bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferric Reduction Is a Potential Iron Acquisition Mechanism forHistoplasma capsulatum
Authors: Timmerman Michelle M. , Woods Jon P.
Published: April 2020

For the fungusHistoplasma capsulatum, and for other microbial pathogens, iron is an essential nutrient. Iron sequestration in response to infection is a demonstrated host defense mechanism; thus, iron acquisition may be considered an important pathogenic determinant.H. capsulatumis known to secrete Fe(III)-binding hydroxamate siderophores, which is one common microbial process for acquiring iron. Here, we reportH. capsulatumferric reduction activities in whole yeast cells and in both high- and low-molecular-weight fractions of culture supernatants. Each of these activities was induced or derepressed by growth under iron-limiting conditions, a phenomenon often associated with specific iron acquisition mechanisms. The high-molecular-weight culture supernatant activity was enhanced by the addition of reduced glutathione, was proteinase K sensitive and heat labile, and could utilize ferric chloride, ferric citrate, and human holotransferrin as substrates. The low-molecular-weight culture supernatant activity was resistant to proteinase K digestion. These results are consistent with the expression byH. capsulatumof both enzymatic ferric reductase and nonproteinaceous ferric reductant, both of which are regulated by iron availability. Such components could be involved in fungal acquisition of iron from inorganic or organic ferric salts, fromH. capsulatumhydroxamate siderophores, or from host Fe(III)-binding proteins, such as transferrin.
Decreased Adherence of Enterohemorrhagic
Escherichia coli
to HEp-2 Cells in the Presence of Antibodies That Recognize the C-Terminal Region of Intimin
Authors: Gansheroff Lisa J. , Wachtel Marian R. , O'Brien Alison D.
Published: April 2020

Antiserum raised against intimin from enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 strain 86-24 has been shown previously by our laboratory to inhibit adherence of this strain to HEp-2 cells. In the present study, we sought to identify the region(s) of intimin important for the effect of anti-intimin antisera on EHEC adherence and to determine whether antisera raised against intimin from an O157:H7 strain could reduce adherence of other strains. Compared to preimmune serum controls, polyclonal sera raised against the histidine-tagged intimin protein RIHisEae (intimin
O157
) or against His-tagged C-terminal fragments of intimin from strain 86-24 reduced adherence of this strain. Furthermore, an antibody fraction purified from the anti-RIHisEae serum that contained antibodies to the C-terminal third of intimin, the putative receptor-binding domain, also reduced adherence of strain 86-24, but a purified fraction containing antibodies to the N-terminal two-thirds of intimin did not inhibit adherence. The polyclonal anti-intimin
O157
serum raised against RIHisEae inhibited, to different degrees, the adherence of another O157:H7 strain, an EHEC O55:H7 strain, one of two independent EHEC O111:NM isolates tested, and one of two EHEC O26:H11 strains tested. Adherence of the other O26:H11 and O111:NM strains and an EPEC O127:H6 strain was not reduced. Finally, immunoblot analysis indicated a correlation between the antigenic divergence in the C-terminal third of intimins from different strains and the capacity of anti-intimin
O157
antiserum to reduce adherence of heterologous strains. Taken together, these data suggest that intimin
O157
could be used as an immunogen to elicit adherence-blocking antibodies against O157:H7 strains and closely-related EHEC.
Optimization of Plasmid Maintenance in the Attenuated Live Vector Vaccine Strain
Salmonella typhi
CVD 908-
htrA
Authors: Galen James E. , Nair Jay , Wang Jin Yuang , Wasserman Steven S. , Tanner Michael K. , Sztein Marcelo B. , Levine Myron M.
Published: April 2020

The broad objective of the research presented here is to develop a noncatalytic plasmid maintenance system for the stabilization of multicopy expression plasmids encoding foreign antigens in a
Salmonella typhi
live-vector vaccine strain such as CVD 908-
htrA
. We have enhanced the maintenance of expression plasmids at two independent levels. First, we removed dependence upon balanced-lethal maintenance systems that involve catalytic enzymes expressed from multicopy plasmids; we accomplished this through incorporation into expression plasmids of a postsegregational killing system based on the noncatalytic
hok-sok
plasmid addiction system from the antibiotic resistance factor pR1. We also included at least one naturally occurring plasmid partition function in our expression plasmids, which eliminates random segregation of these plasmids, thereby enhancing their inheritance and stability; to accomplish this, we incorporated either the
par
locus from pSC101, the
parA
locus from pR1, or both. We monitored the stability of optimized expression plasmids within CVD 908-
htrA
by quantitating expression of a variant of green fluorescent protein (GFPuv) by using flow cytometry. In this report, we demonstrate the utility of this novel plasmid maintenance system in enhancing the stability of our expression plasmids and go on to show that as the copy number of stabilized plasmids increases, the toxicity of GFPuv synthesis also increases. The implications of these observations for the rational design of immunogenic and protective bacterial live vector vaccines are discussed.
Regulation of Human CD4+αβ T-Cell-Receptor-Positive (TCR+) and γδ TCR+T-Cell Responses toMycobacterium tuberculosisby Interleukin-10 and Transforming Growth Factor β
Authors: Rojas Roxana E. , Balaji Kithiganahalli N. , Subramanian Ahila , Boom W. Henry
Published: April 2020

