Search

The scientific field is characterized by the disputes about the delimitation of the field problems, methods and theories that can be considered scientific. The recognition that it is not neutral, that a researcher is a moral subject, and its practices are moral ones, entail that moral reflections, that is, ethics, should be a core process of every researcher. Therefore ethics is not a heteronomous issue, and cannot be reduced to guidelines. In the first part of this article we examine the need to develop an open approach to the construction of guidelines in a plural scientific field that must take into account diverse paradigms, which implies different values. The Brazilian process of writing guidelines on research ethics for social science and humanities in the context of the Ministry of Health will be discussed as an example. In the second part we expand the analysis of research ethics posing a perspective that integrates qualitative research, social justice and discipline trends. In the final considerations we explore the possibility that research ethics is better discussed taking into account the ontology, epistemology and political values rather than one specific methodological approach or from a dichotomic perspective between biomedicine versus social science and humanities.

Blended learning is an emerging paradigm for science education but has not been rigorously assessed. We performed a randomized controlled trial of blended learning. We found that in-class problem solving improved exam performance, and video assignments increased attendance and satisfaction. This validates a new model for science communication and education., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This article addresses the study of document typology in the personal archives of scientists and its importance in the history of science studies and for the archivist's work. A brief history is presented of diplomatic to typological information, emphasizing that identifying document production activity as essential for its classification. The article illustrates personal archive characteristics as regards the diversity of documental types and, in particular, those belonging to physicists. Furthermore, it presents five examples of documental types found in the archives of physicists as examples of research in progress. It also highlights the elaboration of a glossary of different documental kinds and types found in the private archives of Museum of Astronomy and Related Sciences in Rio de Janeiro.

Political homogeneity within a scientific field nurtures threats to the validity of many research conclusions by allowing ideologically compatible values to influence interpretations, by minimizing skepticism, and by creating premature consensus. Although validity threats can crop in any research, the usual corrective activities in science are more likely to be minimized and delayed.

An analysis of more than 1000 research articles in biology reveals that the name of the species being studied is not mentioned in the title or abstract of many articles. Consequently, such data are not easily accessible in the PubMed database. These omissions can mislead readers about the true nature of developmental processes and delay the acceptance of valid species differences. To improve the accuracy of the scientific record, I suggest that journals should require that authors include the name of the species being studied in the title or abstract of submitted papers.

Like a scientist or a playing child, POWERPLAY (Schmidhuber, 2011) not only learns new skills to solve given problems, but also invents new interesting problems by itself. By design, it continually comes up with the fastest to find, initially novel, but eventually solvable tasks. It also continually simplifies or compresses or speeds up solutions to previous tasks. Here we describe first experiments with POWERPLAY. A self-delimiting recurrent neural network SLIM RNN (Schmidhuber, 2012) is used as a general computational problem solving architecture. Its connection weights can encode arbitrary, self-delimiting, halting or non-halting programs affecting both environment (through effectors) and internal states encoding abstractions of event sequences. Our POWERPLAY-driven SLIM RNN learns to become an increasingly general solver of self-invented problems, continually adding new problem solving procedures to its growing skill repertoire. Extending a recent conference paper (Srivastava, Steunebrink, Stollenga, & Schmidhuber, 2012), we identify interesting, emerging, developmental stages of our open-ended system. We also show how it automatically self-modularizes, frequently re-using code for previously invented skills, always trying to invent novel tasks that can be quickly validated because they do not require too many weight changes affecting too many previous tasks., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Science content is one area of general curriculum access that needs more investigation. Explicit instruction is effective for teaching students with high incidence disabilities a variety of skills, including science content. In this study, we taught three elementary aged students with autism spectrum disorder to acquire science descriptors (e.g., wet) and then generalization to novel objects, pictures, and within a science inquiry lesson via explicit instruction. A multiple probe across behaviors with concurrent replication across participants design measured the effects of the intervention. All three participants met criterion, some were able to generalize to novel objects, pictures, and objects within science inquiry lesson. Outcomes are discussed from the perspective of implications for practice and future research investigations.

