Purpose: Along with the increase in the frequency of multiple pregnancies, an increase is observed in the frequency of feto-maternal negativities. In our study, we aimed to determine the levels of iron, ferritin, hemoglobin, zinc, and copper in second-trimester multiparous twin pregnants and to compare them with values in women with the same demographic characteristics. Methods: Three groups were created in the study; control group, single pregnancy group, and twin pregnancy group. Venous blood samples were taken from individuals after 12 hours of fasting. Iron, zinc, copper, and ferritin levels were measured. Results: Compared with the control group, the Fe, Ferritin, and Zn values of the individuals in the single and twin pregnancy groups were statistically low while Cu levels were significantly high (p<0.05). Also, when compared with individuals in a single pregnancy group, a statistically significant decrease was found in Fe, Ferritin, and Zn levels in the twin pregnancy group (p<0.05); Although there was a minimal increase in Cu levels, this increase was not statistically significant. Conclusion: Since changes in trace element levels can lead to feto-maternal adverse effects, we think that dietary habits should be monitored, and zinc, copper, and iron levels should be followed in pregnant women.

The therapeutic use of humanized monoclonal anti-programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) and anti-programmed cell death ligand1 (PD-L1) (atezolizumab, avelumab, durvalumab) as potent anticancer therapies is rapidly increasing. The mechanism of signaling of anti-PD-1/PD-L1 involves triggering cytotoxic CD4+/CD8+T cell activation, which induces specific immunologic adverse events. The anti-PD-1/PD-L1 drugs can cause numerous cases of cutaneous reactions, hence these toxicities are characterized as the most frequent immune-related adverse events (irAEs). The majority of cutaneous irAEs triggered by immune checkpoint inhibitors range from nonspecific eruptions to detectible skin manifestations, which may be self-limiting and present an acceptable skin toxicity profile, while some may produce mild to life-threatening complications. This review aims to illuminate the associated cutaneous adverse events related to the drugs used in oncology along with the relevant mechanism(s). With this review article, an overview of the various adverse cutaneous manifestations of anti-PD-1 (pembrolizumab, and nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab) therapy, as well as suggestions, have been provided, so that their recognition at early stages could help in better management and would prevent treatment discontinuation.

In the present study, we optimized medium components for the production of ergosterol peroxide (EP) by Paecilomyces cicadae based on a mono-factor experiment, a uniform design, and a non-linear regression analysis. A maximum EP yield of 256 μg/L was achieved, which was increased by 5-fold compared with that before the optimization. Structured Monod model, Andrews model, Contois model, and Aibe model were developed to describe the effects of viscosity inhibition, substrate, and production on biomass growth. The results showed that the Monod model could predict biomass growth, and the effects of viscosity and substrate on the EP concentration were significantly higher compared with the effect of production. Moreover, the addition of water and glycerol could decrease the viscosity inhibition and glycerol inhibition, and further increase the EP yield. The newly developed structured model was demonstrated for batch growth of P. cicadae.

Background and aim of the study - The debate on the usefulness of the minimally invasive approach in mitral valve surgery is still open. The aim of this study is to describe a single-center case series of all comers undergoing minimally invasive mitral valve reconstruction. Methods - From 2010 to 2019, all the data recorded in the medical records of 893 consecutive patients undergoing mitral valve reconstruction through a right mini-thoracotomy were retrospectively collected. All patients were contacted by telephone for remote evaluation and integration of echocardiographic information on surgical results. Results - Mean age was 62.2±14.5; 447 (50%) were female and mean log EuroSCORE was 2.5±2.8%. At a mean follow-up of 4.1 ± 2.2 years (median 3.9), a total of 24 deaths (2.68%) were recorded. Twenty-four patients required rehospitalization for cardiac causes, 13 (1.4%) patients had at least moderate mitral insufficiency on follow-up echocardiography and, of these, 7 patients underwent reoperation (0.8%). The cumulative hazard showed that 8.3% of patients experienced at least one event at 5 years. NYHA class improved significantly with 874 patients in NYHA class I, 13 in NYHA class II, 6 in NYHA class III, and 0 in NYHA class IV at last follow-up (p <0.001 from baseline as reference point). Conclusions – In a high-volume center, mitral valve surgery using a minimally invasive approach is a feasible treatment option for all-comers and is associated with excellent results that are maintained at clinical and echocardiographic follow-up.