Mycobacterium tuberculosisis the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control ofM. tuberculosisrequires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory (interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor β [TGF-β]) cytokines. IL-10 and TGF-β are produced byM. tuberculosis-infected macrophages. The effect of IL-10 and TGF-β onM. tuberculosis-reactive human CD4+and γδ T cells, the two major human T-cell subsets activated byM. tuberculosis, was investigated. Both IL-10 and TGF-β inhibited proliferation and gamma interferon production by CD4+and γδ T cells. IL-10 was a more potent inhibitor than TGF-β for both T-cell subsets. Combinations of IL-10 and TGF-β did not result in additive or synergistic inhibition. IL-10 inhibited γδ and CD4+T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4+T cells and, to a lesser extent, for γδ T cells. TGF-β inhibited both CD4+and γδ T cells directly and had little effect on APC function for γδ and CD4+T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression onM. tuberculosis-infected monocytes to a greater extent than TGF-β. Neither cytokine affected the uptake ofM. tuberculosisby monocytes. Thus, IL-10 and TGF-β both inhibited CD4+and γδ T cells but differed in the mechanism used to inhibit T-cell responses toM. tuberculosis.
Protective Immunity againstStreptococcus mutansInfection in Mice after Intranasal Immunization with the Glucan-Binding Region ofS. mutansGlucosyltransferase
Authors: Jespersgaard Christina , Hajishengallis George , Huang Yan , Russell Michael W. , Smith Daniel J. , Michalek Suzanne M.
Published: April 2020

Here we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of thegtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) fromStreptococcus mutansand thioredoxin fromEscherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polypeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P< 0.01) which were sustained to the end of the study (experimental day 100). Following infection withS. mutans, sham-immunized mice maintained high levels of this cariogenic organism (∼60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) inS. mutanscolonization after 3 weeks (P< 0.05). The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) ofS. mutansinfection (P< 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P< 0.01). The protective effects againstS. mutanscolonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio-GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any immunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries.
Differential Decline inLeishmaniaMembrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy
Authors: Anam Khairul , Afrin Farhat , Banerjee Dwijadas , Pramanik Netai , Guha Subhasis K. , Goswami Rama P. , Saha Shiben K. , Ali Nahid
Published: April 2020

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar.
Isogenic Lysogens of Diverse Shiga Toxin 2-Encoding Bacteriophages Produce Markedly Different Amounts of Shiga Toxin
Authors: Wagner Patrick L. , Acheson David W. K. , Waldor Matthew K.
Published: April 2020

We produced isogenic
Escherichia coli
K-12 lysogens of seven different Shiga toxin 2 (Stx2)-encoding bacteriophages derived from clinical Shiga toxin-producing
E. coli
(STEC) isolates of serotypes O157:H7, O145, O111, and O83 to assess the variability among these phages and determine if there were phage-related differences in toxin production. Phage genomic restriction fragment length polymorphisms (RFLP) and superinfection resistance studies revealed significant differences among these phages and allowed the seven phages to be placed into five distinct groups. Experiments revealed striking differences in spontaneous phage and toxin production that were correlated with the groupings derived from the RFLP and resistance studies. These results suggest that the genotype of the Stx2 prophage can influence the level of phage release and toxin expression by host strains and thus may be relevant to STEC pathogenesis.
Metagenomes of Wastewater at Different Treatment Stages in Central Germany
Authors: Schneider Dominik , Aßmann Nils , Wicke Dennis , Poehlein Anja , Daniel Rolf
Published: April 2020

Nine metagenomes derived from university hospital effluent, at different stages of wastewater treatment, and the river adjacent to the wastewater treatment plant in Göttingen, Germany, were analyzed.
Bacteria
was the dominant domain and mainly comprised
Proteobacteria
,
Firmicutes
,
Bacteroidetes
, and
Actinobacteria
. The microbiomes harbored a diverse microbial community with a site-specific structure.
Draft Genome Sequence of Enterococcus faecalis Strain OB15, a Probiotic Strain Recently Isolated from Tunisian Rigouta Cheese
Authors: Baccouri Olfa , Boukerb Amine M. , Nilly Flore , Cambronel Mélyssa , Smaali Issam , Feuilloley Marc G. J. , Abidi Ferid , Connil Nathalie
Published: April 2020

Enterococcus faecalis
OB15 is a probiotic strain that was isolated from rigouta, a popular traditional Tunisian fermented cheese. We report here the draft genome sequence of this strain, consisting of 2,912,159 bp, with an average G+C content of 37.49%.
Draft Genome Sequence of
Saccharomonospora piscinae
KCTC 19743
T
, an Actinobacterium Containing Secondary Metabolite Biosynthetic Gene Clusters
Authors: Ramírez-Durán Ninfa , de la Haba Rafael R. , Vera-Gargallo Blanca , Sánchez-Porro Cristina , Alonso-Carmona Scarlett , Sandoval-Trujillo Horacio , Ventosa Antonio
Published: April 2020

