bluuebunny/crossref_metadata_2025 huggingface dataset:
Integral management of the competitiveness level of agricultural machine-building enterprises products
Authors: Pavlova O. , Oliinyk I.
Published: April 2021

Under the conditions of strengthening competition for each enterprise, preserving and increasing the competitiveness of production is an integral and necessary attribute of the successful modern company. It is proved that the determining condition for the success of management decisions to strengthen products' competitive position in the markets is an objective and timely quantitative assessment of the competitiveness of products. It is determined that the quantitative assessment of the complex indicator of the level of product competitiveness should be carried out on the basis of the integrated indicator of product competitiveness. The analysis of the level of competitiveness of agricultural machinery products is carried out on the example of sprayers. The investigation is carried out on the example of products of one of the largest agricultural machinery enterprises in Ukraine, JSC «Elvorti». According to the results of calculations of the sprayers competitiveness, the conclusion about the competitiveness of the presented model of Tetis 24 sprayer (JSC «Ellvorti») in comparison with analogs: sprayers UX5200 Amazone (Germany), 840 John Deere (USA) 3000 Hardi Navigator (Denmark) and OPK-24 (PJSC «Boguslav Agricultural Machinery») on a certain segment is made. The carried out analysis showed that Tetis 24 sprayer is not competitive with Amazone and John Deere sprayers. At the same time, it is less advantageous to compare the competitiveness of the domestic sprayer with the American model. Compared with sprayers manufactured by PJSC Boguslavska Silhosptekhnika and Hardi Navigator, the sprayer manufactured by JSC Elvorti is competitive. The obtained result can be explained by the low level of solvency of consumers of a certain segment, who have relatively low requirements for quality, service, and marketing promotion of the sprayer. The analysis results make it possible for domestic manufacturers to carry out controlled process of managing the level of products competitiveness depending on the characteristics of its implementation in the market. Increasing the level of product competitiveness will ensure optimal and efficient use of available resources of the enterprise, will allow the most effective planning of marketing activities to enter new markets, increase service, due to the complete meeting the consumers demands.
THE RELATIONSHIP BETWEEN ENROLMENT IN BIOLOGY, HIV/AIDS KNOWLEDGE AND RELATED BEHAVIOUR AMONG SOUTH AFRICAN SCHOOLGIRLS
Authors: Mnguni Lindelani
Published: April 2021

In spite of integrating HIV/AIDS education in South African curricula the prevalence of HIV in 2016 was the highest since 2002. HIV infection rate is particularly high among schoolgirls compared with boys. Using a closed-ended questionnaire, this quantitative survey research compared Biology and non-Biology schoolgirls’ (n=291) behavioural intention, Health Literacy and HIV/AIDS Literacy to determine if enrolling for Biology, and subsequently learning about the scientific nature of HIV/AIDS would reduce risk behaviour among schoolgirls. Results indicate that Biology students have higher Health Literacy and HIV/AIDS Literacy than non-Biology students. The behavioural intentions of both groups were not significantly different. Health Literacy and HIV/AIDS Literacy did not correlate significantly with behavioural intention, which were indicative of risk behaviour. These findings suggest that enrolling for Biology and other science subjects and subsequently learning about HIV/AIDS may not reduce risk behaviour among schoolgirls.
Keywords: behavioural intention, biology students, health literacy, HIV/AIDS literacy, South African schoolgirls.
Management of Stroke During COVID-19 Pandemic: The Challenges in Nepal
Authors: Phuyal Subash , Lamsal Ritesh , Shrestha Gentle Sunder , Paudel Raju , Thapa Lekhjung
Published: April 2021

The COVID-19 pandemic has significantly affected health care delivery globally. COVID-19 is associated with varied neurological manifestations including acute ischemic stroke. In densely populated South Asian nations like Nepal that have suboptimal baseline health care systems, we foresee unique challenges during this pandemic to ensure effective stroke management as well as the safety of health care workers involved in the management of stroke patients.

Keywords: COVID-19; health care workers; safety; stroke management.
Relationships Between Defence Expenditures and Economic Growth in G7 Countries: Panel Bootstrap Causality Analysis
Authors: CANBAY Şerif , KIRCA Mustafa , OFLAZ Erkan
Published: April 2021

It is important to reveal the relationship between defence expenditures and economic growth for both developed countries and developing countries. Dynamic political and economic developments affect defence expenditures. Many macroeconomic variables of countries are affected by the change in defence expenditures. Economic growth comes first among these macroeconomic variables. This study aims to determine the relationships between the economic growth and defense expenditures of the G7 countries for the period 1988-2018. For this purpose, the relationships between variables were examined using bootstrap panel causality analysis developed by Kónya (2006). According to the analysis results, it was found that there is a unidirectional causality relationship from defense expenditures to economic growth in the USA, Germany, Japan, England, and Canada. The sign of causality relationships is negative in the USA, UK, and Canada, and positive in Germany and Japan. On the other hand, in the findings of the study, an insignificant causality relationship was found between variables in France and Italy. Besides, for the G7 countries, an insignificant causality relationship has been determined from economic growth to defense expenditures. Economic and political inferences were made based on the findings obtained at the end of the study.
Dimensi Spiritualitas dalam Kitab Al-Fūyūḍāt Al-Rabbāniyyah bi Tafsīr Ba’ḍi Al-Āyāt Al-Qurʼāniyyah Karya Ahmad Ibn Idris
Authors: Hudori Ahmad
Published: April 2021

