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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.

Visual question answering (VQA) is a challenging task that requires multimodal reasoning and knowledge. In this study, we explored different methods of feature fusion for VQA, using pre-trained models to encode the text and image features, and then applying different attention mechanisms to fuse them. We evaluated our methods on the DAQUAR dataset. We used three metrics to measure the performance of our methods: WUPS, Acc, and F1. We found that concatenating raw text and image features performs slightly better than self-attention for VQA. We also found that using text as query and image as key and value performs worse than other methods of cross-attention or self-attention for VQA, because it does not capture the bidirectional interactions between the text and image modalities. We discussed some possible explanations and examples for these findings.

Title : Synovial Sarcoma of the Maxilla: A Challenging Diagnostic Case Report and Literature ReviewAbstract : Synovial sarcoma, a malignant mesenchymal tumor, is primarily associated with the extremities. Nevertheless, its appearance within the head and neck region, particularly in the maxillary area, is remarkably rare. This rarity underscores the significance of each case in unraveling the complexities of its behavior and management strategies. The core focus of this research is a detailed case report involving a 6-year-old female patient who presented with a conspicuous swelling in the left posterior maxilla. Subsequent incisional biopsy led to microscopic identification of malignant spindle cell proliferation, marked by dysplastic changes and abundant mitoses. Immunohistochemical analysis demonstrated negative reactivity for neural and muscular markers, while positive expression of Vimentin, Bcl-2, and TLE1. These morphological and immunohistochemical findings coalesced to definitively diagnose synovial sarcoma, substantiated by a notable 40% Ki67 proliferative index. The chosen treatment strategy encompassed surgery and radiotherapy, which yielded successful outcomes, with no recurrence observed during the one-year follow-up period. Beyond the specific case, this article undertakes a review of existing literature, meticulously analyzing nine similar cases reported in scholarly sources.Keywords : Case report, Head and neck, Maxilla, Synovial sarcoma

