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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: 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.

The rotating packed bed (RPB) is a typical equipment in chemical process intensification technology due to its excellent mass transfer performance. In this paper，three different single-phase wire screen packing pressure drop models coupled with the interfacial area model were used to construct resistance calculation methods for porous media, respectively. The results show that simulation deviations of the liquid holdup and the pressure drop of the m-K model range from 0.92% to 27.61% and 1.63% to 34.59%, respectively. The m-K model has the highest prediction accuracy at N=500~1500 rpm. At N=2000~2500 rpm, the B model has the highest prediction accuracy. The higher the viscosity of the liquid, the more uniform the axial liquid distribution in the packing, and the longer the liquid mean residence time. The impact of different nozzle designs on liquid distribution has been investigated using a new method based on user-defined functions (UDFs).

Herein, we systematically investigated the reaction mechanism of n-pentane cracking on the Ag/ZSM-5 bifunctional catalyst featuring both dehydrogenation and cracking capabilities. Specifically, overall cracking network of n-pentane was comprehensively constructed to show the roles of metal dehydrogenation sites and acid sites respectively, in which metal Ag could substitute the H of the Brønsted acid site to form the Al-O-Ag linkage with enhanced adsorption and activation of n-pentane, while Brønsted acid site with weak acid strength relay to promote cracking reaction. Thanks to this synergy of the two active sites, the apparent activation energy of n-pentane cracking to light olefins was decreased from 82.77 KJ/mol to 68.26 KJ/mol and the proportion of specific path (C5H12→H2+C5H10) in n-pentane monomolecular cracking reaction increased from 14.62% to 69.24%. In addition, 0.57Ag/ZSM-5 catalyst exhibited the conversion of n-pentane up to 67.55wt%, which improved the performance of the parent ZSM-5 by 13.42wt%.

Hydrogel-based microfluidics offer an in vivo-relevant micro-environments for construction of organs-on-chips. However, the fabrication of heterogeneous microchannels using hydrogels is challenging and fails to mimic the complex structures of organs in vivo. Here we present a new methodology called “layer-by-layer adhesion” for the construction of complex microfluidic chips. A hydrosoluble and photo-crosslinkable adhesive, chitosan methacryloyl (CS-MA), was used to stitch various hydrogels together layer-by-layer to form perfusable microchannels. Our results show that CS-MA can bond different types of hydrogels with adhesion energy ranging from 1.2-140 N/m. Using the layer-by-layer adhesion approach, we constructed heterogeneous hydrogel-based microchannels with various morphologies of snail, spiral, vascular-like, and bilayer. Based on this methodology, liver-on-a-chip was established by entrapping hepatic cells inside a biocompatible Gel-MA layer and covering it with the perfusable microchannels in tough F127-DA layer. The “layer-by-layer adhesion” provides a facile and cytocompatible approach for engineering user-defined hydrogel-based chips potentially for organs-on-chips.

Biomass-derived deep eutectic solvents (DESs) have been introduced as promising pretreatment and fractionation solvents because of their mild processing conditions, easy synthesis, and green solvent components from biomass. In recent DES studies, solvent-based third constituents like water, ethanol, and others improve the processibility of typical binary DESs. However, the impacts of these components are not well understood. Here, two solvent-based constitutions, including water and ethylene glycol, were applied to 3,4-dihydroxybenzoic acid (DHBA)-based DES system for improving the conversion efficiency of cellulose-rich fraction and the properties of lignin fraction. Compositional changes, enzymatic digestibility of carbohydrate components, and transformation of lignin were used to evaluate the impact of each constituent on biomass processing. Ternary DHBA-ChCl DESs exhibited better performances in delignification, fermentable sugar production, and preservation of β–O–4 ether linkage in lignin compared to neat ChCl-DHBA DES.

The much hyped Artificial Intelligence (AI) model known as chat generative pre-trained transformer ( Chat GPT), developed by Open AI can have far-reaching benefits for pathologists saving time so that they can devote their time to more meaningful work. Generative AI is a special class of AI model, that based on patterns and structures learned from existing data can create new data. However, certain hurdles have to be taken care of like integrating ChatGPT with image analysis which will revolutionize the field of pathology by providing assistance with diagnostic accuracy and precision. Generation of meaningful insights from the textual information provided by ChatGPT can be possible by the platform which should have the capability of processing different types of image data, such as medical images, and pathology slides. Due consideration should be given to ethical and legal issues including bias.