This study describes spirituality in classical exegesis literature as an interesting field of study, especially when describing the interpretation of certain figures. The purpose of this research is to find out the spiritual dimension inscribed by Ahmad ibn Idris, a figure of Sufism in the XVIII M century in Morocco, in his tafsir work al-Fūyūḍāt al-Rabbāniyyah bi Tafsīr Ba'ḍi al-Āyāt al-Qurʼāniyyah. This study concludes that there are three spiritual dimensions contained in surah al-Fātiḥah, namely the dimensions of practicing worship, attachment, and universality. These three dimensions have an effect on the great potential in humans. Judging from the perspective of Ahmad ibn Idris in his tafsir book al-Fūyūḍāt al-Rabbāniyyah bi Tafsīr Ba'ḍi al-Āyāt al-Qurʼāniyyah these dimensions are contained in surah al[1]Fātiḥah from verses 13-, part of the dimensions of Worship practice, then verse 4 -5 parts of the dimension of attachment, and verses 67- of the dimension of universal.
Menimbang Teori Kronologi Al-Qur’an Sir William Muir dan Hubbert Grimme
Authors: Ali Fitriana Rahmat
Published: April 2021

Artikel ini merupakan telaah ulang teori kronologi Al-Qur’an yang ditawarkan oleh dua orientalis yang hidup pada abad ke-19, yakni Sir William Muir (1819-1905 M) dan Hubbert Grimme (1864-1942 M). Periodisasi Al-Qur’an yang dilakukan oleh keduanya bertumpu pada pendekatan historis dan teologis. Penelitian ini menggunakan metode deskriptif dengan sumber data primer berupa dua karya kedua orientalis tersebut, yaitu The Coran; Its Composition and Theacing; and the Testimony it Bears to the Holy Scriptures yang ditulis oleh Muir dan juga buku berjudul Mohammed; Einleitung in den Koran System der koranischen Theologie. Hasil dari penelitian ini menyimpulkan bahwa pertama, Versi Muir surah Makkiyah sebanyak 93 surah, sedangkan Madaniyah sejumlah 21 surah. Kedua, Versi Grimme surah Makkiyah sejumlah 92 surah, sementara Madaniyah sebanyak 22 surah.
Waqf dan Ibtidā’ dalam Mushaf Al-Qur’an
Authors: Istiqomah
Published: April 2021

This paper discusses the differences in waqf and ibtidā 'between the Indonesian Standard Manuscripts, Bombay Manuscripts, Holy Manuscripts and Medina Manuscripts based on the waqf signs used in each Mushaf, and their effect on meaning. This research uses a descriptive method. The results of this study conclude that the difference between waqf and ibtidā 'between Indonesian standard manuscripts, Bombay manuscripts, Holy manuscripts and Medina manuscripts lies in the signs used, also in the way they are placed. From these differences give birth to an understanding that may be different from the understanding that arises from waqf and ibtidā 'in other lafazh in the same verse. It's just that the difference in meaning that is born from the difference between the waqf and ibtidā 'signs is not contradictory
Analisis Surat Al-Anfāl Ayat 17: Upaya Mengungkap Sisi Transendental Hermeneutika Double Movement
Authors: Qudsia Miatul , Faishal Haq Muhammad
Published: April 2021

The study of the Koran from a contextual point of view continues to grow. One of the offers that has been continuously studied and applied is the double movement theory initiated by Fazlur Rahman and developed by Abdullah Saeed. The double movement theory emphasizes the socio-historical context of the Koran and the present. To bridge the two periods, a researcher must sensitively take the meaning of the verse being studied or what is called the moral ideal. Thus, the meaning of the purpose of the revelation of the Qur'anic verse will continue to be conveyed at any time. The object of the application of the double movement is indeed law verses, so as to produce a moral ideal that is real or concrete. However, in this study, the researcher found that double movement not only produces concrete moral ideals, but also transcendental ones. The verse studied is the verse of war, surah al-Anfāl verse 17. So that, the result is that the moral ideal which is concrete from this verse is that it is permissible and even required to take the path of war if it is in an emergency and is depressed. For example, there is pressure, discrimination and so on that cause torture. And, the transcendental moral ideal is that there must be an attitude of tawakal and endeavor from every Muslim. That Allah can make real what is considered impossible by humans.
Growth variation of Atlantic salmon Salmo salar at sea affects their population-specific reproductive potential
Authors: Jacobson P , Whitlock R , Huss M , Leonardsson K , Östergren J , Gårdmark A
Published: April 2021

Understanding the processes shaping the dynamics of anadromous fish populations is essential for their management and conservation. Yet, little is known about how variation in performance at sea affects their population dynamics. Here we show that variation in body growth at sea contributes to explaining variation in the reproductive potential for 2 Atlantic salmon Salmo salar populations, but to a varying extent. To this end, we assembled data collected during 50 yr for 2 Baltic salmon populations of hatchery origin, including annually released smolts, survival at sea estimates, size-specific growth at sea, annual length distributions of returning adult females and their reproductive potential. The regression models fitted to explain the reproductive potential of our 2 study populations improved when growth at sea was included as an explanatory variable, in addition to smolt year class abundance and estimates of their survival at sea. This link between body growth at sea and population-level reproductive potential suggests that growth at sea can be important to consider when resolving variation in recovery and dynamics among salmon populations sharing the same sea.
Leukocyte and endothelial adhesion molecules in patients with hypercholesterolemia: the effect of atorvastatin treatment
Authors: Štulc T , Vrablík M , Kasalová Z , Marinov I , Svobodová H , Češka R
Published: April 2021

