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.

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.

Conflict of Interest The authors declare that they have no conflict of interest.

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.

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.

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.

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.

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.

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.

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

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.

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.

Primary renal osteosarcoma is exceedingly rare tumor with poor prognosis. It has tendency to spread to distant sites . we report the case of a 43-year-old female who presented with flank pain, gross hematuria, weakness and weight loss and was treated with diagnosis of primary renal osteogenic sarcoma

Psoriasis is a chronic inflammatory skin disease with unknown etiology and a wide spectrum of clinical presentations. We report the first case of dermatomal psoriasis in a 62-year-old patient in addition to an unusual presentation of psoriasis as a solitary plaque on the ear of a 38-year-old patient.

Soil moisture is an important factor that affects terrestrial vegetation ecosystems and biological growth and development, and water deficit is one of the major environmental factors threatening vegetation restoration in the Loess Plateau. To determine the change in the soil water deficit characteristics from farmland to forestland on the Loess Plateau, in this study, we measured the soil water storage and deficit in abandoned grassland, shrubland, pioneer forestland and climax forestland along with vegetation succession. The results showed that the soil water content and the soil water storage with natural vegetation recovery from the abandoned grassland to shrubland and forestland showed a gradual declining trend, while on the contrary, the soil water deficit was increasing during succession, it was more severe in the deep soil than in the shallow soil layers, and the soil water deficit in July and September of the rainy season as well as that the vigorous growing period of plants was more serious than that in May and November, which are in the non-rainy season of the Chinese Loess Plateau. The vegetation types, soil texture and soil depth were the key factors affecting the soil water deficiency status in the process of vegetation succession. The results could have great potential in the sustainable development of forestry and provide a theoretical basis for effective water management and reasonable vegetation restoration in arid and semiarid loess regions.

Metastatic intrathyroid thymic carcinoma (ITTC) is a rare cancer that has no effective drugs. Herein, we report that comprehensive cancer mutation analysis revealed amplification of CD274 gene encoding PD-L1. Multiplex immunohistochemistry also clarified the presence of an immunosuppressive microenvironment via a PD-1/PD-L1 pathway in metastatic ITTC.

A patient with retroperitoneal fluid retention after vascular surgery had a fever of unknown cause. Re-examination suggested fluid infection. Surgery was performed, and the patient was diagnosed with colon perforation. If the fluid volume reduces or the fluid comes into contact with the colon, colon perforation should be suspected.

Understanding the extent to which predators engage in active search for prey versus incidentally encountering them is important because active search can exert a stabilizing force on prey populations by alleviating predation pressure on low-density prey and increasing it for high-density prey. Parturition of many large herbivores occurs during a short and predictable temporal window in which young are highly vulnerable to predation. Our study aims to determine how a suite of carnivores responds to the seasonal pulse of newborn ungulates using contemporaneous GPS locations of four species of predators and two species of prey. We used step-selection functions to assess whether coyotes, cougars, black bears, and bobcats actively searched for parturient females in a low-density population of mule deer and a high-density population of elk. We then assessed whether searching carnivores shifted their habitat use toward areas exhibiting a high probability of encountering neonates. None of the four carnivore species encountered parturient mule deer more often than expected by chance suggesting that predation of young resulted from incidental encounters. By contrast, we determined that cougar and male bear movements positioned them in proximity of parturient elk more often than expected by chance which is evidence of searching behavior. Although both male bears and cougars searched for neonates, only male bears used elk parturition habitat in a way that dynamically tracked the phenology of the elk birth pulse suggesting that maximizing encounters with juvenile elk was a motivation when selecting resources. Our results support the existence of a stabilizing mechanism to prey populations through active search behavior by predators because carnivores in our study searched for the high-density prey species (elk) but ignored the low-density species (mule deer). We conclude that prey density must be high enough to warrant active search, and that there is high interspecific and intersexual variability in foraging strategies among large mammalian predators and their prey.

