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Two-photon microscopy for the exploration of lung in a murine model of infection with...
Frederic Riviere
Julien Burger

Frederic Riviere

and 5 more

March 31, 2022
Rationale. Influenza is potentially fatal infectious disease that is difficult to both treat and prevent due to the natural range, and unpredictable nature of host immune responses. Studies evaluate immune reaction on quantitative and functional data, but anatomical in only a few cases with histological analysis. Objectives. Could two-photon excitation microscopy (TPEM) improve anatomical description at cell level of pulmonary Influenzavirus infection? Methods. Pulmonary sections from transgenic C57BL/6 mice that had CD11c+ cells expressing yellow fluorescent protein were examined following experimental infection with a red fluorescent protein-expressing Influenza A virus. Measurements. Two-photon lung micrographs were taken on days 1, 2, 3 and 4 post-infections. Flow cytometry analysis and whole-lung cytokine assays were also performed at the same post-infections time points. Results. TPEM showed how the infection resulted in bronchial and bronchiolar epithelial destruction. Initially located in the bronchial and bronchiolar epithelium, virus diffused homogeneously into the alveolar compartment. In response, the host secreted proinflammatory cytokines and rapidly recruited macrophages into the lungs from the perivascular compartment. On day 4 post infection, macrophages were homogeneously distributed throughout the entire pulmonary parenchyma, starting to scavenge cellular debris. Three-dimensional reconstructions of TPEM images provided quantifiable map that traced infection through the lungs. Conclusions. This study demonstrated the added value of using TPEM to map pulmonary viral infections, epithelial lesions, macrophages recruitment and cellular interactions with more precision than histological analysis. Finally, TPEM coupled to cytometry could provide a more precise picture of the cell interactions after a lung infection by influenza virus.
Feasibility and Safety of Extended Posterior Wall Isolation Technique of Laser Balloo...
Takashi Ohkura
Keitaro Senoo

Takashi Ohkura

and 9 more

March 31, 2022
Background Laser balloon ablation (LBA) is a balloon-based catheter ablation technology used for atrial fibrillation (AF) ablation in recent years. The laser balloon has the potential to extend the isolation area because of its changeable balloon size. The purpose of the study was to investigate the feasibility and safety of extended LBA technique, and to compare the isolation area with an established balloon technique using the cryoballoon ablation (CBA). Methods From June 2020 to July 2021, 76 consecutive patients with paroxysmal AF who underwent initial pulmonary vein isolation were enrolled. Of these, 65 patients were included in the study, excluding 11 who met the exclusion criteria; 32 and 33 patients were in the LBA and CBA groups, respectively. In the LBA group, after standard ablation of each PV, additional extended posterior wall ablation was performed by increasing the balloon size to the maximum (the extended LBA technique). In the CBA group, cryoablation was performed using a 28-mm balloon. In both groups, voltage maps were created for measuring the isolated surface area (ISA) by the CARTO mapping system pre- and post-ablation. Results In the LBA group, the extended LBA technique was feasible in all patients. The total ISA after the extended LBA technique was significantly larger than before (32.4±6.5 vs 22.3±4.1 cm 2, p<0.001) and the non-isolated posterior wall area was significantly smaller (8.9 ± 3.5 vs 13.3 ± 3.7 cm2, p<0.001). Although the percentage of esophageal temperature elevation (>39.0°C) was higher during the extended LBA than during the standard LBA (LIPV: 26/32 [81%] vs. 7/32 [22%], p<0.001; LSPV: 10/32 [31%] vs. 2/32 [6%], p<0.001), symptomatic gastric hypomotility or esophageal mucosal injury was not observed in all patients. Comparing the extended LBA and the CBA group, IASA-R (18.1 ± 4.6 vs 15.9 ± 3.5, p=0.033) and non-isolated posterior wall (8.9 ± 3.5 vs 12.4 ± 3.7, p<0.001) were significantly greater in the extended LBA, but cardiac enzyme elevation after ablation was lower than the CBA group. No significant differences were found between the two groups in perioperative major complications or AF-free survival at 3 and 6 months. Conclusions LBA with extended posterior wall isolation technique was safe and feasible. Long-term effectiveness studies should be evaluated in a larger sample size.
Title : Recurrent syncope late after permanent pacemaker implantation - What is the m...
Debabrata Bera
Radhey Shyam Joshi

