Cell viability evaluation is significantly meaningful for cellular assays. Some cells with weak viability are easily killed in the detection of anti-cancer drugs, while others with strong viability survive and proliferate, ultimately leading to the treatment failure or the inaccuracy of biological assays. Accurately evaluating cell viability heterogeneity still remains difficult. This paper proposed a multi-physical property information fusion method for evaluating cell viability heterogeneity based on multiple linear regression (MLR) on a single-channel integrated microfluidic chip. In this method, adhesion strengths τN, that are defined as the magnitude of shear stress needed to detach (100-N) % of cell population, were extracted as the independent variables of MLR model by calculating the linear fitting of the impedance-response curves for shear stress (cell detachment assay). Besides, by calculating the non-linear fitting of the drug dose-response curves for cancer cells (IC50 assay), the half-maximal inhibitory concentration (IC50) was extracted as the dependent variables of MLR model. The results show that the mean relative error of our fusion method reduces by 17.87% and 59.66% compared with the single-parameter method and the cell counting method. Moreover, through the theoretical analysis of the drug resistance heterogeneity model, it proved that there is a qualitative relationship between the cell adhesion strength and cell viability heterogeneity, which provides a theoretical basis for our fusion method.

The increasing attention to precision medicine is widely paid in order to greatly improve the cure rate of cancer. Improving the stability and accuracy of cell viability evaluation is the key of precision medicine, for excess dosage of anti-cancer drugs not only kills the cancer cells, but also does harm to normal cells. Electrochemical impedance sensing (EIS) method is widely accepted as a label-free, non-invasive approach for real-time, online monitoring of cell viability. Due to the large effects of many influencing factors, the existing EIS methods that utilized single-frequency impedances show poor stability and low accuracy of cell viability evaluation. In this paper, we proposed a multi-physical information fusion method based on least squares support vector machine (LS-SVM) for improving the stability and accuracy of cell viability evaluation. The results show that the mean relative error of single-frequency method is about 0.08, while that of fusion method is about 0.04. It means that the prediction results of fusion method are more accurate than that of the single-frequency method. Moreover, the maximum relative error of single-frequency method is up to 0.5 due to the influencing of cell micromotion, while that of fusion method is below 0.07, showing that the fusion method is more stable than single-frequency method.

This case report describes the clinical history of a COVID-19 patient with a non-immediate diagnosis of severe dysphagia that required a gastrostomy positioning. A vocal folds paresis was observed for the first time in the course of a Sars-CoV-2 infection. Thanks to intensive rehabilitation treatment, the outcome was favourable.

Koebner phenomenon regards the formation of a psoriatic lesion after a trauma, including tattoo, insect bite or other injuries. Although this manifestation is not specific for psoriasis, physicians should be aware because early recognition may be helpful in making the diagnosis when present.

Here we report a Turkish child with Ellis-van Creveld syndrome whose presentation was short strature, hypodontia, narrow thorax, dysplastic nails, cardiac abnormality and polydactyly. Genetic analysis revealed novel homozygous mutation in the EVC2 gene (c.3533_3546del). Further research is needed to elucidate the pathophysiological course

In this paper, we consider approximate solutions (also called $\varepsilon$-solutions) for semi-infinite optimization problems that objective function and constraint functions with uncertainty data are all convex, and establish robust counterpart of convex semi-infinite program and then consider approximate solutions for its. Moreover, the robust necessary condition and robust sufficient theorems are obtained. Then the duality results of the Lagrangian dual approximate solution is given by the robust optimization approach under a cone constraint qualification.

