bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of residual submicroscopic Plasmodium falciparum parasites 3 days after initiation of treatment with artemisinin-based combination therapy
Authors: Mwaiswelo Richard , Ngasala Bill
Published: April 2020

Plasmodium falciparum resistance against artemisinin has not emerged in Africa; however, there are reports of the presence of polymerase chain reaction-determined residual submicroscopic parasitaemia detected on day 3 after artemisinin-based combination therapy (ACT). These residual submicroscopic parasites are thought to represent tolerant/resistant parasites against artemisinin, the fast-acting component of the combination. This review focused on residual submicroscopic parasitaemia, what it represents, and its significance on the emergence and spread of artemisinin resistance in Africa. Presence of residual submicroscopic parasitemia on day 3 after treatment initiation leaves question on whether successful treatment is attained with ACT. Thus there is a need to determine the potential public health implication of the PCR-determined residual submicroscopic parasitaemia observed on day 3 after ACT. Robust techniques, such as in vitro cultivation, should be used to evaluate if the residual submicroscopic parasites detected on day 3 after ACT are viable asexual parasites, or gametocytes, or the DNA of the dead parasites waiting to be cleared from the circulation. Such techniques would also evaluate the transmissibility of these residual parasites.
Key components of mechanical work predict outcomes in robotic stroke therapy
Authors: Wright Zachary A. , Majeed Yazan A. , Patton James L. , Huang Felix C.
Published: April 2020

Background

Clinical practice typically emphasizes active involvement during therapy. However, traditional approaches can offer only general guidance on the form of involvement that would be most helpful to recovery. Beyond assisting movement, robots allow comprehensive methods for measuring practice behaviors, including the energetic input of the learner. Using data from our previous study of robot-assisted therapy, we examined how separate components of mechanical work contribute to predicting training outcomes.

Methods

Stroke survivors (n = 11) completed six sessions in two-weeks of upper extremity motor exploration (self-directed movement practice) training with customized forces, while a control group (n = 11) trained without assistance. We employed multiple regression analysis to predict patient outcomes with computed mechanical work as independent variables, including separate features for elbow versus shoulder joints, positive (concentric) and negative (eccentric), flexion and extension.

Results

Our analysis showed that increases in total mechanical work during therapy were positively correlated with our final outcome metric, velocity range. Further analysis revealed that greater amounts of negative work at the shoulder and positive work at the elbow as the most important predictors of recovery (using cross-validated regression, R2 = 52%). However, the work features were likely mutually correlated, suggesting a prediction model that first removed shared variance (using PCA, R2 = 65–85%).

Conclusions

These results support robotic training for stroke survivors that increases energetic activity in eccentric shoulder and concentric elbow actions.

Trial registration

ClinicalTrials.gov, Identifier:NCT02570256. Registered 7 October 2015 – Retrospectively registered,
In response: Letter on update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol
Authors: Lindsell Christopher J. , McGlothlin Anna , Nwosu Samuel , Rice Todd W. , Hall Alex , Bernard Gordon R. , Busse Laurence W. , Ely E. Wesley , Fowler Alpha A. , Gaieski David F. , Hinson Jeremiah S. , Hooper Michael H. , Jackson James C. , Kelen Gabor D. , Levine Mark , Martin Greg S. , Rothman Richard E. , Sevransky Jonathan E. , Viele Kert , Wright David W. , Hager David N.
Published: April 2020

Trial registration

ClinicalTrials.gov: NCT03509350. Registered on 26 April 2018.
Annotation and characterization of Babesia gibsoni apicoplast genome
Authors: Liu Qin , Yu Long , Jiang Fan , Li Muxiao , Zhan Xueyan , Huang Yuan , Wang Sen , Du Xiaoyong , He Lan , Zhao Junlong
Published: April 2020

Background

Babesia gibsoni is an apicomplexan parasite transmitted by ticks, which can infect canine species and cause babesiosis. The apicoplast is an organelle associated with isoprenoids metabolism, is widely present in apicomplexan parasites, except for Cryptosporidium. Available data indicate that the apicoplast is essential for the survival of apicomplexan parasites.

Methods

Here, the apicoplast genome of B. gibsoni was investigated by high-throughput genome sequencing, bioinformatics analysis, and conventional PCR.

Results

The apicoplast genome of B. gibsoni-Wuhan strain (B. gibsoni-WH) consists of a 28.4 kb circular molecule, with A + T content of 86.33%, similar to that of B. microti. Specifically, this genome encodes genes involved in maintenance of the apicoplast DNA, transcription, translation and maturation of organellar proteins, which contains 2 subunits of ribosomal RNAs, 17 ribosomal proteins, 1 EF-Tu elongation factor (tufA), 5 DNA-dependent RNA polymerase beta subunits, 2 Clp protease chaperones, 23 tRNA genes and 5 unknown open reading frames (hypothetical proteins). Phylogenetic analysis revealed high similarity of B. gibsoni apicoplast genome to that of B. orientalis and B. bovis.