Debabrata Bera

and 3 more

March 31, 2022
A 68-yr-old lady underwent a VVI pacemaker implantation 10 years back for infra-hisian complete heart block. Now she presents with 3 episodes of syncope within the last 2 months. Detailed neurological evaluation and pacemaker checkup was initially unremarkable. Real time electrograms during device interrogation were suspicious of lead noise resulting in oversensing. She became alright when the pacing mode was made VOO immediately. After discussion with patient relatives she underwent ventricular lead replacement and upgradation to a dual chamber pacemaker. However, in the immediate post-operative period she became unresponsive requiring immediate resuscitation. Monitor suggested short runs of polymorphic VT which was reproducibly suppressed with higher rate obligatory pacing @ 110 bpm. The runs of VT resurfaced immediately as the rate was lower than 90. She was managed by overdrive pacing at a lower rate of 110 bpm. Over the next 2 months the lower rate was brought down to 70 bpm in a stepwise manner. A retrospective analysis of her initial stored device electrogram suggested that it was all PMVT and no noise at all. The cause of her polymorphic VT is not clear. Relative hypomagnesemia, late presenting long QT syndrome and long term VVI pacing in isolation or combination remain the probable offender. She is presently doing well on oral propranolol.
Morphometric evaluation of facial and vestibulocochlear nerves using magnetic resonan...
Wilhelm Flatz
Annika Henneberger-Kunz

Wilhelm Flatz

and 6 more

March 31, 2022
Objectives: Several studies proposed a loss of neural structures in Menière’s disease (MD). It has also been shown that VIIth and VIIIth cranial nerves are enlarged within MD patients compared to normal controls. We aimed to investigate potential differences in these two nerves in patients with MD. Setting: 71 patients with MD were included, 53 showed clinically unilateral affection. Constructive-interference-in-steady-state(CISS) and 3D-FLAIR-inversion-recovery(IR) sequences with two different slice thicknesses were acquired on a clinical 3T magnetic resonance imaging scanner. We evaluated morphometric properties of the VIIth and VIIIth cranial nerves passing from the cerebellopontine angle to the inner ear modiolus. In patients with clinically unilateral MD, we compared the unaffected to the clinically affected side. In addition, we evaluated the morphology of the nerves in correlation to symptom duration. Results: The clinically unilateral MD-patients showed no significant differences after Bonferroni correction when comparing the affected side to the non-affected side of VIIth and VIIIth cranial nerves. There was no significant difference between patients with different symptom durations. Conclusions: Our data showed no differences in nerve morphometry between the clinically non-affected and the clinically affected side in patients with clinically unilateral MD. There was also no correlation to duration of symptoms, in contrast to previously demonstrated correlations between clinical features and the extent of endolymphatic hydrops. A disease process starting before onset of clinical symptoms could be a potential explanation.
Congenital laryngeal webs:From evaluation to surgical management
peng zhu
Jia rui Chen

peng zhu

and 2 more

March 31, 2022
Objective. To discuss the presentation, evaluation, and management of congenital laryngeal web. Methods.: The Institutional Board of Ethics of shanghai Children’s Hospital approved this retrospective review of all patients who were diagnosed with laryngeal web at our institution within the past 10 years. Charts mined for age at presentation, presenting symptoms, degree/location of web, associated syndromes, number/type of surgical procedures, and postoperative outcomes. Results.: Ten patients were included (6 male, 4female). There were 3 type I、II webs, 7 type III、IV webs; Children with type I and II laryngeal web were mainly presented with hoarseness and discomfort without any obvious respiratory distress(P<0.05). Children were usually older when they were presented to the hospital(p<0.05), All the 3 children with type I and II laryngeal web recovered after a single endoscopic procedure. While children with laryngeal web type III and IV usually had a record of multiple visits to the hospital with multiple treatments(p<0.05) All of these 7 type III、IV webs , the tracheotomy was performed early, The ultimate treatment required for such patients was open laryngoplasty. Conclusions:There is a need for alertness regarding the neonatus exhibiting hoarseness and weak crying. To achieve a satisfactory outcome, it is essential to perform accurate preoperative staging and assessment along with an appropriate choice of treatment and placement of the laryngeal stent.
AMYOTROPHIC LATERAL SCLEROSIS PATIENTS IN OTORHINOLARYNGOLOGY: A RETROSPECTIVE STUDY
Jesper Rautiola
Hannu Laaksovirta

