bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus
Authors: Sene Letícia de Barros , Scarano Wellerson Rodrigo , Zapparoli Adriana , Gontijo José Antônio Rocha , Boer Patrícia Aline
Published: February 2021

Background

Here, we have demonstrated that gestational low-protein (LP) intake offspring present lower birth weight, reduced nephron numbers, renal salt excretion, arterial hypertension, and renal failure development compared to regular protein (NP) intake rats in adulthood. We evaluated the expression of various miRNAs and predicted target genes in the kidney in gestational 17-days LP (DG-17) fetal metanephros to identify molecular pathways involved in the proliferation and differentiation of renal embryonic or fetal cells.

Methods

Pregnant Wistar rats were classified into two groups based on protein supply during pregnancy: NP (regular protein diet, 17%) or LP diet (6%).Renal miRNA sequencing (miRNA-Seq)performed on the MiSeq platform,RT-qPCR of predicted target genes, immunohistochemistry, and morphological analysis of 17-DG NP and LP offspring were performed using previously described methods.

Results

A total of 44 miRNAs, of which 19 were up and 25 downregulated, were identified in 17-DG LP fetuses compared to age-matched NP offspring. We selected 7 miRNAs involved in proliferation, differentiation, and cellular apoptosis. Our findings revealed reduced cell number and Six-2 and c-Myc immunoreactivity in metanephros cap (CM) and ureter bud (UB) in 17-DG LP fetuses. Ki-67 immunoreactivity in CM was 48% lesser in LP compared to age-matched NP fetuses. Conversely, in LP CM and UB, β-catenin was 154%, and 85% increased, respectively. Furthermore, mTOR immunoreactivity was higher in LP CM (139%) and UB (104%) compared to that in NP offspring. TGFβ-1 positive cells in the UB increased by approximately 30% in the LP offspring. Moreover, ZEB1 metanephros-stained cells increased by 30% in the LP offspring. ZEB2 immunofluorescence, although present in the entire metanephros, was similar in both experimental groups.

Conclusions

Maternal protein restriction changes the expression of miRNAs, mRNAs, and proteins involved in proliferation, differentiation, and apoptosis during renal development. Renal ontogenic dysfunction, caused by maternal protein restriction, promotes reduced reciprocal interaction between CM and UB; consequently, a programmed and expressive decrease in nephron number occurs in the fetus.
Enzymatically polymerised polyphenols prepared from various precursors potentiate antigen-specific immune responses in both mucosal and systemic compartments in mice
Authors: Tada Rui , Ogasawara Miki , Yamanaka Daisuke , Sakurai Yasuhiro , Negishi Yoichi , Kiyono Hiroshi , Ohno Naohito , Kunisawa Jun , Aramaki Yukihiko
Published: February 2021

Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.
Whole-genome analyses of extended-spectrum or AmpC β-lactamase-producing Escherichia coli isolates from companion dogs in Japan
Authors: Yasugi Mayo , Hatoya Shingo , Motooka Daisuke , Matsumoto Yuki , Shimamura Shunsuke , Tani Hiroyuki , Furuya Masaru , Mie Keiichiro , Miyake Masami , Nakamura Shota , Shimada Terumasa
Published: February 2021

The emergence and global spread of extended-spectrum or AmpC β-lactamase (ESBL/AmpC)-producing Enterobacteriaceae in companion animals have led to the hypothesis that companion animals might be reservoirs for cross-species transmission because of their close contact with humans. However, current knowledge in this field is limited; therefore, the role of companion animals in cross-species transmission remains to be elucidated. Herein, we studied ESBL/AmpC-producing Enterobacteriaceae,Escherichia coliin particular, isolated from extraintestinal sites and feces of companion dogs. Whole-genome sequencing analysis revealed that (i) extraintestinalE.coliisolates were most closely related to those isolated from feces from the same dog, (ii) chromosomal sequences in the ST131/C1-M27 clade isolated from companion dogs were highly similar to those in the ST131/C1-M27 clade of human origin, (iii) certain plasmids, such as IncFII/pMLST F1:A2:B20/blaCTX-M-27, IncI1/pMLST16/blaCTX-M-15, or IncI1/blaCMY-2from dog-derivedE.coliisolates, shared high homology with those from several human-derived Enterobacteriaceae, (iv) chromosomalblaCTX-M-14was identified in the ST38 isolate from a companion dog, and (v) eight out of 14 tested ESBL/AmpC-producingE.coliisolates (i.e., ST131, ST68, ST405, and ST998) belonged to the human extraintestinal pathogenicE.coli(ExPEC) group. All of thebla-coding plasmids that were sequenced genome-wide were capable of horizontal transfer. These results suggest that companion dogs can spread ESBL/AmpC-producing ExPEC via their feces. Furthermore, at least some ESBL/AmpC-producing ExPECs andbla-coding plasmids can be transmitted between humans and companion dogs. Thus, companion dogs can act as an important reservoir for ESBL/AmpC-producingE.coliin the community.
Applying decision-making capacity criteria in practice: A content analysis of court judgments
Authors: Kane Nuala B. , Keene Alex Ruck , Owen Gareth S. , Kim Scott Y. H.
Published: February 2021

Background/Objectives

Many jurisdictions use a functional model of capacity with similar legal criteria, but there is a lack of agreed understanding as to how to apply these criteria in practice. We aimed to develop a typology of capacity rationales to describe court practice in making capacity determinations and to guide professionals approaching capacity assessments.

