bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity Improvements for Picosecond Ultrasonic Thickness Measurements in Gold and Tungsten Nanoscale Films
Authors: Dong Jiaqi , Yao Chengyuan , Zhu Yuanhao , Li Shaojie , Liu Bowen , Fan JinTao , Hu Chunguang , Song Youjian , Hu Minglie
Published: March 2024

Picosecond ultrasonics, as a nondestructive and noncontact method, can be employed for nanoscale metallic film thickness measurements. The sensitivity of the system, which determines the measurement precision and practicability of this technique, is often limited by the weak intensity of the ultrasonic signal. To solve this problem, we investigate the distinct mechanisms involved in picosecond ultrasonic thickness measurement for two types of metals, namely tungsten (W) and gold (Au). For thickness measurement in W films, theory and simulation show that optimizing the pump and probe laser wavelengths, which determine the intensity and shape of the ultrasonic signal, is critical to improving measurement sensitivity, while for Au film measurements, where acoustic-induced beam distortion is dominant, the signal intensity can be optimized by selecting an appropriate aperture size and sample position. The above approaches are validated in experiments. A dual-wavelength pump–probe system is constructed based on a passively mode-locked ytterbium-doped fiber laser. The smoothing method and multipeak Gaussian fitting are employed for the extraction of ultrasonic time-of-flight. Subnanometer measurement precision is achieved in a series of W and Au films with thicknesses of 43–750 nm. This work can be applied to various high-precision, noncontact measurements of metal film thickness in the semiconductor industry.
What patient-reported outcome measures may be suitable for research involving older adults with frailty? A scoping review
Authors: Long S. O. , Hope S. V.
Published: March 2024

Introduction

The need to develop and evaluate frailty-related interventions is increasingly important, and inclusion of patient-reported outcomes is vital. Patient-reported outcomes can be defined as measures of health, quality of life or functional status reported directly by patients with no clinician interpretation. Numerous validated questionnaires can thus be considered patient-reported outcome measures (PROMs). This review aimed to identify existing PROMs currently used in quantitative research that may be suitable for older people with frailty.

Method

PubMed and Cochrane were searched up to 24/11/22. Inclusion criteria were quantitative studies, use of a PROM, and either measurement of frailty or inclusion of older adult participants. Criteria were created to distinguish PROMs from questionnaire-based clinical assessments. 197 papers were screened. PROMs were categorized according to the domain assessed, as derived from a published consensus ‘Standard Set of Health Outcome Measures for Older People’.

Results

88 studies were included. 112 unique PROMs were used 289 times, most frequently the SF-36 (n = 21), EQ-5D (n = 21) and Barthel Index (n = 14). The most frequently assessed outcome domains included Mood and Emotional Health and Activities of Daily Living, with fewer assessments of Participation in Decision-Making and Carer Burden.

Conclusions

PROM usage in frailty research is highly heterogeneous. Frequently used PROMs omit important outcomes identified by older adults. Further research should evaluate the importance of specific outcomes and identify PROMs relevant to people at different stages of frailty. Consistent and appropriate PROM use in frailty research would facilitate more effective comparisons and meaningful evaluation of frailty interventions.
Training environmental sound classification models for real-world deployment in edge devices
Authors: Goulão Manuel , Bandeira Lourenço , Martins Bruno , L. Oliveira Arlindo
Published: March 2024

The interest in smart city technologies has grown in recent years, and a major challenge is to develop methods that can extract useful information from data collected by sensors in the city. One possible scenario is the use of sound sensors to detect passing vehicles, sirens, and other sounds on the streets. However, classifying sounds in a street environment is a complex task due to various factors that can affect sound quality, such as weather, traffic volume, and microphone quality. This paper presents a deep learning model for multi-label sound classification that can be deployed in the real world on edge devices. We describe two key components, namely data collection and preparation, and the methodology to train the model including a pre-train using knowledge distillation. We benchmark our models on the ESC-50 dataset and show an accuracy of 85.4%, comparable to similar state-of-the-art models requiring significantly more computational resources. We also evaluated the model using data collected in the real world by early prototypes of luminaires integrating edge devices, with results showing that the approach works well for most vehicles but has significant limitations for the classes “person” and “bicycle”. Given the difference between the benchmarking and the real-world results, we claim that the quality and quantity of public and private data for this type of task is the main limitation. Finally, all results show great benefits in pretraining the model using knowledge distillation.
Reviewing the frontier: modeling and energy management strategies for sustainable 100% renewable microgrids
Authors: Elazab Rasha , Dahab Ahmed Abo , Adma Maged Abo , Hassan Hany Abdo
Published: March 2024

