Discover and publish cutting edge, open research.

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.

Background and Purpose Botulinum Neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial repercussions on clinical use. Experimental Approach Here, we combined BoNT/A with two fast-acting inhibitors of excitation-contraction coupling (ECCI), either the µ-conotoxin CnIIIC or dantrolene, and tested the effect of their co-injection on a model of hind-limb paralysis in rodents using behavioral, biochemical, imaging and electrophysiology assays. Key Results We report that the BoNT/A-ECCI combination accelerated the onset of muscle relaxation. Surprisingly, it also potentiated the peak effect and extended the duration of the three BoNT/A commercial preparations onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA. We found that ECCI co-injection increased the number of BoNT/A molecules entering motoneuron terminals, which induced a faster and larger cleavage of SNAP-25 during the onset and peak phases, and prolonged the attenuation of nerve-muscle neurotransmission during the recovery phase. We estimate that ECCI co-injection yields a three-fold potentiation in BoNT/A pharmacological activity. Conclusions and Implications Overall, our results show that the pharmacological activity of BoNT/A can be combined and synergized with other bioactive molecules and uncover a novel strategy to enhance BoNT/A neuromuscular effects without altering the neurotoxin moiety or intrinsic activity, thus maintaining its exceptional safety profile.

AIM: Changes in bird clutch and egg sizes across geographical gradients are issues often debated among ecologists, where latitudinal cline is a central issue in several discussions. There is an understanding that these patterns are primarily driven by climatic characteristics, where latitude acts as a proxy. Many studies attempt to analyse local climatic factors causing variation in life history traits but face methodological limitations. Here, as few studies have been able to, we achieve a robust dataset that covers a large territorial extent to answer this main biogeographical question. LOCATION: American continent (New World). METHODS: We approached the geographically widespread Tyrannus genus (kingbirds) and collected breeding data from 35 scientific egg collections in South and Central America, USA, and Europe. After several data checking layers, including spatial, temporal and taxonomic checking, we analysed the relationship between kingbird’s clutch and egg sizes with different climatic scales. RESULTS: The analyses of 1358 clutches and 4750 eggs confirmed that kingbird’s clutch and egg sizes increase towards the poles. Both breeding traits vary according to main climates, regional sub-climates, and local temperature and precipitation conditions. Regions with more climatic variation had the largest clutches, but sites with colder winters did not have the largest clutches. Tyrannus egg size increased in environments with less extreme dry periods. The increase of egg size with latitude can be explained by the significant relationship between larger eggs with sites with lower temperatures. MAIN CONCLUSIONS: Our findings suggest a robust correlation of residual variation in breeding traits with climatic conditions at both regional and local levels. Highly locally adapted species using climatic parameters as cues should also respond to interannual weather variations. With current discussions about climate change’s effects on ecosystems, the insights provided in this work can assist in understanding how species will cope under future climate scenarios.

Investigations into sensory coding in the visual system have typically relied on the use of either simple, unnatural visual stimuli, or natural images. Simple stimuli, such as Gabor patches, have been effective when looking at single neurons in early visual areas such as V1, but seldom produce large responses from mid-level visual neurons or neural populations with diverse tuning. Many types of “naturalistic” image models have been developed recently which bridge the gap between overly-simple stimuli and experimentally infeasible natural images. These stimuli can vary along a large number of feature dimensions, introducing new challenges when trying to map those features to neural activity. This “curse of dimensionality” is exacerbated when neural responses are themselves high-dimensional, such as when recording neural populations with implanted multielectrode arrays. We propose a method that searches high-dimensional stimulus spaces for characterizing neural population manifolds in a closed-loop experimental design. Stimuli were generated using a deep neural network in each block by using neural responses to previous stimuli to make predictions about the relationship between the latent space of the image model and neural responses. We found that these latent variables from the deep generative image model explained stronger linear relationships with neural activity than various alternative forms of image compression. This result reinforces the potential for deep generative image models for efficient characterization of high-dimensional tuning manifolds for visual neural populations.

Land use change (LUC) is a key factor affecting nutrient budgets in agricultural soils. Comparing the long-term trajectories of nutrient budgets and changes in soils at a regional scale with contrasting LUC is critical to optimizing nutrient management and minimizing adverse environmental effects. We investigated the nutrient budgets and changes in soils in two counties in the south Loess Plateau, China, with contrasting LUCs from 1992 to 2017. Wugong County has cereals as the main crop, whereas Meixian County has the main cereal crops changed to kiwi orchards. We found that nitrogen (N), phosphorus (P), and potassium (K) inputs in two counties increased rapidly, and the nutrient outputs by crop harvests remained relatively stable. This resulted in increasing nutrient surpluses in the soils of two counties. Nutrient surplus in the orchard-dominated county was higher than that of the cereal-dominated county, and nutrient use efficiencies were contrasting. High N surplus in the orchard-dominated county resulted in high nitrate-N accumulation in deeper soil profiles of orchards. High P and K surpluses in the two counties significantly increased available P and K in 0-20 cm depth. Soil available P and K in the orchard-dominated county were significantly higher than in the cereal-dominated county, which was also significantly higher than the threshold values of available P and K contents in soils. We conclude that comprehensive measures should be taken to control nutrient surpluses, which will help to balance nutrient inputs and outputs and minimize nutrient losses in intensive horticultural crop systems.

