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: mpw1001@cam.ac.ukThe 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: wanghesheng@sjtu.edu.cn

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:    rjzhou@cuhk.edu.hk,  rishikesh.pandey@uconn.edu

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.

Temperament is one of the factors that explain individual differences in child cognition, and it is usually measured through parental reports. Few studies showed that temperament reports varied depending on whether the reporter is a parent or a teacher, but a quite unexplored question is how each report predicts child cognition. This study analyzes how temperament reports from parents and teachers, predict the performance in a fluid intelligence task in 87 Argentinean children aged 4-5 years from medium-to-low socioeconomic status. Children were administered the Matrix subtest of KABC-II, and their temperament was evaluated with the CBQ Very Short Form, administered to parents and also to teachers. We will run one multilevel mixed-effects linear regression for CBQ dimensions, including teacher report of child temperament as the first level of nesting, and parental report of child temperament as the second level; the Matrix subtest’s total score will be the dependent variable.

Aggregation-induced emission luminogens (AIEgens) have been regarded as one of the significant prospects for organic light-emitting diodes, sensors, biological therapies, etc. owing to their intense emission in aggregated states. The expanded π-conjugated molecule conformations supposedly acquire the emission with a lower energy, however the optical performance of AIEgens in aggregated states defies this empirical assumption. The unexpected photophysical characteristics of AIEgens make it more challenging to design molecular conformations. Herein, to unveil the crucial factors dominating the optical performance of AIEgens, a series of diphenyldibenzofulvene (DPDBF) derivatives in crystals are utilized. We revealed that the emission energy of DPDBF derivatives in crystals is attributed to the tight connection with the conformation of the planar π-conjugated segment, but not the conformation torsion of phenyl blades or the intermolecular coupling, after systematically analyzing the impact factors, including molecular conformation parameters and intermolecular coupling, and further proved with the calculation results. Although the energy gap between the HOMO and LUMO is somewhat reduced by the expanded π-conjugated molecular conformation of the aforementioned DPDBF derivatives, the Stokes shift effect, which is primarily influenced by the conformation of the planar π-conjugated moiety, can realize to adjust the emission energy in a much more effective manner.

The reproductive investment strategy is important for the survival and reproduction of parents. Yet, due to extra-pair copulation behavior of female, socially monogamous males may end up making reproductive investment in some offspring that, in terms of genetics, are not theirs. Our study centered on varied tits (Sittiparus varius), a socially monogamous species with high proportion of extra-pair paternity. We compared male and female reproductive investment (nest defense and brood investment) and tested if extra-pair paternity, mate’s body condition, and mate’s investment affect their reproductive investment. Results showed that, the nest defense strength of males and females the difference was non-significant; and on feeding frequency, the difference was clear: females were significantly higher than that of males. With or without of extra-pair offspring, mate’s body condition and mate’s feeding frequency were not significantly related to parental reproductive investment. On one kind of reproductive investment, the strength of nest defense, correlation was detected between social mates. The relationship between reproduction investment of the bird’s parents and extra-pair paternity was non-significant, possibly as a result of males’ current reproductive tradeoffs. In summary, the existence of extra-pair paternity does not reduce the reproductive investment of males, the behaviour of mates affects the nest defense strength of individuals, and it is possible that this is a function of the shared environment, the exact reasons for which still need to be further explored.

People may never be able to find a neural mechanism that measures the number of action potentials at the neuron scale. For the entire cerebral cortex, a neuron is merely a geometric point, devoid of spatiotemporal features. Neurons cannot tolerate electrical activity that is consistently higher than the action potential. At a certain point in time, numerous neurons collectively generate an “unbearable neural behavior” that forms a “neural sensation.” This “neural sensation” merges to create “neural information,” which in turn produces a “conscious response” within the entire cerebral cortex. The sensations caused by granule cells in the cerebral cortex are specific, while those caused by projection cells in the cerebral cortex are structural. This is because the distribution of granule cells in the cerebral cortex is highly specialized, while projection cells are homogenized. In a brain, neurons with the same properties possess the same neural sensations.

Optical coherence tomography angiography (OCTA) has successfully demonstrated its viability for clinical applications in dermatology. Due to the high optical scattering property of skin, extracting high-quality OCTA images from skin tissues requires at least six-repeated scans. While the motion artifacts from the patient and the free hand-held probe can lead to a low-quality OCTA image. Our deep-learning-based scan pipeline enables fast and high-quality OCTA imaging with 0.3-second data acquisition. We utilize a fast scanning protocol with a 60 µm/pixel spatial interval rate and introduce Angiography-Reconstruction-Transformer (ART) for 4× super-resolution of low transverse resolution OCTA images. The ART outperforms state-of-the-art networks in OCTA image super-resolution and provides a lighter network size. ART can restore microvessels while reducing the processing time by 85%, and maintaining improvements in structural similarity and peak-signal-to-noise ratio. This study represents that ART can achieve fast and flexible skin OCTA imaging while maintaining image quality.

