bluuebunny/crossref_metadata_2025 huggingface dataset:
Tides and Prejudice: Racial Attitudes during Downturns in the United States 1979–2014
Authors: Jayadev Arjun , Johnson Robert
Published: December 2017

What happens to racial prejudice during economic downturns? This paper analyzes white attitudes towards African Americans in the United States at different points in a business cycle from 1979 to 2014. Using a number of indicators of hostility towards African Americans available from the General Social Survey we develop an indicator of racial prejudice. We combine this with data on unemployment from the Current Population Survey and find robust evidence that racial hostility as measured by our indicator of prejudice is counter cyclical and rises during periods of higher unemployment for whites. Specifically a one standard deviation in the unemployment rate being experienced by whites is associated with a .03 to.05 standard deviation increase in the discrimination index. This is of a magnitude comparable with one year less of education. We undertake a quantile regression to show that this effect is widespread across the distribution of prejudice and that apart from those with initially low levels of prejudice, increasing own group unemployment results in statistically significant increases of similar magnitude in prejudice across that distribution.
Longitudinal relations between adolescents' materialism and prosocial behavior toward family, friends, and strangers
Authors: Yang Zhixu , Fu Xinyuan , Yu Xiaoxia , Lv Yichen
Published: December 2017

The present study examines the short‐term changes and longitudinal relations between adolescents' materialism and prosocial behavior toward family, friends, and strangers over a year. A total of 434 Chinese adolescents (mean age at Time 1 = 11.27; 54% girls) participated in the two time points. From 6th grade to 7th grade, boys' and girls' materialism increased, whereas their prosocial behavior toward family, friends, and strangers declined, despite the stable trend in boys' prosocial behavior toward strangers. Furthermore, a cross‐lagged model was conducted and the results showed that, adolescent materialism was associated longitudinally with decreased prosocial behavior toward friends and strangers, but not toward family. However, earlier prosocial behavior toward family, friends, and strangers were not associated with subsequent adolescent materialism. The findings point toward an understanding of materialism as a precursor rather than an outcome or byproduct to prosocial behavior.
Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation
Authors: Jern Patrick , Johansson Ada , Strohmaier Jana , Treutlein Jens , Piha Juhana , Rietschel Marcella
Published: December 2017

Background

Studies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE).

Aim

To investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE.

Methods

PE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 1,022 controls from a population-based sample. In total, we tested associations between PE and 11 single-nucleotide polymorphisms in the dopamine receptor D1, D2, and D3 genes and in the COMT gene.

Outcomes

We found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMT-linked loci (rs4680 and rs4818) had significant associations after correction for multiple testing.

Results

1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that causes a valine-to-methionine substitution. The other polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus, indicating that they capture the same effect. Surprisingly, the rs4680 variant that was statistically significantly more prevalent in the PE group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels.

Clinical Translation

Drugs targeting the dopaminergic system could affect PE symptoms.

Strengths and Limitations

No replication sample was available for the present study; thus, our findings should be interpreted with caution. Moreover, a limitation of our study is the small sample in the context of genetic association studies (although it should be mentioned that genetically informative samples with phenotypic information about PE symptoms are scarce, and most previous genetic association studies of PE have used samples of similar or smaller size). However, our results are plausible: we report an association between one of the most extensively studied and understood genetic polymorphisms in psychiatric research and PE, and our results are in line with the long-standing hypothesis that dopamine influences human ejaculatory function.

Conclusions

We report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated.
Controlled spin switching in a metallocene molecular junction
Authors: Ormaza M. , Abufager P. , Verlhac B. , Bachellier N. , Bocquet M.-L. , Lorente N. , Limot L.
Published: December 2017

The active control of a molecular spin represents one of the main challenges in molecular spintronics. Up to now spin manipulation has been achieved through the modification of the molecular structure either by chemical doping or by external stimuli. However, the spin of a molecule adsorbed on a surface depends primarily on the interaction between its localized orbitals and the electronic states of the substrate. Here we change the effective spin of a single molecule by modifying the molecule/metal interface in a controlled way using a low-temperature scanning tunneling microscope. A nickelocene molecule reversibly switches from a spin 1 to 1/2 when varying the electrode–electrode distance from tunnel to contact regime. This switching is experimentally evidenced by inelastic and elastic spin-flip mechanisms observed in reproducible conductance measurements and understood using first principle calculations. Our work demonstrates the active control over the spin state of single molecule devices through interface manipulation.
Biomarkers of aging associated with past treatments in breast cancer survivors
Authors: Scuric Zorica , Carroll Judith E. , Bower Julienne E. , Ramos-Perlberg Sam , Petersen Laura , Esquivel Stephanie , Hogan Matt , Chapman Aaron M. , Irwin Michael R. , Breen Elizabeth C. , Ganz Patricia A. , Schiestl Robert
Published: December 2017

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3–6 years after completion of primary treatments in breast cancer survivors (stage 0–IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4–69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P’s < .05). We found that exposure to chemotherapy and/or radiation 3–6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure.
π-Bridge modification of thiazole-bridged DPP polymers for high performance near-IR OSCs
Authors: Sun Kuangshi , Tang Xiaoqin , Ran Yalin , He Rongxing , Shen Wei , Li Ming
Published: December 2017

