of WOF in two aspects. First, the method of using multi-population is employed to address the issue of insufficient algorithmic diversity, while simultaneously reducing the likelihood of converging towards local optima. Secondly, a processing stage is incorporated into MPSOF, where a certain number of individuals are adaptively selected for updating based on the weight information and evolutionary status of different subpopulations, targeting different types of weights. This approach alleviates the impact of repetitive weights on the diversity of newly generated individuals, avoids the drawback of easily converging to local optima when using a single type of weight for updating, and effectively balances the diversity and convergence of subpopulations. Experiments of three types designed on several typical function sets demonstrate that MPSOF exceeds the comparison algorithms in the three metrics for Inverse Generation Distance, Hypervolume and Spacing.
Mesoscopic elasticity controls dynamin-driven fission of lipid tubules
Authors: Bussoletti Marco , Gallo Mirko , Bottacchiari Matteo , Abbondanza Dario , Casciola Carlo Massimo
Published: June 2024

Mesoscale physics bridges the gap between the microscopic degrees of freedom of a system and its large-scale continuous behavior and highlights the role of a few key quantities in complex and multiscale phenomena, like dynamin-driven fission of lipid membranes. The dynamin protein wraps the neck formed during clathrin-mediated endocytosis, for instance, and constricts it until severing occurs. Although ubiquitous and fundamental for life, the cooperation between the GTP-consuming conformational changes within the protein and the full-scale response of the underlying lipid substrate is yet to be unraveled. In this work, we build an effective mesoscopic model from constriction to fission of lipid tubules based on continuum membrane elasticity and implicitly accounting for ratchet-like power strokes of dynamins. Localization of the fission event, the overall geometry, and the energy expenditure we predict comply with the major experimental findings. This bolsters the idea that a continuous picture emerges soon enough to relate dynamin polymerization length and membrane rigidity and tension with the optimal pathway to fission. We therefore suggest that dynamins found in in vivo processes may optimize their structure accordingly. Ultimately, we shed light on real-time conductance measurements available in literature and predict the fission time dependency on elastic parameters.
The role of urine chloride in acute heart failure
Authors: Nawrocka-Millward Sylwia , Biegus Jan , Fudim Marat , Guzik Mateusz , Iwanek Gracjan , Ponikowski Piotr , Zymliński Robert
Published: June 2024

In our retrospective study, we aimed to investigate the relationship between urinary chloride (uCl−) and selected clinical and laboratory biomarkers, renal function, and patient outcomes in the acute heart failure (AHF) population. We divided 248 adult patients (≥ 18 years) with AHF into two groups: low uCl− (< 115 mmol/L) and high uCl−. The mean age of the patient group was 70.2 ± 12.6, and 182 patients were male (73.4%). Clinical endpoints included in-hospital mortality, one-year mortality, and a composite endpoint of one-year mortality and rehospitalization for heart failure. Patients were followed up for at least one year. Relevant clinical and baseline biomarker data were collected, including markers concerning inflammation, liver and kidney function, perfusion and congestion, iron status, cardiac remodeling, gasometry, renin and aldosterone. Low uCl− was associated with worse in-hospital outcomes, including higher in-hospital mortality (7.7% vs. 1.4%, p = 0.014), the need for inotropic support (20.19% vs. 2.08%, p ≤ 0.001), worsening of HF during therapy (17.31% vs. 4.86%, p ≤ 0.001), and the need for treatment in an intensive cardiac care unit (33.65% vs. 15.28%, p ≤ 0.001). Low uCl− was a significant predictor of one-year mortality (40.4% vs. 16.7%, p < 0.05) and the composite outcome (HR 2.42, 95% CI 1.43–4.08, p < 0.001). In the multivariable analysis, uCl− was independently associated with the risk of one-year mortality (HR 0.92, 95% CI 0.87–0.98, p < 0.05) and the composite outcome (HR 0.95, 95% CI 0.92–0.99, p < 0.05). Our findings suggest that low uCl− is a marker of more advanced heart failure, activation of the renin–angiotensin–aldosterone system and is related to worse one-year outcomes.
Ambient temperature-related sex ratio at birth in historical urban populations: the example of the city of Poznań, 1848–1900
Authors: Liczbińska Grażyna , Antosik Szymon , Brabec Marek , Tomczyk Arkadiusz M.
Published: June 2024

This study examines whether exposure to ambient temperature in nineteenth-century urban space affected the ratio of boys to girls at birth. Furthermore, we investigate the details of temperature effects timing upon sex ratio at birth. The research included 66,009 individual births, aggregated in subsequent months of births for the years 1847–1900, i.e. 33,922 boys and 32,087 girls. The statistical modelling of the probability of a girl being born is based on logistic GAM with penalized splines and automatically selected complexity. Our research emphasizes the significant effect of temperature in the year of conception: the higher the temperature was, the smaller probability of a girl being born was observed. There were also several significant temperature lags before conception and during pregnancy. Our findings indicate that in the past, ambient temperature, similar to psychological stress, hunger, malnutrition, and social and economic factors, influenced the viability of a foetus. Research on the effects of climate on the sex ratio in historical populations may allow for a better understanding of the relationship between environmental factors and reproduction, especially concerning historical populations since due to some cultural limitations, they were more prone to stronger environmental stressors than currently.