Good ’ s Syndrome Combined withCMVGastro enteritis: A Case Report and Literature ReviewXiaoran li, Yanbin Liu∗Authors Affiliation: Center of Infectious Diseases, West China Hospital of Sichuan University, 37# Guo Xue Xiang, Chengdu 610041,Sichuan , China∗Corresponding author:[email protected]

Double-Positive Anti-GBM and ANCA Vasculitis : 2 case reports and review of the literature

In the absence of directing auxiliaries, catalytic addition of nucleophiles to unactivated alkynes with accurate control of regioselectivity remains an ongoing challenge in organic chemistry. Herein, we realized a Ag-catalysed regiospecific hydration process of unactivated al-kynes. Computational investigations offered insights into the origin of the regiochemical outcome. The practicability and efficacy of the protocol was exemplified by its simple reaction conditions without incorporation of acidic additives, as well as the tolerance of a wide range of alkynes equipped with various functional groups, leading to the ketone products in up to 98% yield. Direct modification of bioac-tive organic molecules and gram-scale experiments further showcased the application potential of the strategy. The catalyst control prin-ciples are expected to advance efforts towards the development of general site-selective addition of nucleophile to unsaturated sub-strates, removing the requirement for neighboring activating groups.

We aimed to assess the epidemiological characteristics of hepatitis B virus (HBV) infection in Chinese adults at different phases of the coronavirus disease 2019 (COVID‐19) pandemic, that is, before, during the pandemic, and after the easing of restrictive measures. We included 20,357 adult patients who visited Mianyang Hospital and had hepatitis B DNA tests from January 1, 2018, to June 30, 2023. Clinical information and HBV test results were extracted from the laboratory information system. We calculated the positive rate of HBV detection by age groups, gender, seasons, types of patients, and stages of the COVID‐19 pandemic. Nonlinear associations between age and risk of HBV infection in three stages of the pandemic were assessed by restricted cubic spline regression models. Among 20,357 patients, 2,670 (13.1%) were tested as positive. The highest positive rate was observed in the 18-25 age group (i.e., 16%). HBV infection showed an insignificant pattern among seasons. Although there is no statistical significance regarding the positive rate at three phases of the pandemic, we observed that the rate went high during the pandemic and saw a sharp decline after easing the measures among the population ( p < 0.05), which consisted of our regression models. In addition, regression analyses suggested that the age effect became weaker after easing all restrictive measures compared with other stages. Based on our findings, we called for attention from health professionals and caregivers on the new epidemiological characteristics of HBV infection in advance to deal with the potential increase under restrictive measures.

Solvation, the result of the complicated interplay between solvent-solute and solvent-internal interactions, is one of the most important chemical processes. Consequently, a complete theoretical understanding of solvation seems a heroic task. However, it is possible to elucidate fundamental solvation mechanisms by looking into simpler systems, such as ion solvation in atomic baths. In this work, we study ion solvation by calculating the ground state properties of a single ion in a neutral bath from the high-density regime to the low-density regime, finding common ground for these two, in principle, disparate regimes. Our results indicate that a single $^{174}$Yb$^+$ ion in a bath of $^{7}$Li atoms forms a coordination complex at high densities with a coordination number of 8, with strong electrostriction, characteristic of the snowball effect. On the contrary, treating the atomic bath as a dilute quantum gas at low densities, we find that the short range of the ion-atom interaction plays a significant role in the physics of many-body bound states and polarons. Furthermore, in this regime, we explore the role of a putative ion trap, which drastically affects the binding mechanism of the ion and atoms from a quantum gas. Therefore, our results give a novel insight into the universality of ion-neutral systems in the ultracold regime and the possibilities of observing exotic many-body effects.

Abstract Aim As the population continues to age, the occurrence of chronic illnesses and comorbidities that often necessitate the use of polypharmacy has been on the rise. Polypharmacy, among other factors that tend to coincide with chronic diseases such as obesity, impaired kidney and liver function, and older age, can increase the risk of medication errors (MEs). Our study aims to evaluate the prevalence of MEs in the Internal medicine, Cardiology, and Neurology departments at the secondary level university hospital. Methods We conducted a prospective observational study of 145 patients electronic or paper-based data of inpatient prescriptions and patients’ pharmacokinetic risk factors, such as an impairment of renal and/or hepatic function, weight, and age. Results All included patients collectively received 1252 prescribed drugs. The median (Q1; Q3) number of drugs per patient was 8 (7;10). At least one ME was identified in 133 out of the 145 patients, indicating a significantly higher prevalence than hypothesized (91.7% vs. 50%; p < 0.001). There was moderate, positive correlation between the quantity of prescribed drugs and the number of MEs, meaning that the more drugs are prescribed, the higher the number of identified MEs (Spearman’s rho = 0.428; p < 0.001). Conclusion These findings suggest that there is a need of continuous medication education activity for prescribing physicians, continuous evaluation of prescription appropriateness to objectively identify the MEs, and to contribute to more rational patient treatment.

