bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric cancer: a registry based study
Authors: Kim Kyung Won , Lee Koeun , Lee Jung-Bok , Park Taeyong , Khang Seungwoo , Jeong Heeryeol , Ko Chang-Seok , Yook Jeong-Hwan , Kim Byung-Sik , Lee Inseob
Published: October 2020

Background: Patients with gastric cancer have increased nutritional risk and experience a significant skeletal muscle loss after surgery. We aimed to determine whether muscle loss during the first postoperative year and nutritional status are indicators for predicting prognosis. Methods: From a gastric cancer registry, a total of 958 patients who received curative gastrectomy followed by chemotherapy for stage 2 and 3 gastric cancer and survived longer than 1 year were investigated. Clinical and laboratory data were collected. Skeletal muscle index (SMI) was assessed based on the muscle area at the L3 level on abdominal computed tomography. Results: Preoperative nutritional risk index (NRI) and postoperative decrement of SMI (dSMI) were significantly associated with overall survival (hazards ratio: 0.972 [95% CI: 0.958-0.986] and 1.058 [95% CI: 1.033-1.085], respectively) in a multivariate Cox regression analysis. Recurrence, tumor stage, comorbidity, and the preoperative muscle and subcutaneous fat area were also significant prognostic indicators. Kaplan-Meier analyses exhibited that patients with higher NRI had a significantly longer survival than those with lower NRI (3-year overall survival: 84.6% vs. 72.9%, P < 0.001). In addition, a significantly better prognosis was observed in a patient group with less decrease of SMI (3-year overall survival: 85.6% vs. 74.5%, P = 0.009). A logistic regression analysis demonstrated that the performance of preoperative NRI and dSMI in mortality prediction was quite significant (AUC: 0.63, P < 0.001) and the combination of clinical factors enhanced the predictive accuracy to the AUC of 0.90 (P < 0.001). This prognostic relevance of NRI and dSMI was maintained in patients experiencing tumor recurrence. Conclusions: Skeletal muscle loss during the first postoperative year and preoperative NRI are predictors of overall survival in stage 2 or 3 gastric cancer patients regardless of relapse. Our results support the potential importance of exercise and nutritional support along with standard treatment.
A haemagglutination test for rapid detection of antibodies to SARS-CoV-2
Authors: Joly Etienne , Townsend Alain , Rijal Pramila , Xiao Julie , Tan Tiong Kit , Schimanski Lisa , Rahikainen Rolle , Hoosdally Sarah , Street Teresa , Rudkin Justine , Stoesser Nicole , Karpe Fredrik , Neville Matthew , Ploeg Rutger , Oliveira Marta , Mentzer Alexander , Knight Julian , Kwok Andrew , Screaton Gavin , Mongkolsapaya Juthathip , Dejnirattisai Wanwisa , Supasa Piyasa , Klenerman Paul , Dold Christina , Allcock Alice , Bibi Sagida , Clutterbuck Elizabeth , Huang Kuan-Ying , Huo Jiandong , Gupta Nimesh , Crook Derrick , Roberts David , Lamikanra Abigail , Tsang Hoi , Bown Abbie , Vipond Richard , Baillie J , Moore Shona , Semple Malcolm , Turtle Lance , Openshaw Peter , Ainsworth Mark , Beer Sally , Espinosa Alexis , Mendoza Maria , Georgiou Dominique , Lockett Teresa , Martinez Jose , Perez Elena , Sanchez Veronica , Scozzafava Giuseppe , Sobrinodiaz Alberto , Thraves Hannah , Matthews Philippa
Published: October 2020

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, detection of seroconversion after vaccination, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests have a long history in blood typing, and general serology through linkage of reporter molecules to the red cell surface. They do not require special equipment, are read by eye, have short development times, low cost and can be applied as a Point of Care Test (POCT). We describe a red cell agglutination test for the detection of antibodies to the SARS-CoV-2 receptor binding domain (RBD). We show that the Haemagglutination Test (HAT) has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. The HAT can be titrated, detects rising titres in the first five days of hospital admission, correlates well with a commercial test that detects antibodies to the RBD, and can be applied as a point of care test. The developing reagent is composed of a previously described nanobody to a conserved glycophorin A epitope on red cells, linked to the RBD from SARS-CoV-2. It can be lyophilised for ease of shipping. We have scaled up production of this reagent to one gram, which is sufficient for ten million tests, at a cost of ~0.27 UK pence per test well. Aliquots of this reagent are ready to be supplied to qualified groups anywhere in the world that need to detect antibodies to SARS-CoV-2, but do not have the facilities for high throughput commercial tests.
Surge of Severe Acute Respiratory Syndrome Coronavirus 2 Infections Linked to Single Introduction of a Virus Strain in Myanmar, 2020
Authors: Nyunt Myat Htut , Soe Hnin Ohnmar , Aye Kay Thi , Aung Wah Wah , Kyaw Yi Yi , Kyaw Aung Kyaw , Myat Theingi Win , Latt Aung Zaw , Win Min Min , Win Aye Aye , Htun Yin Min , Zaw Khaing Mar , Ei Phyu Win , Hein Kyaw Thu , San Lai Lai , Oo Nan Aye Thida , Lin Htin , Mon Nan Cho Nwe , Yee Khin Than , Htun Khin Lapyae , Aye Lynn Pa Pa , Ko Yamin Ko , Htoo Thitsar Htet Htet , Aung Kham Mo , Azili Hnin , Han Soe Soe , Zaw Ni Ni , Win Su Mon , Thwe Wai Myat , Aye Thin Thin , Hlaing Myat Su , Minn Wai Yan , Thu Pyae Phyo , Thu Hlaing Myat , Htun Zaw Than
Published: October 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major health concern globally. Genomic epidemiology is an important tool to assess the pandemic of the coronavirus disease 2019 (COVID-19). Several mutations have been reported by genome analysis of the SARS-CoV-2. In the present study, we investigate mutational and phylogenetic analysis of 30 whole genome sequences for genomic characteristics of the virus in the specimens collected early phase of pandemic, (March-June, 2020) and sudden surge of infection (August-September, 2020). Phylogenetic analysis revealed that 4 samples of L strain and 1 GR strain in early stage of local transmission, while 6 returnees by rescue flights showed GH (India) and GR strains (China and Philippines) with no evidence of local spread. However, all 19 whole genome sequences in sudden surge of local transmission showed genetically distinct clade GH (Lineage B.1.36). Surge of second wave on SARS-CoV-2 infection was linked to the single-introduction of the GH strain that may be a result of strict restriction of international travel and containment efforts. These genomic data provides the useful information to disease control and prevention strategy.
Changing Clusters of Indian States with respect to number of Cases of COVID-19 using incrementalKMN Method
Authors: Prasad Rabinder Kumar , Sarmah Rosy , Chakraborty Subrata
Published: October 2020