Background: The association between subclinical hypothyroidism (SCH) and cardiovascular risk, particularly with a TSH <10µIU/ml, remains controversial. The objective of our study was to assess the association between SCH and cardiovascular risk through carotid intima-media thickness, and alternatively, to evaluate its change after treatment with levothyroxine. Methods: A total of 54 individuals were included in the study, 18 with SCH, 18 with overt hypothyroidism (OH), and 18 healthy controls (HC). The carotid intima-media thickness was measured in each group. In SCH, follow-up was performed at three and six months after the start of levothyroxine. Results: The mean age of the total population at baseline was 35.8 years. The median TSH in SCH was 6.15 µIU/ml. The carotid intima-media thickness was greater in SCH in comparison to the HC group (Right common carotid artery [RCCA, mm]: 0.486 ± 0.106 and 0.413 ± 0.075 in SCH and HC, respectively, p=0.01. Left common carotid artery [LCCA, mm]: 0.511±0.144 and 0.427±0.090 in SCH and HC, respectively, p=0.03). In patients with SCH, there was a decrease in the carotid intima-media thickness after treatment with levothyroxine (RCCA and LCCA p <0.05 at 3 and 6 months). Conclusions: There is an association between an increase in the carotid intima-media thickness in patients with SCH in comparison to HC, even with a TSH <10 µIU/ml. The increase reversed with levothyroxine therapy. Its association with important cardiovascular outcomes remains uncertain and should be evaluated in future studies.

Objectives: Type 2 diabetes mellitus(T2DM) can accelerate the clinical process of atherosclerosis(AS). Dipeptidyl peptidase-4 inhibitors(DPP-4Is) have potential anti-AS effects. And, we completed a meta-analysis of the changes in carotid intima-media thickness(CIMT), flow-mediated dilation(FMD), and pulse wave velocity(PWV) of DPP-4Is to research the effect of DPP-4Is in the progression of AS in T2DM patients. Materials and methods: We included RCTs that evaluated the impact of DPP-4Is on CIMT, FMD, and PWV compared to other treatments from PubMed, Cochrane trials, and Embase database before October 31, 2020. We selected the random-effect model and calculated the weighted mean difference(WMD) to evaluate the effect of CIMT, FMD, and PWV in T2DM patients. Results：Through the meta-analysis, we found that DPP-4Is can significantly reduce CIMT in T2DM patients(WMD =-0.036, 95% CI:-0.055 to-0.017; p≤0.001). Based on the subgroup analysis, we found that CIMT was significantly decreased in patients with greater than 12 months of intervention and without cardiovascular diseases. Besides, we also found that DPP-4Is had a not significant efficacy on the improvement of FMD in T2DM patients(WMD=0.635, 95% CI: -0.112 to 1.383, p= 0.097). Our subgroup analysis showed that for T2DM patients who have cardiovascular diseases, DPP-4Is can significantly increase their FMD. In addition, we also found that DPP-4Is had an insignificant influence on PWV in T2DM patients(WMD= 0.424, 95% CI: -0.198 to 1.046, p= 0.18). but SGLT2 inhibitors may reduce the PWV of T2DM patients. Conclusions: DPP-4Is can alleviate the development of AS in T2DM patients to a certain extent by reducing CIMT. And, we believe that long-term use of DPP-4Is may be more helpful to alleviate the atherosclerotic development of T2DM without obvious cardiovascular history.

Background: Infection after cardiovascular surgery is multifactorial. We sought to determine whether the anthropometric profile influence the occurrence of infection after isolated coronary artery bypass grafting (CABG). Methods: Between January 2011 and June 2016, 1,777 consecutive adult patients were submitted to isolated coronary artery bypass grafting. Mean age was 61.7 ± 9.8 years and 1,193 (67.1%) were males. Patients were divided into four groups according to the Body Mass Index (BMI) classification: underweight (BMI<18.5 kg/m2: N=17, 0.9%), normal range (BMI 18.5 – 24.99 kg/m2: N=522, 29.4%), overweight (BMI 25 – 29.99 kg/m2: N=796, 44.8%) and obese (>30 kg/m2: N=430, 24.2%). In-hospital outcomes were compared and independent predictors of infection were obtained through multiple Poisson regression with robust variation. Results: Independent predictors of any infection morbidity were female sex (RR 1.47, P=0.002), age > 60 years (RR 1.85, P<0.0001), cardiopulmonary bypass > 120 minutes (RR 1.89, P=0.0007), preoperative myocardial infarction < 30 days (RR 1.37, P=0.01), diabetes mellitus (RR 1.59, P=0.0003), ejection fraction < 48% (RR 2.12, P<0.0001) and blood transfusion (RR 1.55, P=0.0008). Among other variables, obesity, as well as diabetes mellitus, were independent predictors of superficial and deep sternal wound infection. Conclusions: Other factors rather than the anthropometric profile are more important in determining the occurrence of any infection after CABG. However, surgical site infection has occurred more frequently in obese patients. Appropriate patient selection, control of modifiable factors and application of surgical bundles would minimize this important complication.

