bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane protein insertion through a mitochondrial β-barrel gate
Authors: Höhr Alexandra I. C. , Lindau Caroline , Wirth Christophe , Qiu Jian , Stroud David A. , Kutik Stephan , Guiard Bernard , Hunte Carola , Becker Thomas , Pfanner Nikolaus , Wiedemann Nils
Published: January 2018

Making your way through the side of a barrel

The mechanism of membrane insertion and assembly of b-barrel proteins is a central question of outer membrane biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria. Höhr
et al.
developed assays to address this fundamental problem. They systematically mapped precursor proteins transported by the mitochondrial Omp85 channel (Sam50) to elucidate the entire membrane insertion pathway of a precursor in the native membrane environment. Their findings directly demonstrate translocation of precursor proteins through the lumen of the mitochondrial Omp85 channel, signal recognition by β-strand exchange between channel and precursor, and exit through the lateral gate into the membrane.

Science
, this issue p.
eaah6834
Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose
Authors: Thongsomboon Wiriya , Serra Diego O. , Possling Alexandra , Hadjineophytou Chris , Hengge Regine , Cegelski Lynette
Published: January 2018

A naturally modified cellulose

Cellulose is the most abundant biopolymer on Earth and an important component of bacterial biofilms. Thongsomboon
et al.
used solid-state nuclear magnetic resonance spectroscopy to identify a naturally derived, chemically modified cellulose, phosphoethanolamine cellulose (see the Perspective by Galperin and Shalaeva). They went on to identify the genetic basis and molecular signaling involved in introducing this modification in bacteria, which regulates biofilm matrix architecture and function. This discovery has implications for understanding bacterial biofilms and for the generation of new cellulosic materials.

Science
, this issue p.
334
; see also p.
276
Detection and localization of surgically resectable cancers with a multi-analyte blood test
Authors: Cohen Joshua D. , Li Lu , Wang Yuxuan , Thoburn Christopher , Afsari Bahman , Danilova Ludmila , Douville Christopher , Javed Ammar A. , Wong Fay , Mattox Austin , Hruban Ralph H. , Wolfgang Christopher L. , Goggins Michael G. , Dal Molin Marco , Wang Tian-Li , Roden Richard , Klein Alison P. , Ptak Janine , Dobbyn Lisa , Schaefer Joy , Silliman Natalie , Popoli Maria , Vogelstein Joshua T. , Browne James D. , Schoen Robert E. , Brand Randall E. , Tie Jeanne , Gibbs Peter , Wong Hui-Li , Mansfield Aaron S. , Jen Jin , Hanash Samir M. , Falconi Massimo , Allen Peter J. , Zhou Shibin , Bettegowda Chetan , Diaz Luis A. , Tomasetti Cristian , Kinzler Kenneth W. , Vogelstein Bert , Lennon Anne Marie , Papadopoulos Nickolas
Published: January 2018

SEEK and you may find cancer earlier

Many cancers can be cured by surgery and/or systemic therapies when detected before they have metastasized. This clinical reality, coupled with the growing appreciation that cancer's rapid genetic evolution limits its response to drugs, have fueled interest in methodologies for earlier detection of the disease. Cohen
et al.
developed a noninvasive blood test, called CancerSEEK that can detect eight common human cancer types (see the Perspective by Kalinich and Haber). The test assesses eight circulating protein biomarkers and tumor-specific mutations in circulating DNA. In a study of 1000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity of 69 to 98% (depending on cancer type) and 99% specificity.

Science
, this issue p.
926
; see also p.
866
The art of manufacturing molecules
Authors: Hornung Christian H.
Published: January 2018

Additively manufactured monolithic reactors allow on-demand synthesis of drug molecules
Quarks, culture, combogenesis
Quarks to Culture: How We Came to Be
Tyler Volk
Columbia University Press, 2017. 280 pp.
Authors: Wood Barry
Published: January 2018

A multidisciplinary tour of cosmic history charts the “grand sequence” of existence
The milliDelta: A high-bandwidth, high-precision, millimeter-scale Delta robot
Authors: McClintock Hayley , Temel Fatma Zeynep , Doshi Neel , Koh Je-sung , Wood Robert J.
Published: January 2018

A high-bandwidth, millimeter-scale Delta robot offers precise control for microscale applications.
Population Pharmacokinetics of High-Dose Tigecycline in Patients with Sepsis or Septic Shock
Authors: Borsuk-De Moor Agnieszka , Rypulak Elżbieta , Potręć Beata , Piwowarczyk Paweł , Borys Michał , Sysiak Justyna , Onichimowski Dariusz , Raszewski Grzegorz , Czuczwar Mirosław , Wiczling Paweł
Published: January 2018