The novel Coronavirus (COVID-19) incidence in India is currently experiencing exponential rise with apparent spatial variation in growth rate and doubling time. We classify the states into five clusters with low to high-risk category and identify how the different states moved from one cluster to the other since the onset of the first case on $30^{th}$ January 2020 till the end of $15^{th}$ September 2020. We cluster the Indian states into $5$ groups using incrementalKMN clustering \cite{b1}. We observed and comment on the changing scenario of the formation of the clusters starting from before lockdown, through lockdown and the various unlock phases.
Smart Culture Management: Theoretical Aspects
Authors: Milkintas Rytis
Published: October 2020

The aim of the research is the investigation of the essential theoretical aspects of smart culture management. The article formulates the theoretical construct of smart culture management by combining cultural management and management concepts, closely linking cultural management with the implementation of cultural policy and seeing the specifics of smart cultural management.Qualitative analysis was performed of theoretical sources of foreign countries and Lithuania. Also, a comparative analysis of different concepts was carried out, highlighting similarities and differences of concepts (in order to discern correlations between them).Five groups of cultural management concepts are distinguished: cultural management as specific management in art and culture; cultural management as a phenomenon, process reflecting the formation and implementation of cultural policy; cultural management as an institution management; cultural management as a profession and academic discipline; cultural management as leadership-based management. Theoretical analysis of the phenomenon of smartness in cultural management allowed us to distinguish six dimensions of smartness: strategic, creative development, harmonization of interests in the cultural sector, empowered cultural sector parties, the harmony of intellectual and technological capital, the culture of shared value creation.Exploring the urban cultural field situation, using a model that reflects the 6 dimensions of smart culture management and 18 qualities of a smart social system, will highlight the strengths and weaknesses of the cultural field. By analyzing the weaknesses, the researchers will be able to make recommendations on how to improve the current situation. Improving the cultural field at the local level will significantly increase the quality of cultural services provided to the population.In future research, it is planned to apply the theoretical model of smart culture management to the analysis of situation analysis in the selected city. Analysis based on this theoretical model can also be performed at the state level, thus providing a comprehensive view of the cultural field situation.
A Extensão universitária como difusora de mecanismos extraprocessuais de solução de conflitos em escolas
Authors: Alves Abreu Paula Renata
Published: October 2020

O relato em voga tem como objeto o debate, em nível acadêmico, das tarefas executadas no bojo doprojeto denominado “Mediação de Conflitos, Justiça Restaurativa e Cultura de paz em pauta no ambienteescolar”, ligado à Universidade Estadual do Maranhão. A ação extensionista, selecionada por edital, foiconcretizada em 2018 e 2019 por alunos do curso de Direito da aludida instituição, sob chancela de docenteorientador. Ambicionando difundir a essência da administração extraprocessual de conflitos na educaçãobásica, o objetivo central do projeto consistiu na difusão de valores e práticas ligados à mediação e à justiçarestaurativa. Assim, para criar um ambiente pautado na cultura de paz e na tolerância, a equipe de trabalho,valendo-se de debates orais, slideshow e dinâmicas, promoveu diversos encontros em duas escolas públicas deSão Luís/MA. Destarte, o projeto apurou bons resultados, haja vista perceptível mudanças comportamentais dopúblico-alvo após as intervenções realizadas.
Patrones de incidencia del deterioro del arbolado urbano de Bogotá
Authors: Ramirez Sanchez Abraham , Hurtado Vasquez Cristián Camilo , Triana Gómez Max Alejandro
Published: October 2020