The surge in global interest in sustainable energy solutions has thrust 100% renewable energy microgrids into the spotlight. This paper thoroughly explores the technical complexities surrounding the adoption of these microgrids, providing an in-depth examination of both the opportunities and challenges embedded in this paradigm shift. The review examines pivotal aspects, including intricate modelling methodologies for renewable energy sources, real-time energy management systems, and sophisticated strategies for navigating short-term uncertainties. Innovative approaches to real-time energy management are dissected for their potential to tune operational efficiency finely. Furthermore, the study investigates methodological frameworks to address short-term uncertainty, leveraging cutting-edge techniques such as machine learning, robust optimization, and information gap decision theory. Despite the pivotal role short-term uncertainty plays, it frequently occupies a subordinate position in research, eclipsed by the presumption of minimal economic impact. This study challenges this prevalent notion, underscoring the indispensable need for exhaustive research on uncertainty. Such comprehensive exploration is essential to ensure the practicality and sustainability of 100% renewable energy grids. The paper concludes by emphasizing the importance of addressing short-term uncertainty and providing nuanced insights that can facilitate the effective implementation and ongoing development of these grids within the dynamic landscape of electrical energy systems.
A Low Omega-3 Index and High AA/EPA Ratio in American College Football Players are Both Improved Following 5 Weeks of DHA-Rich Algae Oil Supplementation
Authors: Larkin Theresa A. , McKay Benjamin , Sampson John A. , Delaney Jace , Murray Andrew , Pedlar Charles R. , Lewis Nathan A. , Peoples Gregory E.
Published: March 2024

Purpose

Many athletes are deficient in long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA). A consequent low Omega-3 Index (O3I) and high arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio increase cardiovascular disease risk and inflammation. Algae oil is a plant-based, sustainable source of LC n-3 PUFA, suitable for vegans and vegetarians. Effects of algae oil supplementation on whole blood fatty acids among athletes has not been previously reported. This study evaluated the effects of 5 weeks of DHA-rich algae oil supplementation on the whole blood fatty acid profile, O3I and AA/EPA ratio of omnivorous Division I American College Football (ACF) players. Methods: Data, including a spot blood sample, were collected at baseline for all participants (n = 47), then for a subset of players (n = 22) following a 5-week control period (usual diet) and 5 weeks of algae oil supplementation (usual diet + 1575 mg docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) 5 days/week; average 1125 mg/day). Results: Baseline O3I was 4.3% ± 0.1% and AA/EPA ratio was 45.6 ± 23.8. After 5 weeks of algae oil supplementation, the O3I was 6.1% ± 1.0% and the AA/EPA ratio was 25.1 ± 11.6. The O3I was significantly higher and the AA/EPA ratio was significantly lower (P < 0.0001 for both) compared with both baseline and the end of the control period. The increase in O3I from baseline was correlated with calculated DHA + EPA dose per unit body mass (R = 0.641, P = 0.001). Conclusions: Algae oil supplementation for 5 weeks improved both the low baseline O3I and high AA/EPA ratio among ACF players, with body mass specific dose effects.
High Intensity Functional Training for Patients Diagnosed with Cancer: A Study Evaluating the Feasibility of a Pragmatic Intervention
Authors: Christensen Jan , Hessner Andreas L. , Sommer Maja S. , Daugaard Rikke , Larsen Rasmus T.
Published: March 2024

Purpose

To investigate the feasibility of a municipality-based 16-week group-based HIFT-program (e.g. CrossFit) as a part of the physical rehabilitation of cancer survivors at different stages of cancer treatment.

Methods

Non-randomised clinical feasibility study. Younger adult patients (age 18–44 years) diagnosed with cancer who were referred to rehabilitation between August 2019 to December 2019 were eligible for inclusion. The group-based HIFT intervention was designed as a 16-week program with two sessions weekly (1.25 h each). The intervention program was not developed with pre-defined progression in terms of gradually added resistance, intensity, or volume during the 16 weeks period but the physiotherapist leading the sessions was trained in scalability. Feasibility was evaluated as retention, adherence, and accrual rates. Data on quality of life and cancer-related fatigue were measured EORTC QLQ-C-30 and evaluated using paired t-tests or Wilcoxon signed-rank test.

Results

Eighty-three percent of the eligible patients were included and initiated the HIFT program. However, 25% of the patients were not adherent to the intervention and only 34% of the patients were still adherent to the intervention after 4 months. Nonetheless, a significant improvement in cancer specific HRQoL was found from baseline [Mean = 53.4, 95%CI (47.6, 59.1)] to the end of the intervention [Mean = 66.3, 95%CI (60.8, 71.9)].

