We consider the incremental subgradient algorithm employing dynamic step sizes for minimizing the sum of a large number of component convex functions. The dynamic step size rule was firstly introduced by Goffin and Kiwiel [Math. Program., 1999, 85(1): 207-211] for the subgradient algorithm, soon later, for the incremental subgradient algorithm by Nedic and Bertsekas in [SIAM J. Optim., 2001, 12(1): 109-138]. It was observed experimentally that the incremental approach has been very successful in solving large separable optimizations, and that the dynamic step sizes generally have better computational performance than others in the literature. In the present paper, we propose two modified dynamic step size rules for the incremental subgradient algorithm and analyse the convergence properties of them. At last, the assignment problem is considered and the incremental subgradient algorithms employing different kinds of dynamic step sizes are applied to solve the problem. The computational experiments show that the two modified ones converges dramatically faster and stabler than the corresponding one in [SIAM J. Optim., 2001, 12(1): 109-138]. Particularly, for solving large separable convex optimizations, we strongly recommend the second one (see Algorithm 3.3 in the paper) since it has interesting computational performance and is the simplest one.

In this paper, we study Mannheim curves and Mannheim pairs by using the modified orthogonal frame in Minkowski 3-space E31. We give some characterizations of Mannheim Curves and their partner Curves in E31.

This paper investigates the Hölder’s inequality under the condition r-conjugate exponents in the sense that ∑1/p_k=1/r. Successively, we have, under r-conjugate exponents relative to the Lp-norm, investigated generalized Hölder’s inequality, the interpolation of Hölder’s inequality, and generalized s-order Hölder’s inequality which is an expansion of the known Hölder’s inequality.

In this article, we employ the nonlinear complex Hirota-dynamical model which is one of the famous and important standards to the nonlinear Schrödinger equation in which the third derivative term represent the self-interaction in the high-frequency subsystem. Specially, in plasma this term is isomorphic to the so known self-focusing effect. The bright, dark and periodic optical soliton solutions to this equation will realized successfully for the first time in the framework of the solitary wave ansatz method. Furthermore, in this connection at the same time and parallel the extended simple equation method has been applied successfully to achieve new impressive solitary wave solutions to this model. A comparison between the obtained results and that satisfied in previous work has been established.

A document by Prashant Pandey. Click on the document to view its contents.

In this article we show well-posedness for a relatively general semilinear parabolic system under nonhomogeneous Neumann boundary conditions and semi-linearities of (some) equilibrium reaction type. The result in here weakens previously made by Krautle and Mahato (Kra08, Kra11 and MB131, MB132, resp.) on the coefficients of the elliptic operator as well as on the boundary conditions considerably.

Obstructive airway disorders are common in infancy and early childhood. The leading example of such disorder is post-viral wheezing, predominantly the well characterized disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P. Neuroendocrine hyperplasia of infancy (NEHI), while a less common entity, is a disorder of infancy characterized by more severe and long-term obstructive airway disease. NEHI is pathophysiologically characterized by abundance of neuroendocrine cells in the airways containing the neuroimmune mediator bombesin, the release of which is presumed to be the driver of the persistent small airway obstruction and functional air-trapping. Here we review the NANC and NEC neurotransmitter systems and their studied roles in pulmonary diseases with a focus on their role in lung development, and subsequent various pediatric lung diseases. We focus on the juxtaposition of the separate neuroimmune mechanisms underlying the pathogenesis of post-RSV recurrent wheezing and NEHI persistent small airway obstruction. We finally raise the question whether substance P is indeed specific to post-RSV infection and bombesin to NEHI and then propose a unifying concept of post-viral spectrum of respiratory disorders that may encompass these two entities and possibly others.

Vernal keratoconjunctivitis (VKC) is a severe chronic ocular disease characterized by recurring acute and/or chronic corneal-conjunctival inflammation leading to visual sequelae. Since no therapy is universally effective at treating VKC, novel treatments are currently under investigation, such as anti-immunoglobulin (Ig)E [1]. Omalizumab, a recombinant monoclonal antibody (mAb) binding to the Fcε portion of the immunoglobulin (Ig)E, has been licensed by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) as an add-on therapy for the treatment of severe not controlled allergic asthma both in adults and children (age ≥ six years), [2-4] as well as in severe chronic idiopathic urticaria, and even as off-label use in other diseases [5, 6]. Although the clinical efficacy and safety of omalizumab have already been extensively investigated in the treatment of other IgE-mediated diseases [7, 8], very few literature data support the use of omalizumab in VKC [9-14]. In the present study, we report our clinical experience with omalizumab to treat severe VKC unresponsive to standard therapy in two children. An updated overview of the current literature is also provided.