Objectives: During volume targeted ventilation, the ventilator’s algorithm adjusts the peak inspiratory pressure (PIP) to maintain the expired tidal volume close to the target. In hyperventilating infants PIP is frequently very low, just above the level of positive end-expiratory pressure (PEEP). The impact of this on ventilator parameters and blood gases was investigated. Methods: Data were collected and analysed computationally from 195 infants over 968 days of mechanical ventilation. The median ventilator inflating pressure (Pinfl, which is PIP minus PEEP) was determined before each blood gas (n=3,371) for periods of different duration between 15 minutes and 24 hours. Ventilator parameters and blood gases were compared between periods when the inflating pressure was <5 mbar and periods when it was higher. Results: 1-hour periods when median Pinfl was <5 mbar occurred in 30% of the babies. These were associated with similar tidal volumes and minutes ventilation as periods with higher Pinfl, despite the lower target tidal volume. Babies triggered more ventilator inflations, had more spontaneous breaths and had lower their oxygen requirement when Pinfl was low. Low inflating pressures were associated with lower blood carbon dioxide levels and did not lead to acidosis. Lactate levels were higher but the group included more babies with perinatal hypoxia. Analyzing data over shorter (15 or 30 minutes) or longer (up to 24 hours) periods before the blood gases gave similar results. Conclusions: Episodes of low inflating pressure occur frequently in babies receiving volume targeted ventilation. This does not lead to exhaustion, hypercapnia or acidosis.

Background: Emerging novel therapeutics have been developed to hamper the progression of multiple sclerosis. However, the adverse events related to these new agents remain largely unknown. Therefore, we sought to investigate the cardiovascular complications of these drugs. Methods: Utilizing data from the U.S. Food and Drug Administration Adverse Events Reporting System, we comprehensively evaluated the cardiovascular complications of the newly FDA approved anti-multiple sclerosis agents. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval of all the cardiovascular adverse events adverse events since approval till 2021. Results: After vetting the newly approved agents for multiple sclerosis, CD20 and CD25 inhibitors and sphingosine-1-phosphate receptors agonists were the latest approved medications for multiple sclerosis since 2015. Two CD20 (ocrelizumab, ofatumumab) and one CD25 inhibitors (daclizumab) were significantly associated with multiple cardiovascular adverse events. Among all the cardiotoxic events; coronary artery disease, cardiac failure and atrial fibrillation were the most predominant among CD20 or CD25 blockers. Interestingly, Sphingosine-1-phosphate receptors agonists showed much fewer reported cardiac adverse events. However, fingolimod and siponimod were associated with significant bradycardia. Conclusions: Our data revealed the new agents prescribed for multiple sclerosis have cardiotoxic effects, including not only the known adverse effects observed effects for S1P receptor modulators but also undefined cardiovascular complications associated with CD20 and CD25 inhibitors. These findings potentially instigate further studies to personalize prescribing these agents for multiple sclerosis based on patient’s cardiovascular profile.

Despite growing evidence of widespread impacts of humans on the behavior of animals, our understanding of how humans reshape species interactions remains limited. Here, we present a framework that draws on key concepts from behavioral and community ecology to outline four primary pathways by which humans can alter predator-prey spatiotemporal overlap, which may have implications for predator diet, predation rates, population demography, and trophic cascades. We then demonstrate the testability of the hypotheses that emerge from our framework using temporal activity data for 178 predator-prey dyads from published camera trap studies to reveal patterns of human influence on predator-prey activity and overlap. Our framework and case study highlight current challenges, gaps, and advances in linking human-induced animal behavior change to predator-prey dynamics. By using a hypothesis-driven approach to estimate the potential for altered species interactions, we can better predict the ecological consequences of human activities on whole communities.