Conclusion

It is possible to recruit patients diagnosed with cancer to a municipality-based HIFT rehabilitation program, however, adherence to the intervention is found to be difficult for the majority of the patients.
Synthesis of glass FRP-natural fiber hybrid composites (NFHC) and its mechanical characterization
Authors: Pawar Unmesh S. , Chavan Sachin S. , Mohite Dadaso D.
Published: March 2024

This research paper presents the synthesis of Glass-Fiber Reinforced Plastic (Glass-FRP) and Natural Fiber-Hybrid Composites (NFHC) using Hand Lay-up techniques. The aim of the this research is on assessing mechanical characteristics of composites made from different natural fibers, including jute, flax, coir, and hair fibers. The study sought to evaluate the influence of natural fiber addition on mechanical characteristics of the composite material and to emphasize the significance of altering fiber type, orientation, resin type, and curing conditions to optimize composite characteristics for particular applications. The mechanical characteristics of these composites were evaluated using tensile and flexural testing. This study significantly enhances the mechanical properties of Glass-FRP composites by incorporating Jute fibers, showcasing a superior tensile strength of 71.29 MPa and the highest flexural strength of 67.73 MPa. The investigation showed that the combination of natural and glass fibers may produce a lightweight, highly-strengthen composite material with enhanced mechanical characteristics that can be employed in a wide range of technical applications.
In Search of Integrity
Authors: Serpell Robert
Published: March 2024

This Element traces the origins of an individual's philosophical orientation and the processes by which it was elaborated over the course of his life-journey. The author discusses how selected stories from his personal experience reflect the intimate culture of a particular social group of which he was a participant member at the time. The author's life-journey includes a tumultuous period of emerging adulthood in Singapore and Oxford. Moving to Zambia in 1965 aged 21, he conducted research, teaching and writing including sojourns in England and in Maryland USA. He discusses how his perspective in cultural psychology relates to his personal life as a migrant and as a parent, and to his views on how the world can best address the challenges of cooperative communication in the 2020s.
Warplane 05
Authors: Hoogschagen Edwin
Published: March 2024

Designed in 1933, the elegant looking Fokker C.X was outdated from the start. The type was intended as strategic reconnaissance plane but was not suited for this task. More modern, twin-engine types had claimed this specialized role. Instead, the biplane served well as short range scout and light bomber.

The C.X is a little-known member of the Dutch Fokker stable. Just like the D.XXI this biplane served in the air forces of two little neutral countries on the eve of World War II. Both fought gallantly in a war of David versus Goliath proportions, and the complete operational history of the type spans a total of 25 years. In retrospect, the C.X was the last fighting biplane type built by Fokker and the company's last pre-war military type to survive.
Remembering the Dead: Postmortem Guild Membership in Late Medieval England
Authors: Harkes Rachael
Published: March 2024

As in many areas of pre-Reformation devotion, the dead were a conspicuous presence in English religious guilds of all sizes. Members joined in the expectation that the guild would say prayers and perform masses for their souls after death, and previous members and benefactors would be commemorated with regularity. This article, however, investigates a new avenue of the fraternal relationship with the dead: the practice of enrolling people after their death. Doing so shifts the paradigm of our understanding of the multidimensional functions of pre-Reformation society, commemoration, and guilds, privileging the experiences of both the dead and living equally, while highlighting the interplay of the spiritual and socioeconomic. Taking the extensive membership records of England's “great” guilds as its basis, this article reveals that postmortem enrollment was a practice both common and widespread, and it addresses questions of practicalities and motivations. As such, the richness of commemoration in late medieval society is demonstrated, and the importance of postmortem membership brought to the fore.
Effect of gravity settling on the onset of thermal convection in a nanofluid-saturated porous medium layer
Authors: Ruo An-Cheng , Chang Min-Hsing
Published: March 2024

The onset of convection in a horizontal porous medium layer saturated with a nanofluid and heated from below is investigated via linear stability analysis and numerical simulation. The Darcy–Buongiorno model is used to describe the convective transport behaviour of the nanofluid and the settling effect of nanoparticles due to gravity is considered in addition to thermophoresis and Brownian diffusion. The linear stability analysis shows that the gravity settling is a substantial stabilizing mechanism restraining the destabilizing factors such as thermal buoyancy and thermophoresis. The stability threshold is determined by the relative strength of thermophoresis to gravity settling. It is found that the system is destabilized when the thermophoretic mobility prevails. As the nanoparticle size increases, the gravity settling effect is promoted and makes the system more stable. In particular, the onset of instability is dominated by the oscillatory mode once the nanoparticle concentration is in a stably stratified profile across the porous layer. When the Rayleigh–Darcy number

$Ra_D$

exceeds the critical value, the spectrum of the growth rates of the unstable modes rises with increasing

$Ra_D$

and

$Rn$

(i.e. the concentration Rayleigh number), and eventually the unstable modes in the high-wavenumber region exhibit the same instability. The evolution of the convection is further examined by numerical simulation. The results verify the stability characteristics predicted by linear stability analysis. Moreover, the pattern of fingering convection of the nanofluid concentration is observed once the nanofluid concentration is unstably stratified and the density difference across the porous layer is large enough.
Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm
Authors: Lajmi Nesrine , Alves-Vasconcelos Sofia , Tsiachristas Apostolos , Haworth Andrew , Woods Kerrie , Crichton Charles , Noble Theresa , Salih Hizni , Várnai Kinga A. , Branford-White Harriet , Orrell Liam , Osman Andrew , Bradley Kevin M. , Bonney Lara , McGowan Daniel R. , Davies Jim , Prime Matthew S. , Hassan Andrew Bassim
Published: March 2024

