Objective: To analyze the effect of a novel second-line escalating treatment strategy (high-dose dexamethasone (HDD), low-dose rituximab to eltrombopag) for children with severe chronic immune thrombocytopenia (SCITP). Materials and Methods: This study was a single-center, retrospective cohort study. The second-line escalating strategy included 3 steps: Step I (6 courses high-dose dexamethasone: HDD), Step II (HDD combined with low-dose rituximab), and Step III (eltrombopag). Results: A total of 30 cases (18 males and 12 females) were included; the median age was 8.83 (1.42-13.9) year-old, the duration time of ITP was 20.5 (12.0-96.0) months, and the platelet counts were 15 (3-29) ×109/L. After the median 14 (12-37) months’ treatment, the remission rate was 36.7% (11/30), and the sustained response (SR) rate was 68.2% (15/22). In eltrombopag (step III) cases, 47.5% (8/17) maintained platelet ≥50×109/L, 37.5% (3/8) dose tapering, and 25% (2/8) were successfully discontinued from medication. The number of patients at 12th, 24th, and 36th months was 30, 7, and 2, with the total response (TR) and remission rates of 80% (36.7%), 57.1% (28.6%), and 50% (50%), respectively. The total relapse rate was 26.7% (8/30)，three cases(75%, 3/4)from Step II and 5 cases (41.7% ,5/12)from Step III, none in Step I. Conclusion: The new second-line escalating strategy for children SCITP has an effective improving rate with 36.7% remission and 68.2% SR; 30% could benefit and retain stable response from HDD treatment. Combined treatment with eltrombopag can reduce the relapse rate of low-dose rituximab.

Reproductive isolation is often achieved when genes that are neutral or beneficial in their genomic background become functionally incompatible in a foreign genome, causing inviability, sterility or low fitness in hybrids. Recent studies suggest that mitonuclear interactions are among the initial incompatibilities to evolve at early stages of population divergence across taxa. Yet, it is unclear whether mitonuclear incompatibilities involve few or many regions in the nuclear genome. We employ an experimental evolution approach starting with unfit F2 interpopulation hybrids of the copepod Tigriopus californicus, in which compatible and incompatible nuclear alleles compete in a fixed mitochondrial background. After about nine generations, we observe a generalized increase in population size and in survivorship, suggesting efficiency of selection against maladaptive phenotypes. Whole genome sequencing of evolved populations showed some consistent allele frequency changes across the three replicates of each reciprocal cross, but markedly different patterns between mitochondrial background. In only a few regions (~6.5% of the genome), the same parental allele was overrepresented irrespective of the mitochondrial background. About 33% of the genome shows allele frequency changes consistent with divergent selection, with the location of these genomic regions strongly differing between mitochondrial backgrounds. The dominant allele matches the mitochondrial background in 87 and 89% of these genomic regions, consistent with mitonuclear coadaptation. These results suggest that mitonuclear incompatibilities have a complex polygenic architecture that differs between populations, potentially generating genome wide barriers to gene flow between closely related taxa.

The variance tendency of climatic and spatial-temporal equilibrium characteristics of major cities along the SREB were systematically described through moving mean method, Kriging interpolation method, Bernaola-Galvan algorithm and correlation analysis based on monthly scale data of global weather stations released by the National Climatic Data Center website since 1951. Some conclusions cloud be drawn: (1) The precipitation showed a downward trend in other districts with significant seasonal differences except the Europe. The annual precipitation was “N” type distribution in Central Asia, while showed an “inverted V” and a “positive V” distribution in the East Asia and West Asia respectively, and the precipitation change was relatively gentle in Europe. The dominant factors affecting climate were different in different districts. (2) The temperature continued to increase in all districts and the seasonal temperature presented unimodal distribution, the alternation of drying and wetting was obvious in each districts as well as the temperature was complex and changeable in Europe. (3) The mutation point of temperature was detected by using Bernaola-Galvan algorithm in all districts, but the timing of the mutation was not synchronous and the mutation point of precipitation was not detected except in Europe. (4) The precipitation was decreasing from west to east in space, and the temperature showed the morphological distribution characteristics of of low in the middle but high on both sides. (5) The change of temperature were more sensitive than precipitation, the precipitation in Central Asia was inversely correlated with other districts, however, there was a high positive correlation between temperature in all districts. The inversely correlation between temperature and precipitation was the most significant in Central Asia.

