Global warming has affected and continuously changed the hydrometeorological variables such as Rainfall, temperature, and humidity. The present research has focused on the long-term trend of spatio-temporal pattern of rainfall using Mann-Kendall (MK) and innovative trend analysis (ITA), which is the most preferable task for climate change monitoring caused by global warming. The comparative analysis has been performed for eleven meteorological stations of Tumakuru district, India during the year 1952-2019, which reveals the sensitivity of ITA to hidden trends than the classical approach and its reliability towards the mitigation of water-related issues, meteorological drought, and flood management.

Background: Nyiragongo Volcano erupted, and disturbed preventive measures taken by Rwanda to curb the pressure of COVID-19 pandemic transmission. About 232,433 Congolese left their home, and of them, more than 8000 people crossed the border to Rwanda, which disturbed COVID-19 pandemic preventive measures. Objective: This study sought to find out whether the rise in Covid-19 in Rwanda was caused by volcanic eruption in either the exposed area of Rubavu district due to suddenly unpredicted eruption or spread throughout some neighboring areas via Kigali due to the earthquakes. Both Mathematical model and a sequential mathematical preliminary were used. Methods: A sequential mathematical preliminary of Covid-19 was considered to check how it spreads within a large number of population. The model diagram was proposed with four compartmental model. The nonlinear dynamical system was derived from the model. The model was checked for positivity and boundedness in a system. The basic reproduction number was computed using the next generation Matrix. Results: We found that COVID-19 pandemic was positively invariant in a system. The transmission rate was observed with 〖(R〗_0= 25.51). The transmission rate was great than what was determined before the eruption of Nyiragongo Volcano (Ro=3). Since R_0= 25.51 the disease is high in the system. As of the study based, the results finally showed that the rise in Covid-19 in Rwanda was caused by volcanic eruption. Preventive measures should be reinforced by providing a place where people should be kept in case of natural disasters and wars in neighboring countries.

IntroduzioneQuesto elaborato si pone l’obbiettivo di descrivere e analizzare le modalità produttive del genere horror di casa Universal, nel cosiddetto periodo classico di Hollywood.Dietro al successo di un genere, nell’era dello studio system 11Brunetta, Gian Piero, ed. Storia del cinema mondiale . Vol. 2. Einaudi (IT), 1999, non esiste solo un importante componente estetica di carattere prettamente filmico, cinematografico, ma anche, e soprattutto, un insieme di decisioni produttive, un programma distributivo, contratti col personale artistico, un casting e una scelta dei collaboratori, una previsione dei gusti del pubblico, amministrazione delle riprese e del budget, la compra vendita di licenze, accordi con gli esercenti ecc…Tutto questo e molto altro si nasconde dietro ad un film, o ad un genere, prodotto da questa o quella casa di produzione in un periodo in cui, ad Hollywood, il cinema era, sì un evento culturale, ma anche e soprattutto una grande azienda profittevole.Il cinema americano è un’arte classica, ma perché non ammirare in essa ciò che è più ammirevole? Cioè non solo il talento di questo o quel regista, ma anche e soprattutto il genio del sistema 22Schatz, Thomas. The genius of the system: Hollywood filmmaking in the studio era . Macmillan, 1996 (Bazin, 1958)L’elaborato passerà in rassegna un po’ di storia della casa Universal, per capirne le radici ideologiche, fino ad arrivare all’età del sonoro, così da concentrarsi sullo sviluppo e successo dell’horror nella casa, e descrivere come e perché ci si dedicò a questa tipologia di film.

In this paper, we study different ways for introducing memory to a parametric family of optimal two-step iterative methods. We study the convergence and the stability, by means of real dynamics, of the methods obtained by introducing memory in order to compare them. We also perform several numerical experiments to see how the methods behave.

