bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular localization and stability of MITF are modulated by the bHLH‐Zip domain
Authors: Fock Valerie , Gudmundsson Sigurdur Runar , Gunnlaugsson Hilmar Orn , Stefansson Jon August , Ionasz Vivien , Schepsky Alexander , Viarigi Jade , Reynisson Indridi Einar , Pogenberg Vivian , Wilmanns Matthias , Ogmundsdottir Margret Helga , Steingrimsson Eirikur
Published: June 2018

Microphthalmia‐associated transcription factor (MITF) is a member of the basic helix–loop–helix leucine zipper (bHLH‐Zip) family and functions as the master regulator of the melanocytic lineage. MITF‐M is the predominant isoform expressed in melanocytes and melanoma cells, and, unlike other MITF isoforms, it is constitutively nuclear. Mutational analysis revealed three karyophilic signals in the bHLH‐Zip domain of MITF‐M, spanning residues 197–206, 214–217, and 255–265. Structural characterization of the MITF protein showed that basic residues within these signals are exposed for interactions in the absence of DNA. Moreover, our data indicate that neither DNA binding nor dimerization of MITF‐M are required for its nuclear localization. Finally, dimerization‐deficient MITF‐M mutants exhibited a significantly reduced stability in melanoma cells when compared to the wild‐type protein. Taken together, we have shown that, in addition to its well‐established role in DNA binding and dimer formation, the bHLH‐Zip domain of MITF modulates the transcription factor's subcellular localization and stability.
Preservation of common carp germ cells under hypothermic conditions: Whole tissue vs isolated cells
Authors: Lujić Jelena , Marinović Zoran , Kása Eszter , Šćekić Ilija , Urbányi Béla , Horváth Ákos
Published: June 2018

The aim of this study was to optimize the conditions for hypothermic storage of spermatogonial stem cells (SSCs) and oogonial stem cells (OSCs) of common carp Cyprinus carpio. This was conducted by storing gonadal tissue or isolated cells for 24 hr under hypothermic conditions in the first experiment and by testing two different storage media (L‐15 or DMEM supplemented with 10% FBS and 25 mM HEPES) and regular medium change (every 4 days) during two weeks of hypothermic storage in the second experiment. During the first 24 hr, isolated cells showed no decrease in viability, while cells obtained from hypothermically stored tissues displayed significantly lower viability after only 6 hr (Tukey's HSD, p < 0.01) indicating that hypothermic storage of isolated cells is superior to storing tissue pieces. The 2‐week trial demonstrated that storage media have a profound influence, while regular medium exchange does not have a positive effect on cell viability. Viability of SSCs and OSCs after two weeks was approximately 40% and 25%, respectively; however, survival of ~70% was obtained after 10 days of storage for SSCs and 7 days for OSCs. Hypothermic storage developed in this study has many practical applications during the development of surrogate broodstock technologies for common carp, but also in carp hatcheries and for the conservation of genetic resources of closely related cyprinid species.
Heterogeneity in Short‐Term Suicidal Ideation Trajectories: Predictors of and Projections to Suicidal Behavior
Authors: Allan Nicholas P. , Gros Daniel F. , Lancaster Cynthia L. , Saulnier Kevin G. , Stecker Tracy
Published: June 2018

Objective

Little is known about suicidal ideation stability, including whether stability is heterogeneous or homogeneous between individuals. Studies of this kind are necessary to understand the progression from suicidal ideation to action.

Method

This study examined suicidal ideation trajectories, using growth mixture modeling, in a sample of 359 past/current military service members (M age = 32.1 years, SD = 7.7; 88.3% male). Self‐reported suicidal ideation information was collected at baseline and follow‐up sessions at months 1, 3, 6, and 12. Following extraction of the best‐fitting solution, predictors of trajectory status were examined and trajectory status was used to predict suicidal behavior between baseline and month 12 assessments.

Results

Results revealed four trajectories, Low‐Stable (n = 125), Moderate‐Stable (n = 101), High‐Stable (n = 76), and High‐Rapidly Declining (n = 57). In general, the High‐Stable trajectory had the highest levels of perceived burdensomeness, thwarted belongingness, PTSD symptoms, and drug use. The High‐ and Moderate‐Stable trajectories had the highest rates of suicidal behavior between baseline and month 12.

Conclusions

Suicidal ideation, even in individuals with elevated ideation, is not a homogeneous construct over time. Stability of suicidal ideation might be an important risk factor, even if ideation is only moderately elevated.
Population density and proximity to junior developmental teams affect the development of National Hockey League draftees
Authors: Farah Lou , Schorer Jörg , Baker Joseph , Wattie Nick
Published: June 2018

