bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of Germination and Seedling Vigor in Dormant Seeds of African Juniper
Authors: El-Nashar Yasser Ismail , Dewir Yaser Hassan
Published: October 2019

Breaking of dormancy in african juniper (Juniperus procera) seeds is a challenge faced by nurseries attempting to grow large numbers of this plant for restoration projects. The purpose of this study was to develop a protocol for breaking dormancy and stimulating germination in african juniper. Seeds were presoaked in different concentrations (0, 1, 10, or 20 mg·L−1) of gibberellic acid (GA3), indole-3-butyric acid (IBA), and naphthalene acetic acid (NAA), and incubated under different air temperatures (10, 15, and 20 °C). The petri dishes were monitored daily for 84 days, to record germination percentage, rate, and uniformity, and the growth of shoots and roots, and biomass production. The highest germination percentages were obtained under 20 °C with a high concentration of NAA (20 mg·L−1). The greatest seedling growth was under 20 °C with IBA. The greatest seedling length was under 20 °C with a low concentration of IBA (1 mg·L−1). The greatest shoot fresh weight was under 20 °C with medium GA3 concentration (1 mg·L−1). Compared with the control, almost all growth regulator treatments stimulated higher germination percentages and vigor indices with increased temperatures.
Expression of Adhesion Molecule CD56 in Tumor Plasma Cells in Bone Marrow as a Prognostic Factor in Multiple Myeloma
Authors: Firsova Maiia Valer'evna , Mendeleeva L.P. , Kovrigina A.M. , Solov'ev M.V. , Deineko N.L. , Drokov M.Yu. , Savchenko V.G.
Published: October 2019

Aim. To study immunohistochemical parameters of tumor plasma cells in bone marrow and to assess how the expression of adhesion molecule CD56 impacts overall survival (OS) of multiple myeloma (MM) patients. Materials & Methods. The trial included 35 patients (19 men and 16 women) aged 23 to 73 years (with median age of 58 years) with newly diagnosed MM. At disease onset plasmacytoma was diagnosed in 21 patients. In all patients bone marrow core biopsy was performed followed by histologic and immunohistochemical (IHC) examinations. IHC examination was based on the panel of CD56, CD166, CXCR4, Ki-67, and c-MYC/CD138 antibodies. Kaplan-Meier survival curves and significance assessment by means of Cox's F-Test were used. Results. Expression mean values of most of studied markers (CD56, CXCR4, c-MYC, and Ki-67) in bone marrow of patients without plasmacytoma (n = 14) appeared to be higher than in patients with plasmacytoma at MM onset. Expression mean value is understood as percentage ratio of plasma cells expressing a studied marker to total cell count of tumor substrate. High expression of chemo-kine receptors (CXCR4), and adhesion molecules (CD56) probably inhibits plasma cell migration and impedes ex-tramedullary tumor progression. Comparison of protein expression by tumor plasma cells in bone marrow in the groups with bone extramedullary plasmacytoma shows a distinct regularity referring to CD56 adhesion molecule. For example, CD56 expression is significantly (р < 0.05) lower in terms of the count of tumor plasma cells with marker expression in bone marrow of MM patients with extramedullary plasmacytoma compared with patients with bone plasmacytoma (1 ± 1 % vs. 65.71 ± 12.12 %). Comparison of MM patients' OS depending on CD56 expression by tumor plasma cells in bone marrow showed that 4-year OS of patients with CD56 expression in bone marrow was significantly higher being 80 % vs. 38 % in the group with CD56 expression less than in 10 % of tumor cells. Conclusion. Expression of adhesion molecule CD56 in tumor plasma cells in bone marrow can be regarded as a prognostic factor in MM. Probably, when at disease onset CD56 expression is identified in less than 10 % of tumor cells in bone marrow, more detailed additional examination of patients should be carried out to rule out extramedullary lesions in different organs and tissues.
Current Genetic Models for Prediction of Primary Myelofibrosis
Authors: Polushkina Lyubov Borisovna , Shuvaev V.A. , Fominykh M.S. , Krivolapov Yu.A. , Belyakova E.A. , Asaulenko Z.P. , Motyko E.V. , Martynenko L.S. , Bakai M.P. , Tsybakova N.Yu. , Voloshin S.V. , Bessmeltsev S.S. , Chechetkin A.V. , Martynkevich I.S.
Published: October 2019