π-Bridge modification could adjust the molecular energy levels and improve the optical, intramolecular charge transfer and charge transport properties.
3D-Printed seed planter and well array for high-throughput seed germination screening
Authors: Chai Hui Hui , Lu Yao , Fang Can , Li Ya Dan , Kang Yue Jun , Li Chang Ming , Yu Ling
Published: December 2017

A 3D-printed miniaturized well array and seed planter have been developed for in-field studies of seed quality and screening of conditions for seedlings.
Design, synthesis and antibacterial evaluation of a polycationic calix[4]arene derivative alone and in combination with antibiotics
Authors: Consoli G. M. L. , Granata G. , Picciotto R. , Blanco A. R. , Geraci C. , Marino A. , Nostro A.
Published: December 2017

Synthesis of a new polycationic calix[4]arene derivative: intrinsic antibacterial activity and additive effect when combined with antibiotics against ATCC and resistant bacteria.
Writable and patternable organic solar cells and modules inspired by an old Chinese calligraphy tradition
Authors: Mao Lin , Luo Bangwu , Sun Lulu , Xiong Sixing , Fan Jiacheng , Qin Fei , Hu Lin , Jiang Youyu , Li Zaifang , Zhou Yinhua
Published: December 2017

A fabrication technique inspired by an old Chinese calligraphy tradition is developed to fabricate organic solar cells and modules.
Large scale 2D/3D hybrids based on gallium nitride and transition metal dichalcogenides
Authors: Zhang Kehao , Jariwala Bhakti , Li Jun , Briggs Natalie C. , Wang Baoming , Ruzmetov Dmitry , Burke Robert A. , Lerach Jordan O. , Ivanov Tony G. , Haque Md , Feenstra Randall M. , Robinson Joshua A.
Published: December 2017

Large area 2D MoS2 and WSe2 are integrated on 3D GaN by metal organic chemical vapor deposition (MOCVD). The thickness-dependent vertical tunneling and interlayer charge transfer is carefully studied. This work shows that few layer WSe2 film is the appropriate choice towards device application of synthetic 2D/3D heterostructures.
Designing a main-chain visible-light-labile picolinium-caged polymer and its biological applications
Authors: Zhou Tongtong , Liu Tao , Bao Yu , Zhang Ping , Yan Casey , Yao Fujun , Cui Shuxun , Chen Yongming , Chen Xin , Yu You
Published: December 2017

A picolinium-caged main-chain photolabile polymer (MCPP) is reported with a high degradation efficiency (∼95%) upon visible light irradiation (452 nm).
Nano-porous structuresviaself-assembly of amphiphilic triblock copolymers: influence of solvent and molecular weight
Authors: Nehache S. , Semsarilar M. , Deratani A. , In M. , Dieudonné-George P. , Lai Kee Him J. , Bron P. , Quémener D.
Published: December 2017

Self-assembly of ABA triblock copolymer micelles into porous materials which are subsequently used as filtration membranes.
3D graphene foam/ZnO nanorods array mixed-dimensional heterostructure for photoelectrochemical biosensing
Authors: Kang Zhuo , Li Yong , Cao Shiyao , Zhang Zihan , Guo Huijing , Wu Pingwei , Zhou Lixin , Zhang Suicai , Zhang Xiaomei , Zhang Yue
Published: December 2017

We combined a 3D graphene foam network with a ZnO NRs array and further introduced this mixed-dimensional heterostructure into a PEC biosensing system.
A simple route to highly active single-enzyme nanogels
Authors: Beloqui Ana , Kobitski Andrei Yu , Nienhaus Gerd Ulrich , Delaittre Guillaume
Published: December 2017

Just add sugar: the synthesis of single-enzyme nanogels, a class of highly robust nanobiocatalysts, is boosted by the addition of carbohydrates. Our methodology is demonstrated with a dozen commercial proteins, spanning a large size interval and a broad domain of applications. In addition, new in-depth structural characterizations are provided.
Large Interstellar Polarisation Survey
Authors: Siebenmorgen R. , Voshchinnikov N. V. , Bagnulo S. , Cox N. L. J. , Cami J. , Peest C.
Published: December 2017