Differences in rainfall partition into throughfall among different primeval forests distributed along an altitude gradient are inadequately investigated and understood. Through continuous and automatic monitoring of natural rainfall and throughfall along an elevation gradient on Mountain Gongga, we examined the response of throughfall to various rainfall patterns in the broadleaved forest (BF), broadleaved-coniferous mixed forest (MF) and coniferous forest (CF) across individual rain events from May to October in 2019. A series of linear models that estimate throughfall amount were obtained and compared. Results showed that throughfall was jointly controlled by rainfall characteristics (including amount, duration, average and peak intensity) and leaf area index (LAI). Rainfall amount was the primary control for throughfall amount. The models with all rainfall parameters and LAI as variables did not markedly outperform (R2 enhancement by 0-0.02) than the simple linear models with rainfall amount as the only variable; therefore, the latter are recommended due to simplicity and easiness of use. Although the correlation of throughfall with LAI was less prominent compared to rainfall parameters, LAI showed a significant positive linear correlation (p < 0.05) with the estimated rainfall amount threshold (the rainfall required to saturate the canopy) by the single-variable linear models at the monthly scale. Over the study period, penetration proportions of rainfall in BF, MF and CF were 83%, 75% and 80%, respectively. The rainfall amount threshold in CF (0.70 mm) was less than those in BF (0.80 mm) and MF (0.92 mm). Rain events of higher intensity exhibited a higher mean penetration proportion than lower intensity rain events. The use of single-variable linear models developed here, despite some overestimations of throughfall amount, could lead to an overall satisfactory estimation of rainfall redistribution in mountainous areas.

Background Preterm birth is the main cause of child death under 5years of age.The incidence of twin pregnancies is less than 2%, but the incidence of preterm delivery is 50% and the risk of neonatal death is 5 times higher in twin pregnancies than in singleton pregnancies.However,there is still no consensus on the effect of cervical pessary on preventing preterm delivery, prolonging the pregnancy cycle, and improving maternal and infant outcomes in patients with twin pregnancies. Objectives To explore the effect of cervical pessary on the pregnancy outcome of unselected twin pregnancy patients. Search Strategy Up to July 2021,researchers searched PubMed, EMBASE, COCHRANE, Web of Science, Wanfang, Weipu, and CNKI databases for research. Selection Criteria Randomized controlled trials that compared cervical pessary with standard care (no pessary) or alternative interventions(conventional and standard treatment (e.g.Atoxiban therapy) or vaginal progesterone) in patients with twin pregnancies. Data Collection and Analysis Two authors（W-Y and M-D）independently extracted information related to the study characteristics and test results from each of the included literature, and used Revman 5.3 to analyze the data. Conclusion The cervical pessary can extend the gestational week of short-cervix twin pregnancy without clinical symptoms, reduce the premature birth rate before 34 weeks of gestation, improve pregnancy outcome, reduce neonatal mortality, reduce necrotizing enterocolitis incidence, neonatal sepsis incidence, and improve neonatal outcome.

