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

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

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

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

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

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

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

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

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

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

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

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

E3 ligases constitute an important component of proteostasis machinery which plays a critical role in the survival of malaria parasite through post-translational modifications of its protein-substrates. In contrast to humans, parasite E3 ligases have not been extensively studied. Here, we characterize a unique Plasmodium E3 ligase that has both RING and HECT-like features with zinc-coordinating domains. Plasmodium encodes a single RING-between-RING (RBR) E3 ligase that has evolutionarily diverged from human and other intracellular parasites. This RBR-E3 ligase is expressed throughout the erythrocytic phase of P. falciparum lifecycle. Immunoprecipitation experiments showed that Pf RBR-E3 ligase catalyzes K6, K11, K48 and K63 mediated polyubiquitination hinting towards its diverse biological roles (DNA repair, proteasomal degradation, mitochondrial quality control). We observed that Pf RBR-E3 ligase interacts with UBCH5 and UBC13 family of E2-conjugating enzymes. Through mutational analysis, we identified residues in RING1 and RING2 domains that are critical for ubiquitination activity and protein stability of Pf RBR-E3 ligase. Our experiments showed that Pf RBR-E3 ligase participates in maintenance of organellar homeostasis and exhibits differences in immunofluorescence profile upon exposure of parasite to different genotoxic (MMS) and proteotoxic (MG132, FCCP and artemisinin derivative) stress. Our study opens up avenues for exploring the client substrates of Pf RBR-E3 ligase and using this knowledge to design substrate-specific protein degradation based alternative intervention strategies for malaria.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Relapsed/refractory disease is the main cause of death. This study is aimed to determine the prognostic indicators for relapsed/refractory disease in childhood HLH (R/R HLH). Procedure: Infants and children under 18 years of age who were diagnosed with HLH according to HLH-2004 criteria, MAS-HLH criteria for rheumatologic diseases, or H-score undergoing treatment in Chiang Mai University hospital between 2010 – 2022 were included. Demographic data, clinical characteristics, and laboratory parameters were retrospectively reviewed. Results: Out of 86 childhood HLH cases, 30 patients (34.9%) experienced R/R HLH. All patients with primary HLH developed R/R HLH. The most common form of secondary HLH was infection-associated hemophagocytic syndrome (IAHS), comprising 43 cases. Of these, 37.2% had relapsed or refractory disease. Univariable analysis identified several potential risk factors for R/R HLH, including younger age, severe disease status, higher HLH-2004 criteria scores, higher H-scores, overt DIC, higher pSOFA scores, and increased levels of aspartate aminotransferase, total bilirubin, and direct bilirubin. Multivariable logistic regression analysis revealed that a pSOFA score of ≥ 8 and age < 3 years were independent risk factors for R/R HLH, with adjusted odds ratios of 6.35 (95% confidence interval [CI], 1.18 – 34.19; p = 0.032) and 3.62 (95% CI, 1.04 – 12.63; p = 0.044), respectively. Conclusions: Children with HLH who have a pSOFA score of ≥ 8, or are younger than 3 years, are at a higher risk of relapsed or refractory disease. Further evaluation of management strategies in this context is warranted.

Germline genetic testing can aid in difficult diagnostic workups but may reveal variants of unknown significance (VUS), which do not alter patient management or provide definitive diagnoses and may worsen stress on patients and families. VUS are more prevalent in underrepresented populations given their absence in large scale genomic studies. We describe seven pediatric hematology/oncology patients seen in the highly diverse Bronx County in New York City in which VUS or novel pathogenic variant identification influenced clinical management and outcomes. These cases highlight the importance of incorporating underrepresented populations into genomic databases to improve variant characterization and address healthcare disparities.

This paper presents an innovative method for enhance the comprehensibility of Electronic Health Records (EHRs), making it accessible to individuals without specialized clinical knowledge. Our approach entails predicting medical professionals’ impressions, identifying intricate medical terminol- ogy, and clarifying these complex terms. To achieve this, we fine-tuned GPT-3 for predicting doctors’ impressions and integrated the Chain Of Thought (COT) prompting technique to identify and elucidate intricate medical terms. The assessment was conducted using Rouge scores and cosine similarity scores. The outcomes reveal that our proposed approach yields a cosine similarity score surpassing 75, indicative of the model’s exceptional performance. The comparative analysis demonstrates the superiority of our approach concerning doctors’ impressions, detection of complex terminology, and provision of explanations. Furthermore, this work is pioneering in addressing and resolving intricate terminology in EHRs, marking a novel contribution to the field.

In this paper, based on thin film integrated passive device (TF-IPD) technology, compact ultra-wideband (UWB) bandpass filter (BPF) and dual-band bandpass filter (DBBPF) with equal inductance configuration are proposed. The configuration of equal inductance in a circuit contributes to reducing variables, simplifying the physical structure, and shortening the debugging time in the TF-IPD design process. Despite all the inductors being equal in value, wide passband can still be achieved. The measured results show that the center frequency of UBW BPF is 11.43 GHz, the 3-dB fractional bandwidth (FBW) is 133% (3.87 GHz-18.99 GHz). And the 3-dB FBWs of DBBPF centered at 6.5 GHz and 16.2 GHz are 92% (3.51-9.49 GHz) and 35% (13.33-18.98 GHz), respectively. The stopband of UBW BPF and DBBPF can be extended to 47.7 GHz and 44.8 GHz in sizes of 321 um × 856 um and 235 um × 846 um, respectively (excluding measuring pads).