It is well known that the dust properties of the diffuse interstellar medium exhibit variations towards different sight-lines on a large scale. We have investigated the variability of the dust characteristics on a small scale, and from cloud-to-cloud. We use low-resolution spectro-polarimetric data obtained in the context of the Large Interstellar Polarisation Survey (LIPS) towards 59 sight-lines in the Southern Hemisphere, and we fit these data using a dust model composed of silicate and carbon particles with sizes from the molecular to the sub-micrometre domain. Large (≥6 nm) silicates of prolate shape account for the observed polarisation. For 32 sight-lines we complement our data set with UVES archive high-resolution spectra, which enable us to establish the presence of single-cloud or multiple-clouds towards individual sight-lines. We find that the majority of these 35 sight-lines intersect two or more clouds, while eight of them are dominated by a single absorbing cloud. We confirm several correlations between extinction and parameters of the Serkowski law with dust parameters, but we also find previously undetected correlations between these parameters that are valid only in single-cloud sight-lines. We find that interstellar polarisation from multiple-clouds is smaller than from single-cloud sight-lines, showing that the presence of a second or more clouds depolarises the incoming radiation. We find large variations of the dust characteristics from cloud-to-cloud. However, when we average a sufficiently large number of clouds in single-cloud or multiple-cloud sight-lines, we always retrieve similar mean dust parameters. The typical dust abundances of the single-cloud cases are [C]/[H] = 92 ppm and [Si]/[H] = 20 ppm.
Right Ventricular Infarction in Inferior Wall Myocardial Infarction
Authors: Vanajakshamma Velam , Vyshnavi Kancherla , Latheef Kasala , Ramesh Rayi , DamodaraRao Kodem
Published: December 2017

Background Right ventricular infarction (RVI) is common in patients with inferior wall myocardial infarction (IWMI). Right ventricular involvement increases mortality and morbidity in IWMI patients. Clinical presentation of RVI differs, and accordingly treatment and management of patients also differs.

Aim To find out the frequency of RVI among patients with acute IWMI and to determine the utility of clinical examination, electrocardiography (ECG), and echocardiography (ECHO) in the diagnosis of RVI and its severity. Also o study the frequency and complications with reference to sex.

Material and Methods One hundred patients with acute IWMI were recruited. Clinical examination, ECG with right precordial leads, and 2D ECHO (right ventricular end-systolic volume [RVESV] and right ventricular end-diastolic volume [RVEDV], right ventricular stroke volume [RVSV], RVESV index [RVESVI], RVEDV index [RVEDVI], RVSV index [RVSVI], and right ventricular ejection fraction [RVEF]) were done to diagnose RVI and its severity. RVI patients were divided into two groups basing on RVEF as severe RVI (EF < 35%) and mild RVI (EF > 35%).

Results Forty-three (43%) patients had RVI. Thirty-one (72%) patients had mild RVI (EF > 35%) and 12 (28%) had severe RVI (EF < 35%). Clinical examination had less sensitivity (35%) and high specificity (93%) in the diagnosis of RVI whereas it was highly sensitive (100%) and specific (90%) in detecting severe RVI. Total ST elevation of ≥ 3 mm was highly sensitive (92%), and ≥ 5 mm was highly specific (94%) in detecting severe RVI. RVEF (p < 0.01), RVESVI (p < 0.01), RVEDVI (p < 0.01), RVSVI (p < 0.05), and total ST elevation (p < 0.01) were equally effective in detecting severe RVI. Case fatality rate in RVI was 7%. Proportional mortality rate in females was 67%, with higher mortality in females compared with males (p ≤ 0.05).

Conclusion Right-sided leads should be taken in all cases of acute IWMI. Careful clinical examination, total ST elevation in V1, V2, V3R, V4R, ECHO RVESV, RVEDV, RVSV, RVEF, RVESVI, RVEDVI, and RVSVI are useful in detecting severe RVI. Complications were significantly associated with the severity of RVI. Mortality is high in females compared with males.
Comparison of Absorbable and Nonabsorbable Sutures in Columellar Incision Closure in Rhinoplasty and Their Effects to Postoperative Scar
Authors: Bayram Ali , Serin Gediz , Kilavuz Ahmet
Published: December 2017

Open technique septorhinoplasty (SRP) provides better surgical control and stronger anatomical assessment; however, one of its biggest disadvantages is postoperative columellar scar. In this study, the authos aimed to compare the absorbable polyglactin 910 (PG) (Vicryl Rapide 6/0; Ethicon Inc.) and nonabsorbable polypropylene (PP) (Prolene 6/0; Ethicon Inc.) suture materials and their effects on the postoperative columellar scar. In this study, 89 patients (61 females and 28 males) who underwent primary open technique SRP were included; 42 patients were included in the PP group and 47 were included in the PG group. Sutures were removed in PP group on 7th postoperative day. Sutures were left to be absorbed in the PG group. Columellar scar was assessed with visual analog scale (VAS) subjectively and with the modified Stony Brook Scar Evaluation Scale (SBSES) objectively in 6th postoperative month. SBSES results in PG and PP groups were 3.88 ± 0.80 and 3.67 ± 0.80, respectively. There was no statistical significance between the two groups (p = 0.352). VAS results in PG and PP groups were 8.04 ± 0.91 and 7.71 ± 0.85, respectively. There was no statistical significance between the two groups (p = 0.200). No postoperative wound infection was seen in either of the groups. PG delivers good postoperative results in columellar scar. We recommend using PG for columellar incision closure since it provides less discomfort and anxiety for the patient, and less office time for the surgeon during the suture removal.
Role of Camouflage in Management of Facial Trauma Deformities
Authors: Chin Oliver , Tollefson Travis
Published: December 2017

