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.

In an inclined artery with a non-uniform cross-section, this work investigates the changing viscosity and thermal conductivity of a single wall carbon nanotube with numerous, symmetrical stenoses. Assuming that the flow is experiencing no-slip conditions and the stenoses are mild, a mathematical model is proposed. To obtain the equations characterizing heat conduction, axial velocity, flow resistance, and wall shear stress under the effect of SWCNT, governing equations are formulated and solved. The differences resulting from varying amounts of SWCNT are compared numerically. It has been noted that when stenoses get higher, the impedance (or resistance to the flow) λ rises but the wall shear stress (τ) falls. Additionally, flow patterns is illustrated using streamlines.

1 The depletion potential of fossil fuels necessitates the exploration of alternative energy sources.

Good scientific communication is helpful in improvement of cardiovascular health and life due to a number of scientific highlights and conducting the outcomes of both basic studies and clinical trials in cardiovascular disease (CVD). In this article, the author proposed new concepts of scientific communication from conferences/clinical to clinical/conferences (Co2Cl & Cl2Co), discusses related roles in clinical practice and translational studies as well as scientific innovation. Since international scientific conferences or congresses focus on prevention, health promotion, education and training as well as treatment or management and rehabilitation of CVD, Co2Cl & Cl2Co are beneficial to improvement of cardiovascular health and quality of life due to a number of scientific breakthroughs and a series of discoveries in cardiovascular medicine. Both models of Co2Cl & Cl2Co contribute to better cardiovascular scientific communication, excellent clinical practice and translational research as well as better scientific innovation, in particular the pandemic and post-COVID-19 era.

Polyclonal infections are widespread and provide evidence of facilitation, competition, and neutral interactions between parasite clones, even within the same host-parasite system. The outcome of co-infections is usually assessed by parasite infection intensities, while other important fitness-related traits, e.g. larval growth rates, are often ignored. We studied both infectivity and the growth rate of different clones of the common trematode Diplostomum pseudospathaceum in the fish host (Salvelinus malma) and tested how these fitness-related traits changed in double-clone infections compared to single-clone ones. We found that the growth rates of the parasite’s clones were more variable than their infectivity. The relationships of these D. pseudospathaceum traits with host mass were clone-specific. Some clones demonstrated higher infection intensities and growth rates in larger fish. It hints that specialization on different size groups of hosts may occur in this parasite species. In addition, we found positive density-dependent growth (Allee effect), rarely reported for parasites. Interestingly, it was observed only in mixed infections and we discuss the reasons for it. In double-clone infections, both evidence of facilitation and competition between D. pseudospathaceum clones were found. The outcome of co-infections varied not only between genotype combinations but also between tested traits. Clones either ‘cooperated’ when infecting the host or competed when growing. There were no clone pairs, in which interactions changed their type with time or were observed constantly during parasite development.

ABSTRACT Objective. Our aim was to explore the relationship between vertigo symptoms and the prognosis of hearing indicators in patients with sudden sensorineural hearing loss. Data Source. Eligible studies were identified from the “PubMed”, “EMBASE”, and “Web of Science” databases from January 2000 to September 2023. Study Selection. Studies were selected from all original and retrospective or prospective studies that focused on the relationship between vertigo and hearing prognosis in patients with sudden sensorineural hearing loss. Data Extraction and Synthesis. Observational metrics for data extraction included type of study, number of subjects with or without vertigo, treatment regimen, definition of pure tone hearing thresholds, criteria for hearing improvement, treatment duration, follow-up time, and age distribution of subjects. Meta-analysis was performed using Stata 15 software. Main Outcome and Measure. Association of vertigo symptoms and the prognosis of hearing indicators in patients with sudden sensorineural hearing loss. Results.A total of 4290 patients with sudden sensorineural hearing loss were identified in 23 studies. The hearing recovery rate was 40.8% in the group with vertigo and 53.76% in the group without vertigo. Vertigo was significantly associated with poorer hearing recovery (OR = 2.13; 95% CI, 1.63-2.79; I 2 = 68.3%). Subgroup analyses revealed similar results for medication (OR=2.65; 95% CI, 1.84-3.83; I 2 = 50.8%). However, an attenuated association between vertigo and the prognosis of sudden sensorineural hearing loss was observed in the subgroups treated with drugs combined with hyperbaric chambers (OR= 1.76; 95% CI, 0.75-4.15; I 2 = 84.9%) and drugs combined with intratympanic injections (OR= 1.62; 95% CI, 1.02-2.58; I 2 = 65.6%). Conclusions and Relevance. Our study suggested that vertigo may be a negative factor in sudden sensorineural hearing loss.Based on the results of the subgroup analysis,the combined treatment regimen has better efficacy in patients with sudden sensorineural hearing loss with vertigo.