The draft genome sequence of
Saccharomonospora piscinae
KCTC 19743
T
, with a size of 4,897,614 bp, was assembled into 11 scaffolds containing 4,561 open reading frames and a G+C content of 71.0 mol%. Polyketide synthase and nonribosomal peptide synthetase gene clusters, which are responsible for the biosynthesis of several biomolecules, were identified and located in different regions in the genome.
Effect of a web drama video series on HIV and other sexually transmitted infection testing among gay, bisexual and queer men: study protocol for a community-based, pragmatic randomised controlled trial in Singapore: the People Like Us (PLU) Evaluation Study
Authors: Tan Rayner Kay Jin , Koh Wee Ling , Le Daniel , Tan Avin , Tyler Adrian , Tan Calvin , Banerjee Sumita , Wong Chen Seong , Wong Mee-Lian , Chio Martin Tze-Wei , Chen Mark I-Cheng
Published: April 2020

Introduction

Gay, bisexual and queer (GBQ) men are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBQ men are increasing worldwide, they remain suboptimal in a variety of settings.

Methods and analysis

The study is a pragmatic randomised controlled trial designed to evaluate an online video series developed by a community-based organisation in Singapore for GBQ men. A total of 300 HIV-negative GBQ men in Singapore aged 18–29 years old will be recruited for this study. Participants will subsequently be randomised into the intervention arm (n=150) and the control arm (n=150). The intervention arm (n=150) will be assigned the intervention along with sexual health information via a pamphlet, while the control group (n=150) will be assigned only the sexual health information via a pamphlet. Participants should also not have watched the video prior to their participation in this study, which will be ascertained through a questionnaire. Primary outcomes for this evaluation are changes in self-reported intention to test for, actual testing for and regularity of testing for HIV, syphilis, chlamydia and gonorrhoea at the 3 and 6 months after intervention. Secondary outcomes include changes in self-reported risk perception for HIV and other STIs, knowledge of HIV, knowledge of risks associated with acquiring STIs, knowledge of HIV pre-exposure prophylaxis, consistent condom use for anal sex with casual partners, incidence of STIs, connectedness to the lesbian, gay, bisexual and transgender community, self-concealment of sexual orientation, perceived homophobia, internalised homophobia, HIV testing self-efficacy and HIV testing social norms.

Ethics and dissemination

The study has been approved by the National University of Singapore Institutional Review Board (S-19-059) and registered at ClinicalTrials.gov. The results will be published in peer-reviewed academic journals and disseminated to community-based organisations and policymakers.

Trial registration number

NCT04021953
Phenomenology at the LHC of composite particles from strongly interacting Standard Model fermions via four-fermion operators of NJL type
Authors: Leonardi R. , Panella O. , Romeo F. , Gurrola A. , Sun H. , Xue S.-S.
Published: April 2020

A new physics scenario shows that four-fermion operators of Nambu-Jona-Lasinio (NJL) type have a strong-coupling UV fixed point, where composite fermions F (bosons $$\Pi $$Π) form as bound states of three (two) SM elementary fermions and they couple to their constituents via effective contact interactions at the composite scale $$\Lambda \approx {{{\mathcal {O}}}} $$Λ≈O(TeV). We present a phenomenological study to investigate such composite particles at the LHC by computing the production cross sections and decay widths of composite fermions in the context of the relevant experiments at the LHC with pp collisions at $$\sqrt{s}=13$$s=13 TeV and $$\sqrt{s}=14$$s=14 TeV. Systematically examining all the different composite particles F and the signatures with which they can manifest, we found a vast spectrum of composite particles F that has not yet been explored at the LHC. Recasting the recent CMS results of the resonant channel $$pp\rightarrow e^+F \rightarrow e^+e^- q\bar{q}'$$pp→e+F→e+e-qq¯′ (as $$F=E$$F=E), we find that the composite fermion mass $$m_F$$mF below 4.25 TeV is excluded for $$\Lambda $$Λ/$$m_F$$mF = 1. We further highlight the region of parameter space where this specific composite particle F can appear using 3 $$\hbox {ab}^{-1}$$ab-1, expected by the High-Luminosity LHC, computing 3 and 5 $$\sigma $$σ contour plots of its statistical significance.
The Palatini star: exact solutions of the modified Lane–Emden equation
Authors: Sergyeyev Artur , Wojnar Aneta
Published: April 2020

Two exact solutions for $$n=0$$n=0 and $$n=1$$n=1 of the Palatini-modified Lane–Emden equation are found. We have employed these solutions to describe a Palatini–Newtonian neutron or low mass brown dwarf star and compared the result with the pure Newtonian counterpart. It turned out that for the negative parameter of the Starobinsky model the star is heavier and larger.
microRNA-223 promotes autophagy to aggravate lung ischemia-reperfusion injury by inhibiting the expression of transcription factor HIF2α
Authors: Ye Chunlin , Qi Wanghong , Dai Shaohua , Zou Guowen , Liu Weicheng , Yu Bentong , Tang Jian
Published: April 2020