Facial fractures and soft tissue injuries around the eyes, nose, and mouth can be difficult to manage in the primary setting, but if untreated, the secondary correction of facial trauma is very challenging. Prevention of soft tissue contraction by restoring the skeletal framework is ideal. Staged, individualized camouflage techniques can be effective in improving outcomes.
Increased postprandial glucagon-like peptide-1 (GLP-1) production after endoscopic gastrointestinal bypass using the Cousin lumen-apposing stent in a porcine model
Authors: Caiazzo Robert , Branche Julien , Daoudi Mehdi , Solecki Gilles , Hubert Thomas , Quenon Audrey , Raverdy Violeta , Cousin François , Henin François , Dalle Valery , Noel Stéphane , Vanbiervliet Geoffroy , Barthet Marc , Pattou François
Published: December 2017

Background and study aims Endoscopic techniques have demonstrated their effectiveness in metabolic surgery, notably through a gastrointestinal (GI) liner, with a less invasive approach than conventional surgery. Our study evaluates the safety and efficacy of endoscopic GI anastomosis (EGIA) using a lumen-apposing stent to secure the anastomosis.

Materials and methods EGIA was performed using the transgastric approach with a two-channel endoscope with a novel stent (Cousin Biotech). First, a safety study with a follow-up of 12 months was performed on five piglets. Then, metabolic changes were investigated in a minipig model (n = 10) before and after EGIA or open GIA (OGIA).

Results EGIA was technically successful with no complications observed during clinical monitoring. Endoscopic and postmortem examinations during the second part of study showed a secure anastomosis between the stomach and the intestinal limb in all except one minipig. Both minipigs subjected to EGIA and those in the control group (OGIA) exhibited increased postprandial glucagon-like peptide-1 (GLP-1) production (incretin secretion) and impaired D-xylose absorption (malabsorption effect).

Conclusion Performing EGIA with this dedicated stent appears safe, technically feasible, durable, and reproducible in providing a simple and effective endoscopic GI bypass capable of ensuring metabolic effect.
Influence of solvent polarization and non-uniform ion size on electrostatic properties between charged surfaces in an electrolyte solution
Authors: Sin Jun-Sik
Published: December 2017

In this paper, we study electrostatic properties between two similar or oppositely charged surfaces immersed in an electrolyte solution by using the mean-field approach accounting for solvent polarization and non-uniform size effects. Applying a free energy formalism accounting for unequal ion sizes and orientational ordering of water dipoles, we derive coupled and self-consistent equations to calculate electrostatic properties between charged surfaces. Electrostatic properties for similarly charged surfaces depend on the counterion size but not on the coion size. Moreover, electrostatic potential and osmotic pressure between similarly charged surfaces are found to be increased with increasing counterion size. On the other hand, the corresponding ones between oppositely charged surfaces are related to both sizes of positive and negative ions. For oppositely charged surfaces, the electrostatic potential, number density of solvent molecules, and relative permittivity of an electrolyte having unequal ion sizes are not symmetric about the centerline between the charged surfaces. For either case, the consideration of solvent polarization results in a decrease in the electrostatic potential and the osmotic pressure compared to the case without the effect.
Weiss, Barish, and Thorne share 2017 Nobel Prize in Physics
Authors: Grant Andrew
Published: December 2017

Three architects of LIGO are honored for their successful effort to directly detect gravitational waves.
NASA sees a future with nuclear power
Authors: Kramer David
Published: December 2017

The space agency views reactors as options both for propulsion to Mars and as a power source for life on the red planet.
Positive Psychology in SLA
Authors: Mercer Sarah
Published: December 2017

This article begins with an outline of the developments in Positive Psychology (PP) generally and specifically within SLA focusing on theoretical, empirical and practical developments. It moves on to consider PP’s potential contribution to language teaching focusing on how it can help promote emotional, social and psychological wellbeing for language learners and teachers. It explores the concept of ‘Positive Education’ and reflects on possible lessons from these broader developments for a specific approach to ‘Positive Language Education’. It is argued that PP facilitates new ways of thinking about language learning and can provide the ideal vehicle from which to foreground wellbeing as a concept and dual aim in language education.
Lingua e comunità in coro
Authors: Kennedy Claire , Miceli Tiziana
Published: December 2017

This article concerns a special learning space populated by Italians and Italian learners: the choir formed in Brisbane as a joint initiative between a community association and the Italian teaching staff at Griffith University. Our aim, in involving our students in the choir, was to bring them together with L1 speakers in an environment that would be stimulating but supportive, given the collective, creative goal. We envisaged that interaction in this space would help develop the students’ language proficiency, intercultural competence, and cultural knowledge, while also bringing the psychosocial benefits of choral singing identified by recent research. These benefits include positive emotions, social support and friendship, an antidote to anxiety and stress, and a shared sense of commitment. Evaluation of findings from the project suggest that the choir did foster students’ learning together with wellbeing.
Branched-chain amino acids regulate type I tropocollagen and type III tropocollagen syntheses via modulation of mTOR in the skin
Authors: Yamane Takumi , Morioka Yuka , Kitaura Yasuyuki , Iwatsuki Ken , Shimomura Yoshiharu , Oishi Yuichi
Published: December 2017