Jesper Rautiola

and 5 more

March 31, 2022
Abstract OBJECTIVES Given its rarity and the lack of clear clinical markers, amyotrophic lateral sclerosis (ALS) remains a diagnostic challenge. Since bulbar-onset ALS (buALS) presents with impaired speech or swallowing, patients are often primarily referred to an otolaryngologist (ORL) or phoniatrician. We analyzed the role of such specialists in ALS diagnostics and treatment. PARTICIPANTS We reviewed data for all 327 patients treated for ALS through the Hospital District of Helsinki and Uusimaa (HUS) between 2010 and 2014, focusing specifically on 110 (34%) patients presenting with bulbar nerve onset (buALS). MAIN OUTCOME MEASURES The presenting symptoms, referral to specialized care, and to a neurology clinic were assessed. Indications and findings from swallowing studies were reviewed as well as the incidence of percutaneous endoscopic gastrostomy (PEG) and tracheostomy. RESULTS Among the 110 patients with buALS, 64 (58%) were primarily referred to a neurologist, 28 (25%) to an ORL, and 5 (5%) to a phoniatrician. The most common presenting symptom was dysarthria in 89 patients, (81%), followed by dysphagia in 26 (24%). In most cases, an ORL or phoniatrician suspected a neuromuscular disease; however, in 8 (24%) cases, the neurological etiology of symptoms was missed. Overall, 49 (45%) patients underwent a swallowing study and 86 (78%) patients underwent PEG placement. CONCLUSIONS Among buALS patients, 30% initially consulted an ORL or phoniatrician and 45% underwent a swallowing study. Based on our results, swallowing studies rarely lead to immediate PEG placement. An initial visit to other specialists had no impact on diagnostic delays or survival. Five keypoints Amyotrophic lateral sclerosis (or ALS) Motor neuron disease Dysphagia Fiberoptic Endoscopic Examination of Swallowing (or FEES) Percutaneous Endoscopic Gastrostomy (or PEG) Level of Evidence: 3
Variable chemical process and radiative nonlinear impact on MHD Cross nanofluid: An a...
Adil Darvesh
Gilder Cieza  Altamirano

Adil Darvesh

and 4 more

March 31, 2022
Solar energy is basic source of renewable energy, and it is being used for controlling the global pollutions/warming. As cross nanofluid is very useful for upgrading the solar energy systems efficiency so it is engaged for cooling the solar devices. In this paper for analysis of global warming heat equation is modeled by incorporating the nonlinear thermal radiation by using the exponentially extendable surface, because it keeps major role related to solar energy absorption of nanofluid. Furthermore, the mathematical modeling of cross nanofluid involving magnetic effect and diffusion is discussed by using the fact of chemical reaction. Chemical reaction finds astonishing applications regarding pollution studies, chemical processing equipment, polymer production. As a result of this study, it is noticed that more magnetized the conducting fluid controls the motion of fluids for both case of shear thinning and shear thickening. Brownian motion parameter Nb tells the rate the random motion of nanoparticle. Increased Nb temperature is also increases due to these random movement of nanoparticles. That is the reason when pollutant nanoparticles spreading in air as a result global warming increase.
Barriers to adherence to secondary prevention therapy in patients with ischemic heart...
José Raúl Orozco- Moreno
Erique Berríos- Bárcenas

José Orozco- Moreno

and 9 more

March 31, 2022
Background and objectives: Inadequate adherence has been recognized as a constant determinant in the overall burden of ischemic heart disease, particularly in countries with higher income-health inequalities, such as Mexico. The overall impression is that the lack of population-based epidemiological data and low public awareness may account for this problem. This study aimed to determine the level of adherence to secondary cardiovascular prevention therapy in a tertiary hospital in Mexico City and identify the barriers contributing to medication nonadherence. Methods: A cross-sectional study was conducted in the cardiology outpatient department between August 2018 and February 2020. Participants were asked about socio-demographic data, the MMAS-4, and an interview regarding reasons for nonadherence. Results: A total of 991 patients were included, with a median age of 65 (58,72) years old. Inadequate adherence to treatment was reported by 70.3%, with forgetfulness as the most frequent cause (55.4%). Patients on combined pharmacological therapy with PCI or CABG were more adherent than those on optimal medical therapy alone. A higher proportion of patients in the inadequate group were in NYHA classes II and III. Low educational level and the use of optimal medical treatment alone were predictors for poor adherence. Conclusion: These findings provide an initial framework of the current situation of adherence to secondary prevention therapy in Mexico, highlighting the value of promoting national consensus on medication adherence to move towards a population-based strategy to reduce cardiovascular disease burden.
Ant assemblage turnover is greater horizontally than vertically in the world's talles...
Shuang Xing
Amelia Hood