The Nelchina Basin, located west of Glenallen, AK provides important moose (Alces alces) habitat throughout the year. However, previous research in this area has shown that the moose populations appear to be nutritionally limited by the available forage. The Nelchina Basin was deemed an intensive management unit to increase moose populations through predator control efforts and prescribed fires to increase the amount of available forage, including the 2004 Alphabet Hills fire. We quantified the available digestible energy (DE) and digestible protein (DP) during the summer of 2018 and 2019, as well as the winter in between, and availability of forages for moose within the burn perimeter and the adjacent unburned forest during the summer of 2019. We found that total canopy cover of the primary forage species was lower in the burned areas than in the adjacent unburned forest habitats. DP concentration was not significantly different between forested and burned sites, and DE and DP content varied across the summer and winter sampling season. We also found a significant difference in DE and DP across the two sampling years. Although others have shown a positive effect of wildfire for herbivore populations, we found that some areas, including the Alphabet Hills area, may not be suitably adapted to benefit from the quick release of nutrients after fire and may not allocate more resources to biomass as previously expected. This project highlights the importance of research that quantifies both the availability of and the quantity of available food resources for herbivores.

Prevention, the way to go.

Microalgae, historically relevant to aquaculture sector, can effectively contribute to the sustainability in several production chain. The physical and chemical environmental factors play a direct or indirect role in shaping the composition of their intracellular compounds of these organisms. Among these compounds, fatty acids are particularly noteworthy, with various species harboring an extensive array of them. Notably, the marine dinoflagellate Prorocentrum micans excels in the production of essential polyunsaturated fatty acids (PUFA), including DHA and EPA. The objective was to determine which factors contribute to the accumulation of the PUFA in a P. micans strain. A factorial design of 3x3 composed by the following factors: illumination (5, 12.5, 20 µmol photons m-2 s-1), nitrate dose (0, 75, 150 mg ml-1) and inoculum volume (50, 125, 200 ml) was examined to determine the better growth conditions for P. micans. Furthermore, lipid profile and the fatty acids profile were analyzed at the end of the cultivation. The results determined that, maximum averages of DHA (20%) and EPA (1%), in the biomass, were registered in cultures without nitrate, low irradiance (5 µmol photons m-2 s-1) and high volume of inoculum (200 ml). The maximum cell concentration recorded was 3.1×104 cells ml-1, at the end of the culture. So, it can be concluded that the evaluated strain is easily adapted to the culture flow and, the culture conditions to which it was subjected allows its biomass to be considered an interesting alternative as lipid input in aquaculture activity.

”Peritoneal TB: A Challenging Presentation in a Young Woman with Acute Abdominal Symptoms”Samira Dehghani1, Saloomeh Mohammadi2, Atefeh Mahmoudi1, Fatemeh Riyahi Zaniyani3, Sasan Shafiei4, Afrouz Emzaei5, Yasaman Tavakoli6, Roozbeh Narimani Javid7, Athena Behforouz1*1. Preventive Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran2. Department of Pathology, Mahdieh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran3. Faculty of Medicine, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran4. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran5. Hojjat Hospital, Isfahan University of Medical Sciences, Isfahan, Iran6. Student Research Committee, Department of Medicine, Mazandaran University of Medical Sciences, Mazandaran, Iran7. Student Research Committee, Hamadan University of Medical Sciences, Hamadan, IranAbstractIntroduction: Tuberculosis (TB) is a significant health problem worldwide. The rate of active tuberculosis in pregnancy is rising and it is a considerable cause of maternal mortality during pregnancy.Case presentation: This study reports a young woman who was suffering from TB peritonitis, a rare, highly progressive clinical course following the spontaneous abortion of 16-week gestation. She underwent a diagnostic laparotomy that showed several small-scale implants on the peritoneum and viscera. Histopathology revealed chronic caseating granulomas with necrosis. With the possible diagnosis of tuberculosis, anti-mycobacterial therapy was initiated and she received these drugs for 6 months. The patient’s clinical manifestations completely disappeared and the chest CT scan became normal after the treatment.Conclusion: The diagnosis of peritoneal tuberculosis is challenging and it could be made with a combination of CT imaging, explorative laparoscopy, and evaluation of biopsies from specimens and culture or PCR from ascites fluid, or infected tissues.Keywords: TB, peritoneal tuberculosis, extrapulmonary tuberculosis, acute abdomen, pregnancy