Branched-chain amino acids (BCAAs) exhibit many physiological functions. However, the potential link and mechanism between BCAA and skin function are unknown. We examined the effects of deletion of branched-chain α-keto acid dehydrogenase kinase (BDK), a key enzyme in BCAA catabolism, on type I and III tropocollagen syntheses in mice. Leucine and isoleucine levels were significantly lower in the skin of BDK-KO mice compared with wild-type mice. No changes in valine concentrations were observed. The levels of type I and III tropocollagen proteins and mRNAs (COL1A1 and COL3A1) were significantly lower in the skin of BDK-KO mice compared with wild-type mice. The phosphorylation of p70 S6 kinase, which indicates mammalian target of rapamycin (mTOR) activation, was reduced in the skin of BDK-KO mice compared with wild-type mice. These findings suggest that deficiencies of leucine and isoleucine reduce type I and III tropocollagen syntheses in skin by suppressing the action of mTOR.
Structural and functional analysis of the carotenoid biosynthesis genes of aPseudomonasstrain isolated from the excrement of Autumn Darter
Authors: Fukaya Yuki , Takemura Miho , Koyanagi Takashi , Maoka Takashi , Shindo Kazutoshi , Misawa Norihiko
Published: December 2017

There are many reports about carotenoid-producing bacteria and carotenoid biosynthesis genes. In databases for Pseudomonas genome sequences, there are genes homologous to carotenoid biosynthesis genes, but the function of these genes in Pseudomonas has not been elucidated. In this study, we cloned the carotenoid biosynthesis genes from a Pseudomonas sp. strain, named Akiakane, which was isolated from the excrement of the Autumn Darter dragonfly. Using an Escherichia coli functional expression system, we confirmed that the idi, crtE, crtB, crtI, and crtY gene products of the Akiakane strain show predictable catalytic activities. A cluster of six genes was also found, which was comparable to other carotenoid-producing bacteria that belong to the α-Proteobacteria or γ-Proteobacteria class.
Severity of Illness Scores May Misclassify Critically Ill Obese Patients*
Authors: Deliberato Rodrigo Octávio , Ko Stephanie , Komorowski Matthieu , Armengol de La Hoz M. A. , Frushicheva Maria P. , Raffa Jesse D. , Johnson Alistair E. W. , Celi Leo Anthony , Stone David J.
Published: December 2017

Objective:

Severity of illness scores rest on the assumption that patients have normal physiologic values at baseline and that patients with similar severity of illness scores have the same degree of deviation from their usual state. Prior studies have reported differences in baseline physiology, including laboratory markers, between obese and normal weight individuals, but these differences have not been analyzed in the ICU. We compared deviation from baseline of pertinent ICU laboratory test results between obese and normal weight patients, adjusted for the severity of illness.

Design:

Retrospective cohort study in a large ICU database.

Setting:

Tertiary teaching hospital.

Patients:

Obese and normal weight patients who had laboratory results documented between 3 days and 1 year prior to hospital admission.

Interventions:

None.

Measurements and Main Results:

Seven hundred sixty-nine normal weight patients were compared with 1,258 obese patients. After adjusting for the severity of illness score, age, comorbidity index, baseline laboratory result, and ICU type, the following deviations were found to be statistically significant: WBC 0.80 (95% CI, 0.27–1.33) × 109/L; p = 0.003; log (blood urea nitrogen) 0.01 (95% CI, 0.00–0.02); p = 0.014; log (creatinine) 0.03 (95% CI, 0.02–0.05), p < 0.001; with all deviations higher in obese patients. A logistic regression analysis suggested that after adjusting for age and severity of illness at least one of these deviations had a statistically significant effect on hospital mortality (p = 0.009).

Conclusions:

Among patients with the same severity of illness score, we detected clinically small but significant deviations in WBC, creatinine, and blood urea nitrogen from baseline in obese compared with normal weight patients. These small deviations are likely to be increasingly important as bigger data are analyzed in increasingly precise ways. Recognition of the extent to which all critically ill patients may deviate from their own baseline may improve the objectivity, precision, and generalizability of ICU mortality prediction and severity adjustment models.
ANALYSIS OF THE NORMAL PERIPHERAL RETINAL VASCULAR PATTERN AND ITS CORRELATION WITH MICROVASCULAR ABNORMALITIES USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY
Authors: Seo Eoi Jong , Kim June-Gone
Published: December 2017

Purpose:

To describe the retinal peripheral vascular morphology and to elucidate its relationship to microvascular abnormalities in normal fundus using ultra-widefield fluorescein angiography.

Methods:

A total of 242 eyes from 167 consecutive patients were categorized into 3 groups: bilateral normal (n = 64), normal with contralateral eye affected with vascular disease (n = 82), and early diabetic eyes (n = 96). Peripheral vascular morphology was described and classified according to the shape. Microvascular abnormalities such as capillary telangiectasia, microaneurysm, or vascular leakage were documented, and the relationship between those abnormalities in each groups were analyzed.