Methods

We analysed all published cases from courts in England and Wales [Court of Protection (CoP) judgments, or Court of Appeal cases from the CoP] containing rationales for incapacity or intact capacity(n = 131). Qualitative content analysis was used to develop a typology of capacity rationales or abilities. Relationships between the typology and legal criteria for capacity [Mental Capacity Act (MCA)] and diagnoses were analysed.

Results

The typology had nine categories (reliability: kappa = 0.63): 1) to grasp information or concepts, 2) to imagine/ abstract, 3) to remember, 4) to appreciate, 5) to value/ care, 6) to think through the decision non-impulsively, 7) to reason, 8) to give coherent reasons, and 9) to express a stable preference. Rationales most frequently linked to MCA criterion ‘understand’ were ability to grasp information or concepts (43%) or to appreciate (42%), and to MCA criterion ‘use or weigh’ were abilities to appreciate (45%) or to reason (32%). Appreciation was the most frequently cited rationale across all diagnoses. Judges often used rationales without linking them specifically to any MCA criteria (42%).

Conclusions

A new typology of rationales could bridge the gap between legal criteria for decision-making capacity and phenomena encountered in practice, increase reliability and transparency of assessments, and provide targets for decision-making support.
Learning, exploitation and bias in games
Authors: McNamara John M. , Houston Alasdair I. , Leimar Olof
Published: February 2021

We focus on learning during development in a group of individuals that play a competitive game with each other. The game has two actions and there is negative frequency dependence. We define the distribution of actions by group members to be an equilibrium configuration if no individual can improve its payoff by unilaterally changing its action. We show that at this equilibrium, one action is preferred in the sense that those taking the preferred action have a higher payoff than those taking the other, more prosocial, action. We explore the consequences of a simple ‘unbiased’ reinforcement learning rule during development, showing that groups reach an approximate equilibrium distribution, so that some achieve a higher payoff than others. Because there is learning, an individual’s behaviour can influence the future behaviour of others. We show that, as a consequence, there is the potential for an individual to exploit others by influencing them to be the ones to take the non-preferred action. Using an evolutionary simulation, we show that population members can avoid being exploited by over-valuing rewards obtained from the preferred option during learning, an example of a bias that is ‘rational’.
COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience
Authors: Alemanno Federica , Houdayer Elise , Parma Anna , Spina Alfio , Del Forno Alessandra , Scatolini Alessandra , Angelone Sara , Brugliera Luigia , Tettamanti Andrea , Beretta Luigi , Iannaccone Sandro
Published: February 2021

Introduction

COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy).

Material and methods

87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge.

Results

Out of the 87 patients (62 Male, mean age 67.23 ± 12.89 years), 80% had neuropsychological deficits (MoCA and MMSE) and 40% showed mild-to-moderate depression. Group1 had higher scores than Group3 for visuospatial/executive functions (p = 0.016), naming (p = 0.024), short- and long-term memory (p = 0.010, p = 0.005), abstraction (p = 0.024), and orientation (p = 0.034). Group1 was younger than Groups2 and 3. Cognitive impairments correlated with patients’ age. Only 18 patients presented with anosmia. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post-traumatic stress disorder.

Conclusion

Patients with severe functional impairments had important cognitive and emotional deficits which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.
Characterization of Arcobacter spp. Isolated from human diarrheal, non-diarrheal and food samples in Thailand
Authors: Kietsiri Paksathorn , Muangnapoh Chonchanok , Lurchachaiwong Woradee , Lertsethtakarn Paphavee , Bodhidatta Ladaporn , Suthienkul Orasa , Waters Norman C. , Demons Samandra T. , Vesely Brian A.
Published: February 2021

