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CONFORMAL BOUNDS FOR THE FIRST EIGENVALUE OF THE (p,q) -LAPLACIAN SYSTEM
MOHAMMAD JAVAD HABIBI VOSTA KOLAEI
shahroud azami

MOHAMMAD JAVAD HABIBI VOSTA KOLAEI

and 1 more

August 29, 2023
Consider ( M , g ) as an m-dimensional compact connected Riemannian manifold without boundary. In this paper, we investigate the first eigenvalue λ 1 , p , q of the ( p , q ) -Laplacian system on M. Also, in the case of p,q>n we will show that for arbitrary large λ 1 , p , q there exists a Riemannian metric of volume one conformal to the standard metric of S m .
Spontaneous Chronic Subdural hematoma as an initial manifestation of Acute Leukemia i...
Sengua Koipapi
Jay Lodhia

Sengua Koipapi

and 3 more

August 29, 2023
A document by Sengua Koipapi. Click on the document to view its contents.
Longitudinal Study of COVID-19 Vaccination Outcomes in a Low-Income Hispanic Populati...
Christopher Lamb
Christopher Owens

Christopher Lamb

and 3 more

August 29, 2023
Background: The article presents the results of a longitudinal study performed to assess the humoral immune response to the Johnson & Johnson (J&J) COVID-19 vaccine (Ad26.COV2.S) in a low-income, Hispanic patient population. In our work, we evaluate the COVID-19 health status of the patient population following vaccination. This work is a follow-up of a pilot study that analyses additional data to better understand the impact of the vaccine. Methods: Longitudinal cohort study testing the antibody responses of patients each visit within 120 days (initial, 1st follow-up, and 2nd follow-up). This study used the Clungene® SARS-CoV-2 IgG/IgM Rapid Test Cassette to determine the presence of binding antibodies resulting from the J&J COVID-19 vaccine. Results: Fifty-seven (57) patients were eligible for participation in this study after initial baseline antibodies were measured; seventy-four (74) patients were requested to participate, 17 were excluded because moderate to strong immunoglobulin G (IgG)/immunoglobulin M (IgM) responses. High loss to follow-up were multifactorial, but a predominant reason was travel out of state for work or return to country of origin.
PDGFRβ-antagonistic affibody mediated tumor-targeted TNFα for enhanced radiotherapy i...
Xiaohui Tang
Jie Chen

Xiaohui Tang

and 13 more

August 29, 2023
The morbidity and mortality of lung cancer are still the highest among all malignant tumors. Radiotherapy plays an important role in clinical treatment of lung cancer. But the effect of radiotherapy is not ideal due to the radiation resistance of tumor tissues. Abnormalities in tumor vascular structure and function affect blood perfusion and oxygen transport is impeded, making tumor microenvironment hypoxic. Tumor hypoxia is the major cause of radiotherapy resistance. By promoting tumor vessels normalization and enhancing vascular transport function, tumor hypoxia can be relieved to reduce radiotherapy resistance and increase tumor radiotherapy sensitivity. In our previous study, a pericytes-targeted tumor necrosis factor alpha (named Z-TNFα) was firstly constructed and produced by genetically fusing the platelet-derived growth factor receptor β (PDGFRβ)-antagonistic affibody (ZPDGFRβ) to the TNFα, and the Z-TNFα induced normalization of tumor vessels and improved the delivery of doxorubicin, enhancing tumor chemotherapy. In this study, the tumor vessel normalization effect of Z-TNFα in lung cancer was further clarified. Moreover, the tumor hypoxia improvement and radiosensitizing effect of Z-TNFα were emphatically explored in vivo. Inspiring, Z-TNFα specifically accumulated in Lewis lung carcinoma tumor graft, and relieved tumor hypoxia as well as inhibited HIF-1α expression. As expected, Z-TNFα significantly increased the effect of radiotherapy in mice bearing Lewis lung carcinoma tumor graft. In conclusion, these results demonstrated that Z-TNFα is also a promising radiosensitizer for lung cancer radiotherapy.
Short read lengths recover ecological patterns in 16S rRNA gene amplicon data
Stephanie Jurburg