Results:

There were two distinctive peripheral vascular morphologies—loop and branching patterns. Microvascular abnormalities were more frequently found as loop patterns; this difference was most prominent when both eyes were normal. In case of normal eyes with contralateral eye affected with vascular disease or diabetic eyes, branching pattern microvascular abnormalities were relatively increased, whereas loop pattern still showed a large degree of microvascular abnormalities.

Conclusion:

In normal retinal periphery, we observed microvascular abnormalities and their relationship with vascular morphology, which could be influenced by the condition of the contralateral eye or systemic disease such as diabetes mellitus.
PREOPERATIVE FACTORS INFLUENCING VISUAL RECOVERY AFTER VITRECTOMY FOR MYOPIC FOVEOSCHISIS
Authors: Lehmann Mathieu , Devin François , Rothschild Pierre-Raphael , Gaucher David , Morin Bruno , Philippakis Elise , Massin Pascale , Couturier Aude , Tadayoni Ramin
Published: December 2017

Purpose:

To determine the preoperative factors influencing visual recovery after vitrectomy for myopic foveoschisis.

Methods:

Sixty-six eyes of 65 consecutive patients operated on for myopic foveoschisis were retrospectively included. All eyes underwent a preoperative ocular examination including best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography with central foveal thickness measurement and foveal status classification: simple foveoschisis, foveal detachment, or macular hole. To study the impact of preoperative visual acuity, 4 visual acuity groups separated by quartile ranges were defined. Postoperative visits at 1, 3, or 12 months including BCVA measurement and optical coherence tomography were recorded.

Results:

Mean refraction was −15.90 diopters, mean axial length was 30.30 mm, mean central foveal thickness was 590 μm, and mean baseline logarithm of the maximum angle of resolution visual acuity was 0.68 (Snellen equivalent of 20/96). The final BCVA improved significantly from 3 months after surgery until the last follow-up visit; the mean logarithm of the maximum angle of resolution visual acuity at last follow-up was 0.43 (Snellen equivalent of 20/54). Mean central foveal thickness decreased significantly as soon as the first postoperative month (P < 0.0001). The preoperative BCVA was the only independent factor significantly correlated with the final BCVA as opposed to the foveal status (P < 0.0001). The mean BCVA and mean visual gain at the last follow-up visit were significantly different between the four visual acuity groups (P < 0.0001 and P = 0.017, respectively).

Conclusion:

The main factor influencing the postoperative visual acuity is the preoperative visual acuity. Although the preoperative anatomical status seemed important in surgeon decision making, once normalized on visual acuity, it no longer influenced the postoperative visual acuity.
Desmoplastic Melanoma of the Periorbital Region
Authors: Thakar Sudip , Kandl Thomas , Sagiv Oded , Tripathy Devjyoti , Tetzlaff Michael T. , Kapur Sahil , Myers Jeffrey , Hwu Wen-Jen , Jaber Bashar M.Y. , Esmaeli Bita
Published: December 2017

Desmoplastic melanoma (DM) is a rare subtype of melanoma and an even smaller proportion of periocular melanomas. Here, the authors report 2 cases of DM in the periocular region. Staged according to the American Joint Committee on Cancer (AJCC) eighth edition classification, patient 1 presented with a stage IIIC (pT4apN1cM0) DM in the left lateral canthus with upper and lower eyelid and patient 2 presented with a stage IIIB (T4aN1bM0) DM in the left brow and supraorbital region with a parotid lymph node metastasis. In both patients, the lesions were amelanotic, with inflammatory appearance, and had been noted for several years before the correct diagnosis was made. In both patients, wide excision led to large surgical defects, and perineural invasion prompted adjuvant radiation therapy postoperatively. Patient 2 was treated with an immune checkpoint inhibitor for his parotid metastasis. Ophthalmologists should be aware of DM, its neurotrophic nature, and potential to metastasize with locally advanced lesions.
A Case of Congenital Dyserythropoeitic Anemia Type IV Caused by E325K Mutation in Erythroid Transcription Factor KLF1
Authors: Ortolano Rebecca , Forouhar Melissa , Warwick Anne , Harper David
Published: December 2017

Congenital dyserythropoetic anemias (CDA) represent a heterogeneous group of inherited red cell disorders resulting in ineffective erythropoiesis. Several CDA variants have been identified. KLF1 is a transcription factor required for cell division in erythroid differentiation and maturation, and the switch from fetal to adult hemoglobin. Mutations in KLF1 gene can result in a wide range of phenotypes. This case illustrates the E325K mutation in KLF1 presenting with severe anemia in infancy, persistently elevated fetal hemoglobin, and progressive improvement with age. This case of CDA because of KLF1 mutation highlights the common features and expected disease course of CDA type IV.
The Power of the Frame
Authors: Scott Kathy A. , Pringle Janice
Published: December 2017