Letter to the Editor: Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia Aimen Waqar Khan1, Shireen Asifa2, Fatima Monis1, Fareena Wazir3 and Iqra Muneer2AFFILIATION : 1Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.2Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan. 3Department of Medicine, Sir Syed College of Medical Sciences for Girls, Karachi, Pakistan.Dear Editor,We have read with great enthusiasm your study titled “Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia ” by Brik-Simon et al [1]. It was truly an honor to read such a detailed and methodical study that explored the platelet count response and safety of hydroxychloroquine (HCQ) in treating pediatric patients with systemic lupus erythematosus (SLE) related immune thrombocytopenia (ITP). However, after critical appraisal, we believe that certain points warrant discussion in order to alert clinicians and researchers regarding the conclusions drawn.As noted, platelet count response was the main metric outcome in assessing the safety and efficacy of HCQ. While this is pertinent to evaluating how well the said drug manages pediatric ITP, we believe other metrics like quality of life, long-term prognosis, and bleeding severity could offer a more thorough assessment of therapy efficacy [2]. Secondly, it is to be acknowledged that although no side effects linked to HCQ medication were reported, the short follow-up period and retrospective design may have hampered proper safety evaluation. It is therefore important to closely monitor and report long-term safety data on the use of HCQ in pediatric patients including potential eye damage and cardiomyopathy [3]. Furthermore, as females made up the vast majority of patients recruited, the study does not clearly elucidate whether the platelet count was measured keeping menstrual variability in mind and if so, whether the time of measurement was kept constant throughout. It is important to have done so as studies have demonstrated inter-menstrual variability in platelet counts attributable to the physiological changes in hormonal levels [4]. In addition to the number of platelets, we believe bleeding severity should have also been included. Moreover, females have been physiologically reported to have higher platelet counts than men [5] – an important confounder that must be borne in mind. Also, adherence to therapy in this study was assessed by self-reports. When it comes to adherence to medications by self-reports, there are concerns over the validity of the results due to memory recall biases and a tendency to overestimate the patient’s routine in taking the medication. There can also be differences in question phrasing and recall time intervals [6] therefore raising doubts over the validity of the findings reported. Finally, the duration of ITP at HCQ initiation is also different for patients, ranging from .75 to 52 months. Studies have shown that in up to 70-80% of children ITP usually resolves within 6 months [7].To conclude, while we commend the authors’ efforts in conducting this study, we believe addressing the aforementioned limitations will greatly help enhance the credibility of the findings and guide future researches in providing a more refined insight into this topic.

Background: Huashi Baidu granule (HSBD), an approved herbal formula for treating COVID-19, demonstrates safety and efficacy. Despite its market approval, the detailed methodology and identification of its active components remain unexplored, leaving its bioactive constituents and action mechanisms unclear. Methods: This study investigated the potential mechanisms of HSBD’s active ingredient in treating COVID-19. Our approach integrated various techniques, including the GEO database, network pharmacology, surface plasmon resonance, molecular docking and molecular dynamics simulations, to formulate a comprehensive research strategy. Results: The UHPLC-QqQ-MS/MS method employed for HSBD analysis proved stable, reliable, and reproducible. We identified 25 principal components in HSBD, with seven compounds detected in plasma, namely pogostone, p-hydroxybenzoic acid, Paeoniflorin, Rhein, Emodin, ephedrine hydrochloride, and pseudoephedrine hydrochloride. Protein-Protein Interaction (PPI) network analysis identified MMP9 as a pivotal target, while KEGG pathway analysis indicated that HSBD mediates its therapeutic effects on COVID-19 primarily through the TNF-α and PI3K-AKT pathways. Surface plasmon resonance analysis revealed that Paeoniflorin and Rhein exert their antiviral effects by interacting with RBD and ACE2, respectively. In contrast, Emodin’s antiviral mechanism predominantly involves binding to MMP9. Molecular docking results indicated strong binding affinities of Rhein and Paeoniflorin to the hACE2 protein, and high binding affinities of Paeoniflorin, Rhein, and Emodin to the MMP9 protein, all of which were corroborated by molecular dynamics simulations. Conclusion: We investigated the methodology and identified the active components of HSBD, focusing on those absorbed into the plasma, to elucidate the effective material basis of HSBD in the treatment of COVID-19, our research offer insightful exploration into its mechanisms of action against COVID-19.