Lung ischemia-reperfusion (I/R) injury severely endangers human health, and recent studies have suggested that certain microRNAs (miRNAs) play important roles in this pathological phenomenon. The current study aimed to ascertain the ability of miR-223 to influence lung I/R injury by targeting hypoxia-inducible factor-2α (HIF2α). First, mouse models of lung I/R injury were established: during surgical procedures, pulmonary arteries and veins and unilateral pulmonary portal vessels were blocked and resuming bilateral pulmonary ventilation, followed by restoration of bipulmonary ventilation. In addition, a lung I/R injury cell model was constructed by exposure to hypoxic reoxygenation (H/R) in mouse pulmonary microvascular endothelial cells (PMVECs). Expression of miR-223, HIF2α, and β-catenin in tissues or cells was determined by RT-qPCR and Western blot analysis. Correlation between miR-223 and HIF2α was analyzed by dual luciferase reporter gene assay. Furthermore, lung tissue injury and mouse PMVEC apoptosis was evaluated by hematoxylin and eosin (H&E), TUNEL staining, and flow cytometry. Autophagosomes in cells were detected by light chain 3 immunofluorescence assay. miR-223 was expressed at a high level while HIF2α/β-catenin was downregulated in tissues and cells with lung I/R injury. Furthermore, miR-223 targeted and repressed HIF2α expression to downregulate β-catenin expression. The miR-223/HIF2α/β-catenin axis aggravated H/R injury in mouse PMVECs and lung I/R injury in mice by enhancing autophagy. Taken together, miR-223 inhibits HIF2α to repress β-catenin, thus contributing to autophagy to complicate lung I/R injury. These findings provide a promising therapeutic target for treating lung I/R injury.
Lack of cortical or Ia-afferent spinal pathway involvement in muscle force loss after passive static stretching
Authors: Pulverenti Timothy S. , Trajano Gabriel S. , Walsh Andrew , Kirk Benjamin J. C. , Blazevich Anthony J.
Published: April 2020

This study is the first to specifically examine potential sites underlying the decreases in neural activation of muscle and force production after a bout of muscle stretching. However, no changes were found in either the H-reflex or motor-evoked potential amplitude during submaximal contractions.
Vascular Tissue Analysis as a Decisive Tool for Tropical Hardwood Identification: The Case Study of Ekop Species in Cameroon
Authors: Mbarga Pierre Paul , Mala Armand William , Mbolo Marie Marguerite
Published: April 2020

The perforation plates and vessel-ray pitting of tropical hardwoods are typical features that make it possible to mark species within a botanical family. This study aims to bring out a consistent and robust framework for a clear distinction through anatomical features among various Ekop woods based on usual nomenclature on trade. Perforations plates and vessel-ray pitting are determining components for the classification of the species. Indeed, several species exploited under the trade name Ekop because of their grain, color, and wooden decoration patterns do not belong to the same taxonomic class. With the natural structure of cells and their intervessel pits observed in xylem and phloem, it appears that the perforation plates and the vessel-ray pitting are decisive components for the classification of Ekop species. Forty-three wood specimens of Ekop were collected from forests in Ebolowa, Mbalmayo, and Abong Mbang. In addition, 155 microscopic sections of Ekop slides with at least 3 representatives of identified species were observed. Thus, macroscopic observations through a hand magnifying glass were performed on wood carrots. Then, the microscopic sections of slides in the first 63 features of the International Association of Wood Anatomists list were analyzed. Correlations were observed between vessels elements and other main features through component analysis. Four groups of Ekop were differentiated by gathering in each genus a matrix of similar features across their vessels groupings, perforation plates, and vessel-ray pittings. A tabular key was used to further define the identity of the Ekop species. This study makes it possible to recognize Ekop wood beyond the dendrological aspects of vegetative and reproductive organs. Finally, a few typical features used for a precise demarcation were identified, for a taxonomic classification within the Ekop group.
Orlistat‐Induced Gut Microbiota Modification in Obese Mice
Authors: Ke Jing , An Yaxin , Cao Bin , Lang Jianan , Wu Nannan , Zhao Dong
Published: April 2020

Introduction. Accumulating evidence has indicated that alterations of gut microbiota have been involved in various metabolic diseases. Orlistat, a reversible inhibitor of pancreatic and gastric lipase, has beneficial effects on weight loss and metabolism. However, the effect of orlistat on the composition of gut microbiota remains unclear. Objective. We aimed to explore the effect of orlistat on gut microbiota in high‐fat diet (HFD) fed C57BL/6J obese mice. Methods. C57BL/6J mice were randomly divided into three groups: control (NCD), HFD, and HFD + orlistat (ORL). Mice in the NCD group were fed chow diet, while the other groups were fed HFD for 6 months, and orlistat was added in the final 3 months in the HFD + ORL group. After sacrifice, body weight and metabolic parameters were assessed, and the gut microbial composition was analyzed by 16S rRNA gene sequencing. Results. Orlistat treatment exerted beneficial effects on body weight, plasma cholesterol, and glucose tolerance. Meanwhile, orlistat treatment modified the gut microbiota, presenting as reduced total microbial abundance and obvious upregulated bacteria. Moreover, the upregulated bacteria correlated with several metabolic pathways. Conclusions. Orlistat may exert beneficial effects on body weight and glucose tolerance through modifying the composition of gut microbiota.
Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of GermlineCDH1Variants
Authors: Wang Sam C. , Yeu Yunku , Hammer Suntrea T.G. , Xiao Shu , Zhu Min , Hong Changjin , Clemenceau Jean R. , Yoon Lynn Y. , Nassour Ibrahim , Shen Jeanne , Agarwal Deepak , Reznik Scott I. , Mansour John C. , Yopp Adam C. , Zhu Hao , Hwang Tae Hyun , Porembka Matthew R.
Published: April 2020