Conclusions

To our knowledge, this is the first report of annotation and characterization of B. gibsoni-WH apicoplast genome. The results will facilitate the development of new anti-Babesia drug targets.
Predictors of the use of analgesic drugs 1 year after joint replacement: a single-center analysis of 13,000 hip and knee replacements
Authors: Rajamäki Tuomas Jaakko , Puolakka Pia A. , Hietaharju Aki , Moilanen Teemu , Jämsen Esa
Published: April 2020

Background

Pain persists in a moderate number of patients following hip or knee replacement surgery. Persistent pain may subsequently lead to the prolonged consumption of analgesics after surgery and expose patients to the adverse drug events of opioids and NSAIDs, especially in older patients and patients with comorbidities. This study aimed to identify risk factors for the increased use of opioids and other analgesics 1 year after surgery and focused on comorbidities and surgery-related factors.

Methods

All patients who underwent a primary hip or knee replacement for osteoarthritis from 2002 to 2013 were identified. Redeemed prescriptions for acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids (mild and strong) were collected from a nationwide Drug Prescription Register. The user rates of analgesics and the adjusted risks ratios for analgesic use 1 year after joint replacement were calculated.

Results

Of the 6238 hip replacement and 7501 knee replacement recipients, 3591 (26.1%) were still using analgesics 1 year after surgery. Significant predictors of overall analgesic use (acetaminophen, NSAID, or opioid) were (risk ratio (95% CI)) age 65–74.9 years (reference < 65), 1.1 (1.03–1.2); age > 75 years, 1.2 (1.1–1.3); female gender, 1.2 (1.1–1.3); BMI 30–34.9 kg/m2 (reference < 25 kg/m2), 1.1 (1.04–1.2); BMI > 35 kg/m2, 1.4 (1.3–1.6); and a higher number of comorbidities (according to the modified Charlson Comorbidity Index score), 1.2 (1.1–1.4). Diabetes and other comorbidities were not significant independent predictors. Of the other clinical factors, the preoperative use of analgesics, 2.6 (2.5–2.8), and knee surgery, 1.2 (1.1–1.3), predicted the use of analgesics, whereas simultaneous bilateral knee replacement (compared to unilateral procedure) was a protective factor, 0.86 (0.77–0.96). Opioid use was associated with obesity, higher CCI score, epilepsy, knee vs hip surgery, unilateral vs bilateral knee operation, total vs unicompartmental knee replacement, and the preoperative use of analgesics/opioids.

Conclusions

Obesity (especially BMI > 35 kg/m2) and the preoperative use of analgesics were the strongest predictors of an increased postoperative use of analgesics. It is remarkable that also older age and higher number of comorbidities predicted analgesic use despite these patients being the most vulnerable to adverse drug events.
Rationale for using the velocity–time integral and the minute distance for assessing the stroke volume and cardiac output in point-of-care settings
Authors: Blanco Pablo
Published: April 2020

Background

Stroke volume (SV) and cardiac output (CO) are basic hemodynamic parameters which aid in targeting organ perfusion and oxygen delivery in critically ill patients with hemodynamic instability. While there are several methods for obtaining this data, the use of transthoracic echocardiography (TTE) is gaining acceptance among intensivists and emergency physicians. With TTE, there are several points that practitioners should consider to make estimations of the SV/CO as simplest as possible and avoid confounders.

Main body

With TTE, the SV is usually obtained as the product of the left ventricular outflow tract (LVOT) cross-sectional area (CSA) by the LVOT velocity–time integral (LVOT VTI); the CO results as the product of the SV and the heart rate (HR). However, there are important drawbacks, especially when obtaining the LVOT CSA and thus the impaction in the calculated SV and CO. Given that the LVOT CSA is constant, any change in the SV and CO is highly dependent on variations in the LVOT VTI; the HR contributes to CO as well. Therefore, the LVOT VTI aids in monitoring the SV without the need to calculate the LVOT CSA; the minute distance (i.e., SV × HR) aids in monitoring the CO. This approach is useful for ongoing assessment of the CO status and the patient’s response to interventions, such as fluid challenges or inotropic stimulation. When the LVOT VTI is not accurate or cannot be obtained, the mitral valve or right ventricular outflow tract VTI can also be used in the same fashion as LVOT VTI. Besides its pivotal role in hemodynamic monitoring, the LVOT VTI has been shown to predict outcomes in selected populations, such as in patients with acute decompensated HF and pulmonary embolism, where a low LVOT VTI is associated with a worse prognosis.

