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.

Based on the eventual destruction of the solar system and the critical need for human continuation, as well as humans cannot travel to the nearest habitable exoplanet within a lifetime, this article suggests sending synthetic biology- and AI-created plant-like astronauts to the closest habitable exoplanet. These astronauts have green skin, blue blood, and the ability to perform photosynthesis. They can withstand cosmic radiation and extremely low temperatures in space, while generating energy through photosynthesis. This interdisciplinary approach may offer a solution for the survival challenges faced by humanity during its eternal interstellar exploration. As long as these plant-like astronauts possess human consciousness, it is irrelevant whether they are hybrids of carbon- and silicon-based life forms. They will continue their lineage of humanity on exoplanets. Humanity has two survival options. The first option is the Martian migration program led by Elon Reeve Musk, which is both visible and realistic. It could provide an immediate option for human continuation and expansion, although it may not help us escape the future burning of the Sun during its red giant. The second option involves directly sending plant-like astronauts beyond the solar system. This kind of audacious adventure may be worth it: escaping its destruction entirely and preserving our species. Instead of struggling on Mars for thousands of years to reach today’s technological level on Earth and then initiate an “escape from Mars”, it may be more feasible to begin the “escape from Earth” to Teegarden’s Star b now. Should we consider both options simultaneously, much like how humans use their two legs to walk? We must strive with all our might; otherwise, humanity will forever be trapped within the solar system, awaiting the inevitable helium flash to come…

Efficacy and safety of a 7-week immunotherapy protocol with aluminium hydroxide absorbed hymenoptera venomTo the Editor,Hymenoptera venom allergy can cause life threatening anaphylaxis in patients sensitised to wasp and bee venom. Venom immunotherapy is effective in 77%‐84% of patients treated with honeybee venom and in 91%‐96% of patients receiving vespid venom1. Adverse events are usually rare and mild, and symptoms occur in only 4.3%‐11.4% of patients during the updosing1.A variety of therapy regimes exist for the updosing phase, from conventional, rush, ultrarush or clustered modalities1,2. Current conventional protocols are time‐consuming for patients, and some patients decline the potentially life-saving treatment due to the time commitment required for immunotherapy. Adverse events appear to be less frequent in conventional protocols during the updosing phase compared to rush and ultrarush protocols1,2; however, patients may remain unprotected for weeks as it takes considerable time to reach the maintenance dose.The only licensed venom immunotherapy product in the UK is Alutard SQ® (ALK Abelló) for Vespula and Apidae venom. The SPC recommends updosing with a 7-week clustered protocol or 15- or 25-week conventional protocol.To enhance the acceptance of treatment and increase compliance, we reduced the length of the SPC protocol. Another significant factor was the COVID-19 pandemic, which significantly reduced outpatient capacity to comply with social distancing.Based on previous data using the same product3, we introduced a shorter updosing protocol with 8 injections in 7 weeks and monitored its efficacy and safety. We used this in a wider age range of patients, including one patient with indolent mastocytosis and more patients with severe sting reactions.Seventy‐four patients aged 17 to 85 years with a history of a systemic sting reaction to vespid and apidae stings grade 2-4 were included (Table 1). Further information about patient selection and the updosing protocol is in supplementary file S1.We managed to retain all the patients during updosing and maintenance, and no dose reduction was needed.During updosing, there were no objective systemic adverse reactions recorded. Only one objective systemic adverse reaction was documented during maintenance, which was mild and limited to the skin. There were 6 incidences of mild and subjective systemic reactions during updosing and maintenance, which included symptoms of feeling hot, dizzy and itchy. The symptoms were treated with additional antihistamines with no change in regime required. We had a lower incidence of systemic reactions at 1.4% compared to Schrautzer et al3, who reported objective systemic reactions in 3.9% of patients during just the updosing phase.9.5% of our patient cohort reported large localised reactions throughout both the updosing and maintenance phase, which generally only occurred once or twice during the full treatment course.The prevalence of cardiovascular disease and treatment with beta-blockers were not related to the occurrence of side effects.Reactions to field stings were monitored to assess efficacy as sting challenges are not performed in the UK. 20 patients had field stings and all reported localised reactions. Some patients were stung by multiple insects (such as one patient who was stung by 19 insects at one time) and this was more common in beekeepers.We have extended the work of Schrautzer et al3 and demonstrated the efficacy and safety of their 7-week protocol in a large group of patients in a real-world setting. We have also demonstrated safety and efficacy of the 7-week protocol for Alutard SQ® apidae immunotherapy. Our data includes a larger group of patients with more severe reactions. Interestingly, our data also shows a lower number of reactions to immunotherapy treatment.The quicker updosing protocol improved patients’ acceptance of treatment and increased the efficiency of our immunotherapy clinic in terms of time and cost for patients, and medical staff.