Stephanie Jurburg

August 29, 2023
Metabarcoding is an increasingly popular and accessible method for assessing bacterial communities across a wide range of environments, and as the sequence data archives grow, sequence data reuse will likely become an important source of novel insights into the ecology of microbes. While literature on the benefits of longer read lengths for the study of microbial communities, little is known about the (re)usability of shorter (<200 bp) read lengths, but this information is essential to improve the reuse and comparability of metabarcoding data across studies. This study reanalyzed three 16S rRNA datasets targeting aquatic, animal-associated, and soil microbiomes, and evaluated how processing the sequence data across a range of read lengths affected the resulting taxonomic assignments, biodiversity metrics, and differential (i.e., before-after treatment) analyses. Short read lengths successfully recovered ecological patterns, and limited increases in resolution were observed beyond 100 bp reads across environments. Furthermore, abundance-weighted diversity metrics (e.g., Inverse Simpson index or Bray-Curtis dissimilarities) were more robust to variation in read lengths. Importantly, the total number of ASVs detected increased with read length, highlighting the need to consider metabarcoding-derived diversity estimates within the context of the bioinformatics parameters selected. This study provides evidence-based guidelines for the processing of short reads.
A deep learning and physics-based method for multiaxial fatigue life prediction
Changjiang Zhou
Haoye Wang

Changjiang Zhou

and 3 more

August 29, 2023
The prediction of fatigue life for mechanical structures under multiaxial loadings is considered an important task in engineering design, but the conventional models are mostly limited to special loading conditions and materials. In this work, a deep learning and physics-based method is proposed for predicting the multiaxial fatigue life. The relationships between the damage parameters and fatigue life are quantified by establishing a deep belief network (DBN) model. The hyperparameters of the DBN model are adaptively adjusted using a particle swarm optimization (PSO) algorithm. Importantly, the input features of the PSO-DBN model are determined based on the physical model. The proposed method is validated through fatigue tests conducted under various loading paths. The results demonstrate the high effectiveness and applicability of the proposed method for accurately predicting multiaxial fatigue life.
Disabling tinnitus and third nerve palsy following pontine haemorrhage: Application o...
VIJAYA PRAKASH KRISHNAN MUTHAIAH
Ignacio Cornejo

VIJAYA PRAKASH KRISHNAN MUTHAIAH

and 4 more

August 29, 2023
Introduction Spontaneous intracerebral hemorrhage (ICH) accounts for 10-20% of strokes worldwide, with hypertensive vasculopathy being the most common underlying cause [1]. Brainstem hemorrhages represent one-third of ICH and often arise in the pons [2]. Vital sensorimotor pathways and cranial nerve nuclei traverse this region. Thus, characteristic signs of pontine ICH include hemiparesis, cranial nerve palsies, and impaired consciousness [3].Oculomotor nerve involvement causes ipsilateral ptosis and pupillary dilation with preservation of extraocular movements due to sparing of the superior branch [4]. Abducens palsy and internuclear ophthalmoplegia reflect medial longitudinal fasciculus damage [2]. Beyond focal deficits, brainstem hemorrhages frequently precipitate headaches and tinnitus due to vascular irritation of pain and auditory pathways [5]. Persistent, troublesome tinnitus impairs concentration and quality of life [6].The International Classification of Functioning, Disability, and Health (ICF) codifies the multifactorial impacts of health conditions like stroke [7]. The ICF enhances rehabilitation by elucidating specific limitations in body structures/functions, activities, participation, and environmental interactions. ICF-based assessment informs goal setting and interventions to optimize functioning and societal participation.This report presents an ICF profile of a patient with tinnitus and oculomotor palsy following pontine hemorrhage. MRI confirmed the hemorrhagic lesion. ICF components were examined to capture the breadth of disability. Tinnitus management and multidisciplinary therapies were tailored accordingly to promote recovery.
Flood hazard risk prediction and assessment of Guangdong Hong Kong Macao Greater Bay...
Haocheng Zhang
Chunyi Wu