Conclusion

The VTI and minute distance are simple, feasible and reproducible measurements to serially track the SV and CO and thus their high value in the hemodynamic monitoring of critically ill patients in point-of-care settings. In addition, the LVOT VTI is able to predict outcomes in selected populations.
Sonographic signs and patterns of COVID-19 pneumonia
Authors: Volpicelli Giovanni , Gargani Luna
Published: April 2020

The pandemic of COVID-19 is seriously challenging the medical organization in many parts of the world. This novel corona virus SARS-CoV-2 has a specific tropism for the low respiratory airways, but causes severe pneumonia in a low percentage of patients. However, the rapid spread of the infection during this pandemic is causing the need to hospitalize a high number of patients. Pneumonia in COVID-19 has peculiar features and can be studied by lung ultrasound in the early approach to suspected patients. The sonographic signs are non-specific when considered alone, but observation of some aspects of vertical artifacts can enhance the diagnostic power of the ultrasound examination. Also, the combination of sonographic signs in patterns and their correlation with blood exams in different phenotypes of the disease may allow for a reliable characterization and be of help in triaging and admitting patients.
The impact of propranolol on nitric oxide and total antioxidant capacity in patients with resistant hypertension—evidence from the APPROPRIATE trial
Authors: Ranasinghe H. N. , Fernando N. , Handunnetti S. , Weeratunga P. N. , Katulanda P. , Rajapakse S. , Galappatthy P. , Constantine G. R.
Published: April 2020

Objectives

The objective was to assess the effect of propranolol on oxidative stress and anti-oxidant potential in patients with resistant hypertension as a secondary analysis of the APPROPRIATE trial. This randomized double blinded clinical trial recruited patients with resistant hypertension and allocated forty patients to propranolol and placebo in 1:1 ratio. The pro-oxidant state (nitrate and nitrite) was assessed using modified Griess assay. The total anti-oxidant capacity was measured using ABTS assay.

Results

Analysis was performed for 18 patients from the propranolol group and 15 from the placebo group. A decline in end point ambulatory blood pressure (p = 0.031) and greater mean reduction in office SBP (29.7 ± 13.0 mmHg, p = 0.021) was noted in the propranolol arm. Nitrate and nitrite levels were lower at the end of a 90 day follow up period in both arms, with a greater mean reduction with propranolol. A significant increase in the AOC was noted in both arms with higher incremental value with Propranolol. The findings of this study do not demonstrate a statistically significant effect of propranolol on the oxidative stress/antioxidant balance in patients with resistant hypertension. The observed trends merit further evaluation.
The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health
Authors: de Frutos-Lucas Jaisalmer , Cuesta Pablo , López-Sanz David , Peral-Suárez África , Cuadrado-Soto Esther , Ramírez-Toraño Federico , Brown Belinda M. , Serrano Juan M. , Laws Simon M. , Rodríguez-Rojo Inmaculada C. , Verdejo-Román Juan , Bruña Ricardo , Delgado-Losada Maria L. , Barabash Ana , López-Sobaler Ana M. , López-Higes Ramón , Marcos Alberto , Maestú Fernando
Published: April 2020

Background

Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms ofAPOEε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon.

Method

The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated.

Results

A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory).

Conclusions

PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.
The validation of published utility mapping algorithms: an example of EORTC QLQ-C30 and EQ-5D in non-small cell lung cancer
Authors: Gregory Joanne , Dyer Matthew , Hoyle Christopher , Mann Helen , Hatswell Anthony J.
Published: April 2020

Background

Mapping algorithms can be used to generate health state utilities when a preference-based instrument is not included in a clinical study. Our aim was to investigate the external validity of published mapping algorithms in non-small cell lung cancer (NSCLC) between the EORTC QLQ-C30 and EQ-5D instruments and to propose methodology for validating any mapping algorithms.

Methods

We conducted a targeted literature review to identify published mappings, then applied these to data from the osimertinib clinical trial programme. Performance of the algorithms was evaluated using the mean absolute error, root mean squared error, and graphical techniques for the observed versus predicted EQ-5D utilities. These statistics were also calculated across the range of utility values (as well as ordinary least squares and quantile regression), to investigate how the mappings fitted across all values, not simply around the mean utility.

Results

Three algorithms developed in NSCLC were identified. The algorithm based on response mapping (Young et al., 2015) fitted the validation dataset across the range of observed values with similar fit statistics to the original publication (overall MAE of 0.087 vs 0.134). The two algorithms based on beta-binomial models presented a poor fit to both the mean and distribution of utility values (MAE 0.176, 0.178).

Conclusions

The validation of mapping algorithms is key to demonstrating their generalisability beyond the original dataset, particularly across the range of plausible utility values (not just the mean) – perceived patient similarity being insufficient. The identified algorithm from Young et al. performed well across the range of EORTC scores observed, and thus appears most suitable for use in other studies of NSCLC patients.
Preference-based measures of health-related quality of life in congenital mobility impairment: a systematic review of validity and responsiveness
Authors: Bray Nathan , Spencer Llinos Haf , Edwards Rhiannon Tudor
Published: April 2020

Introduction

Mobility impairment is the leading cause of disability in the UK. Individuals with congenital mobility impairments have unique experiences of health, quality of life and adaptation. Preference-based outcomes measures are often used to help inform decisions about healthcare funding and prioritisation, however the applicability and accuracy of these measures in the context of congenital mobility impairment is unclear. Inaccurate outcome measures could potentially affect the care provided to these patient groups. The aim of this systematic review was to examine the performance of preference-based outcome measures for the measurement of utility values in various forms of congenital mobility impairment.