En este artículo se presentan las relaciones geoespaciales entre el arbolado urbano de Bogotá con los registros promedio anuales de contaminación, área de influencia de las vías y sitios de interés (Catastro). Se utilizaron datos para el año 2007 de las variables a relacionar. La metodología utilizada es CRISP-DM (Cross Industry Standard Process for Data Mining). Los patrones de relaciones se evaluaron bajo los algoritmos de árboles de decisión el cual define las variables relevantes para cada Dataset y el análisis clúster el cual analiza las variables relevantes respecto a los tipos de afectaciones evaluadas, teniendo que las variables relevantes de cada Dataset fueron especie, porcentaje de afectación general, porcentaje de afectación en tronco, sitios de interés, ancho de vías, número de carriles y localidades. En los resultados se encontró que las especies Urapán y Sauco fueron las que presentaron relaciones con las variables evaluadas, siendo Urapán la que se relacionaba con las demás variables de cada Dataset. Esta investigación servirá para la toma de decisiones respecto al manejo del arbolado urbano de Bogotá.
Solución de la ecuación de convección difusión mediante las funciones de base radial multicuádricas
Authors: Hernández Marulanda Andrés Felipe , Gaviria Posada Leidy Johana
Published: October 2020

En este paper se propone un algoritmo computacional que resuelve la ecuación de convección difusión unidimensional estacionaria, utilizando un método numérico basado en las funciones de base radial (RBF). Para la aplicación de este algoritmo es necesaria la generación de diferentes valores del número de Peclet para obtener soluciones gráficas, en donde se comparó con la solución analítica reportada por Patankar.
Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling
Authors: Agrawal Shilpi , Maity Sanhita , AlRaawi Zeina , Al-Ameer Musaab , Kumar Thallapuranam Krishnaswamy Suresh
Published: October 2020

Background::

The fibroblast growth factor (FGF) family is comprised of 23 highly regulated
monomeric proteins that regulate a plethora of developmental and pathophysiological processes,
including tissue repair, wound healing, angiogenesis, and embryonic development. Binding of
FGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan,
heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediate
induction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, and
STAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification,
FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions.
Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis,
and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiological
changes.

Objective::

This comprehensive review will discuss the biology, chemistry, and functions of FGFs,
and its current applications toward wound healing, diabetes, repair and regeneration of tissues, and
fatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFR
and aid in mitigating various disorders, such as cancer, are also discussed in detail.

Conclusion::

Inhibitors of FGFR signaling are promising drugs in the treatment of several types of
cancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activation
of other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activity
on FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFR
targeting therapies is the recent focus of several preclinical and clinical studies.
Halogen Bond-Catalyzed Friedel-Crafts Alkylation of Indole with Ketones and Aldehydes for the Synthesis of Symmetrical 3,3’-diindolylmethanes Using Simple Halogen Donor Catalyst
Authors: Zhou Xiao-Yu , Chen Xia
Published: October 2020

The Friedel-Crafts alkylation of indole with ketones and aldehydes had been developed
to prepare 3,3’-diindolylmethanes using iodine or NCS as catalysts. Two mild and efficient catalysis
systems were provided for the activation of carbonyl compounds and indoles. The reaction
proceeded smoothly in ethanol to produce the corresponding products with good to excellent
yields. Furtherly, the mechanism was speculated.
Treatment and Long-Term Sequelae in Childhood Brain Tumors
Authors: Attina Giorgio , Ariano Anna , Maurizi Palma , Triarico Silvia , Capozza Michele Antonio , Coccia Paola , Rizzo Daniela , Mastrangelo Stefano , Ruggiero Antonio
Published: October 2020

In children treated for brain tumors, important deficits in cognitive development have been described. The reduction of Intelligence Quotient (IQ) is correlated with multiple conditions such as tumor location, obstructive hydrocephalus, surgical intervention, and above all, the use of radiotherapy, especially in young children. Demyelinization represents the most striking microscopic alteration following radiation: cerebral white matter’s loss and failure to white matter development could partly account for changes in IQ score.

Recently, combined chemo-radiotherapeutic approaches and the improvement of radiotherapy techniques have enabled the reduction of neurocognitive symptoms and improved the standard of life of childhood brain tumor survivors.
Multiplex PCR Assay for the Simultaneous Detection of the Brucella Genus in Human Whole Blood and Serum
Authors: Zamanian Mohsen , Jahani Elham , Mahmoudi Hassan
Published: October 2020

Background:

Brucellosis disease is a serious zoonosis worldwide and only 17 countries have been recognized as free of brucellosis. The World Health Organization has reported that the incidence of brucellosis is 500,000 cases in a year. Multiplex polymerase chain reaction (PCR) is an ideal method for the identification of brucellosis. The most common primers for the diagnosis of Brucella include B4/B5 and F4/R2. The advantages of multiplex PCR include targeting multiple sequences at the same time, and multiple results are produced in a single test run which saves time and the reagents simultaneously. The purpose of this investigation was to extend and optimize a multiplex PCR for the identification of genus Brucella from serum and whole blood samples.

Methods:

In this experimental and sectional study, blood samples of 25 suspected patients in the acute phase of brucellosis with serum titers higher than 1:80 were collected. Two pairs of specific primers of B4 and B5 the specific gene was amplified. PCR and Multiplex PCR were performed on blood and serum samples.