This study used a Discrete Element Method (DEM) model to investigate the Jenike shear process of flexible, cylindrical particles with different aspect ratios. The model was validated through experiments and analytical solutions. It was found that particle shape and deformation have a significant impact on friction behavior, affecting particle deformation, contact forces, orientation, and internal friction angle. Results indicate an increase in shear stress with normal load, regardless of particle stiffness or shape. Flexible particles showed higher shear stress and internal friction angles than rigid ones, especially for aspect ratios of 6. With aspect ratios of 4 and 5, flexible particles deform significantly during shear with complex reconfiguration, while aspect ratio 6 particles experience a uniform reconfiguration, indicating a solid packing structure that enhances flow resistance. These findings will aid in improving kinetic theories for granular flow of complex irregular particle flows.

Recently, nanomedicine have been successfully applied in the cancer therapy. However, how to precisely control the drug release from nanomedicine in tumor tissue and overcome the hypoxic microenvironment of tumor tissue is still an important challenge in the development of nanomedicine. In this work, a new type of drug-loaded nanoparticles P(AAm-co-AN)-AuNRs@CeO2-DOX (PA-DOX) was prepared by combining high-efficiency photothermal reagents, critical up-conversion temperature polymer layer and anti-cancer drug doxorubicin (DOX) for the treatment of liver cancer. In this system, CeO2 can decompose hydrogen peroxide to H2O2 and O2 alleviate the anaerobic microenvironment of liver cancer cells. As a photothermal reagent, AuNRs@CeO2 can convert near-infrared light into heat energy to achieve local heat to kill cancer cells and ablate solid tumors. In addition, the elevated temperature would enable the polymer layer to undergo a phase transition to release more DOX to achieve a controlled release mechanism, which will open up a new horizon for clinical cancer treatment

Report of Two cases of Schaaf-Yang Syndrome: Same Genotype, Different Phenotype Ana Maria Rodriguez,a MD, Katherine Schain,a MS, CGC, Parul Jayakar,aMD,MS,FACMG, Meredith S. Wright,b,c PhD., Shimul Chowdhury,b PhD., Daria Salyakina,ePhD.a Division of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USA.b Rady Children’s Institute for Genomic Medicine, San Diego, (CA,) USA. c Keck Graduate Institute, Claremont, (CA,) USA. d Personalized Medicine & Health Outcomes Research, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USACorresponding Author: Ana Maria Rodriguez BarretoDivision of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,). 3100 SW 62nd Avenue, Miami, FL, 33155, USA. Tel: 786-624-4717. Fax : 786-624-4704. E-mail: anamaria.rodriguezbarreto@nicklaushealth.orgCo-authors: Katherine Schain: Katherine.Schain@Nicklaushealth.orgParul Jayakar: Parul.Jayakar@Nicklaushealth.orgMeredith S. Wright: MWright3@rchsd.orgShimul Chowdhury: schowdhury@bluestargenomics.comDaria Salyakina: Daria.Salyakina@Nicklaushealth.orgConflicts of Interests Statement: We know of no conflicts of interests associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors.Informed Consent : Written informed consent was obtained from both patients parents.Ethics Declaration: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by The Institutional Review Board (or Ethics Committee) of Nicklaus Children’s Hospital Pediatric Specialists.