The Optical Kerr Effect was investigated for the first time in biological tissues. This nonlinear optical effect was explored in both human brain and avian breast tissues using a time-resolved femtosecond pump-probe Optical Kerr Gate. The Optical Kerr Effect describes the nonlinear change in a material’s refractive index in response to an electric field. It is fundamental to spectral effects that are commonly used in biological science. The tested tissues produced a unique ultrafast (700-800 fs) doubled peaked Kerr signal, which is indicative of temporal interplay between the different components (electronic plasma, and molecular) that make up the Kerr index. Temporal properties varied between samples suggesting that this method could be used as a new diagnostic. Understanding this Kerr behavior can help improve current spectral diagnostic techniques, such as SRS, and potentially create a new Kerr based biopsy method for the detection of diseased tissues, such as cancer and Alzheimer’s.

Haemorrhagic stroke (HS) is a devastating form of stroke with a high fatality rate. The lack of rapid lesion detection limits early diagnosis of HS. Several susceptibility genes of HS found in genome-wide association studies (GWAS) warrant transcriptional-level biomarkers for useful utility. 13 GWAS level loci with minor allele frequency ≥ 0.05 were selected out of 95 loci related to HS. After validation, the mRNA expression in peripheral leukocytes of 11 genes (PMF1, SLC25A44, CASZ1, NINJ2, WNK1, DYRK1A, LRCH1, LDLR, SMARCA4, AQP9, and LIPC) were measured in the HS case-control study (64 HS cases vs. 128 controls), and then verified in an ischemic stroke (IS) case-control study (67 IS cases vs. 61 controls). LIPC (P=0.002) and CASZ1 (P=0.040) were downregulated in HS patients, while SLC25A44 was upregulated (P=0.009). In the IS case-control study, the differential expression of LIPC (P=0.034) and SLC25A44 (P<0.001) was observed. Although CASZ1 expression was not different between IS cases and controls (P=0.419) with fold change (FC) of 1.205, the direction of expression was opposite to that in HS case-control study (FC=0.747). The ROCtrfgs of traditional risk factors and gene score which was estimated by combining LIPC, CASZ1, and SLC25A44 expression weights, improved the utility for HS identification by 14.1% compared with ROCtrf (P=0.001). Expression of LIPC, CASZ1, and SLC25A44 could serve as potential biomarkers for identifying HS. CASZ1 might be a cause-specific indicator for differentiating HS from IS. Transcriptional score of these three genes could improve performance of the traditional risk model for HS identification.

In present research, three plant growth-promoting (PGP) non-pathogenic bacterial strains Proteus mirabilis BUFF12, Pseudomonas aeruginosa BUFF14 and Enterobacter xiangfangensis BUFF38 inhabiting buffalo dung identified and studied for antifungal activity. Among three, P. mirabilis showed broad spectrum antifungal activity against Fusarium oxysporum (62.7%) and Rhizoctonia solani (71.7%). FTIR spectral analysis of crude ethyl acetate extract of P. mirabilis showed the presence of O-H, N-H, O=C=O, C=O, C=N, CH2, C-O, C-H, PO2-, and C-C functional groups. GCMS spectral analysis displayed the presence of eleven bioactive metabolites and the major compounds were 2-cyclopenten1-one, 3-(acetyloxy) (23.87%) followed by Glutarimide, N-(4-ethylphenyl)- (19.34%); 4-methyl-2-oxopentanenitrile (14.49%); 2,3-Cyclododecenopyridine (13.40%). The purified compounds also established multifarious PGP activity in test crop plants during pot study for disease management. 2-cyclopenten-1-one,3-(acetyloxy) recorded significant inhibitory activity against F. oxysporum (62.7%), followed by R. solani (71.7%). Pot trial studies with this strain significantly reduced disease severity in fennel plants challenged with F. oxysporum and R. solani infection. Our findings provide new insights into the antifungal activity of P. mirabilis, and suggest this species may a promising candidate as a biocontrol agent to confer resistance to gummosis and foot rot and other phytopathogens in fennel crop.