Atherogenesis involves the migration of leukocytes into vascular
subendothelial space, a process mediated by endothelial and
leukocyte cell adhesion molecules. Endothelial molecules are
assessed indirectly via serum levels, but leukocyte molecules can
be assessed directly. We have therefore hypothesized that
leukocyte adhesion molecules are altered to a greater degree in
hypercholesterolemia than serum endothelial adhesion molecules.
We examined 29 subjects with hypercholesterolemia and
27 controls at baseline and after 12 weeks of atorvastatin
treatment (20 mg/day). Expression of leukocyte integrins CD11a,
CD11b, CD18, and CD49d and of L-selectin was measured by
flow cytometry. Serum ICAM-1, E-selectin and von Willebrand
factor were measured by ELISA. Expression of leukocyte
adhesion molecules was significantly higher in patients at
baseline than in the controls, except for CD11a. Expression
significantly decreased after atorvastatin in most adhesion
molecules except for CD11b. In contrast, there was no effect of
hypercholesterolemia and/or atorvastatin on the serum
endothelial molecules. Leukocyte but not endothelial adhesion
molecules were influenced by hypercholesterolemia and by lipid
lowering treatment. Leukocyte molecules may therefore be a
more sensitive marker of atherogenesis than endothelial
molecules. Our results support the role of increased leukocyte
adhesiveness in atherogenesis.
Liver glucocorticoid receptor and heat shock protein 70 levels in rats exposed to different stress models
Authors: Filipović D , Gavrilović L , Dronjak S , Demajo M , Radojčić MB
Published: April 2021

The aim of the present study was to define the stress-induced
pattern of cytosolic glucocorticoid receptor (GR) and Hsp70
protein in the liver of male Wistar rats exposed to different stress
models: acute (2 h/day) immobilization or cold (4 °C); chronic
(21 days) isolation, crowding, swimming or isolation plus
swimming and combined (chronic plus acute stress). Changes in
plasma levels of corticosterone were studied by
radioimmunoassay (RIA). The results obtained by Western
immunoblotting showed that both acute stressors led to a
significant decrease in cytosolic GR and Hsp70 levels. Compared
to acute stress effects, only a weak decrease in the levels of GR
and Hsp70 was demonstrated in chronic stress models.
Chronically stressed rats, which were subsequently exposed to
novel acute stressors (immobilization or cold), showed a lower
extent of GR down-regulation when compared to acute stress.
The exception was swimming, which partially restores this downregulation. The observed changes in the levels of these major
stress-related cellular proteins in liver cytosol lead to the
conclusion that chronic stressors compromise intracellular GR
down-regulation in the liver.
Inactivation of Gi proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats
Authors: Zemančíková A , Török J , Zicha J , Kuneš J
Published: April 2021

Treatment with pertussis toxin (PTX) which eliminates the activity
of Gi proteins effectively reduces blood pressure (BP) and
vascular resistance in spontaneously hypertensive rats (SHR). In
this study we have compared the functional characteristics of
isolated arteries from SHR with and without PTX-treatment
(10 μg/kg i.v., 48 h before the experiment). Rings of thoracic
aorta, superior mesenteric artery and main pulmonary artery
were studied under isometric conditions to measure the reactivity
of these vessels to receptor agonists and to transmural electrical
stimuli. We have found that the treatment of SHR with PTX had
no effect on endothelium-dependent relaxation of thoracic aorta
induced by acetylcholine. In PTX-treated SHR, the maximum
contraction of mesenteric artery to exogenous noradrenaline was
reduced and the dose-response curve to cumulative
concentration of noradrenaline was shifted to the right. Similarly,
a reduction in the magnitude of neurogenic contractions elicited
by electrical stimulation of perivascular nerves was observed in
the mesenteric artery from PTX-treated SHR. PTX treatment of
SHR also abolished the potentiating effect of angiotensin II on
neurogenic contractions of the main pulmonary artery. These
results indicate that PTX treatment markedly diminishes the
effectiveness of adrenergic stimuli in vasculature of SHR. This
could importantly affect BP regulation in genetic hypertension.
Tinjauan Etis-Teologis Terhadap Tradisi Belis Di Pulau Sumba Berdasarkan Konsep Mahar Dalam Alkitab
Authors: Kamuri Johanis Putratama , Toumeluk Grace Mariany
Published: April 2021

This paper is aimed to determine the appropriate Christian attitude towards the practice of belis (dowry) in Sumba Island. The biblical, anthropological, and sociological concepts of dowry are the conceptual framework for understanding and analyzing the concept of belis. Based on systematic reviews and asymmetric comparisons of the Sumbanese belis concepts and biblical concept of dowry, it is found that rejection of the practice of belis is unnecessary. Belis can be practiced by Sumbanese Christians with a critical attitude. The goal is the transformation of the belis culture. Transformation is achieved through several actions: doing belis principles that do not conflict with biblical principles; rejecting the principles that conflict with biblical principles; and avoiding the practices of belis which have been distorted by deviating motivations either from the biblical or the rights belis principles.
Keywords: Belis; Dowry; Marapu; Sumba; Cultural Transformation.
Refleksi Pandemi Covid-19: Dampak Dan Peluang Membangun Peradaban Berbasis Solidaritas Global
Authors: Putra Andreas Maurenis
Published: April 2021