Tigecycline is a glycylcycline often used in critically ill patients as the antibiotic of last resort. The pharmacokinetics (PK) of tigecycline in intensive care unit (ICU) patients can be affected by severe pathophysiological changes so that standard dosing might not be adequate. The aim of this study was to describe population PK of high-dose tigecycline in patients with sepsis or septic shock and evaluate the relationship between individual PK parameters and patient covariates. The study population consisted of 37 adult ICU patients receiving a 200-mg loading dose of tigecycline followed by multiple doses of 100 mg every 12 h. Blood samples were collected at 0.5, 2, 4, 8, and 12 h after dose administration. A two-compartment model with interindividual (IIV) and interoccasion (IOV) variability in PK parameters was used to describe the concentration-time course of tigecycline. The estimated values of mean population PK parameters were 22.1 liters/h and 69.4 liters/h for elimination and intercompartmental clearance, respectively, and 162 liters and 87.9 liters for volume of the central and peripheral compartment, respectively. The IIV and IOV in clearance were less than 20%. The estimated values of distribution volumes were different from previously published values, which might be due to pathophysiological changes in ICU patients. No systematic relationship between individual PK parameters and patient covariates was found. The developed model does not show evidence that individual tigecycline dosing adjustment based on patient covariates is necessary to obtain the same target concentration in patients with sepsis or septic shock. Dosing adjustments should be based on the pathogens, their susceptibility, and PK targets.
FKS2
and
FKS3
Genes of Opportunistic Human Pathogen Candida albicans Influence Echinocandin Susceptibility
Authors: Suwunnakorn Sumanun , Wakabayashi Hironao , Kordalewska Milena , Perlin David S. , Rustchenko Elena
Published: January 2018

Candida albicans
, a prevailing opportunistic fungal pathogen of humans, has a diploid genome containing three homologous
FKS
genes that are evolutionarily conserved. One of these, the essential gene
FKS1
, encodes the catalytic subunit of glucan synthase, which is the target of echinocandin drugs and also serves as a site of drug resistance. The other two glucan synthase-encoding genes,
FKS2
and
FKS3
, are also expressed, but their roles in resistance are considered unimportant. However, we report here that expression of
FKS1
is upregulated in strains lacking either
FKS2
or
FKS3
. Furthermore, in contrast to what is observed in heterozygous
FKS1
deletion strains, cells lacking
FKS2
or
FKS3
contain increased amounts of cell wall glucan, are more resistant to echinocandin drugs, and consistently are tolerant to cell wall-damaging agents. Our data indicate that
C. albicans
FKS2
and
FKS3
can act as negative regulators of
FKS1
, thereby influencing echinocandin susceptibility.
HIV Replication and Latency in a Humanized NSG Mouse Model during Suppressive Oral Combinational Antiretroviral Therapy
Authors: Satheesan Sangeetha , Li Haitang , Burnett John C. , Takahashi Mayumi , Li Shasha , Wu Shiny Xiaqin , Synold Timothy W. , Rossi John J. , Zhou Jiehua
Published: January 2018

Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, these models cannot accurately represent the quiescent cellular environment of primary latently infected cells
in vivo
. For this reason,
in vivo
humanized murine models have been developed for screening antiviral agents, identifying latently infected T cells, and establishing treatment approaches for HIV research. Such models include humanized bone marrow/liver/thymus mice and SCID-hu-thy/liv mice, which are repopulated with human immune cells and implanted human tissues through laborious surgical manipulation. However, no one has utilized the human hematopoietic stem cell-engrafted NOD/SCID/IL2rγ
null
(NSG) model (hu-NSG) for this purpose. Therefore, in the present study, we used the HIV-infected hu-NSG mouse to recapitulate the key aspects of HIV infection and pathogenesis
in vivo
. Moreover, we evaluated the ability of HIV-infected human cells isolated from HIV-infected hu-NSG mice on suppressive cART to act as a latent HIV reservoir. Our results demonstrate that the hu-NSG model is an effective surgery-free
in vivo
system in which to efficiently evaluate HIV replication, antiretroviral therapy, latency and persistence, and eradication interventions.

IMPORTANCE
HIV can establish a stably integrated, nonproductive state of infection at the level of individual cells, known as HIV latency, which is considered a primary barrier to curing HIV. A complete understanding of the establishment and role of HIV latency
in vivo
would greatly enhance attempts to develop novel HIV purging strategies. An ideal animal model for this purpose should be easy to work with, should have a shortened disease course so that efficacy testing can be completed in a reasonable time, and should have immune correlates that are easily translatable to humans. We therefore describe a novel application of the hematopoietic stem cell-transplanted humanized NSG model for dynamically testing antiretroviral treatment, supporting HIV infection, establishing HIV latency
in vivo
. The hu-NSG model could be a facile alternative to humanized bone marrow/liver/thymus or SCID-hu-thy/liv mice in which laborious surgical manipulation and time-consuming human cell reconstitution is required.
Prediction of rate constants of important chemical reactions in water radiation chemistry in sub and supercritical water – non-equilibrium reactions
Authors: Liu Guangdong , Landry Cody , Ghandi Khashayar
Published: January 2018