This paper compares the transborder wonen on the Sino-DPRK and the US-Mexico border. By focusing on the transborder work and living conditions and the impact of repatriation, it documents that the actual functions of the two boundaries are opposite to the metaphors represented by their physical buildings. The Sino-DPRK border bridges represent the friendship between China and North Korea and the close economic cooperation, the Mexico-US border wall represents the attitude of the US government towards illegal immigrants and the corresponding management measures. However, the wall does not become a taboo for Mexican border crossers, and the bridges cannot play a role in promoting exchanges between China and NK. Mexican trans-border women convert the wall to a bridge through their cross-border activities and close ties with the societies on both sides of the border. Women from NK are subject to strict labor management models, indoctrinated beliefs and a fear of heavy punishment, and thus resist all contact with both the host society and the home country, turning the bridge into a wall in imagery. These two groups, as representatives of the two extremes, indicate the irrelevance between the boundary entity representing the national will and people's trans-border practices.

Objective: Clinical psychology, a pivotal aspect of psychology, combines research and practice. This study aims to assess the recent decade’s clinical psychology research, particularly post-COVID-19 paradigm shifts. Method: Analyzing 69,295 clinical psychology publications from 2010 to 2022 in the Web of Science database, we used advanced bibliometrics tools (CiteSpace and Mapequation) to scrutinize authorship networks, publishing trends, and research focus in the US, the field’s rigin. Results: We found a significant upswing in clinical psychology research prompted by the advent of the pandemic, particularly in the study of psychological trauma caused by issues such as family conflict, elder abuse, collective trauma, and so on. Clinical psychology research has been profoundly formed with a dynamic group of scholars and institutions, surrounding mainly higher education systems. Research participants are widely diverse, with a progressive focus transition to the populations on gender and race minorities, maternal, and adolescents. Mental disorder, such as PTSD, anxiety, and suicidal behaviors have caught more attention especially during the pandemic. Therapeutic approaches have long been another focus in clinical psychology, interventions such as mindfulness-based practice and AI-assisted technologies have started to gain prominence. Conclusions: This paper serves as the first large-scale bibliometrics analysis in clinical psychology, which offers an interdisciplinary collaboration potential with information science besides the originality of documenting publication trends in psychology. The integration of open data initiatives, machine learning, augmented reality, and virtual reality technologies shows promise in assessing mental health and fostering well-being, indicating an evolving landscape in clinical psychology research.

We are considered with the following nonlinear Schrödinger equation −∆ u+( λa( x)+1) u= f( u) ,x∈ V, on a locally finite graph G=( V,E), where V denotes the vertex set, E denotes the edge set, λ>1 is a parameter, f( s) is asymptotically linear with respect to s at infinity, and the potential a: V→[0 ,+∞) has a nonempty well Ω. By using variational methods we prove that the above problem has a ground state solution u λ for any λ>1. Moreover, we show that as λ→∞, the ground state solution u λ converges to a ground state solution of a Dirichlet problem defined on the potential well Ω.

The production of vaccines for diseases depends entirely on its analysis. However, to test every disease extensively is costly as it would involve the investigation of every known gene related to a disease. This issue is further elevated when different variations of diseases are considered. As such the use of different computational methods are considered to tackle this issue. This research makes use of different machine learning algorithms in the identification and prediction of Single Nucleotide Polymorphism. This research presents that Gradient Boosting algorithm performs better in comparison to other algorithms in genic variation predictions with an accuracy of 70%.