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary.

Significance:

Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.
Primary Hepatic Angiosarcoma: A Rare Liver Malignancy – Varying Manifestations but Grave Prognosis
Authors: Rujeerapaiboon Natthapat , Wetwittayakhlang Panu
Published: April 2020

Primary hepatic angiosarcoma (PHA) is a rare mesenchymal liver tumor, accounting for 0.1–2% of primary liver malignancies. The clinical presentations of PHA are variable, from asymptomatic to liver failure or complicated with tumor rupture. The diagnosis of PHA is difficult due to the lack of specific clinical manifestation and investigation results, which can be confused with other liver tumors resulting in late diagnosis. However, there is currently a paucity of effective therapeutic approaches. We advocate early diagnosis with radiological imaging and histopathology because most of them are diagnosed in late-stage and carry a grave prognosis. Surgical resection remains the mainstay of treatment, which can significantly prolong survival. Chemotherapy, including transarterial chemoembolization, is an option for palliative treatment. Unfortunately, molecular treatment has limited efficacy and liver transplantation is also not recommended due to high rate of recurrence. We present a case series of four patients with biopsy-proven PHA which had distinct presentations and clinical courses.
Effect of Interleukin-2 Receptor Antibody Induction Therapy on Survival in Renal Transplant Patients Receiving Tacrolimus
Authors: Ali Hatem , Sharma Ajay , Halawa Ahmed
Published: April 2020

Background: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients’ outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Methods: The study population involved all standard-risk renal transplant patients from 2000 till 2015 who were registered in the UK transplant registry and followed up till May 2018. Standard risk transplants were defined as patients with <2DR mismatch, calculated reaction frequency <20%, live donors or donors after brain death and patients with no previous renal transplantation transplant. We used inverse probability weights to adjust different covariates between the groups. Cox regression analysis for adjusted data and treatment effects model were used to assess outcomes. Results: In all, 3,597 renal transplant patients were included in the study. Two groups were identified; induction group (n = 2,858) which included patients who received IL-2 receptor blocker induction therapy and the no-induction group (n = 739). There was no significant difference between both groups in terms of estimated glomerular filtration rate (eGFR) rate at 1-year post-transplant (correlation co-efficient = 1.224, 95% CI ranges from –0.347 to 2.796). Average eGFR was 59.922 mL/min/1.73 m2 in the induction group (SD 29.171) and 64.557 mL/min/1.73 m2 in the no-induction groups (SD 46.763). There was no significant difference between both groups regarding graft survival at 5 years post-transplant (hazard ratio [HR] 0.944, 95% CI ranges from 0.599 to 1.485, p = 0.804), patient survival at 5 years post-transplant (HR 0.809, 95% CI ranges from 0.477 to1.372, p = 0.433). Conclusion: In the standard risk renal transplant population, the IL2 receptor blocker induction regimen does not affect eGFR at 1 year or renal and graft outcomes at 5 years.
Unusual Presentation of Cutaneous Spindle Cell Squamous Cell Carcinoma: A Case Report
Authors: Wernheden Erika , Trøstrup Hannah , Pedersen Pilt Anette
Published: April 2020

Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare and often aggressive subtype of squamous cell carcinoma (SCC), which usually appears in sun-exposed areas, in areas that have received prior ionizing radiation, or in immunosuppressed individuals. SpSCCs are histologically characterized by keratinocytes infiltrating the dermis as single cells with elongated nuclei rather than as cohesive nests or islands and, in contrast to conventional SCC, are lacking features of keratinization. Immunohistochemical studies are useful to distinguish SpSCC from other spindle cell neoplasms, such as spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, and atypical fibroxanthoma. We present a rare case of a patient with SpSCC in the gluteal region with regional lymph node metastasis. The patient was treated with wide excision of the tumor, inguinal lymph node dissection, and adjuvant radiotherapy. Cutaneous SpSCC is clinically similar to conventional SCC but can demonstrate more aggressive behavior. This case is rare since it was localized in the gluteal region of an otherwise healthy man.
LATIN PHRASEOLOGICAL FUND AS A SOURCE OF DEVELOPING FUTURE PHYSICIANS’ LEXICAL COMPETENCE
Authors: Kolodnytska O. D. , Palasiuk H. B. , Vorona I. I.
Published: April 2020

The article reviews Latin proverbs and sayings, short quotes, statements of historical figures as a means of aphorism; it summarizes the importance of learning Latin aphorisms, quotes, proverbs and sayings and their corresponding equivalents in English and Ukrainian by medical students on Latin classes.