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.
Prayer for Family and Friends: The Body and Religion in Eighteenth-Century Britain
Authors: Harvey Karen , Vine Emily
Published: March 2024

This article explores how writers, predominantly adhering to a variety of different Christian denominations but also including Jewish writers, discussed religion and the body in letters throughout the long eighteenth century. It draws on a corpus of over 2,500 familiar letters written by men and women of different denominations between 1675 and 1820. That these letters were not chosen because of their religious content makes them a good ‘test’ of the role of faith in everyday understandings of the body. This article underscores the continued centrality of religious discourse and devotional practice in eighteenth-century everyday life. Our research finds that religion was a commonplace register deployed when discussing bodily matters throughout the long eighteenth century. Significantly, this was the case for individuals who otherwise made scant reference to their faith. Discussion of the physical body encouraged recourse to providence, a public discussion of doctrine, and the shared expression of devotion. The ongoing force of religion in people’s lives was thus intimately tied to their embodied experiences. Letters not only expressed but actively maintained this widely shared religious framework for understanding the body.
Trinity, simplicity, and contradictory theology: a theologian's reflections
Authors: McCall Thomas H.
Published: March 2024

I explore the promise of Beall's proposal for a long-standing challenge for traditional theology. I first offer a sketch of the problem and a brief overview of some of the more common responses to it. I then show how Beall's proposal holds initial promise; following this I highlight some concerns and raise some questions.
The Principal Principle and the contingent a priori
Authors: Bradley Richard
Published: March 2024

In Chapter 6 of Objects of Credence, Anna Mahtani argues that the opacity of credence raises difficulties for the Principal Principle and proposes a revised principle relating credence and chance that avoids it. In this comment on her book, I both defend Mahtani’s proposed principle against a charge of triviality and argue that the opacity of belief does not threaten the role of chance in guiding credence.
BOUNDED SUPPORT IN LINEAR RANDOM COEFFICIENT MODELS: IDENTIFICATION AND VARIABLE SELECTION
Authors: Hermann Philipp , Holzmann Hajo
Published: March 2024

We consider linear random coefficient regression models, where the regressors are allowed to have a finite support. First, we investigate identification, and show that the means and the variances and covariances of the random coefficients are identified from the first two conditional moments of the response given the covariates if the support of the covariates, excluding the intercept, contains a Cartesian product with at least three points in each coordinate. We also discuss identification of higher-order mixed moments, as well as partial identification in the presence of a binary regressor. Next, we show the variable selection consistency of the adaptive LASSO for the variances and covariances of the random coefficients in finite and moderately high dimensions. This implies that the estimated covariance matrix will actually be positive semidefinite and hence a valid covariance matrix, in contrast to the estimate arising from a simple least squares fit. We illustrate the proposed method in a simulation study.
NT-proBNP cardiac value in COVID-19: a focus on the paediatric population
Authors: Sleem Bshara , El Rassi Christophe , Zareef Rana , Bitar Fadi , Arabi Mariam
Published: March 2024

NT-proBNP is a peptide related to brain natriuretic peptide, a cardiac biomarker and a member of the natriuretic family of peptides. NT-proBNP has demonstrated its clinical utility in the assessment of a wide spectrum of cardiac manifestations. It is also considered a more precise diagnostic and prognostic cardiac biomarker than brain natriuretic peptide. With the appearance of the Severe Acute Respiratory Syndrome Coronavirus 2 virus and the subsequent COVID-19 pandemic, diagnosis of heart implications began to pose an increasing struggle for the physician. Echocardiography is considered a central means of evaluating cardiac disorders like heart failure, and it is considered a reliable method. However, other diagnostic methods are currently being explored, one of which involves the assessment of NT-proBNP levels. In the literature that involves the adult population, significant positive correlations were drawn between the levels of NT-proBNP and COVID-19 outcomes such as high severity and fatality. In the paediatric population, however, the literature is scarce, and most of the investigations assess NT-proBNP in the context of Multiple Inflammatory Syndrome in Children, where studies have shown that cohorts with this syndrome had elevated levels of NT-proBNP when compared to non-syndromic cohorts. Thus, more large-scale studies on existing COVID-19 data should be carried out in the paediatric population to further understand the prognostic and diagnostic roles of NT-proBNP.
Environmentally Induced Displacement: When (Ecological) Vulnerability Turns into Resilience (and Asylum)
Authors: Ippolito Francesca
Published: March 2024