ALSTROM HALLGREN SYNDROME WITH CLASSICAL FINDINGS: A RARE CASE REPORT OF MONOGENIC CILIOPATHY CO-OCCURRENCE IN TWINS.Clinical Message: With the prevalence of 1 in million cases Alstorm Hallgren syndrome is one of the rare genetic disorder with poor prognosis. In our case we present classical findings in twins who were diagnosed as Alstrom syndrome concurrently and further diseases progressed simultaneously .Keywords: Alstrom Hallgren syndrome, monogenic ciliopathy, twinsCorresponding Author :1Sagun ghimire,KIST medical college and Teaching Hospital, Gwarko, Lalitpur, NepalSagunghimire01@gmail.comCo-authors:2Suman simkhada, KIST medical college and teaching hospital,gwarko, lalitpur, Nepalsimkhadasuman@gmail.com3Samir Thapa, KIST medical college and teaching hospital, gwarko,lalitpur, NepalThapasamir32@gmail.com4Kiran Ghising, KIST medical college and teaching hospital, gwarko,lalitpur, NepalKiran.ghising98@gmail.com1 . INTRODUCTION:Alström syndrome is a rare autosomal recessive genetic disorder,thought to have a prevalence of less than one per million in the general population. It is characterized by the progressive development of multi-organpathology [1]. It is caused by recessive mutations in ALMS1 (Chr 2q13). Although its function is not completely understood, evidence to date suggests that ALMS1 plays roles in ciliary function, cell cycle regulation, endosomal trafficking, cell migration, and extracellular matrix production [2]. Diagnosis of Alström Syndrome can be difficult because some features begin at birth and others emerge as the child develops. There is considerable variation both within and among families. The major phenotypes usually observed in children with Alström Syndrome include cone–rod retinal dystrophy beginning in infancy and leading to eventual juvenile blindness, sensorineural hearing impairment, insulin resistance, and obesity. In some cases, infants present with congestive heart failure (CHF) due to dilated cardiomyopathy (DCM). As patients reach adolescence, more of the major phenotypes develop, including type 2 diabetes mellitus (T2DM), hypertriglyceridemia, and adolescent-onset DCM. Short stature, scoliosis, alopecia, and male hypogonadism and hyperandrogenism in female patients may be present when patients reach adulthood. Pulmonary, hepatic, and renal phenotypes are progressive. Fibrosis in multiple organs has been described [3]. Currently there are no specific treatments for Alström syndrome that can cure the disease, prevent the complications, or reverse the complications. A multidisciplinary approach is currently preferred to detect, predict, and treat the complications of Alström syndrome[4]. The article is presented in accordance with CARE guidelines for case reports[5]. Here, we present a case of twin siblings with signs and symptoms consistent with AS and associated with two AMLS1 variants.2. CASE SUMMARYPatients Demography :In this report we describe monochorionic, diamniotic twin boys who were born pre term at 36 weeks to a healthy 28 year old mother and healthy 32 year old father, with natal history of low birth weight of in one twin and in another twin with APGAR score of 6\10 and 7\10 and post natal history of raised total serum bilirubin for which both twins were kept under phototherapy. There is no history of delay in attainment of age related milestones . Parents are of Asian heritage who deny consanguinity, both alive and well as well as two twins siblings currently aged 16 years . The family structure is outlined in( Figure 1). Family history was not significant for any genetic disease on the paternal and maternal side.Clinical Evaluation :On physical examination, there was evidence of central obesity in both twins with the body mass index ( in both) being 34.9 kg/m2. Their blood pressure was within normal percentile with a regular pulse of 80 beats per minute. Behaviorally, they do not demonstrates several features concerning for autism spectrum disorder, including poor eye contact, lack of a social smile, and disinterest in social interaction. Their weight since birth has been seen to in increasing trend, and height within mid parental range. There was no evidence of poly- or syndactyly or any other features suggestive of Bardet-Biedl syndrome. Features of hirsutism was also absent on the face, abdomen, and arms. There was significant history of decreased vision in both eyes since neonatal period .Both the twins presented at four years of age with visual symptoms suggestive of photosensitivity. There was features suggestive of rotatory nystagmus . Amsler grid and color vision tests were normal. Visual field revealed concentric contraction in both eyes. The fundoscopy showed pale optic discs, atrophic maculopathy, golden appearance of peripheral and midperipheral fundus, coarser pigmentary changes with a ”bone-spicule” configuration and arteriolar narrowing. The red free pictures demonstrated the atrophy of internal retinal layers and the infrared pictures revealed the atrophy of the external layers of the retina in posterior pole of the fundus. The flash ERG showed reduced amplitude of photopic and scotopic b-wave. The multifocal ERG demonstrated the normal function of the central retina. revealed decreased Arden ratio in both eyes. The pattern VEP revealed the P100 amplitude reduction by 80% and elongation of latency by 120% in the right eye and normal in the left eye. Subsequent ophthalmologic exam showed visual acuity of counting finger from 2 and half meter binocularly only due to high hyperopia with amblyopia. The findings were consistent with cone-rod dystrophy through electroretinography (ERG). Subsequently there was progressive visual loss and legal blindness was declared to both of the twins at the age of 11 years. The cardiovascular examination was unremarkable with no any significant Echocardiography and electrocardiography findings . There was not any features suggestive of congestive heart failure, myocarditis, dilated cardiomyopathy. Cardiac catheterization and Endomyocardial biopsy were not done . A comprehensive systemic panel did not identify any disease causing mutations and screening for evidence of metabolic and mitochondrial diseases was negative. The patient also showed features such as weight loss, polyuria, polydipsia, predilection to sweet foods.

INTRODUCTION Type 1 diabetes mellitus (T1DM) is an autoimmune disorder leading to the destruction of insulin producing pancreatic beta cells, resulting in elevated blood sugar levels 1. Polyuria, polydipsia and weight loss are the key presenting symptoms 2. A systematic review and meta-analysis reported the global T1DM prevalence of 9.5%, with an incidence of 15 per 100,000 people3. Diabetic ketoacidosis (DKA) is a grievous complication of diabetes mellitus caused by insufficient insulin, resulting in elevated blood glucose, ketonemia and acidosis. The overall DKA prevalence across 13 countries over 13 years was 29.9%, with a 3.5% prevalence in Nepal. 4,5.The most common risk factors leading to DKA include missed insulin doses and infections, while other factors like stress-inducing events or the initial onset of diabetes can also trigger DKA. The clinical manifestations of DKA encompass a range of symptoms, including nausea, severe vomiting, dehydration, polyuria, polydipsia, abdominal pain or discomfort, presence of acetone breath odor, Kussmaul breathing, overall profound fatigue with altered consciousness, disorientation, confusion or occasionally coma when the condition is severe 6. Typical diagnosing criteria for DKA include blood glucose greater than 250 mg/dl, arterial pH less than 7.3, serum bicarbonate less than 15 mEq/l, and the presence of ketonemia or ketonuria 7.Immediate intervention is crucial that includes restoring the circulatory volume, correcting electrolyte abnormalities, insulin therapy and addressing the underlying cause 8. Failure to promptly treat DKA can result in the breakdown of compensatory mechanisms and cause electrolyte abnormalities like hyponatremia, hyperkalemia and ultimately lead to life threatening complications including cerebral edema, acute respiratory distress syndrome, and sepsis.  Nursing management for a patient with Diabetic Ketoacidosis (DKA) involves a comprehensive approach that involves monitoring vital signs, blood sugar levels, and electrolytes, administering fluids, assessing renal function and mental status, monitoring intake output, checking for signs of infection, assessing lung sound; educating the patient on insulin injection techniques, medication compliance, promoting lifestyle changes like smoking cessation and diabetic diet9.In DKA, dilutional hyponatremia is common due to rising glucose level that creates osmolar gradient causing water to shift from cells into the intravascular space. However, on rare occasion, hypernatremia is found that happens when there’s a deficit of water intake and excessive loss of free water, which outweighs electrolyte loss through various factors10. This report emphasizes the significance of a fluid management strategy for DKA patients, even when encountering the unusual occurrence of hypernatremia.