To gauge the current commitment to scientific research in the United States of America (US), we compared federal research funding (FRF) with the US gross domestic product (GDP) and industry research spending during the past six decades. In order to address the recent globalization of scientific research, we also focused on four key indicators of research activities: research and development (R&D) funding, total science and engineering doctoral degrees, patents, and scientific publications. We compared these indicators across three major population and economic regions: the US, the European Union (EU) and the People's Republic of China (China) over the past decade. We discovered a number of interesting trends with direct relevance for science policy. The level of US FRF has varied between 0.2% and 0.6% of the GDP during the last six decades. Since the 1960s, the US FRF contribution has fallen from twice that of industrial research funding to roughly equal. Also, in the last two decades, the portion of the US government R&D spending devoted to research has increased. Although well below the US and the EU in overall funding, the current growth rate for R&D funding in China greatly exceeds that of both. Finally, the EU currently produces more science and engineering doctoral graduates and scientific publications than the US in absolute terms, but not per capita. This study's aim is to facilitate a serious discussion of key questions by the research community and federal policy makers. In particular, our results raise two questions with respect to: a) the increasing globalization of science: "What role is the US playing now, and what role will it play in the future of international science?"; and b) the ability to produce beneficial innovations for society: "How will the US continue to foster its strengths?"

The Internet has the potential to provide wider access to biological taxonomy, the knowledge base of which is currently fragmented across a large number of ink-on-paper publications dating from the middle of the eighteenth century. A system (the CATE project) is proposed in which consensus or consolidated taxonomies are presented in the form of Web-based revisions. The workflow is designed to allow the community to offer, online, additions and taxonomic changes ('proposals') to the consolidated taxonomies (e.g. new species and synonymies). A means of quality control in the form of online peer review as part of the editorial process is also included in the workflow. The CATE system rests on taxonomic expertise and judgement, rather than using aggregation technology to accumulate taxonomic information from across the Web. The CATE application and its system and architecture are described in the context of the wider aims and purpose of the project.

Artists try to understand how we see, sometimes explicitly exploring rules of perspective or color, visual illusions, or iconography, and conversely, scientists who study vision sometimes address the perceptual questions and discoveries raised by the works of art, as we do here.

In the present paper we reflect on some critically important issues in theory construction from the point of view of a practicing scientist. The starting point is to suggest the need for a minimal base of common agreement on the role of successfully working theories. It is proposed that scientific knowledge is not composed of singular facts but rather of relational structures connecting facts. Useful theories are both receptive and productive. Theories provide models, i.e., idealised representations of reality, expressed, in their most developed phases, in a mathematically formalised language. We further focus on the notions of rationality and universality, and show that these are mutually related and actually inseparable. Universality means description of observable phenomena in terms of universally valid laws that are essentially of a rational character, i.e., stated in terms of relational invariants preserved in variant, contingent conditions. Law-like components of a theory are universal by definition, not given by circumstances, and rational by their form, not by their content. Facts, on the other hand, are irrational elements unless they can be derived from law-like relations of another theory. Relational definition of rationality is self-consistent and independent from vaguely defined notions like 'reason'. Pertinent to studies of human nature, including psychophysiology, is the problem of individuality. To reconcile the claim of universality with an adequate account of unique individuality, we advocate a 'distributed nomothesis', distinguishing first-order laws ruling in an individual 'idioversum', from the higher-order, universal laws. Idioversal laws play the role of 'facts' in construction of universal theories.

C.P. Snow's articulation of a two-culture divide rested on a particular view of science that has been elaborated and superseded by interdisciplinary science studies. Thus, comparisons of the 'science wars' of recent years to the Snow-Leavis controversy fail to recognize basic structural differences between the two sets of debates. In this article, I present these differences and offer some views of what has changed in the intervening years.

A new method of calculating PCO2 based on mathematical expressions derived from a measured 'Davenport diagram' is described. The measured 'Davenport diagram' is constructed from in vitro buffer curves relating total CO2 to pH at PCO2 levels which adequately encompass the in vivo range of the acid-base status for the species in question. The 'Davenport diagram' is described by three linear equations such that PCO2 can be accurately calculated from in vivo measured CCO2 and pH. The equations are specific for a given species at a given temperature and hemolymph ionic strength, as are the constants in the more classical Henderson-Hasselbalch equation. The accuracy of the method is equal to calculations using the Henderson-Hasselbalch equation with corrected values for pK1' and alpha CO2 and in vivo PCO2 measured directly. This procedure is equally applicable to fluids with dissolved pigments such as hemolymph from freshwater and marine crustaceans and to human blood. The major benefit of this method of calculating PCO2 is that correction nomograms for the constants in the Henderson-Hasselbalch equation are not required.

Abstract Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study “Trust in Science and Science-Related Populism” (TISP). The questionnaire contained comprehensive measures for individuals’ trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.