Aim. To study the relationship of karyotype, JAK2, CALR, and MPL driver mutations and ASXL1 mutation status with the progression and prediction of primary myelofibrosis (PMF). Materials & Methods. The trial included 110 PMF patients (38 men and 72 women), median age was 59 years (range 18-82) with median follow-up after diagnosis of 2.6 years (range 0.1-23). The patients were examined for JAK2, CALR, MPL, and ASXL1 mutations. Restriction fragment length polymorphism technique was used for the analysis of V617F substitution in JAK2 and 515 codon mutation in MPL. CALR (exon 9) and ASXL1 (exon 12) mutation tests were performed using Sanger direct sequencing. In 48 (44 %) out of 110 patients bone marrow cell karyotype was determined. Clinical and hematological parameters and median overall survival (OS) of patients were analyzed with regard to detected genetic aberrations and combinations of them. Results. JAK2, CALR, MPL mutations were detected in 55 (50 %), 28 (25.5 %), and 7 (6.4 %) out of 110 patients, respectively. Triple negative (TN) status was identified in 20 (18.2 %) out of 110 examined patients. ASXL1 mutations were detected in 22 (20 %) out of 110 patients. Out of 48 patients in 32 (66.7 %) normal karyotype, in 3 (6.3 %) favorable karyotype, in 4 (8.3 %) intermediate-prognosis karyotype, and in 9 (18.7 %) unfavorable karyotype were detected. The comparison of clinical and hematological parameters showed a number of significant differences. JAK2-positive patients had a higher hemoglobin level (median 129 g/L; p = 0.021). TN was associated with a high IPSS risk (p = 0.011), low hemoglobin level (median 101 g/L; p = 0.006), drop in platelet count (median 266 x 109/L; p = 0.041), increased lymphocyte count (median 26.9 х 109/L; р = 0.001). The detection of terminating mutations in ASXL1 correlated with palpable enlarged spleen (р = 0.050), reduced platelet count (median 184 х 109/L; р = 0.016), leukocyte count > 25 х 109/L (р = 0.046), and blast count > 1 % (р < 0.001). Univariate regression analysis showed that terminating mutations in ASXL1 (hazard ratio [HR] 2.9; р = 0.018), unfavorable karyotype (HR 8.2; р < 0.001), and TN (ОР 8.1; р < 0.001) had prognostic value for OS. ASXL1 mutation was associated with significantly worse OS in TN patients. Median OS of ASXL1-negative patients without high-risk chromosomal aberrations was significantly longer than in patients with high-risk karyotype and/ or ASXL1 mutation. Conclusion. Several genetic defects in tumor cells are associated with phenotypic manifestations of PMF. Based on the results of cytogenetic analysis and mutation determination of JAK2, CALR, MPL, and ASXL1, patients can be classified in different “genetic” risk groups when PMF is diagnosed.
Heme Oxygenase-1/Ferritin in Protection of Leukemia Cells from Oxidative Stress Induced by Catalytic System “Teraphtal + Ascorbic Acid”
Authors: Sidorova Tat'yana Aleksandrovna , Ryabaya O.O. , Prokof'eva A.A. , Khochenkov D.A.
Published: October 2019

Background. As is well known, cytotoxic mechanism of antitumor agent, i.e. catalytic system “teraphtal + ascorbic acid” (“TF+AA”), is associated with production of reactive oxygen species (ROS) and induction of oxidative stress in it. The “heme oxygenase-1/ferritin” (HO-1/Ft) system contributes to antioxidant defense. Aim. To analyze HO-1/Ft value in protection of leukemia cells from toxicity induced by antitumor agent “TF+AA”. Materials & Methods. The study was based on human leukemia cell lines K562 and U937. HO-1/Ft basal and drug-induced expression on mRNA and protein levels was analyzed by real-time RT-PCR and Western blot, ROS concentration in cells was determined by flow cytometry, and drug cytotoxicity was measured by MTT assay. Results. Our data showed constitutively active HO-1 in U937 myelomonoblasts whereas in K562 erythroblasts the expression of this protein was blocked on the mRNA level. Hemin, HO-1 agonist, induces HO-1 and Ft co-expression in U937 cells on the mRNA and protein levels. HO-1/Ft activation by hemin in U937 cells does not affect their “TF+AA” sensitivity and doubles, for example, the cytarabine sensitivity. “TF+AA” appeared to cause up-regulation of HO-1/ Ft genes, the expression of which quadruples or increases by half, respectively, compared with basal level. Preincubation of U937 myelomonoblasts with deferoxamine, iron chelator, results in doubling of their “TF+AA” resistance. However, the use of iron-containing TF analogs leads to its doubled cytotoxicity. Conclusion. In leukemia cell line U937 with constitutively active НО-1/Ft the heme-dependent activation of it does not considerably contribute to protection of cells from “TF+AA” toxicity. The system “TF+AA” is НО-1 and Ft expression inducer in U937 myelomonoblasts. Cytotoxic mechanism of “TF+AA” involves intracellular pool of “labile” non-heme iron, the level of which affects the drug sensibility of leukemia cells.
A Case of M-Paraprotein-Associated Polyneuropathy with Stable Response to Rituximab Therapy
Authors: Potapenko Vsevolod Gennad'evich , Kiselev V.N.
Published: October 2019

Monoclonal gammopathy of undetermined significance is diagnosed on the basis of an extensive search for a diagnostic reason as paraprotein secretion occurs in different diseases. One of such is demyelinating polyneuropathy associated with monodonal IgM and antibodies to myelin-assosiacted glycoprotein (AMDP). The first-line treatment of this disease is based on prednisolone, and intravenous immunoglobulin. The second-line therapy of treatment-resistant patients is not determined. The case report of patient with AMPD who received therapy with prednisone, azathio-prine, plasmapheresis is presented. Stable response was reached by rituximab.
Identification of Morphological and Pomological Characteristics of Iraq Pomegranate (Punica granatum L.) Variety Salakhani and Comparing with Variety Zivzik
Authors: AL-JABBARİ Khabbat Hasan , PAKYÜREK Mine , YAVİÇ Adnan
Published: October 2019