Inconsistencies in community size effects found between and within countries (Baker et al Eur J Sport Sci. 2009;9:329‐339; Bruner et al J Sports Sci. 2011;29:1337‐1344; Wattie et al J Sports Sci. 2018;36:436‐444) suggest population size may not be an accurate predictor of athlete development and that other proxies of early environmental characteristics are needed. Researchers have begun to explore the influence of population density and proximity to local sport clubs on athlete development in European countries; however, similar analysis remains to be conducted in Canadian ice hockey. The current study focused on National Hockey League (NHL) draftees and explored whether population density and proximity to Canadian Hockey League teams were associated with the number of draftees produced. Linear regression analyses showed a significant positive relationship between population density and the development of draftees in all provincial regions; however, a significant negative relationship between proximity to CHL teams and NHL draftee development was observed in four out of six provincial regions (British Columbia, Ontario, Quebec, and the Atlantic Provinces). Moreover, population density appeared to be a better predictor of NHL talent development than proximity to CHL teams. Future research may benefit from exploring the effects of these two variables within population size categories, as well as between different regions within provinces.
Struma ovarii – ultrasound features of a rare tumor mimicking ovarian cancer
Authors: Weinberger Vit , Kadlecova Jana , Minář Luboš , Felsinger Michal , Anton Milan , Ovesna Petra , Bednaříková Markéta , Číhalová Marta , Jandáková Eva , Hausnerová Jitka , Zikán Michal
Published: June 2018

Aims: To describe the ultrasound features of benign struma ovarii that often mimic ovarian cancer in the background of complex clinical and histopathological pictures.Material and methods: We retrospectively identified patients with histologically confirmed benign struma ovarii, treated in our institution between 2003–2016 with complete imaging, clinical, nd histopathological data available. Ultrasound findings were drawn from images, and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied.Results: In all, 19 patients were identified; 10 with pure and 9 with impure struma. Median age was 47 (range 24–69); 10 (53%) were premenopausal. Only four (21%) patients presented with pain, others were asymptomatic. Using pattern recognition, 74% strumas (14/19) were uni-/multilocular solid or solid tumors. The solid components were roundish with smooth contours. Six struma pearls were detected. The subjective color score was moderate or abundant in the majority of solid components. Only 5 (26%) tumors were purely cystic.Conclusions: The ultrasound characteristics differ widely from typical mature ovarian teratoma. Features such as, solid roundish components with smooth contours, struma pearls, acoustic shadowing and occasionally signs of dermoid are clues and may help preoperatively to differentiate benign struma from malignant adnexal lesions.
A rare sonographic finding for suprascapular nerve entrapment: engorged suprascapular artery not vein
Authors: Wu Wei-Ting , Chang Ke-Vin , Özçakar Levent , Martinoli Carlo
Published: June 2018

.
The influence of tonal categories and prosodic boundaries on the creakiness in Mandarin
Authors: Kuang Jianjing
Published: June 2018

This study examines the distribution of creaky voice as a function of various prosodic structures in a large-scale corpus of continuous speech of Mandarin. Both tonal categories and prosodic boundaries have strong effects on the likelihood of creak and relative creakiness. It was found that (1) creaky voice in Mandarin is indeed largely driven by the occurrence of low pitch and weakening; (2) Tone 3 sandhi and Tone 2 are different in both pitch and voice quality; (3) the creakiness of Tone 3 (low tone) and the neutral tone (weakening) is realized differently. Moreover, females and males do not differ in how they use creaky voice linguistically.
Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus
Authors: Lee Hyukmin , Yoon Eun-Jeong , Kim Dokyun , Kim Jung Wook , Lee Kwang-Jun , Kim Hyun Soo , Kim Young Ree , Shin Jong Hee , Shin Jeong Hwan , Shin Kyeong Seob , Kim Young Ah , Uh Young , Jeong Seok Hoon
Published: June 2018

A total of 281 nonduplicated
Staphylococcus aureus
blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant
S. aureus
(MRSA). Cefoxitin-disk diffusion tests and the
mecA
gene PCR revealed that 56.6% (159/281) of the
S. aureus
isolates were MRSA, and most belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281).
Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance
Authors: Judd Alec M. , Matthews Melinda K. , Hughes Rachel , Veloz Madeline , Sexton Corinne E. , Chaston John M.
Published: June 2018

Extending descriptive studies of animal-associated microorganisms (microbiota) to define causal mechanistic bases for their influence on animal traits is an emerging imperative. In this study, we reveal thatD. melanogasterstarvation resistance (SR), a model quantitative trait in animal genetics, responds to the presence and identity of the microbiota. Using a predictive analysis, we reveal that the amino acid methionine has a key influence onD. melanogasterSR and show that bacterial methionine metabolism mutants alter normal patterns of SR in flies bearing the bacteria. Our data further suggest that these effects are additive, and we propose the untested hypothesis that, similar to bacterial effects on fruit fly triacylglyceride deposition, the bacterial influence may be through dietary modification. Together, these findings expand our understanding of the bacterial genetic basis for influence on a nutritionally relevant trait of a model animal host.
Cytochromes
c
Constitute a Layer of Protection against Nitric Oxide but Not Nitrite
Authors: Meng Qiu , Sun Yijuan , Gao Haichun
Published: June 2018

It is widely accepted that the antibacterial effects of nitrite are attributable to nitric oxide (NO) formation, suggesting a correlation of bacterial susceptibilities to these two chemicals. However, compared to
E. coli
,
S. oneidensis
is highly sensitive to nitrite but resistant to NO, implying the presence of robust NO-protective systems. Here, we show that
c
-type cytochromes (cytochromes
c
) play a main role in protecting
S. oneidensis
against damages from NO but not from nitrite. In their absence, impacts of proteins that promote NO tolerance and that are targets of NO inhibition become evident. Our data thus reveal the specific activity of cytochromes
c
in alleviating the stress caused by NO but not nitrite.
A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens
Authors: Cameron David R. , Shan Yue , Zalis Eliza A. , Isabella Vincent , Lewis Kim
Published: June 2018