Microbially mediated plant-soil feedbacks drive patterns of plant growth, competitive ability, succession, and community composition. Although rare plant species maintain unique functional traits that often facilitate negative feedbacks, there is not a consensus on the belowground drivers nor the effects of phylogenetic origin of previously plant-conditioned soil on aboveground traits associated with rare species. Using a common garden, we connect belowground fungal colonization to aboveground traits in species varying in rarity, and soil conditions varying in the phylogenetic relatedness of conditioning plant species, to demonstrate the mechanistic relationship between belowground ectomycorrhizal fungal (ECM) colonization and aboveground total plant biomass in 14 Eucalyptus species varying in their rarity status. Specifically, we found that while the rarest species displayed 88% less total biomass than common species, the rarest species also maintained 62% greater ECM colonization than common counterparts. Further, negative feedbacks resulted in reduced biomass coupled with positive feedbacks that resulted in increased ECM colonization that varied on the basis of phylogenetic relatedness. The rarest species decreased by 71% - 94% in total biomass but increased by 96% - 114% in ECM colonization in phylogenetically similar and distant soil compared to conspecific soil conditions. The effect size of ECM colonization directly affected the effect size of total biomass in phylogenetically distant conditions with a significant negative correlation (r^2 = -0.83) to show that biomass may be a function of ECM colonization acting differently among species varying in rarity. Consequently, rare plant species may utilize stronger associations with belowground mycorrhizal mutualists than common plant species, to facilitate geographic, competitive, and functional persistence, even while maintaining lower biomass.

Biogenic amines (BAs) are naturally present in various foods, and high levels of them have a negative impact on human health. Pichia kudriavzevii MZ5 exhibits excellent potential in degrading biogenic amines. Among the tested addition of the culture medium components, Mg2+ is the most effective factor of enhancing the ability of P. kudriavzevii MZ5 to degrade biogenic amines. After 72 h of cultivation, the total biogenic amines degradation rate increased from 14.2 % to 43.39 % when Mg2+presented in the medium. The biomass of P. kudriavzevii MZ5 decreased, but there was no correlation between the yeast biomass and the biogenic amines degradation rate in this experiment. The addition of Mg2+ in the medium increased the GSH of P. kudriavzevii MZ5 from 0.34 mg/mg prot to 0.82 mg/mg prot, GST from 2.76 U/mg prot to 3.30 U/mg prot, and Ca2+- Mg2+- ATPase activity from the original 5.36 U/mg prot to 17.36 U/mg prot. These results indicate that Mg2+ significate influenced the degradation ability of P. kudriavzevii MZ5 towards biogenic amines, which suggest that Mg2+ may have a great potential as a promoter for microbial degradation of biogenic amines.

During plant-pathogen interaction, plant exhibits a strong defense system utilizing diverse groups of proteins to suppress the infection and subsequent establishment of the pathogen. However, in response, pathogens trigger an anti-silencing mechanism to overcome the host defense machinery. Among plant viruses, geminiviruses are the second largest virus family with a worldwide distribution and continue to be production constraints to food, feed, and fiber crops. These viruses are spread by a diverse group of insects, predominantly by whiteflies, and are characterized by a single-stranded DNA (ssDNA) genome coding for four to eight proteins that facilitate viral infection. The most effective means to managing these viruses is through an integrated disease management strategy that includes virus-resistant cultivars, vector management, and cultural practices. Dynamic changes in this virus family enable the species to manipulate their genome organization to respond to external changes in the environment. Therefore, the evolutionary nature of geminiviruses leads to new and novel approaches for developing virus-resistant cultivars and it is essential to study molecular ecology and evolution of geminiviruses. This review summarizes the multifunctionality of each geminivirus-encoded protein. These protein-based interactions trigger the abrupt changes in the host methyl cycle and signaling pathways that turn over protein normal production and impair the plant antiviral defense system. Studying these geminivirus interactions localized at cytoplasm-nucleus could reveal a more clear picture of host-pathogen relation. Data collected from this antagonistic relationship among geminivirus, vector, and its host, will provide extensive knowledge on their virulence mode and diversity with climate change