Background and Purpose: Astrocytic nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a potential therapeutic target of ischemic preconditioning (IPC). Icariside Ⅱ (ICS Ⅱ) is a naturally occurring flavonoid derived from Herba Epimedii with Nrf2 induction potency. This study was designed to clarify whether ICS Ⅱ simulates IPC neuroprotection and to decipher if the astrocytic-Nrf2 is contributed to ICS Ⅱ preconditioning against ischemic stroke. Experimental Approach: Mice with transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia and oxygen-glucose deprivation (OGD)-injured primary astrocytes were used to explore the neuroprotective of ICS Ⅱ preconditioning. Additionally, Nrf2-deficient mice were pretreated with ICS Ⅱ to determine whether ICS Ⅱ exerts its neuroprotection by activating Nrf2. Key results: ICS Ⅱ pre-treatment dramatically mitigated the cerebral injury in ischemic stroke mice along with restoring long-term recovery. Furthermore, proteomics screening identified Nrf2 is a crucial gene evoked by ICS Ⅱ stimulation and is required for the anti-oxidative effect and anti-inflammatory effect of ICS Ⅱ. Most interestingly, ICS Ⅱ directly bound with Nrf2 and reinforced the transcriptional activity of Nrf2 after MCAO. Moreover, ICS Ⅱ pre-treatment exerted cytoprotective effect on astrocytes after lethal oxygen-glucose deprivation insult via promoting Nrf2 nuclear translocation and mediating OXPHOS/NF-κB/ferroptosis axis. While, abrogated neuroprotection in Nrf2-deficient mice and astrocyte potently supports Nrf2-dependent neuroprotection of ICS Ⅱ. Conclusions and implications: ICS Ⅱ preconditioning confers robust neuroprotection against ischemic stroke via astrocytic Nrf2-mediated OXPHOS/NF-κB/ferroptosis axis, it is concluded that ICS Ⅱ will be serve as a promising Nrf2 activator to rescue ischemic stroke.

Background and Purpose: Opioids are widely used in the treatment of moderate and severe pain. Nociceptive stimulation and classical opioids have been reported to potentially promote microglial activation and neuroinflammation, which also reduces the analgesic effect of opioid drugs and causes chronic pain sensitization. The aim of this study was to demonstrate whether the novel opioid agonist MEL-0614 could inhibit activated microglia and neuroinflammation while facilitating recovery from persistent pain. Experimental approach: Mice were administered lipopolysaccharide and formalin to induce allodynia. Von Frey test was used to detect the anti-allodynia effect of MEL-0614 before and after LPS and formalin injection. In the spinal cord, the levels of proinflammatory cytokines and microglial activation were determined after MEL-0614 administration. BV2 and primary microglia were cultured to further explore the effect of MEL-0614 on LPS-induced microglial activation and key signalling pathways involved. Key results: MEL-0614 prevented and reversed allodynia induced by LPS and formalin in vivo, which was not inhibited by the μ opioid receptor antagonist CTAP. MEL-0614 also downregulated the activation of microglia and related proinflammatory cytokines in the spinal cord. Additionally, in BV2 and primary microglia, MEL-0614 inhibited the LPS-induced upregulation of proinflammatory factors, which was unaffected by CTAP. The NOD-like receptor protein 3-related signalling pathway may be involved in the interaction between MEL-0614 and microglia. Conclusion and Implications: The opioid agonist MEL-0614 inhibited the activation of microglia and the subsequent upregulation of proinflammatory factors both in vivo and in vitro. Notably, this effect is not mediated by the opioid receptors.

Objectives: The current study aimed to compare the efficacy of the two different prophylactic antibiotic regimens (2-days vs. 7-days) in preventing surgical site infection in coronary artery bypass grafting (CABG). Methods: Patients undergoing CABG were included in this randomized, double-blind, placebo-controlled trial. From 2016 to 2017, 370 cases were allocated to one of two groups. The groups received prophylactic antibiotic therapy for either 2-days or 7-days. All CABG patients were followed for days for surgical site infections. Two of the patients died after surgery, and 3 patients did not show up during the three-month follow-up evaluation and thus did not meet the study criteria. Results: Of the remaining 365 patients who participated in the full study, 198 (54.2%) were male, and 167 (45.7%) were female patients. The mean age of these cases was 58.64± 11.4. Of the 365 study participants who received prophylactic antibiotics prior to surgery, 16 patients developed surgical site infections (legs and sternum). Among these 16 patients, nine cases belong to the 7-days prophylactic antibiotic therapy group (2.4%), and seven cases belong to the 2-day prophylactic antibiotic therapy group (1.9%) (P=0.771). Conclusion: Comparison of two 2-day and 7-day prophylactic antibiotic regimens showed no significant difference in the incidence of post-surgical infection in the two groups.