Abstract Enhancement of security, personalization, and safety in advanced transportation systems depends on driver identification. In this context, this work suggests a new method to find drivers by means of a Random Forest model optimized using the osprey optimization algorithm (OOA) for feature selection and the salp swarm optimization (SSO) for hyperparameter tuning based on driving behavior. The proposed model achieves an accuracy of 92%, a precision of 91%, a recall of 93%, and an F1-score of 92%, significantly outperforming traditional machine learning models such as XGBoost, CatBoost, and Support Vector Machines. These findings show how strong and successful our improved method is in precisely spotting drivers, thereby providing a useful instrument for safe and quick transportation systems.

Abstract Unsustainable wild meat hunting poses a significant threat to wildlife and tropical forest ecosystems. While high levels of extraction linked to commercial trade have received significant attention, the sustainability of subsistence hunting by Indigenous Peoples in Africa has been less studied. Understanding how changing lifestyles, particularly the sedentarisation of former hunter-gatherers, have affected the use of forest resources is crucial for wildlife conservation and livelihoods. The spatial management of hunting through the establishment of no-take zones, which act as sources for adjacent hunting areas, offers promise for the sustainability of Indigenous livelihoods. We conducted an extensive camera trap study in hunting areas subject to source-sink dynamics used by 10 sedentarised Baka communities. We compared species richness, occupancy, abundance, and community composition to a relatively non-hunted reference area in the adjacent Dja Faunal Reserve. Subsistence hunting by the Baka had a limited impact on species richness but significantly altered community composition and the abundance of carnivores, seed dispersers and granivores. These changes highlight that even the spatial management of hunting may have consequences for the sustainability of hunting systems and the functional ecology of tropical forests.

Abstract Understanding the dynamic tumor immune microenvironment (TIME) is important in guiding immunotherapy. We have previously validated signatures predictive of checkpoint inhibitor efficacy which distinguish immunomodulatory, mesenchymal stem-like, and mesenchymal phenotypes. Here we use twenty tumor types (7162 samples) to identify potentially conserved immune biology within these TIME spaces, genes co-expressed across distinct cell types involved these immune processes, and the association of these signatures with ICI response. One signature, which contained multiple B-cell markers, was associated with immunotherapy efficacy in three cohorts, including IMvigor210. This signature of potentially conserved B-cell biology in co-infiltrated immune cell ecosystems had a more consistent association with outcome than comparable single cell type models and likely reflects a complex immunological response involving multilayered relationships between distinct immune effector cell types. These signatures were most highly expressed in tumors with prominent immune cell invasion, however there was consistent identification of infiltrate presence in relatively immune restricted cases. This suggests that these immune population signatures may identify conserved immune cell type co-infiltrate physiology of the TIME that best captures immune physiology with potential clinical utility.

Abstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro—a new group-II intron-encoded RT—to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and three mouse tissues and show that, while the landscape of modifications is highly variable throughout the tRNA sequence framework, it is stabilized for modifications that are required for reading of the genetic code. The coordinated changes have fundamental importance for development of tRNA modifications in protein homeostasis.

Abstract In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer’s disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma Aβ42/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by APOE4 genotype. The median age was 74.0 years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (β = -0.08, p = 0.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n = 58, β = -0.09 p = 0.04). After stratification, the association was only significant in APOE4 carriers (n = 43, β = -0.21 p = 0.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.

Abstract The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is a major pest of global citriculture. In the Americas and in Asia, D. citri vectors the phloem-limited bacterium, Candidatus Liberibacter asiaticus (CLas), which causes the fatal citrus disease huanglongbing, or citrus greening. Cell lines derived from D. citri can provide insight into both the basic biology of this pest and D. citri-associated pathogens including CLas. We previously identified CLG#2 as the optimal medium for long-term growth of D. citri primary cell cultures. Here we report on the establishment and characterization of three continuous D. citri cell lines, Dici1, Dici3, and Dici5, that have been passaged for > 40 times. Based on morphological and transcriptomic data, the Dici1 and Dici3 cell lines include undifferentiated and neurogenic progenitor cells. Dici1 and Dici5 are infected with Wolbachia. Both Dici1 and Dici5 are infected with D. citri reovirus, and Dici5 is also infected with D. citri-associated C virus. Dici3 is free of both Wolbachia and virus infection. These cell lines provide an ideal platform for the study of inter-microbial relationships as well as microbe interaction with host insect cells.

