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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: [email protected]

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    [email protected],  [email protected]

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

A document by Rauno Harvima. Click on the document to view its contents.

Multi-arm harvesting robots offer a promising solution to the labor shortage in fruit harvesting, due to their ability to improve harvesting efficiency. However, multi-arm harvesters necessitate additional visual sensors to acquire distribution information of fruits within larger working spaces. Greater demands are consequently imposed on graphics computation, leading to increased costs in computing hardware of robot system. To balance the graphics computing cost and reduce energy consumption, distributed graphics computation frameworks for multi-arm robot vision system are proposed in this study. First, a host-edge framework is proposed to assign the tasks of image inference and depth alignment to host computer and edge computing modules through a decentralized mode of local connection. Moreover, to increase the endurance time of robot in application, the edge computing modules are reduced and the fifth generation mobile communication is integrated into robot graphics computing system to transfer on-board image processing to a remote computing server with MQTT protocol. To verify the effectiveness of the proposed framework, comprehensive experiments were performed, demonstrating that, compared with traditional computing framework, the proposed local distributed framework reduced 35.6% average time consumption, and over 20 FPS average processing speed can be achieve. The remote distributed framework has reduced the computational power consumption of the on-board system by approximately 23.1% while ensuring the performance is not lower than the local distributed framework. Finally, by discussing the two frameworks in terms of stability and cost, we present the commercial viability for the application of multi-arm harvesting robot.

Background Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV-bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children < 6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. Methods In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV-bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. Results 234 patients were included. RSV was detected in 141/234(60.2%), being less common in the immunized group (37% vs 75%, p<0.001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral co-infections, the need for NIV/CMV or length of hospital stay. Conclusions This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-LRTI hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral co-infections nor differences in clinical severity once admitted.

Background: Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT assessing their specificity and sensitivity in diagnosing peanut allergy. Methods: Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. Results: On the eleven studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients was studied as well with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). Conclusion: BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanut. More investigations on the potential for MATs diagnostic methods are warranted.

The re-emergence of the monkeypox virus (MPXV) three years after the start of the SARS-CoV-2 epidemic further emphasizes the need to develop broad spectrum antivirals (BSAs) that might control the spread of poorly understood pathogens. The induction of innate immune responses to a viral infection triggers rapid expression of type-I-interferon (IFN-I), which subsequently results in the differential expression of more than 300 genes that foster an antiviral state. Whereas the expression of a majority of these “interferon-stimulated genes” (ISGs) are enhanced, , other ISGs’ expression are suppressed, including some involved in lipid metabolism which is hijacked to promote viral growth. Herein, we report that the expression of fatty acid synthase (FASN), an enzyme involved in de novo biosynthesis of fatty acids, was significantly reduced upon MPXV infection. Moreover, MPXV infection was impaired in FASN knockout cells, and biological inhibitors of FASN significantly inhibited MPXV. Interestingly, the ISG chosterol-25-hydroxylase was induced in MPXV-infected cells, and its enzymatic product, 25-hydroxychlosterol (25HC), blocked MPXV infection. Overall, this study indicates that 25HC and FASN inhibitors are highly potent BSAs and may have therapeutic applications in combating understudied infectious diseases in early outbreak settings when targeted therapies have not yet been developed.

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the non-uniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions . Furthermore, the clinical effectiveness and robustness of this model was validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination.

A document by Kenji Yamada. Click on the document to view its contents.

The goal was to evaluate the hysteresis performance of segmented buckling resistant braces with low yield point steel LYP160, the monotonic tensile and cyclic loading tests of LYP160 were conducted and the corresponding laws have been obtained. According to the load-displacement curves of the specimen, the low yield point steel was characterized by good ductility and energy absorption ability. With the consideration of Chaboche model on the materials, the cyclic loading was simulated by ABAQUS and the cyclic hardening parameters of low yield point steel were obtained. On this basis, the hysteretic properties of buckling resistant braces under cyclic loads were simulated and analyzed. After the analysis and comparison of buckling resistant braces specimens with isotropic core plate and segmented variable section core plate, it can be found that: When the buckling resistant braces with isotropic core plate was loaded to L/100, the lateral deformation of BRB would reach 17mm and the seriously squeezed would observe on lateral constraint members. The buckling resistant braces would fail due to the accumulation of deformation on lateral constraint members at both ends of BRB. When the segmented buckling resistant braces was applied, the core plate with variable section would yield first in the middle part, other parts could still continue to consume energy due to the action of the limit plate. It would avoid the phenomenon that other parts could not continue to consume energy after the core plate failed at one point first. Under the action of cyclic loads, the stiffness of the segmented buckling resistant brace was constant and the better ability to consume energy was reflected.

