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Machine Learning Global Ecological Niche Modelling of Indigofera oblongifolia (Forssk...
Preet Mathur
manish mathur

Preet Mathur

and 1 more

April 01, 2023
The goal of this study was to identify the global geographical distribution patterns of a lesser known indigenous legume species, Indigofera oblongifolia, using three bio-climatic timeframes (current, 2050, and 2070) and four greenhouse gas scenarios (RCPs 2.6, 4.5, 6.0, and 8.5), as well as non-climatic predictors like global livestock population, human modification of terrestrial ecosystem (GHMTE), global fertilizers application (nitrogen and phosphorus). In addition, we assess the degree of indigenousness using the area, habitat suitability categories, and number of polygons, and we identify the temporal effects of various bio-climatic variables on its fundamental and realized niche. The AUC for models built using current climate data and RCPs for the years 2050 and 2070 was 0.90. This research reveals that climatic predictors outperform non-climatic predictors in terms of improving model quality. Precipitation Seasonality is one of the most important factors influencing this species’ optimum habitat suitability up to 150 mm for the current, 2050-RCP 8.5, and 2070-RCPs 2.6, 4.5, and 8.5. The range of this parameter has altered from 79–176.9 to 85–196 as the climatic conditions and RCPs have improved. Our ellipsoid niche modelling extends the range of these bioclimatic variables to 637 mm and 26.5-31.80 degrees Celsius, respectively. India has a higher indigenous score in the optimal class than the African region. These findings indicate that this species inhabits more continuous areas in Africa, whereas it is fragmented into a number of smaller meta-populations in India (group of spatially separated population of the same species).
Sex in a virtual reality: experimental evidence for sexual isolation due to variation...
Juan Peralta-Rincón
Fatima Zohra Aoulad-Taher

Juan Peralta-Rincón

and 2 more

March 31, 2023
Differential perception and subsequent differential use of habitats can generate local adaptation, especially when natural selection cannot. However, this local adaptation is not maintained into future generations unless mating happens within the chosen habitats. We currently have no experimental data on whether differential perception of environments results in sexual isolation. We induced differential perception of environments by stimulating different olfactory neurons via light pulses (optogenetics) in two groups of fruit flies. These flies were released in a cage of which only one section received light pulses. One group of flies perceives this optogenetic stimulation as the smell of a harmful concentration of CO2 and was found to avoid the illuminated section. The other group perceives it as the smell of food-related compounds and was found to be attracted to the illuminated section. Due to this self-imposed spatial segregation, we subsequently observed a considerable degree of sexual isolation between the two groups of flies. In contrast, in two control treatments preventing differential perception of the environment, sexual isolation was virtually absent. Our results show that differential perception of the environment can easily and rapidly generate spatial segregation and sexual isolation among individuals that are ecologically different. This can maintain local adaptation, especially under conditions when natural selection cannot, which are increasingly common due to human-induced rapid environmental change.
Roots prime microbes to extract nitrogen and stabilize soil organic matter
Joanna Ridgeway
Jennifer Kane

Joanna Ridgeway

and 4 more

March 31, 2023
Plant-microbe interactions in the rhizosphere shape carbon and nitrogen cycling in soil organic matter (SOM). However, there is conflicting evidence on whether these interactions lead to a net loss or increase of stable SOM. In part, this conflict is driven by uncertainty in how litter forms new stable SOM with living roots in the field. To address these uncertainties, we traced the fate of isotopically labeled litter into SOM using root and fungal ingrowth cores incubated in a Miscanthus x giganteus field . Roots selectively mobilized nitrogen from litter without additional carbon release, and transferred litter carbon into more stable, aggregate-associated SOM. Litter rapidly formed minerally-protected SOM, but native minerally-protected SOM was also rapidly lost. Overall, our fundings suggest that roots stimulate litter decomposition to selectively release nitrogen. We also highlight there may be a rapidly cycling component of minerally-protected SOM that is accessible to roots and microbes.
Tackling local ecological homogeneity: managing divergences in local populations of M...
Lorenzo Maria Iozia
Laura Varone