Results:

Among 25 blood samples, 15 cases (60%) and 9 cases (36%) and among 25 serum samples, 23 cases (92%) and 13 cases (52%) were positive for B4/B5 and F4/R2 in PCR, respectively. In multiplex PCR, among 25 blood samples, 5 cases (20%) showed both bands, 11 cases (44%) showed band 222bp, 4 cases (16%) showed band 905bp and 5 cases (20%) showed no bands. Among 25 serum samples, 6 cases (24%) showed both bands, 15 cases (60%) showed band 222bp, 3 cases (12%) showed band 905bp and 1 case (4%) showed no bands.

Conclusion:

The results of this study show that this multiplex PCR can be used for the diagnosis of brucellosis with high sensitivity in clinical laboratories routinely and it can serve as an alternative substitution for risky culture method and nonspecific serological methods.
Container Elasticity: Based on Response Time using Docker
Authors: Yadav Mahendra Pratap , Akarte Harishchandra A. , Yadav Dharmendra Kumar
Published: October 2020

Objective::

Cloud computing is an approach to provide the computing resources (machine) to end-users for running their application over the Internet. The computing resources consist of various things (e.g. RAM, Memory, CORE, etc.). These resources are allocated to an application without human intervention for managing the fluctuating workload. To manage the real-time fluctuating workload, cloud providers use VM based or Container-based virtualization to host the client services. Adding/removing resources dynamically as per the demand of application through cloud is known as elasticity. Cloud providers use the auto-scaling mechanism to implement elasticity. A machine that hosts an application can be either overloaded or under-loaded due to the real-time fluctuating workload. The cloud providers use an auto-scaling mechanism to automatically scale up or down the computing resources at the right moment for managing the real-time fluctuating workload. The failure of allocation/de-allocation of resources at right time leads to SLA violation, service unavailability, customers lost, more power consumption, minimum throughput and maximum response time. Hence, the allocation/de-allocation of resources at right moment becomes critical for successful completion of task in dynamic environment efficiently.

Methods::

Resource provisioning for managing dynamic and fluctuating workload has been achieved through an algorithm (PID with dynamic HAProxy) which is based on decision-making approach that depends on response time of container using mechanism of control theory.

Results::

The proposed work has improved performance of the system in terms of resource utilization and response time to manage the fluctuating workload.

Conclusion::

The addition/removal of containers dynamically to manage fluctuating workload can be achieved more efficiently.
Perceived Organizational Support, Job Satisfaction, Task Performance and Organizational Citizenship Behavior in China
Authors: Miao Ren-Tao
Published: October 2020

We examined the relationships of perceived organizational support and job satisfaction with organizational citizenship behavior and task performance in China. Employees from two large-scale state-owned enterprises (SOE) completed measures of perceived organizational support and job satisfaction and their immediate supervisors completed measures of task performance and four facets of organizational citizenship behavior. Data analyzed using zero-order correlation and hierarchical regression analysis showed positive correlations of perceived organizational support and job satisfaction with task performance, and also showed positive associations of perceived organizational support and job satisfaction with organizational citizenship behavior and each of its four dimensions.
Relationship of gene polymorphism with the nature of target organ damage in patients with arterial hypertension
Authors: Drobotya N. V. , Arutyunyan L. V. , Pirozhenko A. A. , Kaltukova V. V.
Published: October 2020

Objective: to assess the relationship of polymorphism of the main genes involved in the pathogenesis of arterial hypertension (AH) with indicators reflecting the state of target organs in the group of patients with arterial hypertension.

Material and methods: we examined 100 patients with arterial hypertension who underwent standard diagnostic procedures, as well as molecular genetic research.

Results: in patients with arterial hypertension statistically significant associations of AGTR2, GNB3, and NOS3 gene polymorphism with left ventricular hypertrophy, CYP11B2 and NOS3 gene polymorphism with left ventricular diastolic dysfunction, and NOS3 gene polymorphism with increased vascular wall stiffness were found (p < 0.05).

Conclusions: the results of the study indicate that patients with arterial hypertension are a genetically heterogeneous group in terms of the relationship of specific gene polymorphism with indicators that characterize the state of target organs. The use of genetic approaches is promising for early screening of patients with arterial hypertension, belonging to the high-risk group, in order to ensure timely and effective organoprotection.
The relationship between sleep duration and cardiometabolic parameters in patients with diabetes mellitus
Authors: Volkova N. I. , Dzherieva I. S. , Plyashkevich M. V. , Brovkina S. S. , Krivobokova T. S.
Published: October 2020

Objectives: to study the relationship between sleep duration and cardiometabolic parameters in patients with diabetes mellitus.

Materials and methods: the study included patients with type 1 and type 2 diabetes mellitus in the absence of acute metabolic decompensation. The exclusion criteria were: the presence of a depressive episode, the presence of alcohol dependence. In addition, the study did not include patients with cancer, erythrocytosis, sleep apnea syndrome. The duration of the patient’s sleep was determined by answering the question: less than 6 hours, more than 6 hours and up to 8 hours inclusive and more than 8 hours and up to 10 hours inclusive. In addition, the patients were questioned about their compliance with the doctor’s recommendation to take hypolipidemic hypoglycemic and antihypertensive drugs during the last 6 months preceding the survey. Statistical data processing was carried out using the Kolmogorov-Smirnov test. Since the sample was nonparametric, the data are presented by Me (Q25; Q75), where Me is the median, Q25 is the 25th percentile, and Q75 is the 75th percentile, and Spearman’s rank correlation coefficient (P) was calculated to assess the relationship between events.