Antibiotic treatment of
P. aeruginosa
residing in the lung of cystic fibrosis patients is ineffective. Treatment failure is attributed in part to antibiotic-tolerant phenotypic variants known as persister cells. Understanding how these cells emerge will likely inform future therapeutic strategies. In the current study, we identified
carB
, which codes for the large subunit of carbamoyl-phosphate synthetase, as a persister gene that contributes to multidrug tolerance in
P. aeruginosa
. Disruption of
carB
resulted in a metabolic perturbation that increased cellular ATP and reduced persister formation. Conversely, lowering ATP in the mutant restored antibiotic tolerance. Our data support the hypothesis that a drop in intracellular ATP is a general mechanism of persister formation in bacteria.
Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus
Authors: Wu Cong-Cong , Jiang Xuan , Wang Xian-Zhang , Liu Xi-Juan , Li Xiao-Jun , Yang Bo , Ye Han-Qing , Harwardt Thomas , Jiang Man , Xia Hui-Min , Wang Wei , Britt William J. , Paulus Christina , Nevels Michael , Luo Min-Hua
Published: June 2018

Human cytomegalovirus (HCMV) infections are a leading cause of brain damage, hearing loss, and other neurological disabilities in children. We report that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by which a common virus may cause damage to the developing nervous system and suggest novel targets for medical intervention.
CD8
+
T-Cell Response-Associated Evolution of Hepatitis B Virus Core Protein and Disease Progress
Authors: Zhang Yu , Wu Yan , Deng Mengmeng , Xu Dongping , Li Xiaodong , Xu Zhihui , Hu Jun , Zhang Han , Liu Kefang , Zhao Yingze , Gao Feng , Bi Shengli , Gao George F. , Zhao Jingmin , Liu William J. , Meng Songdong
Published: June 2018

The specific patterns of sequence polymorphisms of T-cell epitopes and the immune mechanisms of the HBV epitope mutation-linked disease progression are largely unclear. In this study, we systematically evaluated the contribution of CD8
+
T cells to the disease progress-associated evolution of HBV. By evaluation of patient T-cell responses based on the peptide repertoire, we comprehensively characterized the association of clinical parameters in chronic hepatitis B with the antiviral T-cell response-associated mutations of the viruses from the single-epitope level to the overall HLA-I-restricted peptide levels. Furthermore, we investigated the molecular basis of the HLA-A2-restricted peptide immune escape and found that the solvent-exposed C-terminal portion of the epitopes is highly variable under CDR3β recognition. Our work may provide a comprehensive evaluation of viral mutations impacted by the host CTL response in HBV disease progression in the context of the full repertoire of HBc-derived epitopes.
A Novel Method of Serum Resistance by Escherichia coli That Causes Urosepsis
Authors: Coggon Carrie F. , Jiang Andrew , Goh Kelvin G. K. , Henderson Ian R. , Schembri Mark A. , Wells Timothy J.
Published: June 2018

UropathogenicEscherichia coli(UPEC) is the most common cause of urinary tract infection, which in some patients can develop into life-threatening urosepsis. Serum resistance is a key virulence trait of strains that cause urosepsis. Recently, we identified a novel method of serum resistance in patients withPseudomonas aeruginosalung infections, where patients possessed antibodies that inhibited complement-mediated killing (instead of protecting against infection). These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen component of lipopolysaccharide (LPS) and coated the bacterial surface, preventing bacterial lysis by complement. As this mechanism could apply to any Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may represent an uncharacterized mechanism of serum resistance in UPEC. To test this, 45 urosepsis patients with paired blood culture UPEC isolates were screened for serum titers of IgG2 specific for their cognate strain’s LPS. Eleven patients had sufficiently high titers of the antibody to inhibit serum-mediated killing of UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O-antigen restored sensitivity of the isolates to the cognate patient serum. Importantly, the isolates from these 11 patients were more sensitive to killing by serum than isolates from patients with no inhibitory antibodies. This suggests the presence of inhibitory antibodies may have allowed these strains to infect the bloodstream. The high prevalence of patients with inhibitory antibodies (24%) suggests that this phenomenon is an important mechanism of UPEC serum resistance. LPS-specific inhibitory antibodies have now been identified against three Gram-negative pathogens that cause disparate diseases.

IMPORTANCEDespite improvements in the early detection and management of sepsis, morbidity and mortality are still high. Infections of the urinary tract are one of the most frequent sources of sepsis withEscherichia colithe main causative agent. Serum resistance is vital for bacteria to infect the bloodstream. Here we report a novel method of serum resistance found in patients with UPEC-mediated sepsis. Antibodies in sera usually protect against infection, but here we found that 24% of patients expressed “inhibitory antibodies” capable of preventing serum-mediated killing of their infecting isolate. Our data suggest that these antibodies would allow otherwise serum-sensitive UPEC strains to cause sepsis. The high prevalence of patients with inhibitory antibodies in this cohort suggests that this is a widespread mechanism of resistance to complement-mediated killing in urosepsis patients, invoking the potential for the application of new methods to prevent and treat sepsis.
Shigella
-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection
Authors: Willis Alexandra R. , Torraca Vincenzo , Gomes Margarida C. , Shelley Jennifer , Mazon-Moya Maria , Filloux Alain , Lo Celso Cristina , Mostowy Serge
Published: June 2018

Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection.
Shigella flexneri
is a Gram-negative enteroinvasive pathogen controlled by neutrophils. In this study, we use a
Shigella
-zebrafish (
Danio rerio
) infection model to investigate emergency granulopoiesis
in vivo
. We show that stem cell-driven neutrophil production occurs in response to
Shigella
infection and requires macrophage-independent signaling by granulocyte colony-stimulating factor (Gcsf). To test whether emergency granulopoiesis can function beyond homoeostasis to enhance innate immunity, we developed a reinfection assay using zebrafish larvae that have not yet developed an adaptive immune system. Strikingly, larvae primed with a sublethal dose of
Shigella
are protected against a secondary lethal dose of
Shigella
in a type III secretion system (T3SS)-dependent manner. Collectively, these results highlight a new role for emergency granulopoiesis in boosting host defense and demonstrate that zebrafish larvae can be a valuable
in vivo
model to investigate innate immune memory.

IMPORTANCE
Shigella
is an important human pathogen of the gut. Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection and is widely considered a homoeostatic mechanism for replacing exhausted leukocytes. In this study, we developed a
Shigella
-zebrafish infection model to investigate stem cell-driven emergency granulopoiesis. We discovered that zebrafish initiate granulopoiesis in response to
Shigella
infection, via macrophage-independent signaling of granulocyte colony-stimulating factor (Gcsf). Strikingly, larvae primed with a sublethal dose of
Shigella
are protected against a secondary lethal dose of
Shigella
in a type III secretion system (T3SS)-dependent manner. Taken together, we show that zebrafish infection can be used to capture
Shigella
-mediated stem cell-driven granulopoiesis and provide a new model system to study stem cell biology
in vivo
. Our results also highlight the potential of manipulating stem cell-driven granulopoiesis to boost innate immunity and combat infectious disease.
The Rickettsial Ankyrin Repeat Protein 2 Is a Type IV Secreted Effector That Associates with the Endoplasmic Reticulum
Authors: Lehman Stephanie S. , Noriea Nicholas F. , Aistleitner Karin , Clark Tina R. , Dooley Cheryl A. , Nair Vinod , Kaur Simran Jeet , Rahman M. Sayeedur , Gillespie Joseph J. , Azad Abdu F. , Hackstadt Ted
Published: June 2018

Strains ofRickettsia rickettsii, the tick-borne agent of Rocky Mountain spotted fever, vary considerably in virulence. Genomic comparisons ofR. rickettsiistrains have identified a relatively small number of genes divergent in an avirulent strain. Among these is one annotated asRickettsiaankyrin repeat protein 2 (RARP-2). Homologs of RARP-2 are present in all strains ofR. rickettsii, but the protein in the avirulent strain Iowa contains a large internal deletion relative to the virulent Sheila Smith strain. RARP-2 is secreted in a type IV secretion system-dependent manner and exposed to the host cell cytosol. RARP-2 of Sheila Smith colocalizes with multilamellar membranous structures bearing markers of the endoplasmic reticulum (ER), whereas the Iowa protein shows no colocalization with host cell organelles and evidence of proteolytic degradation is detected. Overexpression of Sheila Smith RARP-2 inR. rickettsiiIowa converts this avirulent strain’s typically nonlytic or opaque plaque type to a lytic plaque phenotype similar to that of the virulent Sheila Smith strain. Mutation of a predicted proteolytic active site of Sheila Smith RARP-2 abolished the lytic plaque phenotype but did not eliminate association with host membrane. RARP-2 is thus a type IV secreted effector and released from the rickettsiae into the host cytosol to modulate host processes during infection. Overexpression of Sheila Smith RARP-2 did not, however, restore the virulence of the Iowa strain in a guinea pig model, likely due to the multifactorial nature of rickettsial virulence.

IMPORTANCEMembers of the genusRickettsiaare obligate intracellular bacteria that exhibit a range of virulence from harmless endosymbionts of arthropods to the etiologic agents of severe disease. Despite the growing number of available genomes, little is known regarding virulence determinants of rickettsiae. Here, we have characterized an ankyrin repeat-containing protein, RARP-2, which differs between a highly virulent and an avirulent strain ofR. rickettsii, the agent of Rocky Mountain spotted fever. RARP-2 is secreted by a type IV secretion system into the cytosol of the host cell, where it interacts with and manipulates the structure of the endoplasmic reticulum. RARP-2 from the avirulent strain is truncated by the loss of seven of 10 ankyrin repeat units but, although secreted, fails to alter ER structure. Recognition of those rickettsial factors associated with virulence will facilitate understanding of regional and strain-specific variation in severity of disease.
Long-Term
In Vitro
Culture of the Syphilis Spirochete
Treponema pallidum
subsp.
pallidum
Authors: Edmondson Diane G. , Hu Bo , Norris Steven J.
Published: June 2018

Investigation of
Treponema pallidum
subsp.
pallidum
, the spirochete that causes syphilis, has been hindered by an inability to culture the organism continuously
in vitro
despite more than a century of effort. In this study, long-term logarithmic multiplication of
T. pallidum
was attained through subculture every 6 to 7 days and periodic feeding using a modified medium (
T. pallidum
culture medium 2 [TpCM-2]) with a previously described microaerobic, rabbit epithelial cell coincubation system. Currently, cultures have maintained continuous growth for over 6 months with full retention of viability as measured by motility and rabbit infectivity. This system has been applied successfully to the well-studied Nichols strain of
T. pallidum
, as well as to two recent syphilis isolates, UW231B and UW249B. Light microscopy and cryo-electron microscopy showed that
in vitro
-cultured
T. pallidum
retains wild-type morphology. Further refinement of this long-term subculture system is expected to facilitate study of the physiological, genetic, pathological, immunologic, and antimicrobial susceptibility properties of
T. pallidum
subsp.
pallidum
and closely related pathogenic
Treponema
species and subspecies.