Haocheng Zhang

and 5 more

August 29, 2023
Against the backdrop of global climate change and rapid urbanization, climate disaster events are frequent. In highly urbanized areas, floods pose the greatest threat and destruction. Therefore, evaluating and predicting the risk distribution of flood disasters through appropriate methods can minimize the loss and damage of disasters, which is of great significance. In this study, based on the Random Forest (RF) algorithm, a model is constructed to evaluate and predict a flood disaster process in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China. We use remote sensing (RS) images and GIS tools to extract the area submerged by the flood when the disaster occur, select 15 risk indicators, create 221975 samples to train and test the model and obtain the importance of each indicator to the prediction results. In addition, we select two machine learning algorithm models for accuracy comparison with the RF model. The results show that: (1) High flood areas are mainly distributed in urban agglomerations in the central and southern parts of GBA, including Guangzhou, Foshan, Dongguan, Shenzhen, Macau etc. (2) Flood risk prediction and evaluation methods using RS and GIS, combined with RF models, are easy to analyze the spatial pattern and influencing factors of flood risk, and have good applicability. Compared with other models, it has higher prediction accuracy and reliability. The overfitting phenomenon is also not obvious. (3) The maximum 1/3/6/9 and DEM elevation indicators are the most important five of the 15 risk indicators, and the Relative Position Index (RPI) is the least important, while other indicators are of general importance. This study provides a new method for evaluating and predicting flood disaster risks, and the evaluation results provide a reference for flood risk management, prevention, reduction of life and property losses in the study area.
A GaN based Power Amplifier Module for 5G Basestations
BURAK TÜRK
HÜSEYİN SAVCI

BURAK TÜRK

and 1 more

August 29, 2023
This study presents a compact and low-cost Power Amplifier Module (PAM) for the RF power generation of 5G sub-6GHz massive Multiple Input and Multiple Output small-cell base stations. The module is a hybrid design realized on a 6mm x 10mm Rogers RO4350B RF laminate with bare-die Gallium Nitride (GaN) High Electron Mobility (HEMT) transistors for amplification and lumped components for filtering, matching, biasing circuits, and stabilization networks. The operating frequency is centered at 3.5GHz, a commonly deployed 5G New Radio (NR) band. The module has two amplification stages, which operate in Class-AB mode with differing conduction angles to equalize AM-AM and AM-PM responses for higher compression point, linearity and power-added efficiency (PAE). The design has a 24dB gain with 38 % PAE at 5W output power. The input and output return losses are 8 dB and 6 dB, respectively. The large and small signal measurement results agree with simulation results, with some performance shifts over the frequency explained in the letter. The back-fitting procedures are developed, and the measurement data is verified with an optimized circuit.
Systemic IL-26 correlates with improved asthma control in children sensitized to dog...
Melissa A. Kovach
Ulrika Käck

Melissa A. Kovach

and 5 more

August 29, 2023
Background: Interleukin (IL)-26 is produced by T helper type 17 (Type 17) cells and exerts immunomodulatory plus antimicrobial effects. Previous studies show that local IL-26 concentrations in the airways are higher in patients with uncontrolled than in those with controlled asthma, and that this intriguing cytokine bears biomarker potential. Here, we determined how systemic IL-26 relates to allergen sensitization, asthma severity, and to IL-17A in children. Methods: Serum samples were obtained from children with (n=60) and without (n=17) sensitization to dog allergen, and IL-26 and IL-17A protein concentrations were measured using ELISA. Self-reported history, including medication use and validated symptom-based questionnaire scores, was recorded. Results: The serum concentrations of IL-26 were enhanced in allergen-sensitized subjects and correlated with those of IL-17A in a positive manner. However, the IL-26 concentrations did not markedly differ between allergen-sensitized subjects with and without asthma, eczema, allergic rhinitis, or a history of food allergy. Notably, IL-26 concentrations correlated with increasing Asthma Control Test (ACT) scores in a positive manner and with inhaled corticosteroid in a negative manner, amongst sensitized subjects with asthma. Moreover, subjects with asthma requiring ≥1 course of oral corticosteroids in the preceding 12 months had decreased IL-26 concentrations. Conclusion: This study forwards evidence that systemic IL-26, just like IL-17A, is involved in allergen sensitization among children. The association of systemic IL-26 with improved asthma control is compatible with the cellular sources being recruited into the airways in severe asthma, which supports that this kinocidin bears potential as a biomarker and therapeutic target.
The Effect of Papyrus Wetlands on Flow Regulation in a Tropical River Catchment
Alem Oyarmoi
stephen.birkinshaw