Results: a total of 92 patients were interviewed. 7 patients were excluded from the sample due to the identification of a depressive episode and four patients due to the presence of alcohol dependence. Thus, the study included 81 patients, of whom 21 patients were observed for type 1 diabetes mellitus and 60 patients for type 2 diabetes mellitus. Spearman’s correlation coefficient showed that there is a direct relationship between sleep duration and HbA1c level (p < 0.01).

Conclusion: in our pilot study, the relationship between the level of glycated hemoglobin as an indicator of compensation for carbohydrate metabolism and sleep duration was confirmed.
Optimization of prediction of UC relapse and adjustment of adequate therapy in patient with ulcerative colitiss
Authors: Tkachev A. V. , Mazovka K. E. , Mkrtchyan L. S. , Makarenko A. S. , Takidze L. T.
Published: October 2020

Objective: to improve the assessment of activity of ulcerative colitis and the ability to predict the development of relapse of the disease, as well as the selection of adequate therapy.

Materials and methods: the study included 90 people: 70 patients with ulcerative colitis and 20 healthy volunteers. The disease activity was evaluated using 7 disease activity indices. The expression of matrix metalloproteinase -9 (MMP-9) in the colon mucosa was evaluated by immunohistochemistry.

Results: data were obtained on the activity of MMP-9 in colonobioptates in patients with ulcerative colitis with varying degrees of disease severity, which complements our knowledge of the pathogenetic mechanisms of UC and, based on the developed mathematical model, allows predicting the development of recurrence of UC. Based on the analysis of clinical indices of UC activity, an algorithm for evaluating the effectiveness of basic therapy has been developed.

Conclusion: tools are provided to improve the prognosis of UC relapse, and a personalized approach to evaluating the effectiveness of the alternatives of drug therapy is developed.
Circulating neurotransmitter levels in irritable bowel syndrome: correlation of laboratory tests and clinical findings
Authors: Vidiker R. V. , Trubina N. V. , Babaeva A. R.
Published: October 2020

Objective: to estimate blood levels of serotonin and melatonin neurotransmitters in patients with irritable bowel syndrome and to evaluate the role of neurohumoral imbalance in the development and clinical manifestations of irritable bowel syndrome phenotypes.

Materials and methods: the study included 60 patients (range, 18 – 45 years) diagnosed with irritable bowel syndrome according to the Roman IV criteria for irritable bowel syndrome (2016). 20 patients with a confirmed diagnosis of ulcerative colitis (UC) were assigned to a comparison group. The control group was composed of 45 apparently healthy subjects. All subjects were assigned to subgroups based on the prominent clinical presentation: irritable bowel syndrome with constipation (IBS-C), irritable bowel syndrome with diarrhea (IBS-D) and mixed irritable bowel syndrome (IBS-M). In addition to all the necessary procedures (clinical, laboratory and instrumental), blood concentrations of endogenous serotonin and melatonin were measured using enzyme-linked immunosorbent assay (ELISA).

Results: the concentrations of endogenous serotonin and melatonin were significantly lower in patients with irritable bowel syndrome as compared with those having ulcerative colitis or healthy individuals. The detection rates of lowering serotonin levels were 53.3 % and 65 % — for melatonin. Low levels of melatonin were detected both in IBS-D and IBS-C patients. 69.57 % of IBS-D patients had elevated levels of serotonin as compared with the reference values for healthy subjects. We found a strong correlation between the severity of bloating and abdominal pain on the one hand, and low levels of endogenous serotonin and melatonin, on the other hand.

Conclusion: our findings suggest that serotonin and melatonin neurotransmitters play a significant role in the pathophysiology and clinical manifestations of estimate blood levels of serotonin and melatonin neurotransmitters in patients with irritable bowel syndrome.
Schmidt syndrome in clinical practice
Authors: Vorobyev S. V. , Khripun I. A. , Kuzmenko N. A. , Streltsova E. M. , Petrovskaya E. Y.
Published: October 2020

The analysis of this clinical case is devoted to the need for strategic forecasting in the diagnosis of endocrine diseases. Autoimmune aggression is not directed against one organ, the progression of autoimmune damage is often slow, which increases the chances of missing a disease, and sometimes leads to a diagnosis at the time of crisis and decompensation. With timely suspicion of autoimmune polyglandular syndromes, the appointment of the necessary screening 1 time in 2-3 years, as well as patient education, we save them from years of diagnostic research, and timely compensatory therapy significantly improves the quality of life of patients.
Diabetic cardiomyopathy: definition, diagnosis criteria, treatment directions and prevention of heart failure
Authors: Koziolova N. A. , Karavaev P. G. , Veklich A. S.
Published: October 2020

The topical review discusses various points of view related to terminology, diagnostic criteria, difficulties in assessing the prevalence and stages of diabetic cardiomyopathy, presents used in clinical practice and potential instrumental and laboratory diagnostic methods, provides therapeutic methods and strategic directions for the treatment of this condition and the prevention of chronic heart failure.
The Development and Implementation of Alfalfa: A Smartphone Application for Remote Adjustment of Warfarin Dose (Preprint)
Authors: Jiang Shaojun , Lv Meina , Wu Tingting , Wenjun Chen , Zhang Jinhua
Published: October 2020

BACKGROUND

Patients taking warfarin need to spend substantial time, money, and energy frequently visiting the hospital in order to adjust its dose. With the development of mobile medicine and the increasing number of mobile-phone users, these patients can conveniently adjust their warfarin dose remotely.