This work aims to study and observe all the existing score functions that help to rank the single-valued neutrosophic set (SVNS) as well as interval-valued neutrosophic set (IVNS) to make a better choice among all the available alternatives in multi-criteria decision-making (MCDM) problems. An intensive study about all these existing score functions reveals that there holds some limitations in the method of ranking order which is misleading the results in decision-making problems. These observations about the existing score functions of the SVNS and IVNS have been claimed with the help of well-defined examples, illustrating an inefficiency of all these existing score functions. Thus, to propose a valid score function for ranking SVNS and IVNS for making a better selection among all the other available alternatives in MCDM problems is still an open challenging research problem.

Functional annotation aims to assess the biochemical and biological functions of sets of genomic or transcriptomic sequences yielded after next-generation sequencing experiments. One common way to perform functional annotation of a set of sequences obtained from a next-generation sequencing experiment, is by searching for homologous sequences and accessing to the related functional information deposited in genomic databases. Functional annotation is especially challenging in de novo assemblies of transcriptomes of non-model organisms, like many plant species. In such cases, existing commercial and open access general purpose applications may not offer complete and accurate results. We present TOA (Taxonomy-oriented annotation), a user-friendly open-access application designed to establish functional annotation pipelines geared towards non-model plant species. TOA performs homology searches against proteins stored in the PLAZA platform databases, NCBI RefSeq Plant, Nucleotide Database and Non-Redundant Protein Sequence Database, and retrieves functional information for several gene ontology systems. The software performance was validated by comparing the runtimes, total number of annotated sequences and accuracy of the functional information obtained for several plant benchmark datasets with TOA and other open-access functional annotation solutions. TOA outperformed the other software in terms of number of annotated sequences and accuracy of the annotation, and constitutes a good alternative to improve functional annotation in plants. TOA is especially recommended for gymnosperms or for low quality sequence datasets of non-model plants.

Objectives: To analyze preterm birth related factors for single intrauterine death in monochorionic twins. Design: Retrospective case-control study. Setting: A single medical centre in Shenyang, China, 2012-2018. Sample: preterm delivery with intrauterine fetal death in monochorionic twins (cases, n = 35) were compared with a group of full term birth (controls, n = 4). Methods: Related factors were compared in the two groups and logistic regression was used to adjust for confounding. Main outcome measures: Odds ratio (OR) and 95% confidence interval (CI) for the related factors of preterm birth Results: This study included 39 monochorionic twins following single intrauterine death. The significant risk factor associated with preterm birth is the gestational age of single intrauterine death (OR=1.317, 95% CI: 1.027-1.689). The timing of prolong gestational age shorten with the increasing gestational age of single intrauterine death. We found that in all monochorionic twins cases and spontaneous preterm birth cases, increases in the gestational age at single intrauterine death was associated with shorter prolongation of gestational age in the surviving twin. Conclusions: The gestational age of single intrauterine death was a risk factor of preterm delivery. Increases in the gestational age at single intrauterine death led to a shorter prolongation in gestation of the surviving twin. Funding: This study was funded by Prenatal diagnosis, intrauterine intervention and prognosis evaluation of complicated twins (No. 2018YFC1002902) Tweetable abstract: The gestational age of intrauterine fetal death was a risk factor of preterm delivery. Keywords Gestational age; Prolongation of gestational age; Twin pregnancy；

BACKGROUND: The benefit of mitral valve repair over replacement in patients with ischemic mitral regurgitation is still controversial. We report our early postoperative outcomes of repair versus replacement. METHODS: Data were collected for patients undergoing first-time mitral valve surgery for ischemic mitral regurgitation between 1990 and 2009 (n = 393). Patients who underwent combined procedures for papillary muscle rupture, post-infarction ventricular septal defect, endocarditis, or any previous cardiac surgery were excluded. Preoperative demographics, operative variables, and hospital outcomes were analyzed, and multivariable regression analysis was employed to identify independent predictors of hospital mortality. RESULTS: Valve repair was performed in 42% (n=164) of patients and replacement in 58% (n=229). Patients who underwent replacement were older and had a higher prevalence of unstable angina, New York Heart Association class IV symptoms, preoperative cardiogenic shock, preoperative myocardial infarction, peripheral vascular disease, renal failure, and urgent or emergency surgery (all p < 0.05). Unadjusted hospital mortality was higher in patients undergoing valve replacement (13% versus 5%, p = 0.01). Valve repair was associated with a lower prevalence of postoperative low cardiac output syndrome. Multivariable analysis revealed that age, urgency of operation, and preoperative left ventricular function were independent predictors of hospital mortality. Importantly, mitral valve repair versus replacement was not an independent predictor of hospital mortality. CONCLUSION: Our data did not suggest an early survival benefit to mitral valve repair over replacement for ischemic mitral regurgitation. However, age, left ventricular dysfunction, and the need for urgent surgery were independently associated with hospital mortality.