Introduction:Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is a group of conditions that share common characteristics and is characterized by the absence of ≥50% stenosis of coronary arteries and without any evidence of atherosclerotic plaque rupture [1]. A study conducted by Waller et al. reported that 4% to 7% of all patients diagnosed with AMI, do not have underlying atherosclerotic coronary disease on autopsy or angiography [2].Coronary artery embolism is a rare and important non-atherosclerotic cause of acute myocardial infarction (AMI), and the first case of AMI secondary to coronary embolism was reported in 1856 by Rudolf Virchow and was classified initially as a precipitating factor for type-II MI, now recognized as one of the cause of MINOCA [3]. Coronary embolism (CE) is more frequently reported in infective endocarditis patients and it mainly involves the left main coronary artery system due to flow characteristics and aortic morphology [4, 5]. CE may also originate from mural thrombus within the left-sided cardiac chambers, but it has rarely been reported in the literature [6]. Most cases of coronary embolism in the literature have been reported secondary to infective endocarditis, valvular heart diseases, and atrial fibrillation [7-9]. Here, we are reporting a case of a 74-year-old female, who had a chronic history of atrial fibrillation on anticoagulation with questionable compliance and was admitted with sepsis and takotasubo cardiomyopathy and later developed AMI secondary to coronary embolism to the left anterior descending artery.

A rare case of Heme oxygenase deficiency: A case report & literature review

Introduction: Despite a reported understanding of basic radiation physics principles, students face barriers that hinder effective translation of this knowledge into clinical practice, potentially leading to suboptimal outcomes.The objectives of this cross-sectional descriptive research are to assess the level of radiation physics knowledge among clinical radiography students, evaluate their ability to apply this knowledge in clinical settings, identify barriers hindering successful application, and provide recommendations for improved integration. Material and method: The study was conducted among clinical students (4 th year and 5 th year) of the department of radiography and radiological sciences, University of Nigeria, Enugu campus, Enugu state. The study design was a cross-sectional descriptive study which enables to collect data at a specific point in time. The study population comprised of students who are currently in 4 th and 5 th year in the department of medical radiography and radiological sciences. The population has a total number of 500 students. All clinical radiography students who are willing to participate in this research were included in this research Results: Among 220 participants from the University of Nigeria’s Department of Radiography and Radiological Sciences, 81.4% expressed thorough teaching of radiation physics during pre-clinical training, while 68.3% reported an excellent understanding. However, 64.3% cited disinterest due to perceived complexity, 42.0% noted a gap between theoretical teaching and practical application, and 84.6% mentioned a lack of fear of radiation’s biological effects. Suggestions for improvement included a dedicated curriculum (90.0%), increased teaching duration (69.7%), expert involvement (95.10%), hands-on training (95.5%), interactive learning methods (93.2%), and collaborative training approaches (95.0%). Conclusion: This research underscores the importance of refining radiation physics education to bridge theory and practice effectively.

India's environmental policy framework has undergone significant transformation since independence, but effective implementation remains a challenge. This research examines the evolution of environmental policy in India, focusing on key challenges and promising sustainable development initiatives. The study adopts a comprehensive approach, analyzing relevant legal documents, policy reports, scientific literature, and data from government agencies. It also incorporates stakeholder perspectives and insights from civil society organizations. The research identifies air and water pollution, land degradation, deforestation, and climate change as major environmental challenges facing India. Promising sustainable development initiatives include renewable energy, energy efficiency, waste management, and sustainable agriculture. However, these initiatives face challenges related to implementation, enforcement, and long-term effectiveness evaluation. The research proposes a series of recommendations, including policy reforms, institutional capacity building, innovation and technological advancements, green financing mechanisms, and international cooperation. It emphasizes the importance of public participation, inter-agency collaboration, and leveraging technology for effective environmental governance. The research concludes that India needs to prioritize effective implementation of existing policies and explore innovative approaches to address emerging environmental challenges. By adopting a holistic strategy that integrates environmental considerations into all policy domains, empowers communities, leverages technology, and fosters international collaboration, India can achieve a cleaner, greener, and more sustainable future.