IMPORTANCE
Syphilis, a sexually transmitted disease with a global distribution, is caused by a spiral-shaped bacterium called
Treponema pallidum
subspecies
pallidum
. Previously,
T. pallidum
was one of the few major bacterial pathogens that had not been cultured long-term
in vitro
(in a test tube), greatly hindering efforts to better understand this organism and the disease that it causes. In this article, we report the successful long-term cultivation of
T. pallidum
in a tissue culture system, a finding that is likely to enhance our ability to obtain new information applicable to the diagnosis, treatment, and prevention of syphilis.
Asymptomatic Intestinal Colonization with ProtistBlastocystisIs Strongly Associated with Distinct Microbiome Ecological Patterns
Authors: Nieves-Ramírez M. E. , Partida-Rodríguez O. , Laforest-Lapointe I. , Reynolds L. A. , Brown E. M. , Valdez-Salazar A. , Morán-Silva P. , Rojas-Velázquez L. , Morien E. , Parfrey L. W. , Jin M. , Walter J. , Torres J. , Arrieta M. C. , Ximénez-García C. , Finlay B. B.
Published: June 2018

Given the results of our study and other reports of the effects of the most common human gut protist on the diversity and composition of the bacterial microbiome,Blastocystisand, possibly, other gut protists should be studied as ecosystem engineers that drive community diversity and composition.
Minimally invasive perventricular versus open surgical ventricular septal defect closure in infants and children: a randomised clinical trial
Authors: Liu Hong , Lu Feng-xia , Zhou Jie , Yan Fei , Qian Si-chong , Li Xin-ya , Zheng Si-qiang , Chen Jun-quan , Zhong Ji-sheng , Feng Qiao-Ling , Ding Tong , Fan Jun , Gu Hai-tao , Liu Xiao-cheng
Published: June 2018

Background

Robust evidence is lacking regarding the clinical efficacy, safety and cardiopulmonary performance of perventricular closure. This study investigated the perioperative efficacy, safety and cardiorespiratory performance of perventricular closure of perimembranous ventricular septal defects (pmVSDs).

Methods

Operation-naïve infants and young children aged 5–60 months with isolated pmVSDs were randomised to receive either standard open surgical or minimally invasive perventricular closure via direct entry into the ventricle with a catheter from a subxiphoid incision. The primary outcomes included complete closure at discharge, major and minor adverse events and the changes in perioperative cardiorespiratory performance from baseline. Complete closure was mainly analysed in the modified intention-to-treat (mITT) population, with sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT) populations (non-inferiority margin −5.0%).

Results

We recruited 200 patients with pmVSDs for this study (mean age 24.38 months, range 7–58 months, 104 girls), of whom 100 were randomly allocated to one of the study groups. The non-inferiority of perventricular to surgical closure regarding complete closure at discharge was not shown in the ITT (absolute difference −0.010 (95% CI −0.078 to 0.058)) and mITT populations (−0.010 (95% CI −0.069 to 0.048)), but was shown in the PP (0.010 (95% CI −0.043 to 0.062)) and AT populations (0.048 (95% CI −0.009 to 0.106)). Perventricular closure reduced the rate of compromising cardiac haemodynamics, electrophysiological responses, cardiomyocyte viability, respiratory mechanics, ventilatory and gas exchange function and oxygenation and tissue perfusion compared with surgical closure (all between-group P<0.05).

Conclusions

For infants and young children with pmVSD, perventricular closure reduced the rate of postoperative cardiorespiratory compromise compared with surgical closure, but the non-inferiority regarding complete closure should be interpreted in the context of the specific population.

Trial registration number

NCT02794584 ;Results.
Limiting access to lethal means: applying the social ecological model for firearm suicide prevention
Authors: Allchin Adelyn , Chaplin Vicka , Horwitz Joshua
Published: June 2018

This paper outlines a novel application of the social ecological model (SEM) for firearm suicide prevention. It focuses on four levels of intervention (societal, relationship, community and individual) to reduce access to firearms, a practical contributor to the capacity to attempt suicide, from individuals when they are at an elevated risk for suicide. There is substantive research linking easy access to firearms with an increased risk of firearm suicide, and suicide prevention interventions that address access to lethal means are critical components of a comprehensive suicide prevention strategy. Potential interventions using the SEM framework include: at the policy level—extreme risk laws, voluntary self-prohibition policies and policies that reduce the availability of firearms; at the community level—gun shop projects; at the relationship level—lethal means safety counselling; and at the individual level—safer storage. Taken together with upstream interventions, such as increased access to mental health services and substance use treatment, a multilevel approach for suicide prevention that addresses access to firearms can save lives.
Essential(ist) medicine: promoting social explanations for racial variation in biomedical research
Authors: Gutin Iliya
Published: June 2018