In this study, morphological and pomological characteristics of Salakhani, local variety of Iraq and Zivzik (Punica granatum L.), local variety of Siirt, were compared. Salakhani variety, which is one of the well-known pomegranate cultivars in Halabja region, has been cultivated for centuries in this region, North of Iraq. Zivzik variety is considered to be one of the important local varieties in Siirt province in the South East of Turkey. Salakhani variety was collected from their natural area in Halabja and Zivzik variety was collected from Zivzik Village in Şirvan. This is the first study comparing both varieties in point of pomological and morphological features. Our study has shown that two varieties are similiar on account of some features on the other hand are also different with regard to some properties. In addition to that the study showed Salakhani has more bigger fruit size and with soft seed than Zivzik pomegranate; conversely, Zivzik cv. has also very juicy fruit and high quality of fruit juice compare with Salakhani. This study has shown the superior characteristics of these two varieties can be the subject of different breeding studies in developing new pomegranate varieties.
Macroeconomic factors and LQ45 stock price index: evidence from Indonesia
Authors: Hadi Utomo Sugeng , Wulandari Dwi , Shandy Narmaditya Bagus , Handayati Puji , Ishak Suryati
Published: October 2019

This paper provides the relationship between macroeconomic variables, including exchange rate, BI rate and inflation, and stocks performance, particulary bluechip stocks listed in LQ45 index in Indonesia Stock Exchange. The study particularly gives insights on bluechip stocks listed in LQ45 stock price index in Indonesia Stock Exchange between 2015 and 2017. The data were obtained from various sources during the period, including the Indonesia Stock Exchange (IDX), the Central Bank of Indonesia (BI), and the Ministry of Trade. This study followed a Vector Error Correction Model (VECM) attempting to estimate the relationship between variables both in the short term and in the long term. The findings of the study showed that in the long run, exchange rate, BI rate and inflation have a negative impact on stock market performance, particularly on LQ45 index in Indonesia Stock Exchange. It implies that an increase in macroeconomic variables results in the decline of stock market performance. Meanwhile, in the short run, two variables, namely the exchange rate and inflation, positively affect stock market performance in Indonesia. On the contrary, the relationship between BI rate and stock market performance showed a negative correlation. These findings have significant implication for the understanding of how macroeconomic variables affect the stock market performance, particularly LQ45 price index in Indonesia Stock Exchange.
Fütürizm Akımının Tarihsel Süreci Bağlamında Fotoğraf Sanatına Kısa Bir Bakış
Authors: Akalın Tolga
Published: October 2019

Bilim, sanayi ve teknoloji alanındaki gelişmeler insanlık tarihini ve
dolayısı ile geleceğini pek çok acıdan etkilemiştir. 20. yy. teknolojik açıdan
oldukça hızlı geçmiş ve değişime uğramıştır. Toplumların sosyal ve ekonomik
yaşam biçimlerindeki bu dönüşüm, insanların beğeni düzeylerini, istek ve
arzularını da farklılaştırmıştır.

Sanat, bu değişimden kendi payına düşüne almıştır. Çeşitli sanat
akımları ortaya çıkmış ve bu akımlar başka akımların ilham kaynağı olmaya veya
tam tersi bir etki ile karşıt görüş oluşturmaya başlamıştır. Bu akımların
içerisinde yıkımı, şiddeti ve kökten değişimi isteyen Fütürizm
Akımı, ortaya çıktığı dönemde oldukça ses getirmiştir.

Fütürizm akımının temsilcisi Marinettiy
ile birlikte, Fütüristler geçmişin sanatını ve kültürlerini reddetmişlerdir.
Geleceğin yeni olanda saklı olduğunu ve buna ulaşmak içinde geçmişin tozlu
raflarında kalan sanatsal ve kültürel tüm etkinliklerin ve birikimlerin yok
sayılması gerektiğini hatta bu durumu biraz daha ileriye götürerek bunların
tamamının yok edilmesi ve yıkılması gerektiğini şiddetli bir şekilde
savunmuşlardır.

Fütüristler savunmalarını yaparken sanatın
her kolundan yararlanmışlardır. Resim, heykel, tiyatro, edebiyat, sinema gibi
alanlar onların başlıca kaynakları olmuştur. Ancak bu akımın kullanılan teknik
açısından istek ve arzularını en iyi şekilde yansıttığı alan fotoğraf alanı olmuştur.
Çalışmada, fütürizm akımının genel durumu incelendikten sonra fotoğraf
alanındaki teknikler tartışılarak ele alınmış ve bu akım içerisinde yer alan
sanatçılar ve yaptıkları işler irdelenmiştir.
A Computational Method for the Identification of Endolysins and Autolysins
Authors: Xu Lei , Liang Guangmin , Chen Baowen , Tan Xu , Xiang Huaikun , Liao Changrui
Published: October 2019

Background:

Cell lytic enzyme is a kind of highly evolved protein, which can destroy
the cell structure and kill the bacteria. Compared with antibiotics, cell lytic enzyme will not cause
serious problem of drug resistance of pathogenic bacteria. Thus, the study of cell wall lytic
enzymes aims at finding an efficient way for curing bacteria infectious. Compared with using
antibiotics, the problem of drug resistance becomes more serious. Therefore, it is a good choice for
curing bacterial infections by using cell lytic enzymes. Cell lytic enzyme includes endolysin and
autolysin and the difference between them is the purpose of the break of cell wall. The
identification of the type of cell lytic enzymes is meaningful for the study of cell wall enzymes.