Methods

Ten databases were searched, including Science Direct, CINAHL and PubMed. Screening of reference lists and hand-searching were also undertaken. Descriptive and narrative syntheses were conducted to combine and analyse the various findings. Results were grouped by condition. Outcome measure performance indicators were adapted from COSMIN guidance and were grouped into three broad categories: validity, responsiveness and reliability. Screening, data extraction and quality appraisal were carried out by two independent reviewers.

Results

A total of 31 studies were considered eligible for inclusion in the systematic review. The vast majority of studies related to either cerebral palsy, spina bifida or childhood hydrocephalus. Other relevant conditions included muscular dystrophy, spinal muscular atrophy and congenital clubfoot. The most commonly used preference-based outcome measure was the HUI3. Reporting of performance properties predominantly centred around construct validity, through known group analyses and assessment of convergent validity between comparable measures and different types of respondents. A small number of studies assessed responsiveness, but assessment of reliability was not reported. Increased clinical severity appears to be associated with decreased utility outcomes in congenital mobility impairment, particularly in terms of gross motor function in cerebral palsy and lesion level in spina bifida. However, preference-based measures exhibit limited correlation with various other condition-specific and clinically relevant outcome measures.

Conclusion

Preference-based measures exhibit important issues and discrepancies relating to validity and responsiveness in the context of congenital mobility impairment, thus care must be taken when utilising these measures in conditions associated with congenital mobility impairments.
A note on degenerate Genocchi and poly-Genocchi numbers and polynomials
Authors: Kim Taekyun , Kim Dae San , Kwon Jongkyum , Kim Han Young
Published: April 2020

Recently, Dolgy–Jang introduced the poly-Genocchi polynomials and numbers arising from the modified polyexponential function. In this paper, we study the degenerate poly-Genocchi polynomials and numbers constructed from the modified degenerate polyexponential function. We derive explicit expressions for those polynomials and numbers. Also, we obtain identities involving those polynomials and numbers and some other special numbers and polynomials. In addition, we investigate the higher-order degenerate Genocchi polynomials and find identities involving those polynomials and the higher-order Changhee polynomials.
EFL Teachers’ Conceptions of Professional Development during the Practicum: Retrospective Perceptions and Prospective Insights
Authors: Aghabarari Mozhgan , Rahimi Mehrak
Published: April 2020

The current study probes into English as a Foreign Language (EFL) teachers’ conceptions of their professional development during practicum course. The study merits a mixed methods approach and has utilized both quantitative and qualitative data gathering and analysis. To gather quantitative data, 100 EFL teachers were asked to complete a questionnaire that measured their retrospective perceptions of the role of practicum in their professional development. To gather qualitative data, 20 student-teachers (STs) of Teaching English as Foreign Language (TEFL) were asked to write narrations while they were taking part in their practicum courses for two years. The results of quantitative data analysis revealed that the participants had roughly positive retrospective perceptions of the practicum course and its role in their professional development. It was also found that novice teachers (with 1-5 years of experience), those participants whose practicum course lasted longer (two semesters or longer), and those who had taken part in the practicum after teacher education curriculum change had more positive perceptions of the practicum course.The result of qualitative analysis revealed that STs were generally satisfied with the content, methodology and assessment of the practicum. They reported certain challenges they faced during the practicum including relation with cooperating teachers and their supervisors’ strictness. They also believed that the practicum helped them expand their pedagogical insights on EFL theories and practices, although they needed help on certain issues including assessment of students’ learning.
An efficient load flow solution for distribution system with addition of distributed generation using improved harmony search algorithms
Authors: Tyagi Arjun , Kumar Krishan , Ansari M. A. , Kumar Bhavnesh
Published: April 2020

The distribution system analysis is very important to know the system condition at any given point of time. This distribution power flow plays an important role. Many power flow techniques have been proposed in the past for distribution power flow (DPF). The implicit Z-bus Gauss–Seidel (GS) method is good when dispersed generations are modelled as PQ nodes in the distribution system but, when dispersed generations are modelled as PV nodes, it leads to divergence problems. In a Newton-like method, a slight change in the execution of the bus-type switching logic leads to an unlike convergence characteristic. Though backward/forward (BW/FW) method is effective and efficient, it slows down under heavy-load condition. Now, with the addition of distributed generation (wind/solar, etc.) at the distribution level, the classical configuration of the distribution system is also changed. This poses a need for more robust and efficient technique. This paper investigates the application of a new algorithm known as improved harmony search (IHS) for DPF. The IHS can determine multiple power flow solutions which fix the limitations of other methods while determining a solution for the highly stressed condition. The results for a standard test system are taken with IHS, Newton–Raphson (NR) and BW/FW method without and with the impact of the wind energy system, to show the potential of the proposed algorithm.
Section 136: the ‘grey zone’ after the 24-h validity period lapses
Authors: Ramesh Yathooshan , Kripalani Mukesh
Published: April 2020