IntroductionInfective endocarditis (IE) is a severe and life-threatening disease worldwide (1). However, because of non-specific clinical presentations, confirmation and prescription of effective treatment are sometimes not simple tasks. History may help significantly in the diagnosis of IE; for example, it is more common among drug addicts, particularly Intravenous drug users (2, 3).Approximately 5% of IE cases have negative blood cultures (4, 5), and its risk factors are exposure to slow-growing bacteria such as Bartonella species, fastidious nonbacterial organisms, previous antibiotic use, underlying valvular heart disease, and intracardiac or vascular device or other foreign bodies in contact with the blood (6).Most patients have nonspecific symptoms such as fever, fatigue, and weight loss. In a case series comprising 348 blood culture-negative endocarditis cases from France, almost all the patients had a fever as a presenting symptom. In contrast, about 50 to 70% had symptoms of heart failure, such as exertional dyspnea, and about 50% had insidious weight loss(9).Bartonella spp. is a small, intracellular, gram-negative, and very fastidious rod mainly transmitted by vectors; they are the second most common cause of culture-negative endocarditis. Among the cases of Bartonella endocarditis, two species predominantly implicated in causing culture-negative endocarditis are B. henselae and B. quintana(7).These bacteria have been isolated from many mammalian species, including cats and dogs. It can cause mild infection to severe and life-threatening endocarditis in humans and dogs. In dogs, several Bartonella species have been identified; one of the most common ones is B. henselae.It should be mentioned that in recent years, more cases of culture-negative endocarditis have been reported from developing countries(8).This report presents a case of a patient with culture-negative B. henselae endocarditis from Iran, diagnosed using a combined diagnostic approach that included clinical evaluation, imaging, epidemiology, serology, echocardiography, and transthoracic echocardiography (TTE).Patient InformationThe patient was a 38 years old male, single and unemployed with a history of addiction, who had received care from a treatment camp for six months. He was discharged when he was on methadone maintenance therapy just before his first hospital admission. He was an IV drug abuser with a history of regularly using amphetamine, cocaine, and heroin. He also smoked cigarettes for 20 years. He also exposed that he had unsafe sex and lost contact with dogs and cats.Clinical Findings TimelineThe symptoms onset was 20 days before admission when he had fever and chills besides shortness of breath in the camp. The patient was hospitalized in another care center for five days as a suspected COVID-19 case and he was treated with Remdesivir, but his nasopharyngeal and oropharyngeal COVID-PCR tests were negative. Having been discharged from the hospital, he started using amphetamine again, which deteriorated his condition.This time he was admitted to our center, as a referral center, with severe dyspnea, high fever (40), chills, chest pain, myalgia, and hemoptysis. The patient was ill and, on physical examination, he had tachycardia (Heart rate=107) and tachypnea (Respiratory rate=28), with low blood pressure (90/60), fluctuated oxygen saturation which was less than 92%, normal heart auscultation, no clubbing, no splenomegaly, and no lymphadenopathy. Table 1 summarizes the lab results.