Circular RNAs (circRNAs) are endogenous RNA formed by the back splicing process. They are ubiquitous, stable, evolutionally conserved, and are tissue-specific. CircRNAs have numerous latent modes of action, from acting as sponges for microRNAs and RNA binding proteins to serving as transcriptional regulators, epigenetic alterations, etc. Dysregulated functioning of several circular RNAs leads to the progression of a plethora of diseases. CircRNAs have paved the way for advanced clinical studies as a novel method of disease diagnosis. This review systematically summarized and evaluated the role of differentially expressed circRNAs in four human diseases, including neurodegenerative diseases, diabetes, osteoarthritis, and cardiovascular diseases.

In the context of ex vivo gene therapy or CAR-T cell therapy, vector copy number (VCN) analysis in transduced cells by lentiviral vectors enables the assessment of risk and therapeutic efficiency in patients. In this study, we show that a ddPCR-based method can replace easily a TaqMan qPCR assay for VCN analysis, by measuring the number of pro-viral DNA copies per host cell genome in blood samples. Firstly, we have identified key elements of sample preparation and set-up to further improve the performance characteristics of ddPCR method, resulting in an accurate analysis of VCN without the need for multiple replicates or an external calibrator, as required in qPCR methods. Secondly, we found that genomic DNA (gDNA) quantification by fluorometry allows a better prediction of the genomic copy number detected in ddPCR than by spectrophotometry. Then, we applied this new technology to analyze VCN in blood cells and also in colony-forming cells (CFC) derived from transduced CD34+ cells, using a NaOH cell lysis-based approach. Finally, we conclude that the multiplex ddPCR is able to analyze VCN more precisely than qPCR in all transduced hematopoietic cells, an assay useful for clinical applications.

Background: To evaluate the analytical performance of a magnetic bead-based automatic extraction platform DAAN Stream SP96 combined with quantitative real-time PCR (qPCR) in detection of BK virus. Methods: A total of 70 clinical specimens from renal transplant recipients (RTR) were analyzed. The evaluation was carried out according to CLSI EP documents. The performance parameters included precision, accuracy, linearity, detection limit, interference test, cross-reactivity, and method comparison. Results: The coefficient of variation (CV) for within-run and intermediate precision of the high-, middle-, and low-level samples were all <5％. For the accuracy, the mean percent bias was 0.6% compared with the reference method. The linear range was 5.0 × 103～5.0 × 108 copies/mL, and the limit of detection (LOD) was 1.23×103 copies/mL. For anti-interference ability, 280 μmol/L bilirubin, 18mmol /L triglycerides, and 20g /L hemoglobin had no apparent effects on testing results. This assay didn’t show cross-reaction with some common pathogenic viruses. The automated magnetic bead-based DNA extraction combined qPCR has a good correlation (R2= 0.8978) with the manual boiling extraction combined qPCR. Conclusion: The DAAN Stream SP96 magnetic bead-based automatic extraction platform combined qPCR showed good analytical performance in the BKV DNA quantitative detection, which can meet the clinical testing requirements well.

The understanding of Coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in adult with COVID-19 is thrombotic thrombocytopenic purpura (TTP). We report a pediatric case with features suggestive of multisystem inflammatory syndrome in children (MIS-C) with coronary artery ectasia, TTP, autoimmune hemolytic anemia (AIHA) and thrombocytopenia with new onset SLE as well.

This study aims at investigating the numerical analysis of pollutant transport in homogenous porous media in the presence of plate stacks. The investigation is performed for solid objects of the same size placed in an inline arrangement in a homogenous porous media. The pollutant transport equation (i.e., steady-state and time-dependent advection-diispersion) is chosen in mathematical modeling. Furthermore, on basis of dispersion coefficient, three more cases arise which include uniformly constant, dependence on the magnitude of velocity, and dependence on both magnitude of velocity and its direction. Such models have a wide range of applications. Generally, the analytical solution of such problems doesn’t exist, so all the work is done numerically. The governing partial differential equation of pollutant concentration is approximated by using finite difference technique. Central and one-sided finite difference formulae are used to discretize the domain. MATLAB software is used to compute approximations to velocity potential and stream function. Then equipotential lines and streamlines are visualized in form of contours. Both, velocity potential and stream function satisfy Laplace’s equation and they are harmonic. Fluid flow lines and pollutant concentration are represented graphically for various parameters involved. It is observed that the size, shape, and position of pervious objects, entrance length of the domain affect fluid flow and pollutant transport. However, there is no significant effect of heated objects on pollutant transport. Moreover, advection and dispersion depend upon the permeability of porous media and the properties of the solid matrix.

A mildly dehydrated dog was presented at Veterinary Teaching Hospital, Paklihawa Campus, with symptoms of urinary inconsistency, haematuria, and inappetence. Radiography and ultrasonography revealed the presence of calculus in the urinary bladder. Cystolithotomy was performed and the dog responded to the intervention and recovered uneventfully.