This article aims to reflect on ‘ecological vulnerability’ – which makes evident the relationship, flows and interactions between the human being/body and the environment/non-human world – as applied in the context of environmentally induced migration. In particular, the dual role of the law vis-à-vis environmentally displaced migrants as a generator and exacerbator of their vulnerability as well as potential antidote, valuable for attaining protection, will be highlighted. Namely, on one hand, the analysis will show how a lack of conceptualisation of the notion to understand the spatial and temporal patterns of climate change-related migration, as well as its consequences for societal well-being, contributes to generate and exacerbate the vulnerability of that category of migrants. On the other hand, the critical understanding of vulnerability, as developed in some recent legal reasoning of international and national jurisdictions, will be proposed as a key element for ensuring the resilience of both environmental migrants and the law itself, for both virtuously expanding traditional asylum norms and flexibilising access to international protection for those migrants.
Interpretable zero-inflated neural network models for predicting admission counts
Authors: Jose Alex , Macdonald Angus S. , Tzougas George , Streftaris George
Published: March 2024

In this paper, we construct interpretable zero-inflated neural network models for modeling hospital admission counts related to respiratory diseases among a health-insured population and their dependants in the United States. In particular, we exemplify our approach by considering the zero-inflated Poisson neural network (ZIPNN), and we follow the combined actuarial neural network (CANN) approach for developing zero-inflated combined actuarial neural network (ZIPCANN) models for modeling admission rates, which can accommodate the excess zero nature of admission counts data. Furthermore, we adopt the LocalGLMnet approach (Richman & Wüthrich (2023). Scandinavian Actuarial Journal, 2023(1), 71–95.) for interpreting the ZIPNN model results. This facilitates the analysis of the impact of a number of socio-demographic factors on the admission rates related to respiratory disease while benefiting from an improved predictive performance. The real-life utility of the methodologies developed as part of this work lies in the fact that they facilitate accurate rate setting, in addition to offering the potential to inform health interventions.
Quantifying Anthropogenic Influences on Global Wave Height Trend During 1961–2020 With Focus on Polar Ocean
Authors: Patra Anindita , Dodet Guillaume , Min Seung‐Ki , Hochet Antoine
Published: March 2024

This study investigates the contribution of external forcings on global and regional ocean wave height change during 1961–2020. Historical significant wave height (Hs) produced for different CMIP6 external forcings and preindustrial control conditions following the Detection and Attribution Model Intercomparison Project (DAMIP) are employed. The internal variability ranges are compared with different external forcing scenario. Statistically significant linear trends in Hs computed over regional ocean basins are found to be mostly associated with anthropogenic forcings: greenhouse gas‐only (GHG) and aerosol‐only (AER) forcing. For Hs, GHG signals are robustly detected and dominant for most of the global ocean, except over North pacific and South Atlantic, where AER signals are dominant. These results are supported by multi‐model analysis for wind speed. The remarkable increase in Hs over the Arctic (22.3%) and Southern (8.2%) Ocean can be attributed to GHG induced sea‐ice depletion and larger effective fetch along with wind speed increase.
Active forgetting and neuropsychiatric diseases
Authors: Berry Jacob A. , Guhle Dana C. , Davis Ronald L.
Published: March 2024

Recent and pioneering animal research has revealed the brain utilizes a variety of molecular, cellular, and network-level mechanisms used to forget memories in a process referred to as “active forgetting”. Active forgetting increases behavioral flexibility and removes irrelevant information. Individuals with impaired active forgetting mechanisms can experience intrusive memories, distressing thoughts, and unwanted impulses that occur in neuropsychiatric diseases. The current evidence indicates that active forgetting mechanisms degrade, or mask, molecular and cellular memory traces created in synaptic connections of “engram cells” that are specific for a given memory. Combined molecular genetic/behavioral studies using Drosophila have uncovered a complex system of cellular active-forgetting pathways within engram cells that is regulated by dopamine neurons and involves dopamine-nitric oxide co-transmission and reception, endoplasmic reticulum Ca2+ signaling, and cytoskeletal remodeling machinery regulated by small GTPases. Some of these molecular cellular mechanisms have already been found to be conserved in mammals. Interestingly, some pathways independently regulate forgetting of distinct memory types and temporal phases, suggesting a multi-layering organization of forgetting systems. In mammals, active forgetting also involves modulation of memory trace synaptic strength by altering AMPA receptor trafficking. Furthermore, active-forgetting employs network level mechanisms wherein non-engram neurons, newly born-engram neurons, and glial cells regulate engram synapses in a state and experience dependent manner. Remarkably, there is evidence for potential coordination between the network and cellular level forgetting mechanisms. Finally, subjects with several neuropsychiatric diseases have been tested and shown to be impaired in active forgetting. Insights obtained from research on active forgetting in animal models will continue to enrich our understanding of the brain dysfunctions that occur in neuropsychiatric diseases.
Identification of unique rectal cancer-specific subtypes
Authors: Kisakol Batuhan , Matveeva Anna , Salvucci Manuela , Kel Alexander , McDonough Elizabeth , Ginty Fiona , Longley Daniel B. , Prehn Jochen H. M.
Published: March 2024

Background

Existing colorectal cancer subtyping methods were generated without much consideration of potential differences in expression profiles between colon and rectal tissues. Moreover, locally advanced rectal cancers at resection often have received neoadjuvant chemoradiotherapy which likely has a significant impact on gene expression.