Editorial comment on the Special Issue “Omics in Food Allergy”Riccardo Castagnoli1,2, Ivan Taietti1,2,*, Agnes Sze-Yin Leung3, Philippe Eigenmann41. Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy2. Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy3. Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, China4. Pediatric Allergy Unit, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Geneva, SwitzerlandORCID:Riccardo Castagnoli: 0000-0003-0029-9383Ivan Taietti: 0000-0002-0372-523XAgnes Sze-Yin Leung: 0000-0001-8249-4478Philippe Eigenmann: 0000-0003-1738-1826Corresponding author:Ivan Taietti, MD;Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, [email protected]; +39 340 7092400.Food allergy (FA), defined as an adverse reaction to food mediated by the immune system, is a significant public health issue with increasing prevalence over the past decades. Although FA affects up to 10% of children, the precise mechanisms underlying FA development and persistence remain inadequately understood1. Food immunotherapy has been successful in increasing the threshold of tolerance in individuals with persistent FA (desensitization), and in a subset, sustained unresponsiveness (remission) can be achieved. A combination of environmental and genetic factors is considered to be involved in the tolerance induction to food allergens. However, to date, it has been difficult to fully dissect the complexity of the biological determinants involved in FA.The emergence of “omics” sciences, including genomics, transcriptomics, proteomics, and metabolomics, is revolutionizing the basic and translational research approach, allowing for the comprehensive study of biological processes through analyzing and integrating multiple datasets from various biological perspectives.Moreover, epigenetic studies that evaluate the role of gene expression modifiers are deepening our understanding of the interaction between genetic predisposition and environmental influences.The Special Issue “Omics in Food Allergy” aims to present current knowledge and future perspectives in the field of FA through the lenses of omics sciences.Chun et al. and Lehmann et al. provide a detailed overview of epigenetic mechanisms involved in FA, including DNA methylation and microRNA (miRNAs)2,3. DNA methylation refers to the covalent addition of a methyl group, typically to a cytosine in a CpG dinucleotide in DNA. This limits access for transcription, frequently in the promoter region, leading to reduced gene expression. Moreover, miRNAs are small RNAs transcribed from intergenic or intronic genomic loci that decrease gene expression by mRNA degradation and translational inhibition. Of note, Chun et al. described two different approaches in investigating FA mechanisms: (i) the epigenome-wide research approach and (ii) candidate-gene investigations. The epigenome-wide research approach identified genomic regions differently methylated and regulated, involved in FA causation, antigen presentation, T cell development, and reaction severity. Candidate-gene investigations focused on Th1, Th2, T regulatory, and innate genes of interest in FA, highlighting the importance of methylation changes in specific candidate genes. In this context, for cow’s milk allergy (CMA), the attention is focused on novel genetic loci involved in Th1/Th2 differentiation pathways and potential B-cell dysfunction4. Of note, miRNA seems to be involved in CMA as demonstrated by the downregulation of mi193a-5p, a post-transcriptional regulator of IL-4 expression, in infants with CMA5. Moreover, methylation levels in peripheral blood mononuclear cells for IL-4, IL-5, IL-10, and IFN-γ negatively correlate with their respective serum cytokine concentrations and vary according to CMA status (active, resolved, or non-CMA). Finally, Chun et al. reviewed ongoing research aimed at finding DNA methylation predictors of food challenges. Initial work based on the concept of epigenetic markers as biomarkers of disease and treatment demonstrated promise for applying DNA methylation markers to potentially improve how we assess and manage patients with FA, but further validation in larger cohorts and work to practically translate such biomarkers to clinical practice is advocated2.Metabolomics may reflect the integration of genetic, transcriptomic, and proteomic variations with environmental factors, thus reflecting molecular processes of diseases. A metabolome approach would facilitate the identification of surrogate metabolite markers correlating with the disease activity and prognosis. Lee et al. reported an updated overview of metabolomics’s current application in the FA field. Alterations to the gut microbiota induced by Western dietary patterns are likely to profoundly affect host immunity and play a significant role in FA. Metabolites of interest include short-chain fatty acids (SCFAs), bile acid metabolites, and tryptophan metabolites due to their essential roles in normal immune development and homeostasis. SCFAs appear to be reduced in FA patients. Of note, it has been shown that bacterial SCFAs could protect against FA as a consequence of a high-fiber diet in mice. Accordingly, a reduction in Bifidobacterium during infancy, with a consequent reduction in SCFA levels is associated with an increased risk of allergy6. In peanut allergy, oral dysbiosis, reduced oral SCFA levels, and increased oral mucosal Th2 cytokine secretion characterize patients affected, and low fecal SCFAs at a young age could raise the risk of developing FA. Bile acid levels in stool seem to be involved in FA development and persistence, but blood level measurements are advocated to better characterize their role. Moreover, sphingolipids may modulate the function of invariant natural killer T cells and contribute to maintaining intestinal balance and protecting against FA through the modulation of the mast cells’ responsiveness. Sphingolipid dysmetabolism is involved in FA development as a consequence of immune dysregulation in modulating the differentiation of regulatory T cells and Th17 cells that is relevant in FA. Interestingly, some fecal sphingolipids seem to confer protection against FA while reduction of other of them seems to be associated with increased risk of FA, likewise the reduction in serum sphingolipids. Unfortunately, no definitive evidence is available to distinguish whether the sphingolipids modulating this FA effect are dietary or microbial-derived. Metabolites of tryptophan from kynurenine and indole pathways are linked to the function of the intestinal barrier and mucosal immune responses (mainly T regulatory cells) and contribute to intestinal homeostasis. A reduction in these pathways is linked to multiple FA in children. To date, the role of omega-3-polyunsaturated fatty acids metabolites is not clearly defined in FA. However, 17-hydroxy-docosahexaenoic acid (17-HDHA) has been reported to inhibit IgE production by B cells and to suppress the differentiation of naïve B cells into IgE-secreting cells7.The gut microbiome (GM) and its metabolic product, as previously mentioned, play an important role in FA development. TheBifidobacteriaceae family and bacteria of theLactobacillales order are consistently reported lower in CMA children. At the same time, the Firmicutes phylum, primarily associated with the Clostridia class, is consistently increased in mice and human studies. It seems discordant with the observation that infants with resolved CMA were reported to have enrichedClostridia class at 3-6 months but with non-conclusive data. However, Savova et al. showed that GM with enriched Clostridiaclass, reduced Lactobacillales order, and reducedBifidobacterium genus is associated with CMA in early life. Emerging evidence shows that prebiotics, probiotics, and symbiotics, may be a promising adjuvant in promoting tolerance acquisition. ElevatedBifidobacterium genus and reduced Clostridia class members were consistently observed post-treatment with Bifidobacteriumstrains probiotics or after lactose-supplemented extensively hydrolyzed formula (EHF) treatment strategy but with decreased levels ofLactobacillus genus in those treated with Bifidobacteriumstrains probiotics. Gaps remain in understanding the relationship between microbiome and immune response and between transcriptomics (including genes related to the immune response) and GM. In vivo ,Bifidobacterium bifidum has been shown to reduce allergy symptoms, lower serum IgE and raise IgG2 levels, decrease the pro-inflammatory cytokines (TNFα, IL- 1β, and IL-6), and increase the anti-inflammatory cytokine IL-10 in CMA-patients8. Recently, fiber diet has been shown to modulate the disease course of FA through diet-driven changes in the GM9. It is necessary to conduct further research on the impact of GM on FA development and persistence.Lastly, oral immunotherapy (OIT) may provide an active treatment that enables to increase the amount of food that the patient can intake without reaction during treatment (i.e., desensitization), and reduces the risk of potential life-threatening allergic reaction in the event of accidental ingestion10 Unfortunately, there are still significant gaps in understanding the immune mechanisms following OIT, but increasing knowledge about transcriptional pathways associated with its outcomes is available to date11. Ashley et al.12 show that OIT-induced remission of FA is linked to the anergic T cell state mediated by anergy of memory T cells associated with mantained T regulatory cell activity. Suppression of the Th2 transcriptional signals in Th2A-like cells was linked to desensitization following OIT. Moreover, the dampened Th2 and Th1 signatures in effector cells are linked with FA remission, while baseline inflammatory signals in Th1 and Th17 effector cells were associated with poorer outcomes following OIT. Type I interferons were recently identified as potential regulators of remission following OIT because of their key role in the suppression of the Th2 antigen response through regulatory action on GATA3 and the high-affinity IgE receptor. Moreover, an early transient increase in TGF-β producing cells one year into treatment seems to be associated with good clinical outcomes. In addition, persistent activation of FOXP3, expressed by T regulatory cells, may be a critical requirement for lasting persistence of remission12.Comprehensive multi-omics studies are essential to understand FA mechanistically, as highlighted by this Special Issue. “Omics” studies of FA are of great interest as they allow for a thorough understanding of the complexity of FA development and therapeutic outcomes. This has a fundamental impact on approaches to precision medicine.