Abstract High-dimensional photon states (qudits) are pivotal to enhance the information capacity, noise robustness, and data rates of quantum communications. Time-bin entangled qudits are promising candidates for implementing high-dimensional quantum communications over optical fiber networks with processing rates approaching those of classical telecommunications. However, their use is hindered by phase instability, timing inaccuracy, and low scalability of interferometric schemes needed for time-bin processing. As well, increasing the number of time bins per photon state typically requires decreasing the repetition rate of the system, affecting in turn the effective qudit rates. Here, we demonstrate a fiber-pigtailed, integrated photonic platform enabling the generation and processing of picosecond-spaced time-bin entangled qudits in the telecommunication C band via an on-chip interferometry system. We experimentally demonstrate the Bennett-Brassard-Mermin 1992 quantum key distribution protocol with time-bin entangled qudits and extend it over a 60 km-long optical fiber link, by showing dimensionality scaling without sacrificing the repetition rate. Our approach enables the manipulation of time-bin entangled qudits at processing speeds typical of standard telecommunications (10 s of GHz) with high quantum information capacity per single frequency channel, representing an important step towards an efficient implementation of high-data rate quantum communications in standard, multi-user optical fiber networks.

Abstract Complex-valued neural networks process both amplitude and phase information, in contrast to conventional artificial neural networks, achieving additive capabilities in recognizing phase-sensitive data inherent in wave-related phenomena. The ever-increasing data capacity and network scale place substantial demands on underlying computing hardware. In parallel with the successes and extensive efforts made in electronics, optical neuromorphic hardware is promising to achieve ultra-high computing performances due to its inherent analog architecture and wide bandwidth. Here, we report a complex-valued optical convolution accelerator operating at over 2 Tera operations per second (TOPS). With appropriately designed phasors we demonstrate its performance in the recognition of synthetic aperture radar (SAR) images captured by the Sentinel-1 satellite, which are inherently complex-valued and more intricate than what optical neural networks have previously processed. Experimental tests with 500 images yield an 83.8% accuracy, close to in-silico results. This approach facilitates feature extraction of phase-sensitive information, and represents a pivotal advance in artificial intelligence towards real-time, high-dimensional data analysis of complex and dynamic environments.

Abstract Variants of SARS-CoV-2 have continued to emerge across the world and cause hundreds of deaths each week. Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies, additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, we screen 2.8 billion compounds from a DNA-encoded chemical library and identify small molecules that are non-covalent inhibitors targeting the conserved 3CL protease of SARS-CoV-2 and other coronaviruses. We perform structure-based optimization, leading to the creation of a series of potent, non-covalent SARS-CoV-2 3CL protease inhibitors, for coronavirus infections. To characterize their binding mechanism to the 3CL protease, we determine 16 co-crystal structures and find that optimized inhibitors specifically interact with both protomers of the native homodimer of 3CL protease. Since 3CL protease is catalytically competent only in the dimeric state, these data provide insight into the design of drug-like inhibitors targeting the native homodimer state. With a binding mode different from the covalent 3CL inhibitor nirmatrelvir, the protease inhibitor in the COVID drug Paxlovid, these compounds may overcome resistance reported for nirmatrelvir and complement its clinical utility.

Abstract Arctic permafrost is undergoing rapid changes due to climate warming in high latitudes. Retrogressive thaw slumps (RTS) are one of the most abrupt and impactful thermal-denudation events that change Arctic landscapes and accelerate carbon feedbacks. Their spatial distribution remains poorly characterised due to time-intensive conventional mapping methods. While numerous RTS studies have published standalone digitisation datasets, the lack of a centralised, unified database has limited their utilisation, affecting the scale of RTS studies and the generalisation ability of deep learning models. To address this, we established the Arctic Retrogressive Thaw Slumps (ARTS) dataset containing 23,529 RTS-present and 20,434 RTS-absent digitisations from 20 standalone datasets. We also proposed a Data Curation Framework as a working standard for RTS digitisations. This dataset is designed to be comprehensive, accessible, contributable, and adaptable for various RTS-related studies. This dataset and its accompanying curation framework establish a foundation for enhanced collaboration in RTS research, facilitating standardised data sharing and comprehensive analyses across the Arctic permafrost research community.

Abstract New and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could improve our understanding of viral biology and highlight new variants that warrant further study. Here we develop a generic, analytical epidemiological model to infer the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that substantially affect the transmission rate, both within and outside the Spike protein. The mutations that we infer to have the largest effects on transmission are strongly supported by experimental evidence from prior studies. Importantly, our model detects lineages with increased transmission even at low frequencies. As an example, we infer significant transmission advantages for the Alpha, Delta, and Omicron variants shortly after their appearances in regional data, when they comprised only around 1-2% of sample sequences. Our model thus facilitates the rapid identification of variants and mutations that affect transmission from genomic surveillance data.

Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.