Disulfide bond reduction has been a challenging issue in antibody manufacturing, as it leads to reduced product purity, failed product specifications and more importantly, impacting drug safety and efficacy. Scientists across industry have been examining the root causes and developing mitigation strategies to address the challenge. In recent years, with the development of high-titer mammalian cell culture processes to meet the rapidly growing demand for antibody biopharmaceuticals, disulfide bond reduction has been observed more frequently. Thus, it is necessary to continue evolving the disulfide reduction mitigation strategy and development of novel approaches to achieve high product quality. Additionally, in recent years as more complex molecules emerge such as bispecific and trispecific antibodies, the molecular heterogeneity due to incomplete formation of the interchain disulfide bonds becomes a more imperative issue. Given the disulfide reduction challenges that our industry are facing, in this review, we provide a comprehensive contemporary scientific insight into the root cause analysis of disulfide reduction during process development of antibody therapeutics, mitigation strategies and recovery based on our expertise in commercial and clinical manufacturing of biologics. First, this paper intended to highlight different aspects of the root cause for disulfide reduction. Secondly, to provide a broader understanding of the disulfide bond reduction in downstream process, this paper discussed disulfide bond reduction impact to product stability and process performance, analytical methods for detection and characterization, process control strategies and their manufacturing implementation. In addition, brief perspectives on development of future mitigation strategies will also be reviewed, including platform alignment, mitigation strategy application for bi- and tri-specific antibodies and using machine learning to identify molecule susceptibility of disulfide bond reduction. The data in this review are originated from both the published papers and our internal development work.

Abstract Aim: This study’s aim was to evaluate the epidemiological characteristics of COVID-19 patients and risk factors affecting mortality. Methods: This cross-sectional study included 1003 patients whose PCR (Polymerase Chain Reaction) test were positive for SARS-CoV-2 in XXX province until July 2020. Results: Of the patients evaluated, 88% were adults and 12% of them were children (<18 years old). While 24.2% of all patients, and 40.8% of the patients under the age of 18 were asymptomatic. The most common symptoms in adults were fatigue (47.9%), myalgia (44.7%), loss of smell and taste (32.4%), and the symptoms in children were fever (37.5%), fatigue (12.5%) and myalgia (11.7%). Pneumonia was observed in 35.4% of COVID-19 patients. Pneumonia was associated with advanced age, lack of BCG vaccination, presence of additional disease, hypertension, diabetes mellitus, cardiovascular, respiratory and kidney disease. Overall case-fatality rate was 2.6 percent. The mean age of the patients who died was 76.5 years. The mortality rate in patients over 65 years of age was found to be %11.5. In multivariate analysis, presence of nephrological disease, neurological disease, cardiovascular disease, cigarette exposure, dyspnea, loss of smell and taste, presence of diabetes mellitus, being over 65 years of age, number of drugs used and income status were found to be determinative factors. Conclusion: We found that the independent risk factors for COVID-19 mortality included older age, history of neurological, nephrological, or cardiovascular disease, smoking, and dyspnea symptom. In addition, we found patients with disturbed smell and taste had a better prognosis. Knowing the determinants of mortality can help clinicians to predict patients’ prognosis at an earlier stage. Keywords: COVID 19; epidemiology; pneumonia; mortality

In this work, we apply the notion of D-homothetic deformation on an almost paracontact metric manifolds and show that the structure after the deformation is also almost paracontact metric structure. Also, we state the classes of almost paracontact metric structures having parallel characteristic vector field and get some results about D- homothetic deformations on these classes.