Title: Comment on: A pilot study of ruxolitinib as a front-line therapy for 12 children with secondary hemophagocytic lymphohistiocytosisAuthors: Huan Xu1, Hongbo Chen1Affiliations: 1 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCorrespondence: Hongbo Chen, Address: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China, Telephone: +86-13006114930, Email: hbchen@hust.edu.cn.Word Count for Main Text: 505Running Heads： Ruxolitinib therapy for HLH in childrenKeywords: Ruxolitinib, HLH, therapy

A document by Jonathan Marron. Click on the document to view its contents.

Background: Bedqauiline (BDQ) is a relatively new agent for multidrug (MDR) and extremely drug resistant (XDR) TB. It is important to look for cardiac safety and the bizarre adverse reactions after initiation of the drugs from the real world studies. Methods: An observational study was conducted on the institutionalized MDR and XDR patients under the conditional access program of BDQ in India. Daily ECG, adverse events and change in laboratory values for first two weeks were recorded with mortality and serious adverse events till first three months of initiation of BDQ containing regimen. Results: Among the total of 49 patients, nausea (n=33) was the most reported side effect. Though a mean rise of QTcF (12%) was noted after 14 days, individually, both prolongations (QTcF >440 ms) and shortening (from baseline values) of QTcF were noted in 95.92% (n=47) and 89.8% (n=44) patients. Three distinct QT patterns noted in ECG were, a) initial rise then fall (n=8), b) initial fall then rise (n=9) and c) rise followed by further rise (32). There was no serious adverse event leading to drug withdrawal or mortality in the first three months. Conclusions: Prolongation of QTcF occurs in alarming numbers during first two weeks of BDQ therapy as well as shortened QT. However, BDQ was otherwise tolerated well by the real world MDR & XDR-TB patients in short term. Intensive ECG and clinical monitoring is recommended to detect possible serious implications of such ECG changes in the long term.

Addis Ababa, the capital of Ethiopia, is urbanizing rapidly in recent years mainly through the destruction of environmental resources. This study aimed at the dynamics of urban green spaces (UGS). Remote Sensing and Geographical Information System (GIS) was used to extract land use and land cover data. The Landscape Expansion Index (LEI) was employed to measure urban growth patterns. The result showed that a more noticeable growth was observed in the peri-urban zone (40.1km2 to 176.1km2), followed by the inner urban zone (from 67.1km2 to 105km2). The expansion in the urban core zone was marginal and followed a non-unidirectional trend i.e. increased in the first period (1989-1999) and second period (1999-2009) by (0.11% and 4.2%), while decreased in the third period (2009-2019) by 3.6%. The result for LEI dynamics showed that the city experienced a pronounced outlying growth (98%) pattern, while edge expansion and infilling growth were insignificant. Conversely, the UGS declined in the inner urban zone by (18.03%), (28.61%) and (18.97%) in the first, second, and third periods. Similarly, in the peri-urban zone, the UGS persistently declined by (11.5%), (17.1%) and, (28.03%). The directional analysis showed that urban areas significantly expanded in SEE, SSE, SSW, and NEE with a net increase of 5.35, 4.4 km, 2.83, and 2.3 km2/year, respectively. Conventional large-scale /citywide/ dynamics investigations are not robust enough to represent the actual magnitude and directions of change, while the zonal and directional study is more effective in characterizing the Spatio-temporal dynamics for better urban planning towards.

Targeted gene flow is an emerging conservation tool which involves introducing a cohort of individuals with particular traits to locations where they can produce a conservation benefit. This approach is being proposed to adapt recipient populations to a known threat, but questions remain surrounding how best to maximize conservation outcomes during periods of continuous directional environmental change. Here we introduce a new management objective — to keep the recipient population extant and with maximum diversity of local alleles — and we explore how varying the timing and size of an introduction can achieve this. Our results reveal that management levers can often optimize this so that nearly 100% of the allelic diversity is preserved. These optimum outcome sets are robust to the shape of the environmental change but are highly sensitive to the the maximum magnitude of change and the level of outbreeding depression in the system.

Detailed analysis of the UFO structure along with Field Propulsion has been provided in this paper subject to Anti-Gravity, Electrohydrodynamics and warp drive with superluminal speeds violating General, Special Relativity and Newton's laws of motion. 

In this study, the Scheibel column with the regular packing structure was investigated in the extraction process of lanthanum and cerium ions. Mass transfer coefficients identified the column performance in the transport stage of La(III) and Ce(III) from the aqueous phase to the organic phase. The variations in operating conditions were investigated to optimize the extraction of ions. The backflow model (BFM), axial dispersion model (ADM), and forward mixing model (FMM) were investigated to evaluate the mass transfer performance. The result showed that the description of the volumetric overall mass transfer coefficient with forward mixing model is more significant than two other models. The medium of average absolute relative error obtained by the FMM model is ~4.45% and ~18.40% (lanthanum extraction) and ~10.75% and ~14.99% (cerium extraction) for continuous and dispersed phase, respectively. It indicated that the applied model has a remarkable accuracy for description of mass transfer performance

Plasma transfusion should never be used as child's play as the dire consequences of the plasma transfusion exercise can trigger a re-virulence of VZV at any point of time with failing immunocompetence of the body of a plasma transfusion recipient and catastrophic impacts of any negligent blood transfusion with and without the knowledge of the plasma transfusion recipient through willful ignorance perhaps or failing memory.

SIR model is one of the simplest methods used in prediction of endemic/pandemic outbreaks. We examined SIRD model for development of COVID-19 in Kuwait which was started on 24 February 2020 by 5 patients in Kuwait. This paper investigates sensitivity of SIRD model for development of COVID-19 in Kuwait based on duration of progressed days of data. For Kuwait, we have fitted SIRD model to COVID-19 data for 20, 40, 60, 80, 100, and 116 days of data and assessed sensitivity of the model with number of days of data. The parameters of SIRD model are obtained using an optimization algorithm (lsqcurvefit) in MATLAB. The total population of 50,000 is equally applied for all Kuwait time intervals. Results of SIRD model indicates that after 40 days the peak infectious day can be adequately predicted; althogh, error percentage from sensetivity analysis indicates that different exposed population sizes are not correctly predicted. SIRD type models are too simple to robustly capture all features of COVID-19 and more precise methods are needed to tackle nonlinear dynamics of a pandemic. 2

Eruption of COVID-19 patients in 215 countries worldwide have urged for robust predictive methods that can detect as early as possible size and duration of the contagious disease and also providing precision predictions. In many recent literatures reported on COVID-19, one or more essential parts of such investigation were missed. One of crucial elements for any predictive method is that such methods should fit simultaneously as many data as possible; these data could be total infected cases, daily hospitalized cases, cumulative recovered cases and deceased cases and so on. Other crucial elements include sensitivity and precision of such predictive methods on amount of data as the contagious disease evolved day by day. To show importance of these aspects, we have evaluated the standard SIRD model and a newly introduced Gaussian-SIRD model on development of COVID-19 in Kuwait. It is observed that SIRD model quickly pick up main trends of COVID-19 development; but Gaussian-SIRD model provides precise prediction at longer period of time.

Aims: Non-small-cell lung cancer (NSCLC) is the most common clinical lung cancer. Polymorphonuclear-myeloid derived suppressor cells (PMN-MDSCs), which are the major population of MDSCs, are involved in NSCLC progression. Recently, it was found that lectin-type oxidized LDL receptor 1 (LOX-1) could identify humsn PMN-MDSCs. However, the role of CD15+LOX-1+ PMN-MDSCs in NSCLC early diagnosis has not been revealed. Here, we tried to confirm the application of the newly-identified CD15+LOX-1+ PMN-MDSCs in the early diagnosis of NSCLC. Methods: Flow cytometry (FCM) was used to detect the proportion of CD15+LOX-1+ PMN-MDSCs in the peripheral blood (PB) of healthy controls (HC) and NSCLC patients. The correlation of CD15+LOX-1+ PMN-MDSC frequency with levels of cytokeratin 19-fragments (CYFRA21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) was analyzed. Receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficacy of CD15+LOX-1+ PMN-MDSCs for NSCLC. Additionally, the association of CD15+LOX-1+ PMN-MDSC frequency with NSCLC prognosis/recurrence after surgery was explored. Results: The proportion of CD15+LOX-1+ PMN-MDSCs increased in PB of NSCLC patients. CD15+LOX-1+ PMN-MDSC proportion was positively correlated with levels of CEA and CYFRA21-1. The area under the ROC curve (AUC) of PMN-MDSC percentage was higher than CYFRA21-1, CEA and CA125. The proportion of CD15+LOX-1+ PMN-MDSCs decreased in patients after surgery. The frequency of CD15+LOX-1+ PMN-MDSCs was lower in NSCLC patients without recurrence compared to those with recurrence after surgery. Conclusions: Circulating CD15+LOX-1+ PMN-MDSCs are a potential diagnostic marker for NSCLC, and are associated with NSCLC prognosis and recurrence after surgery.

The susceptible-infectious-recovered-deceased (SIRD) model is an essential model for outbreak prediction. This paper evaluates the performance of the SIRD model for the outbreak of COVID-19 in Kuwait, which initiated on 24 February 2020 by five patients in Kuwait. This paper investigates the sensitivity of the SIRD model for the development of COVID-19 in Kuwait based on the duration of the progressed days of data. For Kuwait, we have fitted the SIRD model to COVID-19 data for 20, 40, 60, 80, 100, and 116 days of data and assessed the sensitivity of the model with the number of days of data. The parameters of the SIRD model are obtained using an optimization algorithm (lsqcurvefit) in MATLAB. The total population of 50,000 is equally applied for all Kuwait time intervals. Results of the SIRD model indicate that after 40 days, the peak infectious day can be adequately predicted. Although error percentage from sensitivity analysis suggests that different exposed population sizes are not correctly predicted. SIRD type models are too simple to robustly capture all features of COVID-19, and more precise methods are needed to tackle the correct trends of a pandemic.

Objectives The aim of the present study was to investigate the effect of treatment on IL-1, IL-6, IL-8 and neopterin levels in patients with non-muscle invasive bladder cancer (NMIBC). Methods Thirty patients with NMIBC and 30 age-matched controls were included in the study. Preoperative, postoperative first control (at two weeks after second transurethral resection of bladder tumor (TURBT)) and second control (at the end of intravesical immunotherapy) blood samples were analyzed by ELISA to determine IL-1, IL-6, IL-8 and neopterin levels. The mean cytokine levels of the patients were statistically compared as well as comparing the patients’ and controls’ levels. Results There were no statistically significant differences between the mean IL-1, IL-6, IL-8 and neopterin levels of the patient and control group before initial TURBT. In the patient group, there were no statistically significant differences in the IL-6 and IL-8 levels after both TURBT and intravesical BCG therapy. The mean of preoperative IL-1 and neopterin levels significantly decrease after TURBT (p<0.05=). However this reduction do not continue after intravesical BCG instillations. Conclusions The finding of this study showed that the IL-1, IL-6, IL-8 and neopterin levels of the patients with NMIBC were similar to the levels of healthy controls. The IL-1 and neopterin levels significantly decreased after TURBT. But this reductions did not continue after intravesical BCG instillation. These findings demonstrate that IL-1 and neopterin levels decrease after TURBT due to the reduction of tumor weight or tumor removal.