The rate constants for reactions involved in the radiolysis of water under relevant thermodynamic conditions in supercritical water-cooled reactors are estimated for inputs in simulations of the radiation chemistry in Generation IV nuclear reactors. We have discussed the mechanism of each chemical reaction with a focus on non-equilibrium reactions. We found most of the reactions are activation controlled above the critical point and that the rate constants are not significantly pressure dependent below 300 °C. This work will aid industry with developing chemical control strategies to suppress the concentration of eroding species.
Ordinal Distance Metric Learning with MDS for Image Ranking
Authors: Yu Panpan , Li Qingna
Published: January 2018

Image ranking is to rank images based on some known ranked images. In this paper, we propose an improved linear ordinal distance metric learning approach based on the linear distance metric learning model. By decomposing the distance metric [Formula: see text] as [Formula: see text], the problem can be cast as looking for a linear map between two sets of points in different spaces, meanwhile maintaining some data structures. The ordinal relation of the labels can be maintained via classical multidimensional scaling, a popular tool for dimension reduction in statistics. A least squares fitting term is then introduced to the cost function, which can also maintain the local data structure. The resulting model is an unconstrained problem, and can better fit the data structure. Extensive numerical results demonstrate the improvement of the new approach over the linear distance metric learning model both in speed and ranking performance.
Joint Operational and Financial Collaboration in a Capital-Constrained Supply Chain Under Manufacturer Collateral
Authors: Bi Gongbing , Fei Yalei , Yuan Xiaoyong , Wang Dong
Published: January 2018

Operational collaboration in a supply chain is important due to the fierce competition among supply chains. However, the collaboration in a supply chain is often hindered by its distribution channel’s lack of funds. It is of significance to alleviate the capital constraint problem of the distribution channel and explore new joint operational and financial collaboration solutions. In this paper, we focus on exploring the optimal solution of operational collaboration in the presence of manufacturer collateral. We consider a supply chain consisting of a well-capitalized manufacturer and a capital-constrained retailer that faces difficulties obtaining credit from the bank. To help the retailer access financing for a purchase order, the manufacturer promises to pay the lender a proportion of the retailer’s loan if the retailer goes bankrupt. We find that when the bank credit with manufacturer collateral is considered as a mix of trade credit and bank credit, the retailer’s financing equilibrium depending on the maximum wholesale price what the manufacturer can set, can be neither trade credit nor bank credit alone, but a combination of them. Moreover, the retailer’s order quantity and the chain’s operational collaboration level will benefit from the manufacturer collateral.
Quantum world return to a realistic view
Authors: Croca J. R.
Published: January 2018

Orthodox quantum mechanics, or at least some extreme interpretations of it, adopts a nonrealistic stance by assuming, in its fifth, or reduction postulate, that Reality is, in last instance, a making of the observer consciousness. The enormous empirical success of orthodox quantum mechanics lead most of the scientific community to accept without reserve this highly idealistic posture even without fully realizing its deep implications. Now, almost a century after its formulation, a return to a realistic view of Physics seems possible.
Graphene-Based Nanomaterials for Theranostic Applications
Authors: Roy Shounak , Jaiswal Amit
Published: January 2018

Graphene and graphene-based nanomaterials such as graphene oxide (GO), reduced graphene oxide (rGO) and graphene quantum dots (GQDs) have gained a lot of attention from diverse scientific fields for applications in sensing, catalysis, nanoelectronics, material engineering, energy storage and biomedicine due to its unique structural, optical, electrical and mechanical properties. Graphene-based nanomaterials emerge as a novel class of nanomedicine for cancer therapy for several reasons. Firstly, its structural properties like high surface area and aromaticity enables easy loading of hydrophobic drugs. Secondly, presence of oxygen containing functional groups improve its physiological stability and also act as site for biofunctionalization. Thirdly, its optical absorption in the NIR region enable them to act as photoagents for photothermal and photodynamic therapies of cancer, both in vitro and in vivo. Finally, its intrinsic fluorescence property helps in bioimaging of cancer cells. Overall, graphene-based nanomaterials can act as agents for developing multifunctional theranostic platforms for carrying out more efficient detection and treatment of cancers. This review provides a detailed summary of the different applications of graphene-based nanomaterials in drug delivery, nucleic acid delivery, phototherapy, bioimaging and theranostics.
Visual Background Recommendation for Dance Performances Using Deep Matrix Factorization
Authors: Wen Jiqing , She James , Li Xiaopeng , Mao Hui
Published: January 2018