Lorenzo Maria Iozia

and 1 more

March 31, 2023
Local homogeneity is a common assumption in ecology, which can lead to the aggregation of populations without regard for their unique needs and characteristics. Here we discuss whether this assumption is justified, and we hypothesize an approach to formulate an informed decision, by discerning the source of variation between plasticity and adaptation. We test this approach on plants, performing a common garden experiment to guide our choice discerning between the two at a local scale (~60 Km). Using functional trait measurements for three species, Quercus ilex, Pistacia lentiscus and Cistus salviifolius, hailing from three sites chosen along a local aridity gradient, we were able to reject the local homogeneity assumption for Q. ilex and C. salviifolius at this scale due to the adaptive divergence observed among neighbouring populations. We conclude that gathering empirical evidence can provide with solid bases to decide whether to adopt the local homogeneity assumption.
Molecular characterization of head and neck infection causing bacterial communities u...
Smarita  Lenka
Subrat  Swain

Smarita Lenka

and 7 more

March 31, 2023
Multidrug resistance (MDR) is a global threat due to either improper diagnosis or overuse of antibiotics. Head and neck infections (HNI) are serious diseases that involve several species of microorganisms. Common complications of HNI developing through bacterial colonization that leads to airway obstruction, pus collection, and sepsis. During this study, we collected 264 clinical samples (2020–2022) from Odisha, a state of eastern India to investigate bacterial communities associated with HNI followed by their antibiotic susceptibility characteristics, and the evaluation of their diversity by comparing with global isolates. We found 218 positive bacterial isolates and 25 multidrug-resistant bacteria, and accomplished their molecular characterization along with phylogenetic analysis utilizing the 16S rRNA gene. Population genetic parameters revealed the haplotype diversity (Hd) and nucleotide diversity (π) ranged from0.558-0.828 and 0.03236-0.28428 respectively. This study helps to disseminate the prevalence of these neglected pathogens within this rarely focused geographical area and its transboundary potential to navigate better therapeutic approaches.
A Review on Coated Value Added Phosphatic Fertilizers for Better Environment
adnan Muhammad
Shakeel Ahmad

adnan Muhammad

and 3 more

March 31, 2023
Abstract Plants utilize only up to 25% of the applied phosphatic fertilizers and 75% of the applied phosphatic fertilizers become unavailable due to two major reactions, the adsorption on mineral surface and the precipitation reactions. More and more fertilizers have to be applied exogenously. More energy is required for fertilizer production and transportation by the factories which influence our environment badly.The fixed fertilizers prevails in the environment, causing ecosystem imbalances. More over, phosphatic fertilizers are expensive than nitrogenous and potassic fertilizers, hence need to be managed. There are different techniques to improve fertilizer utilization by plants, however value addition of fertilizers such as surface modifications of fertilizers proved to be more fruitful because these manipulate the supply of nutrients with crop demand. These may slow down, control or stabilize the release of nutrients from the fertilizers by reducing the direct contact of the soil with fertilizer particles. It may become a tool for sustainable production, minimizing the remaining of synthetic chemicals in the environment, by more plants utilization. This paper is an effort to highlight the production processes, different coating materials used, how these value added fertilizers release nutrients in distilled water and in soil and their impact on crop. In the later part of this article, challenges for their adoptions will be discussed . Keywords: Coated fertilizers; Fertilizer use efficiency; Slow release fertilizers; Value addition. Alternate Keywords: Phosphorus utilization enhancement; Phosphorus availability approaches; Uptake techniques; Nutrient use efficiency
Assessment of Vestibulotoxicity of Henna Leaf (Lawsomnia Inermis) in A Rat Animal Mod...
Abdul Azim Al-Abrar Ahmad Kailani
Azliana Aziz

Abdul Azim Al-Abrar Ahmad Kailani

and 2 more

March 31, 2023
BACKGROUND: Otomycosis is complicated for patients and otologists since it always needs long-term care and follow-up, but the recurrence rate remains high. Management is targeted toward intensive aural toileting with the administration of topical antifungals. Classical antifungal agents, including azoles and polyenes, have shown increased resistance. This has contributed to studies into medicinal plants as an alternative therapy for fungal infections. OBJECTIVE: This research aims to examine the potential vestibulotoxic effects of the henna leaf (Lawsomnia inermis), an ancient folk medicine, on the inner ear of a rat animal model. METHODS: Twenty-four healthy, adult male Wistar Kyoto rats were categorized into three groups (A, B, C) with eight rats each. Baseline vestibular parameters were tested before endoscopic-guided transtympanic instillation of aqueous and ethanol henna extract into the right middle ear of rats in Group A and B, respectively. At the same time, normal saline was instilled in the right middle ear of rats in Group C. Vestibular parameter testing was conducted on rats post-instillation of transtympanic Henna at intervals of 4 hours, 24 hours, 48 hours, 72 hours, one week, two weeks and three weeks. RESULTS: All vestibular parameters documented were not affected after the instillation of henna extract into the middle ear. CONCLUSION: Henna extract is a safe and potential alternative in treating otomycosis even with tympanic membrane perforation, as it has no vestibulotoxic adverse effects.
Horror Movies: A trigger for PTSD and Anxiety
Nathalie Akiki
Malak Wehbe