Stable isotopic methods in hydroclimate monitoring are powerful for improving water resources management, but applications are limited, especially in semi-arid regions where such management is needed most. In this study, we show that we can address shortcomings related to lack of a seasonal signal using stable water isotopic signatures measured over the eastern San Francisco Bay Area of California during two contrasting events. We use hydrometric data from a gauged watershed in the study area and isotopic signatures of rain sampled at more than 20 locations during two contrasting storm events (Winter Storm Olive in February, 2023 and a warmer atmospheric river event in March 2023), and apply a solute transport model with a travel-time approach to examine predicted watershed responses and potential water tracing applications. The observed range in δ 18O in the rain samples is similar for both storms, about 5‰. However, the distributions do not overlap – the mean air temperature during Olive was about 2 0C, and the mean δ 18O of the rain samples is -12‰, while the AR event had a mean temperature of about 9 0C and a mean δ 18O of -6‰, close to the long-term average δ 18O measured in local precipitation. In the model results, event size exerts a strong control on the relative amounts of runoff vs pre-event water in the stream, while uncertainty in stream hydrograph separation is related to the degree of contrast between precipitation/runoff and pre-event water. Key to flood prediction, adaptation and mitigation, especially in coastal urban areas, is knowledge of the contributing water sources and timing of flows in streams and other features susceptible to flooding. The strong contrast in stable isotopes between these two events over the same area, illustrates the potential to use stable isotope signatures to track the transport and mixing of event water through natural and engineered watersheds.

Importance: To provide a current evaluation of bibliometric trends in the Otolaryngology literature focused on randomized controlled trials (RCTs). RCTs hold an important role in research as bias controlled assessments of clinical interventions. Objective: The purpose of this study is to evaluate the proportion of published RCTs in the Otolaryngology literature. Design: Quality Improvement scoping bibliometric review. Setting: Published articles in eight Otolaryngology journals from January 1, 2016 - December 31, 2020. Main Outcomes and Measures: Included articles were categorized as a RCT, secondary research, other clinical research, case report, primary basic science, or other study type. Additionally, studies were categorized as American, Canadian, British, or other international origin according to the corresponding author’s institutional address. The proportion of published RCTs were compared by national origin and to an earlier bibliometric analysis investigating Otolaryngology journal publications from 2008-2012 using Pearson’s Chi-Squared testing with Bonferroni correction. Results: A total of 6797 articles were reviewed and included for analysis. There was a significant difference in the proportion of RCTs published by national origin, 1.3% USA, 2.2% Canada, 2.7% UK, 3.4% other (p < 0.01). There was a significant decrease in the proportion of RCTs published from 2008-12 to 2016-2020 (3.1% vs. 2.3% respectively, p < 0.01). Conclusions: Although the current study analyzed only a select sample of all Otolaryngology research output, this study suggests that North American researchers are publishing less RCTs than researchers in other countries. Moreover, RCTs are declining as a proportion of the published Otolaryngology literature over time, which is a threat to the evidence base for current and future Otolaryngological practice.

The immune system is crucial in defending the body against pathogens, with, specifically immunoglobulins G (IgG) and immunoglobulins E (IgE), playing key roles in immune defense and regulation. During infections, B cells can undergo class switching to produce IgG antibodies recognize specific epitopes on microbial antigens and enhance their phagocytosis by immune cells like macrophages and neutrophils. They can engage in opsonization, neutralization, and complement activation, all contributing to the immune response against pathogens. During allergic reactions, class switching of IgE takes place when B cells produce IgE rather than other classes of antibodies. The choice between IgG and IgE antibody production involves intricate regulatory mechanisms influenced by factors such as the type of antigen encountered, the microenvironment, and the presence of cytokines. IgG responses are typically associated with effective microbial clearance and long-term immune memory, while IgE responses are more relevant for defense against parasites and are responsible for allergic disorders. Microbial interactions within the gut can influence the balance between IgG and IgE responses, potentially impacting susceptibility to both infections and allergies. In conclusion, the balance between IgG and IgE responses is essential for maintaining immune homeostasis and effective defense against microbes. A deeper understanding of class-switching mechanisms and factors influencing production is essential for developing strategies to manage allergies and enhance immune responses against infections. This review will focus on the advance research in this field that holds promise for uncovering novel therapeutic approaches that leverage the interplay between IgG, IgE, and microbial interactions. Graphical abstract: Diagrammatic representation of class-switching mechanism during microbial infection. (The class switching process ensures the initiation of the diverse aggregation of antibodies which are capable of mounting effective immune response against wide range of microbes.) (Figure created by using BioRender)

This article reports an interesting case of a 63-year-old woman with no previous medical history who presented with non-specific symptoms and pancytopenia and was diagnosed with myelodysplastic syndrome with excess blasts (MDS-EB). The paper provides a detailed description of the patient’s clinical and laboratory findings, including peripheral blood, bone marrow aspirate, and trephine biopsy. The report highlights the differences in the classification of myeloid neoplasms between the current WHO-HAEM4R (2017), the previous edition (WHO -HAEM4 [2008]), and the forthcoming WHO-HAEM5 and ICC. The case is significant as it illustrates the characteristic morphology, diagnostic investigations, and the importance of comprehensive risk stratification in MDS-EB. The case reported here has a complex karyotype with five chromosomal abnormalities, which underlines the poor outcome of this entity. This article also discusses the proposed change in nomenclature from MDS-EB to MDS with increased blast percentage (MDS-IB) and ‘myelodysplastic neoplasm’ replacing the term ‘myelodysplastic syndrome’ in the forthcoming WHO classification (WHO-HAEM5) and why this case may be better classified using WHO-HAEM5.