Alem Oyarmoi

and 3 more

July 28, 2023
Papyrus wetlands, native to central and eastern Africa and attaining heights up to 5 to 6 m, occur as rooted or floating marshes in riverine and lacustrine landscapes. This study assessed and quantified the impacts of these papyrus wetlands on historical baseflow and quickflow, and future flood and low flows in the Mpologoma catchment in Uganda. By estimating the Wetland Specific Impact (metric of increase or decrease in flow to wetland area) for a 30-year historical period and indices of flow duration, magnitude, and frequency for the future period, it was possible to demonstrate the role that papyrus-dominated floodplain wetlands play in regulating river flow at the catchment scale. Assessment over the historic period shows that wetlands strongly attenuate quickflow while moderately enhancing baseflow. They play a moderating role in most months, except for the first dry season (June and July), due to the reversal of flows between wetlands and rivers that often occurs during this period. Annual estimates show that wetlands are four times better at regulating quickflow than baseflow. Examination of changes at 2 and 4°C global warming levels (GWLs) indicate that wetlands will play critical roles in mitigating flood risks, with a lesser role in supporting low flows. Wetlands are predicted to lower future mean flood magnitude by 5.2 and 7.8% at GWL2 and GWL4, respectively, as well as halving the average number of flood events in a year, irrespective of the warming level. However, the mean flood duration is expected to increase by 77.8% (56 days) and 80.3% (49 days), respectively. This study highlights the need for the conservation and protection of papyrus-dominated wetlands.
Macroinvertebrates Community Annual Dynamics in Taitema Lake after ecological water t...
Hongguang Zou
Shuping Wang

Hongguang Zou

and 4 more

August 29, 2023
In lakes, analyses of community structure and relationships of macroinvertebrates with environmental factors are often used to judge the status of watershed ecosystems and for scientific ecological management. However, this method has been less applied to lakes in arid regions. Here, a seasonal ecological survey was conducted in Lake Taitema (including the Tarim River, the Chelchen River, Lake Taitema, and Lake Kanlak) during 2021-2022 to explore the spatial and temporal patterns of macroinvertebrates communities in the basin and their relationships with environmental factors. The aim is to provide a scientific basis for the subsequent ecological health management of Lake Taitema and relevant content for the study of macroinvertebrates communities in arid lakes. This survey, 552 macroinvertebrates were collected and identified, belonging to 17 species of 13 families in 2 phyla, 3 orders, and 6 classes. The community composition, diversity, and dominant species changed seasonally, but no apparent spatial distribution differences between rivers and lakes existed. The correlation between environmental factors and the macroinvertebrates community showed different effects each season. DCA analysis revealed that the main environmental impact factors in winter were chloride ions (Cl-); in spring, were Cr and salinity (SAL); in summer, was pH. The main dominant species were more dominant to the overall community in Lake Taitema.
An elastic framework construction method based on task migration in edge computing
Yonglin Pu
Ziyang Li

Yonglin Pu

and 4 more

August 28, 2023
Edge computing (EC) is an efficient technology that enables end users to achieve the goal of high bandwidth and low latency by offloading computationally intensive tasks from mobile devices to edge servers. However, a major challenge arises when the processing load fluctuates continuously, leading to a performance bottleneck due to the inability to rescale edge node (EN) resources. To address this problem, the approach of task migration is introduced, and the resource constrained model, optimal communication overhead model, and optimal task migration model are built to form a theoretical foundation from which to propose a task migration based resilient framework construction method in EC. With the aid of the domino effect and the combined effect of task migration, a dynamic node-growing algorithm (DNGA) and a dynamic node-shrinking algorithm (DNSA), both based on the task migration strategy, are proposed. Specifically, the DNGA smoothly expands the EN scale when the processing load increases, while the DNSA shrinks the EN scale when the processing load decreases. The experimental results show that for standard benchmarks deployed on an elastic framework, the proposed method realizes a smooth scaling mechanism in the EC, which reduces the latency and improves the reliability of data processing.
One-step Preparation of Binder-free Nickel Containing Graphene Foam Electrode for Sup...
Sirin SIYAHJANI GULTEKIN
Aziz Ahmad KARIMI

Sirin SIYAHJANI GULTEKIN

and 3 more

August 28, 2023
A nickel hydroxide (Ni(OH) 2)-modified reduced graphene oxide (rGO) foam electrode for supercapacitor application is presented in this study. The electrode was made without binder through a one step process. In order to compare the supercapacitor performance of as synthesized graphene foam electrode, rGO and rGO:carbon black (CB) standard electrodes with PVDF-HFP binder were also synthesized . All electrodes were then characterized structurally (XPS, EDS, RAMAN, XRD, and FT-IR) and morphologically (SEM). Ni-containing electrodes were found in the α-Ni(OH)2:rGO structure. NirGO3 has 800 Fg -1 capacitance, while rGO:CB has 900. Thus NirGO3 has the best capacitive performance among binder-free electrodes, comparable to rGO:CB.
Procedure-Specific Simulation for Vaginal Surgery Training: A Randomised Controlled T...
Roxana Geoffrion
Nicole Koenig