The pharmacokinetic rationale of Ivermectin for COVID-19 therapy.Alfonso Duenas-GonzalezUniversidad Nacional Autonoma de Mexico Instituto de Investigaciones Biomedicas.Ivermectin can claim the title of ’wonder drug.’ It has a significant impact on the health and well-being of humankind. Initially approved in humans in 1987 for onchocerciasis, Ivermectin has improved billions of people’s well-being worldwide. Moreover, Ivermectin is used to treat billions of livestock and pets worldwide, helping boost the production of food and leather products and keep billions of companion animals healthy. Nowadays, Ivermectin is taken annually by close to 250 million people [1].The ”revival” of Ivermectin stems from its repurposing for COVID-19. The massive interest in this drug is evident from the hundreds of published studies that is only exceeded by its high presence in the press involving doctors, scientists, the general public, and health and global regulatory organizations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the World Health Organization (WHO). We could summarize that scientific evidence suggests but does not prove its efficacy. From a regulatory and political perspective, the world’s most influential health regulatory authorities, such as the FDA, the EMA, and the WHO, explicitly do not recommend its use outside of clinical trials. In the last of a series of publications entitled ”Timeline of ivermectin-related events in the COVID-19 pandemic”, the author concludes that the Ivermectin controversy for COVID-19 will remain out of reach if scientists are riddled with subconscious biases, fundamentally unsound methodologies, and dominancy of commercial interests [2].Here we comment on the issue of Ivermectin dose, an overlocked pharmacokinetic (PK) key factor in the current clinical development of Ivermectin for COVID-19 therapy. In January 2020, Caly and colleagues reported that Vero‐hSLAM cells treated with 5 μM Ivermectin after two hours post-infection with SARS‐CoV‐2 reduces the viral RNA load by 99.98% at 48 hours [3]. This finding initiated the avalanche of finished and ongoing clinical trials of Ivermectin for the disease. Of note, all trials have used the recommended standard dose as antiparasitic (usually 200-400 μg/Kg, or 600 μg/Kg the fewer) either a single dose or daily for three consecutive days. In March 2021, a letter published in BJCP stated that the 99.98% viral load reduction at 5 μM for 48 h concentration is not achievable clinically. The authors stated that at the highest reported dose of Ivermectin, approximately 1700 μg/Kg (8.5 times the FDA‐approved dose of 200 μg/kg), the Cmax was only 0.28 μM [4]. Since then, at the time of this writing, 26 clinical trials or meta-analyses argue on ”unattainable Cmax” as a partial explanation for the unsatisfactory results of Ivermectin for COVID-19 treatment. International press as well discourages its use, arguing that ”horse doses” are needed.Surprisingly, Cmax and not the Area Under the Curve (AUC), which relates to both concentration and time, is taken as the determining PK parameter of the efficacy of Ivermectin for COVID-19. Antimicrobial agents are generally classified into three classes based on in vitro pharmacodynamics (PD) drug effect: 1) Time>MIC(Minimal Inhibitory Concentration) -time-dependent - 2) Cmax/MIC-concentration-dependent - or 3) AUC/MIC -concentration/time-dependent -. Asit can be seen, the factor of time of exposure is present in these three classes asMIC accounts for concentration and time.A key PK/PD aspect on the efficacy and toxicity of most drugs relates to the drug concentration-time at a receptor site to biological response. Since the drug concentration at the receptor site can rarely be measured directly, it is more usual to measure the drug concentration in the plasma and assume that it reflects that at the receptor site. From this, it can be appreciated that plasma concentration alone may mean nothing if time (duration of exposure) is not accounted for. Therefore, the Cmax only informs on the plasma concentration’s peak (amount of drug/volume) after a dose. Thus, what matters is how much drug is circulating in the plasma per unit of time (h/mL) and, therefore, be available to reach its potential site of action, which is measured by the AUC μg/h/mL (amount/time/volume).Accordingly, the first randomized trial demonstrating improved survival in acute lymphoblastic leukemia in children used the AUC as a target and not the Cmax [5], which is not surprising as the in vitro cytotoxicity of antineoplastic drugs depend on both drug concentration and duration of drug exposure. Recent reviews show that for both cytotoxic and targeted anticancer agents, response and toxicity correlate with drug exposure, reflected in the AUC [6,7]. Translating this information to Ivermectin, it is clear that the Cmax of 5 µM, which reduces 99.98% of the viral load, is not clinically feasible. However, the AUC (5,249 µM/h) that reflects the plasma concentration of the drug over time is achievable when using a dose of 2 mg/Kg. Table 1 shows these data estimated at different doses. It also shows that at a dose of 2 mg/Kg in a 5-day scheme, said concentration is reached since day 2 and on. Moreover, it shows that no significant dose accumulation occurs as the steady-state is reached at day 9.In the Oncology arena, using the drugs pharmacokinetic information [8] and the IC50 to 1000 human cancer cell lines (https://www.cancerrxgene.org), we observe that among 32 agents, 28 have a Cmax well below (18.3-fold less) the corresponding IC50 in cancer cell lines (median Cmax1.0 µM (0.021-133), and median IC50 13.8 µM (1.32-80.1). Despite that, these 28 drugs are FDA-approved because they are efficacious. Remdesivir, the only drug FDA-approved for COVID-19, shows an EC50 of 26.9 µM [9] while the Cmax is 5.504 µM (5-fold less) [10]. Should Cmax were the parameter to correlate with clinical feasibility and efficacy, none of these compounds, including remdesivir, could have developed.In summary, the dose needed of Ivermectin to reduce 99.98% of the viral load in vitro is clinically feasible. It could be 2 mg/Kg, which appears safe. Ideally, a dose-finding study with PK/PD correlations should be done before beginning phase III clinical trials. As there is no commercial interest in developing Ivermectin and only independent researchers with limited resources can do it, it is imperative to optimize the studies to establish whether Ivermectin is useful for treating COVID-19. It is a fact that today, almost a third of the world population (28%) uses Ivermectin to treat COVID-19; hence the need for refuting or confirming its efficacy is paramount. (https://ivmstatus.com).