Even though the theme discussed in this paper is the Covid-19 pandemic, the real background is the world that behind the Covid-19 pandemic, namely, civilization which today has filled with fear, conspiracy, group interests, indifference and injustice. They are actually caused by the humans themselves. Based on this context, the author tries to show that the Covid-19 pandemic is not only a disaster but also an opportunity to lead for a new civilization of global solidarity in the world. Using the literature method (library research), this research was conducted by, first, reading the phenomenon about Covid-19 from the literature. Second, comparing it with central areas in life, and third, draws normative ethical implication which is global solidarity and theological implications in faith inspires a global solidarity movement, especially for Christians, rests on the cross and the resurrection.
Keywords: Covid-19; Civilization; Normative-Ethical Implication; Theological Implication; Global Solidarity.
EKSTENSION FUNNEL DAN FUNNEL STAND UNTUK MEMPERMUDAH MEMASUKKAN CAIRAN ASPAL KE PICNOMETER 50 ML GUNA MENGUKUR MASSA JENIS ASPAL
Authors: Adi Wiyono
Published: April 2021

Abstract - Picnometer is a tool made of glass that has a shape that resembles a perfume bottle. Picnometer is a tool used to measure density or fluid density. There are various sizes of picnometer, but what is often used in the laboratory is the size of 50 ml. Constraints that often occur when measuring density are measurements that cannot run optimally and result in specific gravity taking takes longer. The reason is when moving the asphalt liquid to an asphalt liquid picnometer about the neck of the picnometer, so that repetitive displacement is carried out. When measuring material density, the asphalt temperature ranges from 150 ° C - 170 ° C. Here a PLP (Education Laboratory Staff) of Malang State Polytechnic makes an improvement on the asphalt liquid density. Modifying asphalt density measuring aids, namely funnel extension (funnel) and funnel stand. With the modification, it is hoped that the density measuring instrument can function optimally and become an international standard laboratory
KOMPARASI UNJUK KERJA PERALATAN SPEKTROFOTOMETER UV-VIS PERKIN ELMER LAMBDA 3 DENGAN HITACHI U-2900 PADA PENENTUAN TOTAL PHENOLIC CONTENT
Authors: Lia Agustin  , Rilla Agustina
Published: April 2021

Komparasi dua alat Spektrofotometer dengan merk dan tahun pemakaian yang berbeda diperlukan untuk mengetahui unjuk kerja alat. Pengujian dilakukan pada penentuan kandungan fenolik total (TPC) metode Folin-Ciocalteu. Hasil analisa TPC dari dua alat spektrofotometer kemudian dikomparasi dengan menggunakan uji paired t-test. Uji paired t- test merupakan uji membandingkan rata-rata hasil pengujian dari kedua alat tersebut. Hasil pengujian dikatakan akurat apabila hasil keduanya tidak berbeda signifikan. Uji t berpengaruh positif dan signifikan apabila hasil perhitungan t hitung lebih besar dari t tabel (t- hitung > t- tabel). Hasil penelitian menunjukkan nilai d rata-rata sebesar 85.934, dan standar deviasi bernilai 51130.27368. Nilai tersebut digunakan untuk menghitung nilai t. Nilai t yang didapatkan sebesar 0,0053. Dengan nilai α sebesar 0,05 maka didapat t tabel sebesar 2,262. Karena nilai T-hitung < T-tabel, maka H0 diterima dan H1 ditolak, sehingga dapat dikatakan kinerja hasil uji kedua alat sama.
Facile Exfoliation for High-Quality Molybdenum Disulfide Nanoflakes and Relevant Field-Effect Transistors Developed With Thermal Treatment
Authors: Zhang Yu , Chen Xiong , Zhang Hao , Hu Shaozu , Zhao Guohong , Zhang Meifang , Qin Wei , Wang Zhaohua , Huang Xiaowei , Wang Jun
Published: April 2021

Molybdenum disulfide (MoS2), a typical member of the transition metal dichalcogenides (TMDs) group, is known for its excellent electronic performance and is considered a candidate next-generation semiconductor. The preparation of MoS2 nanoflakes for use as the core of semiconducting devices depends on mechanical exfoliation, but its quality has not yet been optimized. In this paper, a novel exfoliation method of achieving MoS2 nanoflakes is proposed. We find that the size and yield of the exfoliated flakes are improved after thermal treatment for 2 h at a temperature of 110°C followed by precooling for 10 min in ambient air. The new method has the advantage of a 152-fold larger size of obtained MoS2 flakes than traditional mechanical exfoliation. This phenomenon may be attributable to the differences in van Der Waals force and the increase in surface free energy at the interface induced by thermal treatment. In addition, a field-effect transistor (FET) was fabricated on the basis of multilayer MoS2 prepared according to a new process, and the device exhibited a typical depleted-FET performance, with an on/off ratio of ~105 and a field-effect mobility of 24.26 cm2/Vs in the saturated region when VG is 10 V, which is generally consistent with the values for devices reported previously. This implies that the new process may have potential for the standard preparation of MoS2 and even other 2D materials as well.
Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells
Authors: Nakazono Akira , Nakamaru Yuji , Ramezanpour Mahnaz , Kondo Takeshi , Watanabe Masashi , Hatakeyama Shigetsugu , Kimura Shogo , Honma Aya , Wormald P. J. , Vreugde Sarah , Suzuki Masanobu , Homma Akihiro
Published: April 2021

Background

From the first detection in 2019, SARS-CoV-2 infections have spread rapidly worldwide and have been proven to cause an urgent and important health problem. SARS-CoV-2 cell entry depends on two proteins present on the surface of host cells, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). The nasal cavity is thought to be one of the initial sites of infection and a possible reservoir for dissemination within and between individuals. However, it is not known how the expression of these genes is regulated in the nasal mucosa.