Nathalie Akiki

and 2 more

March 31, 2023
Horror movies have been produced, filmed and broadcasted for decades. It has been thought that people watching such movies, tend to get influenced by harsh scenes, leading to psychological distress. This review highlights the impact of horror movies in developing post-exposure reactions, such as Post Traumatic Stress Disorder, and anxiety and discusses the different risk factors and mechanisms behind such manifestations.
A Qualitative Study of Military Service Members Undergoing Medical Separation
Marjan Ghahramanlou Holloway
Su Yeon Lee-Tauler

Marjan Ghahramanlou Holloway

and 12 more

March 31, 2023
Objective: A qualitative study sought to understand the transition experiences of United States (U.S.) military Service members found “unfit for duty” following medical and physical evaluation boards (MEBs and PEBs). Methods: Confidential telephone interviews were conducted with 25 current and prior Service members. Participants were asked to share their experiences before, during, and after the MEB and PEB processes. To that end, interview questions were designed to gather the following types of transition experiences: (1) health conditions experienced during the medical disability evaluation process; (2) reactions to being recommended for separation, (3) transition-related stress and challenges, and (4) coping strategies. Salient themes were identified across chronological narratives. Results: Conditions that participants’ experienced included debilitating physical (e.g., injury) and/or mental health (e.g., post-traumatic stress disorder) conditions. In response to the “unfit for duty” notice, some participants reported emotional distress (e.g., anxiety, sadness, anger) connected to a sense of uncertainty about the future. Other participants reported relief connected to a sense of progression toward their medical disability claim status. Transition stress included the length of the MEB/PEB process, impact of the COVID-19 pandemic on the process, experiences of financial stress, impact on family life, and the compounded effect of these stressors on emotional distress, including depression and suicidal thoughts. Participants reported using adaptive (e.g., psychotherapy) and maladaptive (e.g., excessive drinking) strategies to cope with stress. Conclusions: The notable emotional distress and transition stress experienced by Service members found “unfit for duty” highlight the need for increased support and interventions to facilitate adaptive coping strategies during this vulnerable period.
A Review on Machine Process Parameters of Laser Engineered Net Shaping
Tamiru  Hailu Kori
Dawit Muluneh Yona

Tamiru Hailu Kori

and 3 more

March 31, 2023
Manufacturing sectors are shifting their interest toward additive manufacturing technologies, where components are fabricated directly from CAD models layer by layer. Laser engineered net shaping most known to produce a near net shape of functionally graded materials. In this paper, process parameters that affect mechanical properties, surface topology and physical properties are reviewed. Powder feed rate, hatch distance and layer thickness more related to porosity of the parts that being produced. Mechanical properties get affected by laser power scan speed. Density and hardness sensitive to focal distance of the optimal convergence of the maximal laser intensity and the localized spatial concentration of the powder beam. To get homogeneous microstructure shorter focal distance is preferable. However, working distance has no such impact on density.
A Case Report: The First Show Phenomenon In The Treatment Of Spinal Cord Injury With...
Rita Boulos
lea nemer

Rita Boulos

and 5 more

March 31, 2023
A Case Report: The First Show Phenomenon In The Treatment Of Spinal Cord Injury With Regentime Procedure Using Autologous Bone Marrow-Derived Stem CellsRita T. Boulos a†, Lea I. Nemerb†, Vanessa J. Mansour c†, Cynthia F. Najjoumd††,Elsa A. Asmar e†† and Nassim H. Abi Chahinef*† Authors’ equal contribution†† Authors’ equal contributionStem Cell Transplantation/Neurology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Molecular Biology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Infectious Diseases/Immunology, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Functional Genomics/Proteomics, ACE Cells Lab Limited, Beirut, LBStem Cell Transplantation/Neurological Surgery, ACE Cells Lab Limited, Beirut, LB* Correspondence to:Dr. Nassim H. Abi ChahineTel: +9613082498E-mail: info@regentime.com
Spherocytosis in Newborn Secondary to Novel Heterozygous Mutation in SPTB Gene
Daphna Varadi
Benjamin Caplan