Roxana Geoffrion

and 9 more

August 28, 2023
OBJECTIVE: To investigate whether procedure-specific skills acquired in a surgical lab, versus usual training, result in improved operative competence. DESIGN: randomised controlled trial. Didactic and procedural training occurred using three low fidelity vaginal surgery models: anterior repair (AR), posterior repair (PR), vaginal hysterectomy (VH). POPULATION/SETTING: Junior gynaecology residents at three academic centres. METHODS: The primary outcome was performance evaluated by attending staff blinded to group, via global rating scale (GRS) in the real operating room and for corresponding procedures. Prespecified secondary outcomes included procedural steps knowledge, overall performance impression, resident satisfaction, self-confidence and intraoperative parameters. A priori sample size estimated 50 residents (20% absolute difference in GRS score, 25% SD, 80% power, alpha 0.05). RESULTS: 83 residents were randomised to intervention or control and 55 completed the trial (2012-22). All characteristics were similar between groups. Adjusted GRS scores (by age, level and baseline knowledge) showed a significant group difference overall (mean difference 8.2; 95% CI 0.2,16.1; p=0.044) and for VH (mean difference 12.0; 95% CI 1.8, 22.3; p=0.02), but not for AR or PR. The intervention group also had significantly higher procedural steps knowledge, satisfaction and self-confidence for VH and PR (p<0.05 for all). Estimated blood loss, operative time and complications were similar between groups. CONCLUSIONS: Compared to usual training, surgical education modules using procedure-specific low fidelity models for vaginal surgery resulted in significant improvements in actual operative performance and several other skill parameters. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, [www.clinicaltrials.gov](http://www.clinicaltrials.gov), NCT05887570
Redlisting  genetics: towards linking genetic data and conservation management      ...
Chloee McLaughlin

Chloee M. McLaughlin

and 4 more

April 23, 2024
Genetic diversity is critical for adaptation in response to changing environments and provides a valuable metric for predicting species’ extinction risk. The International Union for Conservation of Nature (IUCN) and broader scientific community have acknowledged that genetic diversity is a critical component to biodiversity conservation. However, there remain gaps in the incorporation or application of genetic data to extinction risk assessments and conservation management programs. While contemporary international policy lacks explicit guidelines for the application of genetics to conservation, new working groups are collating expertise to provide resources for research, interpretation, and policy. Here, we contribute to the discussion of how conservation efforts can be enhanced with the use of genetic and genomic data. Specifically, we describe how different genetic and genomic diversity metrics can inform species extinction risk and complement the existing IUCN Red List of Threatened Species reporting criteria. We conclude by advocating for standardized reporting and data sharing to facilitate the use of genomic data by different parties, and recommend changes to the infrastructure of IUCN and the National Center for Biotechnology Information (NCBI) GenBank® so that life history and sequence data are viewed together. We expect our recommendations will complement ongoing work by the IUCN Species Survival Commission’s Conservation Genetics Specialist Group to protect genetic diversity and biodiversity globally.
Unlocking the Potential of Weight of Evidence and Entity Embedding Encoding for Categ...
Anitha 1∗ M ME
Nickolas PhD 1∗ S

Anitha 1∗ M ME

and 3 more

August 28, 2023
A document by Anitha 1∗ M ME. Click on the document to view its contents.
A Rare Case of Massive Intrapartum Hemorrhage Following by Inner Myometrial Laceratio...
Bahareh Khakifirooz
Arian Shojaei

Bahareh Khakifirooz

and 2 more

August 28, 2023
A document by Bahareh Khakifirooz. Click on the document to view its contents.
Large Tumoral Pseudoangiomatous Stromal Hyperplasia with ER/PR stromal negativity in...
Somar Mansour
Seif-Aldin Abdul Rahman

Somar Mansour

and 6 more

August 28, 2023
A document by Somar Mansour. Click on the document to view its contents.
Update on Pharmacological Activities, Security, and Pharmacokinetics of Aloe-emodin
Haimeng Luo
Xiaoyun Ji