Arcobacter butzleri is an emerging zoonotic food-borne and water-borne pathogen that can cause diarrhea in humans. The global prevalence of A. butzleri infection is underestimated, and little is known about their phenotypic and genotypic characterization. The aim of this study was to determine antimicrobial susceptibility (AST) profiles, detect related virulence genes, and classify sequence type (ST) of A. butzleri isolates obtained from human stool and food samples. A total of 84 A. butzleri isolates were obtained from human diarrheal (n = 25), non-diarrheal (n = 24) stool, and food (n = 35) samples in Thailand. They were evaluated for phenotypic identification by conventional microbiological procedures and AST by Kirby-Bauer disc diffusion method as well as virulence genes detection. Representative isolates from each origin were selected based on the presence of virulence genes and AST profiles to analyze genetic diversity by multilocus sequence typing (MLST). All isolates showed resistance to nalidixic acid 40.5% (34/84), ciprofloxacin 11.9% (10/84), azithromycin 8.3% (7/84), and erythromycin 3.6% (3/84). Regarding the ten virulence genes detected, cj1349, mviN and pldA had the highest prevalence 100% (84/84), followed by tlyA 98.8% (83/84), cadF 97.6% (82/84), ciaB 71.4% (60/84), hecA and hecB 22.6% (19/84), iroE 15.5% (13/84) and irgA 10.7% (9/84), respectively. Three virulence genes were present among A. butzleri isolates of human diarrheal stool and food samples, with a significant difference observed among isolates; hecB [36% (9/25) and 8.6% (3/35)], hecA [36% (9/25) and 5.7% (2/35)], and irgA [24% (6/25) and 2.9% (1/35)] (p < 0.05), respectively. The hecA and hecB virulence genes functions are related to the mechanism of hemolysis, while irgA supports a bacterial nutritional requirement. MLST analysis of 26 A. butzleri isolates revealed that 16 novel STs exhibited high genetic diversity. The results of this study is useful for understanding potentially pathogenic and antimicrobial-resistant A. butzleri in Thailand. The pathogenic virulence markers hecB, hecA, and irgA have the potential to be developed for rapid diagnostic detection in human diarrheal stool. No significant relationships among STs and sources of origin were observed. Little is known about A. butzleri, the mechanism of action of these virulence genes, is a topic that needs further investigation.
Decreased content of ascorbic acid (vitamin C) in the brain of knockout mouse models of Na+,K+-ATPase-related neurologic disorders
Authors: Ikeda Keiko , Tienda Adriana A. , Harrison Fiona E. , Kawakami Kiyoshi
Published: February 2021

Na+,K+-ATPase is a crucial protein responsible for maintaining the electrochemical gradients across the cell membrane. The Na+,K+-ATPase is comprised of catalytic α, β, and γ subunits. In adult brains, the α3 subunit, encoded by ATP1A3, is predominantly expressed in neurons, whereas the α2 subunit, encoded by ATP1A2, is expressed in glial cells. In foetal brains, the α2 is expressed in neurons as well. Mutations in α subunits cause a variety of neurologic disorders. Notably, the onset of symptoms in ATP1A2- and ATP1A3-related neurologic disorders is usually triggered by physiological or psychological stressors. To gain insight into the distinct roles of the α2 and α3 subunits in the developing foetal brain, whose developmental dysfunction may be a predisposing factor of neurologic disorders, we compared the phenotypes of mouse foetuses with double homozygous knockout of Atp1a2 and Atp1a3 (α2α3-dKO) to those with single knockout. The brain haemorrhage phenotype of α2α3-dKO was similar to that of homozygous knockout of the gene encoding ascorbic acid (ASC or vitamin C) transporter, SVCT2. The α2α3-dKO brain showed significantly decreased level of ASC compared with the wild-type (WT) and single knockout. We found that the ASC content in the basal ganglia and cerebellum was significantly lower in the adult Atp1a3 heterozygous knockout mouse (α3-HT) than in the WT. Interestingly, we observed a significant decrease in the ASC level in the basal ganglia and cerebellum of α3-HT in the peripartum period, during which mice are under physiological stress. These observations indicate that the α2 and α3 subunits independently contribute to the ASC level in the foetal brain and that the α3 subunit contributes to ASC transport in the adult basal ganglia and cerebellum. We propose that decreases in ASC levels may affect neural network development and are linked to the pathophysiology of ATP1A2- and ATP1A3-related neurologic disorders.
Utilizing a large-scale biobanking registry to assess patient priorities and preferences for cancer research and education
Authors: Hathaway Cassandra A. , Siegel Erin M. , Chung Christine H. , Pabbathi Smitha , Vidrine Jennifer , Vadaparampil Susan , Tworoger Shelley S.
Published: February 2021

Patients consented to biobanking studies typically do not specify research conducted on their samples and data. Our objective was to gauge cancer biobanking participant preferences on research topics. Patient-participants of a biobanking study at a comprehensive cancer center who had an appointment within the last 5 years, had a valid email address, and with a last known vital status of alive, were emailed a newsletter containing a link to a survey about preferences and priorities for research. The survey assessed demographics and research interest in three domains: cancer site, cancer-related topics, and issues faced by cancer patients. 37,384 participants were contacted through email to participate in the survey. 16,158 participants (43.2%) opened the email, 1,626 (4.3% overall, 10% of those who opened the email) completed the survey, and 1,291 (79.4% of those who completed the survey) selected at least one research priority. Among those who selected at least one research priorities for cancer-relevant topics, the most commonly selected were cancer treatment (66%), clinical trials (54%), and cancer prevention (53%). Similarly, the most selected priorities for cancer-related issues faced by patients were physical side effects of cancer (57%), talking to the oncologist (53%), and emotional challenges due to cancer (47%). Differences by gender were observed, with females reporting more interest in research generally. Cancer patients participating in a biobanking protocol prioritized research on treatments, prevention and side effects, which varied by gender.
The NKG2D ligand ULBP4 is not expressed by human monocytes
Authors: Lazarova Mariya , Kim Younghoon , Steinle Alexander
Published: February 2021