According to historical conditions, Latin has lost its communicative function, but it has gained great historical and educational significance and has become an inexhaustible source of universal human culture and a link between antiquity and modernity. Learning Latin helps the deeper acquisition of knowledge from many specialties, and plays an important role in the artistic and aesthetic education of future physicians.

Phraseological funds of many modern languages have been replenished by Latin and Greek aphorisms borrowed by new languages mainly through Latin. The Latin phraseological fund contains numerous proverbs and sayings borrowed by world’s languages in the translated form.

Many Latin words were borrowed by Ukrainian, and it is not only the international terminological vocabulary used by scholars in various branches of knowledge but also everyday words (forum – форум (forum), colleague – колега (collega), professor – професор (professor), etc.).

Latin is a basis of all medical terminology facilitating professional communication between languages. The study of Latin obviously helps future physicians to better understand and learn the medical terminology of Greek-Latin origin. Learning Latin not only introduces folk wisdom (learning of aphorisms, proverbs, and sayings), but also lays the foundations of scientific knowledge, promotes the formation of a professional language, which allows to carry out communicative tasks of medical staff.
Blood lactate concentrations following maximal incremental test in male runners with different ages
Authors: Peserico Cecília Segabinazi , Mezzaroba Paulo Victor , Silva Danilo Fernandes da , Kravchychyn Ana Claudia Pelissari , Alves Júlio César Camargo , Machado Fabiana Andrade
Published: April 2020

The aim of this study was to investigate the effect of age on peak blood lactate concentration following a maximal incremental treadmill test in male recreational runners. Seventy runners from four age groups, ≤25 years; 26-35 years; 36-45 years; >45 years,  performed an incremental treadmill test starting at 8 km·h-1, and increasing by  1 km·h-1 every three minutes until volitional exhaustion. Blood samples were collected at baseline and at the zero, third, fifth and seventh minutes after test to determine lactate concentrations. Peak lactate concentration (LApeak) was defined for each participant as the highest value among the four samples. The lactate concentrations were influenced by the participants’ age (r = -0.47), with LApeak of the younger runners (10.8 ± 2.6 mmol·L) being higher than the values for the older age categories (8.1 ± 3.1, 7.0 ± 1.1 and 6.9 ± 2.8 mmol·L for those 26-35, 36-45 and >45 years, respectively). The LApeak occurred more frequently at the third and fifth minute after the initiation of the test. In conclusion, the lactate concentrations were higher in the younger group (< 25) and reached peak more frequently at the third and fifth minute after the incremental test.
Análisis fisiológico de las tareas de entrenamiento en fútbol sala
Authors: Lago-Fuentes Carlos , Bores-Cerezal Antonio , López-Nieto Martín , Paz-Franco Adrián , Mecías-Calvo Marcos , Abelairas-Gómez Cristian , Barcala-Furelos Roberto , Rey-Eiras Ezequiel
Published: April 2020

El objetivo del estudio fue obtener un perfil condicional de las tareas en fútbol sala, analizándolas en función de 5 variables (tiempo de intervención, duración, FCMáx, FCMedia y concentración de lactato). Participaron 8 jugadores profesionales, con una muestra total de 70 tareas agrupadas en 8 subcategorías. El análisis estadístico fue realizado con el SPSS 20.0, y consta de análisis descriptivos generales y dos pruebas ANOVA de un factor con corrección de Bonferroni. Los resultados muestran que las tareas de juego real no alcanzan la carga fisiológica de la competición. Además, las tareas de resistencia a la velocidad alcanzan una lactacidemia superior al resto. Finalmente, las tareas de transición, movilidad, campo completo, 4x4 y portero-jugador tienen características condicionales similares, adecuadas para el desarrollo de la resistencia mixta y umbral anaeróbico. Se concluye que las tareas analizadas sirven para el desarrollo de las diferentes vías metabólicas características del fútbol sala.
Aging male’s strength reduction: population based study
Authors: Corrêa Leandro Quadro , Silva Marcelo Cozzensa da , Domingues Marlos , Rombaldi Airton José
Published: April 2020

We conducted a population-based cross-sectional study to identify the prevalence of aging male’s strength reduction (AMSR) and factors associated to this condition. The study included 421 men aged 40 years or older, living in the urban area of Pelotas, Southern Brazil. The questionnaire covered sociodemographic, behavioral and health variables and, to assess the aging male’s strength reduction, one question of the Aging Male’s Symptoms Scale was used. The prevalence of AMSR was 19.0% (CI95% 15.2 - 22.8). After controlling for confounders, the AMSR was significantly associated with aging, smoking, physical activity score and self-perceived health status. Our findings reinforce the need to keep healthy behaviors such as not smoking and regular physical activity as a healthier lifestyle could reduce the AMSR acceleration and increase life quality and expectancy.
Qualidade de vida e funcionalidade de indivíduos amputados praticantes e não praticantes de esportes
Authors: Zanona Aristela de Freitas , Guerra Danilo Ribeiro , Souza Raphael Fabricio de , Andraus Rodrigo Antonio Carvalho
Published: April 2020