Objective:

In this article, our motivation is to predict the type of cell lytic enzyme. Cell lytic
enzyme is helpful for killing bacteria, so it is meaningful for study the type of cell lytic enzyme.
However, it is time consuming to detect the type of cell lytic enzyme by experimental methods.
Thus, an efficient computational method for the type of cell lytic enzyme prediction is proposed in
our work.

Method:

We propose a computational method for the prediction of endolysin and autolysin. First,
a data set containing 27 endolysins and 41 autolysins is built. Then the protein is represented by
tripeptides composition. The features are selected with larger confidence degree. At last, the
classifier is trained by the labeled vectors based on support vector machine. The learned classifier is
used to predict the type of cell lytic enzyme.

Results:

Following the proposed method, the experimental results show that the overall accuracy
can attain 97.06%, when 44 features are selected. Compared with Ding's method, our method
improves the overall accuracy by nearly 4.5% ((97.06-92.9)/92.9%). The performance of our
proposed method is stable, when the selected feature number is from 40 to 70. The overall accuracy
of tripeptides optimal feature set is 94.12%, and the overall accuracy of Chou's amphiphilic
PseAAC method is 76.2%. The experimental results also demonstrate that the overall accuracy is
improved by nearly 18% when using the tripeptides optimal feature set.

Conclusion:

The paper proposed an efficient method for identifying endolysin and autolysin. In
this paper, support vector machine is used to predict the type of cell lytic enzyme. The experimental
results show that the overall accuracy of the proposed method is 94.12%, which is better than some
existing methods. In conclusion, the selected 44 features can improve the overall accuracy for
identification of the type of cell lytic enzyme. Support vector machine performs better than other
classifiers when using the selected feature set on the benchmark data set.
Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques
Authors: Ali Syed Saqib , Zia Mohammad Khalid , Siddiqui Tooba , Ahsan Haseeb , Khan Fahim Halim
Published: October 2019

Background:

Ascorbic acid is a classic dietary antioxidant which plays an important role
in the body of human beings. It is commonly found in various foods as well as taken as dietary
supplement.

Objective:

The plasma ascorbic acid concentration may range from low, as in chronic or acute
oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2-
macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with
antiproteinase activity, found in sheep’s blood.

Methods:

In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was
explored in the presence of visible light by utilizing various spectroscopic techniques and
isothermal titration calorimetry (ITC).

Results:

UV-vis and fluorescence spectroscopy suggests the formation of a complex between
ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary
structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings
suggest the induction of subtle conformational changes in α2M induced by ascorbic acid.
Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an
enthalpy-driven process.

Conclusion:

It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M
by inducing changes in the secondary structure of the protein.
Molecular Markers of Regulatory T Cells in Cancer Immunotherapy with Special Focus on Acute Myeloid Leukemia (AML) - A Systematic Review
Authors: Kaboli Parham Jabbarzadeh , Zhang Lingling , Xiang Shixin , Shen Jing , Li Mingxing , Zhao Yueshui , Wu Xu , Zhao Qijie , Zhang Hanyu , Lin Ling , Yin Jianhua , Wu Yuanlin , Wan Lin , Yi Tao , Li Xiang , Cho Chi Hin , Li Jing , Xiao Zhangang , Wen Qinglian
Published: October 2019

The next-generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review discusses tumor treatment strategies using regulatory T (Treg) cell therapy in a Tumor Microenvironment (TME). It also discusses factors affecting TME instability as well as relevant treatments to prevent future immune disorders. It is prognosticated that PD-1 inhibitors are risky and their adverse effects should be taken into account when they are administered to treat Acute Myeloid Leukemia (AML), lung adenocarcinoma, and prostate adenocarcinoma. In contrast, Treg molecular markers FoxP3 and CD25 analyzed here have stronger expression in almost all kinds of cancers compared with normal people. However, CD25 inhibitors are more effective compared to FoxP3 inhibitors, especially in combination with TGF-β blockade, in predicting patient survival. According to the data obtained from the Cancer Genome Atlas, we then concentrate on AML immunotherapy and discuss different therapeutic strategies including anti-CD25/IL-2, anti-CTLA-4, anti-IDO, antityrosine kinase receptor, and anti-PI3K therapies and highlight the recent advances and clinical achievements in AML immunotherapy. In order to prognosticate the risk and adverse effects of key target inhibitors (namely against CTLA-4, FoxP3, CD25, and PD-1), we finally analyzed and compared the Cancer Genome Atlas derived from ten common cancers. This review shows that Treg cells are strongly increased in AML and the comparative review of key markers shows that Tregbased immunotherapy is not effective for all kinds of cancer. Therefore, blocking CD25(+)FoxP3(+) Treg cells is suggested in AML more than other kinds of cancer; meanwhile, Treg markers studied in other cancers have also great lessons for AML immunotherapy.
In Vitro Antioxidant, Antithrombotic, Antiatherogenic and Antidiabetic Activities of Urtica dioica, Sideritis euboea and Cistus creticus Water Extracts and Investigation of Pasta Fortification with the Most Bioactive One
Authors: Vasiliki Georgakopoulou , Charalampia Dimou , Haralabos Karantonis Christos
Published: October 2019

Background:

The present work evaluated the in vitro antioxidant, antithrombotic, antiatherogenic and antidiabetic activities of Urtica dioica, Sideritis euboea and Cistus creticus and investigated pasta fortification with the most bioactive one. The methods employed were total phenolic content (TPC) in mg of gallic acid equivalents per g of dried-herb, 2,2'-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) free radical scavenging in mg of dried-herb, cupric reducing antioxidant capacity (CUPRAC) in micromol trolox equivalent per g of dried-herb, platelet aggregation inhibition (PAF-PAI); plasma oxidation inhibition (POxI); and alpha glucosidase inhibition (a-GaseI) all in mg of dried-herb. Pasta fortified with the most bioactive herb was also studied for the above activities.