Objective

In this study, we examined whether the expression of ACE2 and TMPRSS2 is affected by innate immune signals in the nasal mucosa. We also investigated how fluticasone propionate (FP), a corticosteroid used as an intranasal steroid spray, affects the gene expression.

Methods

Primary human nasal epithelial cells (HNECs) were collected from the nasal mucosa and incubated with Toll-like receptor (TLR) agonists and/or fluticasone propionate (FP), followed by quantitative PCR, immunofluorescence, and immunoblot analyses.

Results

Among the TLR agonists, the TLR3 agonist Poly(I:C) significantly increased ACE2 and TMPRSS2 mRNA expression in HNECs (ACE2 36.212±11.600-fold change, p<0.0001; TMPRSS2 5.598±2.434-fold change, p=0.031). The ACE2 protein level was also increased with Poly(I:C) stimulation (2.884±0.505-fold change, p=0.003). The Poly(I:C)-induced ACE2 expression was suppressed by co-incubation with FP (0.405±0.312-fold change, p=0.044).

Conclusion

The activation of innate immune signals via TLR3 promotes the expression of genes related to SARS-CoV2 cell entry in the nasal mucosa, although this expression is suppressed in the presence of FP. Further studies are required to evaluate whether FP suppresses SARS-CoV-2 viral cell entry.
Evaluation of Loopamp™ Leishmania Detection Kit and Leishmania Antigen ELISA for Post-Elimination Detection and Management of Visceral Leishmaniasis in Bangladesh
Authors: Hossain Faria , Picado Albert , Owen Sophie I. , Ghosh Prakash , Chowdhury Rajashree , Maruf Shomik , Khan Md. Anik Ashfaq , Rashid Md. Utba , Nath Rupen , Baker James , Ghosh Debashis , Adams Emily R. , Duthie Malcolm S. , Hossain Md. Sakhawat , Basher Ariful , Nath Proggananda , Aktar Fatima , Cruz Israel , Mondal Dinesh
Published: April 2021

With reduced prevalence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), direct and field deployable diagnostic tests are needed to implement an effective diagnostic and surveillance algorithm for post-elimination VL control. In this regard, here we investigated the diagnostic efficacies of a loop-mediated isothermal amplification (LAMP) assay (Loopamp™ Leishmania Detection Kit, Eiken Chemical CO., Ltd, Japan), a real-time quantitative PCR assay (qPCR) and the Leishmania antigen ELISA (CLIN-TECH, UK) with different sampling techniques and evaluated their prospect to incorporate into post-elimination VL control strategies. Eighty clinically and rK39 rapid diagnostic test confirmed VL cases and 80 endemic healthy controls were enrolled in the study. Peripheral blood and dried blood spots (DBS) were collected from all the participants at the time of diagnosis. DNA was extracted from whole blood (WB) and DBS via silica columns (QIAGEN) and boil & spin (B&S) methods and tested with qPCR and Loopamp. Urine was collected from all participants at the time of diagnosis and was directly subjected to the Leishmania antigen ELISA. 41 patients were followed up and urine samples were collected at day 30 and day 180 after treatment and ELISA was performed. The sensitivities of the Loopamp-WB(B&S) and Loopamp-WB(QIA) were 96.2% (95% CI 89·43-99·22) and 95% (95% CI 87·69-98·62) respectively. The sensitivity of Loopamp-DBS(QIA) was 85% (95% CI 75·26- 92·00). The sensitivities of the qPCR-WB(QIA) and qPCR-DBS(QIA) were 93.8% (95% CI 86·01-97·94) and 72.5% (95% CI 61·38-81·90) respectively. The specificity of all molecular assays was 100%. The sensitivity and specificity of the Leishmania antigen ELISA were 97.5% (95% CI 91·47-99·70) and 91.95% (95% CI 84·12-96·70) respectively. The Leishmania antigen ELISA depicted clinical cure at day 180 in all the followed-up cases. Efficacy and sustainability identify the Loopamp-WB(B&S) and the Leishmania antigen ELISA as promising and minimally invasive VL diagnostic tools to support VL diagnostic and surveillance activities respectively in the post-elimination era.
PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease
Authors: Grassi Germana , Vanini Valentina , De Santis Federica , Romagnoli Alessandra , Aiello Alessandra , Casetti Rita , Cimini Eleonora , Bordoni Veronica , Notari Stefania , Cuzzi Gilda , Mosti Silvia , Gualano Gina , Palmieri Fabrizio , Fraziano Maurizio , Goletti Delia , Agrati Chiara , Sacchi Alessandra
Published: April 2021

Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage.
The Role of Sirtuin-1 in Immune Response and Systemic Lupus Erythematosus
Authors: Qiu Yueqi , Zhou Xingyu , Liu Yu , Tan Siqi , Li Yaping
Published: April 2021

Systemic lupus erythematosus (SLE) is a potentially fatal multisystem inflammatory chronic disorder, the etiology and pathogenesis of which remain unclear. The loss of immune tolerance in SLE patients contributes to the production of autoantibodies that attack multiple organs and tissues, such as the skin, joints, and kidneys. Immune cells play important roles in the occurrence and progression of SLE through amplified immune responses. Sirtuin-1 (SIRT1), an NAD+-dependent histone deacetylase, has been shown to be a pivotal regulator in various physiological processes, including cell differentiation, apoptosis, metabolism, aging, and immune responses, via modulation of different signaling pathways, such as the nuclear factor κ-light-chain-enhancer of activated B cells and activator protein 1 pathways. Recent studies have provided evidence that SIRT1 could be a regulatory element in the immune system, whose altered functions are likely relevant to SLE development. This review aims to illustrate the functions of SIRT1 in different types of immune cells and the potential roles of SIRT1 in the SLE pathogenesis and its therapeutic perspectives.
Exploring the Role of Matrix Metalloproteinases as Biomarkers in Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. A Pilot Study
Authors: Terraneo Silvia , Lesma Elena , Ancona Silvia , Imeri Gianluca , Palumbo Giuseppina , Torre Olga , Giuliani Lisa , Centanni Stefano , Peron Angela , Tresoldi Silvia , Cetrangolo Paola , Di Marco Fabiano
Published: April 2021

Background: Lymphangioleiomyomatosis can develop in a sporadic form (S-LAM) or in women with tuberous sclerosis complex (TSC). The matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes potentially involved in cystic lung destruction, and in the process of migration of LAM cells. The aim of the study was to explore the role of MMP-2 and MMP-7, such as vascular endothelial growth factor (VEGF) -C and -D in women with LAM, including patients with minor pulmonary disease (i.e., <10 lung cysts), and TSC with or without LAM.

Methods: We evaluated 50 patients: 13 individuals affected by S-LAM, 20 with TSC-LAM, of whom six with minor pulmonary disease, and 17 with TSC without pulmonary involvement. Sixteen healthy women were used as controls.

Results: MMP-2 resulted higher in LAM compared to healthy volunteers, and TSC patients (p = 0.040). MMP-7 was higher in TSC-LAM patient, with even greater values in patients with TSC-LAM minor pulmonary disease, than in S-LAM patients, and in controls (p = 0.001). VEGF-D level was lower than 800 pg/mL in all healthy controls and resulted higher in S-LAM and TSC-LAM than in TSC patients and controls (p < 0.001). VEGF-C values were not statistically different in the study population (p = 0.354). The area under ROC curves (AUCs) of MMP-2, and MMP-7 for predicting LAM diagnosis were of 0.756 ± 0.079 (p = 0.004), and 0.828 ± 0.060 (p < 0.001), respectively. Considering only patients with TSC, the AUCs for MMP-2, and MMP-7 in predicting LAM were 0.694 ± 0.088 (p = 0.044), and 0.713 ± 0.090 (p = 0.027), respectively.

Conclusions: Our data suggest that MMP-2 and MMP-7 could be promising biomarkers for LAM diagnosis.
Impact of mcr-1 on the Development of High Level Colistin Resistance in Klebsiella pneumoniae and Escherichia coli
Authors: Zhu Xiao-Qing , Liu Yi-Yun , Wu Renjie , Xun Haoliang , Sun Jian , Li Jian , Feng Yaoyu , Liu Jian-Hua
Published: April 2021

Plasmid-mediated colistin resistance genemcr-1generally confers low-level resistance. The purpose of this study was to investigate the impact ofmcr-1on the development of high-level colistin resistance (HLCR) inKlebsiella pneumoniaeandEscherichia coli. In this study,mcr-1-negativeK. pneumoniaeandE. colistrains and their correspondingmcr-1-positive transformants were used to generate HLCR mutantsviamultiple passages in the presence of increasing concentrations of colistin. We found that forK. pneumoniae, HLCR mutants with minimum inhibitory concentrations (MICs) of colistin from 64 to 1,024 mg/L were generated. Colistin MICs increased 256- to 4,096-fold formcr-1-negativeK. pneumoniaestrains but only 16- to 256-fold for themcr-1-harboring transformants. ForE. coli, colistin MICs increased 4- to 64-folds, but only 2- to 16-fold for theirmcr-1-harboring transformants. Notably,mcr-1improved the survival rates of bothE. coliandK. pneumoniaestrains when challenged with relatively high concentrations of colistin. In HLCRK. pneumoniaemutants, amino acid alterations predominately occurred incrrB, followed byphoQ,crrA,pmrB,mgrB, andphoP, while inE. colimutants, genetic alterations were mostly occurred inpmrBandphoQ. Additionally, growth rate analyses showed that the coexistence ofmcr-1and chromosomal mutations imposed a fitness burden on HLCR mutants ofK. pneumoniae. In conclusion, HLCR was more likely to occur inK. pneumoniaestrains thanE. colistrains when exposed to colistin. Themcr-1gene could improve the survival rates of strains of both bacterial species but could not facilitate the evolution of high-level colistin resistance.
Glioblastoma Primary Cells Retain the Most Copy Number Alterations That Predict Poor Survival in Glioma Patients
Authors: Chen Chia-Hua , Lin Ya-Jui , Lin You-Yu , Lin Chang-Hung , Feng Li-Ying , Chang Ian Yi-Feng , Wei Kuo-Chen , Huang Chiung-Yin
Published: April 2021