The stage background is one of the most important features for a dance performance, as it helps to create the scene and atmosphere. In conventional dance performances, the background images are usually selected or designed by professional stage designers according to the theme and the style of the dance. In new media dance performances, the stage effects are usually generated by media editing software. Selecting or producing a dance background is quite challenging and is generally carried out by skilled technicians. The goal of the research reported in this article is to ease this process. Instead of searching for background images from the sea of available resources, dancers are recommended images that they are more likely to use. This work proposes the idea of a novel system to recommend images based on content-based social computing. The core part of the system is a probabilistic prediction model to predict a dancer’s interests in candidate images through social platforms. Different from traditional collaborative filtering or content-based models, the model proposed here effectively combines a dancer’s social behaviors (rating action, click action, etc.) with the visual content of images shared by the dancer using deep matrix factorization (DMF). With the help of such a system, dancers can select from the recommended images and set them as the backgrounds of their dance performances through a media editor. According to the experiment results, the proposed DMF model outperforms the previous methods, and when the dataset is very sparse, the proposed DMF model shows more significant results.
Mature gastric chief cells are not required for the development of metaplasia
Authors: Kinoshita Hiroto , Hayakawa Yoku , Niu Zhengchuan , Konishi Mitsuru , Hata Masahiro , Tsuboi Mayo , Hayata Yuki , Hikiba Yohko , Ihara Sozaburo , Nakagawa Hayato , Hirata Yoshihiro , Wang Timothy C. , Koike Kazuhiko
Published: January 2018

During human gastric carcinogenesis, intestinal metaplasia is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism. The origin of SPEM in mice is presently under debate. It is postulated that stem or progenitor cells acquire genetic alterations that then supply metaplastic cell clones, whereas the possibility of transdifferentiation or dedifferentiation from mature gastric chief cells has also been suggested. In this study, we report that loss of chief cells was sufficient to induce short-term regenerative SPEM-like lesions that originated from chief cell precursors in the gastric neck region. Furthermore, Lgr5+ mature chief cells failed to contribute to both short- and long-term metaplasia, whereas isthmus stem and progenitor cells efficiently contributed to long-term metaplasia. Interestingly, multiple administrations of high-dose pulsed tamoxifen induced expansion of Lgr5 expression and Lgr5-CreERT recombination within the isthmus progenitors apart from basal chief cells. Thus we conclude that short-term SPEM represents a regenerative process arising from neck progenitors following chief cell loss, whereas true long-term SPEM originates from isthmus progenitors. Mature gastric chief cells may be dispensable for SPEM development.

NEW & NOTEWORTHY Recently, dedifferentiation ability in gastric chief cells during metaplasia development has been proposed. Our findings reveal that lesions that were thought to be acute metaplasia in fact represent normal regeneration supplied from neck lineage and that isthmus stem/progenitors are more responsible for sustained metaplastic changes. Cellular plasticity in gastric chief cells may be more limited than recently highlighted.
Serotonin 2A receptor inhibition protects against the development of pulmonary hypertension and pulmonary vascular remodeling in neonatal mice
Authors: Delaney Cassidy , Sherlock Laurie , Fisher Susan , Maltzahn Joanne , Wright Clyde , Nozik-Grayck Eva
Published: January 2018

Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens clinical outcomes in former preterm infants. Increased serotonin (5-hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and progression in adults. We hypothesized that increased 5-HT signaling contributes to the pathogenesis of neonatal PH, complicating BPD and neonatal lung injury. Thus, we investigated 5-HT signaling in neonatal mice exposed to bleomycin, previously demonstrated to induce PH and alveolar simplification. Newborn wild-type mice received intraperitoneal PBS, ketanserin (1 mg/kg), bleomycin (3 U/kg) or bleomycin (3 U/kg) plus ketanserin (1 mg/kg) three times weekly for 3 wk. Following treatment with bleomycin, pulmonary expression of the rate-limiting enzyme of 5-HT synthesis, tryptophan hydroxylase-1 (Tph1), was significantly increased. Bleomycin did not affect pulmonary 5-HT 2A receptor (R) expression, but did increase pulmonary gene expression of the 5-HT 2BR and serotonin transporter. Treatment with ketanserin attenuated bleomycin-induced PH (increased RVSP and RVH) and pulmonary vascular remodeling (decreased vessel density and increased muscularization of small vessels). In addition, we found that treatment with ketanserin activated pulmonary MAPK and Akt signaling in mice exposed to bleomycin. We conclude that 5-HT signaling is increased in a murine model of neonatal PH and pharmacological inhibition of the 5-HT 2AR protects against the development of PH in neonatal lung injury. We speculate this occurs through restoration of MAPK signaling and increased Akt signaling.
Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair
Authors: Jin Huiyan , Ciechanowicz Andrzej K. , Kaplan Alanna R. , Wang Lin , Zhang Ping-Xia , Lu Yi-Chien , Tobin Rachel E. , Tobin Brooke A. , Cohn Lauren , Zeiss Caroline J. , Lee Patty J. , Bruscia Emanuela M. , Krause Diane S.
Published: January 2018