OBJECTIVE

The aim of this article is (a) to describe the design process and implementation of a smartphone application that can provide anticoagulation management services remotely, and (b) to evaluate its usability.

METHODS

After repeated discussions, professional anticoagulant clinical pharmacists, doctors in relevant departments, and software engineers determined the target population and main functions of the health application called Alfalfa, and gradually improved its functions by adding new functional modules based on user feedback. The usability of Alfalfa was evaluated by the System Usability Scale (SUS).

RESULTS

The mobile-phone application Alfalfa, based on the official WeChat account platform, was designed and developed. Alfalfa can provide remote management of warfarin. In addition, Alfalfa also has functions to remind patients to take their medication, popularize knowledge of warfarin, and connect with the anticoagulant community. The average SUS score was 78.0 out of a possible score of 100.

CONCLUSIONS

Alfalfa can be used to remotely adjust the dose of warfarin. Its usability scores show that it is acceptable to users, and its learnability has room for further improvement.

CLINICALTRIAL

ChiCTR1900021920
The bidirectional association between Internet addiction and depression: a large-sample longitudinal study among Chinese university students (Preprint)
Authors: Guo Wan-Jun , Yang Xia , Tao Yu-Jie , Meng Ya-Jing , Wang Hui-Yao , Li Xiao-Jing , Zhang Ya-Min , Zeng Jin-Kun , Tang Wan-Jie , Wang Qiang , Deng Wei , Zhao Lian-Sheng , Ma Xiao-Hong , Li Ming-Li , Xu Jia-Jun , Li Jing , Liu Yan-Song , Tang Zhen , Du Xiang-Dong , Hao Wei , Coid Jeremy W. , Lee Sing , Greenshaw Andrew J , Li Tao
Published: October 2020

BACKGROUND

Evidence indicates that Internet addiction (IA) is associated with depression, but longitudinal studies have rarely been reported, and no studies have yet investigated potential common vulnerability or a possible specific causal relationship between these disorders.

OBJECTIVE

To overcome these gaps, the present 12-month longitudinal study based on a large-sample employed a cross-lagged panel model (CLPM) approach to investigate the potential common vulnerability and specific cross-causal relationships between IA and CSD (or depression).

METHODS

IA and clinically-significant depression (CSD) among 12 043 undergraduates were surveyed at baseline (as freshmen) and in follow-up after 12 months (as sophomores). Application of CLPM revealed two well-fitted design between IA and CSD, and between severities of IA and depression, adjusting for demographics.

RESULTS

Rates of baseline IA and CSD were 5.47% and 3.85%, respectively; increasing to 9.47% and 5.58%, respectively at follow-up. Among those with baseline IA and CSD, 44.61% and 34.48% remained stable at the time of the follow-up survey, respectively. Rates of new-incidences of IA and CSD over 12 months were 7.43% and 4.47%, respectively. Application of a cross-lagged panel model approach (CLPM, a discrete time structural equation model used primarily to assess causal relationships in real-world settings) revealed two well-fitted design between IA and CSD, and between severities of IA and depression, adjusting for demographics. Models revealed that baseline CSD (or depression severity) had a significant net-predictive effect on follow-up IA (or IA severity), and baseline IA (or IA severity) had a significant net-predictive effect on follow-up CSD (or depression severity).

CONCLUSIONS

These correlational patterns using a CLPM indicate that both common vulnerability and bidirectional specific cross-causal effects between them may contribute to the association between IA and depression. As the path coefficients of the net-cross-predictive effects were significantly smaller than those of baseline to follow-up cross-section associations, vulnerability may play a more significant role than bidirectional-causal effects.

CLINICALTRIAL

Ethics Committee of West China Hospital, Sichuan University (NO. 2016-171)
Alignment of Key Stakeholders’ Priorities for Patient-Facing Tools in Digital Health: Mixed Methods Study (Preprint)
Authors: Lyles Courtney Rees , Adler-Milstein Julia , Thao Crishyashi , Lisker Sarah , Nouri Sarah , Sarkar Urmimala
Published: October 2020

BACKGROUND

There is widespread agreement on the promise of patient-facing digital health tools to transform health care. Yet, few tools are in widespread use or have documented clinical effectiveness.

OBJECTIVE

The aim of this study was to gain insight into the gap between the potential of patient-facing digital health tools and real-world uptake.

METHODS

We interviewed and surveyed experts (in total, n=24) across key digital health stakeholder groups—venture capitalists, digital health companies, payers, and health care system providers or leaders—guided by the Consolidated Framework for Implementation Research.

RESULTS

Our findings revealed that external policy, regulatory demands, internal organizational workflow, and integration needs often take priority over patient needs and patient preferences for digital health tools, which lowers patient acceptance rates. We discovered alignment, across all 4 stakeholder groups, in the desire to engage both patients and frontline health care providers in broader dissemination and evaluation of digital health tools. However, major areas of misalignment between stakeholder groups have stymied the progress of digital health tool uptake—venture capitalists and companies focused on external policy and regulatory demands, while payers and providers focused on internal organizational workflow and integration needs.