Abstract It is generally accepted that a weakening of the North Atlantic thermohaline circulation caused the Younger Dryas cooling. Although the role of seasonality was emphasized previously, this aspect is rarely considered yet, and it remains elusive how this impacted hydroclimate during winters and summers across Central Europe. Here, we coupled biomarker-based δ18O and δ2H from Bergsee in southern Germany to reconstruct deuterium excess as a proxy for evaporation history from the Bølling-Allerød to the Preboreal. We compared this dataset with other biomarker isotope records in Central Europe. They are all lacking a strong isotopic depletion during the Younger Dryas, which is best explained by the summer sensitivity of the biomarker proxies: As Younger Dryas summers were relatively warm, there is an absence of the strong winter cooling signals recorded in annual water isotope records like Greenland or Lake Steißlingen. Lake evaporation at Bergsee together with other paleohydrological reconstructions draw a coherent picture of the Late Glacial hydroclimate, with strong evidence for warm and dry Younger Dryas summers. Rather than a southward shift of the Westerlies during winter, we suggest that a recently proposed feedback mechanism between North Atlantic sea ice extend, strong winter cooling and summer atmospheric blocking serves as a suitable explanation for summer dryness. Additional confidence to the robustness of these biomarker records is provided by the overall agreement of paleohydrological fluctuations during the Preboreal.

Abstract Over-coverage occurs when individuals who reside in a country leave or pass away, and this demographic event is not recorded in population registers, leading to population size overestimation. This problem can have important policy and decision-making consequences. With the increased reliance on incomplete but overlapping official registers for documenting whole populations or subgroups of populations, there is a need for more sophisticated modelling techniques that reliably estimate population size, and hence over-coverage, from such registers. Previous approaches have considered multiple systems estimation (MSE) for monitoring over-coverage, but MSE does not naturally extend to cases where individuals are followed over time. In this paper, motivated by the case study of Sweden, we develop a capture-recapture (CR) modelling framework for population registers that allows us to estimate the population size each year, the probability of presence for each individual in the population, conditional on their records, each year and to quantify the effect of demographic characteristics on the probability of emigration and re-immigration, amongst other parameters. Our results suggest that the CR approach, which accounts for the whole time series for each individual, gives a more realistic estimate of the population size compared to existing, deterministic approaches, especially when considering the subgroup of newly arrived individuals, and that it provides new insights on individual behaviour in terms of migration patterns than existing MSE approaches.

Abstract Diabetic Retinopathy (DR) stands as a significant global cause of vision impairment, underscoring the critical importance of early detection in mitigating its impact. Addressing this challenge head-on, this study introduces an innovative deep learning framework tailored for DR diagnosis. The proposed framework utilizes the EfficientNetB0 architecture to classify diabetic retinopathy severity levels from retinal images. By harnessing advanced techniques in computer vision and machine learning, the proposed model aims to deliver precise and dependable DR diagnoses. Continuous testing and experimentation shows to the efficiency of the architecture, showcasing promising outcomes that could help in the transformation of both diagnosing and treatment of DR. This framework takes help from the EfficientNet Machine Learning algorithms and employing advanced CNN layering techniques. The dataset utilized in this study is titled ’Diagnosis of Diabetic Retinopathy’ and is sourced from Kaggle. It consists of 35,108 retinal images, classified into five categories: No Diabetic Retinopathy (DR), Mild DR, Moderate DR, Severe DR, and Proliferative DR. Through rigorous testing, the framework yields impressive results, boasting an average accuracy of 86.53% and a loss rate of 0.5663. A comparison with alternative approaches underscores the effectiveness of EfficientNet in handling classification tasks for diabetic retinopathy, particularly highlighting its high accuracy and generalizability across DR severity levels. These findings highlight the framework’s potential to significantly advance the field of DR diagnosis, given more advanced datasets and more training resources which leads it to be offering clinicians a powerful tool for early intervention and improved patient outcomes.

Abstract Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer’s Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

Pico Island is one of the islands of the Azores archipelago located in the North Atlantic Ocean, where there are very specific conditions for vine cultivation. In this context, there is scarce knowledge related to grape ripening under these conditions. Thus, the aim of this study was to evaluate several physicochemical parameters, the phenolic composition, antioxidant capacity, and varietal aromatic potential, of the “Merlot”, Syrah”, and “Saborinho” grape varieties cultivated on Pico Island over three vintages. The outcomes obtained demonstrated that “Merlot” grapes showed a tendency for significantly higher values of estimated alcohol degree, total phenols, flavonoid and non-flavonoid phenols, total anthocyanins, color intensity, and antioxidant capacity over the three vintages. In addition, for individual anthocyanins, “Merlot” and “Syrah” grapes showed a predominance of acetyl-anthocyanins in relation to p-coumaroylated forms, while for “Saborinho” grapes, an oppositive tendency was observed. For varietal aromatic potential, only in the 2021 vintage was it possible to detect significantly different values between the three grape varieties studied. In this case, “Merlot” and “Syrah” grapes showed the significantly highest values. Considering all parameters analyzed, the results obtained for the “Merlot” grape variety seem to show a better adaptation of this variety to the conditions of Pico Island than the remaining two varieties studied.

