Small cell osteosarcoma is a rare sub-type of osteogenic malignant tumors. Rib localization is uncommon. Histological examination is an important step to make the difference with similar tumors like Ewing sarcoma. Surgical resection is the unique curative treatment. Prognosis remains poor even with adjuvant treatment

In this paper we propose a numerical method for American multi-asset options under jump-diffusion model based on the combination of the exponential time differencing (ETD) technique for the differential operator and Gauss-Hermite quadrature for the integral term. In order to simplify the computational stencil and improve characteristics of the ETD-scheme mixed derivative eliminating transformation is applied. The results are compared with recently proposed methods.

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vHPvSD ablation represents a quantum leap from the RF settings that have traditionally been used in electrophysiology. If used to its full potential, it may improve procedural efficiency by reducing ablation and procedure times. However, with great power comes great responsibility; we need to ensure that we use it judiciously and safely.

Catheter based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and functional atrioventricular block. There is now increasing convergence amongst enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, pre- and post-procedure management, necessary equipment, and its potential limitations.

Through the comprehensive analysis of ab initio and experimental results of a large number of diatomic systems, the systematic deviation of ab initio method in vibrational energies prediction caused by physical/mathematical simplification is located. A joint ab initio and machine learning method based on information across molecules is proposed to deal with the problem. Starting from an ab initio model, and then systematically modifying it through machine learning, the vibrational energies prediction of many diatomic systems (SiC, HBr, NO, PC, N2, SiO, O2, ClF, etc.) have been improved, and significantly surpassed the more complex ab initio model. In addition to the improvement of accuracy, the new method also greatly reduces the computational expense, and is applicable for the systems without experimental data.

Title pageTitle: Letter to the Editor: Aortic valve repair in patients with ventricular septal defectArticle type: Letter to the editorDeepak RajaniContact: +923350326757 Email: [email protected]: Shaheed Mohtarma Benazir Bhutto Medical College Liyari,KarachiAddress: Maira garden,Garden west, KarachiCo-author: Zoaib Habib TharwaniContact: +923343975434 Email: [email protected]: Dow University of health Sciences (DUHS), Dow Medical College, KarachiAddress: Al-Yasrab, Garden East, KarachiSatesh KumarContact:+92-3325252902 Email: [email protected]: Shaheed Mohtarma Benazir Bhutto Medical College Liyari,KarachiAddress: Parsa citi near police headquarter Garden East Karachi

Cancer is one of the major health-related issues affecting the population worldwide and subsequently accounts for the second-largest death. Genetic and epigenetic modifications in oncogenes or tumor suppressor genes affect the regulatory systems that lead to the initiation and progression of cancer. Conventional methods, including chemotherapy/radiotherapy/appropriate combinational therapy and surgery, are being widely used for theranostics of cancer patients. Surgery is useful in treating localized tumors, but it is ineffective in treating metastatic tumors, which spread to other organs and result in a high recurrence rate and death. Also, the therapeutic application of free drugs is related to substantial issues such as poor absorption, solubility, bioavailability, high degradation rate, short shelf-life, and low therapeutic index. Therefore, these issues can be sorted out using nano lipid-based carriers (NLBCs) as promising drug delivery carriers. Still, at most, they fail to achieve site targeted drug delivery and detection. This can be achieved by selecting a specific ligand/antibody for its cognate receptor molecule expressed on the cancer cell surface. In this review, we have mainly discussed the various types of ligands used to decorate NLBCs. A list of the ligands used to design nanocarriers to target malignant cells specifically has been extensively undertaken, and the approved ligand decorated lipid-based nanomedicines with their clinical status has been explained in tabulated form to provide a wider scope to the readers regarding ligand coupled NLBCs.

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for Acute Respiratory Infection (ARI) surveillance in Primary care, and a network of sentinel hospitals for Severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 VE against hospitalization, by age group, vaccine type, time since vaccination and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA surveillance system, with a network of sentinel hospitals in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations, monitor the circulation of SARS-CoV-2 and other respiratory viruses, and provide data to measure the effectiveness of COVID-19 vaccination in the population under surveillance. Our results add to evidence of high VE of mRNA vaccines against severe COVID-19 and waning protection with time since vaccination.

We measured the content of nitrogen and phosphorus, as well as nitrogen stable isotopes in plant biomass and marmot faeces in a distance gradient up to 20 meters from marmot burrows in an extremely arid glacier valley in Eastern Pamir, Tajikistan. The goal of this study was to test well-known mechanisms of ecosystem engineering by burrowing animals in previously unstudied conditions. We captured aerial images of the area inhabited by marmots to study the spatial distribution of vegetation. There was no relationship between the presence of burrows and vegetation cover. Burrow mounds were not colonised by plants, as opposed to other ecosystems, where mounds are often microhabitats that enhance plant diversity. A significant increase in N and P in aboveground green plant biomass in the proximity of burrows was found in one out of six studied species. Stable N isotopes did not give further insight into N routing, contrary to our expectations. We assume that plant growth is strongly limited by water availability, which prevents them from utilizing the local increase in nutrients, certainly provided by marmot activity. The results are contrary to numerous studies which showed that the role of burrowing animals as ecosystem engineers increases with increasing abiotic stress, including aridity. This shows a lack of this type of study in the end of the gradient of abiotic factors.

Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy is unknown. We used data from 10 pregnant patients with preterm preeclampsia, and 49 non-pregnant individuals to develop a population pharmacokinetic model of esomeprazole. A two-compartment model described the data well. In pregnant patients after single dose, clearance was 42.2% (14.9%– 61.6%) lower compared to non-pregnant, most likely due to downregulation of CYP2C19. In non-pregnant after repeated dosing, clearance was 54.9% (48.2% – 63.5%) lower in extensive metabolizers and bioavailability was 33% (10.0% – 52.0%) higher compared to single dosing, which could be due to autoinhibition of CYP2C19. Esomeprazole pharmacokinetics during pregnancy appears to be more dependent on CYP3A4.

We evaluated uptake and factors associated with COVID-19 vaccination among health workers (HWs) in Azerbaijan. Among 1,575 HWs, 73% had received at least one dose and 67% received two doses; all received CoronaVac. Factors associated with vaccination uptake included no previous COVID-19 infection, older age, belief in the vaccine’s safety, previous vaccination for influenza, having patient-facing roles, and good or excellent health by self-assessment. These findings could inform strategies to increase vaccination uptake as the campaign continues.

Background: Accessory mitral valve tissue (AMVT) is an extremely rare causes left ventricular outflow tract (LVOT) obstruction and is usually incidentally detected in childhood. It is often associated with other cardiac and vascular congenital malformations. Case Presentation: In this case, we present a 15-year-old girl was diagnosed with AMVT by transesophageal echocardiography, resulting in LVOT obstruction during systole. Interestingly enough, the patient’s accessory mitral valve remained undetected for years until he became symptomatic for wide ASD. Successful closure of the ASD with resection of the AMVT was performed with a transaortic approach. The patient was hemodynamically stable postoperatively. There were no abnormalities in the mitral valves and LVOT. Conclusion: It was also unusual to see AMVT with ASD instead of other frequently associated other congenital anomalies. Accessory mitral valve should be considered a rare but important cause of left ventricular outflow tract obstruction in childhood.

Tricuspid annuloplasty for moderate to severe TR (Class I, IIb) is the current standard of practice to restore the normal tricuspid annular dimension and function (1,2). The current controversy in atrioventricular surgery concerns the indication for concomitant TA in patients with moderate TR and significant annular dilatation of at least > 40 mm or at least 21 mm/m2 indexed for body surface area (Class IIb) during mitral valve surgery proposed by the American Heart Association/American College of Cardiology and European Society of Cardiology (1,2,3)

AIMS This study analysed the clinical features of children with intracranial germ cell tumours (IC-GCTs) treated at two European centres. We retrospectively reviewed timelag between symptoms onset, clinic-radiological findings, diagnosis and outcomes. METHODS Symptoms at diagnosis were divided into four groups: 1)raised intracranial pressure (RICP); 2)visual impairment; 3)endocrinopathy; 4)other. Total diagnostic interval (TDI), defined as the interval between symptom onset (including retrospective recall of symptoms) and definitive diagnosis of IC-GCT, was calculated and compared to survival rates. RESULTS Our cohort included 55 children with a median follow-up of 78.9 months (0.5-249.9). The majority (63.6%) had germinomas and 10.9% were metastatic at diagnosis. IC-GCTs were suprasellar (41.8%), pineal (36.4%), bifocal (12.7%) or in atypical sites (9.1%). The most common presenting symptoms were related to RICP (43.6%); however, by the time of tumour diagnosis, 50.9% of the patients had developed endocrine dysfunctions. All pineal GCTs manifested with RICP or visual impairment. All suprasellar GCTs presented with endocrinopathies. TDI ranged between 0.25-58.5 months (median 4 months). Pineal GCTs had the shortest TDI (median TDI 1 month versus 24 months in suprasellar GCTs, p<0.001). TDI >6 months was observed in 47.3% of patients and was significantly associated with endocrine presenting symptoms. No statistically significant difference was found in progression-free survival and overall survival between patients with TDI >6 months and with TDI 6 months. CONCLUSION Approximately half of our patients had TDI >6 months, mostly with endocrine deficiencies as presenting symptoms. TDI >6 months was not associated with increased relapse rate or mortality.

Background Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet little is known about pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers’ beliefs, practices, motivators, and barriers for providing contraceptive care to female AYA with SCD. Methods Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess providers’ practices. Survey links were distributed nation-wide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S. accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, logistic regression. Results Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Counseling practices significantly differed in trainees versus established providers (54% vs. 85%, p<0.001) with a similar trend for prescribing (p=0.05). Prescription practices did not differ significantly by provider beliefs regarding potential teratogenicity of hydroxyurea. Key motivators included patient request and disclosure of sexual activity. Key barriers included inadequate provider training, limited visit time, and perceived patient/parent interest. Conclusion Provider contraceptive practices for female AYA with SCD varied, especially by provider status. Health beliefs regarding teratogenic potential of hydroxyurea did not correlate with contraceptive practices. Clinical guidelines, provider training, and patient/parent decision-making tools may be tested to assess whether provider contraceptive practices could be improved.

The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida ( GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12- ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 g/L or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.

The motion of plane curves specified by hyperbolic inverse mean curvature with a constant force term is considered. We proved that this flow remains the convexity for any forced term. Furthermore, we give an example to understand how the constant forced term $c$ affects this hyperbolic inverse mean flow. Particularly, the asymptotic behavior of the flow under different initial conditions is discussed.