CONCLUSIONS

Misalignment of the priorities of digital health companies and their funders with those of providers and payers requires direct attention to improve uptake of patient-facing digital health tools and platforms.
Assessing Health-Related Quality of Life, Morbidity, and Survival Status for Individuals With Down Syndrome in Pakistan (DS-Pak): Protocol for a Web-Based Collaborative Registry (Preprint)
Authors: Siddiqui Ayat , Ladak Laila Akbar , Kazi Abdul Momin , Kaleem Sidra , Akbar Fizza , Kirmani Salman
Published: October 2020

BACKGROUND

Down syndrome is the most common chromosomal disorder, with a global incidence of 1 in 700 live births. However, the true prevalence, associated morbidities, and health-related quality of life (HRQOL) of these individuals and their families are not well documented, especially in low- and middle-income countries such as Pakistan. Disease-specific documentation in the form of a collaborative registry is required to better understand this condition and the associated health outcomes. This protocol paper describes the aims and processes for developing the first comprehensive, web-based collaborative registry for Down syndrome in a Pakistani cohort.

OBJECTIVE

This study aims to assess the HRQOL, long-term survival, and morbidity of individuals with Down syndrome by using a web-based collaborative registry.

METHODS

The registry data collection will be conducted at the Aga Khan University Hospital and at the Karachi Down Syndrome Program. Data will be collected by in-person interviews or virtually via telephone or video interviews. Participants of any age and sex with Down syndrome (trisomy 21) will be recruited. After receiving informed consent and assent, a series of tablet-based questionnaires will be administered. The questionnaires aim to assess the sociodemographic background, clinical status, and HRQOL of the participants and their families. Data will be uploaded to a secure cloud server to allow for real-time access to participant responses by the clinicians to plan prompt interventions. Patient safety and confidentiality will be maintained by using multilayer encryption and unique coded patient identifiers. The collected data will be analyzed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corporation), with the mean and SD of continuous variables being reported. Categorical variables will be analyzed with their percentages being reported and with a P value cutoff of .05. Multivariate regression analysis will be conducted to identify predictors related to the HRQOL in patients with Down syndrome. Survival analysis will be reported using the Kaplan-Meier survival curves.

RESULTS

The web-based questionnaire is currently being finalized before the commencement of pilot testing. This project has not received funding at the moment (ethical review committee approval reference ID: 2020-3582-11145).

CONCLUSIONS

This registry will allow for a comprehensive understanding of Down syndrome in low- and middle-income countries. This can provide the opportunity for data-informed interventions, which are tailored to the specific needs of this patient population and their families. Although this web-based registry is a proof of concept, it has the potential to be expanded to national, regional, and international levels.

INTERNATIONAL REGISTERED REPORT

PRR1-10.2196/24901
Incidence and mortality rate for gestational trophoblastic disease. (Preprint)
Authors: Roszkowski Igor , dos Santos Lander , Dutra Amanda Carvalho , Carvalho Maria Dalva De Barros , Pelloso Sandra Marisa
Published: October 2020

BACKGROUND

Gestational trophoblastic disease is a pregnancy anomaly that represents a series of invasive diseases that can metastasize or lead to death. Risk factors are genetic, racial, nutritional, and social.

OBJECTIVE

Analyze the number of cases of gestational trophoblastic disease, the incidence and risk factor among all patients hospitalized in Brazil from 2012 to 2017.

METHODS

Data collected from all hospitalizations across Brazil for hospitalized by gestational trophoblastic disease from 2012 to 2017. The incidences were calculated based on data from live births and mortality with data obtained from the Brazilian public health system. Risk factor were statistically analyzed based in race, region and age of the patients.

RESULTS

There were 20,534 cases of gestational trophoblastic disease with an incidence of 1.17 per 1000 live births in this period. The highest incidence was among “Asians” race (3.73 per 1000 live births; P<.001). The Brazilian regions had similar incidences, except for the Northern region, which had a lower incidence of 0.83 per 1000 live births (P=.03). The extremes of age (younger than 14 years and over 40 years) had a higher incidence compared to other women (P<.001). There were 35 deaths, and the mortality rate was 0.17% (35/20,534). The risk factors for death were living in the North region (P< .001) and “black” race (P<.001) or brown patients of color (P=.01).

CONCLUSIONS

The incidence found was similiar to North America and Europe. A higher incidence among "Asian" race and confirmation of higher incidence in the young and older women.
Z-Generation and Challenges of Education System in the XXI Century
Authors: Matani Rana , NATOUR Yumna
Published: October 2020

The authors of this paper present Z-generation of pupils and education system challenges in the XXI century, trying to teach these new learners in the most effective ways.
Pancreato-protective PANCREATOPROTECTIVE EFFECT OF SILYMARIN ON OXIDATIVE STRESS IN ALLOXAN-INDUCED HYPERGLYCEMIA IN MALE WISTAR RATS
Authors: UMA NARAYANAMURTHY  , SYLVIA SANTHAKUMARI A  , NIRMALA P
Published: October 2020

Objective: The objective of the study was to study the silymarin’s pancreatoprotective effect in alloxan-induced Type I diabetes mellitus. Numerous studies have evidence to prove the fact that antioxidant defense mechanism of flavonoids has overcome the progression of chronic diabetic complications.