Objectives: To determine the time to ventilator liberation and decannulation after tracheostomy placement in children with bronchopulmonary dysplasia (BPD) and pulmonary hypertension. Methods: A prospective cohort study included all children (<18 years old) who underwent tracheostomy between 2015 and 2021 with or without a diagnosis of BPD. The primary outcome measures were times to mechanical ventilator liberation, tracheostomy decannulation, or death with tracheostomy in place. Patient demographics, associated comorbidities, and outcomes were compared between groups. Results: A total of 318 children met inclusion with a median (interquartile, IQR) age at tracheostomy of 6.9 (IQR: 4.1 – 49.2) months and 54% (N=170) were male. A diagnosis of BPD was made for 43% (N=136) and this group was younger at tracheostomy placement (5.2 vs. 24.5 months, P<.001) and more often had pulmonary hypertension (65% vs. 24%, P<.001) than children without BPD. Children with BPD spent a median of 2.92 years (IQR: 1.60 – 4.03) on mechanical ventilation compared to 1.84 years (IQR: 0.84 – 3.60) for children without BPD ( P=.003). Unadjusted estimation of time to decannulation was longer for children with BPD (HR=0.92, 95% CI: 0.62 – 1.38). The adjusted survival analysis for time to mortality included pulmonary hypertension as a variable of significance (aHR= 2.5, 95% CI: 1.43 – 4.40). Conclusion: The presence of BPD is associated with an increased duration of mechanical ventilation and time to tracheostomy decannulation. Pulmonary hypertension is associated with an increased mortality risk among this vulnerable population of children.