Background and Purpose: The development of effective therapeutic strategies against Alzheimer’s disease (AD) remains a challenge. I2 Imidazoline receptors (I2-IR) ligands have a neuroprotective role in AD. While co-treatment of acetylcholinesterase inhibitors with neuroprotective agents have shown better effects on the prevention of dementia. Here, we assessed the potential therapeutic effect of the I2-IR ligand LSL60101, donepezil and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses of LSL60101 (1mg/kg/day), donepezil (1mg/kg/day), and donepezil plus LSL60101 (1+1mg/kg/day), during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze and three-chamber tests were employed to evaluate the cognitive and behavioural status of the mice after treatment. The effects of the treatments on AD-like pathology were assessed with immunohistochemistry, Western blot and qPCR. Key results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments decreased Aβ-pathology and Tau hyperphosphorylation, and these alterations were accompanied by decreased microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60601 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60601 treatment significantly increased the levels of the synaptic markers post-density 95 (PSD95) and synaptophysin (SYN). Conclusion and implications: Our results suggest that chronic low dose treatment with selective I2-IR ligands can be an effective treatment for AD and provide insights into combination treatments of symptomatic and disease-modifying drugs

Some of the commonly prevalent malignancies may rarely metastasize to aberrant locations in the body. Such cases have not been described adequately in the literature. Two cases presented here show unusual sites of spread, not congruent with present knowledge of metastasis.

This paper presents an iterative analytic algorithm for the approximate solution of nonlinear fractional-order oscillators. He fractional transform was applied to convert the fractional-order model, defined by a modified Riemann-Liouville derivative, to a model in continuous spacetime. Then, the approximate solution of the continuous model was applied to obtain an approximate solution for the fractional-order oscillator. The solution was obtained using the continuous piecewise linearization method (CPLM), which is a simple, accurate and efficient analytic algorithm. The applicability of the CPLM was demonstrated using representative examples in science and engineering and the maximum relative error of the approximate solution was found to be less than 0.2%. This paper provides an analytical tool that can be applied in the study of fractional-order oscillations arising in various physical systems and technological processes.

Title: Misleading Title and Communication.Regarding Brief Communication: First clinical use of real-time remote programming in cardiac implantable electronic devices.  Dr. Toshimasa Okabe et al. J Cardiovascular Electrophysiol. 2020;31:2759-2761. DOI:10.1111/jce.14698Author: Dr. Esteban Martin Kloosterman

HOW ACCURATELY CAN UROLOGISTS PREDICT ELIGIBLE PATIENTS FOR IMMEDIATE POSTOPERATIVE INTRAVESICAL CHEMOTHERAPY IN BLADDER CANCER?Hüseyin Alperen Yıldız a,*, Müslim Doğan Değerb, Güven Aslan ca Department of Urology, Malazgirt State Hospital, Muş, Turkeyb Department of Urology, Edirne State Hospital, Edirne, Turkeyc Department of Urology, Dokuz Eylül University, School of Medicine, İzmir, TurkeyShort Title: CAN UROLOGISTS CHOOSE RIGHT PATIENTS FOR SI?*Corresponding Author: Hüseyin Alperen YıldızMalazgirt State Hospital, Department of UrologyAddress: Saltukgazi Mahallesi, Hastane Cd., Malazgirt, Muş, Turkey, 49400Tel: +902324443511E-mail: h.alperenyildiz@gmail.comAcknowledgments:NoneDisclosure Statement:The authors have no conflicts of interest to declare.Funding Sources:The authors received no specific funding for this work.

Objective: The aim of this study is to evaluate the outcome of ablation therapy in our clinic for the treatment of patients with small renal mass Materials and Methods: We retrospectively evaluated the technic and follow-up data of 30 patients with 36 tumors who underwent Radiofrequency Ablation (RFA) and Microwave Ablation (MWA) in our clinic. Demographic data, ablation type, tumor characteristics, peroperative and postoperative complications and treatment success of the patients were evaluated. Results: A total of 36 tumors who underwent ablation treatments, 23 were treated with RFA, 13 with MWA. The mean tumor size was 28.9 ± 6.92 mm in RFA and 29.3 ± 7.70 mm in MWA. 12 (52.1%) of the RFA procedures were applied to the right kidney while 11 (47.8%) were applied to the left kidney. 6 (46.1%) of the MWA procedures were performed on the right kidney and 7 (53.8%) on the left kidney. Of the 36 tumors, 4 (11.1%) were located central and 32 (88.8%) were peripheral. Complications occurred in 2 patients. In one of these patients, acute renal failure and urea creatinine were found to be elevated. In the other patient, local pain was found in the ablation side and minor bleeding was detected at the ablation site in USG. The mean follow-up period was 49.6 ± 24.7 months in patients with RFA and mean follow-up was 16 ± 8,05 months in MWA treatments. The overall success in MWA administration was calculated as 76.9%, while the overall success in RFA was 80%. Conclusion: Long-term oncologic efficacy of RFA appears to be successful in the treatment of T1a renal carcinomas. Further studies can be conducted to elucidate the influence of MWA on long-term oncological outcomes.