The C-type lectin-like receptor NKG2D contributes to the immunosurveillance of virally infected and malignant cells by cytotoxic lymphocytes. A peculiar and puzzling feature of the NKG2D-based immunorecognition system is the high number of ligands for this single immunoreceptor. In humans, there are a total of eight NKG2D ligands (NKG2DL) comprising two members of the MIC (MICA, MICB) and six members of the ULBP family of glycoproteins (ULBP1 to ULBP6). While MICA has been extensively studied with regard to its biochemistry, cellular expression and function, very little is known about the NKG2DL ULBP4. This is, at least in part, due to its rather restricted expression by very few cell lines and tissues. Recently, constitutive ULBP4 expression by human monocytes was reported, questioning the view of tissue-restricted ULBP4 expression. Here, we scrutinized ULBP4 expression by human peripheral blood mononuclear cells and monocytes by analyzing ULBP4 transcripts and ULBP4 surface expression. In contrast to MICA, there was no ULBP4 expression detectable, neither by freshly isolated monocytes nor by PAMP-activated monocytes. However, a commercial antibody erroneously indicated surface ULBP4 on monocytes due to a non-ULBP4-specific binding activity, emphasizing the critical importance of validated reagents for life sciences. Collectively, our data show that ULBP4 is not expressed by monocytes, and likely also not by other peripheral blood immune cells, and therefore exhibits an expression pattern rather distinct from other human NKG2DL.
Knowledge, attitude and practice towards insulin self-administration and associated factors among diabetic patients at Zewditu Memorial Hospital, Ethiopia
Authors: Nasir Beshir Bedru , Buseir Miftah Shafi , Muhammed Oumer Sada
Published: February 2021

Background

Diabetes mellitus is a common health problem worldwide. Proper insulin administration plays an important role in long term optimal blood sugar control. Adequate knowledge and attitude about insulin self-administration could also improve the management of diabetes and eventually improve the quality of life. This study aimed to assess knowledge, attitude and practice towards insulin self-administration and associated factors among diabetic patients at Zewditu Memorial Hospital (ZMH), Ethiopia.

Methods

An institution-based cross-sectional study was conducted among 245 diabetic patients who were selected by systematic random sampling during follow-up at ZMH. The data was collected using an interviewer-administered structured questionnaire and analyzed by SPSS v.20. Binary logistic regression was used to identify associated factors of patients’ knowledge andP < 0.05was used to declare the association.

Results

Among 245 patients enrolled, 53.9% were male with a mean age of 53.26 ±13.43 years and more than 84% of the patients can read and write. The overall patients’ knowledge was 63.4%. Better knowledge was observed concerning timing (78.4%) and site of insulin injection (89.4%), while knowledge on the angle of inclination during insulin administration (43.3%) and complications of insulin therapy (49%) were low. Patients who were male gender, never married, government or NGO employees, urban residents, who completed elementary and higher education had a higher knowledge than their comparators. The majority (62%) of the study patients had a favorable attitude on insulin self-administration. Although the majority 177(72.2%) of the study patients have administered insulin themselves, only 120(49.0%) of the patients injected insulin appropriately at 450. Frequent repetition of the injection site was practiced among 176(71.8%) patients and 139(56.7%) injected insulin before or immediately after food intake.

Conclusion

Patients’ knowledge and attitude seem suboptimal and malpractice of insulin self-administration was reported. Therefore, the gaps should be addressed through patient education and demonstration of insulin injection during each hospital visit.
Signs of neuroaxonal injury in preeclampsia—A case control study
Authors: Andersson Malin , Oras Jonatan , Thörn Sven Egron , Karlsson Ove , Kälebo Peter , Zetterberg Henrik , Blennow Kaj , Bergman Lina
Published: February 2021

Background

Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma.

Methods

CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum.

Results

Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy.