Daphna Varadi

and 3 more

March 31, 2023
This case report describes a novel mutation of the SPTB gene as a potential pathogenic cause of spherocytosis. A three-week-old male presented with clinical and laboratory signs consistent with hemolytic spherocytosis (HS), including jaundice, hyperbilirubinemia, anemia, reticulocytosis, negative Coombs test, no ABO or Rh incompatibility, and a peripheral blood smear notable for numerous spherocytes. His lab work demonstrated persistent anemia despite daily folate prompting next-generation sequencing (NGS) which revealed a novel mutation in the SPTB gene resulting in a non-functioning protein product. Correlation of the genetic finding with clinical presentation may help guide management for this and future patients.
Is Smoke the Signal for Surgery? : Should the Moyamoya Syndrome “Puff of Smoke” trigg...
Lewis Hsu

Lewis Hsu

March 31, 2023
Stroke in Sickle Cell Revascularization Surgery Retrospective Study (SiSCRS) in this issue reports retrospective data from 15 medical centers to examine the benefit of cerebral revascularization surgery (CRS) in children with sickle cell disease (SCD) who also have Moyamoya Syndrome (SCD-MMS). The American Society of Hematology guidelines “suggests evaluation for revascularization surgery in addition to regular blood transfusion” for treating SCD-MMS combined with a history of stroke or transient ischemic attack but categorizes this as a “conditional recommendation based on very low certainty in the evidence about effects”. The research presented in this article is aimed at reducing the uncertainty surrounding revascularization surgery as a treatment using retrospective data from 15 medical centers with expertise in CRS for SCD-MMS. Even with the 78 children with CRS (Surgery group) and 63 children in the non-surgery (Conservative group), the differences between the two groups had mixed statistical significance in multivariate analyses. SiSCRS is an important retrospective analysis but must be interpreted with caution. The benefit of CRS attains statistical significance only in some of the comparisons. The rate of stroke in pediatric SCD decreases with age, creating a bias in favor of the older group (i.e., the Surgery Group) to have fewer CVEs, The additional role of aspirin and the bias of patient selection for surgery also weaken the ability to make definitive statements. The SiSCRS results suggest a likely retrospective benefit of CRS, but the benefit must be demonstrated with more rigorous studies in the future.
Mechanism of Acute Pacing Threshold Elevation During Simultaneous Micra Leadless Pace...
Racine HP
Nicolas Dognin

Racine HP

and 6 more

March 31, 2023
Background In patients with refractory atrial fibrillation (AF), atrioventricular nodal (AVN) ablation and permanent pacemaker implantation is recommended. The Micra Transcatheter Pacing System™ (Micra) is a single chamber leadless pacemaker (LPM) and thus offers the possibility of AV node (AVN) ablation in the same procedure. Pacing threshold (PT) elevation after radiofrequency (RF) ablation is a potential complication. Methods We conducted a single center retrospective cohort study. All patients implanted with a Micra (n=84) and concomitant or delayed AVN ablation (n=12) from 2014 to 2022 were included. We describe two cases of acute Micra PT elevation immediately following RF AVN ablation requiring device retrieval and implantation of a new Micra. Procedural characteristics and electrophysiological parameters were analyzed, and computer modelling was performed to determine factors responsible for acute PT elevations. Results A total of 84 patients were included. Mean age was 74±10 and 48% were women. Twelve patients (14%) underwent AVN ablation. Two patients had acute PT elevation requiring device retrieval despite no direct contact of the ablation catheter with the Micra. Computer modelling shows that significant dissipated power due to electrical field coupling can occur at the tip or ring electrode if the catheter is not kept at a safe distance (≥15 mm) from the Micra. Conclusion Concurrent AVN ablation and Micra implantation is safe in most patients. To prevent acute PT elevation, keeping a safe distance of ≥15 mm from the tip and ring electrodes of the Micra and using lower power output may prevent this complication.
GINGIVAL NEUROFIBROMA IN NON SYNDROMIC NEUROFIBROMATOSIS TYPE 1
homeira saebnoori
ASOMA AWUDU