Background: Coronavirus disease 2019 (COVID-19) has become pandemic in 2020 and recently mutated coronavirus has emerged in many countries. This study firstly identified the clinical characteristics and risk factors for COVID-19 patients in Zhengzhou for clinical prevention and management. Methods: A total of 70 patients hospitalized with COVID-19 were enrolled between 21th January and 29th February 2020, in Zhengzhou, China. Clinical characteristics, hematological findings, neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and inflammatory index on admission were selected from medical records and the comparison between COVID-19 patients with different outcomes were evaluated. Results : The median age was 55 years. Forty-three (43%) patients were classified as severe or critical cases. Eighteen (12.8%) patients died in hospital and the remaining fifty-two were discharged. Patients who died tend to old aged, expectoration, with chronic obstructive pulmonary disease. Compared to survivor, non-survivor has significantly higher leucocytes, neutrophils, NLR, AST, GGT, TBIL, DBIL, LDH, PT, D-dimer, CRP, and decreased platelet, lymphocyte, UA, ALB, CHE, PTA. Multiple logistic regression analysis identified leucocytes, platelet, PLR, NLR, AST, and ALB as independent factors for poor outcomes. The AUC of combination of leucocyte, PLR, NLR, and AST have the largest area under curve at 0.87, with the sensitivity of 0.83 and specificity of 0.81. Conclusion : Our results identified the risk factors among COVID-19 patients in-hospital fatality. Leucocyte, PLR, NLR, and AST could have important reference value for prognostic prediction and early intervention.

Endometriosis is a chronic disease, affecting approximately 10% of women of reproductive age. Ovarian endometriotic cysts or endometriomas are of particular relevance to fertility due to the negative impacts of both the disease and its treatment on prognosis. It is important for clinicians, especially those in non-fertility settings, to be aware of the evolving evidence and options for treatment in these women. The role of assisted reproduction techniques, prior to or alongside surgery need to be carefully considered. We outline an evidence-based framework to help facilitate fertility-friendly discussion, counseling and management of this complex disease.

• A high index of suspicion is needed when otitis externa not improving and there are symptoms of significant pruritis. • Signs of fungal debris, either obvious spores or black particles in debris should alert one to take a microbiology swab for fungal culture, which may yield Candida or Aspergillus species. • Treat patients with regular and prompt microsuctioning and application of topical antifungals for up to a month: Aspergillus can be particularly aggressive and lead to tympanic membrane erosions, ulceration and perforation. • Flumetasone/Clioquinol drops are effective in Aspergillus fungal otitis externa • Consider surgical repair if tympanic membrane not healed with medical treatment.

Optimal treatment for aortic thrombus remains to be determined, but surgical treatment is indicated when there is a risk for thromboembolism. We report a rare case of a fluttering cord-like thrombus extending from the ascending aorta to the left carotid artery that was removed under hypothermic circulatory arrest and direct cannulation of the left carotid artery to avoid carotid thromboembolism. The patient had an uneventful postoperative course and was discharged 9 days after surgery.

Objectives: To examine real-world patterns of antipsychotic use in Australia. Methods: This retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample data. Included data were for patients aged 16-years or older who initiated treatment for the first time with a PBS-reimbursed antipsychotic medication for schizophrenia between July 2013 and September 2017. Patterns of treatment usage were summarised descriptively. Differences in prescribing patterns by age and prescribing year were reported. Treatment persistence was estimated using Kaplan-Meier methods, with differences explored using log-rank tests. Values of p<0.05 were considered statistically significant. Results: 6,740 patients, representing 8,249 non-unique patients, received prescriptions for antipsychotic medications. Patients were aged 16 years to over 85 years (54.5% were < 55 years) and two-thirds of patients were male (61%). The majority (62%, n=5139/8249) were prescribed an atypical oral antipsychotic. Typical long-acting antipsychotic therapies (LATs) were prescribed 19% of the time (n=1,608/8,249. There was a small increase in prescribing of atypical LAT and typical LAT and a small decrease in atypical oral and clozapine prescribing over the study period. Treatment persistence was greatest in patients treated with clozapine, than in those treated with atypical LATs. Conclusions: While the majority of patients receive atypical antipsychotic medications, one in five continue to user older typical LAT therapies. Patient age and time on therapy may be associated with choice of therapy. Persistence to atypical LAT therapy is better than for other treatment modalities in this real-world cohort.