Methods:

Cistus creticus extract was more bioactive (p < 0.05) compared to Sideritis euboea and Urtica dioica in all but antithrombotic assay, where Sideritis euboea was superior to the others (TPC: 37.9 ± 0.56 versus 9.6 ± 0.83 and 5.4 ± 0.70; SA50-ABTS: 0.040 ± 0.001 versus 0.400 ± 0.010 and 0.520 ± 0.008; ACUPRAC: 860 ± 6.23 versus 170 ± 4.25 and 80 ± 3.63; IA50-PAF: 1.8 ± 0.14 versus 1.2 ± 0.10 and 5.2 ± 0.21; POxI: 0.095 ± 0.016 versus 0.216 ± 0.021 and 0.534 ± 0.029; IA50-aGase: 0.2 ± 0.01 versus 2.1 ± 0.16 and 1.7 ± 0.12).

Results:

Fortified pasta with cistus creticus extract exhibited significantly higher levels (p < 0.05) in all assays compared to plain pasta (TPC: 0.392 ± 0.064 versus 0.137 ± 0.020; SA50-ABTS: 9.4 ± 0.2 versus 126.9 ± 2.7; ACUPRAC: 5.4 ± 0.5 versus 0.9 ± 0.1; IA50-PAF: 1.87 ± 0.04 versus 2.28 ± 0.06; POxI: 3.21 ± 0.18 versus 12.2 ± 0.73; IA50-aGase: 8.9 ± 1.1 versus 18.2 ± 0.9).

Conclusion:

The current findings add to the mounting evidence on the potential health benefits to be derived from consuming pasta fortified with herbal extracts and indicate that Cistus creticus could form an ideal raw material towards the production of fortified pasta with increased nutritional value.
Analyzing Structural and Functional Characteristics of Collagenase from Bacillus cereus MH19 via in silico Approaches
Authors: Chen Shihua , Ma Meihu , Fu Xing
Published: October 2019

Background:

Collagenase is a type of proteolytic enzyme that specifically hydrolyzes native
collagen with a three-dimensional helical structure. The structure and properties of collagenase
vary with different sources and types. In addition to the well-characterized Clostridium collagenase,
other collagenases are largely unknown. Various gene and protein databases have been widely used to
mine novel functional genes in the genome. Gene mining and sequence analysis are effective methods
for studying these enzymes.

Objective:

The present study aimed to understand the molecular, structural, and functional characteristics
of collagenase from Bacillus cereus MH19 using a bioinformatics approach.

Method:

Based on the three-generation sequencing PacBio technique, Sequencing the Bacillus cereus
MH19 genome. Function annotation is completed by blasting genes with different databases. Collagenases
were investigated based on the physiochemical properties, phylogenetic relation, and domain
architecture. The 3D structure model of the selected collagenase has been constructed and verified by
SAVES.

Results:

There were 5 collagenases in Bacillus cereus MH19 with a molecular weight distribution
ranging from 36-110 kDa. The analysis of evolutionary relationship between different collagenases
indicating that the BCC000504 and BCC003388 collagenase gene sequences are closer to the typical
collagenase genes ColG, ColA, and ColH, followed by BCC003615. The domain and function analysis
showed that the collagenases BCC000504 and BCC003388 were similar to the collagenases ColG,
ColA and ColH. BCC004271 was similar to BCC004272, and BCC003615 might be quite different
from other collagenases. The secondary structure of collagenase was analyzed. The SAVES evaluation
indicates that 3D structural modeling of the selected collagenase is acceptable.

Conclusion:

This study provides an overview of the molecular, functional, and structural characteristics
of collagenase from Bacillus cereus MH19, which helps to understand the bacterial collagenase. The
characterization of the collagenase will certainly expand the application range of collagenase.
A Molecular Approach on the Protective Effects of Mangiferin Against Diabetes and Diabetes-related Complications
Authors: Aswal Sonali , Kumar Ankit , Chauhan Ashutosh , Semwal Ruchi Badoni , Kumar Abhimanyu , Semwal Deepak Kumar
Published: October 2019

Background:

Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets.

Aim:

The aim of this study is to review available knowledge of mangiferin focusing on its mode of action.

Methods:

Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript.

Results:

Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal.

Conclusion:

This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.
iATP: A Sequence Based Method for Identifying Anti-tubercular Peptides
Authors: Chen Wei , Feng Pengmian , Nie Fulei
Published: October 2019

Background:

Tuberculosis is one of the biggest threats to human health. Recent studies have demonstrated that anti-tubercular peptides are promising candidates for the discovery of new anti-tubercular drugs. Since experimental methods are still labor intensive, it is highly desirable to develop automatic computational methods to identify anti-tubercular peptides from the huge amount of natural and synthetic peptides. Hence, accurate and fast computational methods are highly needed.