Shuang Xing

and 3 more

March 31, 2022
Abiotic and biotic factors structure species assembly in ecosystems both horizontally and vertically. However, the way community composition changes along comparable horizontal and vertical distances in complex three-dimensional habitats, and the factors driving these patterns, remain poorly understood. By sampling ant assemblages at comparable vertical and horizontal spatial scales in a tropical rain forest, we compared observed patterns with those predicted according to environmental filtering by microclimate and microhabitat structure. We found that although dissimilarity between ant assemblages increased with vertical distance, the dissimilarity was higher horizontally but was independent of distance. The pronounced horizontal and vertical structuring of ant assemblages across short distances is likely explained by a combination of microclimate and microhabitat connectivity. Our results demonstrate the importance of considering three-dimensional spatial variation in local assemblages and reveal how highly diverse communities can be supported by complex habitats.
Repeated Acute Lower Limb Ischemia due to Occlusive Thrombosis of an Artificial Vesse...
Yamato Tamura
Takehisa Abe

Yamato Tamura

and 1 more

March 31, 2022
A 60-year-old woman with bilateral superficial femoral artery occlusion underwent femoral-popliteal bypass surgery. Six months later, left vascular prosthesis occlusion occurred; 1.5 years later, an occlusive embolus developed in the deep femoral artery. The proximal prosthesis aspect was detached from the native vessel. The limb was salvaged with bypass surgery.
Findings of a fractured dental needle; A case report.
Nazia Khan
mzubanzi mabongo

nazia khan

and 2 more

March 31, 2022
The following case report describes a patient that presented with a dental needle that fractured during an inferior alveolar nerve block. Upon presentation, the patient had surgical emphysema that resolved and trauma to adjacent soft tissue. The needle was not removed, however the findings are presented.
Cavernous hemangioma of mesentery involving the jejunum causing intestinal obstructio...
Srijana Thapa
Udaya Koirala

Srijana Thapa

and 4 more

March 31, 2022
We present a rare case of 45-year-old man with complaints of abdominal pain and features suggestive of intestinal obstruction. CT scan of the abdomen demonstrated a large mesenteric mass in the pelvic region involving the distal segment of jejunum. Surgical excision of the lesion and histo-pathological examination confirmed cavernous hemangioma.
Central mucoepidermoid carcinoma of mandible deriving from an odontogenic cyst: A cas...
Andrea Loreti
Ornella Abate

Andrea Loreti

and 7 more

March 31, 2022
Mucoepidermoid Carcinoma (MEC) it can origin from a mandibular odontogenic cyst. We report the case of a 63-year-old man with MEC of the right retromolar trigonum of the mandibula. We performed a wide mandibular excision and immediate reconstruction with a fibula bone free flap.
Two-Year Clinical Outcomes of Pars Plana Vitrectomy as initial treatment for Refracto...
jizhu li
Ying Lin

jizhu li

and 15 more

March 31, 2022
Abstract Purpose To evaluate the safety and efficacy of pars plana vitrectomy (PPV) for recalcitrant vitreous seeding from retinoblastoma and concurrent retinal detachment. Methods In this retrospective interventional case series, intravitreal chemotherapy-assisted PPV was performed in 6 patients with persistent retinoblastoma vitreous seeds and concurrent retinal detachment. Globe salvage, retinal reattachment, and visual preservation at last follow-up visit were calculated. Results Six eyes, initially classified as group D (n=4) or E (n=2) with sphere and (or) cloud vitreous seeds, received standard systemic with intravitreal chemotherapy and subsequently developed refractory vitreous seeds with concurrent retinal detachment. PPV produced complete elimination of vitreous seeds in all 6 eyes and no vitreous seeding recurred over a mean follow-up of 29.6 months. Globe salvage and complete retina reattachment were attained in all 6 eyes (100%). Last follow-up vision acuity was assessable in 4 eyes with 80% (3/4) better than 0.4. Three eyes (50%) received repeated systemic or focal treatment because of the recurrent retinal tumor. There was no case of extraocular tumor extension or systemic metastasis. Conclusion Administration of intravitreal chemotherapy-assisted PPV appears to be a safe and effective alternation for the initial treatment of refractory vitreous seeds from retinoblastoma. It is also a promising therapeutic strategy to repair concurrent retinal detachment and preserve the remaining visual function.
De Novo Draft Assembly and Annotation of Pakistani Moringa Oleifera Genome
Muhammad Tariq  Pervez
Masroor Ellahi  Babar