Duckweed plants play important roles in aquatic ecosystems worldwide. They rapidly accumulate biomass and have potential uses in bioremediation of water polluted by fertilizer runoff or other chemicals. Here we studied the assimilation of two major sources of inorganic nitrogen, nitrate (NO3-) and ammonium (NH4+), in six duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna aequinoctialis, Lemna turionifera, Lemna minor, and Wolffia globosa. All six duckweed species preferred NH4+ over NO3- and started using NO3- only when NH4+ was depleted. Using the available genome sequence, we analyzed the molecular structure and expression of eight key nitrogen assimilation genes in S. polyrhiza. The expression of genes encoding nitrate reductase and nitrite reductase increased about 10-fold when NO3- was supplied and decreased when NH4+ was supplied. NO3- and NH4+ induced the glutamine synthetase (GS) genes GS1;2 and the GS2 by 2- to 5-fold, but repressed GS1;1 and GS1;3. NH4+ and NO3- upregulated the genes encoding ferredoxin- and NADH-dependent glutamate synthases (Fd-GOGAT and NADH-GOGAT). A survey of nitrogen assimilation gene promoters suggested complex regulation, with major roles for NRE-like and GAATC/GATTC cis-elements, TATA-based enhancers, (GA/CT)n repeats, and G-quadruplex structures. These results will inform efforts to improve bioremediation and nitrogen use efficiency.

Novel human astrovirus (HAstV) strains have been recently shown to cause fatal encephalitis in immunocompromised patients. We report two cases from our institution. A 2-year old female undergoing treatment for acute lymphoblastic leukemia and a 9-year old male with refractory acute myeloid leukemia. Both were found to have HAstV-VA1 in the cerebrospinal fluid (CSF) by metagenomics next generation sequencing (m-NGS) after the initial evaluation did not reveal any etiology. Patient 1 remains alive, in remission, showing gradual neurological improvement after treatment with steroids, intravenous immunoglobulin, ribavirin, nitazoxanide and Peg-INF-alpha 2b. Patient 2 died 7 weeks later while receiving palliative care.

The model of two-dimensional plane waves is studied in a generalized micropolar-thermoelastic medium with microtemperatures in the three-phase-lag model (3PHL), dual-phase-lag model (Dual), and the Green-Naghdi theory with energy dissipation (G-N III). Harmonic representation of waves is used to find the solution to the problem. Numerical values of the physical fields are visualized graphically to display the effects of the gravity field magnetic field, and viscosity.

Background and aim: Anemia is a public health problem in developing countries. In our study, it is aimed to investigate the relationship between the presence of anemia in pregnancy and the factors which influence anemia. Method: Our study was conducted with 567 voluntary pregnant contributors who attended as outpatients to Gulhane Education and Research Hospital Obstetrics Polyclinics between December 2018 and February 2019. The assessment questionnaire included questions about sociodemographic information, obstetric history and medication adherence, and Patient Health Questionnaire-9 forms. Results: Mean age of 567 voluntary pregnants was 28.1 ± 5.0 (18-43) years and mean hemoglobin values were 12.4±1.3 (6.1- 15.6) g/dL. Of the contributors, %12.3 had hemoglobin values <11 g/dL of which was described as anemia. Patients who had taken their medication regularly were less likely to have anemia than the ones were not under the regular treatment [%9.6, vs.%16.2,(38),(p=0.018)]. Patients with a chronic disease before pregnancy showed significantly lower anemia prevalence [%6.3] compared to patients without the chronic disease [%61 (p=0.034)]. Based on PHQ-9 scores, %43.9 of contributors showed mild signs of depression. A statistically significant difference between anemia presence and depression signs was not detected. Conclusion: Anemia was more frequent in pregnant women who were treated for anemia in their previous pregnancy, and pregnant with a chronic disease before pregnancy were less likely to have anemia. Since early diagnosis and treatment of anemia, which significantly affects maternal and infant health, can be possible during pregnancy, anemia should be evaluated in all women planning and conceiving a pregnancy.

Objective Laryngeal contact granuloma (LCG) is a kind of benign lesion that related with improper use of voice, habitual throat clearing and laryngopharyngeal reflux. Under 3 months standardized treatment, those who have no improvement or disease recurrence are called refractory LCG. The purpose of this study was to explore an advanced surgical method with local flipped pedicle microflap combined with botulinum toxin A injection in the treatment of refractory LCG. Design A retrospectively analysed of totally 11 patients with refractory LCG from January 2018 to December 2020. After CO2 laser granuloma resection with local flipped pedicle microflap combined with botulinum toxin A injection, the patients were followed up at 1, 3, 6 and 12 months after operation to evaluate the effect of the surgery. Descriptive statistical methods were used to analyze and summarize the improvement of postoperative symptoms and signs of laryngoscope. Results During follow-up, 4 of 11 patients had residual pseudomembrane under the electronic laryngoscope, and had smooth mucosa when subsequent follow-up. The remaining 7 cases of electronic laryngoscope granuloma disappeared. Up to now their symptoms disappeared, and there were no systemic and local complications. Conclusion CO2 laser granuloma resection with local flipped pedicle microflap combined with botulinum toxin A injection can achieve the lesion clearance, restore the integrity of vocal fold cover-body, preserve the perichondrium, and reserve a time window for microflap recovery. It is based on the principle of preserving normal mucosa, with high cure rate and no recurrence. It is worthy of clinical promotion.