Methods: A total of 24 male Wistar rats were divided into four groups (n=6): Group I normal control, Group II, Group III, and Group IV were induced diabetes with alloxan. Group I and Group II diabetic rats received the vehicle (PO). Group III was treated with silymarin 400 mg/kg (PO). Group IV was treated with glibenclamide 0.5 mg/kg, per orally for 21 days. Fasting blood samples were collected from all four groups of animals at the end of 21 days to evaluate serum glucose and glycosylated hemoglobin (HbA1c). Pancreatic tissue extraction, to perform lipid peroxidation and histopathological study confirms the level of oxidative damage to tissues and recovery after treatment.

Results: The serum glucose and HbA1c levels significantly increased in untreated diabetic rats, also a significant rise in lipid peroxidation and necrosis of beta cells in the pancreatic tissue. The rise in serum glucose levels was ameliorated in rats treated with silymarin, pancreatic tissue showed increased antioxidant levels, decreased lipid peroxides, and minimal changes and signs of regeneration of beta cells.

Conclusion: This study adds experimental evidence to the fact that silymarin is an effective nutritional supplement to treasure pancreatic beta-cell reserve and to delay diabetic complications.
ISOLATION AND CHEMICAL CHARACTERIZATION OF BIOACTIVE ALKALOID FROM ARGYREIA SPECIOSA LINN. HAVING ACTION ON ISOLATED RAT LEYDIG CELLS
Authors: NIRAJ VYAS  , KANAN GAMIT  , MANAN RAVAL  , SAMIR PATEL
Published: October 2020

Objective: Present study was aimed to isolate and chemically characterize bioactive constituent from alkaloid enriched fraction, prepared from roots of Argyreia speciosa Linn.
Materials and methods: Literature review revealed presence of ergoline type of alkaloids in roots. Alkaloidal fraction was prepared and screened for its action on testosterone biosynthesis, in- vitro, using isolated rat leydig cells. Dehydroepiandosterone was used as positive control. This bioactive fraction was subjected to open column chromatography followed by flash chromatography, to isolate constituent. One compound (A1) was isolated from the fraction and its purity was ascertained using TLC and HPLC studies. A1 was chemically characterized by IR, Mass and 1H-NMR studies, to elucidate probable chemical structure. A1 was screened for action on testosterone synthesis too, using isolated rat Leydig cells model. The fraction was standardized with respect to amount of A1 present.  
Results: Alkaloidal fraction (1000 µg/ml) incubated Leydig cells showed nearly, 22 fold increase in testosterone content as compared to untreated cells. The studies also yielded increase in testosterone content, in cells treated with test fractions and as observed in case of positive control. TLC studies indicated that A1 might possess ergoline moiety in the structure. IR, Mass and 1H NMR spectral studies suggested that A1 might be N-methyl ergometrine. This was the first report included isolation and chemical characterization of N-methyl ergometrine from Argyreia speciosa. A1 (1000 µg/ml) was found to stimulate testosterone content, by 14.62 fold, in culture media of Leydig cells after incubation. Conclusion: The results of in vitro studies, confirmed that the standardized alkaloid fraction as well as A1 had ability to stimulate Leydig cells to secrete testosterone. A1 might be N-methyl ergometrine and being ergometrine derivative it might act through oxytocine receptors expressed on the Leydig cells and stimulates testosterone synthesis.
APPLICATION OF SYNTHETIC AND NATURAL POLYMERS IN PREPARATION AND CHARACTERIZATION OF DOMPERIDONE FAST-DISSOLVING FILMS
Authors: SARIPILLI RAJESWARI  , PATIBANDLA SAMEERA  , KONCHADA ALEKHYA  , KURALLA HARI
Published: October 2020

Objective: The present research work is mainly focused on solubility enhancement of domperidone which is a biopharmaceutical classification system Class II drug using natural and synthetic polymers.
Methods: The solubility was enhanced by the kneading method with the drug: polymer (1:0.5, 1:0.75, and 1:1) using β-cyclodextrin. The fast dissolving films (FDFs) of domperidone were prepared by incorporating the solid dispersion (SD) SDK3 by solvent casting method using hydroxypropyl methylcellulose K15 M (HPMC) and gellan gum in various concentrations for preparing FDFs. Various pre- and post-compression parameters, drug and excipients compatibility studies were evaluated by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD).
Results: The maximum drug release of 98.86 % was achieved within 30 min for 1:1 ratio of solid dispersion using β-cyclodextrin, was optimized and taken for further development of FDFs. From the in vitro drug release studies films prepared with 10% w/w of HPMC K 15 (FH5) and 10% w/w of gellan gum (FG5) showed enhanced dissolution rate compared to other formulations. The formulation FHG with combination of polymers, namely, HPMC K 15 and gellan gum in 1:1 ratio showed drug release of 97.22% within 15 min only when compared with the optimized formulations. FTIR and DSC studies revealed that there were no interactions between drug and excipients. XRD studies revealed slight conversion of crystalline form to amorphous. The optimized formulation FHG found to be stable under accelerated stability studies.
Conclusions: The polymers in combination are a potential candidate for use in the formulation of FDF.