Conclusion

NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.
Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
Authors: Song Nan , Chen Lihong , Zhou Zhemin , Ren Xingmei , Liu Bo , Zhou Siyu , Wang Caihong , Wu Yun , Waterfield Nicholas R. , Yang Jian , Yang Guowei
Published: February 2021

Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits. Currently the pathogenic roles and distribution of Tc toxins among different bacterial genera remain unclear. Here we have performed a comprehensive genome-wide analysis, and established a database that includes 1,608 identified Tc loci containing 2,528 TcC proteins in 1,421 Gram-negative and positive bacterial genomes. Our findings indicate that TcCs conform to the architecture of typical polymorphic toxins, with C-terminal hypervariable regions (HVR) encoding more than 100 different classes of putative toxic domains, most of which have not been previously recognized. Based on further analysis of Tc loci in the genomes of all Salmonella and Yersinia strains in EnteroBase, a “two-level” evolutionary dynamics scenario is proposed for TcC homologues. This scenario implies that the conserved TcC RHS core domain plays a critical role in the taxonomical specific distribution of TcC HVRs. This study provides an extensive resource for the future development of Tc toxins as valuable agrochemical tools. It furthermore implies that Tc proteins, which are encoded by a wide range of pathogens, represent an important versatile toxin superfamily with diverse pathogenic mechanisms.
Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry
Authors: Schafer Adam , Xiong Rui , Cooper Laura , Nowar Raghad , Lee Hyun , Li Yangfeng , Ramirez Benjamin E. , Peet Norton P. , Caffrey Michael , Thatcher Gregory R. J. , Saphire Erica Ollmann , Cheng Han , Rong Lijun
Published: February 2021

Many small molecules have been identified as entry inhibitors of filoviruses. However, a lack of understanding of the mechanism of action for these molecules limits further their development as anti-filoviral agents. Here we provide evidence that toremifene and other small molecule entry inhibitors have at least three distinctive mechanisms of action and lay the groundwork for future development of anti-filoviral agents. The three mechanisms identified here include: (1) direct binding to the internal fusion loop region of Ebola virus glycoprotein (GP); (2) the HR2 domain is likely the main binding site for Marburg virus GP inhibitors and a secondary binding site for some EBOV GP inhibitors; (3) lysosome trapping of GP inhibitors increases drug exposure in the lysosome and further improves the viral inhibition. Importantly, small molecules targeting different domains on GP are synergistic in inhibiting EBOV entry suggesting these two mechanisms of action are distinct. Our findings provide important mechanistic insights into filovirus entry and rational drug design for future antiviral development.
A Public-Private Partnership Magyarországon– egy félreértés volt? (Public-Private Partnerships in Hungary – was it a mistake?)
Authors: Kozma Miklós
Published: February 2021

Az elemzés a PPP (Public-Private Partnership) magyarországi felfutásának és visszaesésének izgalmas éveit tárja fel, amelynek alapján megállapítható, hogy a magyar gyakorlatban körvonalazódó PPP nem az a PPP, amely a nemzetközi tapasztalatok alapján a közfeladatok megvalósításának közgazdaságilag megalapozott eszköze lehetne. A szerző úgy gondolja, hogy nem a PPP-módszer elvetése a megfelelő válasz a létező hibákra, hanem alkalmazásának módján kell javítani, a fokozatosan halmozódó tapasztalatok értő felhasználásával. ______ Public-Private Partnership (PPP) has quickly become a well-known phenomenon in Hungary. Despite its proliferation in various areas of activities, and the fact that most of these projects are still running, interest for starting new PPP projects has ceased, and even the cancellation of the project has become an issue. My research objective was to understand better how the concept of PPP has been interpreted by the wider public, through the assessment of the projects appearance in the main economic newspapers. The analysis shows that what has been implemented as PPP projects in Hungary are conceptually different from what PPP as an economically justified concept substantiates. PPP seems to be a phenomenon grossly misunderstood in Hungary.
On the Interaction of the Electron with the Vacuum Fluctuations of Electromagnetic Field
Authors: Tong Xiaowen
Published: February 2021

A new approach is proposed for evaluating the interaction energy between the electron and the vacuum fluctuations of electromagnetic field. It is applied to two cases: when the electron is free and when it is in a potential-a hydrogen atom. The results are consistent with previous relevant treatments of people.
Morphophysiology of the passion fruit ‘BRS Rubi do Cerrado’ irrigated with saline waters and nitrogen fertilization
Authors: Maria de Sousa Silva Neta Alzira , Lauriane Almeida dos Anjos Soares  , Geovani Soares de Lima  , Luderlandio de Andrade Silva  , Fagner Nogueira Ferreira  , Pedro Dantas Fernandes
Published: February 2021