Methods

We collected mRNA expression profiles for rectal and colon cancer samples (n = 2121). We observed that (i) Consensus Molecular Subtyping (CMS) had a different prognosis in treatment-naïve rectal vs. colon cancers, and (ii) that neoadjuvant chemoradiotherapy exposure produced a strong shift in CMS subtypes in rectal cancers. We therefore clustered 182 untreated rectal cancers to find rectal cancer-specific subtypes (RSSs).

Results

We identified three robust subtypes. We observed that RSS1 had better, and RSS2 had worse disease-free survival. RSS1 showed high expression of MYC target genes and low activity of angiogenesis genes. RSS2 exhibited low regulatory T cell abundance, strong EMT and angiogenesis signalling, and high activation of TGF-β, NF-κB, and TNF-α signalling. RSS3 was characterised by the deactivation of EGFR, MAPK and WNT pathways.

Conclusions

We conclude that RSS subtyping allows for more accurate prognosis predictions in rectal cancers than CMS subtyping and provides new insight into targetable disease pathways within these subtypes.
Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
Authors: Middha Pooja , Thummalapalli Rohit , Betti Michael J. , Yao Lydia , Quandt Zoe , Balaratnam Karmugi , Bejan Cosmin A. , Cardenas Eduardo , Falcon Christina J. , Faleck David M. ,   Princess Margaret Lung Group, Leighl Natasha B. , Bradbury Penelope A. , Shepherd Frances A. , Sacher Adrian G. , Eng Lawson , Gubens Matthew A. , Huntsman Scott , Johnson Douglas B. , Kachuri Linda , Khan Khaleeq , Li Min , Lovly Christine M. , Murray Megan H. , Patel Devalben , Werking Kristin , Xu Yaomin , Zhan Luna Jia , Balko Justin M. , Liu Geoffrey , Aldrich Melinda C. , Schoenfeld Adam J. , Ziv Elad
Published: March 2024

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.
Direct imaging of magnetohydrodynamic wave mode conversion near a 3D null point on the sun
Authors: Kumar Pankaj , Nakariakov Valery M. , Karpen Judith T. , Cho Kyung-Suk
Published: March 2024

Mutual conversion of various kinds of magnetohydrodynamic (MHD) waves can have profound impacts on wave propagation, energy transfer, and heating of the solar chromosphere and corona. Mode conversion occurs when an MHD wave travels through a region where the Alfvén and sound speeds are equal (e.g., a 3D magnetic null point). Here we report the direct extreme ultraviolet (EUV) imaging of mode conversion from a fast-mode to a slow-mode MHD wave near a 3D null point using Solar Dynamics Observatory/Atmospheric Imaging Assembly (SDO/AIA) observations. An incident fast EUV wavefront associated with an adjacent eruptive flare propagates laterally through a neighboring pseudostreamer. Shortly after the passage of the fast EUV wave through the null point, a slow-mode wave appears near the null that propagates upward along the open structures and simultaneously downward along the separatrix encompassing the fan loops of the pseudostreamer base. These observations suggest the existence of mode conversion near 3D nulls in the solar corona, as predicted by theory and MHD simulations. Moreover, we observe decaying transverse oscillations in both the open and closed structures of the pseudostreamer, along with quasiperiodic type III radio bursts indicative of repetitive episodes of electron acceleration.
Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes
Authors: Meijer Marieke , Öttl Miriam , Yang Jie , Subkhangulova Aygul , Kumar Avinash , Feng Zicheng , van Voorst Torben W. , Groffen Alexander J. , van Weering Jan R. T. , Zhang Yongli , Verhage Matthijs
Published: March 2024

Tomosyns are widely thought to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario. In a novel mouse model, tomosyn-1/2 deficiency lowered the fusion barrier and enhanced the probability that synaptic vesicles fuse, resulting in stronger synapses with faster depression and slower recovery. While wild-type tomosyn-1m rescued these phenotypes, substitution of its SNARE motif with that of synaptobrevin-2/VAMP2 did not. Single-molecule force measurements indeed revealed that tomosyn’s SNARE motif cannot substitute synaptobrevin-2/VAMP2 to form template complexes with Munc18-1 and syntaxin-1, an essential intermediate for SNARE assembly. Instead, tomosyns extensively bind synaptobrevin-2/VAMP2-containing template complexes and prevent SNAP-25 association. Structure-function analyses indicate that the C-terminal polybasic region contributes to tomosyn’s inhibitory function. These results reveal that tomosyns regulate synaptic transmission by cooperating with synaptobrevin-2/VAMP2 to prevent SNAP-25 binding during SNARE assembly, thereby limiting initial synaptic strength and equalizing it during repetitive stimulation.
Nitrogen and phosphorus trends in lake sediments of China may diverge
Authors: Ji Panpan , Chen Jianhui , Chen Ruijin , Liu Jianbao , Yu Chaoqing , Chen Fahu
Published: March 2024