Haimeng Luo

and 6 more

August 28, 2023
Aloe-emodin (AE), a naturally occurring anthraquinone derivative, represents one of the principal active components found in various Chinese herbs such as Cassia occidentalis, Rheum palmatum L., Aloe vera, and Polygonum multiflorum Thunb. AE has been shown to possess a diverse range of pharmacological effects including anticancer, antivirus, anti-inflammatory, antibacterial, neuroprotective, and hepatoprotective properties. These remarkable therapeutic attributes provide a solid foundation for treating an array of diseases ranging from influenza virus, inflammation, sepsis, Alzheimer’s disease, glaucoma, malaria, liver fibrosis, psoriasis, Type 2 diabetes, growth disorders, and several types of cancers. However, despite its promising potential, clinical application of AE is somewhat limited by poor intestinal absorption, short elimination half-life, and low bioavailability. Furthermore, AE may exhibit potential liver and kidney toxicity. Therefore, this paper aims to review the pharmacological effects of AE along with its mechanism, pharmacokinetics, and safety studies, in order to offer valuable insights into the development and application of AE.
Cardioprotective effect of Cinnamamide derivative compound 10 against myocardial isch...
Wenhua Xue
Jingjing Liu

Wenhua Xue

and 5 more

August 28, 2023
Background and Purpose: Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated. Experimental Approach: The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to H2O2. Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members. Key Results: Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased P-mTOR and increased LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10’s regulation on mTOR, leading to interrupted cardiac autophagic flux. Conclusions and Implications: Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury. Keywords: Myocardial ischemia-reperfusion; Cinnamamide derivatives; Autophagic flux; Sirt1; mTOR;
Lysine is a Potential Antidote for Paraquat Poisoning Induced Pulmonary Fibrosis
Wenyu Yang
Xiaoxiao Meng

Wenyu Yang

and 11 more

August 28, 2023
Background and Purpose Pulmonary fibrosis (PF) is an irreversible lung disease with little efficient treatments. Epithelial-mesenchymal transition (EMT) in alveolar type II (AT II) cells is an initial process for PF in response to multiple insults. We previously identified paraquat (PQ), inducing acute lung injury and PF, as an agonist for STIM1, promoting STIM1-TRPC1 association for intracellular calcium burden and thus EMT. Here, we investigated the strategy targeting STIM1-TRPC1 association and excessive calcium influx in treating PF. Experimental approach Co-immunoprecipitation was for STIM1-TRPC1 association analysis. Western blotting and Real-time quantitative reverse transcription PCR (QPCR) were for EMT analysis. Calcium imaging, flow cytometry, and luciferase report assay were for analyzing calcium signaling. ELISA, histomorphology, and PQ-poisoned mice or cynomolgus model were for evaluating the efficacy of lysine in treating PF. Retrospective analysis was for analyzing the correlation between the severity of PQ poisoning and blood calcium levels. Key Results Lysine treatment significantly reduces PQ-raised STIM1-TRPC1 association, excessive calcium influx, and thus EMT in AT II cells. As a result, lysine treatment strikingly decreases the mortality of PQ-poisoned mice, with a fully recovery of PQ-induced PF. Immune cells activation, largely occurred accompanied with epithelial damages and PF, are almost normalized with lysine treatment in PQ-poisoned cynomolgus model. A negative correlation between the blood calcium levels and the prognosis were observed in PQ-poisoned patients. Conclusions and Implications These results demonstrate lysine as a potential antidote for PQ-induced PF and provide evidence for maintaining calcium homeostasis as a potential strategy for treating PF.
Academic challenges on ATMPs’ development: a regulatory perspective
Eulàlia Olesti
Yoana Nuevo

Eulàlia Olesti

and 6 more

August 28, 2023
Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Academic centres have often been at the forefront of basic research, preclinical phases, and translational studies for the clinical development of ATMPs for several approved drugs. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most challenging aspect for academic development, considering the limited experience and resources compared with pharmaceutical companies. The aim of this review is to present and discuss the key aspects to be considered when developing novel ATMPs from an academic perspective, based on our own experience. Emphasis is placed on understanding the regulatory requirements during the early phases of the drug development process, particularly for the preparation of a Clinical Trial Application. In general, academic centres do not possess experience in product-related documentation (such as the Investigational Medicinal Product Dossier), and therefore, early interaction with regulators is crucial to understand their requirements and receive guidance to comply with them. Tips are provided on how to manage quality, non-clinical, clinical, and risk and benefit documentation, based on our own experience and challenges. We believe this review will contribute to providing key regulatory knowledge to academic and clinical environments with the purpose of smoothing the regulatory path of ATMPs.
COVID-19 Induced Immune Thrombocytopenia (ITP) Management Approach: A Case Report And...
Hatem Alahwal
Mansour Alsharif

Hatem Alahwal

and 8 more

August 28, 2023
A document by Hatem Alahwal. Click on the document to view its contents.
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