Gliomas are solid tumors that originate from glial cells in the brain or spine and account for 74.6% of malignant primary central nervous system tumors worldwide. As patient-derived primary cells are important tools for drug screening and new therapy development in glioma, we aim to understand the genomic similarity of the primary cells to their parental tumors by comparing their whole-genome copy number variations and expression profile of glioma clinicopathologic factors. We found that the primary cells from grade II/III gliomas lost most of the gene copy number alterations (CNAs), which were mainly located on chromosome 1p and 19q in their parental tumors. The glioblastoma (GBM) primary cells preserved 83.7% of the gene CNAs in the parental GBM tumors, including chromosome 7 gain and 10q loss. The CNA gains of LINC00226 and ADAM6 and the chromosome 16p11 loss were reconstituted in primary cells from both grade II/III gliomas and GBMs. Interestingly, we found these CNAs were correlated to overall survival (OS) in glioma patients using the Merged Cohort LGG and GBM dataset from cBioPortal. The gene CNAs preserved in glioma primary cells often predicted poor survival, whereas the gene CNAs lost in grade II/III primary cells were mainly associated to better prognosis in glioma patients. Glioma prognostic factors that predict better survival, such as IDH mutations and 1p/19q codeletion in grade II/III gliomas, were lost in their primary cells, whereas methylated MGMT promoters as well as TERT promoter mutations were preserved in GBM primary cells while lost in grade II/III primary cells. Our results suggest that GBM primary cells tend to preserve CNAs in their parental tumors, and these CNAs are correlated to poor OS and predict worse prognosis in glioma patients.
Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer
Authors: Novillo Apolonia , Fernández-Santander Ana , Gaibar Maria , Galán Miguel , Romero-Lorca Alicia , El Abdellaoui-Soussi Fadoua , Gómez-del Arco Pablo
Published: April 2021

Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4—the core component of the nucleosome remodeling and deacetylase (NuRD) complex—may be mutated in patients with this disease. However, information on CHD4 mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking. The present work examines mutations in CHD4 reported in patients with breast cancer and included in public databases and attempts to identify their roles in its development. The databases revealed 81 point mutations across different types of breast cancer (19 of which also appeared in endometrial, intestinal, nervous system, kidney, and lymphoid organ cancers). 71.6% of the detected mutations were missense mutations, 13.6% were silent, and 6.2% nonsense. Over 50% affected conserved residues of the ATPase motor (ATPase and helicase domains), and domains of unknown function in the C-terminal region. Thirty one mutations were classified in the databases as either ‘deleterious’, ‘probably/possibly damaging’ or as ‘high/medium pathogenic’; another five nonsense and one splice-site variant were predicted to produce potentially harmful truncated proteins. Eight of the 81 mutations were categorized as putative driver mutations and have been found in other cancer types. Some mutations seem to influence ATPase and DNA translocation activities (R1162W), while others may alter protein stability (R877Q/H, R975H) or disrupt DNA binding and protein activity (R572*, X34_splice) suggesting CHD4 function may be affected. In vivo tumorigenecity studies in endometrial cancer have revealed R975H and R1162W as mutations that lead to CHD4 loss-of-function. Our study provides insight into the molecular mechanism whereby CHD4, and some of its mutants could play a role in breast cancer and suggest important implications for the biological comprehension and prognosis of breast cancer, identifying CHD4 as a novel therapeutic target for BC patients.
Hengshun Aromatic Vinegar Improves Glycolipid Metabolism in Type 2 Diabetes Mellitus via Regulating PGC-1α/PGC-1β Pathway
Authors: Li Guoquan , Tan Xuemei , Zhang Bao , Guan Linshu , Zhang Yidan , Yin Lianhong , Gao Meng , Zhu Shenghu , Xu Lina
Published: April 2021

Hengshun aromatic vinegar (HSAV), produced by typical solid-state or liquid-state fermentation techniques, is consumed worldwide as a food condiment. HSAV shows multiple bioactivities, but its activity in type 2 diabetes mellitus (T2DM) and possible mechanisms have not been reported. In this study, the effects of HSAV against T2DM were evaluated in insulin-induced HepG2 cells and high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. Then, the mechanisms of HSAV against T2DM were explored by Real-time PCR, Western blot, immunofluorescence assays, siRNA transfection and gene overexpression experiments. Results indicated that HSAV significantly improved glucose consumption and reduced triglycerides (TG) contents in metabolic disordered HepG2 cells. Meanwhile, HSAV obviously alleviated general status, liver and kidney functions of T2DM rats, and decreased hyperglycemia and hyperlipidemia, improved insulin resistance, and reduced lipid accumulation in liver. Mechanism studies indicated that HSAV markedly down-regulated the expression of proliferator-activated receptor γ coactivator-1α (PGC-1α), then regulated peroxisome proliferators-activated receptor α (PPAR-α)/protein kinase B (AKT) signal pathway mediated gluconeogenesis and glycogen synthesis. Meanwhile, HSAV significantly up-regulated proliferator-activated receptor γ coactivator-1β (PGC-1β), and subsequently decreased sterol regulatory element binding protein-1c (SREBP-1c) pathway mediated lipogenesis. In conclusion, HSAV showed potent anti-T2DM activity in ameliorating dysfunction of glycolipid metabolism through regulating PGC-1α/PGC-1β pathway, which has a certain application prospect as an effective diet supplement for T2DM therapy in the future.
The Key Target and Molecular Mechanism of the Volatile Component of Scutellaria baicalensis Georgi in Acute Lung Injury Based on Network Pharmacology
Authors: Zhu Guosong , Zhang Jiaqiang , Yang Yali , Zhang Haoran , Jin Wenwen , Su Fangchu , Liang Junting , Wang Kaiwei , Zhang Jianhua , Chen Chuanliang
Published: April 2021