The brief history of monitoring nutrient levels in Chinese lake waters limits our understanding of the causes and the long-term trends of their eutrophication and constrains effective lake management. We therefore synthesize nutrient data from lakes in China to reveal the historical changes and project their future trends to 2100 using models. Here we show that the average concentrations of nitrogen and phosphorus in lake sediments have increased by 267% and 202%, respectively since 1850. In the model projections, 2030–2100, the nitrogen concentrations in the studied lakes in China may decrease, for example, by 87% in the southern districts and by 19% in the northern districts. However, the phosphorus concentrations will continue to increase by an average of 25% in the Eastern Plain, Yunnan–Guizhou Plateau, and Xinjiang. Based on this differentiation, we suggest that nitrogen and phosphorus management in Chinese lakes should be carried out at the district level to help develop rational and sustainable environmental management strategies.
Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling
Authors: Creekmore Benjamin C. , Kixmoeller Kathryn , Black Ben E. , Lee Edward B. , Chang Yi-Wei
Published: March 2024

Ultrastructure of human brain tissue has traditionally been examined using electron microscopy (EM) following fixation, staining, and sectioning, which limit resolution and introduce artifacts. Alternatively, cryo-electron tomography (cryo-ET) allows higher resolution imaging of unfixed cellular samples while preserving architecture, but it requires samples to be vitreous and thin enough for transmission EM. Due to these requirements, cryo-ET has yet to be employed to investigate unfixed, never previously frozen human brain tissue. Here we present a method for generating lamellae in human brain tissue obtained at time of autopsy that can be imaged via cryo-ET. We vitrify the tissue via plunge-freezing and use xenon plasma focused ion beam (FIB) milling to generate lamellae directly on-grid at variable depth inside the tissue. Lamellae generated in Alzheimer’s disease brain tissue reveal intact subcellular structures including components of autophagy and potential pathologic tau fibrils. Furthermore, we reveal intact compact myelin and functional cytoplasmic expansions. These images indicate that plasma FIB milling with cryo-ET may be used to elucidate nanoscale structures within the human brain.
Association of antibiotic exposure with residual cancer burden in HER2-negative early stage breast cancer
Authors: Kulkarni Amit A. , Jain Aditya , Jewett Patricia I. , Desai Nidhi , Van ’t Veer Laura , Hirst Gillian , Yee Douglas , Blaes Anne H. ,   ISPY2 consortium
Published: March 2024

Antibiotic exposure during immunotherapy (IO) has been shown to negatively affect clinical outcomes in various cancer types. The aim of this study was to evaluate whether antibiotic exposure in patients with high-risk early-stage HER2-negative breast cancer (BC) undergoing treatment with neoadjuvant pembrolizumab impacted residual cancer burden (RCB) and pathologic complete response (pCR) in the pembrolizumab-4 arm of the ISPY-2 clinical trial. Patients received pembrolizumab for four cycles concurrently with weekly paclitaxel for 12 weeks, followed by four cycles of doxorubicin plus cyclophosphamide every 2 or 3 weeks. Patients who received at least one dose of systemic antibiotics concurrently at the time of immunotherapy (IO) were included in the antibiotic exposure group (ATB+). All other participants were included in the control group (ATB-). RCB index and PCR rates were compared between the ATB+ and ATB- groups using t-tests and Chi-squared tests, and linear and logistic regression models, respectively. Sixty-six patients were included in the analysis. 18/66 (27%) patients were in the ATB+ group. Antibiotic use during IO was associated with a higher mean RCB index (1.80 ± 1.43 versus 1.08 ± 1.41) and a lower pCR rate (27.8% versus 52.1%). The association between antibiotic use and the RCB index remained significant in multivariable linear regression analysis (RCB index-coefficient 0.86, 95% CI 0.20–1.53, P = 0.01). Our findings suggest that concurrent antibiotic exposure during neoadjuvant pembrolizumab in HER2-negative early-stage BC is associated with higher RCB. Further validation in larger cohorts is needed to confirm these findings.
Conceptual framework for tinnitus: a cognitive model in practice
Authors: Ghodratitoostani Iman , Vaziri Zahra , Miranda Neto Milton , de Giacomo Carneiro Barros Camila , Delbem Alexandre Cláudio Botazzo , Hyppolito Miguel Angelo , Jalilvand Hamid , Louzada Francisco , Leite Joao Pereira
Published: March 2024