homeira saebnoori

and 1 more

March 31, 2023
Neurofibromatosis type 1 may present as a gingival neurofibroma in a patient with no family history. Accurate diagnosis will lead to successful management of oral lesions. The present case is a report of sporadic gingival neurofibroma in an 18 year old male.
Electrocardiographic characteristics of ventricular arrhythmias originating from diff...
lin jia-feng
Yifan Lin

lin jia-feng

and 7 more

March 31, 2023
Background: This study aimed to explore the electrocardiographic (ECG) characteristics of ventricular arrhythmia (VA) arising from epicardial and endocardial areas adjacent to mitral annual (MA). Methods: This study involved 283 patients with MA-VA who received radiofrequency catheter ablation at the center. The ECG characteristics of these patients were analyzed retrospectively. Results: The origin of MA-VA was judged based on the ECG variables. Among all MA-VAs, IDT > 77 ms or MDI > 0.505 predicted the VAs arising from epicardium (sensitivity of 70.20% and 73.51%, specificity of 94.70% and 82.58%, positive predictive value (PPV) of 93.81% and 82.84%, and negative predictive value (NPV) of 73.53% and 73.15%). Among all epicardial MA-VAs, the RV1/RV2 ratio > 0.87 predicted the VAs originating from the epicardial anteroseptal wall adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 62.86%, 98.06%, 91.67%, and 88.60%, respectively. Among all endocardial MA-VAs, Q(q)R(r) morphology in lead V1 predicted the VAs arising from the endocardial septal wall adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 92.98%, 100%, 100%, and 94.94%, respectively. Among all endocardial septal MA-VAs, a predominant positive wave in lead II and a predominant negative wave in lead III predicted the VAs arising from the endocardial mid-septal portion adjacent to MA. It had sensitivity, specificity, PPV, and NPV of 86.04%, 100%, 100%, and 70.00%, respectively. Conclusion: ECG characteristics of VAs from the different sites adjacent to MA can judge the arrhythmia’s origin and design the ablation plan accordingly.
Whole bowel irrigation should not be used routinely in the management of poisoned pat...
Euan Sandilands

Euan Sandilands

March 31, 2023
Whole bowel irrigation is a method of gastric decontamination in the poisoned patient involving administration of large volumes of osmotically balanced polyethylene glycol-electrolyte solution to empty the gastrointestinal tract of ingested toxins before absorption, limiting systemic toxicity. While this approach may seem intuitive and it can lead to expulsion of tablets or packets in the rectal effluent, there is a lack of evidence correlating this with improved patient outcomes. Administration of whole bowel irrigation is also challenging to the inexperienced physician and associated with adverse effects, which may be serious. Recommendations for the consideration of whole bowel irrigation are limited to patients who have ingested modified release preparations, those of have ingested pharmaceuticals not adsorbed by activated charcoal, and for the removal of packages in body packers. Until more robust evidence is available from high-quality prospective studies demonstrating efficacy, the use of whole bowel irrigation should not be used routinely in poisoned patients.
A novel high-efficiency multi-layer carbon/polyester cotton fabric vaporizer and its...
Jiugang Li
Jiahao He

Jiugang Li

and 6 more

March 31, 2023
Solar-driven evaporation of seawater by the photothermal materials (PM) is considered to be a promising strategy to solve the global water shortage. Fiber-based photothermal material is one of the most important PM materials. However, traditional single-layer fabrics have the demerits of heat-losses and salt-crystallize on the evaporation zone during the long-term seawater desalination, which significantly reduces the evaporation rate of the products. Herein, a novel three-layered 3D spacer carbon/polyester cotton spacer woven fabric (SWF) evaporator is designed. This novel SWF consist of a top water evaporate layer, a middle water transfer/thermal insulation/salt crystal layer and a bottom water absorption layer. The above rational three-layered 3D structure guarantees the fast water-transformation of SWF evaporator while avoid the heat loss from the top layer. The evaporation rate of 3D SWF with 6 mm interval space reaches 2.1 kg·h-1·m-2 in a solar-wind (1 kW·m−2, 2 m·s-1) coupled field, which is proved to be competent for the actual seawater desalinate application.
Entry and leaving arcs of turnpikes: their exact computation in the calculus of varia...
Pedro Fortuny Ayuso
Luis Bayon