Aim: In this study, we aimed to evaluate the anxiety and depression status of prostate cancer (PCa) patients whose planned operations in the urology clinic of our hospital, which is serving as a pandemic hospital in Turkey have been postponed due to the coronavirus disease 2019 pandemic. Methods: This survey study was conducted at urology clinic of Ankara City Hospital between March 1 and June 1, 2020 and included 24 male patients who agreed to answer the questionnaires (State-Trait Anxiety Inventory [STAI] I and II and Beck Depression Inventory [BDI]). Demographical and clinical data (age, time since diagnosis, total serum prostate specific antigen (PSA) levels, risk groups according to the D’Amico classification system, smoking, alcohol habitus, major surgical history, and comorbidities) of the patients were collected from hospital software. Results: The mean STAI-I score of the patients (46.7 ± 1.4 [44–49]) was significantly higher than their STAI-II score (41.7 ± 2.4 [39–47]) (p < 0.001). The negative correlation between the decrease in age and STAI-I score was found to be statistically significant (r = 0.439, p < 0.05). The mean BDI score of the patients was 4.3 ± 3.2 (0–13), which was compatible with mild depression. There was no statistically significant difference between the time elapsed from diagnosis, PSA levels, smoking and alcohol habitus, major surgical history and comorbidity status, and STAI-I, STAI-II, and BDI scores (p > 0.05). Conclusion: Prostate cancer patients with postponed operations should be guided properly in order to manage their anxiety status especially young patients.

Gli ecosistemi rappresentano una tematica delicata alla quale si sta ponendo sempre più attenzione. L’importanza degli habitat e delle specie animali e vegetali che costituiscono gli ecosistemi ha portato a definire strategie di conservazione a livello europeo concretizzatesi nella Rete Natura 2000. Secondo il rapporto ambientale “State of nature in the UE” dell’European Environment Agency (EEA), pubblicato ad Ottobre 2020, risulta che l’81% degli habitat esaminati si trovano in condizioni scarse o pessime, registrando un trend negativo rispetto al rapporto precedente. Tra le maggiori minacce per la conservazione degli ecosistemi vi è l’azione antropica, le cui incidenze vengono valutate mediante la Valutazione di Incidenza Ambientale (VI). Nel seguente lavoro viene trattato il caso di un aumento di capacità di un impianto di stoccaggio per il trattamento di rifiuti inerti derivanti da processi di demolizione e scavo.

Background COVID‐19 is usually mild, but patients can present with pneumonia, acute respiratory distress syndrome (ARDS) and circulatory shock. Although the symptoms of the disease are predominantly respiratory, involvement of the cardiovascular system is common. Patients with heart failure (HF) are particularly vulnerable when suffering from COVID‐19. Aim of the Review To examine the challenges faced by healthcare organisations, and mechanical circulatory support management strategies available to patients with heart failure, during the COVID-19 pandemic. Results Extracorporeal membrane oxygenation (ECMO) can be lifesaving in patients with severe forms of ARDS, or refractory cardio-circulatory compromise. The Impella RP can provide right ventricular circulatory support for patients who develop right side ventricular failure or decompensation caused by COVID-19 complications, including pulmonary embolus. HT are reserved for only those patients with a high short-term mortality. LVAD as a bridge to transplant may be a viable strategy to get at-risk patients home quickly. Elective LVAD implantations have been reduced and only patients classified as INTERMACS profile 1 and 2 are being considered for LVAD implantation. Delayed recognition of LVAD‐related complications, misdiagnosis of COVID‐19, and impaired social and psychological well‐being for patients and families may ensue. Remote patient care with virtual or telephone contacts is becoming the norm. Conclusions HF incidence, prevalence, and undertreatment will grow as a result of new COVID-19-related heart disease. ECMO should be reserved for highly selected cases of COVID-19 with a reasonable probability of recovery. Special considerations are needed for patients with advanced HF, including those supported by durable LVADs.