This study aimed to evaluate the gas exchanges and growth of the purple passion fruit cultivar ‘BRS Rubi do Cerrado’ as a function of the salinity levels of the irrigation water and nitrogen fertilization. The research was conducted in pots adapted as drainage lysimeters, placed within a plant nursery, using a Regolithic Neosol of sandy texture, in the municipality of Pombal-PB, Brazil. A randomized block design was used, testing five levels of electrical conductivity of irrigation water (0.3, 1.1, 1.9, 2.7, and 3.5 dS m-1) associated with four doses of nitrogen (50, 75, 100, and 125% of the recommendation). The irrigation water salinity above 0.3 dS m-1 compromised the leaf area and the relative water content of the purple passion fruit ‘BRS Rubi do Cerrado’. High doses of nitrogen enhance the deleterious effects of irrigation water salinity on stomatal conductance, transpiration, internal CO2 concentration, CO2 assimilation rate, number of leaves, stem diameter, and height of purple passion fruit plants. When waters with salinity levels of up to 1.3 dS m-1 are used, the dose of 125 mg of N kg-1 of soil is recommendation for providing increases in the CO2 assimilation rate of the purple passion fruit ‘BRS Rubi do Cerrado’ at 70 days after sowing (DAS). Water salinity increases electrolyte leakage, regardless of nitrogen doses.
Concentrations of indolebutyric acid on air-layering of guava cv. Paluma
Authors: Tamwing Gabriela da Silva , Elviro de Araújo Neto Sebastião , De Almeida Rodrigues Isabela , Ferreira de Oliveira Rosely , Jhosef de Souza Bruno , Barbosa Mota Bárbara
Published: February 2021

Nowadays, the predominant technique for the commercial propagation of guava seedlings is through cuttings, using herbaceous cuttings that need a specialized infrastructure with intermittent misting, clean water, exhausters, water filters, and fans. As an alternative to plant propagation by cuttings, this study aimed to evaluate the influence of concentrations of indolebutyric acid (IBA) on the rooting of branches of the guava cv. Paluma by air-layering. The experimental design was in randomized blocks, with four replications and 10 air layers per plot. The treatments consisted of six concentrations of IBA powder mixed with industrial talcum: 0, 1,000, 2,000, 3,000, 4,000, and 5,000 mg.kg-1. Four adult guava parents that were in the off-season period were used. For the preparation of the air layers, the stems were girdled with a 4.0 cm width, using a steel blade, by removing the bark until exposing the cambium region, followed by IBA application and wrapping of the branches with a plastic bag containing moist organic substrate. The following variables were evaluated 120 days after air-layering: percentage of rooted and callused air layers, longest root length, and root dry matter. The analysis of variance indicated no significant differences between the IBA concentrations for all variables, but the rooting percentages were high (68.6 to 92.2%) regardless of the application of the exogenous auxin.
Trends in the Mortality of Biliary Tract Cancers Based on Their Anatomical Site in the United States From 2009 to 2018
Authors: Kim Donghee , Konyn Peter , Cholankeril George , Bonham Clark Andrew , Ahmed Aijaz
Published: February 2021

INTRODUCTION:

Recent trends in the incidence and mortality of biliary tract cancers are unknown. We estimated the trends in biliary tract cancers–related incidence and mortality stratified by anatomical site, age, sex, and race/ethnicity in the US adults.

METHODS:

We performed a population-based trend analysis using the US national incidence (2009–2017) and mortality records (2009–2018). We identified age-standardized incidence and mortality from intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer using appropriate ICD-10 code. Temporal mortality was calculated by joinpoint trend analysis with estimates of annual percentage change (APC) described as each trend segment.

RESULTS:

The incidence rates of ICC increased linearly (APC 8.9%, 95% confidence interval [CI] 7.8%–10.0%) while gallbladder cancer-related incidence rates remained stable early and decreased significantly later in the study (APC −2.8%, 95% CI −5.5% to −0.0% [2014–2017]). Age-standardized mortality from biliary tract cancers steadily increased with an annual increase of 2.0% (95% CI 1.6%–2.3%). Although there was a linear increase in the ICC-related mortality (APC 3.5%, 95% CI 3.1%–3.8%), extrahepatic cholangiocarcinoma–related mortality tended to remain stable earlier and increased later (APC 7.0%, 95% CI 4.6%–9.5% [2013–2018]). By contrast, gallbladder cancer–related mortality steadily decreased over 10 years (APC −1.6%, 95% CI −2.1% to −1.1%). Significant differences in mortality and changes in trends over time were observed in non-Hispanic blacks, Hispanics, and non-Hispanic Asians.

DISCUSSION:

In this analysis of nationally representative data, changing mortality trends in various biliary tract cancers was noted with a disproportionately higher burden of fatality in minorities.
Do Not Skip the Retroflexion: A Case of Disseminated Anorectal Mucosal Melanoma
Authors: Chittajallu Vibhu , Simons-Linares Carlos Roberto , Oshilaja Olaronke , Chahal Prabhleen
Published: February 2021

Less than 4% of melanomas are of mucosal origin, with primary anorectal mucosal melanomas comprising a small subset. Mucosal melanomas are often diagnosed at an advanced stage due to delay in patient presentation and obscured tumor origins leading to a more aggressive behavior and less favorable prognosis when compared with cutaneous melanomas. We present a case of metastatic anorectal mucosal melanoma with a negative colonoscopy 1 year earlier.
No Effect in Alcoholic Hepatitis of Gut-Selective, Broad-Spectrum Antibiotics on Bacterial Translocation or Hepatic and Systemic Inflammation
Authors: Støy Sidsel , Laursen Tea Lund , Eriksen Lotte Lindgreen , Grønbæk Henning , Vilstrup Hendrik , Sandahl Thomas Damgaard
Published: February 2021

INTRODUCTION:

In alcoholic hepatitis (AH), translocation of gut bacteria may drive hepatic macrophage activation and systemic inflammation. We investigated the effect of oral non-absorbable, broad-spectrum antibiotic treatment on bacterial translocation and liver and systemic inflammation in AH.