Introduction: In critically ill patients, Transfusion Related Acute Lung Injury (TRALI) remains the leading cause of transfusion-related fatalities in critical care setting and associated with inflammation and oxidative stress state. Recent research raised the potential efficacy of high dose intravenous ascorbic acid in critically ill patients. Objective: The aim of this trial was to investigate the effect of high dose intravenous ascorbic acid (VC) as a targeted therapy for TRALI in terms of serum proinflammatory (interleukin-8, interleukin-1β, C-reactive protein), anti-inflammatory (interleukin-10), oxidative stress (superoxide dismutase, malondialdehyde) markers, and plasma VC levels. Secondary outcomes were oxygenation (PaO2/FiO2 ratio), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality. Methods: Eighty critically ill patients with TRALI (n=80) were randomized to receive 2.5gm/6hr intravenous vitamin C for 96 hours (ASTRALI group) or placebo. Patients were followed-up to measure the outcomes initially (T0) and at the end of treatment (T96). Results: When compared to control group, ASTRALI group at T96, showed significantly higher median of interleukin-10 (31.6 ± 25.8 Vs. 17.7 ± 12.0 pg/mL, p<0.0001) levels and superoxide dismutase (12876 ± 4627 U/L Vs. 5895 ± 6632 U/L, p<0.0001) activities, lower median C-reactive protein (76 ± 50 Vs. 89 ± 56 mg/L, p=0.033), interleukin-8 (11.8 ± 7.3, 35.5 ± 19.8 pg/mL, p<0.0001), and malondialdehyde (0.197 ± 0.034 Vs. 0.234 ± 0.074 µM/L, p=0.002) levels. Conclusion: High dose ascorbic acid was associated with significantly reduced oxidative stress, reduced pro-inflammatory markers except IL-1β, elevated anti-inflammatory marker, and elevated plasma VC levels

Toluene diisocyanate (TDI) is an important chemical intermediate prepared by phosgenation reaction between toluene diamine and phosgene with two steps name cold and thermal phosgenation respectively. In this paper, the reactive distillation model for the thermal phosgenation reaction based the kinetics equations was established for an industrial installation, and the effects of the different parameters on the process performance were studied firstly; then based on the analysis results, a thermal coupling process between the towers of reactive distillation and phosgene purification was presented and investigated; finally, the optimal operation scheme was simulated and the results showed that the proposed process can save the heat and cold energy with 7.29% and 32.78%, respectively, and reduce the total annual cost about 17.11%. The result of the paper can be used to guide the operation configuration or the revampment of the TDI production equipment.

Aim and Methods: Erenumab and galcanezumab have shown great results for migraine prevention in several clinical trials. However, strict inclusion criteria, absence of concomitant medication and selective outcome report may sometimes be barely representative of the real-world daily practice. Therefore, this observational, retrospective, non-comparative study was aimed to evaluate the effectiveness and safety of erenumab 140 mg and galcanezumab 120 mg in real-world patients with difficult-to-treat episodic or chronic migraine, who previously did not respond to up to three well-stablished pharmacological alternatives for migraine prevention. A combination of objective well-defined tools and vastly used patient reported outcome measurements were evaluated at baseline and after the administration of 3 and 6 doses. Results: from 180 patients, 142 matched inclusion criteria for the present study. Data here reported shows that erenumab and galcanezumab reduced mean headache days, acute migraine specific medication days, Headache Impact Test score, Migraine Disability Assessment Test score and Visual Analogue Scale score after 3 and 6 doses in real-world patients diagnosed with difficult to treat chronic or episodic migraine (p<0.01). Moreover, acute migraine specific medication days were reduced by a half in, at least, a 50% of the patients enrolled in each of the groups of the study. Both treatments exhibited a great safety profile, rarely leading to discontinuation because of poor tolerance. Conclusions: Erenumab and galcanezumab seem effective and well tolerated for migraine prevention in real-world patients with episodic or chronic migraine who previously failed to oral preventive therapies.

   In this paper we will present a new exact formula for the fine-structure constant in terms of the golden angle,the relativity factor and the fifth power of the golden mean. A new interpretation and a very accurate value of the fine-structure constant has been discovered in terms of the golden radio. We propose the exact equivalent mathematical expression for the proton to electron mass ratio using Fibonacci and Lucas numbers and two other exact mathematical expressions for the proton to electron mass ratio. We present the exact mathematical expressions that connect the proton to electron mass ratio and the fine-structure constant. Also we will find a new formula for the Planck length and a new formula for the Avogadro's number. First we will find the beautiful unity formula that connects the gravitational coupling constant and the fine-structure constant. This equation is the simple unification of the  gravitational and the electromagnetic interactions. We will present the exact mathematical formulas that connect six dimensionless physical constants. The six dimensionless physical constants are the proton to electron mass ratio μ,the fine-structure constant α,the ratio Ν1 of the electric force to the gravitational force between electron and proton,the Avogadro's number NA,the gravitational coupling constant αG of the electron and the gravitational coupling constant αG(p) of the proton. Also we will find a new formula for the gravitational constant G. Finally we will be presented the formula for the cosmological constant Λ. This unity formula is a simple analogy between atomic physics and cosmology.  All these equations are simple,elegant and symmetrical in a great physical meaning.