Surfactant protein C (SPC), a key component of pulmonary surfactant, also plays a role in regulating inflammation. SPC deficiency in patients and mouse models is associated with increased inflammation and delayed repair, but the key drivers of SPC-regulated inflammation in response to injury are largely unknown. This study focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout) mice, which represent a novel sterile injury model that mimics clinical acute respiratory distress syndrome (ARDS). SPC-TK mice express the inducible suicide gene thymidine kinase from by the SPC promoter, which targets alveolar type 2 (AT2) cells for depletion in response to ganciclovir (GCV). We compared GCV-induced injury and repair in SPC-TK mice that have normal endogenous SPC expression with SPC-TK/SPC-KO mice lacking SPC expression. In contrast to SPC-TK mice, SPC-TK/SPC-KO mice treated with GCV exhibited more severe inflammation, resulting in over 90% mortality; there was only 8% mortality of SPC-TK animals. SPC-TK/SPC-KO mice had highly elevated inflammatory cytokines and granulocyte infiltration in the bronchoalveolar lavage (BAL) fluid. Consistent with a proinflammatory phenotype, immunofluorescence revealed increased phosphorylated signal transduction and activation of transcription 3 (pSTAT3), suggesting enhanced Janus kinase (JAK)/STAT activation in inflammatory and AT2 cells of SPC-TK/SPC-KO mice. The level of suppressor of cytokine signaling 3, an anti-inflammatory mediator that decreases pSTAT3 signaling, was significantly decreased in the BAL fluid of SPC-TK/SPC-KO mice. Hyperactivation of pSTAT3 and inflammation were rescued by AZD1480, a JAK1/2 inhibitor. Our findings showing a novel role for SPC in regulating inflammation via JAK/STAT may have clinical applications.
Role of selected polymorphisms in determining muscle fiber composition in Japanese men and women
Authors: Kumagai Hiroshi , Tobina Takuro , Ichinoseki-Sekine Noriko , Kakigi Ryo , Tsuzuki Takamasa , Zempo Hirofumi , Shiose Keisuke , Yoshimura Eiichi , Kumahara Hideaki , Ayabe Makoto , Higaki Yasuki , Yamada Ryo , Kobayashi Hiroyuki , Kiyonaga Akira , Naito Hisashi , Tanaka Hiroaki , Fuku Noriyuki
Published: January 2018

Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene ( ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia-inducible factor 1 α gene ( rs11549465 ), vascular endothelial growth factor receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene ( rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I ( r = −0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women.

NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene ( ACTN3) R577X polymorphism was associated with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D) polymorphism, in contrast to a previous finding, was associated with a higher proportion of MHC-I in men. In addition, the combined genotype of these polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men. Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition in Japanese men.
Biomechanical Evaluation of a Novel Apatite-Wollastonite Ceramic Cage Design for Lumbar Interbody Fusion: A Finite Element Model Study
Authors: Bozkurt Celal , Şenköylü Alpaslan , Aktaş Erdem , Sarıkaya Baran , Sipahioğlu Serkan , Gürbüz Rıza , Timuçin Muharrem
Published: January 2018

Objectives. Cage design and material properties play a crucial role in the long-term results, since interbody fusions using intervertebral cages have become one of the basic procedures in spinal surgery. Our aim is to design a novel Apatite-Wollastonite interbody fusion cage and evaluate its biomechanical behavior in silico in a segmental spinal model. Materials and Methods. Mechanical properties for the Apatite-Wollastonite bioceramic cages were obtained by fitting finite element results to the experimental compression behavior of a cage prototype. The prototype was made from hydroxyapatite, pseudowollastonite, and frit by sintering. The elastic modulus of the material was found to be 32 GPa. Three intact lumbar vertebral segments were modelled with the ANSYS 12.0.1 software and this model was modified to simulate a Posterior Lumbar Interbody Fusion. Four cage designs in different geometries were analyzed in silico under axial loading, flexion, extension, and lateral bending. Results. The K2 design had the best overall biomechanical performance for the loads considered. Maximum cage stress recorded was 36.7 MPa in compression after a flexion load, which was within the biomechanical limits of the cage. Conclusion. Biomechanical analyses suggest that K2 bioceramic cage is an optimal design and reveals essential material properties for a stable interbody fusion.
Antibacterial Effects of Leaf Extract of Nandina domestica and the Underlined Mechanism
Authors: Guo Zhao-Yu , Zhang Zhuo-Yang , Xiao Jia-Qi , Qin Jin-Hong , Zhao Wei
Published: January 2018

Aim. The study was conducted to investigate the antibacterial and antiasthmatic effects of Nandina domestica leaf extract, to find out its active components, and to assess its safety issue. Methods. (1) Solid‐phase agar dilution method was used for antibacterial activity test of nandina leaf extract and the change of bacterial morphology after treatment was observed under the transmission microscope; (2) guinea pig model of asthma was used to test the asthma prevention effect of nandina leaf extract; (3) alkaloids and flavones were separated from nandina leaf extract and were further analyzed with HPLC‐MS; (4) mice model was used to assessment of the safety issue of nandina leaf extract. Results. (1) Nandina leaf extract inhibited the growth of bacteria and destroyed bacterial membrane; (2) nandina leaf extract alleviated animal allergy and asthma; (3) the components reextracted by ethyl acetate were active, in which alkaloids inhibited Gram‐positive bacteria and prevented asthma and flavones inhibited Gram‐negative bacteria; (4) nandina leaf extract had no toxic effect on mice. Conclusion. Nandina leaves inhibit bacterial growth and prevent asthma through alkaloids and flavones, which had integrated function against chronic bronchitis. This study provided theoretical basement for producing new Chinese medicine against chronic bronchitis.
Leaseback
Authors: Herman Alfonso
Published: January 2018