Tinnitus is a conscious attended awareness perception of sourceless sound. Widespread theoretical and evidence-based neurofunctional and psychological models have tried to explain tinnitus-related distress considering the influence of psychological and cognitive factors. However, tinnitus models seem to be less focused on causality, thereby easily misleading interpretations. Also, they may be incapable of individualization. This study proposes a Conceptual Cognitive Framework (CCF) providing insight into cognitive mechanisms involved in the predisposition, precipitation, and perpetuation of tinnitus and consequent cognitive-emotional disturbances. The current CCF for tinnitus relies on evaluative conditional learning and appraisal, generating negative valence (emotional value) and arousal (cognitive value) to annoyance, distress, and distorted perception. The suggested methodology is well-defined, reproducible, and accessible, which can help foster future high-quality clinical databases. Perceived tinnitus through the perpetual-learning process can always lead to annoyance, but only in the clinical stage directly cause annoyance. In the clinical stage, tinnitus perception can lead indirectly to distress only with experiencing annoyance either with (“$${\underset{{\mathcal {C}}}{{{\varvec{Ind-1}}}}}$$

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n
d
-
1

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” = 1.87; 95% CI 1.18–2.72)[“1st indirect path in the Clinical stage model”: Tinnitus Loudness $$\rightarrow$$
→
Attention Bias $$\rightarrow$$
→
Cognitive-Emotional Value $$\rightarrow$$
→
Annoyance $$\rightarrow$$
→
Clinical Distress]or without (“$${\underset{{\mathcal {C}}}{{{\varvec{Ind-2}}}}}$$

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n
d
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2

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”= 2.03; 95% CI 1.02–3.32)[ “2nd indirect path in the Clinical stage model”: Tinnitus Loudness $$\rightarrow$$
→
Annoyance $$\rightarrow$$
→
Clinical Distress] the perpetual-learning process. Further real-life testing of the CCF is expected to express a meticulous, decision-supporting platform for cognitive rehabilitation and clinical interventions. Furthermore, the suggested methodology offers a reliable platform for CCF development in other cognitive impairments and supports the causal clinical data models. It may also enhance our knowledge of psychological disorders and complicated comorbidities by supporting the design of different rehabilitation interventions and comprehensive frameworks in line with the “preventive medicine” policy.
Simultaneous impregnation and microencapsulation of CaCl2 using silica gel and methyl cellulose for thermal energy storage applications
Authors: Shervani Suboohi , Strong Curtis , Tezel F. Handan
Published: March 2024

Thermal energy storage utilizing the adsorption of moisture from air is a promising energy storage technology due to its high energy density and minimum heat losses. Salt hydrates and salt hydrate composites, such as calcium chloride (CaCl2) and CaCl2-based composites, have shown favourable energy storage properties in this area of research. However, these materials have shown issues with stability due to swelling and deliquescence. In this work, CaCl2 was stabilized using three methods: impregnation into silica gel, encapsulation in methyl cellulose, and both impregnation and encapsulation stabilization techniques used simultaneously. Therefore, three CaCl2-based composites were synthesized. For the first composite, silica gel was impregnated with CaCl2. For the second composite, CaCl2 was encapsulated by methyl cellulose. For the third composite, silica gel was impregnated with CaCl2 and the CaCl2 was encapsulated with methyl cellulose. These samples were structurally characterized using scanning electron microscopy as well as Brunauer-Emmett-Teller (BET) to  determine surface area, pore size distribution and nitrogen adsorption isotherms at 77 K. Water vapour adsorption isotherms were also determined at 25 °C for different relative humidities by dynamic vapor sorption (DVS). Similarly, LiCl-based composites were also synthesized and examined in this work, but issues of deliquescence, swelling, and agglomeration made the materials impractical to work with. To determine the prepared materials’ thermal energy storage performance, 2–6 g of each sample was tested in a lab-scale apparatus. This process uses the exothermic adsorption of moisture from ambient air in an open thermal energy storage system. The CaCl2 impregnated silica gel that was encapsulated in methyl cellulose showed reasonably high stability and energy storage performance after 3 hydration and dehydration cycles with minimum agglomeration. An energy storage density of 241 kWh/m3 (0.87 GJ/m3) and specific energy of 630 Wh/kg (2268 kJ/kg) was achieved with this material for 90% inlet relative humidity after a regeneration at 90 °C.
Life truncated multiple dependent state plan for imprecise Weibull distributed data
Authors: Rao Gadde Srinivasa , Aslam Muhammad , Josephat Peter Kirigiti , Al-Husseini Zainalabideen , Albassam Mohammed
Published: March 2024

This paper aims to provide a multiple dependent state (MDS) sampling technique for light-emitting diode luminous intensities under indeterminacy by employing time truncated sampling schemes and the Weibull distribution. This indicates that ASN is significantly impacted by the indeterminacy parameter. Furthermore, a comparison is shown between the existing, indeterminate sampling plans and the recommended sample designs. The projected sampling technique is illustrated by calculating the luminous intensities of LEDs using the Weibull distribution. Based on the findings and practical example, we conclude that the suggested strategy needs a smaller sample size than SSP and the current MDS sampling plan.