CASE REPORTMucinous tubular and spindle cell carcinoma: A rare kidney tumourAmina Bani (1), Salwa Nechi (1), Sataa Sallemi (2), Hamza Ichaoui (2), Mohamed Ali Bedoui (2), Amel Douggaz (1), Abir Chaabène (1), Mohamed Karim Mfarrej (1), Emna Chelbi (1).(1) Mohamed Taher Maamouri University Hospital, Pathology Department, Nabeul, Tunisia.(2) Mohamed Taher Maamouri University Hospital, Urology Department, Nabeul, Tunisia.

Purpose: Bleomycin is a chemotherapeutic agent that causes lung toxicity. Bleomycin is mostly used in the treatment of germ cell tumors(GCT) and Hodgkin Lymphoma(HL) in childhood cancers. In this study, we aimed to detect bleomycin toxicity to the lung in the early period. Materials and methods: Pulmonary functions of patients aged 5 years and older who were admitted to the Division of Pediatric Oncology with germ cell tumors and Hodgkin Lymphoma between 2012 and 2022, who received bleomycin treatment and were in remission for at least 6 months were evaluated. The evaluation of respiratory function was based on history, physical examination, posteroanterior chest radiography and pulmonary function test. Results: There were 109 patients with GCT and 122 patients with HL. The number of patients with GCT who entered follow-up and lived were 59, those with HL were 89]. The number of patients who received bleomycin treatment, were in remission for at least 6 months and underwent PFTs were 46 for HL and 12 for GCT. There were 21 patients with PFT abnormalities. Of these patients, 3 were diagnosed with GCT and 18 were diagnosed with HL. The type of PFT abnormality in the majority of patients was restrictive disorder. Conclusion: The absence of respiratory symptoms in 90% of patients with PFT abnormalities shows the importance of PFT in asymptomatic patients. Patients who have received bleomycin as part of treatment should also be followed-up for late pulmonary toxicity.

The Moore-Gibson-Thompson equation with a viscoelastic memory and a forcing is considered. The existence and uniqueness of a local solution is obtained via the Faedo-Galerkin's method. Furthermore, blowing-up solutions with or without a positive initial energy exist due to the nonlinear forcing.

Introduction: Acute lymphoblastic leukemia (ALL) represents the most prevalent childhood malignancy. Despite high cure rates, several questions regarding predisposition, response to treatment, and prognosis of the disease remain. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL present a distinct metabolomic fingerprint at diagnosis when compared: i) to a control group; ii) to children with a different (sub)type of ALL; iii) to the end of the induction treatment. Methods: This prospective case-control study (NCT03035344) analyzed plasma and urinary metabolites in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analysis was conducted by SIMCAP and scripts under R programming language. Results: Metabolome analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the group of patients differed significantly between common B and pre-B ALL, and between D0 and D33, reflecting the effect of treatment. We have further identified the main components of this metabolic dysregulation that indicate shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipids metabolism and in glutaminolysis/TCA cycle. Conclusions: The notable type and disease time point specific metabolic alterations observed in pediatric ALL may offer the potential for the discovery of new prognostic biomarkers and therapeutic targets.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating side effect seen in children undergoing chemotherapy. Objective: To synthesize the evidence on physiotherapy for CIPN symptoms and deficits in children with cancer. Methods: A systematic review was conducted with the following PICOS approach: children with cancer, physiotherapy, control group or standard care, and randomized controlled trials and controlled clinical trials comprising range of motion, muscle strength, motor function, balance, gait, functional mobility, foot posture, pain, and adverse events outcomes. Searches were conducted in five electronic databases, reference lists, grey literature, and clinical trial websites in May 2023. Results: Nine full-text studies met the inclusion criteria. Although benefits were seen for some outcomes related to physical function, evidence is not at a stage to provide recommendations for clinical practice. Conclusion: Research is needed that includes CIPN-specific outcome measures to better inform the incidence, natural progression, and the benefits of physiotherapy interventions.