Health care leaders are responsible for oversight of multiple and competing change interventions. These interventions regularly fail to achieve the desired outcomes and/or sustainable results. This often occurs because of the mental models and approaches that are used to plan, design, implement, and evaluate the system. These do not account for inherent characteristics that determine the system's likely ability to innovate while maintaining operational effectiveness. Theories exist on how to assess a system's readiness to change, but the definitions, constructs, and assessments are diverse and often look at facets of systems in isolation. The Systems Transformation Framework prescriptively defines and characterizes system domains on the basis of complex adaptive systems theory so that domains can be assessed in tandem. As a result, strengths and challenges to implementation are recognized before implementation begins. The Systems Transformation Framework defines 8 major domains: vision, leadership, organizational culture, organizational behavior, organizational structure, performance measurements, internal learning, and external learning. Each domain has principles that are critical for creating the conditions that lead to successful organizational adaptation and change. The Systems Transformation Framework can serve as a guide for health care leaders at all levels of the organization to (1) create environments that are change ready and (2) plan, design, implement, and evaluate change within complex adaptive systems.
Cytomegalovirus infection is a risk factor for TB disease in Infants
Authors: Muller Julius , Tanner Rachel , Matsumiya Magali , Snowden Margaret A. , Landry Bernard , Satti Iman , Harris Stephanie A. , Tanner Rachel , O’Shea Matthew K. , Stockdale Lisa , Marsay Leanne , Chomka Agnieszka , Harrington-Kandt Rachel , Thomas Zita-Rose Manjaly , Naranbhai Vivek , Stylianou Elena , Mbandi Stanley Kimbung , Hatherill Mark , Hussey Gregory , Mahomed Hassan , Tameris Michele , McClain J. Bruce , Evans Thomas G. , Hanekom Willem A. , Scriba Thomas J. , McShane Helen , Fletcher Helen A.
Published: December 2017

Immune activation is associated with increased risk of tuberculosis (TB) disease in infants. We performed a case-control analysis to identify drivers of immune activation and disease risk. Among 49 infants who developed TB disease over the first two years of life, and 129 matched controls who remained healthy, we found the cytomegalovirus (CMV) stimulated IFN-γ response at age 4-6 months to be associated with CD8+ T-cell activation (Spearman’s rho, p=6×10−8). A CMV specific IFN-γ response was also associated with increased risk of developing TB disease (Conditional Logistic Regression, p=0.043, OR 2.2, 95% CI 1.02-4.83), and shorter time to TB diagnosis (Log Rank Mantel-Cox p=0.037). CMV positive infants who developed TB disease had lower expression of natural killer cell associated gene signatures and a lower frequency of CD3-CD4-CD8-lymphocytes. We identified transcriptional signatures predictive of risk of TB disease among CMV ELISpot positive (AUROC 0.98, accuracy 92.57%) and negative (AUROC 0.9, accuracy 79.3%) infants; the CMV negative signature validated in an independent infant study (AUROC 0.71, accuracy 63.9%). Understanding and controlling the microbial drivers of T cell activation, such as CMV, could guide new strategies for prevention of TB disease in infants.
Aberrant splicing in B-cell acute lymphoblastic leukemia
Authors: Black Kathryn L. , Naqvi Ammar S. , Hayer Katharina E. , Yang Scarlett Y. , Gillespie Elisabeth , Bagashev Asen , Pillai Vinodh , Tasian Sarah K. , Gazzara Matthew R. , Carroll Martin , Taylor Deanne , Lynch Kristen W. , Barash Yoseph , Thomas-Tikhonenko Andrei
Published: December 2017

Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3’UTR was pervasively misspliced, yielding the transcript subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs were consistent with reduced translation of DICER1 mRNA. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis.
Rapid evolution of gained essential developmental functions of a young gene via interactions with other essential genes
Authors: Lee Yuh Chwen G. , Ventura Iuri M. , Rice Gavin R. , Chen Don-Yuan , Long Manyuan
Published: December 2017

New genes originated relatively recently and are only present in a subset of species in a phylogeny. Accumulated evidence suggests that new genes, like old genes that are conserved across species, can also take on important functions and be essential for the survival and reproductive success of organisms. While there are detailed analyses of the mechanisms underlying gained fertility functions by new genes, how new genes rapidly became essential for viability remains unclear. We focused on a young retro-duplicated gene (CG7804, which we namedCocoon) inDrosophilathat originated three million years ago. We found that, unlike its evolutionarily conserved and broadly expressed parental gene,Cocoonhas evolved rapidly under positive selection since its birth and accumulates many amino acid divergences at functional sites from the parental gene. Despite its young age,Cocoonis essential for the survival ofD. melanogasterat multiple developmental stages, including the critical embryonic stage, and its expression is essential in different tissues from its parental gene. Functional genomic analyses found thatCocoongained multiple DNA binding targets, which regulates the expression of genes that have other essential functions and/or have multiple gene-gene interactions. Our observations suggest thatCocoonacquired essential function to survival through forming interactions that have large impacts on the gene interaction network. Our study is an important step towards deciphering the evolutionary trajectory by which new genes functionally diverge from the parental gene and become essential.
Tau hyperphosphorylation on T217 in cerebrospinal fluid is specifically associated to amyloid-β pathology
Authors: Barthélemy Nicolas R. , Bateman Randall J. , Marin Philippe , Becher François , Sato Chihiro , Lehmann Sylvain , Gabelle Audrey
Published: December 2017

Introduction

Modification of CSF tau phosphorylation in AD remains controversial since total-tau and phospho-tau levels measured by immunoassays are highly correlated.