Methods and Results:

In this study, a support vector machine based method was proposed to identify anti-tubercular peptides, in which the peptides were encoded by using the optimal g-gap dipeptide compositions. Comparative results demonstrated that our method outperforms existing methods on the same benchmark dataset. For the convenience of scientific community, a freely accessible web-server was built, which is available at http://lin-group.cn/server/iATP.

Conclusion:

It is anticipated that the proposed method will become a useful tool for identifying anti-tubercular peptides.
Drug Withdrawal Due to Safety: A Review of the Data Supporting Withdrawal Decision
Authors: Craveiro Nuno Sales , Lopes Bruno Silva , Tomás Lara , Almeida Sofia Fraga
Published: October 2019

Introduction:

Several drugs were withdrawn from the market due to safety.

Objective:

The aim of this study was to describe data supporting drug withdrawal from the market
due to safety reasons in countries belonging to the World Health Organization.

Methods:

We analyzed drugs withdrawn from the market between 1990 and 2010. All medicine
agencies of the countries belonging to the Program for International Drug Monitoring of the World
Health Organization were contacted. To complete data, Medline, reference books and available
drug databases were also searched. Information sources on which authorities based their withdrawal
were categorized and the average time between the first date of exposure and withdrawal
was calculated and stratified.

Results:

A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the
market due to safety reasons in the period reviewed (1990 - 2010). Hepatotoxicity (n=36, 27.1%),
cardiac disorders (n=25, 18.8%), hypersensitivity (n=17, 12.8%) and nephrotoxicity (n=14, 9.8%)
were the major reasons responsible for 69.2% of all drugs withdrawn. In most cases, Information
Sources for drug withdrawal were spontaneous reports and/or case reports (n=86, 64.7%), followed
by clinical trials (n=24, 18.0%). The average time between the introduction of a drug and its
withdrawal due to safety reasons was 20.3 years (SD±13.8).

Conclusion:

According to available and published evidence, there is no gold standard to identify
risks associated with drug exposure. These findings strengthen the role of different information
sources within the drug safety review process.
Prospective Study of Microbial Colorants under the Focus of Patent Documents
Authors: Gonçalves Brisa R.P. , Machado Bruna A.S. , Hanna Samira A. , Umsza-Guez Marcelo A.
Published: October 2019

Background:

Colorant-producing microorganisms are quite common in nature. These
biomolecules present many biological activities such as antitumoral, antimicrobial and antioxidant,
in addition to the various nuances of color, making them of special technological importance
to the industrial sectors.

Objective:

This study aims to conduct a technological mapping in the patent, at European patent
Office (EPO), in order to evaluate the global panorama of the use of microbial colorants.

Methods:

The experimental design was acquired by the keyword-driven approach through the advanced
search in the Espacenet database European Patent Office (EPO). The keywords selected
were bacteria or fungi* or yeast or algae or microorganism* but not plant* and pigment* or color*
or colorant* or dye* and the International Patent Classification code, C09B61, for prospecting of
interest.

Results:

There has been a linear increase in patents developed in the last 20 years, with Japan as
the largest depositor in the area. The companies Dainippon Ink and Chemicals and Ajinomoto,
both being Japanese, are the largest depositors with 20% of all patents. Among the microorganisms,
the filamentous fungi appeared in the first place with 32% of documents and the fungi of the
genus Monascus were the most frequently used.

Conclusion:

The use of microbial colorants has been growing among industries, mainly in food
sectors, due to the growing demand for products of natural origin. Thus, the increase in research
and technological development in the area of microbial colorants can become an economically viable
and promising strategy for the various industrial sectors.
Molecular Docking Studies and Pharmacophore Modeling of Some Insulin Mimetic Agents from Herbal Sources: A Rational Approach towards Designing of Orally Active Insulin Mimetic Agents
Authors: Pradhan Joohee , Panchawat Sunita
Published: October 2019

Background::

Many herbal drugs have been found to possess oral insulin mimetic
property as evidenced from the literature. Although, to date there is no efficient, synthetic
orally active insulin-mimetic drug available clinically. Computer-Aided Drug Design
(CADD) may help in the development of such agents through Pharmacophore modeling.

Objective::

The present work is aimed at the In-silico designing of Pharmacophore that defines
the structural requirements of a molecule to possess oral insulin-mimetic properties.

Methods::

A set of 16 orally active insulin-mimetic natural compounds available through literature
was used to develop a structure-based pharmacophore in a “three-step filtration process”
comprised of Lipinski’s rule of 5, Minimum binding energy with the receptor and
Ghose filter to the Lipinski’s rule for oral bioavailability of the drugs. The selected ligands
were docked with phosphorylated insulin receptor tyrosine kinase in complex with peptide
substrate and ATP analog (PDB ID: 1IR3) using Autodock 4.2 and their interaction with the
receptor was analyzed followed by the generation of shared and merged feature pharmacophore
by Ligandscout 4.2.1.

Results::

There are three important structural features that contribute to interaction with the
active site of the insulin receptor: these are hydrogen bond donor groups, hydrogen bond acceptor
groups and hydrophobic interactions. It is important to note that positive or negative
ionizable groups or the presence of aromatic rings are not important for the activity.