Ethnopharmacological relevance:Scutellaria baicalensis georgi is one of the most widely studied TCMs; its effects in ALI have been studied in a large number of experiments, and the efficacy of volatile oil from TCM remains to be studied.

Aim: The volatile component of Scutellaria baicalensis georgi was selected to act on the key target of acute lung injury and was preliminarily studied for its specific molecular mechanism.

Methods: The volatile active substances of Scutellaria baicalensis georgi were extracted by GC–MS, and the active ingredients related with the occurrence and development of acute lung injury were searched and matched by the TCMSP database. The pharmacologic data and analysis platform of TCM were used to retrieve and screen for the volatile active components and the possible therapeutic targets of Scutellaria baicalensis georgi. In addition, acute lung injury was searched in the disease target database to identify the corresponding disease target proteins, thereby establishing a protein–protein interaction network. Finally, the effects of wogonin on the apoptotic and inflammatory factors in the acute lung injury cell model were analyzed experimentally.

Results: We identified 100 candidate targets and successfully constructed a complex target network. The targets identified by the above gene enrichment analysis played important roles in the autoimmune disease cell cycle apoptosis and related signaling pathways. The KEGG pathway analysis showed that most of the target genes were involved in the inflammatory response regulation of the TRP, PI3K-Akt, and IL-17 signaling pathways. The participation of wogonin in the specific regulatory pathways of PI3K-Akt signaling and IL-17 signaling was verified through experiments. In the lung-injured cell model, the results showed that wogonin inhibited the apoptosis of injured lung cells by inhibiting the expression of BAD gene and the activation of cleaved caspase-3 gene while increasing Bcl-2 expression. In addition, wogonin inhibited the expression of the abovementioned inflammatory factors and further inhibited the inflammatory response in the lung injury cells.

Conclusion: The results of pharmacological network analysis can predict and explain the regulation mechanism of multi-target and multi-pathway of TCM components. This study identified the potential target and important pathway of wogonin in regulating acute lung injury. At the same time, the accuracy of network pharmacological prediction is also preliminarily verified by molecular biology experiment.
Efficacy and Safety of Berberine Alone for Several Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Ye Yu , Liu Xiufen , Wu Ninghua , Han Yanqi , Wang Jiawen , Yu Yuandong , Chen Qingjie
Published: April 2021

Background: Metabolic activity is the basic life activity of organisms and the fundamental for maintaining body functions. With the improvement of living standards, the incidence of metabolic disorder is also increasing. At present, most of the clinical treatment strategies and meta-analysis for metabolic disorder uncover that combined medicines with berberine ameliorate several metabolic disorders. However, evidence to disclose the therapeutic effect of berberine treatment alone and the possible factors affecting the efficacy is limited. Therefore, we have formulated strict inclusion criteria and selected more reliable data for meta-analysis through more refined screening strategies to provide evidence and guidance for clinical decision-making and understand the effect of berberine treatment alone and the factors affecting its efficacy.

Methods and results: Using meta-analysis of “Cochrane Handbook for Systematic Reviews of Interventions” as guidelines, we searched PubMed, GeenMedical, Cochrane library, and china national knowledge infrastructure (CNKI) for trials reporting clinical treatment data of berberine. Another 417 trials were included through other sources to increase confidence in results. Among the 1,660 related documents retrieved from the four databases, 18 eligible documents were selected for analysis. Given the differences in trial design and measurement units, we used the standardized mean difference (SMD) method to eliminate the differences and then summarize the data for analysis. The main factors are triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), homeostasis model assessment-insulin resistance (HOMA-IR), and fasting plasma glucose (FPG). Random-effect model analysis was performed: TG (SMD: 0.94; 95%CI: 0.49,1.38; p = 0.00), TC (SMD: 1.06; 95%CI: 0.64, 1.48; p = 0.00), LDL (SMD: 1.77; 95%CI: 1.11,2.44; p = 0.00), HDL (SMD: −1.59; 95%CI: −2.32, −0.85; p = 0.00), HOMA-IR (SMD: 1.25; 95%CI: 0.25,2.24; p = 0.01), and FPG (SMD: 0.65; 95%CI: 0.28,1.03; p = 0.00). This study aimed to conduct a systematic review and meta-analysis of the literature to evaluate the therapeutic effect of berberine singly on metabolic diseases.

Conclusion: Berberine can improve obesity and hyperlipidemia by reducing TG, TC, and LDL and increasing HDL; reduce insulin resistance to improve type Ⅱ diabetes; and prevent diabetic encephalopathy.