Biomedical research has a long and complicated history as a tool of oppression, exemplary of the racial science used to legitimise and maintain racial hierarchies in the USA and abroad. While the explicit racism and racial inferiority supported by this research has dissipated and modern methods of inquiry have increased in sophistication and rigor, contemporary biomedical research continues to essentialise race by distilling racial differences and disparities in health to an underlying, biogenetic source. Focusing on the persistence of essentialism in an era of genomic medicine, this paper examines the deep social origins and social implications of the essentialist viewpoint in biomedicine and how it relates to the broader construction of social and scientific knowledge. Invoking Hacking’s ‘looping effects’ as a useful conceptual tool, I then demonstrate how sociohistorical forces influence scientific and medical research in producing evidence that favours and legitimises a biological construction of race. I extend the looping framework to consider a parallel ‘louping’ process whereby applying a socially rooted meaning to race in biomedical research results becomes magnified to influence social norms and ideas about race. As many biomedical researchers are motivated by a desire to eliminate racial disparities in outcomes, I argue that greater social acuity allows scientists to avoid individualising and racialising health, challenge preconceived assumptions about the meaning of racial variation in health and medicine and thus promote and strengthen a socioenvironmental focus on how to best improve individuals’ and population health. Concluding with a call for structural competency in biomedical research, I suggest that empowering scientists to more freely discuss sociostructural factors in their work allows for the continued use of race in biological and medical research, while social scientists and medical humanities scholars stand to benefit from seeing their work imbued with the cultural authority currently granted to biomedicine.
MicroRNA-126 attenuates cell apoptosis by targeting TRAF7 in acute myeloid leukemia cells
Authors: Ding Qian , Wang Qing , Ren Yi , Zhu Hong Qian , Huang ZhuYun
Published: June 2018

Acute myeloid leukemia (AML) has a 5-year survival rate of only about 30%–40% due to the self-renewal and differentiation ability of leukemia stem-like cells (LSCs). To address the potential for novel therapeutic targets in LSCs, we investigated the roles of miRNA-126 and tumor necrosis factor receptor-associated factor 7 (TRAF7) in AML. We used qRT-PCR and Western blot to investigate the expression levels of miRNA-126 and TRAF7 in AML cell lines. Then, we uncovered the effect of miRNA-126 on AML cell proliferation and apoptosis by MTT assay and flow cytometric analysis, respectively. Furthermore, dual-luciferase assay and Western blot were used to determine the target of miRNA-126 in AML and the potential mechanism by which cell apoptosis is suppressed by miRNA-126. We found that miRNA-126 was highly expressed in all of the AML cell lines, and that inhibition of miRNA-126 significantly induced cell death through apoptosis. The suppression of apoptosis in AML with high expression of miRNA-126 was caused by down-regulating TRAF7, which blocked the c-FLIP pathway. The role of miRNA-126 in AML makes it a potential therapeutic target to improve clinical outcomes for patients with AML.
State-space models to infer movements and behavior of fish detected in a spatial array of acoustic receivers
Authors: Dorazio Robert M. , Price Melissa
Published: June 2018

We developed state-space models for inferring movements and behaviors of fish implanted with acoustic transmitters and detected within a spatial array of stationary acoustic receivers. In these models, fish movements and behavior switching are specified using a hidden Markov model of the changes in an individual’s latent activity center. The observed number of detections at each acoustic receiver is modeled as a function of the distance between the receiver and a fish’s activity center. To illustrate these models, we analyzed the detections of individual Gulf sturgeon (Acipenser oxyrinchus desotoi) that moved within a spatial array of acoustic receivers placed in the Suwannee River, Florida. Our models of these detections provided estimates of the locations of individual sturgeon and the periods when individuals switched between spawning and resting behaviors. We anticipate that these models will be used to analyze acoustic surveys of other species and help design new surveys.
Freshwater influence is associated with differences in bone mineral density and armour configuration in threespine stickleback (Gasterosteus aculeatus)
Authors: Jamniczky Heather A. , Le Amie , Barry Tegan N. , Rogers Sean M.
Published: June 2018

Threespine stickleback ( Gasterosteus aculeatus Linnaeus, 1758) exhibit a well-documented reduction in plate number associated with adaptation to freshwater environments. We tested the hypothesis that changes in plate number are accompanied by changes in plate bone mineral density and plate shape, reflecting the presence of a complex plate “armour” phenotype and a complex adaptive response to different selective pressures in changing habitats. We used traditional and novel morphometric techniques to characterize armour traits from stickleback occupying three marine habitats and one tidally influenced freshwater stream in southwestern British Columbia. Stickleback inhabiting marine environments share a conserved plate phenotype that includes a full complement of highly mineralized plates that exhibit a characteristic density profile along the plate. Stickleback inhabiting tidally influenced fresh water display an average reduction in plate number along with increased variation in number and reduced total mineralization despite maintenance of a marine-like density profile. Further, we found that although mineralization and armour shape are correlated with size, after accounting for size variation in both traits remains attributable to habitat. Our results hint at an important role for development in structuring phenotypic variation during the process of adaptive change in stickleback.
Neuronal Activation Detection Using Vector Phase Analysis with Dual Threshold Circles: A Functional Near-Infrared Spectroscopy Study
Authors: Zafar Amad , Hong Keum-Shik
Published: June 2018