A amputação consiste na ablação total ou parcial de um membro, de forma traumática ou cirúrgica acarretando em danos físicos, psicológicos e sociais, com considerável redução da qualidade de vida (QV) e na funcionalidade em atividades cotidianas. A orientação esportiva tem sido recomendada como estratégia complementar a realibilitação e reintegração social. O objetivo do estudo foi analisar a qualidade de vida e a funcionalidade de adultos com amputação de membros inferiores praticantes e não praticantes de esportes. Foi realizado um estudo transversal composto por 45 amputados, divididos em dois grupos: esportista GE (n=23) e não esportista GNE (n=22). Os instrumentos utilizados foram o The Short Form Health Survey (SF-36) e a Medida Canadense de Desempenho Ocupacional (COPM). Para análise dos dados demográficos foi utilizado o teste qui-quadrado, T de Student para os dados paramétricos e de Mann-Whitney para os não paramétricos, adotado nível de significância p<0,05. O GE apresentou maiores escores em todos os domínios avaliados pelo SF-36 funcionamento físico (p<0,001), funções limitadas devido a saúde física (p<0,001), dor (p=0,010), estado geral de saúde (p<0,001), energia/fadiga (p=0,006) funcionamento social (p<0,001), funções limitadas devido a problemas emocionais (p<0,001) e bem estar emocional (p<0,001); da mesma forma quando avaliado o desempenho ocupacional (p<0,001) e a satisfação na performance nas atividades do cotidiano (p<0,001). Foi concluído que amputados praticantes de esportes apresentaram melhores níveis de qualidade de vida e capacidade funcional quando comparados a não esportistas.
“The Secret Life of Human Donor Hearts”
Authors: Lei Ienglam , Wang Zhong , Chen Y. Eugene , Ma Peter X. , Huang Wei , Kim Elaine , Lam Hugo Y.K. , Goldstein Daniel R. , Aaronson Keith D. , Pagani Francis D. , Tang Paul C.
Published: April 2020

Background:

Ischemic tolerance of donor hearts has a major impact on the efficiency in utilization and clinical outcomes. Molecular events during storage may influence the severity of ischemic injury.

Methods:

RNA sequencing was used to study the transcriptional profile of the human left ventricle (LV, n=4) and right ventricle (RV, n=4) after 0, 4, and 8 hours of cold storage in histidine-tryptophan-ketoglutarate preservation solution. Gene set enrichment analysis and gene ontology analysis was used to examine transcriptomic changes with cold storage. Terminal deoxynucleotidyl transferase 2´-Deoxyuridine, 5´-Triphosphate nick end labeling and p65 staining was used to examine for cell death and NFκB activation, respectively.

Results:

The LV showed activation of genes related to inflammation and allograft rejection but downregulation of oxidative phosphorylation and fatty acid metabolism pathway genes. In contrast, inflammation-related genes were down-regulated in the RV and while oxidative phosphorylation genes were activated. These transcriptomic changes were most significant at the 8 hours with much lower differences observed between 0 and 4 hours. RNA velocity estimates corroborated the finding that immune-related genes were activated in the LV but not in the RV during storage. With increasing preservation duration, the LV showed an increase in nuclear translocation of NFκB (p65), whereas the RV showed increased cell death close to the endocardium especially at 8 hours.

Conclusions:

Our results demonstrated that the LV and RV of human donor hearts have distinct responses to cold ischemic storage. Transcriptomic changes related to inflammation, oxidative phosphorylation, and fatty acid metabolism pathways as well as cell death and NFκB activation were most pronounced after 8 hours of storage.
Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System
Authors: Wiegn Phi , Chan Rodrigo , Jost Charles , Saville Benjamin R. , Parise Helen , Prutchi David , Carson Peter E. , Stagg Angela , Goldsmith Rochelle L. , Burkhoff Daniel
Published: April 2020

Background:

Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system.

Methods:

Patients with New York Heart Association III/IVa symptoms despite medical therapy, left ventricular ejection fraction 25% to 45%, and not eligible for cardiac resynchronization therapy could participate. All subjects received an Optimizer 2-lead implant. The primary end point was the estimated difference in the change of peak VO
2
from baseline to 24 weeks between FIX-HF-5C2 (2-lead system) subjects relative to control subjects from the prior FIX-HF-5C (3-lead system) study. Changes in New York Heart Association were a secondary end point. The primary safety end point was a comparison of device-related adverse events between FIX-HF-5C2 and FIX-HF-5C subjects.