METHODS:

We consecutively recruited 31 patients with AH. Fourteen were given vancomycin 500 mg, gentamycin 40 mg, and meropenem 500 mg once daily for 7 days. Seventeen patients were a reference group receiving standard-of-care. Circulating markers of bacterial translocation and inflammation were measured at baseline, by day 7 and 90. Gut bacteriome profiling was performed before the intervention and at day 7.

RESULTS:

At study entry, blood lipopolysaccharide-binding protein was multifold higher than normal, remained unchanged at day 7, but decreased at day 90 (P < 0.001) with no difference between the study groups. The macrophage activation markers sCD163 and sCD206 showed the same pattern (P < 0.001, day 90), still without group differences. The systemic inflammation markers tumor necrosis factor—alpha, interleukin (IL)-6, IL-8, and IL-10 showed similar dynamics without group differences. There was no difference in 90-day mortality (total of 6 deaths) between the groups. The remnant gut bacteriome was markedly diversified by the intervention with growth of bacterial species rare for human flora.

DISCUSSION:

In patients with AH, gut-targeted antibiotic treatment does not change markers of bacterial translocation and liver and systemic inflammation. This suggests that bacterial translocation is less important once the inflammatory process is established or that bacteriome reduction is less important than composition.

JOURNAL/cltg/04.03/01720094-202102000-00001/inline-graphic1/v/2023-10-30T212951Z/r/image-tiff
METHODOLOGICAL BASIS OF LEGAL ENTITIES POLITICAL ACTIVITY IN RUSSIA IN THE PARADIGM OF THE THEORY OF POLITICAL MANAGEMENT
Authors:   , соискатель ученой степени кандидата политических наук, кафедра политической теории, Московский государственный институт международных отношений (университет) Министерства иностранных дел Российской Федерации., Avetisyan A. S.
Published: February 2021

The article is devoted to the analysis of the methodological basis of the political activity of legal entities in Russia in the paradigm of the theory of political management. The article is current. The relevance of the article is due to the need to study the political activity of legal entities, taking into account the beginning of the transition of the Russian economy to market social relations, which involves the suppression of unfair competition between the relevant economic entities.The author examines the methodological basis of the legal entities political activity in Russia, taking into account the modern aspect of political management, which needs in-depth research in the context of the realities of Russian science
IT IS NECESSARY TO CHANGE THE EDITING OF ARTICLE 58 OF THE CRIMINAL PROCEDURE CODE
Authors:   Doctor of Law, Professor, Professor of the Department of Criminal Procedure, Criminalistics and Forensic Science, South Ural State University. 4, Vinitsky L.V.
Published: February 2021

The article is devoted to the analysis of the content of Art. 58 of the Code of Criminal Procedure of the Russian Federation and, in particular. the expression «the use of technical means in the study of the materials of the criminal case». Attention is drawn to the fact that changing the wording of the article in this part will legally expand the competence of a specialist. He will receive a wider range of opportunities for using technical means to assist in the detection, fixation and seizure of objects and documents, and, in addition, the study of the materials of the criminal case.
PROBLEMIC ISSUES OF THE CONSIDERATION OF A CRIMINAL CASE IN THE COURT OF FIRST INSTANCE IN THE ORDER OF CHAPTER 40 OF THE RF CRIMINAL PROCEDURE CODE
Authors:   Doctor of Law, Professor, Professor of the Department of Criminal Procedure, Forensic Science and Forensic Science, South Ural State University, Vinitskiy L.V. , Burnosova Y.L. ,   assistant judge of the Smolensk Regional Court.
Published: February 2021

The article is devoted to a critical analysis of the content of chapter 40 of the RF Criminal Procedure Code. It is proposed to acquaint the accused who agrees with the accusation, not after familiarizing himself with the materials of the criminal case, but after questioning him as an accused. Provide the right to the prosecutor, and not only the state prosecutor, to express his opinion on the possibility of considering a criminal case in a special order
PROCEDURAL AND FACTUAL ASPECTS OF RETENTION PROBLEMS IN CRIMINAL PROCESS
Authors:   , Candidate of Law, Associate Professor of the Department of Criminal Process, Criminalistics and Judicial Expertise, South Ural State University (NRU), Yastrebova T.I.
Published: February 2021