Abstract There is much interest in analysing RNA, particularly with RNA Sequencing, across both research and diagnostic domains. However, its inherent instability renders it susceptible to degradation. Given the imperative for RNA integrity in such applications, proper storage and biobanking of blood samples and successful subsequent RNA isolation is essential to guarantee optimal integrity for downstream analyses. Especially for larger collections, it would be particularly beneficial if these methods would additionally offer affordability, minimal blood volume requirements and also long-term storage. In this study, RNA of high quality, suitable for transcriptomics, has been successfully isolated from 400 µL of EDTA and citrated whole blood samples in Boom’s lysis buffer stored at −85 °C for 10 years. Isolation was carried out using a modified Zymo Research Quick-RNA kit protocol. This isolation method showed significant improvement in RNA integrity when compared to RNA extracted using the original Boom method. RNA Sequencing provided high-quality data comparable to that of other studies using recently frozen blood in RNA stabilisation tubes. Additionally, sequencing data from blood collected in citrate and EDTA anticoagulants also showed excellent correlation.

Abstract In this article an 8-port annular ring-shaped MIMO antenna for 5G and 5G advanced applications is presented. An annular ring on the radiating plane and novel isolator structure on the ground plane are etched over a Rogers RT/Duorid (5870 tm) substrate to achieve high performance antenna for mm wave applications. A systematic study is performed, and an optimized single port antenna (Design-4) is selected among Designs (1-4). The intended 8-port MIMO antenna resonates at 36.4 GHz and exhibits 6.1 GHz (34.2-40.3 GHz) wide bandwidth $$|S_{11}| < -10 \, \text {dB}$$ and 40 dB high isolation level. The proposed antenna covers a complete band of 5G NR-n260 which supports time division duplexing (TDD) mode. Moreover, a unique design of suggested antenna attains a high-level gain of 8.3 dB at 39 GHz and more than 85.2 % radiation efficiency. MIMO characteristics such as ECC, TARC, MEG and CCL are studied and found them in acceptable limit. Additionally, an approach toward massive antenna with 16-port for mmWave applications is also demonstrated. The proposed 16-port massive antenna with more than 22 dB isolation exhibits two bands: first band in 30-33 GHz for ports P9-P16 and second band in 33.5-40.9 GHz for ports P1-P8. A prototype of suggested 8-port antenna is fabricated, tested and validated and found it in close agreement of simulated results.

Abstract Patients with gastrointestinal bleeding (GIB) exhibit varying tolerances to acute blood loss. We aimed to investigate the effect of relative Hb decrease (ΔHb%) on GIB outcomes. Participants enrolled in the Hungarian GIB Registry between 2019 and 2022 were analyzed. The primary outcome, defined as a composite endpoint, included in-hospital bleeding-related mortality and the need for urgent intervention. Four groups were created based on the lowest Hb measured during hospitalization (nadirHb), along with four subgroups categorized by ΔHb%. Regardless of the nadirHb, participants with higher ΔHb% had a higher probability of reaching the composite endpoint. A 30–40% ΔHb% decrease to a nadirHb of 80–90 g/L resulted in a similar likelihood of reaching the primary endpoint as a 0–10% ΔHb% to 70–80 g/L or 60–70 g/L, respectively (10% vs. 12%, p = 1.00; 10% vs. 10%, p = 1.00). Our results showed that a higher Hb decrease in GIB is associated with an increased untoward outcome rate even when the lowest hemoglobin exceeds the recommended transfusion thresholds. New randomized controlled trials investigating transfusion thresholds should consider ΔHb% as a potential key variable and risk factor.