Changes in water and nitrogen availability can affect the structure and function of arid ecosystems. How these resources affect aboveground primary productivity (ANPP) remains far from clear. We examined the N and water limitation of ANPP from the species to the community level and the response of ANPP to annual precipitation in a Patagonian steppe. We conducted a 7-year field experiment with water addition (+W), nitrogen addition (+N), and +NW. Destructive methods for grasses and allometric relationships for shrubs were used to assess ANPP and vegetation indices (NDVI and MSAVI2) to estimate community ANPP. An increase in ANPP of one grass species ( Papposstipa humilis) and a decrease of the grass Poa ligularis under +N were observed. Some shrubs species exhibited mortality under nitrogen addition. Nitrogen exerted a positive effect on grass ANPP and amplified the sensitivity of grass ANPP to annual precipitation. However, +N had not effects on the shrub ANPP and shrub ANPP-precipitation relationship. Water addition by itself had no effect on ANPP for either shrubs or grasses. However, shrubs responded positively to an unusually wet year regardless of treatment and were also more sensitive to changes in annual precipitation than grasses. Total ANPP increased significantly in +N relative to the C and +W, but without changes in the sensitivity to annual precipitation. The results suggest that the responses of grasses and shrubs to water inputs is driven by soil moisture redistribution and rooting depth and that grass and community ANPP is more limited by N than by water.

Abstract As part of this study, a unique method for automatic real-time analysis of sentiment in product reviews for online shopping applications is provided. The main goal is to create a model that has a high level of accuracy and is able to categorize product reviews with either a positive, negative, or neutral sentiment. To achieve this goal, a combination of natural language processing (NLP) strategies and machine learning algorithms is employed. The first step in the process, known as pre-processing, cleans up the text data by removing any noise and then applies tokenization and stemming techniques to it so that significant features can be extracted. A variety of machine learning models, such as B. Support Vector Machines (SVM), Naive Bayes and Random Forest, are trained and evaluated using an extensive data set of labeled customer reviews of various products. The development of a web application was chosen as the implementation method for the system in order to enable easy integration with the online trading platform. This solution ensures that processing occurs in real-time, allowing for effective analysis and quick response to users. Users can better understand product reviews and make more informed purchasing decisions when sentiment analysis is integrated into the online shopping experience. The proposed approach is a major advance in the development of sentiment analysis for online trading related applications. His ability to conduct real-time sentiment analysis allows him to uncover key insights into customers’ thoughts and preferences. The method provides a viable way for companies to assess consumer satisfaction and sentiment trends by properly classifying product reviews. As a result, companies can ultimately improve the quality of the products and services they provide. Keyword: Online shopping applications, Sentiment analysis, Product reviews, Natural language processing (NLP), support vector machines (SVM), Naive Bayes, Random forest.

The development of the Internet of Things (IoT), which enables communication between people, things, data, and virtual platforms in the environment, is a result of the exponential rise of information technology (IT). Recently, numerous decision support systems in the medical industry have been offered via IoT and cloud-based e-health services. Owing to the developments in IoT-enabled medical gadgets and sensing devices. Chronic diseases are often considered as a major source of concern and a threat to public health on a global scale. The kidneys are one of the body’s most complicated organs and perform several tasks. The elimination of waste materials by the kidneys during the formation of urine helps to cleanse the blood. When the kidneys begin to lose function, Chronic Kidney Disease (CKD) occurs. The accurate diagnosis of CKD is an important and crucial step in medical informatics. An earlier diagnosis can save more human lives. But, it is complicated task due to similar symptoms, inaccurate data and information, lack of knowledge, etc. It is also seen that the presence of missing values and outliers can also complicate the prediction task and, in turn, produce less accurate results. The primary objective of this research work is to develop an IoT framework for collecting the real time CKD dataset and also to handle the two well-known issues of medical data, i.e. outlier detection and CKD prediction. This work proposes the Chicken Swarm Optimization (CSO) algorithm to enhance the raw data and diagnose CKD diseases using k-NN.