Muhammad Tariq Pervez

and 4 more

March 31, 2022
Moringa oleifera is a famous tree species often known as horseradish tree or drumstick tree, belongs to the family Moringaceae. It is an evergreen and mineral rich plant that grows quickly, used in herbal medicine, agriculture, and the livestock sector. So far, only one draft genome assembly is available publicly for M. oleifera. Sparse availability of the genomic resources limits its use in genetic and genomic studies. So, we sequenced and de-novo assembled a draft genome of M. oleifera from Pakistan. The sequencing was performed using Illumina HiSeq platform with paired-end libraries. The draft assembled genome was 205,248,313 bp in size, and comprised of 13,872 scaffolds with N50 value of 17,279 bp. Annotation of the assembled genome revealed 26,215 protein coding genes. The draft de novo assembled genome is close to the genome size predicted by k-mers distribution and covers 83.09% and 84.68% of completeness and plant orthologous groups in BUSCO and CEGMA, respectively. This genome assembly would be an invaluable resource in understanding the genetic potential of this species, as well as in functional, comparative and evolutionary genomics within this species and in Moringa genus.
Effect of conventional haemodialysis on the apixaban plasma concentration
Tim Poel
Nikki de Rouw

Tim Poel

and 6 more

March 31, 2022
Apixaban is a factor Xa inhibitor and is used in patients undergoing haemodialysis treatment. Apixaban can be cleared by haemodialysis, which might lead to decreased apixaban plasma concentrations and insufficient anticoagulation during and after haemodialysis. The objective of this study was to investigate the effect of haemodialysis on apixaban plasma concentrations in patients treated with apixaban 2,5 mg twice daily on conventional haemodialysis with standard low molecular weight heparin (LMWH) anticoagulation ( nadroparin 3800-7600IU). A significant difference was observed between the apixaban concentration before and after dialysis (mean before dialysis 141.03 ng/ml; mean after dialysis 102.71 ng/ml; p=0.003). Nonetheless, both apixaban plasma concentrations and anti-Xa levels remained within reference range. Anti-Xa levels have a strong correlation with the apixaban concentrations (r=0.935, p=0.000).Thus, anti-Xa activity might be used as a surrogate for apixaban plasma concentration. There seems to be no need for dose adjustments of apixaban and co-administration of LMWH next to apixaban might be unnecessary.
VAERS reported new-onset seizures following use of Covid 19 vaccinations as compared...
Jagannadha Avasarala
Christopher McLouth

Jagannadha Avasarala

and 5 more

March 31, 2022
The incidence of new-onset seizures, which we defined as de novo seizures occurring within four weeks of receiving any of the FDA-approved Covid 19 vaccinations as reported in patient-reported data compiled in the US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data (CDC VAERS) has not been explored. The VAERS database contains de-identified patient-reported adverse events following vaccinations and represents post-marketing surveillance and analysis of vaccine safety. After adjusting for time at risk, this resulted in estimated incidence rates of 3.19 seizures per 100,000 persons per year for either Pfizer, Moderna or Janssen vaccines and 0.090 seizures per 100,000 persons per year for the influenza vaccine. A data-driven, individualized dataset that is comprehensive and coupled with a longitudinal follow-up in larger numbers of vaccinated individuals is needed to expand on our preliminary findings of vaccine-related seizures. The VAERS database helps in the identification of a safety signal detection and is fundamentally a hypothesis-generating system; the data or results cannot be used to analyze cause and effect.
The effect of isotretinoin on insulin resistance and serum adiponectin levels in acne...
Eleni Paschalidou
Georgios Katsaras