Experience of general anesthesia in a patient with menstrual-associated coronary spasmAya Kawachi, Saho Sudo, Yusuke Ishida and Koichi NakazawaDepartment of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Flagella dermatitis is a rare skin lesion due to bleomycin use: A Case ReportZuhat Urakçı1,Yasin Sezgin2,Oğur Karhan3,Suat Morkuzu4,Zeynep Oruç1,Mehmet Küçüköner1,Muhammet Ali Kaplan1,Abdurrahman Işıkdoğan11Dicle University Department of Medical Oncology, Diyarbakir,Turkey2Siirt University, Department of Medical Oncology,Siirt,Turkey3Liv Hospital, Department of Medical Oncology, Gaziantep,Turkey4Institute for Reconstructive Surgery,Houston Methodist Hospital,Houston,Texas,USAAbstract: Flagella dermatitis is a rare skin lesion that appears due to bleomycin use. It is generally seen in itchy and linear styles. Here, we present a case of flagella dermatitis in a male patient who was on bleomycin therapy with a diagnosis of germ cell tumor. When itchy skin lesions develop in patients using bleomycin, it should be kept in mind among the differential diagnoses.Keywords: Flagella dermatitis,bleomycin,germ cell tumor.Introduction: Bleomycin is a glycopeptide-structured cytotoxic drug obtained from Streptomyces verticillus (1). It is often used in the treatment of some malignant tumors, such as Hodgkin lymphoma, squamous cell carcinoma, and germ cell tumors (1). While various side effects occur in the gastrointestinal tract, respiratory system, and skin due to bleomycin, general symptoms such as fever and weakness can also be seen. Skin reactions are common side effects and usually occur as a late finding. On the skin, erythema, hyperkeratosis, rash, vesicle, hyperpigmentation, alopecia, and, in rare cases, Flagella dermatitis (FD) can be seen (2). FD was defined by Moulin et al. in 1970 as linear hyperpigmentation after bleomycin use (1). Its incidence has been reported to be between 8 and 20% in patients using bleomycin (3). Here, a case of FD developed in a 21-year-old male patient using bleomycin due to a germ cell tumor is presented.Case report: A twenty-one-year-old male patient was admitted to our clinic with complaints of shortness of breath and cough that started about 45 days ago. A patient was diagnosed with a mediastinal mass, and a biopsy was performed. The patient, who was reported as a germ cell tumor as a result of a biopsy, was given every 21 days from when bleomycin (30 mg/day, 1, 8 and 15 days), etoposide (100 mg / m2, 1-5 days) and cisplatin (20 mg / m2, 1-5 days), was started. In our patient, hyperpigmented skin lesions that developed with itching, mostly in the chest, abdomen, and back, developed after the 2nd dose of bleomycin (Figure 1.2). Due to the development of the lesions after bleomycin, and in a linear style, FD was considered in our patient. The patient was given oral antihistamine therapy. The dexamethasone that was given before each chemotherapy cycle was continued. During the follow-up, the patient’s itching passed and the skin lesions regressed. The patient’s bleomycin treatment was continued, and there was no itching again.Discussion: The term ”Flagella dermatitis” is used because the hyperpigmented eruptions on the body appear to be whipped (4). In the case of HIV infection, FD may also develop after the consumption of some poisonous mushrooms or after the use of certain chemotherapeutic agents such as peplomycin and docetaxel (5). Bleomycin is an anti-neoplastic drug belonging to the group of glycopeptides, and bleomycin is destroyed by hydrolase. The concentration of the bleomycin hydrolase enzyme is significantly lower in the skin and lungs. Therefore, the accumulation of bleomycin in the skin and lungs is higher and related toxicities develop. Generally, when the cumulative dose reaches 90–285 mg, bleomycin toxicity begins to occur. However, in some cases, it has been reported that toxicity develops at as low as 15 mg intravenously (6). Multiple lesions occur suddenly in many parts of the body. Generally, it develops between the 1st and 9th weeks of bleomycin treatment, but this period may take up to 6 months (7). In our case, FD developed at week 4. Although FD can rarely be asymptomatic, it usually progresses with itching, redness, and darkening of the skin. Indeed, in our case, there was severe itching, redness, and hyperpigmentation of the skin. The diagnosis is made according to the characteristic features of the skin lesions. Linear-style eruptions occur as if they were whipped, characteristically on the skin. The lesions are itchy and usually occur on the upper body and extremities (8). Linear hyperpigmented skin lesions are generally localized in areas where itching and pressure are applied (9). The development mechanism of FD is not known precisely. However, it has been suggested that locally increased melanogenesis, insufficient pigmentation secondary to inflammation, change in normal pigmentation pattern, and neutrophilic eccrine hydradenitis can be caused (10). Patients usually benefit from corticosteroids and anti-histaminics used in treatment. It reduces itching and limits the lesions to the skin. These lesions usually limit themselves after 3-4 months of discontinuation and begin to regress and disappear after 6-8 months. However, after the use of bleomycin again, the lesions may reappear (11). In our case, corticosteroid and anti-histaminic therapy completely alleviated the symptoms.Conclusion: When itchy lesions develop in patients using bleomycin, FD should be kept in mind among the differential diagnoses, and physicians should be careful about the toxicity of bleomycin.Conflict of interest: The authors declared that there is no conflict of interest.

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Title: AngioinvasiveTrichophyton rubrum associated necrotizing fasciitis in an immunocompromised patientAuthors: Michael J. Davis, DO, MPH1-3*; Katelyn J. Rypka, BS3-6*; Alexandra K. Perron, BA6; John Keilty, BS6; Benjamin Wils, MS 6; Joshua Levine, BA 6; Anthony T. Rezcallah, MD7-8; Robin Solomon, MD9; Noah Goldfarb, MD3-5†; Anjum Kaka, MD1, 3†Affiliations:1Department of Infectious Disease, Minneapolis VA Health Care System, Minneapolis, MN2Department of Infectious Disease, University of Minnesota, Minneapolis, MN3Department of Internal Medicine, Minneapolis VA Health Care System, Minneapolis, MN4Department of Dermatology, Minneapolis VA Health Care System, Minneapolis, MN5Department of Dermatology, University of Minnesota, MN6University of Minnesota Medical School, Minneapolis, MN7Department of Surgery, Minneapolis VA Health Care System, Minneapolis, MN8Department of Surgery, University of Minnesota, Minneapolis, MN9Department of Pathology, Minneapolis VA Health Care System, Minneapolis, MN*These authors contributed equally†These authors contributed equally