If a Mental Health Act section 136 lapses at 24 h because no in-patient bed is available, the legal grounds to continue holding an individual in the place of safety are dubious. Duty of candour and a senior clinical review are essential. The use of common law and the Mental Capacity Act have limitations, the latter also raising a question about whether deprivation of liberty safeguards would also apply. Clarity of this dilemma is needed through legislation.
A stable sub-complex between GCP4, GCP5 and GCP6 promotes the assembly of γ-tubulin ring complexes
Authors: Haren Laurence , Farache Dorian , Emorine Laurent , Merdes Andreas
Published: April 2020

γ-Tubulin is the main protein involved in the nucleation of microtubules in all eukaryotes. It forms two different complexes with proteins of the GCP family (γ-tubulin complex proteins): γ-tubulin small complexes (γTuSCs) that contain γ-tubulin, and GCPs 2 and 3; and γ-tubulin ring complexes (γTuRCs) that contain multiple γTuSCs in addition to GCPs 4, 5 and 6. Whereas the structure and assembly properties of γTuSCs have been intensively studied, little is known about the assembly of γTuRCs and the specific roles of GCPs 4, 5 and 6. Here, we demonstrate that two copies of GCP4 and one copy each of GCP5 and GCP6 form a salt (KCl)-resistant sub-complex within the γTuRC that assembles independently of the presence of γTuSCs. Incubation of this sub-complex with cytoplasmic extracts containing γTuSCs leads to the reconstitution of γTuRCs that are competent to nucleate microtubules. In addition, we investigate sequence extensions and insertions that are specifically found at the N-terminus of GCP6, and between the GCP6 grip1 and grip2 motifs. We also demonstrate that these are involved in the assembly or stabilization of the γTuRC.
Essential Role of Heterocyclic Structure of N-Alkylated 2-Pyrrolidone Derivatives for Recycling Uranium from Spent Nuclear Fuels
Authors: Inoue Tsubasa , Kazama Hiroyuki , Tsushima Satoru , Takao Koichiro
Published: April 2020

In a simple and versatile reprocessing method for recycling U and Pu from spent nuclear fuels, cyclic amides like N-alkylated 2-pyrrolidone derivatives (NRPs) are exclusively employed. However, there has been no convincing rational to explain why such a heterocyclic structure is required. To answer this question, we employed N-cyclohexyl-2-pyrrolidone (NCP) and N-cyclohexylformamide (NCF) as cyclic and acyclic monodentate amides, and focused on the following 3 topics in this study; (1) structural chemistry of their uranyl dinitrato complexes, (2) precipitation behavior of UO22+ from HNO3(aq) by using these amides, and (3) their chemical stability in HNO3(aq) simulating the reprocessing conditions for spent nuclear fuels. Fundamental coordination chemistry of UO2(NO3)2(L)2 (L = NCP, NCF) was found to be common to both L, regardless of the presence or absence of the pyrrolidone ring. Furthermore, both L exhibit comparable capability in precipitation of UO22+ from HNO3(aq). The most critical difference between NCP and NCF was found in their chemical stability in HNO3(aq), where NCF was gradually decomposed through acid-catalyzed hydrolysis, while NCP remained intact for at least 4 h. In conclusion, the pyrrolidone ring of NRPs plays an important role to sterically protect the carbonyl C from nucleophilic hydrolysis which initiates the amide C(=O)–N bond cleavage.
Over-expression of Ki-67 as a predictor of lymph node metastasis in penile cancer patients
Authors: Warli Syah Mirsya , Siregar Ginanda Putra
Published: April 2020

Introduction: Penile cancer is a moderately common malignancy in developing countries. Metastasis to regional lymph nodes is an essential factor in a patient’s prognosis, as its occurrence predicts poor patient prognosis. As micro-metastasis occurs in more than 25% of cases, the need for more accessible diagnostic tools is necessary. Ki-67 is commonly used as a marker of proliferation associated with tumor grade and lymph node metastasis.

Methods: Samples were taken from penile cancer patients between 2013 to 2018, in the form of formalin-fixed paraffin-embedded (FFPE) blocks were analyzed. Patient demographic data, current and pre-cancer condition, cancer staging, outcomes, and other results of adjuncts and treatment modalities were obtained from medical records. Immunohistochemistry analysis was carried out on FFPE preparations. Under 20% of nuclei stained was considered as low-expression and more than 20% of nuclei stained was considered as Ki-67 over-expression. Data processing and analysis were carried out using SPSS software. 