El Leaseback es un contrato financiero que utilizan las empresas para obtener liquidez a partir de sus activos fijos. En la práctica, una institución financiera compra los activos de una empresa, para luego arrendárselos a esta misma por un periodo determinado. Este artículo presenta una breve historia de la primera operación de leaseback que se realizó en Chile, a principios de 1980, narrada por uno de sus protagonistas.
Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?
Authors: Sanchis-Bonet Angeles , Barrionuevo-González Marta , Bajo-Chueca Ana , Morales-Palacios Nelson , Sanchez-Chapado Manuel
Published: January 2018

Introduction: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. Materials and Methods: A total 172 men with total prostate-specific antigen of 2–10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Results: Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. Conclusions: PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient.
Parallel Effects of Methamphetamine on Anxiety and CCL3 in Humans and a Genetic Mouse Model of High Methamphetamine Intake
Authors: Huckans Marilyn , Wilhelm Clare J. , Phillips Tamara J. , Huang Elaine T. , Hudson Rebekah , Loftis Jennifer M.
Published: January 2018

Background: Methamphetamine (MA) abuse causes immune dysfunction and neuropsychiatric impairment. The mechanisms underlying these deficits remain unidentified. Methods: The effects of MA on anxiety-like behavior and immune function were investigated in mice selectively bred to voluntarily consume high amounts of MA [i.e., MA high drinking (MAHDR) mice]. MA (or saline) was administered to mice using a chronic (14-day), binge-like model. Performance in the elevated zero maze (EZM) was determined 5 days after the last MA dose to examine anxiety-like behavior. Cytokine and chemokine expressions were measured in the hippocampus using quantitative polymerase chain reaction (qPCR). Human studies were also conducted to evaluate symptoms of anxiety using the General Anxiety Disorder-7 Scale in adults with and without a history of MA dependence. Plasma samples collected from human research participants were used for confirmatory analysis of murine qPCR results using an enzyme-linked immunosorbent assay. Results: During early remission from MA, MAHDR mice exhibited increased anxiety-like behavior on the EZM and reduced expression of chemokine (C-C motif) ligand 3 (ccl3) in the hippocampus relative to saline-treated mice. Human adults actively dependent on MA and those in early remission had elevated symptoms of anxiety as well as reductions in plasma levels of CCL3, relative to adults with no history of MA abuse. Conclusions: The results highlight the complex effects of MA on immune and behavioral function and suggest that alterations in CCL3 signaling may contribute to the mood impairments observed during remission from MA addiction.
Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years: a Propensity Score Analysis
Authors: Chang Wen Xiu , Xu Ning , Kumagai Takanori , Iijima Ryutaro , Waki Kaito , Yamanaka Masaki , Nagura Michito , Arai Shigeyuki , Tamura Yoshifuru , Shibata Shigeru , Fujigaki Yoshihide  , Uchida Shunya
Published: January 2018

Background/Aims: Higher level of serum uric acid (SUA) predicts early entry to dialysis in chronic kidney disease (CKD) patients. However, a short-term effect of SUA remains to be elucidated using a novel surrogate endpoint. Methods: Japanese CKD stage 3 to 4 patients were retrospectively examined (n= 701). The follow-up level of SUA was estimated as time-averaged uric acid (TA-UA). A propensity score for 6.0, 6.5 or 7.0 mg/dL of TA-UA was respectively calculated using baseline 23 covariates. The time-to-event analysis was performed for 30% decline in estimated GFR over 2 years. Results: Incidence rates over 2 years were 90 of 440 in men and 36 of 261 in women (p = 0.03). Despite the negative result of baseline SUA, stratified Cox regression on the quintiles of the estimated propensity score showed that higher TA-UA of the three thresholds were all significant (crude HR 2.10 to 2.44) even after adjusting for the confounders. Kaplan-Meier analysis after propensity score matching likewise showed worse survival in the patients with the higher TA-UA (HR 3.11 to 4.26). Conclusion: Higher SUA increases likelihood of reaching a surrogate endpoint over 2 years. Early intervention for SUA less than 6.0 mg/dL is recommended for slowing CKD progression.
Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study
Authors: Chin Melanie P. , Bakris George L. , Block Geoffrey A. , Chertow Glenn M. , Goldsberry Angie , Inker Lesley A. , Heerspink Hiddo J.L. , O’Grady Megan , Pergola Pablo E. , Wanner Christoph , Warnock David G. , Meyer Colin J.
Published: January 2018

Background: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods: Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.
СИМУЛЯЦІЙНЕ НАВЧАННЯ СТУДЕНТІВ ЯК ОДИН ІЗ ПЕРСПЕКТИВНИХ МЕТОДІВ ФОРМУВАННЯ ТА ВДОСКОНАЛЕННЯ ПРОФЕСІЙНИХ ХІРУРГІЧНИХ НАВИЧОК У МАЙБУТНІХ ЛІКАРІВ
Authors: Fira D. B.
Published: January 2018