Eleni Paschalidou

and 8 more

March 31, 2022
Aim: Isotretinoin, the drug of choice for severe - nodulocystic acne, might be associated with an increase in insulin resistance. We aimed to investigate this association. Methods: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. A systematic search in PubMed/MEDLINE, SCOPUS and Cochrane databases was conducted until the 12th of January 2022 using the PICO tool (Patient, Intervention, Comparison, Outcome). Studies with a published full text in English regarding acne patients under isotretinoin were included. Insulin, glucose and adiponectin serum levels before and after isotretinoin treatment were recorded and insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA–IR). For Meta-analysis, the Review Manager (RevMan) 5.4.1 software was utilized. The quality assessment of the included studies was performed using the ROBINS-I tool. Results: Fifteen studies were included. The meta-analysis revealed a statistically significant increase in post-treatment adiponectin [SMD = 0.86; 95% confidence interval (CI) = 0.48 - 1.25, p-value <0.0001; I2 = 58%]. Subgroup analysis by study type revealed the same results [cohort studies pooled SMD = 1.2, 95% CI = 0.81 -1.61, p-value <0.00001; I2 = 8% and case-control studies pooled SMD = 0.53, 95% CI = 0.16 - 0.9, p-value=0.005; I2 = 27%)]. No statistically significant results were shown for insulin, glucose levels and HOMA-IR. Conclusion: Although isotretinoin exposure is not clearly associated with insulin resistance, it seems that it can increase serum adiponectin levels. Further research is needed to clarify this association.
Non-bacterial thrombotic endocarditis with atypical presentation as overt congestive...
Giuseppe Andò
Davide Restelli

Giuseppe Andò

and 7 more

March 31, 2022
Introduction. Non-Bacterial Thrombotic Endocarditis (NBTE) is a form of endocarditis associated with malignancy or autoimmune disorders. Diagnosis remains a challenge as patients are often asymptomatic up to embolic events or, rarely, valve dysfunction. We report a case of NBTE with uncommon clinical presentation and identified with multimodal echocardiography. Case presentation. An 82-year-old man presented to our outpatient clinic reporting dyspnea. Past medical history included hypertension, diabetes, kidney disease, and unprovoked deep vein thrombosis. On physical examination, he was apyretic, mildly hypotensive and hypoxemic, had a systolic murmur and lower limbs edema. Transthoracic echocardiography revealed severe mitral regurgitation due to verrucous thickening of the free margin of both leaflets, increased pulmonary pressure, and dilated inferior vena cava. Multiple blood cultures were negative. Transesophageal echocardiography confirmed “thrombotic” thickening of mitral leaflets. Nuclear investigations were highly suggestive of multi-metastatic pulmonary cancer. We did not further proceed in the diagnostic workup and prescribed palliative care. Discussion. Lesions seen on echocardiography were suggestive of NBTE: they involved both sides of mitral leaflets, close to the edges, had irregular shape and echo-density, a broad base, and no independent motion. Criteria for infective endocarditis were not met and the final diagnosis was paraneoplastic NBTE due to underlying lung cancer. We remark the lack of definitive recommendations about treatment of NBTE and the only role of anticoagulation to prevent systemic embolism. Conclusions. We report a case of NBTE presenting with atypical symptoms and likely related to the prothrombotic state induced by underlying lung cancer. Provided the unconclusive microbiological tests, multimodal imaging played a crucial role for the final diagnosis.
Lieb's and Lions' type theorems on Heisenberg Group and applications
Sainan Wang

Sainan Wang

March 31, 2022
In this paper, we make an effort to establish Lieb's and Lions' type theorems on Heisenberg Group, and then apply them to study the existence of solution for variational problem on Heisenberg group.
Reduced order finite difference scheme based on POD for fractional stochastic advection...
Zoleikha Soori
A.  Aminataei

Zoleikha Soori

and 1 more

March 31, 2022
This paper introduce a numerical solution of time fractional stochastic advection-diffusion equa- tion (FSA-DE) wherein time fractional derivative is described in Caputo sence of order α (0 < α < 1). First, a L1 approximation is employed to estimate the Caputo derivative. Then, the spatial derivative is discretized by a second-order finite difference scheme. Moreover, we combine the implicit finite difference (IFD) scheme with the proper orthogonal decomposition (POD) method to reduce the used cpu time. In other words, we obtain POD based reduced-order IFD scheme. As a result, the new scheme can be viewed as the modification of the exiting job (Mirzaee et al., 2020 [23]). The numerical results provide to verify the feasibility and efficiency of the new method.
PGAP6 drives chemotherapy resistance in Ewing sarcoma
Yonghua  Yu
Lili Zhang