Results: In total, 48 FFPE samples were analyzed, with a mean patient age of 50.79 (±9.51 SD). For all patients, the type of pathology was squamous cell carcinoma. Node metastasis was positive in 34 patients (70.8%) and negative in 14 patients (29.2%). Statistical analysis was carried out using the Chi-Square test, resulting in a significant correlation between the expression of Ki-67 and lymph node metastasis in penile squamous cell carcinoma (p=0.045).

Conclusion: Over-expression of Ki-67 were found in penile cancer patients with lymph node metastasis. Therefore, Ki-67 might be useful in predicting lymph node metastasis in penile cancer patients.
New developments in chondrocyte ER-stress and related diseases
Authors: Briggs Michael D. , Dennis Ella P. , Dietmar Helen F. , Pirog Katarzyna A.
Published: April 2020

Cartilage comprises a single cell type, the chondrocyte, embedded in a highly complex extracellular matrix. Disruption to the cartilage growth plate leads to reduced bone growth and results in a clinically diverse group of conditions known as genetic skeletal diseases (GSDs). Similarly, long-term degradation of articular cartilage can lead to osteoarthritis (OA), a disease characterised by joint pain and stiffness. As professionally secreting cells, chondrocytes are particularly susceptible to endoplasmic reticulum (ER) stress and this has been identified as a core disease mechanism in a group of clinically and pathologically related GSDs. If unresolved, ER stress can lead to chondrocyte cell death. Recent interest has focused on ER stress as a druggable target for GSDs and this has led to the first clinical trial for a GSD by repurposing an antiepileptic drug. Interestingly, ER stress markers have also been associated with OA in multiple cell and animal models and there is increasing interest in it as a possible therapeutic target for treatment. In summary, chondrocyte ER stress has been identified as a core disease mechanism in GSDs and as a contributory factor in OA. Thus, chondrocyte ER stress is a unifying factor for both common and rare cartilage-related diseases and holds promise as a novel therapeutic target.
Financial markets
Authors: Evsin Maksim , Spesivcev Valeriy
Published: April 2020

Tutorial on the discipline "Financial markets" covers all the course topics provided by the curriculum: the role and function of financial markets in the economy; securities market; the derivatives market; institutions of financial markets.
Contains a large number of modern examples and test tasks of different difficulty options that will allow to generate the required Federal state educational standards of professional competence.
Meets the requirements of Federal state educational standards of higher education of the last generation.
For students enrolled in the direction 38.03.01 "Economics", it may be useful to undergraduate students of other areas.
Psychology of cognition preschooler in professional and pedagogical activity of the teacher
Authors: Uruntaeva Galina , Gosheva Ekaterina
Published: April 2020

The monograph is devoted to analysis of professional and pedagogical activity of educator of preschool educational organizations in the aspect of cognition of preschool children. Describes the conceptual presentation of these activities, including structural-functional model of the activities to knowledge and activities for analysis of its process and results in order to assess its effectiveness. In accordance with the business model for knowledge of child the proposed system of professional training of future educators for its development in the learning process at the University, partly experimentally tested.
Intended for researchers, professional and pedagogical activity of the teacher of preschool educational institutions, teachers and practitioners of preschool education and teachers and students of psychological and pedagogical universities.
On the Budget Investment of Central District Hospitals in the Region in the Conditions of Digitalization of the Economy
Authors: Sycheva I. , Sycheva N. , Zharova D. , Solokolovskiy V. , Fatuev V. , Sabinina A.
Published: April 2020

The work is devoted to the study of sources and mechanisms of financing investment activities of health care institutions in the region at the municipal level. It is established that out of the three state-controlled sources of financing, only the Federal budget and the budget of the subject of the Federation are allocated for investment purposes as part of the implementation of the region's sectoral state health program. The results of the reorganization of Central district hospitals conducted in 2019 are studied. in Kaluga region. Significant amounts of allocated funds and a lot of "pain points" for investment create a problem of their effective distribution between inter-district and district Central hospitals. The methodical approach to its solution based on the evaluation of the ratio of supply and demand for health services in each municipality in the study, the proposals of the Central district hospitals according to the volume and quality of medical services and demand for them with the position of the current and future needs of the population in the conditions of formation and use of regional information and consultancy platforms of the Unified state information system of health (USISH).
Research Potential of Digital Transformation of the Tyumen Region
Authors: Mahmudova Muhabbat
Published: April 2020

Intensive penetration of digital technologies in business structures, in the economy, as well as in most areas of human activity, opens up new opportunities in management, production of goods and services, changes the structure of consumption, labor and entrepreneurial activities, etc. At the same time, maintaining the momentum digitalization and ensuring the high efficiency of this process at the national level and in the regions implies the presence and permanent development of research potential. It is the state and level of development of the research potential of the regions that shape its competitive advantages in the pace of digital transformation of the economy. The article analyzes current trends in the dynamics of statistical indicators of the state and development of the research potential of the Tyumen region.
Current Trends in the Dynamics of Consumer Lending in Russia
Authors: Terehova N.
Published: April 2020