In this paper, a new vector phase diagram differentiating the initial decreasing phase (i.e. initial dip) and the delayed hemodynamic response (HR) phase of oxy-hemoglobin changes ([Formula: see text]HbO) of functional near-infrared spectroscopy (fNIRS) is developed. The vector phase diagram displays the trajectories of [Formula: see text]HbO and deoxy-hemoglobin changes ([Formula: see text]HbR), as orthogonal components, in the [Formula: see text]HbO–[Formula: see text]HbR polar coordinates. To determine the occurrence of an initial dip, dual threshold circles (an inner circle from the resting state, an outer circle from the peak values of the initial dip and the main HR) are incorporated into the phase diagram for making decisions. The proposed scheme is then applied to a brain–computer interface scheme, and its performance is evaluated in classifying two finger tapping tasks (right-hand thumb and little finger) from the left motor cortex. Three gamma functions are used to model the initial dip, the main HR, and the undershoot in generating the designed HR function. In classifying two tapping tasks, the signal mean and signal minimum values during 0–2.5[Formula: see text]s, as features of initial dip, are used. The linear discriminant analysis was utilized as a classifier. The experimental results show that the active brain locations of the two tasks were quite distinctive ([Formula: see text]), and moreover, spatially specific if using the initial dip map at 4[Formula: see text]s in comparison to the map of HRs at 14[Formula: see text]s. Also, the average classification accuracy was improved from 59% to 74.9% when using the phase diagram of dual threshold circles.
Splitting types of bundles of logarithmic vector fields along plane curves
Authors: Abe Takuro , Dimca Alexandru
Published: June 2018

We give a formula relating the total Tjurina number and the generic splitting type of the bundle of logarithmic vector fields associated to a reduced plane curve. By using it, we give a characterization of nearly free curves in terms of splitting types. Several applications to free and nearly free arrangements of lines are also given, in particular a proof of a form of Terao’s Conjecture for arrangements having a line with at most four intersection points.
Breather wave, rogue wave and lump wave solutions for a (3+1)-dimensional generalized Kadomtsev–Petviashvili equation in fluid
Authors: Li Ming-Zhen , Tian Bo , Sun Yan , Wu Xiao-Yu , Zhang Chen-Rong
Published: June 2018

Under investigation in this paper is a (3[Formula: see text]+[Formula: see text]1)-dimensional generalized Kadomtsev–Petviashvili equation, which describes the long water waves and small-amplitude surface waves with the weak nonlinearity, weak dispersion and weak perturbation in a fluid. Via the Hirota method and symbolic computation, the lump wave, breather wave and rogue wave solutions are obtained. We graphically present the lump waves under the influence of the dispersion effect, nonlinearity effect, disturbed wave velocity effects and perturbed effects: Decreasing value of the dispersion effect can lead to the range of the lump wave decreases, but has no effect on the amplitude. When the value of the nonlinearity effect or disturbed wave velocity effects increases respectively, lump wave’s amplitude decreases but lump wave’s location keeps unchanged. Amplitudes of the lump waves are independent of the perturbed effects. Breather waves and rogue waves are displayed: Rogue waves emerge when the periods of the breather waves go to the infinity. When the value of the dispersion effect decreases, range of the rogue wave increases. When the value of the nonlinearity effect or disturbed wave velocity effects decreases respectively, rogue wave’s amplitude decreases. Value changes of the perturbed effects cannot influence the rogue wave.
Stability analysis of two-lane lattice hydrodynamic model considering lane-changing and memorial effects
Authors: Zhai Cong , Wu Weitiao
Published: June 2018

In this paper, a new lattice two-lane hydrodynamic model is proposed by considering the lane changing and the optimal current change with memory effect. The linear stability condition of the model is obtained through the linear stability analysis, which depends on both the lane-changing rate and the memory step. A modified Korteweg–de Vries (mKdV) equation is derived through nonlinear analysis to describe the propagating behavior of traffic density wave near the critical point. To verify the analytical findings, numerical simulation was carried out, which confirms that the optimal current change with memory of drivers and the memory step contribute to the stabilization of traffic flow, and that traffic congestion can be suppressed efficiently by taking the lane-changing behavior into account in the lattice model.
True Three-Valued Ternary Content Addressable Memory Cell Based On Ambipolar Carbon Nanotube Transistors
Authors: Hellkamp Daniel , Nepal Kundan
Published: June 2018

Carbon nanotube-based transistors (CNTFETs) have been shown to exhibit ambipolar field-effect transistor behavior, allowing circuit designers to easily choose between [Formula: see text]- and [Formula: see text]-conduction channels by applying correct voltages at a polarity gate. In this paper, we explore this ambipolar behavior of the CNTFET to design both binary and ternary content addressable memory (AM) cells. Using SPICE simulation, we show the designs of a traditional ternary CAM (TCAM) and a true three-valued TCAM (T3-CAM) functionality of the proposed cells and show that the ambipolar design can lead to a savings of up to 31% in terms of transistor count over a traditional design. We also explore issues related to matchline leakage, cell stability and design in the presence of metallic tubes.
A Method for Partner Selection of Supply Chain Using Interval-Valued Fuzzy Sets — Fuzzy Choquet Integral and Improved Dempster–Shafer Theory
Authors: Yu Guodong , Zhang Li , Sun Huiping
Published: June 2018