Yonghua Yu

and 2 more

March 31, 2022
Abstract Background: The prognosis of recurrent and metastatic Ewing sarcoma (EWS) is extremely poor and the problem of drug resistance is significant; thus, it is extremely important to identify the mechanisms underlying chemotherapy resistance. This study aimed to explore the genes associated with chemotherapy resistance in EWS. Procedure: Gene expression profile data of GSE12102 and GSE63155were downloaded from GEO to screen for differentially expressed genes (DEGs). GO functional annotation analysis was performed on common DEGs. Twenty-one patients were divided into good response (tumor necrosis rate ≥90%) (n=4) and poor response (tumor necrosis rate <90%) (n=17) groups to chemotherapy. Formalin-fixed paraffin-embedded (FFPE) tissues of 21 patients after chemotherapy and 5 patients who are in poor response group before chemotherapy were collected. Real-Time Quantitative Reverse Transcription PCR(qRT-PCR) was used to verify gene expression differences.. The relationship between prognosis and gene expression level verified by GSE17679 Results: The PGAP6 expression level after chemotherapy in the poor response group (2.78 ± 2.36) was higher than that in the good response group (1.16 ± 0.65) (P = 0.024). Expression of PGAP6 after chemotherapy (16.70 ± 13.78) was higher than that before chemotherapy (1.16 ± 0.62; P = 0.071). Verified by external datasets, the expression level of PGAP6 was related to prognosis. Conclusions: PGAP6 drives EWS chemoresistance and may be associated with acquired resistance. The expression levels of PGAP6 correlated with EWS prognosis. PGAP6 can be used as a new target for reversing chemotherapy resistance of EWS. KEYWORDS: Ewing sarcoma; chemotherapy; drug resistance; PGAP6; TMEM8A
Model-Based Meta-analysis for the Population Pharmacokinetics of Iberdomide and Its M...
Yiming Cheng
Yongjun Xue

Yiming Cheng

and 7 more

March 31, 2022
Aim A parent-metabolite population pharmacokinetic (popPK) model of iberdomide was developed and the influence of demographic and disease-related covariates on popPK parameters was assessed based on data from three clinical studies of iberdomide (dose range, 0.1 to 6 mg) in healthy subjects (N=81) and subjects with relapsed and refractory multiple myeloma (N=245). Methods Nonlinear mixed effects modeling was used to develop the popPK model based on data from 326 subjects across 3 clinical studies. Results The pharmacokinetics (PK) of iberdomide were adequately described with a two-compartment model with first-order absorption and elimination. A first order conversion rate was used to link the one-compartment linear elimination metabolite model with the parent model. Subject type (multiple myeloma subjects vs. healthy subject) was a statistically significant covariate on apparent clearance (CL/F) and apparent volume of distribution for the central compartment (V1/F), suggesting different PK between subjects with multiple myeloma and healthy subjects. Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and sex were statistically but not clinically relevant covariates on CL/F. Metabolite (M12) PK tracked the PK of iberdomide. The metabolite to parent ratio was consistent across doses and combinations. Conclusion In conclusion, the parent-metabolite population pharmacokinetic model adequately described the time course PK data of iberdomide and M12. Iberdomide and M12 show robust PK exposure, not complicated by demographic factors, combination, hepatic or (mild and moderate) renal impairments. The model can be used to guide the dosing strategy for special patient population and inform future iberdomide study design.
Isolated epitrochlear lymphadenopathy as unique rare onset of Hodgkin lymphoma
Eliodoro Faiella
Domiziana Santucci

Eliodoro Faiella

and 7 more

March 31, 2022
We report a case concerning an Hodgkin lymphoma in a 55-yo male with isolated epitrochlear lymphadenopathy of his right arm. The aim is to recapitulate the possible background diseases arising on the basis of an asymptomatic epitrochlear lymphadenopathy and to review the Hodgkin lymphoma presenting with this localization.
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