The immune deregulation and disease-modifying anti-rheumatic drugs (DMARDs) make patients with autoimmune rheumatic diseases (ARD) more susceptible to infection. We aimed to investigate the prevalence and clinical outcome of COVID-19 in ARD patients with different treatments. PubMed, Embase, Medline, Cochrane Library, Web of Science were searched to identify the relevant evidence up to March 20, 2023. The overall prevalence of COVID-19 in ARD patients was 0.061. The ARD patients with glucocorticoids (GC) treatment had the highest prevalence[0.088(95%CI:0.065-0.110)] compared to biological (b) DMARDs[0.041(95%CI:0.031-0.051)], conventional synthetic (cs) DMARDs[0.055(95%CI:0.043-0.067)], and anti-TNF therapy[0.029(95%CI:0.003-0.056)]. In contrast, those receiving anti-TNF therapy had the lowest prevalence. The overall hospitalization rate, ICU admission rate, and mortality of ARD patients due to COVID-19 were 0.402(95%CI:0.330-0.476), 0.077(95%CI:0.051-0.107), and 0.073(95%CI:0.046-0.104). Using bDMARDs had lower hospitalization rates[0.216(95%CI:0.147-0.286)], ICU admission rates[0.010(95%CI:0.000-0.037)], and mortality[0.039(95%CI:0.007-0.087)]. Regression analysis showed a significant negative relationship between bDMARDs monotherapy and ICU admission rates(regression coefficient:-0.156, 95%CI:-0.260 - -0.051, P=0.006). Patients using csDMARDs had higher hospitalization rates[0.607(95%CI:0.450-0.755)], ICU admission rates[0.055(95%CI:0.037-0.075)], and mortality[0.074(95%CI:0.041-0.114)]. Patients using GC had a higher hospitalization rate[0.703(95%CI:0.449-0.910)], higher ICU admission rate[0.094(95%CI:0.046-0.152)], and lower mortality[0.070(95%CI:0.033-0.114)]. Regression analysis showed a significant positive correlation between GC monotherapy and hospitalization(regression coefficient:0.484, 95%CI:0.146-0.822, P=0.006). For ARD patients, csDMARDs were associated with disease severity in COVID-19, bDMARDs were associated with a reduced risk of severe disease, and GC was effective in patients with severe COVID-19-related respiratory failure.

Objective: To explore the positivity of EBV DNA from different disease departments and different sample types in Beijing, China and to help clinicians to choose the appropriate specimens for detection. Methods: A retrospective study was performed on EBV DNA detection by quantitative real time PCR (qPCR) between 2015 and 2021. Data from total 5494 samples were collected. According to the results of EBV DNA detection, the positivity was analyzed by the age, gender, the types of specimens and different clinical departments respectively. Results: Of 5494 samples, the positivity detection rate of EBV DNA was 13.65%. The positivity of EBV DNA in male patient was higher than that of female patient samples (14.87% vs 12.07%, p=0.003). The positivity of EBV DNA in adult samples was higher than that of pediatric samples (14.58% vs 11.71%, p=0.004). Pediatrics at 3-6 years had the highest EBV DNA positivity rate (17.77%) among all pediatric samples. Adults aged 40-50 years has the highest EBV DNA positivity rate (17.50%) among all adult samples. Pediatrics samples from department of Pediatric Hematology had the highest EBV DNA positivity rate (36.36%), followed by that of Pediatric Infection Department (23.23%). Among adult group, the EBV DNA positivity was detected highest in department of Hematology (26.27%), followed by department of Dermatology (21.05%). Of all samples, EBV DNA was detected positively mostly in lymphocyte (48.04%) and respiratory tract specimens (36.00%), which were much higher than those of serum samples (5.58%) ( p<0.05). Conclusions: EBV DNA test should pay more attention in 3-6 years children and 40-50 years adults, especially patients with hematological diseases. Besides, in order to improve the detection rate of EBV DNA, specimens such as lymphocyte and respiratory tract specimens may be collected as a priority selection according to disease.

Introduction Zanubrutinib is a second generation Bruton’s tyrosine kinase inhibitor (BTKi) often used to treat B cell malignancies such as marginal zone lymphoma. BTKis belong to a protein tyrosine kinase family that plays an essential role in the proliferation, differentiation, and survival of B cells. The side effects of BTKis include infection, diarrhea, skin rash, and atrial fibrillation. Invasive fungal infections have been previously described with Ibrutinib (a first generation BTKi) but seldom with second generation BTKis such as zanubrutinib.

Leaves of Alstonias cholaris (L.) R. Br. are sensitive to particulate matter pollution. Thus these leaves show morphological and anatomical changes to counter the effect of particulate matter pollution. To evaluate this, samples of the said leaves were collected from three site of Orange Line Train Route (polluted). Peeling and cross sections were used to study morphological and anatomical features of the leaves of the said tree. The samples were preserved using FAA (Formaline, Acetic acid and Alcohol solution). Sections of the leaves were cut using free hand sectioning techniques and stained using toluidine blue. Then their anatomy was compared to the leaves obtained from Botanical garden of Forman Christian College (unpolluted). Studied carried out on these leaves showed that no significant changes are there in the epidermal cells of both types. But size and number of stomata and size of mesophyll cells showed marked differences. It is necessary to understand the molecular mechanism behind defense mechanism employed by the plant to mitigate the negative effects of particulate matter pollution.