Supply chain partner selection (SCPS) is an important issue for firms to remain highly competitive. SCPS is generally formulated as a fuzzy multi-criteria decision-making problem, of which the most crucial step is how to cope with the fuzzy correlations of multi-criteria and individual differences of experts. To gain more exact results, we adopt interval-valued intuitionistic fuzzy sets to express the fuzziness of multi-criteria. Fuzzy Choquet integral model is developed to explain correlations of multi-criteria and calculate the evaluation results of each expert. An improved Dempster–Shafer theory is utilized to reconcile differences and synthesize each expert decision results. Additionally, an example is presented to illustrate the potential application of the proposed method.
FIFI-LS: The Field-Imaging Far-Infrared Line Spectrometer on SOFIA
Authors: Fischer Christian , Beckmann Simon , Bryant Aaron , Colditz Sebastian , Fumi Fabio , Geis Norbert , Hamidouche Mourad , Henning Thomas , Hönle Rainer , Iserlohe Christof , Klein Randolf , Krabbe Alfred , Looney Leslie , Poglitsch Albrecht , Raab Walfried , Rebell Felix , Rosenthal Dirk , Savage Maureen , Schweitzer Mario , Trinh Christopher , Vacca William
Published: June 2018

We describe the design of the Field-Imaging Far-Infrared Line Spectrometer (FIFI-LS), operated as a Facility-Class instrument on the Stratospheric Observatory for Infrared Astronomy (SOFIA). FIFI-LS is an imaging spectrometer for medium resolution spectroscopy. Since being commissioned in 2014, it has performed over 50 SOFIA commissioning and science flights. After operating as a principal investigator instrument in 2014 and early 2015, it was accepted as a Facility Science Instrument in 2015. In addition to the description of the design, we report on the in-flight performance and the concept of operation. We also provide an overview of the science opportunities with FIFI-LS and describe how FIFI-LS observations complement and complete observations with the PACS instrument on the Herschel observatory.
Spectral and Spatial Characterization and Calibration of FIFI-LS — The Field Imaging Spectrometer on SOFIA
Authors: Colditz Sebastian , Beckmann Simon , Bryant Aaron , Fischer Christian , Fumi Fabio , Geis Norbert , Hamidouche Mourad , Henning Thomas , Hönle Rainer , Iserlohe Christof , Klein Randolf , Krabbe Alfred , Looney Leslie , Poglitsch Albrecht , Raab Walfried , Rebell Felix , Rosenthal Dirk , Savage Maureen , Schweitzer Mario , Vacca William
Published: June 2018

The field-imaging far-infrared line spectrometer (FIFI-LS) is a science instrument for the Stratospheric Observatory for Infrared Astronomy (SOFIA). FIFI-LS allows simultaneous observations in two spectral channels. The “blue” channel is sensitive from 51[Formula: see text][Formula: see text]m to 125[Formula: see text][Formula: see text]m and the “red” channel from 115[Formula: see text][Formula: see text]m to 203[Formula: see text][Formula: see text]m. The instantaneous spectral coverage is 1000–3000[Formula: see text]km/s in the blue and 800–2500[Formula: see text]km/s in the red channel with a spectral resolution between 150[Formula: see text]km/s and 600[Formula: see text]km/s. Each spectral channel observes a field of five by five spatial pixels on the sky. The pixel size in the blue channel is 6.14 by 6.25 square arc seconds and it is 12.2 by 12.5 square arc seconds in the red channel. FIFI-LS has been operating on SOFIA since 2014. It is available to the astronomical community as a facility science instrument. We present the results of the spectral and spatial characterization of the instrument based on laboratory measurements. This includes the measured spectral resolution and examples of the line spread function in the spectral domain. In the spatial domain, a model of the instrument’s point spread function (PSF) and the description of a second pass ghost are presented. We also provide an overview of the procedures used to measure the instrument’s field of view geometry and spectral calibration. The spectral calibration yields an accuracy of 15–60[Formula: see text]km/s depending on wavelength.
How to choose the suitable animal model of polycystic ovary syndrome?
Authors: Tamadon Amin , Hu Wei , Cui Peng , Ma Tong , Tong Xiaoyu , Zhang Feifei , Li Xin , Shao Linus R. , Feng Yi
Published: June 2018

Polycystic ovary syndrome (PCOS) is a gynecological metabolic and endocrine disorder with uncertain etiology. To understand the etiology of PCOS or the evaluation of various therapeutic agents, different animal models have been introduced. Considering this fact that is difficult to develop an animal model that mimics all aspects of this syndrome, but, similarity of biological, anatomical, and/or biochemical features of animal model to the human PCOS phenotypes can increase its application. This review paper evaluates the recently researched animal models and introduced the best models for different research purposes in PCOS studies. During January 2013 to January 2017, 162 studies were identified which applied various kinds of animal models of PCOS including rodent, primate, ruminant and fish. Between these models, prenatal and pre-pubertal androgen rat models and then prenatal androgen mouse model have been studied in detail than others. The comparison of main features of these models with women PCOS demonstrates higher similarity of these three models to human conditions. Thereafter, letrozole models can be recommended for the investigation of various aspects of PCOS. Interestingly, similarity of PCOS features of post-pubertal insulin and human chorionic gonadotropin rat models with women PCOS were considerable which can make it as a good choice for future investigations.