Purpose: We aim to identify risk factors associated with pathological upgrading/downgrading after conization in patients with cervical high-grade squamous intraepithelial lesion and provide risk stratification management based on machine learning predictive model. Methods: 1. This retrospective study included patients who visited Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, and were diagnosed with cervical high-grade squamous intraepithelial lesion (HSIL) by colposcopy directed biopsy (CDB) and subsequently underwent conization. A wide variety of data were collected from medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. Patients were categorized into three groups according to their post-conization pathological results: LSIL or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). 2. Univariate and multivariate analysis were conducted to obtain the independent risk factors for pathological changes in cervical HSIL patients. 3. Machine learning prediction models were established and evaluated, subsequently verified in external testing data. Results: 1. A total of 1585 patients were included, with 65 cases (4.1%) being upgraded to cervical cancer after conization, 1147 cases (72.4%) remaining HSIL, and 373 cases (23.5%) being downgraded to LSIL or below. 2. Multivariate analysis results showed that a 2% decrease in the incidence of pathologic downgrade was found for each additional year of age and each 1% increase in lesion area. Patients with cytology >LSIL (OR=0.33, 95%CI: 0.21-0.52), HPV infection (OR=0.33, 95%CI: 0.14-0.81), HPV 33 infection (OR=0.37, 95%CI: 0.18-0.78), coarse punctate vessels on colposcopy examination (OR=0.14, 95%CI: 0.06-0.32), HSIL lesions in endocervical canal(OR=0.48, 95%CI: 0.30-0.76) , and HSIL impression (OR=0.02, 95%CI: 0.01-0.03) were less likely to experience pathologic downgrading after conization. 3. The independent risk factors of pathological upgrading to cervical cancer after conization including: age (OR=1.08, 95%CI: 1.04-1.12), HPV16 infection (OR=4.07, 95%CI: 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR=2.21, 95%CI: 1.08-4.50), atypical vessels (OR=6.87, 95%CI: 2.81-16.83), and HSIL lesions in endocervical canal (OR=2.91, 95%CI: 1.46-5.77). 4. In 6 machine learning prediction models, the BP neural network model demonstrated highest and most uniform predictive performance in the downgrading group, HSIL group, and upgrading group, with AUCs of 0.90, 0.84, and 0.69, respectively, sensitivities of 0.74, 0.84 and 0.42, specificities of 0.90, 0.71 and 0.95, accuracies of 0.74, 0.84 and 0.95. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with the overall AUC of 0.91. Thus, a web-based prediction tool (http://115.29.79.17:8082/) was developed. Conclusion：BP neural network prediction model has excellent predictive performance and can be used for risk stratification of CDB diagnosed HSIL patients.

CRISPR/Cas9 technology in conjunction with somatic cell nuclear transplantation (SCNT) provides the primary approach to producing gene-edited pigs, and targeting nuclear donors with CRISPR/Cas9 is crucial. Gene-edited nuclear donors are inefficient due to poor editing efficiency and low delivery efficiency, which are highly associated with CRISPR/Cas9 form selection. Nevertheless, there is not a straightforward method to evaluate CRISPR/Cas9 editing efficiency on the porcine genome. In this study, a fluorescence report signal and micropattern arrays-based platform was developed to visually assess the efficiency of CRISPR/Cas9 editing. Based on the quantity and state of cells grown on micropattern arrays, 200 μm in diameter and 150 μm in spacing were optimal specifications for culturing porcine cells. The editing efficiency of three different CRISPR/Cas9 system forms: DNA, mRNA, and Ribonucleoprotein (RNP) were rapidly evaluated using this platform, with mRNA proving the most effective. Subsequently, four homozygotes with β4GalNT2 gene knockout were quickly obtained by mRNA-based form, which lays the groundwork for the subsequent generation of gene-edited pigs. This platform makes gene knockout efficiency evaluation rapid, intuitive, and efficient. It also holds great promise for customizing evaluation platforms for different cell types, evaluating delivery techniques, and swiftly testing innovative gene editing tools.

Over the past decade, our research group has found that plant responses to combined abiotic stresses are unique and cannot be inferred from studying plants exposed to individual stresses. Adaptive mechanisms involve changes in gene expression, ion regulation, hormonal balance, and metabolite biosynthesis or degradation. Understanding how these mechanisms integrate from stress perception to biochemical and physiological adjustments is a major challenge in abiotic stress signaling studies. Today, vast amounts of -omics data (genomics, transcriptomics, proteomics, metabolomics, phenomics) are readily available. Additonally, each –omic level is regulated and influenced by the others, highlighting the complexity of plant metabolism’s response to stress. Considering abscisic acid (ABA) as a key regulator in plant abiotic stress responses, in our study, ABA-deficient plants (flc) underwent single or combined salinity and heat stresses were evaluated and different -omics analyses were conducted. Significant changes in biomass, photosynthesis, ions, transcripts, and metabolites occurred in mutant plants under single or combined stresses. Exogenous ABA application in flc mutants did not fully recover plant phenotypes or metabolic levels but induced cellular reprogramming with changes in specific markers. Multi-omic analysis aimed to identify ABA-dependent, ABA-independent, or stress-dependent markers in plant responses to single or combined stresses. We demonstrated that studying different -omics together identifies specific markers for each stress condition not detectable individually. Our findings provide insight into specific metabolic markers in plant responses to single and combined stresses, highlighting specific regulation of metabolic pathways, ion absorption, and physiological responses crucial for plant tolerance to climate change.