A fifteen-year-old warmblood gelding was presented with recurrence of a histologically confirmed osteosarcoma of the left second and third metacarpal bones three years after initial diagnosis and treatment. Initially, surgical excision was performed, followed by local injection of carboplatin 11 weeks later. The horse was sound after surgery and was used for low level dressage and jumping. Three years later, the horse developed acute onset of lameness in the left forelimb and a painful soft tissue swelling at the proximomedial metacarpal region. Radiographs showed a spiculated periosteal reaction on the medial aspect of the third metacarpal bone, indicating re-activation of the lesion. Stereotactic radiation therapy was performed with a protocol consisting of three fractions under general anaesthesia (Mo-We-Fr schedule), and a total dose of 30 Gy. The technique used was volumetric modulated arc therapy guided by cone beam computed tomography for daily positioning. Following the radiation therapy, the horse became sound at walk and one month later, it became sound at trot. Follow-up by veterinary examination eighteen months after final treatment revealed no lameness at walk and trot, and a stable radiographic appearance.

Purpose: The current study aimed to evaluate the drug utilization pattern in pediatric outpatients suffering from Upper Respiratory Tract Infection (URTI) in a tertiary care center. Materials and methods: A cross-sectional study was carried out in a tertiary care hospital for period of six months (December-May) on pediatric patients (age≤12years) diagnosed with URTI. Data like demographic details, diagnosis, World Health organization (WHO) prescribing indicators, different class of drugs prescribed, antibiotic treatment, and different dosage forms etc. were gathered from pediatric outpatient’s department (OPD). Results: A total of 153 prescriptions were evaluated, of these 84(54.9%) were males and rest 69(45.1%) were females. Mainly school children 89(58.17%) of age group between 6-12 years visited outpatient’s pediatric department. Fever and cough were the commonly recorded clinical symptoms in the prescription analyzed, accounting for 81% and 66.7% respectively. The average number of drugs prescribed were 2.38 per prescription; most commonly prescribed medication for the management of URTI was antipyretics 111(72.5%), antihistamines 94(61.3%) followed by antibiotics 55(35.9%). Amoxiclav {amoxicillin + clavulanic acid} (31.66%) and cefixime (30%) were the common antibacterial prescribed. Majority of medications (85%) were from WHO model list of essential medicines, and 36.43% were prescribed by their generic name. Moreover, it was observed that more than 90% of the antibiotics were prescribed without investigations for bacterial infections. The most preferred route for administration of drugs were oral (86.3%) followed by parenteral and nasal. Conclusion: Symptomatic treatment was offered in most of the prescriptions audited and antibiotics were prescribed with no definite evidence of bacterial infection. Initiation of Antimicrobial Stewardship programs and National Action Plan on Antimicrobial Resistance (NAP-AMR) guidelines in health care institutes can help prescribers to follow rational drug therapy.

Lung cancer is one of the most fatal malignancies, with the highest death rates (~19%), of which NSCLC type, contributes to ~85%. In the search for new treatments, antimicrobial peptides have received much attention due to their propensity for selective destruction of cancer cells. In the current study, we evaluated the efficacy of metastasis-specific tumour-homing-TMTP1peptide against lung cancer using inhalable hybrid-nano-assemblies of PEG–PLGA-copolymer as a carrier for pulmonary delivery which was assessed for aerodynamic and physicochemical properties, along with peptide-release profile, physical stability, cellular uptake & biocompatibility, generation of reactive-oxygen-species, cell migration, autophagic flux, and apoptotic cell death in A549 lung cancer cells. Optimization of inhaled dose, lung retention, and efficacy studies was conducted to evaluate the formulation in NNK (Nicotine-derived nitrosamine ketone) induced tumour-bearing lung cancer, murine model. After inhalation, the formulation with nano-scale physiognomies showed good lung deposition, retention, and metabolic stability. The inhalable-nano-assemblies have shown enhanced generation of reactive-oxygen-species with increased autophagy-flux and apoptotic-cell death. Pre-clinical animal trials show substantial tumour regression by inhalable-TMTP1-based-nano-formulation with limited side effects. Our results on metastasis targeting and tumour-homing peptide TMTP1 exhibit effective tumour targeting and tumour-killing efficacy and provide a reference for the development of new therapeutics for NSCLC.