Pedro Fortuny Ayuso

and 3 more

March 31, 2023
We settle the question of how to compute the entry and leaving arcs for turnpikes in autonomous variational problems, in the one-dimensional case using the phase space of the vector field associated to the Euler equation, and the initial/final and/or the transversality condition. The results hinge on the realization that extremals are the contours of a well-known function and that that the transversality condition is (generically) a curve. An approximation algorithm is presented and an example included for completeness.
Frequency and burden of disease for SARS-CoV-2 and other viral respiratory tract infe...
Marie Latouche
Mahdi Ouafi

Marie Latouche

and 6 more

March 31, 2023
Background: To evaluate the frequency and burden of disease of SARS-CoV-2 and other respiratory viruses in children under the age of 2 months. Methods: A retrospective, cross-sectional, single-center study was conducted between March 2021, and February 2022. All children under the age of 2 months and tested for SARS-CoV-2 were included. The frequency of SARS-CoV-2, of other respiratory viruses and the burden of disease caused by SARS-CoV-2 and other respiratory viruses were evaluated. Results: 727 children with an RT-PCR test for SARS-CoV-2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT-PCR test for SARS-CoV-2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT-PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS-CoV-2 were less likely to have required respiratory support (p=.001), enteral nutrition (p=.03), or intensive care admission (p=.01) and had a shorter hospital stay than children with other respiratory viruses (5d vs. 7d, p=.007). Conclusion: In this young population of children, SARS-CoV-2 infection was less frequent and less severe than other viral respiratory infections.
Non-fragile containment control of nonlinear multi-agent systems via a disturbance ob...
Tuo Zhou
Quanli Liu

Tuo Zhou

and 2 more

March 31, 2023
In this paper, we consider the non-fragile containment control problem of nonlinear multi-agent systems (MASs) with exogenous disturbance where the communication links among agents under consideration is directed. Firstly, based on relative output measurements between the agent and its neighbors, a disturbance observer-based control protocol is proposed to solve the containment control problem of MASs with inherent nonlinear dynamics and exogenous disturbances. Secondly, because of the additional tuning of parameters in the real control systems, uncertainties in the designing of observer and controller gains always occur, and as a result, an output feedback controller with disturbance rejection is conceived and the containment control problem of nonlinear MASs with non-fragility is thoroughly investigated. Then, depending on matrix transformation and inequality technique, sufficient conditions of the designed controller gains exist, which is derived from the asymptotic stability analysis problem of some containment error dynamics of MASs. Finally, two simulation examples are exploited to illustrate the effectiveness of the proposed techniques.
Long-term prognosis after low-dose peanut challenge for patients with history of anap...
Nobuko Akamatsu
Ken-ich  Nagakura