Мета роботи – дослідити взаємозв’язок між симуляційними методами навчання та формуванням професійних навичок у студентів.Основна частина. У роботі проаналізовано ефективність використання Міжкафедрального навчально-тренінгового центру симуляційного навчання ДВНЗ “Тернопільський державний медичний університет імені І. Я. Горбачевського МОЗ України” у відпрацюванні практичних навичок студентів з дисципліни “Загальна хірургія”. Засвоєння матеріалу і відпрацювання навичок студентами на фантомах дозволяють залучати їх до виконання певних маніпуляцій на пацієнтах під ретельним контролем з боку викладачів (промивання шлунка, катетеризація сечового міхура, перев’язки та ін.). Опанування на симуляторах таких навичок, як внутрішньовенна та внутрішньом’язова ін’єкції, навичок серцево-легеневої реанімації необхідне для навчання студентів на будь-якій клінічній кафедрі.Симуляційний центр, створений у ТДМУ, забезпечує теоретичну частину, вивчення практичних випадків, відеосесію, тренінг мануальних навичок та вмінь, роботу на анімальних моделях, спеціалізовані тренінги, участь у конференціях. Для адекватного засвоєння навичок виділено понад 10 % від загального навчального навантаження.Висновок. Використання симуляційних методів значно покращує якість презентації навчального матеріалу й ефективність його засвоєння студентами, збагачує зміст навчального процесу, підвищує мотивацію до навчання та дозволяє об’єктивно оцінити досягнутий рівень професійної підготовки кожного студента.
THE USE OF ENGLISH PROFESSIONAL TEXTS-RELATED EXERCISE SET FOR DEVELOPING COMMUNICATIVE COMPETENCE OF MEDICAL STUDENTS
Authors: Prokop I. A.
Published: January 2018

Мета роботи – запропонувати й обґрунтувати спеціально розроблений комплекс завдань та вправ для розвитку навичок роботи з професійно орієнтованими текстами, які дають змогу формувати у студентів-медиків вміння спілкуватися на професійні теми.Предметом дослідження є система вправ для формування навичок іншомовного професійного спілкування майбутніх медиків у межах тематичного циклу навчальних занять з дисципліни “Англійська мова за професійним спрямуванням”. Запропоновано зразки вправ до фахового автентичного тексту “Травна система” для розвитку рецептивних і продуктивних видів мовленнєвої діяльності студентів-медиків з даної тематики. У дослідженні використані теоретичні методи наукового дослідження (аналіз, синтез, узагальнення, пояснення, класифікація тощо).Основна частина. Вивчення професійно орієнтованої іноземної мови здійснюється на автентичних фахових текстах, які є мовною та інформаційною основою. Текст може і повинен виступати засобом навчання, окреслюючи проблематику для подальшого його обговорення, що безпосередньо сприяє розвитку комунікативної компетентності студентів і значно оптимізує процес засвоєння іноземної мови, роблячи його містким та ефективним за умови, якщо він будується на основі продуманої, систематичної та цілеспрямованої роботи з використанням вдало підібраної системи завдань та вправ.Вправи та завдання, як засіб формування мовної компетентності, мають відповідати таким вимогам: бути спрямованими на вирішення конкретного завдання відповідно до кінцевої мети навчання; враховувати рівень мовної підготовки студентів; забезпечувати поетапне формування професійних знань, навичок та умінь; мати проблемний характер, що суттєво сприяє активізації критичного мислення студентів та їх активному залученню до навчання.Висновок. Запропонована система завдань і вправ забезпечує активну роботу студентів-медиків з автентичним фаховим текстом на практичному занятті, сприяє розвитку їхніх комунікативних умінь і навичок, що дасть змогу брати активну участь у різних видах спілкування. Описані у статті зразки завдань не вичерпують усього розмаїття форм і методів роботи студентів при опрацюванні фахових текстів іноземною мовою, що створює перспективу для подальших наукових досліджень.
ДИСТАНЦІЙНЕ НАВЧАННЯ В СИСТЕМІ МЕДИЧНОЇ ОСВІТИ (ПЕРШИЙ ДОСВІД КАФЕДРИ НОРМАЛЬНОЇ ФІЗІОЛОГІЇ ЗДМУ)
Authors: Kushch О. G. , Omelyanchik V. M. , Bessarab G. I. , Zhernova N. P. , Stepanova N. V. , Tykhonovska M. A. , Morozova O. V. , Sukhomlinova I. Ye.
Published: January 2018