The article reveals issues related to the nature of detention as a measure of criminal procedural coercion. As a measure of coercion, the criminal procedure law provides for the arrest of a suspect, however, the law uses two definitions of “suspect” and “suspect of a crime”. These concepts are proposed to be considered as equivalent. The detention of a suspect is characterized as a separate institution of criminal procedure. The article analyzes the problems of criminal procedural (legal) and actual detention. Suggestions are made to improve legislation in the process of applying this enforcement measure
Analisis Pemangku Kepentingan dalam Pengembangan Kawasan Cagar Budaya sebagai Destinasi Wisata Kota Pontianak
Authors: Putri Putu Ayu Vindytha Amanda , Santoso Eko Budi
Published: February 2021

Cultural heritage area in Pontianak needs to be preserved by developing and transforming it as a tourism destination. To do this development, it involves some groups of people or organization as acting stakeholders. The study aimed to identify their involvement and relationship in the management of and strategies for cultural heritage area in Pontianak City. The study used data which was analyzed using qualitative descriptive and stakeholder analysis methods. Then the results were incorporated into pentahelix modeling to explain further the roles and functions of each stakeholder. The results identified those acting stakeholders were of the Local Development Planning Agency of Pontianak City, the Youth, Sports and Tourism Agency of Pontianak City, the Pontianak City Tourism Promotion Board and the East Pontianak District Government with high influence and high importance. The community leaders such as historians and tourists were the stakeholders with low influence and high interests. Lastly, travel agents and tourism supporting business actors were the stakeholders with low influence and low interests.
Catch-up and Convergence: Mechanism Design for Economic Development
Authors: Gottinger Hans W.
Published: February 2021

A globalization process can be conceived as an evolving distributed algorithmic mechanism design (DAMD) that induces technology racing with natural catch-up processes of regional or country-wide competition.

We describe the architecture of DAMD as the basis for development economics that lead to natural ongoing shifts in industrial performance and catch-up development. The link between implementation of DAMD and a dynamic system of country-wide industrial evolution is essential for understanding the diverse pattern of inter-country or inter-regional competition.

By selectively reviewing a cross section of the catch-up literature on economic growth it is shown which essential elements of long-run sustainable growth dominate to achieve superior performance and why informationally efficient mechanism design of the Hayek-Hurwicz type is a superior vehicle for industry based economic growth in a globalized economy.
Effect of Sales Promotion on Consumers Towards Fast-Moving Consumer Goods in Al-Dakhliyah Governorate.
Authors: Al Riyami Moosa
Published: February 2021

The importance of consumer sales promotion in the marketing mix of the fast moving consumer goods (FMCG) category throughout the world has increased. Companies spend considerable time in planning such activities. However, there are few studies conducted in the Middle East  to find out effectiveness of promotions. This aims to investigate consumer’s perceptions regarding sales promotion. Results indicate that there is a moderate correlation between consumers’ expectations and sales promotion in  Al-Dakhliyah Governorate.
THE EFFECT OF FINANCIAL LITERATION IMPLEMENTATION ON THE PERFORMANCE OF FINANCIAL MANAGEMENT IN MIDDLE SMALL MICRO ENTERPRISES IN TOMOHON CITY
Authors: Untu Victoria N.
Published: February 2021

The research that will be carried out by the team refers to one of the Higher Education Research Master Plans, in this case Sam Ratulangi University, which is about matters related to the social, humanities and culture fields, with the topic of increasing the competitiveness of MSMEs and cooperatives. In this 21st century, the ability to manage money and finances effectively is becoming increasingly important, not only for professionals but for everyone who is responsible for managing financial affairs in everyday life. This ability is included in the term financial literacy. Financial literacy is not limited to understanding knowledge, skills and beliefs of existing financial institutions, products and services, but attitudes and behavior also have an influence in increasing financial literacy for the realization of public welfare. This study aims to determine how much influence the implementation of financial literacy has on financial management for MSME actors in Tomohon City. As for the sample in this study are the 70 micro, small and medium enterprises in Tomohon city. The final result or output of this research is in the form of a study on the implementation of good financial literacy in financial management performance in micro, small and medium enterprises in Tomohon city In addition, what is also the outcome of this research is the publication of National and International Journals.

Keywords: financial literacy, financial management, MSMEs
The THE EFFECT OF PROFITABILITY, FIRM SIZE, EQUITY OWNERSHIP AND FIRM AGE ON FIRM VALUE (LEVERAGE BASIS): Evidence from the Indonesian Manufacturer Companies
Authors: Lambey Robert
Published: February 2021

This study examines the effect of profitability, firm size, equity ownership and firm age on firm value. This is a quantitative research study. Samples were taken from 65 manufacturing companies that go-public and listed at the Indonesian Stock Exchange from 2012 to 2019. Data were analysed by Path Analysis with Amos SPSS 24. Findings indicate that profitability and firm size influence firm value significantly and positively. Whilst, firm value is affected by profitability and firm size, it is not influenced significantly and positively by firm age. On the other hand, owner’s equity provides a negative effect to firm value.