Nobuko Akamatsu

and 4 more

March 31, 2023
Long-term prognosis after low-dose peanut challenge for patients with history of anaphylaxisNobuko Akamatsu, MD, PhD1,2, Ken-ichi Nagakura, MD, PhD1, Sakura Sato, MD3, Noriyuki Yanagida, MD, PhD1,3,*, Motohiro Ebisawa, MD, PhD3 1Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan2Department of Pediatrics and Adolescent Medicine, Tokyo Medical University Hospital, Tokyo, Japan3Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, JapanRunning title: Prognosis after low-dose peanut challenge*Corresponding author: Noriyuki Yanagida, MD, PhDDepartment of Pediatrics, National Hospital Organization, Sagamihara National Hospital,18-1, Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, JapanE-mail: yana@foodallergy.jpWord count: 1190Number of figures: 2 Number of tables: 0Conflict of interest: Motohiro Ebisawa and Sakura Sato have received speaker honoraria from Viatris. All other authors declare that they have no conflicts of interest.Financial support: This paper has not received any financial support.Keywords : low-dose oral food challenge, peanut, food allergy, low-dose-tolerant, tolerant, pediatric, anaphylaxisTo the Editor,Peanuts cause severe allergic reactions, and only 20% of peanut-allergic patients acquire tolerance.1 Peanut oral food challenge (OFC) has a high risk of severe symptoms such as anaphylaxis, and OFC is avoided in children with an immediate history, especially with a history of anaphylaxis.1Peanut-allergic patients and their guardians have a lower quality of life because of worry that anaphylaxis may occur at any time.2 Low-dose OFC may be useful to manage children with a history of anaphylaxis,3 but it has not been used to evaluate prognosis. This study investigated long-term prognosis after low-dose peanut OFC for patients with a history of immediate reactions, including anaphylaxis.We retrospectively analyzed participants with a history of immediate symptoms due to peanut ingestion, who received baseline low-dose OFC with 133 mg of peanut protein from August 2013–August 2017 at Sagamihara National Hospital (Figure 1), and evaluated two-year tolerance acquisition.We defined tolerance as passing an OFC with 795 mg protein (medium-dose OFC) and ingesting more than 795 mg protein without symptoms at home; consuming this dose enables cessation of strict avoidance in daily life. We defined baseline low-dose OFC negative patients as the low-dose-tolerant group and positive patients as the low-dose-reactive group. The low-dose-tolerant group was instructed to consume 133 mg at home twice a week. Then, based on guardians’ preference, patients received a medium-dose OFC every 6 months or gradually increased peanut ingestion to 795 mg at home under a physician’s direction. The low-dose-reactive group completely avoided peanuts and received low-dose OFC every 6 months. When the low-dose-reactive group passed low-dose OFC, they received medium-dose OFC (Supplementary Figure 1).Anaphylaxis was defined according to the World Allergy Organization Guidelines.4 OFC protocol is described in the supplementary information.5 The percentage of patients who acquired tolerance within two years was estimated using Kaplan-Meier curves. The co-factors for tolerance acquisition were analyzed using Cox regression analysis. Multivariate analysis was performed on the results of low-dose OFC, total IgE, peanut-specific IgE (Pn-sIgE), and history of peanut-related anaphylaxis. SPSS (version 27.0; SPSS Inc., Chicago, IL) was used for all analyses; p <0.05 was considered statistically significant. The Ethics Committee of The Sagamihara National Hospital (2016-015) approved the study according to the Helsinki Declaration. Written informed consent was obtained from all patients’ guardians.Fifty-three patients (median age, 7.1 years) were enrolled; 43% had a history of anaphylaxis. The median Pn-sIgE level was 20.7 (interquartile range 7.0–57.5) kUA/L. The median Ara h 2-specific IgE level was 10.4 (4.98–28.3) kUA/L. The median thresholds of past immediate symptoms were 26.6 mg (13.3–133) (Supplementary Table 1).Twenty-one patients (40%) passed the low-dose OFC and were defined as the low-dose-tolerant group, and 32 (60%) failed and were defined as the low-dose-reactive group (Supplementary Table 1); 35% of patients with a history of anaphylaxis passed the low-dose OFC. During low-dose OFC, oral mucosal symptoms were most common (72%), then gastrointestinal (63%) and respiratory symptoms (63%). Three patients required intramuscular adrenaline (Supplementary Table 2). When the low-dose-tolerant patients ingested low-dose peanuts at home, six (29%) had mild reactions like oral and throat discomfort; most reactions resolved naturally and did not require medical attention.In the low-dose-tolerant group, 13 patients (62%) acquired tolerance within 2 years, including five patients with a history of anaphylaxis, whereas in the low-dose-reactive group, one patient (3%), with no history of anaphylaxis, acquired tolerance (p <0.001) (Figure 2). In the low-dose-reactive group, 6% of patients passed low-dose OFC within two years.The predictive factors of failure to acquire tolerance have been positive reactions to low-dose OFC (crude hazard ratios of total IgE, Pn-sIgE: 0.37 [95% confidence interval 0.15–0.94, p =0.04), and log (Pn-sIgE) 2.23 [1.01–4.92], p =0.048) (Supplementary Table 3). In 23 patients with a history of anaphylaxis, five (22%) acquired tolerance. In 30 patients with no history of anaphylaxis, nine (30%) acquired tolerance. History of anaphylaxis did not significantly affect tolerance acquisition (Supplementary Figure 2).This is the first report showing that low-dose OFC can be undergone relatively safely with tolerance acquisition in some peanut-allergic patients, including patients with a history of anaphylaxis. Patients with a history of anaphylaxis have a lower quality of life because of worry that anaphylaxis may occur at any time.6 Therefore, these results are significant because if patients realize that low-dose peanuts can be ingested, complete avoidance becomes unnecessary, and tolerance acquisition could be assessed. The low-dose-reactive group was less likely to develop tolerance and required careful follow-up to prevent accidental ingestion.Previous studies of long-term prognosis after peanut OFC excluded patients with a history of anaphylaxis,1 therefore, their tolerance acquisition based on the results of OFC was unknown. In our current study, more than half of patients in low-dose-tolerant groups acquired tolerance within two years, even those with a history of anaphylaxis. Furthermore, one-fifth of patients with a history of anaphylaxis tolerated peanuts, and there was no significant difference between patients with and without a history of anaphylaxis in acquiring tolerance. Therefore, passing low-dose OFC could be considered to assess tolerance acquisition, regardless of the history of anaphylaxis.It has been reported that peanut OFC is high risk because it often causes anaphylaxis and other serious symptoms.1 In the previous studies of peanut OFC, subjects have no history of anaphylaxis or as few as 10%, while this study had 40%, but the occurrence of anaphylaxis in OFC was comparable.1,7 Furthermore, there is a report of a group of subjects, 83% of whom had a history of anaphylaxis, and all patients reacted with anaphylaxis in OFC.8 It has been reported that the incidence of anaphylaxis with OFC was higher with progression up to the total OFC ingested.7 Therefore this study suggests that low-dose OFC is relatively safe in patients with a history of anaphylaxis.Recently, some trials of low-dose oral immunotherapy showed that ingesting low-dose peanuts (133-300 mg) could induce immunological changes and allow the intake of larger amounts.9Similarly, daily ingestion of low-dose wheat is effective in increasing consumption dose and preventing accidental symptoms, even in patients with a history of anaphylaxis.10 Therefore, twice weekly ingestion of 133 mg in the low-dose-tolerant group may yield oral tolerance. In addition, few serious reactions were observed in the low-dose-tolerant group during the subsequent at-home dose escalation in this study.This study has several limitations. First, 33 subjects were excluded because their two-year course could not be tracked. Although the excluded and included patients’ backgrounds were similar (Supplementary Table 4), predictors of tolerance acquisition, such as anaphylaxis may be different with more subjects. Second, there was a lack of information on several points. Although at-home intake methods were unified, the frequency of home peanut intake and adherence was unknown. Additionally, we couldn’t confirm thresholds of past immediate symptoms in 25% of subjects. However, the median thresholds were 26.6 mg in 75% of subjects who were able to assess the threshold. Therefore, we assume that thresholds in the remaining children were similar.For peanut-allergic patients with a history of anaphylaxis, low-dose OFC is relatively safe and effective in the assessment of tolerance acquisition. Low-dose OFC results may effectively stratify peanut-allergic patients with anaphylaxis history with good and poor tolerance acquisition to select optimal management plans.Nobuko Akamatsu, MD, PhD1,2, Ken-ichi Nagakura, MD, PhD1, Sakura Sato, MD3, Noriyuki Yanagida, MD, PhD1,3, Motohiro Ebisawa, MD, PhD3,1Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan2Department of Pediatrics and Adolescent Medicine, Tokyo Medical University Hospital, Tokyo, Japan3Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa, Japan
Dupilumab therapy in children aged 6 months to 12 years with uncontrolled moderate-to...
Jie Li
Bingjing Zhou