Stilling basins are used to dissipate the kinetic energy of the flow. USBR VI stilling basin is one of the oldest energy dissipators designed for dissipating the pipe outlet flow. This basin looks like a box with the intermediate baffle and an endsill. In this paper, the effect of the USBR VI stilling basin geometry on the entropy generation has been studied numerically by solving the RANS equations. In this research, the entropy generation analysis is used for the first time in the USBR VI stilling basin. In this study, the total entropy generation is introduced as an index for designing the USBR VI stilling basin. The effect of the W/D ratio (Basin width to incoming flow depth to the basin) on the flow field, entropy generation rate, and total entropy generation is analyzed. The results showed that variations of the total entropy generation have a good agreement with variations of the total hydraulic head loss along the basin, mean and maximum velocity on the endsill, and shear velocity near the downstream channel bed. The results also demonstrated that a large W/D ratio is beneficial for the best performance and highest energy dissipation.

The effect of different tubes geometrical parameters on its flow field analysis and thermal heat transfer performance are investigated in current research work. The hydraulic thermal fluid coupling with computational simulations are applied. The numerical results are solving used flow transport and heat transfer equations then these results are validated with available experimental data. Behaviour of hydraulic and thermal flow in the corrugated tube are discussed with different geometrical parameters position and shape. Turbulent flow in tube is calculated in 3D numerical simulations with optimisation of multi-objective algorithm are analysed. The influences of various design parameters for instance, number of corrugated rings around tube, distance between each corrugated ring, diameter of ring and pitch of ring are investigated firstly in flow field and then optimised by using design of experiment (DOE). The influence of flow structural modifications such as static pressure, dynamic pressure, and pressure drop are taken into consideration as analysed performance parameters. DOE Method is investigated based on implements and variances the L16 orthogonal arrays is chosen as the experimental strategy. Furthermore, the optimisation results found that the maximum value of pressure difference was for corrugated diameter. The numerical method using DOE has enhanced heat transfer rate as compared to the smooth pipe. The outcomes illustrate that the performance evaluation factor (PEF) ratio of the corrugated pipe with different geometrical configuration is changed and increased as the corrugated pipe geometrical changed and the value of PEF is more than 1.3.

In this paper, we are concerned with a nonlinear optimal control problem of ordinary differential equations. We consider a discretization of the problem with the discontinuous Galerkin method with arbitrary order $r \in \mathbb{N}\cup \{0\}$. Under suitable regularity assumptions on the cost functional and solutions of the state equations, we provide sharp estimates for the error of the approximate solutions. Numerical experiments are presented supporting the theoretical results.

Aim: Our aim was to investigate the relationship between prothrombintime(PT), activated partial thromboplastin time (aPTT), INR (International Normalized Ratio) and D-dimer levels, platelet (PLT)levels at admission to hospital and positivity or negativity of Polymerase Chain Reaction (PCR) result in patients with suspected COVID-19 followed at COVID-19 services. Material and Method: 238 people who applied with suspicion of COVID-19 in March-April-May of 2020 were included in the study. According to COVID-19 results, PCR negative 119 participants and PCR positive 119 patients were included in the study. PT, aPTT, Ddimer, INR and PLT levels were examined. Results: While PCR negative participants had a mean PT value of 11.46±0.86 sec, PCR positive patients had a mean PT value of 12.97±3.65 sec (p<0.001). There was no significant difference in mean aPTT values of PCR positive and negative patients. Whereas INR, D-dimer increased significantly in PCR positive patients. PLT value decreased from mean value of 266.75±71.36*109/L in PCR negative participants to 241.18±96.64*109/L in PCR positive patients (p=0.002). Conclusion: In our study, it was found that in patients who were admitted to Samsun Training and Research Hospital with COVID-19 suspicion and followed up in COVID-19 services, PT, D-dimer, INR, PLT values were important in detecting Coagulopathy and Thrombocytopenia in the group who were PCR positive according to COVID-19 results. Keywords: COVID-19, PT, aPTT, D-dimer, INR, PLT