A characteristic feature of the current stage of economic development is an increase in current consumption by households while reducing their savings. This is a peculiar phenomenon of the Russian practice of economic development. Since this transition is an indicator of a steadily developing economic environment. However, the current inflationary processes in the Russian economy and the instability of the national currency have a negative impact on the dynamics of monetary incomes of the population and their forced departure from the savings model. In order to meet current needs and purchase necessary goods and services, Russians are increasingly using credit funds, whose interest rates are currently characterized by a downward trend. However, the expansion of the purchasing power of the population at the expense of credit funds leads to an increase in the risk of non-return and the decline in the solvency citizens. The article analyzes the dynamics of the volume and structure of consumer lending for the period 2016–2019. The article analyzes changes in loan rates, the volume of overdue debt, and regional features of lending to the country’s population.
Development of the Potential of the Middle Class of Society As a Factor in the Implementation of the Strategy of Socio-Economic Development of the Vologda Region Until 2030
Authors: Tulina T.
Published: April 2020

The article examines the possible use of the potential of the middle class as factor of realization of strategy of socio-economic development of Vologda oblast for the period up to 2030. The authors found that the potential of the middle class has many useful characteristics, which makes it one of the most important factors in the development of the territory. For the convenience of analyzing the characteristics of the middle class, their classification by spheres of social life is proposed: economic, spiritual, social and political. The author shows how using the characteristics of the potential of the middle class in each sphere of public life and implementing a strategy for their development, it is possible to achieve the indicators of the strategy of socio-economic development of the Vologda region for the period up to 2030, and its main goal-people saving.
Realization of Scientific and Technological Capability: Federal, Regional and Production Aspects of Innovative Economic Development
Authors: Levin Yuriy , Visitaev M.
Published: April 2020

The article examines aspects of the implementation of the Russian economy scientific and technological potential from a systematic point of view. The authors proceed from the hypothesis that the low competitiveness of the Russian economy is determined by the profile of its innovation system. The article examines the dynamics of innovation activity costs and analyzes the reasons for the continuing decline in innovation activity that characterizes the current economic situation in Russia. Economic activity at each level will only be a determinant of the innovation development mechanism when it is aimed at creating and implementing new developments in order to generate higher revenues than those that provided the innovation development. It is pointed out that economic policy focused on building national competitive advantages is inseparable from creating a national innovation system. Ways of influence of innovative activity on the solution of social and economic problems are given. The author substantiates the socio-economic conditions necessary for the innovative development of regions. The importance of exports and the development of the enterprise's export potential for the transition to the phase of active structural transformations is evaluated. It is concluded that the formation of the national innovation system requires a balance of scientific and technical potential built into the framework of the state – industry – region – enterprise.
On Robust Fractional 0-1 Programming
Authors: Mehmanchi Erfan , Gillen Colin P. , Gómez Andrés , Prokopyev Oleg A.
Published: April 2020

We study single- and multiple-ratio robust fractional 0-1 programming problems (RFPs). In particular, this work considers RFPs under a wide range of disjoint and joint uncertainty sets, where the former implies separate uncertainty sets for each numerator and denominator and the latter accounts for different forms of interrelatedness between them. We first demonstrate that unlike the deterministic case, a single-ratio RFP is nondeterministic polynomial-time hard under general polyhedral uncertainty sets. However, if the uncertainty sets are imbued with a certain structure, variants of the well-known budgeted uncertainty, the disjoint and joint single-ratio RFPs are polynomially solvable when the deterministic counterpart is. We also propose mixed-integer linear programming (MILP) formulations for multiple-ratio RFPs. We conduct extensive computational experiments using test instances based on real and synthetic data sets to evaluate the performance of our MILP reformulations as well as to compare the disjoint and joint uncertainty sets. Finally, we demonstrate the value of the robust approach by examining the robust solution in a deterministic setting and vice versa.
High-intensity interval training in patients with heart failure
Authors: Callum Kara J , Gorely Trish , Crabtree Daniel R , Muggeridge David J , Leslie Stephen J
Published: April 2020

Cardiac rehabilitation is a key component in the secondary prevention of cardiovascular disease. However, uptake and adherence to programmes is suboptimal, especially for patients with heart failure. Traditionally, cardiac rehabilitation programmes have involved moderate-intensity continuous training; however, there is growing evidence that high-intensity interval training can produce equal or superior effects in both healthy and diseased populations. High-intensity interval training has already been shown to be both safe and effective, but the optimal protocols and delivery mechanisms are yet to be determined. Despite this, high-intensity interval training has the potential to offer an alternative mechanism of cardiac rehabilitation delivery to patients with heart failure, with the possibility of overcoming some of the challenges usually faced (such as patients' lack of time) in implementing successful cardiac rehabilitation programmes. This article aims to summarise the current knowledge surrounding the inclusion of high-intensity interval training in cardiac rehabilitation programmes, specifically focusing on those patients living with heart failure.
AMPK-mediatedhy Poglycemic Effect of Banana Stem Juice on Type 2 Diabetes
Authors: Thi Dong Nguyen , Thanh Huong Phung
Published: April 2020