Methods

Stoichiometry of phosphorylation of CSF tau was monitored on five sites by mass spectrometry. We compared 50 participants with AD at mild to moderate stages, others tauopathies and controls then confirmed our results in a cohort of 86 participants cognitively normal or with mild cognitive impairment and stratified according to amyloid-β status.

Results

Changes in tau phosphorylation rates were observed in AD participants but not in other tauopathies. T181 appeared slightly hyperphosphorylated in AD. In comparison, T217 phosphorylation, was considerably modified. We demonstrated T217 hyperphosphorylation occurred systematically in amyloid positive participants even at preclinical stage (AUC 0.999). T217 phosphorylation change specificity overpasses other phosphorylated tau sites investigated in this study, but also CSF total-tau and p-tau levels.

Discussion

CSF T217 hyperphosphorylation defines a specific tauopathy status concomitant with ß-amyloidosis.
Gene Expression Distribution Deconvolution in Single Cell RNA Sequencing
Authors: Wang Jingshu , Huang Mo , Torre Eduardo , Dueck Hannah , Shaffer Sydney , Murray John , Raj Arjun , Li Mingyao , Zhang Nancy R.
Published: December 2017

Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene’s expression distribution across cells, thus allowing the assessment of the dispersion, burstiness, and other aspects of its distribution beyond the mean. These statistical characterizations of the gene expression distribution are critical for understanding expression variation and for selecting marker genes for population heterogeneity. However, scRNA-seq data is noisy, with each cell typically sequenced at low coverage, thus making it difficult to infer properties of the gene expression distribution from raw counts. Based on a re-examination of 9 public data sets, we propose a simple technical noise model for scRNA-seq data with Unique Molecular Identifiers (UMI). We develop DESCEND, a method that deconvolves the true cross-cell gene expression distribution from observed scRNA-seq counts, leading to improved estimates of properties of the distribution such as dispersion and burstiness. DESCEND can adjust for cell-level covariates such as cell size, cell cycle and batch effects. DESCEND’s noise model and estimation accuracy are further evaluated through comparisons to RNA FISH data, through data splitting and simulations, and through its effectiveness in removing known batch effects. We demonstrate how DESCEND can clarify and improve downstream analyses such as finding differentially bursty genes, identifying cell types, and selecting differentiation markers.
The GCTx format and cmap{Py, R, M} packages: resources for the optimized storage and integrated traversal of dense matrices of data and annotations
Authors: Enache Oana M. , Lahr David L. , Natoli Ted E. , Litichevskiy Lev , Wadden David , Flynn Corey , Gould Joshua , Asiedu Jacob K. , Narayan Rajiv , Subramanian Aravind
Published: December 2017

Motivation

Computational analysis of datasets generated by treating cells with pharmacological and genetic perturbagens has proven useful for the discovery of functional relationships. Facilitated by technological improvements, perturbational datasets have grown in recent years to include millions of experiments. While initial studies, such as our work on Connectivity Map, used gene expression readouts, recent studies from the NIH LINCS consortium have expanded to a more diverse set of molecular readouts, including proteomic and cell morphological signatures. Sharing these diverse data creates many opportunities for research and discovery, but the unprecedented size of data generated and the complex metadata associated with experiments have also created fundamental technical challenges regarding data storage and cross-assay integration.

Results

We present the GCTx file format and a suite of open-source packages for the efficient storage, serialization, and analysis of dense two-dimensional matrices. The utility of this format is not just theoretical; we have extensively used the format in the Connectivity Map to assemble and share massive data sets comprising 1.7 million experiments. We anticipate that the generalizability of the GCTx format, paired with code libraries that we provide, will stimulate wider adoption and lower barriers for integrated cross-assay analysis and algorithm development.

Availability

Software packages (available in Matlab, Python, and R) are freely available athttps://github.com/cmap

Supplementary information

Supplementary information is available at clue.io/code.

Contact

oana@broadinstitute.org
SNPTB: nucleotide variant identification and annotation in Mycobacterium tuberculosis genomes
Authors: Gupta Aditi
Published: December 2017

Whole genome sequencing (WGS) has become a mainstay in biomedical research. The continually decreasing cost of sequencing has resulted in a data deluge that underlines the need for easy-to-use bioinformatics pipelines that can mine meaningful information from WGS data. SNPTB is one such pipeline that analyzes WGS data originating from in vitro or clinical samples of Mycobacterium tuberculosis and outputs high-confidence single nucleotide polymorphisms in the bacterial genome. The name of the mutated gene and the functional consequence of the mutation on the gene product is also determined. SNPTB utilizes open source software for WGS data analyses and is written primarily for biologists with minimal computational skills.

Availability and implementation

SNPTB is a python package and is available from https://github.com/aditi9783/SNPTB

Contact

ag1349@njms.rutgers.edu

Supplementary information

Tutorial for SNPTB is available at https://github.com/aditi9783/SNPTB/blob/master/docs/SNPTB_tutorial.md