INTRODUCTION. Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness in young children and can also cause influenza-like illness (ILI). Here we investigated the epidemiological features of RSV infection in pediatric ILI cases in Lombardy (a region in Northern Italy accounting nearly 10-million inhabitants) from 2014-2015 to 2020-2021 winter seasons. MATERIAL AND METHODS. Data for this study were retrieved and statistically analyzed from the database of virological influenza surveillance of the regional reference laboratory for Lombardy within the Italian influenza surveillance network (InfluNet). RESULTS. RSV accounting for nearly 19% of pediatric ILI with a risk of infection nearly 2-fold greater than that of individuals ≥15 years. The RSV positivity rate increased to 28% considering 0-5 years old children. Although in children ≤5 years the risk of infection from influenza viruses resulted nearly 2-fold higher than the risk of RSV infection, the age group 4-6 months and 7-12 months showed 5-fold greater risk of infection from RSV than from influenza. Children ≤5 years of age with presence of one or more comorbidities had a nearly 5-fold greater risk of getting RSV infection than otherwise healthy 0-5 years old children. DISCUSSION. The use of the ILI sentinel surveillance allowed us to identify groups at higher risk of RSV and influenza infection and to define the start, duration, timing and intensity of the RSV and influenza community circulation, determining thresholds based on historical data. This surveillance approach can be implemented to assess the nearly real-time RSV circulation and impact.

Background and Aim: We showed in our anatomical review, ventricular septal defects existing as multiple entities can be considered in terms of three major subsets. We address here the diagnostic challenges, associated anomalies, the role and techniques of surgical instead of interventional closure, and the outcomes. including reinterventions, for each subset. Methods: We reviewed 80 published investigations, noting radiographic findings, and the results of clinical imaging elucidating the location, number, size of septal defects, and associated anomalies, and the effect of severe pulmonary hypertension. Results: Overall, perioperative mortality for treatment of residual multiple defects has been cited to be between zero and 14.2%, with morbidity estimated between 6% to 13%. Perioperative mortality is twice as high for perimembranous compared to muscular defects, with need for reoperation is over four times higher. Perventricular hybrid approaches are useful for closure of high anterior or apical defects. Overall, results have been unsatisfactory. Pooled data reveals incidences between 2.8% and 45% for device-related adverse events. Currently, however, outcomes cannot be assessed on the basis of the different anatomical sub-sets. Conclusions: We have addressed the approaches, and the results, of therapeutic treatment in terms of co-existing discrete defects, the Swiss-cheese septum, and the arrangement in which a solitary apical muscular defect gives the impression of multiple defects when viewed from the right ventricular aspect. Treatment should vary according to the specific combination of defects.

We experienced an advanced breast cancer patient who failed to receive diagnostic imaging despite regular video conferences with her physician during the COVID-19 pandemic, resulting in delayed liver metastasis detection. Recognizing shortcomings of telemedicine and collaboration among medical institutions for uninterrupted cancer care is imperative during the pandemic.

In March 2021, Lao People’s Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam, and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.

Due to its availability and minimal invasive harvesting human adipose tissue-derived extracellular matrix (dECM) is often used as a biomaterial in various tissue engineering and healthcare applications. Next to dECM, cell-derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. So far both types of ECM were investigated extensively towards their application as (bio)material in tissue engineering and healthcare. However, a systematic characterization and comparison of soft tissue dECM and cdECM is still missing. In this study, we characterized dECM from human adipose tissue, as well as cdECM from human adipose-derived stem cells (ASCs), towards their molecular composition, structural characteristics, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans (sGAGs) compared to cdECMs. Structural characteristics revealed an immature state of the fibrous part of cdECM samples. By the identified differences, we aim to support researchers in the selection of a suitable ECM-based biomaterial for their specific application and the interpretation of obtained results.

In the age of the next-generation computer, the role of the cloud, the internet, and smart devices will become stronger. These days we all know the word smart well. This word is often used in our daily lives. The Internet of Things (IoT) will generate a variety of information from a variety of resources. It can store big data in the cloud. Fog computing acts as a signal between the cloud and IoT. Fog extensions in this framework apply to the material under IoT. IoT devices are called Fog nodes, which can be accessed anywhere within the network range. A blockchain is a novel way of recording in a secure sequence. Creating a new framework in the development of the Internet of Things is one of the critical problems of wireless communication. Solving such a problem can lead to continued growth in the use and popularity of IoT. Proposed research creates a framework for providing a framework for middleware on the internet of smart devices network for using blockchains technology. Our great offering connects new research that integrates blockchains into the Internet of Things and provides a secure Internet connection for smart devices. Blockchain (BC) Internet of Things (IoT) is a new technology that works with low-level, distributed, public, and real-time leaders to maintain transactions between IoT sites. A blockchain is a series of blocks. Each block is linked to its previous blocks. All blocks have cryptographic hash code, previous block hash, and its data. Transactions in BC are the basic components used to transfer data between IoT nodes. IoT nodes are a variety of portable but smart devices with embedded sensors, actuators, systems, and the ability to communicate with other IoT nodes. The role of BC in IoT is to provide a process for processing secure data records using IoT nodes. BC is a protected technology that can be used publicly and openly. IoT requires this type of technology to allow secure communication between IoT nodes in different environments. Events in BC can be tracked and monitored by anyone who is certified to communicate within IoT.

Some studies had shown that there is a relationship between the state of the economy of a country and COVID-19 incidence and mortality rates. However, these studies are mostly done on countries that are already developed. This study aims to find the relationship between GDP and GDP per capita and COVID-19 incidence and mortality rates in all countries. In addition, they will also be analyzed based on their different income levels. The data collected are from databases from World Bank and WHO and are analyzed through MS Excel and JASP. Spearman’s rho is used to analyze the overall data and stratified data. It has been found that the GDP per capita and incidence (rs = .656, p < .001) and mortality rates (rs = .521, p < .001) have a strong and moderate correlation, respectively. GDP’s relationship with incidence (rs = .295, p < .001) and mortality rates (rs = .346, p < .001) resulted in both weak correlations. Stratified analysis resulted in no significant relationships, except for GDP per capita’s relationship with incidence (rs = .362, p = .011) and mortality rates (rs  = .348, p = .014) in low-middle countries, which yielded both weak correlations. These results show that there is indeed a relationship between the incidence and mortality rates and the economic status of a country before a pandemic, however, more factors need to be accounted for in order to help countries improve their pandemic response in the future.

Objective: To explore a new index that predict lymph node metastasis(LNM) of ovarian cancer(OC). Design: A cross-sectional study of two medical centers. Setting: Two medical centers from Nantong, China. Sample: There were 447 patients included as the training set meanwhile 284 patients were included in the validation set. Methods: A total of 447 patients diagnosed with OC from January 2008 to June 2019 were included in this retrospective study as the training set. A total of 284 patients were included in the validation set. The optimal cut-off critical value of indicator CA125 combined with D-dimer(ICD) was evaluated by the receiver operating characteristic curves(ROC), and the maximum Youden index (sensitivity + specificity-1). Univariate and multivariate analysis were used to evaluate ICD as a predictor of LNM in OC. Main outcome measures: LNM burden. Results: According to ROC curve, area under curve(AUC) of ICD (AUC=0.706, p<0.001) was significantly larger than that of CA125 (AUC=0.671, p<0.001) and D-dimer (AUC=0.562, p=0.022) alone. Multivariate analysis showed that ICD (HR 2.651, 95% CI 1.273–5.520, p=0.009) was an independent predictor of LNM rather than overall survival(OS) in OC. It has also been verified in another medical center. Conclusions: ICD can be used to screen and predict the development process of OC. ICD is an independent predictor of LNM in ovarian cancers, which is helpful for clinicians to draw up individual treatment plans. Funding Scientific Research Project of “333 Project” in Jiangsu Province (BRA2019030). Nantong Science and Technology Foundation grant (MS22019008). Keywords: OC, CA125, D-dimer, ICD, NLM

Medulloblastoma is a highly malignant frequent paediatric brain tumor. It can be misdiagnosed for other diseases when symptoms are non-specific and neurological examination is normal during evaluation. Physicians must be vigilant not only of suggestive neurological status but also of non -specific symptoms that are persistence and recurring in nature.

Bronchial chondromas are very rare pulmonary benign tumors. Despite their rarity, clinicians should pay attention to the possibility of endobronchial tumor in patients with unexplained respiratory symptoms. Treatment modalities for complete excision of the tumor should be initiated to prevent complications and malignant transformation based on the individual tumor situation,

In vitro systems serve as compact and manipulate models to investigate interactions between different cell types. A homogeneous population of cells predictably and uniformly responds to external factors. In a heterogeneous cell population, the effect of external growth factors is perceived in the context of intercellular interactions. Indirect cell co-cultivation allows one to observe the paracrine effects of cells and separately analyze cell populations. The article describes an application of custom-made cell co-cultivation systems based on protein membranes separated from the bottom of the vessel by the 3d printed holder or kept afloat by a magnetic field. Using the proposed co-cultivation system, we analyzed the interaction of A549 cells and fibroblasts, in the presence and absence of growth factors. During co-cultivation of cells, the expression of genes of the activation for epithelial and mesenchymal transitions decreases. The article proposes the application of a newly available system for the co-cultivation of different cell types.

Glycation on lysine side chains of recombinant monoclonal antibodies (mAb) is a well known phenomenon in manufacturing processes of biopharmaceuticals that potentially alter the efficacy of the therapeutic protein. Previously, we reported a method to quantify the level of glycation formation directly from cell culture supernatants using boronate affinity chromatography (BAC). In this study, we report kinetic studies of glycation formation of the model protein Adalimumab, related to glucose and non-glycated protein in six CHO fed batch cultivations. An in-vivo model was demonstrated from glycation kinetic studies that is capable of estimating the reaction rate constant in static and dynamic bioprocesses, respectively. As anticipated, pseudo first order reactions with respect to present glucose concentration or non-glycated mAb were not sufficient to describe the glycation formation during the bioprocesses. However, second order reactions did not reveal linear relationship of glycated mAb to the product of glucose and non-glycated mAb, suggesting a reconsideration of kinetic equation. With the introduction of a constraint using only the newly formed product, i.e., the nascent protein, the second-order reaction was successfully implemented. These results show that the process knowledge derived from dynamic can be transferred to static experiments and vice versa. Hence, intensified DoE can be an applicable and useful tool in product quality studies in cell culture processes.

The present study is focused on designing an easy-to-use novel perfusion system for articular cartilage (AC) tissue engineering and using it to elucidate the mechanism by which interstitial shear upregulates matrix synthesis by articular chondrocytes (AChs). Porous chitosan-agarose (CHAG) scaffolds were synthesized, freeze-dried, and compared to bulk agarose (AG) scaffolds. Both scaffold types were seeded with osteoarthritic human AChs and cultured in a novel perfusion system for one week with a shear-inducing medium flow velocity of 0.33 mm/s corresponding to an average surficial shear of 0.4 mPa and a CHAG interstitial shear of 40 mPa. While there were no statistical differences in cell viability for perfusion vs. static cultures for either scaffold type, CHAG scaffold cultures exhibited 3.3-fold higher (p<0.005) cell viability compared to AG scaffold cultures. Effects of combined superficial and interstitial perfusion for CHAG showed 150- and 45-fold (p<0.0001) increases in total collagen (COL) and 13- and 2.2-fold (p<0.001) increases in glycosaminoglycans (GAGs) over AG’s scaffold non-perfusion and perfusion cultures, respectively, and a 1.5-fold and 3.6-fold (p<0.005) increase over non-perfusion CHAG cultures. Contrasting CHAG perfusion and static cultures, chondrogenic gene comparisons showed a 3.5-fold increase in collagen type II/type I (COL2A1/COL1A1) mRNA ratio (p<0.05), and a 1.3-fold increase in aggrecan mRNA. Observed effects are suggested to be the result of inhibiting the inflammatory NF-κB signal transduction pathway as confirmed by a further study that indicated a reduction by 3.2-fold (p<0.05) upon exposure to perfusion. Our results demonstrate that the presence of pores plays a critical role in improving cell viability and that interstitial flow caused by medium perfusion through the porous scaffolds enhances the expression of chondrogenic genes and ECM components through the downregulation of NF-κB1.