Conclusion::

Taking a clue from the developed pharmacophore, one may design new lead
having necessary groups required for the insulin-mimetic activity that can be elaborated synthetically
to get a series of compounds with possible oral insulin-mimetic activity.
Young People's Response to Six Smartphone Apps for Anxiety and Depression: Focus Group Study
Authors: Garrido Sandra , Cheers Daniel , Boydell Katherine , Nguyen Quang Vinh , Schubert Emery , Dunne Laura , Meade Tanya
Published: October 2019

Background

Suicide is one of the most frequent causes of death in young people worldwide. Depression lies at the root of this issue, a condition that has a significant negative impact on the lives of those who experience it and on society more generally. However, 80% of affected young people do not obtain professional help for depression and other mental health issues. Therefore, a key challenge is to find innovative and appealing ways to engage young people in learning to manage their mental health. Research suggests that young people prefer to access anonymous Web-based programs rather than get face-to-face help, which has led to the development of numerous smartphone apps. However, the evidence indicates that not all of these apps are effective in engaging the interest of young people who are most in need of help.

Objective

The study aimed to investigate young people’s response to six currently available smartphone apps for mental health and to identify features that young people like and dislike in such apps.

Methods

Focus groups were conducted with 23 young people aged 13 to 25 years in which they viewed and used six smartphone apps for mental health. A general inductive approach following a realist paradigm guided data analysis.

Results

The results revealed that young people value autonomy and the opportunity to personalize experiences with these apps above other things. Finding a balance between simplicity and informativeness is also an important factor.

Conclusions

App developers need to consider using participant-design frameworks to ensure that smartphone apps are providing what young people want in a mental health app. Solutions to the need for personalization and increasing user engagement are also crucially needed.
Characterizing the Rural Opioid Use Environment in Kentucky Using Google Earth: Virtual Audit
Authors: Crawford Natalie Danielle , Haardöerfer Regine , Cooper Hannah , McKinnon Izraelle , Jones-Harrell Carla , Ballard April , von Hellens Sierra Shantel , Young April
Published: October 2019

Background

The opioid epidemic has ravaged rural communities in the United States. Despite extensive literature relating the physical environment to substance use in urban areas, little is known about the role of physical environment on the opioid epidemic in rural areas.

Objective

This study aimed to examine the reliability of Google Earth to collect data on the physical environment related to substance use in rural areas.

Methods

Systematic virtual audits were performed in 5 rural Kentucky counties using Google Earth between 2017 and 2018 to capture land use, health care facilities, entertainment venues, and businesses. In-person audits were performed for a subset of the census blocks.

Results

We captured 533 features, most of which were images taken before 2015 (71.8%, 383/533). Reliability between the virtual audits and the gold standard was high for health care facilities (>83%), entertainment venues (>95%), and businesses (>61%) but was poor for land use features (>18%). Reliability between the virtual audit and in-person audit was high for health care facilities (83%) and entertainment venues (62%) but was poor for land use (0%) and businesses (12.5%).

Conclusions

Poor reliability for land use features may reflect difficulty characterizing features that require judgment or natural changes in the environment that are not reflective of the Google Earth imagery because it was captured several years before the audit was performed. Virtual Google Earth audits were an efficient way to collect rich neighborhood data that are generally not available from other sources. However, these audits should use caution when the images in the observation area are dated.
Detection of Atrial Fibrillation Using a Ring-Type Wearable Device (CardioTracker) and Deep Learning Analysis of Photoplethysmography Signals: Prospective Observational Proof-of-Concept Study (Preprint)
Authors: Kwon Soonil , Hong Joonki , Choi Eue-Keun , Lee Byunghwan , Baik Changhyun , Lee Euijae , Jeong Eui-Rim , Koo Bon-Kwon , Oh Seil , Yi Yung
Published: October 2019

BACKGROUND

Continuous photoplethysmography (PPG) monitoring with a wearable device may aid the early detection of atrial fibrillation (AF).

OBJECTIVE

We aimed to evaluate the diagnostic performance of a ring-type wearable device (CardioTracker, CART), which can detect AF using deep learning analysis of PPG signals.

METHODS

Patients with persistent AF who underwent cardioversion were recruited prospectively. We recorded PPG signals at the finger with CART and a conventional pulse oximeter before and after cardioversion over a period of 15 min (each instrument). Cardiologists validated the PPG rhythms with simultaneous single-lead electrocardiography. The PPG data were transmitted to a smartphone wirelessly and analyzed with a deep learning algorithm. We also validated the deep learning algorithm in 20 healthy subjects with sinus rhythm (SR).

RESULTS

In 100 study participants, CART generated a total of 13,038 30-s PPG samples (5850 for SR and 7188 for AF). Using the deep learning algorithm, the diagnostic accuracy, sensitivity, specificity, positive-predictive value, and negative-predictive value were 96.9%, 99.0%, 94.3%, 95.6%, and 98.7%, respectively. Although the diagnostic accuracy decreased with shorter sample lengths, the accuracy was maintained at 94.7% with 10-s measurements. For SR, the specificity decreased with higher variability of peak-to-peak intervals. However, for AF, CART maintained consistent sensitivity regardless of variability. Pulse rates had a lower impact on sensitivity than on specificity. The performance of CART was comparable to that of the conventional device when using a proper threshold. External validation showed that 94.99% (16,529/17,400) of the PPG samples from the control group were correctly identified with SR.