Objective: Although elderly patients undergoing surgery for acute type A aortic dissection (ATAAD) is increasing, their physical activities are not fully understood. We report the physical activities and surgical outcomes in the elderly patients who underwent ATAAD. Methods: From 2009 to 2019, 103 consecutive patients underwent surgery for ATAAD at our institution. Surgical outcomes along with pre- and postoperative physical activities in 52 elderly patients (≥70 years old) were compared with those in 51 younger patients (<70 years old). Postoperative walking difficulty was defined as taking ≥30 days to regain the ability to walk 200 m postoperatively or as the inability to walk at discharge. Results: It took longer for elderly patients to regain the ability to walk 100 or 200 m postoperatively. ROC analysis revealed the AUC of the duration for walking 200 m postoperatively as a prognostic indicator for late deaths was 0.878, with the highest accuracy at 30 days (sensitivity = 83.3%, specificity = 91.8%). Hospital mortality within 30 days was 3.8%, and 1-, 3-, and 5-years survival rates were 92%, 84.7%, 84.7%, respectively, for elderly patients, with no significant differences between groups. Cox proportional hazard analysis showed postoperative walking difficulty was an independent risk factor for late mortality in all cohorts (P = 0.017). Conclusions: Elderly patients undergoing surgical ATAAD repair showed acceptable surgical outcomes. However, they were more likely to decrease their physical activities postoperatively. Postoperative difficulty in walking was an independent risk factor for the late mortality in patients with ATAAD.

Type A aortic dissection most often requires emergent surgery to prevent malperfusion, stroke, and/or rupture of aorta. The conduct of the surgery is mostly targeted at restoring true lumen flow. In this regard, institution of cardiopulmonary bypass and circulation management is key to allow adequate systemic flow, perfusion of brain and visceral organs and comprehensive systemic cooling to achieve circulatory arrest when needed. Different strategies have been used with varying success rates, with the most common being femoral cannulation. More recently axillary and central cannulation strategies have shown satisfactory results with the promise of antegrade flow. Cannulation approach should, therefore, depend on individual patient characteristics, presentation and true lumen anatomy.

Rationale, aims and objectives: Consistent data demonstrates negative psychological effects of caregiving on front-line health professionals. Evidence that psychological resilience factors can help minimise distress and the potential for low-cost interventions have created interest in resilience-based development programmes; yet evidence of perceived value amongst health professionals is lacking. This study explored health professionals’ experiences and perceptions of a novel, resilience-based intervention designed to pro-actively prepare staff for coping with error; to investigate their perceptions of what resilience meant to them, the relevance of the intervention, and impact of participation on ability to cope with error. Method: Semi-structured interviews 4-6 weeks post intervention with 23 randomly selected participants from seven cohorts (midwives, paediatricians, obstetrians/gynaecologists, paramedics) and trainees (physician associates, mammographers, sonographers). Thematic analysis of interview data. Findings: Participants reported various interpretations of, and a shift in perception regarding what the concept of psychological resilience meant to them and their practice. These included for example, resilience as a positive or negative concept and their awareness and response to a range of personal, organisational and system factors influencing personal resilience. They valued the prophylactic, clinically relevant, interactive and applied nature of the intervention; having developed and applied valuable skills beyond the context of involvement in error, noting that individuals needed to be willing to explore their own coping mechanisms and human fallibility to gain maximum benefit. There was also consensus that whilst proactively developing individual level psychological resilience is important, so too is addressing the organisational and system factors that affect staff resilience which are outside individual staff control. Conclusion: Enhancing resilience appears to be considered useful in supporting staff to prepare for coping with error and the wider emotional burden of clinical work, but such interventions require integration into wider system approaches to reduce the burden of clinical work for health professionals.