Abstract Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD). A four-class machine-learning algorithm was trained using age and nine sleep biomarkers from patients with clinically-diagnosed manifest and prodromal NDDs, including Alzheimer’s disease dementia (AD = 27), Lewy body dementia (LBD = 18), and isolated REM sleep behavior disorder (iRBD = 15), as well as a control group (CG = 58). The algorithm was validated in a total of 381 recordings, which included the training data set plus an additional AD = 10, iRBD = 18, Parkinson disease without dementia (PD = 29), mild cognitive impairment (MCI = 78) and CG = 128. Test–retest consistency was then assessed in LBD = 10, AD = 9, and CG = 46. The agreement between the NDD profiles and their respective clinical diagnoses exceeded 75% for the AD, LBD, and CG, and improved when NDD participants classified Likely Normal with NDD indications consistent with their clinical diagnosis were considered. Profiles for iRBD, PD and MCI participants were consistent with the heterogeneity of disease severities, with the majority of overt disagreements explained by normal sleep characterization in 27% of iRBD, 21% of PD, and 26% of MCI participants. For test–retest assignments, the same or similar NDD profiles were obtained for 88% of LBD, 86% in AD, and 98% of CG participants. The potential utility for NDD subtyping based on sleep biomarkers demonstrates promise and requires further prospective development and validation in larger NDD cohorts.

Abstract 8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers. Potassium bromate (KBrO3)-induced 8-oxoGs occur with similar sequence preferences as their derived substitutions, indicating that the reactivity of specific oxidants dictates mutation sequence specificity. While 8-oxoG occurs uniformly across chromatin, 8-oxoG-induced mutations are elevated in compact genomic regions, within nucleosomes, and at inward facing guanines within strongly positioned nucleosomes. Cryo-electron microscopy structures of OGG1-nucleosome complexes indicate that these effects originate from OGG1’s ability to flip outward positioned 8-oxoG lesions into the catalytic pocket while inward facing lesions are occluded by the histone octamer. Mutation spectra from human cells with DNA repair deficiencies reveals contributions of a DNA repair network limiting 8-oxoG mutagenesis, where OGG1- and MUTYH-mediated base excision repair is supplemented by the replication-associated factors Pol η and HMCES. Transcriptional asymmetry of KBrO3-induced mutations in OGG1- and Pol η-deficient cells also demonstrates transcription-coupled repair can prevent 8-oxoG-induced mutation. Thus, oxidant chemistry, chromatin structures, and DNA repair processes combine to dictate the oxidative mutational landscape in human genomes.

Abstract The mungbean yellow mosaic India virus (MYMIV, Begomovirus vignaradiataindiaense) causes Yellow Mosaic Disease (YMD) in mungbean (Vigna radiata L.). The biochemical assays including total phenol content (TPC), total flavonoid content (TFC), ascorbic acid (AA), DPPH (2,2-diphenyl-1-picrylhydrazyl), and FRAP (Ferric Reducing Antioxidant Power) were used to study the mungbean plants defense response to MYMIV infection. A wide range was recorded for the Area Under Disease Progress Curve (AUDPC; 1.75-1266.98) and coefficient of infection (CI; 0.33–45.53). In YMD susceptible genotypes, significant variations were observed for TPC [2001.27-2834.13 mgGAE/100 g dry weight (DW)], TFC (252.65–341.30 mg/100 g DW), AA (40.33–64.69 mg/100 g DW), DPPH (32.11–53.47% scavenging effect DW), and FRAP (48.99-101.22 µmol Fe2+/g DW). Similarly, in resistant genotypes also wide range was recorded for TPC (1788.50-2286.38 mgGAE/100 g DW), TFC (206.12–337.32 mg/100 gDAS samples varied from 384. 6.46–47.64% scavenging effect DW), and FRAP (53.68-114.24 µmol Fe2+/g DW). Except for FRAP, other studied parameters were in the lower range in the resistant genotypes than the susceptible genotypes. Genome-wide association studies (GWAS) of 132 genotypes have identified 31,953 single nucleotide polymorphism (SNPs). MLM (Mixed Linear Model) and BLINK (Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway) models have identified 119 shared SNPs for various biochemical traits and MYMIV resistance. The key candidate genes include VRADI09G06940 (YMD resistance, TIR-NBS-LRR class, chr. 9), VRADI01G05030 [flavonoid biosynthesis; MYB65 transcription factor (TF); chr. 1], VRADI03G07600 (phenol biosynthesis; GATA TF 16; chr. 3), VRADI04G08470 (ascorbic acid; heat shock protein 70 kDa protein; chr. 4), VRADI04G07510 (FRAP; subtilisin-like protease SBT1.9; chr. 4), and VRADI05G02870 (DPPH; vacuolar protein sorting-associated protein 2; chr. 5). The identified genomic resources will enhance mungbean genomics and facilitate the advancement of genomic-assisted breeding in mungbean.