CONCLUSIONS

A ring-type wearable device with deep learning analysis of PPG signals could accurately diagnose AF without relying on electrocardiography. With this device, continuous monitoring for AF may be promising in high-risk populations.

CLINICALTRIAL

ClinicalTrials.gov NCT04023188; https://clinicaltrials.gov/ct2/show/NCT04023188
WeChat as a Platform for Problem-Based Learning Among Hematological Postgraduates: Feasibility and Acceptability Study (Preprint)
Authors: Luo Ping , Pang Wenwen , Wang Yingying , Liu Minghui , Zhou Shu , Liu Shuai , Zhang Xian , Liu Li , Liu Yanan , Zhou Fuling
Published: October 2019

BACKGROUND

Hematological medicine is a practical discipline that is difficult to study. Problem-based learning (PBL) is an innovative student-centered teaching method wherein students define their own learning objectives from clinically based problems. Considering that WeChat is the most popular communication app in China, we selected it as a new platform for online PBL to reduce the limitations of traditional PBL in hematology teaching.

OBJECTIVE

This study aims to explore a new pedagogical method called WeChat-PBL, which is based on real micro clinical cases for postgraduates majoring in hematology and to demonstrate its feasibility and acceptability.

METHODS

A total of 48 hematological postgraduates and 7 tutors participated in this study. We divided the participants into 7 groups where students can learn theoretical knowledge. After each course, the members of each group were required to complete in-class quizzes. Moreover, the students and tutors were required to fill out periodic (after each class) and overall (after each semester) evaluations.

RESULTS

A total of 8 micro clinical cases were presented in WeChat-PBL. The average quiz score for acute myelogenous leukemia, chronic myeloid leukemia, multiple myeloma, acute promyelocytic leukemia, and lymphoma were 89.0%, 86.0%, 83.4%, 88.8%, and 77.5%, respectively. Periodic evaluations showed that both students and tutors were satisfied with the process of WeChat-PBL. The overall evaluation results showed that WeChat-PBL was able to positively impact the learning experiences of hematological postgraduates.

CONCLUSIONS

Our results indicate the feasibility and acceptability of the WeChat-PBL teaching method for postgraduates majoring in hematology.
The Mediator Roles of Problematic Internet Use and Perceived Stress Between Health Behaviors and Work-Life Balance Among Internet Users in Germany and China: Web-Based Cross-Sectional Study (Preprint)
Authors: Gao Lingling , Gan Yiqun , Whittal Amanda , Yan Song , Lippke Sonia
Published: October 2019

BACKGROUND

Work-life balance is associated with health behaviors. In the face of digitalization, understanding this link requires a theory-based investigation of problematic internet use and perceived stress, which are so far unknown.

OBJECTIVE

On the basis of the compensatory carry-over action model, this study aimed to determine whether problematic internet use and perceived stress mediate the relationship between health behaviors and work-life balance in two groups of internet users from different environments (residents in Germany and China). We also investigated whether the place of residence was a moderator.

METHODS

An online questionnaire (N=877) was administered to residents from Germany (n=374) and China (n=503) in 3 languages (German, English, and Chinese). Moderated mediation analyses were run with health behaviors as the independent variable, work-life balance as the dependent variable, problematic internet use and perceived stress as the mediator variables, and place of residence as a potential moderator.

RESULTS

On a mean level, individuals in Germany reported less problematic internet use and more health behaviors than individuals in China; however, they also had lower work-life balance and higher perceived stress. Results showed that health behaviors seem to be directly related to work-life balance in both groups. Among the residents of Germany, a partial mediation was revealed (β=.13; P=.01), whereas among the residents of China, a full mediation was found (β=.02; P=.61). The mediator role of perceived stress was compared with problematic internet use in all the serial models and the parallel model. Residence moderated the relationship between health behaviors and work-life balance: The interrelation between health behaviors and work-life balance was stronger in Germany (β=.19; P<.001) than in China (β=.11; P=.01) when controlling for other variables.

CONCLUSIONS

The findings of this study are in line with the compensatory carry-over action model. To promote work-life balance, individuals should perform health behaviors to help overcome problematic internet use and perceived stress. Both problematic internet use and perceived stress mediated health behaviors and work-life balance partially in German study participants and fully in Chinese study participants.
Con promesas de libertad. El enrolamiento de esclavos en la guerra de independencia del Perú, 1820-1825
Authors: Contreras Cruces Hugo
Published: October 2019

This article studies the enrollment process of slaves for the armies that fought for the independence of Peru. This was marked by the conjunctures of the conflict and in few occasions, it was due to a planned effort for adding new troops. The willingness of the slaves themselves to enlist, the donations of their masters and, even, the forced recruitment made by the patrols of the military corps in the streets of Lima, were how these serfs became a part of the army. On the other hand, the promises of immediate liberty or after a certain amount of years’ service also depended on the wars’ conjunctures. The worse the military situation for the patriots, of whom this article is principally about, the faster liberty could be reached. This was reflected in the decrees that regulated the recruitment of the black troops, leading to diverse legal statuses and to continuous disputes with the once masters of the enlisted slaves, evidenced in long trials after the war was over and the independence of Peru was secured.