Мета роботи – дослідження доцільності впровадження масових відкритих онлайн-курсів у систему вищої медичної освіти.Основна частина. У даній статті поставлена проблема переходу вузів України від традиційного дистанційного навчання до масового електронного навчання на основі відкритих онлайн-курсів, обґрунтована її актуальність. Проведено аналіз найважливіших передумов для успішного переходу на даний вид навчання (затребуваність освітніх інтернет-ресурсів, які використовуються з мобільних пристроїв; наявність великої кількості різних електронних ресурсів, які успішно використовуються вузами на практиці в дистанційних освітніх технологіях; наявність досвіду ведення електронних журналів успішності студентів для планування й оцінювання результатів навчання). Визначені ключові завдання переходу до розробки онлайн-курсів.Висновки. Впровадження масових відкритих онлайн-курсів дозволяє:1) урізноманітнити методи подання інформації, а саме використання текстових, графічних, ілюстрованих та відеоматеріалів, що дозволяє викладачеві підвищити рівень доступності інформації до сприйняття студентами;2) спростити процес контролю кінцевого рівня знань за допомогою системи тестового контролю Ратос;3) здійснити диференціацію та індивідуалізацію навчання, забезпечити вибір індивідуальної траєкторії навчання;4) надати вільний доступ до значної кількості наочних та дидактичних матеріалів, що сприяє підвищенню рівня зацікавленості предметом і рівня знань взагалі;5) використання сучасних засобів комунікації між викладачами та студентами дозволяє урізноманітнити форми навчання.
ОПТИМІЗАЦІЯ НАВЧАЛЬНОГО ПРОЦЕСУ ДЛЯ УДОСКОНАЛЕННЯ ДОПОМОГИ НОВОНАРОДЖЕНИМ ІЗ ПЕРИНАТАЛЬНОЮ ПАТОЛОГІЄЮ НЕРВОВОЇ СИСТЕМИ
Authors: Likhacheva N. V. , Litovchenko T. A. , Tondiіy O. L. , Ekzarhova A. I. , Sukhonosova O. Y.
Published: January 2018

Мета роботи – представлення досвіду автора щодо удосконалення навчального процесу для поліпшення допомоги новонародженим із перинатальною патологією нервової системи.Основна частина. Розглянуто шляхи вдосконалення навчального процесу з теоретичних питань дитячої неврології, а також важливість навчання практичних навичок на базі кафедри в університетській клініці – перинатальному центрі.Представлено результати вдосконалення навчального процесу, які охоплюють  не тільки теоретичну частину навчання, а й досвід оволодіння практичними навичками на базі університетської клініки – у Харківському міському перинатальному центрі.Висновки. Навчання і підвищення кваліфікації лікарів дитячих неврологів на кафедрі неврології і дитячої неврології  ХМАПО гарантують високий методичний рівень викладання лекційного матеріалу, а освоєння практичних навичок і можливість брати участь у діагностичному та лікувальному процесі саме в такій університетській клініці, як ХМПЦ, є запорукою успішного засвоєння і вдосконалення складного розділу дитячої неврології – перинатальної неврології. Підготовка досвідчених фахівців у галузі дитячої неврології – запорука кваліфікованої допомоги дітям, які народилися з перинатальною патологією нервової системи, що  буде сприяти зниженню захворюваності  та інвалідності.
ДОСВІД ОРГАНІЗАЦІЇ САМОСТІЙНОЇ РОБОТИ СТУДЕНТІВ IV КУРСУ У ПРОЦЕСІ ВИВЧЕННЯ ВНУТРІШНЬОЇ МЕДИЦИНИ
Authors: Radetska L. V. , Pasyechko N. V. , Yarema N. I. , Bob A. O. , Smachylo I. V. , Savchenko I. P. , Gavrylyuk M. E. , Naumova L. V. , Chomicka A. I. , Krytskyy T. I. , Mandziy Z. P.
Published: January 2018

Мета роботи – вдосконалення організації самостійної роботи студентів медичного факультету з використанням інтерактивних методів педагогіки.Основна частина. У статті, з метою інтеграції навчального процесу до Європейського простору, висвітлено питання організації самостійної роботи студентів в освітньому процесі з урахуванням можливостей сучасних інформаційних технологій навчання. Проаналізовано власний досвід проведення практичних занять для студентів ІV курсу медичного факультету на основі наявних у наукових публікаціях даних про результати впровадження даної форми навчання у вищих медичних навчальних закладах України.У рамках традиційної парадигми навчання наявні добре відпрацьовані структури забезпечення викладацької діяльності, що зводяться в основному до читання лекцій і проведення семінарських та практичних занять у лекційно-дискусійному форматі. Дотримуючись точки зору про те, що самостійна робота – це вид навчально-пізнавальної діяльності студента з освоєння професійної освітньої програми за партнерської участі викладача у її плануванні й оцінці досягнення конкретного результату, слід визнати, що можна говорити лише про певний ступінь самостійності при виконанні різних типів самостійних робіт.Основне завдання викладача зводиться не до викладу готових знань, а до організації навчання. Головна мета викладача в такій моделі навчання – навчити студента “як вчитися”.Висновок. Вміле педагогічне управління, використання різних індивідуально-орієнтованих форм навчання дозволяє досягти більшої самостійності і ставить студента у такі умови, в яких у нього з’являються освітні потреби і, як наслідок, намагання оволодіти професійними знаннями та вміннями, а в результаті у майбутньому стати професіоналом.