Jie Li

and 5 more

March 31, 2023
Article type: Research LetterTitle: Dupilumab therapy in children aged 6 months to 12 years with uncontrolled moderate-to-severe atopic dermatitis: a Chinese real-world study
Examine the advantages of an integrated scalability approach at various cloud stack l...
Ahmed Alobaidi
SeyedEbrahim Dashti

Ahmed Alobaidi

and 1 more

March 31, 2023
The development of cloud computing has significantly altered how services are built, deployed, and made accessible to users outside of the organization. In actuality, the pay-as-you-go model of dispersed IT supported by the cloud computing paradigm calls for the outsourcing of software services and applications. In this situation, the capacity to ensure effective cloud performance management and to facilitate automated scalability become fundamental prerequisites. Users of the cloud are becoming more and more interested in a transparent and coherent image of the cloud, where performance is guaranteed in a variety of situations and under a variety of loads. In this essay, We examine the advantages of an integrated scalability approach at various cloud stack layers, concentrating on the database and compute infrastructure layers. In order to achieve this, we offer various performance measurements and a set of rules based on them to assess the cloud stack’s condition and scale it as needed to maintain stable performance. Then, using a proof-of-concept architecture, we empirically investigate three scaling scenarios for cloud performance: database only, computing infrastructure solely, and the scenario where computing infrastructure and database compete for resources.
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