Providing complex therapies such as ECMO during outbreaks of infectious diseases has singular challenges. The impact of the SARS-CoV-2 pandemic has implied a mentality change by force of circumstances, and cardiac surgery has not been stranger to this trend. The need to treat critically ill patients with an unknown evolution has compelled cardiovascular surgeons to decide whether or not to implant an ECMO system, despite the limited scientific evidence available in the context of COVID-19. To add some confusion, doubts were raised about its potential deleterious outcome in COVID-19 patients, due to its effect on lymphocyte counts and interleukin-6 concentrations. The care of the critically ill patient in a moment of national emergency in Spain took precedence over those possible formal doubts. The Spanish perspective on Ventricular Assist Devices during and after the COVID-19 pandemic, focused on ECMO as a particular case of mechanical circulatory support, is presented. We address both the challenges posed by the pandemic and the organizational model established in Spain; changes in ECMO therapy and some lessons learned for the next outbreaks are also described. It is not about reinventing the wheel in each country; it is enough to learn from experience and take advantage of the knowledge generated by those who have already gone through similar situations in our environment.

A 36-year-old woman was referred to a local hospital with cough and fever. She had a history of facial erythema and cough that began 2 months ago. Her status developed into rapid progressive interstitial lung disease (RP-ILD) with mediastinal emphysema and subcutaneous emphysema after admission, and venovenous extracorporeal membrane oxygenation (V-V ECMO) was initiated. After several failed attempts to wean the patient from ECMO, a decision was made to place the patient on the lung transplant waitlist. She underwent a double lung transplant on ECMO day 31 and received tacrolimus as an immunosuppressive regimen. The patient presented with positive anti-MDA5 and anti-Ro-52 antibodies and a high ferritin level, all of which indicated the presence of clinically amyopathic dermatomyositis (CADM). The patient was weaned from ECMO at 3 days after transplantation, but the patient’s state of consciousness deteriorated, and head CT was considered for posterior reversible encephalopathy syndrome (PRES). After the temporary cessation of calcineurin inhibitors and a dosage reduction, the patient’s state of consciousness returned to normal. Because of another disturbance of consciousness, the patient declined further treatment and was discharged 14 days after transplantation.

COVID-19 hit hard worldwide. There has been an impact on global activity of cardiac surgery. Spain has been one of the hardest hit countries with one of the highest per population incidences and death. Cardiac surgical activity has suffered a negative impact all over the country. The following is an overview of the epidemiology and impact on resources, the caseload and surgical societal implemented recommendations, the description of the ECMO activity and nosocomial transmission among healthcare workers.

Asymptomatic cardiac neoplasms are often diagnosed incidentally. Right atrial mass close to septum needs careful evaluation and multimodality imaging to manage appropriately. This case highlights the utilization of multimodality imaging and heart team approach in the management of the right atrial mass.

Sphincter reconstruction and stoma in situ is an exploratory surgery for abdominoperineal resection of rectal cancer; its functional outcome is a major concern. This is a rare case of long-term survival with unilateral gluteus maximus fasciculus reconstruction, in a patient with the ability to control defecation and distinguish gas.

Background: Children and adolescents with cancer are at risk of a poor health-related quality of life. Exercise interventions to enhance movement may be a valid strategy for managing some symptoms, including fatigue. Methods: Forty-four consecutive patients (20 females; aged 5-21 years old, median 15.5 years), without any contraindications significantly limiting their movements were invited to join an in-hospital 6-week supervised exercise program, and asked afterwards to complete the PedsQL-4.0 quality of life Generic Core Scales and the PedsQL Multidimensional Fatigue Scale. The program consisted of personalized workout sessions of aerobic, resistance and flexibility exercises. The results obtained on the scales were compared between patients who engaged in the exercise program (GYM group, n=21) and those who did not (No-GYM, n=23), with the aim of examining the different dimensions of health-related quality of life (physical, emotional, cognitive, social) and fatigue (general, sleep/rest, cognitive) comparing the two groups. Results: For 43 of 44 patients, being diagnosed with cancer initially prompted a drop-out from previous physical exercise or sports routines despite no contraindications to their continuation. After 6 weeks, the scores for patients in the GYM group showed a statistically significant better perceived emotional functioning, and a possible indication of improved social functioning compared with the No-GYM group. Conclusion: These findings suggest that to exercise improves the satisfaction of children and adolescents with cancer with their physical, mental and social functioning. It is worth further investigating the value of systematically including exercise workouts in their routine cancer practices.