Aim Extracorporeal shockwave therapy (ESWT) is known as one of the most effective treatment methods in plantar fasciitis (PF). Low-dye taping, which is the most preferred method of banding treatments, provides an analgesic effect by correcting biomechanics. It was aimed to compare the efficacy of adjuvant low-dye kinesio-taping (KT), sham-taping, or extracorporeal shockwave therapy (ESWT) alone in plantar fasciitis (PF). Methods In this double-blind, sham-controlled study, forty-five patients with PF were randomized to 3-group (Group 1: ESWT plus low-dye KT, n=15; Group 2: ESWT plus Sham-taping, n=15; and Group 3: ESWT only, n=15) five-session ESWT were administrated. KT was performed and changed every 1-week for the ESWT sessions in Groups 1 and 2. The main outcome measures were the visual analog scale (VAS) change, the heel tenderness index (HTI), foot function index (FFI). The patients were evaluated at the beginning and end of the treatment and the 4-week follow-up. Results The demographic characteristics and baseline outcomes between groups were similar (p>0.05). VAS and HTI changes were observed in all three groups, there was no difference between groups. Repeated-measures ANOVA showed a significant interaction between the time and the groups in FFI-total (F3.919= 2.607; p=.043). At the 4-week follow-up, when Groups 1 and 2 were evaluated, the lower FFI-total, FFI-disability, and FFI-activity limitation were statistically significant in Group 1 (p=0.027; p=0.026; p=0.029, respectively). When Group 1 and 3 were compared, the decrease in FFI-pain and FFI-activity limitation were significant in Group 1 (p=0.042; p=0.035, respectively). Conclusions Low-dye KT, in addition to ESWT, is more effective than sham-taping and ESWT in pain relief and foot function improvement due to PF at a 4-week follow-up.

Background/Aim: There is insufficient data on physiological and psychological alterations that may occur among health-care workers wearing various face masks during novel coronavirus-2019 (COVID-19) pandemic. In this study, we aimed to investigate the physiological effects of various types of face masking and associated discomfort among health-care workers. Methods: This prospective study included 33 healthy health-care workers. Each participant was asked to wear a single surgical mask, double mask, N95 type mask, and surgical mask on N95 type mask for an uninterrupted period of 2 hours. Oxygen saturation, heart pulse, blood pressure, respiratory rate, and step counts were recorded at baseline and every 30 min of 2 hours with a total of five times for each mask type. Self-assessment of fatigue, exhaustion, and headache were also graded. Intra- and inter-group analyses were performed. Results: There was no significant difference in the oxygen saturation, pulse and respiratory rates among the participants including intra- and inter-groups (p>0.05) Although no significant difference was seen in diastolic blood pressure, systolic blood pressures gradually and significantly increased with a double surgical mask (p<0.05). Headache and exhaustion scores increased gradually and significantly over time at every measurement time-point with every mask type (p<0.05) Fatigue scores also increased in intra-group comparison of mask types without any difference in-between. Conclusion: Our study results show that, during 2 hours of period, face mask types affect only subjective parameters such as headache, exhaustion, and fatigue without any change in the objective parameters such as oxygen saturation, and pulse and respiratory rates among health-care workers.

Introduction: This study aims to investigate the outcomes and complication rates of patients undergoing retrograde intrarenal surgery (RIRS) at the live surgery events organized as boutique course series. Materials and Methods: Eight RIRS courses were organized between November 2017 and February 2020. Data of 24 patients who were operated in the live surgery events (as LSE group) for renal stone were matched with the data of 24 substitute patients (as control group) who underwent regular RIRS on the same period at the same centers.. Results: Stone free status of groups was similar (88% in LSE and 79% in the control group; p=1). There was no significant difference in terms of complication and need for additional procedure rates, operation and fluoroscopy and hospitality times between the two groups (p=1, p=1, p=0.12, p=0.58 and p=0.94, respectively). Fifty-four % (13/24) of LSE operations were performed by guest surgeons. No statistically significant difference was found between the patients who operated by host and guest surgeons. However, the operation times of the operations performed by guest surgeons were longer than those performed by the host surgeons (96.5±28 and 66.5±30 minute, respectively, p=0.07). Conclusion: Our study is the first report on this area. RIRS live surgery can be performed with low complication and high stone-free rates without jeopardizing patient safety. If the surgeon is not familiar with the operating room set-up or staffs, the live surgery must performed by the host surgeon to avoid extended operating time.

Purpose: To investigate the prediction values of the preoperative NLR, LMR, PLR, MPV, RDW for recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC). Methods: In this prospective study, 94 consecutive patients, newly diagnosed with NMIBC between July 2017 - August 2018 were included. The blood samples were collected from patients before transurethral resection of bladder tumor (TURB) and NLR, LMR, PLR, RDW, MPV values were calculated. The effect of these preoperative inflammatory parameters and other clinicopathological parameters on recurrence and progression rates were evaluated. Kaplan-Meier and multivariate Cox regression analyses were performed to identify significant prognostic variables. Results: The mean follow-up was 11 ± 6.4 months. Recurrence was observed in 35.1% and progression was detected in 7.4% of the patients. Neutrophil-lymphocyte ratio was statistically significantly associated with both recurrence (p = 0.01) and progression (p = 0.035) whereas lymphocyte-monocyte ratio was only associated with recurrence (p = 0.038). In the survival analyses, the relationship between recurrence and LMR was confirmed in both univariate (p = 0.021) and multivariate (p = 0.022) analyses. The relationship between NLR and recurrence was confirmed in univariate analysis (p = 0.019), however in multivariate analysis was found to be statistically insignificant (p = 0.051). Conclusions: Lymphocyte-monocyte ratio might be an easy obtainable, non-invasive and cost-effective method for predicting recurrence of disease in patients with non-muscle invasive bladder cancer.

A document by Deep Bhattacharjee . Click on the document to view its contents.

A non-isothermal pressure-balanced bubble-growth (PBB) model has been proposed based on mass, momentum and energy conservation, which additionally considered the decrease in the internal energy of gas due to the work done by gas expansion in bubble. The model could accurately predict the bubble size and expansion ratio for the melt foaming of four polymers for a wide range of cell densities from 1.5×1013 to 1.9×1015 cells/m3. Furthermore, the simulation results indicate that the bubble shell resisted bubble growth and consumed significant energy, preventing the growth of some small nucleations. During the melt foaming process, the energy cost of the linear polymer had a long-term effect, which reduced the bubble size, while that of the long-chain branched polymer had a short-term effect, thereby increasing the expansion ratio. Finally, we defined the gas efficiency of the foaming agent to evaluate the economic feasibility of the foaming agent in a foaming process.

The asymmetric sulfoxidation catalyzed by soybean pod peroxidase (SPP) in water-in-oil microemulsions were carried out with the yield of 91.56% and e.e of 96.08% at the activity of SPP of 3200 U ml-1 and 50℃ for 5 h. The mechanism with a two-electron reduction of SPP-I is accompanied with a single-electron transfer to SPP-I and nonenzymatic reactions, indicating that three concomitant sub-mechanisms contribute to the asymmetric oxidation involving five enzymatic and two nonenzymatic reactions, which can represent the asymmetric sulfoxidation of organic sulfides to form enantiopure sulfoxides. With 5.44% of the average relative deviation, a kinetic model fitting experimental data was developed. The enzymatic reactions may follow ping-pong mechanism with substrate inhibition of H2O2 and product inhibition of esomeprazole, while nonenzymatic reactions, a power law. Those results indicate that SPP with a lower cost and higher thermal stability may be used as an effective substitute for Horseradish Peroxidase.

Machine Learning (ML) algorithms can be combined with the modular automation protocol (MTP) and recognize the flooding behavior of laboratory fluids separation columns. Hence, artificial intelligence (AI) tools with deep learning (DL) offer a high potential for the process industry and allow to capture operating states that are otherwise difficult to detect or model. However, the advanced methods are only hesitantly applied in practice. This article provides an overview on how artificial intelligence-based algorithms can be implemented in existing laboratory plants. Process sensor data as well as image data are used to model the flooding behavior of distillation and extraction columns and the system is adapted to the existing modular automation standard of the Module Type Package (MTP).