Results:

Sixty subjects, 88% male, 66±9 years old with left ventricular ejection fraction 34±6% were included. Baseline characteristics were similar between FIX-HF-5C and FIX-HF-5C2 subjects except that 15% of FIX-HF-5C2 subjects had permanent atrial fibrillation versus 0% in FIX-HF-5C. CCM delivery did not differ significantly between 2- and 3-lead systems (19 892±3472 versus 19 583±4998 CCM signals/day, CI of difference [−1228 to 1847]). The change of peak VO
2
from baseline to 24 weeks was 1.72 (95% Bayesian credible interval, 1.02–2.42) mL/kg per minute greater in the 2-lead device group versus controls. 83.1% of 2-lead subjects compared with 42.7% of controls experienced ≥1 class New York Heart Association improvement (
P
<0.001). There were decreased Optimizer-related adverse events with the 2-lead system compared with the 3-lead system (0% versus 8%;
P
=0.03).

Conclusions:

The 2-lead system effectively delivers comparable amount of CCM signals (including in subjects with atrial fibrillation) as the 3-lead system, is equally safe and improves peak VO
2
and New York Heart Association. Device-related adverse effects are less with the 2-lead system.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03339310
The Role of the Judiciary in Promoting the Right to a Clean Environment in Kuwait, Egypt and the United States
Authors: Al-Otaibi Ahmad S. , Minan John H.
Published: April 2020

The judiciary has a very significant role to play in safeguarding the environment and promoting the right to a clean environment. This study focuses on the role of the judiciary in promoting the right to a clean environment, and, in this regard, will examine the Kuwaiti and Egyptian experience, as both legal systems are among the civil law practice. In addition, it is of importance to expand the study to a different legal practice, such as the common law system. Therefore, this research will also shed light on the role of the judiciary in the United States of America to establish a comparison between three different legal systems. In the course of this study, constitutional, administrative, and other legal provisions will be examined. In addition, significant cases of concern will be provided and discussed in a descriptive, analytical, and critical manner.
Book Reviews
Authors: Sarumpaet J.P. , Soebardi  , Alisjahbana S. Takdir , Danoesoegondo Poerwanto , Verguin Joseph , Teeuw A. , Roolvink R. , Soebardi  , Skinner Cyril , Graaf H.J. , Lie T.S. , Reid Anthony , Resink G.J. , Soebardi  , Beerling R.F. , Sarumpaet J.P. , Soebardi
Published: April 2020

- Soebardi, Poerwanto Danoesoegondo, Bahasa Indonesia for beginners. Sydney University Press, 1966, Book I, 160 pp.- Soebardi, J.P. Sarumpaet, The structure of bahasa Indonesia. Department of Indonesian and Malayan Studies, University of Melbourne, 1966, 167 pp. Off-set Print.- Soebardi, J.P. Sarumpaet, Introduction to Bahasa Indonesia. Melbourne University Press, 1967, 111 pp., J.A.C. Mackie (eds.)- Soebardi, T.S. Lie, Introducing Indonesian. Sydney, Angus & Robertson Ltd. Book I, 1965, 115 pp. Book II, 1966, 184 pp.- A. Teeuw, Joseph Verguin, Le Malais. Essai d’analyse fonctionnelle et structurale. Cahiers de l’Homme, Ethnologie - Géographie - Linguistique. Nouvelle Série VII. Mouton & Co. Paris, La Haye 1967, 146 pp.- R. Roolvink, Cyril Skinner, The civil war in Kelantan in 1839. Monographs of the Malaysian Branch of the Royal Asiatic Society, II, 1965. vii, 175 pp., 3 maps.- H.J. de Graaf, Generale missiven van Gouverneur-Generaal en Raden aan Heren XVII der Verenidge Oostindische Compagnie. Deel III: 1655-1674. Uitgegeven door Dr. W. Ph. Coolhaas. ‘s-Gravenhage. Rijks Geschiedkundige Publicatiën. Grote Serie 125. Verkrijkbaar bij Martinus Nijhoff. 1968.- Anthony Reid, G.J. Resink, Indonesia’s history between the myths: Essays in legal history and historical theory. Selected Studies on Indonesia, Vol. 7; The Hague, Van Hoeve, 1968, 457 pp.- R.F. Beerling, S. Takdir Alisjahbana, Values as integrating forces in personality, society and culture. University of Oxford Press, Kuala Lumpur, 1966, 248 bldz.
On the taxonomy of the desert lizard Liolaemus stolzmanni (Steindachner, 1891): A third point of view (Squamata: Liolaemidae)
Authors: TRONCOSO-PALACIOS JAIME , ESCOBAR-GIMPEL VÍCTOR
Published: April 2020

Recently, two publications, Langstroth (2011) and Valladares-Faúndez et al. (2018), have provided relevant information on the taxonomy of the poorly know South American lizard, Liolaemus stolzmanni (Steindachner 1891).. However, these publications contradict each other, in regards to L. reichei (Werner 1907) as junior synonym of L. stolzmanni and did not solve the problem of the type locality of L. stolzmanni. In fact, currently the type locality of L. stolzmanni is thought to be imprecise because the description (Steindachner 1891), written in German, stated it as “Hoch Peru” (High Peru), which has been erroneously understood as “northern Peru” or “high altitudes from Peru”, a zone in which L. stolzmanni has been never found. Here, we used the book of memories of Jan Stanisław Sztolcman, the Polish collector, a historical data never taken in account before, to restrict the type locality and provide comments on its taxonomy.