Abstract The goal of this study was to determine how radiologists’ rating of image quality when using 0.5T Magnetic Resonance Imaging (MRI) compares to Computed Tomography (CT) for visualization of pathology and evaluation of specific anatomic regions within the paranasal sinuses. 42 patients with clinical CT scans opted to have a 0.5T MRI scan for this study. Scans were completed from June 2021 to June 2022 with an average of 65.2 days from CT to MRI. A neuroradiologist and neuroradiology fellow evaluated the images to answer several questions and provide a confidence score for each based on image quality. Responses between the CT and MRI scans were compared for intramodality and intermodality agreement. The Likert scores demonstrate that MRI performed well in assessing mucosal thickening. Performance was not adequate for anatomical questions for presurgical planning. 0.5T MRI is able to produce high quality imaging of the sinuses. This could be used as a radiation free test to correlate mucosal thickening with patient’s symptoms. However, a CT would be needed to screen for ostiomeatal obstruction and anatomical visualization of critical variants for presurgical planning.

Abstract Network energy has been conceptualized based on structural balance theory in the physics of complex networks. We utilized this framework to assess the energy of functional brain networks under cognitive control and to understand how energy is allocated across canonical functional networks during various cognitive control tasks. We extracted network energy from functional connectivity patterns of subjects who underwent fMRI scans during cognitive tasks involving working memory, inhibitory control, and cognitive flexibility, in addition to task-free scans. We found that the energy of the whole-brain network increases when exposed to cognitive control tasks compared to the task-free resting state, which serves as a reference point. The brain selectively allocates this elevated energy to canonical functional networks; sensory networks receive more energy to support flexibility for processing sensory stimuli, while cognitive networks relevant to the task, functioning efficiently, require less energy. Furthermore, employing network energy, as a global network measure, improves the performance of predictive modeling, particularly in classifying cognitive control tasks and predicting chronological age. Our results highlight the robustness of this framework and the utility of network energy in understanding brain and cognitive mechanisms, including its promising potential as a biomarker for mental conditions and neurological disorders.

Abstract E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5). BALF samples were analyzed by Luminex multiplex assay, RNA sequencing, and mass spectrometry. After treating BEAS-2B lung epithelial cells with vaping and non-vaping BALF, LDH release was quantified. THC-EVALI BALF had significant increases in IFNγ, CCL2, CXCL5, and MMP2 relative to non-vaping patients. RNA sequencing showed enrichment for biological oxidation, glucuronidation, and fatty acid metabolism pathways. Oleic acid and arachidonic acid metabolites were increased in THC-EVALI, as were oxidized phosphatidylethanolamines (PE) such as PE(38:4). THC-EVALI BALF induced more LDH release compared to BALF from non-vaping patients. Thus, THC-EVALI is characterized by altered phospholipid composition, accumulation of lipid oxidation products, and increased pro-inflammatory mediators that may contribute to epithelial cell death. These findings serve as a framework to study novel oxidized phospholipids implicated in the pathogenesis of EVALI.

Abstract Postpartum urinary retention has a wide range of publicized incidences, likely caused by frequent misdiagnosis of this puerperal complication. Especially covert postpartum urinary retention has a high number of missed diagnoses due to the lack of symptoms and the time-extensive diagnostics via ultrasound, leading to no treatment and no appropriate follow-up. To simplify the diagnosis and establish a screening tool we analyzed the application of portable handheld-ultrasound devices (PUD) as used in Point-of-care diagnostics in comparison to established standard ultrasound devices (SUD). This prospective study aimed to evaluate the reliability of non-piezo, chip-based PUD in comparison to the measurement withSUD, containing a piezo transducer, as golden standard for the ultrasound diagnosis of postpartum urinary retention. Randomly, 100 participants between the first and seventh day after delivery in an obstetric ward underwent ultrasound examinations using a EPIQ 5 W (Philips) as SUD and a Butterfly iQ (Butterfly Network) as PUD to compare the accuracy in bladder size after micturition and the estimated post-void residual volume. Intraclass correlation coefficients, Bland-Altman plots, and Pearson correlation coefficients were used for analyzing the reliability and agreement between the measurements of these devices and were calculated for subgroups as body mass index, mode of delivery and timepoint of delivery. The results show a near-perfect agreement (0.994) and correlation (r = 0.982) for estimated post-void residual volume and for most measurements between the two types of ultrasound devices. The agreement rate for the diagnosis of covert postpartum urinary retention is 100%. Subgroup analyses lack a significant difference reflected by agreement and correlation rates. These findings affirm the high reliability of PUD for the diagnosis of postpartum urinary retention and supports their integration into daily clinical practice, thereby simplifying regular controls of the bladder by physicians during daily rounds on the ward. This technology may allow a higher diagnosis rate so that patient care can be optimized and the long-term impact on continence and quality of life can be studied and analysed.