ABSTRACT: Musa paradisiaca L. (Musaceae) or banana is a common plant in the tropics. Its stem juice has been long used as a traditional cure for diabetic people in several tropical countries. Its hypoglycemic effect has been reported on some experimental hyperglycemic models. However, there has not been any study revealing the hypoglycemic effect and mechanism of banana stem juice in type 2 diabetes. The current study aimed at discovering its effects by a glucose tolerant test on experimental type 2 diabetic rats and an in vitro test on adenosine monophosphate - activated protein kinase (AMPK), a key enzyme in metabolic regulation. The glucose tolerance test was done after 2 weeks of banana stem juice treatment. The glucose AUC of the treated rats was significantly lower (p<0.05%) compared with that of the controls. At the concentration of 50 µg/ml, the banana sample significantly increased the quantity of phosphorylated AMPK, the active form of AMPK, in C2C12 skeleton cells (p<0.001). In conclusion, the glucose tolerance enhancing effect of the banana stem juice was explained by the activation of AMPK which plays an essential role in metabolic homeostasis.
Factors associated with burnout syndrome in surgeons: a systematic review
Authors: Galaiya R , Kinross J , Arulampalam T
Published: April 2020

Introduction

To date, studies have shown a high prevalence of burnout in surgeons. Various factors have been found to be associated with burnout, and it has significant consequences personally and systemically. Junior doctors are increasingly placing their own health and wellbeing as the most important factor in their decisions about training. Finding ways to reduce and prevent burnout is imperative to promote surgical specialties as attractive training pathways.

Methods

The MEDLINE, PsychInfo and EMBASE databases were searched using the subject headings related to surgery and burnout. All full text articles that reported data related to burnout were eligible for inclusion. Articles which did not use the Maslach Burnout Inventory or included non-surgical groups were excluded; 62 articles fulfilled the criteria for inclusion.

Findings

Younger age and female sex tended to be associated with higher levels of burnout. Those further in training had lower levels of burnout, while residents suffered more than their seniors. Burnout is associated with a lower personal quality of life, depression and alcohol misuse. Academic work and emotional intelligence may be protective of burnout. Certain personality types are less likely to be burnt out. Mentorship may reduce levels of burnout.

Conclusions

Workload and work environment are areas that could be looked at to reduce job demands that lead to burnout. Intervening in certain psychological factors such as emotional intelligence, resilience and mindfulness may help to reduce burnout. Promoting physical and mental health is important in alleviating burnout, and these factors likely have a complex interplay.
PLANEJAMENTO URBANO: UM HISTÓRICO SOBRE SERRINHA-BA
Authors: Oliveira Luiz Eduardo Freire de Lima
Published: April 2020

A temática sobre o planejamento urbano é cada vez mais discutida e debatida no meio acadêmico e profissional. Ao compreender suas limitações, entende-se que para que haja uma evolução na busca por um projeto cidade é primordialfazer o exercício de planejar, mesmo que esse não tenha resultados imediatos. Tratando o planejamento como um processo dinâmico, mutável e que não termina com a elaboração de um plano, o entendimento do passado, ou seja, como a sociedade pensava a organização da cidade, permite que sejam avaliadas as ações ou as ausências dessas e suas consequências. Portanto, neste artigo, serão apresentados conceitos sobre planejamento urbano e uma análise histórica de como foi o desenvolvimento desse na cidade de Serrinha-BA. Para isso, foi realizado levantamento bibliográfico e da legislação, utilização de conhecimento empírico e dados secundários. Apesar do avanço com relação à legislação, existe a necessidade de implementação de um conjunto de fatores que conduza a prática efetiva do aparato legal que norteia o planejamento na cidade e para que esse abarque toda complexidade que existe, sendo multidisciplinar, participativo, elaborado com base em características sociais ecorrelacionado com a questão financeira.
State-generating matrix for differential Mueller matrices of depolarizing optical media
Authors: Devlaminck V. , Charbois J. M.
Published: April 2020

Unlike the Mueller matrix, where parameters are not directly accessible for physical interpretation, the state-generating matrix recently introduced [J. Opt. Soc. Am. A 34, 80 (2017)JOAOD60740-323210.1364/JOSAA.34.000080] provides a powerful mathematical tool for formulating all properties of nondepolarizing systems. Extending this notion to the case of depolarizing differential Mueller matrices is the issue we address in this paper. We show that the formulation of the problem using complex random vectors makes it possible to directly introduce the formalism of a state-generating matrix in the case of differential depolarizing matrices. Examples of physical interpretations that can be obtained are presented specifically for a homogeneous medium. Illustrations are given when the complex vector degenerates into a complex scalar and when a Gaussian random processes hypothesis is made.