CPX-351 is a promising new therapeutic option for patients with treatment related (tAML) or secondary acute myeloid leukemia (sAML). It exceeded classic 7+3 therapy in overall survival (OS) and complete remission rates (CR) while providing a similar risk profile. Until now, this sub-group of AML patients had a worse overall

Abstract Background: the survival of Wilms tumor is very low when evaluated in 2008. The impact of establishing pediatric oncology service on survival is studied, and the obstacles of treating Wilms tumor patients were identified. Procedure: All Wilms tumor patients from 2005 to 2014 were analyzed retrospectively. Patients received treatment based on the NWTS IV protocol. Patients were analyzed for overall survival, and event-free survival, and these outcomes were correlated with age, sex, stage at presentation, and histology. Results: We analyzed 143 files of Wilms tumor. The male to female ratio is 1.75. The mean age of patients at diagnosis is 3.5. The follow-up period is five years. Most patients (83%) had advanced disease stage 3, and 4.There is a very high abandonment rate (37%). The event-free survival among patients who completed treatment is 75.6%, and the overall survival is 43.4% Conclusions: There is a remarkable improvement in Wilms tumor survival from 11% to 43 % and 75.6%. Much needs to be done to reduce abandonment rates and establish a surgical pediatric oncology service.

Objective: Antihistamines are among the most prescribed medicines in otorhinolaryngology. This drug is excellent for rhinorrhea, sneezing and itching, however, it has a debatable effect in rhinosinusitis. At this point, it is useful to examine the relationship between antihistamine and the incidence of sinusitis based on large-cohort data analysis. Design: Retrospective study Setting: A Nationwide cohort study which used population-based insurance data (consisting of data from approximately 1 million patients). Participants: The antihistamine (AH) group consisted of patients who were diagnosed with allergic rhinitis (AR) between January 1, 2003 and December 31, 2003, taking at least one dose of antihistamine. Non-antihistamine (non-AH) group of patients who did not take antihistamines was obtained by 1:4 propensity score matching. Main outcome measures: Primary endpoint was the occurrence of sinusitis. Results: The adjusted hazard ratio for the sinusitis in the AH group was 1.53 [95% CI: 1.36-1.72] compared with the non-AH group. Sinusitis was more frequent in women (HR: 1.34), and less frequent the older the age (HR: 0.74, 0.58, 0.46, respectively) after exposure to antihistamine. In the subgroup analysis regarding the AH usage duration, there was no significant difference between the four subgroups. Conclusion: Antihistamines are probably the most prescribed medicines in the rhinologic area. But as all things have advantages and disadvantages, this large-scale longitudinal study shows that antihistamines are closely associated with sinusitis regardless of prescription duration and thus should be cautiously prescribed.

In this study, the binding of multimodal chromatographic ligands to the IgG1 FC domain were studied using nuclear magnetic resonance and molecular dynamics simulations. Nuclear magnetic resonance experiments carried out with chromatographic ligands and a perdeuterated 15N-labeled FC domain indicated that while single mode ion exchange ligands interacted very weakly throughout the FC surface, multimodal ligands interacted with specific clusters of residues with relatively high affinity, forming distinct binding regions on the Fc. The multimodal ligand binding sites on the FC were concentrated in the hinge region and near the interface of the CH2 and CH3 domains. Further, the multimodal binding sites were primarily composed of positively charged, polar and aliphatic residues in these regions, with histidine residues exhibiting some of the strongest binding affinities with the multimodal ligand. Interestingly, comparison of protein surface property data with ligand interaction sites indicated that the patch analysis on FC corroborated molecular level binding information obtained from the nuclear magnetic resonance experiments. Finally, molecular dynamics simulation results were shown to be qualitatively consistent with the nuclear magnetic resonance results and to provide further insights into the binding mechanisms. An important contribution to multimodal ligand-FC binding in these preferred regions was shown to be electrostatic interactions and pi-pi stacking of surface exposed histidines with the ligands. This combined biophysical and simulation approach has provided a deeper molecular level understanding of multimodal ligand-FC interactions and sets the stage for future analyses of even more complex biotherapeutics.

The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein based biologic drugs. Here we describe Leap-In Transpoasase® platform, a novel transposon-based mammalian (e.g. CHO) cell line development system that produces high titer stable pools with productivity and product quality attributes that are highly comparable to clones that are subsequently derived therefrom. The productivity distributions of clones are strongly biased towards high producers and both genetic and expression stability is consistently high. By avoiding the poor integration rates, concatemer formation, detrimental transgene recombination, low average expression level, unpredictable product quality and inconsistent genetic stability characteristic of non-homologous recombination methods, Leap-In provides several opportunities to de-risk programs early and reduce timelines and resources.

The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51th day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain.