bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Acceptability of Cariprazine in Acute Exacerbation of Schizophrenia
Authors: Zhao Ming-jun , Qin Bin , Wang Jin-bao , Zhang Yan-ping , Zhao Jian-ting , Mao Ya-ge , Zhang Xiang-yang , Zhang Rui-ling
Published: December 2017

Purpose

The purpose of this study was to assess the efficacy and acceptability of cariprazine treatment in acute exacerbation of schizophrenia.

Methods

This review included randomized controlled trials of patients with acute exacerbation of schizophrenia in relation to efficacy and acceptability. The efficacy outcomes were assessed by pooling standardized mean differences (SMDs) calculated from the difference in the reduction in the mean of the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive and negative scores, and response rate. The primary acceptability outcomes were determined by pooling the risk ratios (RRs) of discontinuation for any reason, the incidence of serious adverse events, and treatment emergent events.

Findings

Four randomized controlled trials consisting of 1843 patients met all inclusion and exclusion criteria. Efficacy analysis showed significant positive effects in relation to cariprazine therapy (SMD: −0.37, P < 0.00001 for PANSS total score change; SMD: −0.32, P < 0.00001 for PANSS positive score change; SMD: −0.32, P < 0.0001 for PANSS negative score change; RR, 1.41; 95% confidence interval [CI], 1.19–1.67; P < 0.0001 for response rate). For primary acceptability outcomes, less patients taking cariprazine discontinued treatment for any reason compared with patients receiving placebo (RR, 0.90; 95% CI, 0.78–1.04; P = 0.16). Significantly less patients on cariprazine had serious adverse events during the double-blind treatment period compared with patients taking placebo (RR, 0.55; 95% CI, 0.34–0.89; P = 0.01). Significantly more patients on cariprazine had treatment emergent events compared with those receiving placebo (RR, 1.10; 95% CI, 1.03–1.18; P = 0.006).

Implications

Results suggest that cariprazine may be an effective and acceptable treatment for schizophrenia and future research is warranted.
Improving the Clinical Pharmacologic Assessment of Abuse Potential
Authors: Sellers Edward M.
Published: December 2017

Purpose

This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance.

Procedures

The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk.

Findings

The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system–active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development.

Conclusions

If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.
Psychometric Evaluation of the Chinese Respiratory Distress Observation Scale on Critically Ill Patients With Cardiopulmonary Diseases
Authors: CHAN Ya-Hsiang , WU Hua-Shan , YEN Chih-Ching , CAMPBELL Margaret L.
Published: December 2017

Background:

Respiratory distress is a common and distressing experience that strikes most critically ill patients with cardiopulmonary diseases. Now, most dyspnea assessment tools rely on patient’s self-report. Only one instrument, the Respiratory Distress Observation Scale (RDOS), is valid for assessing respiratory distress when the patient cannot provide a dyspnea self-report.

Purpose:

The aims of this study were to develop the Chinese version of RDOS through two-way translation and examine its reliability and validity.

Methods:

The first step was the translation and back-translation to establish the Chinese RDOS and examine the semantic equivalence between the back-translation version and the original one. The second step was the psychometric testing of the Chinese RDOS including internal reliability, interrater reliability, concurrent validity, convergent validity, and content and construct validity.

Results:

The Chinese RDOS was reported with an internal consistency (Cronbach’s α value) of .73, an interobserver reliability of .97, and a content validity index of .97. In the conscious critically ill patients, significant correlations were found between the Chinese RDOS and Spielberger State Anxiety Inventory scores or Dyspnea Vertical Visual Analog Scale scores (r = .69 and r = .76, respectively; p < .001). In the unconscious critically ill patients, there was a significantly positive correlation between the Chinese RDOS scores and fraction of inspiration O2 (r = .26, p < .05) and a significantly negative correlation between the Chinese RDOS scores and saturation peripheral oxygen (SpO2; r = −.42, p = .001). In addition, it also could effectively identify the dyspnea differences between the first and last days in the intensive care units (p < .001).

Conclusions:

The Chinese RDOS showed good reliability and validity in conscious critically ill patients. The assessment with the Chinese RDOS could be completed within a short period no matter whether the assessor has nursing background in respiratory care or not. It could help the professionals systematically manage and track the change of respiratory distress in patients.
Testing the Psychometric Properties of the Postpartum Sleep Quality Scale in Turkish Women
Authors: BOZ İlkay , SELVI Nida
Published: December 2017

Background:

Postpartum sleeplessness has been observed to be an important health problem in Turkey. However, no scale is currently available to evaluate quality of sleep in Turkish postpartum women.

Purpose:

The aim of this study was to test the validity and reliability of the Turkish Postpartum Sleep Quality Scale (T-PSQS).

Methods:

The sample of this methodological study surveyed 100 women during their first 2 postpartum weeks. Data were obtained using a personal characteristics form and the PSQS. The PSQS is a 5-point scale ranging from 0 to 4. The validity of the PSQS was tested using content validity index and confirmatory and exploratory factor analyses, and the reliability of the scale was tested using Cronbach’s alpha.

Results:

The opinions of eight experts were canvassed to test the validity of the T-PSQS. The content validity index showed that the scale had high validity (.92). The factor analysis that was conducted to test the construct validity of the scale indicated that the scale was composed of three factors with eigenvalues over 1.00 and that the total Cronbach’s alpha coefficient was .88. The Cronbach’s alpha for the subscales “Infant night care-related daytime dysfunction,” “ Physical symptoms-related sleep inefficiency,” and “Sleep quality or sleep” were .82, .86, and .80, respectively.

Conclusions:

Content validity, construct validity, and reliability analyses of the T-PSQS revealed that the scale may be used to measure postpartum sleeplessness levels and sleep quality in Turkish women.
A Cryptic NUP214-ABL1 Fusion in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Tsujimoto Shin-ichi , Nakano Yoshiko , Osumi Tomoo , Okada Keiko , Ouchi-Uchiyama Meri , Kataoka Keisuke , Fujii Yoichi , Ohki Kentaro , Seki Masafumi , Tamagawa Nobuyoshi , Takita Junko , Ogawa Seishi , Kiyokawa Nobutaka , Hara Junichi , Kato Motohiro
Published: December 2017

Fluorescent in situ hybridization (FISH) analysis is the standard methods for screening ABL1 fusions, which is recurrently translocated in pediatric acute lymphoblastic leukemia (ALL), and potentially targetable by kinase inhibitors. Here we demonstrated a case of B-cell precursor ALL with NUP214-ABL1 fusion, which break-apart FISH assay for ABL1 failed to detect. The cryptic fusion was generated by small duplication from ABL1 to NUP214, which was detected by copy number analysis using genomic microarray and confirmed by PCR. In the context of precision medicine, we should establish how to screen targetable abnormalities for minimizing risk of false-negative.
The Relationship Between Childhood Trauma and Poor Sleep Health in Adulthood
Authors: Brindle Ryan C. , Cribbet Matthew R. , Samuelsson Laura B. , Gao Chenlu , Frank Ellen , Krafty Robert T. , Thayer Julian F. , Buysse Daniel J. , Hall Martica H.
Published: December 2017

Objective

Childhood trauma has been related to adverse behavioral, mental, and health outcomes later in life. Sleep may be a potential mechanism through which childhood trauma is related to adverse health. The current retrospective study aimed to characterize the relationship between childhood trauma exposure and sleep health, a novel multidimensional measure of sleep.

Methods

Participants (N = 161; mean [standard deviation] age = 59.85 [9.06] years; 67.7% female) retrospectively reported trauma exposure using the Trauma History Questionnaire. Childhood trauma was defined as the number of reported traumatic events before 18 years of age. Trauma exposure after 18 years of age and across the life-span was also recorded. Sleep health was derived both from diary- and actigraphy-assessed measures of sleep regularity, timing, efficiency, and duration, subjective sleep satisfaction, and daytime sleepiness from the Epworth Sleepiness Scale. The relationships between childhood trauma exposure and sleep health were examined using hierarchical linear regression, controlling for relevant covariates.

Results

In unadjusted models, a greater number of childhood trauma exposures were associated with poorer diary- and actigraphy-measured sleep health in adulthood. After adjustment for current stress, depression history, and other sociodemographic covariates, greater childhood trauma remained significantly associated with poorer sleep health (diary: β = −0.20, ΔR
2 = 0.032; actigraphy: β = −0.19, ΔR
2 = 0.027). Trauma exposure after 18 years of age and across the life-span did not relate to diary- or actigraphy-based sleep health.

Conclusions

Childhood trauma may affect sleep health in adulthood. These findings align with the growing body of evidence linking childhood trauma to adverse health outcomes later in life.
Child and Adult Socioeconomic Status and the Cortisol Response to Acute Stress: Evidence From the Multi-Ethnic Study of Atherosclerosis
Authors: Lê-Scherban Félice , Brenner Allison B. , Hicken Margaret T. , Needham Belinda L. , Seeman Teresa , Sloan Richard P. , Wang Xu , Diez Roux Ana V.
Published: December 2017

Objective

A long-hypothesized pathway through which low socioeconomic status (SES) harms health is through dysregulation of the physiologic stress response systems. No previous studies have tested this hypothesis by investigating cortisol reactivity and recovery to acute stress in relation to SES at different times in the life course in adults. Alteration of the cortisol response to an acute stressor could signal dysregulation of the hypothalamic-pituitary-adrenal axis and has been associated with chronic illness.

Methods

We used data on 997 adults 54 years or older from a multiethnic, multisite United States study to examine associations between life course SES and cortisol response to a laboratory stress challenge. Informed by life course theory, we hypothesized that lower child and adult SES would be associated with lower reactivity (i.e., smaller increase in cortisol) and a slower recovery rate (i.e., slower rate of decline in cortisol after the challenge).

Results

In demographics-adjusted multilevel piecewise linear regression models, low child and adult SES were associated with a 19% (95% CI = 4%–50%) and 27% (7%–55%) slower recovery rate compared with high child and adult SES, respectively. Compared with participants with stable high SES, those with stable low SES had a 48% (16%–70%) slower recovery rate. Differences in reactivity by SES were small.

Conclusions

Our results support the hypothesis that low SES throughout life affects the hypothalamic-pituitary-adrenal axis and in turn the ability to recover from exposure to acute stressors. This mechanism can help explain how socioeconomic disparities contribute to disparities in chronic disease.
Quantifying Dental Office–Originating Adverse Events: The Dental Practice Study Methods
Authors: Tokede Oluwabunmi , Walji Muhammad , Ramoni Rachel , Rindal Donald B. , Worley Donald , Hebballi Nutan , Kumar Krishna , van Strien Claire , Chen Mengxia , Navat-Pelli Shaked , Liu Hongchun , Etolue Jini , Yansane Alfa , Obadan-Udoh Enihomo , Easterday Casey , Enstad Chris , Kane Sheryl , Rush William , Kalenderian Elsbeth
Published: December 2017

Background

Preventable medical errors in hospital settings are the third leading cause of deaths in the United States. However, less is known about harm that occurs in patients in outpatient settings, where the majority of care is delivered. We do not know the likelihood that a patient sitting in a dentist chair will experience harm. Additionally, we do not know if patients of certain race, age, sex, or socioeconomic status disproportionately experience iatrogenic harm.

Methods

We initiated the Dental Practice Study (DPS) with the aim of determining the frequency and types of adverse events (AEs) that occur in dentistry on the basis of retrospective chart audit. This article discusses the 6-month pilot phase of the DPS during which we explored the feasibility and efficiency of our multistaged review process to detect AEs.

Results

At sites 1, 2, and 3, respectively, 2 reviewers abstracted 21, 11, and 23 probable AEs, respectively, from the 100 patient charts audited per site. At site 2, a third reviewer audited the same 100 charts and found only 1 additional probable AE. Of the total 56 probable AEs (from 300 charts), the expert panel confirmed 9 AE cases. This equals 3 AEs per 100 patients per year. Patients who experienced an AE tended to be male and older and to have undergone more procedures within the study year.

Conclusions

This article presents an overview of the DPS. It describes the methods used and summarizes the results of its pilot phase. To minimize threats to dental patient safety, a starting point is to understand their basic epidemiology, both in terms of their frequency and the extent to which they affect different populations.
Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival
Authors: De Giacomi Federica , Raghunath Sushravya , Karwoski Ronald , Bartholmai Brian J. , Moua Teng
Published: December 2017

Purpose:

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP).

Materials and Methods:

Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings.

Results:

IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, −6.3% vs. −1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (−220 vs. −37.7 mL; P=0.045) and total lung volumes (−198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality.

Conclusions:

Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.
Soluble Epoxide Hydrolase Plays a Vital Role in Angiotensin II-Induced Lung Injury in Mice
Authors: Tao Wei , Li Ping-Song , Xu Gang , Luo Yi , Shu Yu-Sheng , Tao Yong-Zhong , Yang Liu-Qing
Published: December 2017

Background:

Angiotensin II plays a vital role in the pathogenesis of acute respiratory distress syndrome (ARDS). However, its mechanism is not well defined. Angiotensin II upregulates the expression of soluble epoxide hydrolase (sEH; Ephx2). sEH is suggested as a potential pharmacologic target for ARDS. The present study investigates whether the sEH is involved in the angiotensin II-triggered pulmonary inflammation and edema using an angiotensin II-induced lung injury animal model.

Methods:

Lung injury was induced by angiotensin II intratracheally instillation in wild-type or Ephx2 deficient mice.

Results:

sEH activities were markedly increased in wild-type mice treated with angiotensin II. Angiotensin II markedly increased the levels of tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid, worsened alveolar capillary protein leak and lung histological alterations, and elevated activity of activator protein-1 and nuclear factor-κB. However, these changes were significantly improved in Ephx2 deficient mice. Moreover, Losartan, an angiotensin II receptor 1 antagonist, abolished the sEH induction and improved mortality.

Conclusions:

Angiotensin II-induced lung injury was improved in sEH gene deleted mice. The angiotensin II-triggered pulmonary inflammation is mediated, at least in part, through the sEH.
Development of Noninvasive in Vivo Approach to Assess Vascular Permeability in Inflammation Using Fluorescence Imaging
Authors: Shimazui Takashi , Nakada Taka-aki , Fujimura Lisa , Sakamoto Akemi , Hatano Masahiko , Oda Shigeto
Published: December 2017

Introduction:

In vivo fluorescence imaging can quantify vascular permeability without requiring sacrifice of animals. However, use of this noninvasive approach for vascular permeability assessment in remote organ injury caused by systemic inflammatory disease has not been reported.

Methods:

Evans blue (EB) and Genhance 750 fluorescent dye were mixed and injected into mice. The lung as a remote organ and the footpad as a noninvasive observational site were assessed in a cecal ligation and puncture (CLP)-induced systemic inflammation mouse model and compared with sham and hydrocortisone pretreated (CLP + HC) mouse models. Extraction of EB in harvested tissues was assessed as a conventional indicator of vascular permeability. Fluorescent intensities in the footpad or harvested lung were assessed and their correlation was analyzed to investigate this novel, noninvasive approach for estimation of lung vascular permeability.

Results:

Fluorescent intensity in the footpad and harvested lung in the CLP group was significantly higher than in the other groups (footpad, sham vs. CLP, P < 0.0001; CLP vs. CLP + HC, P = 0.0004; sham vs. CLP + HC, P = 0.058; lung, sham vs. CLP, P < 0.0001; CLP vs. CLP + HC, P < 0.0001; sham vs. CLP + HC, P = 0.060). The fluorescent intensity in the footpad was strongly correlated with that in the lung (r = 0.95).

Conclusions:

This fluorescent technique may be useful for vascular permeability assessment based on EB quantification. Footpad fluorescent intensity was strongly correlated with that in the lung, and may be a suitable indicator in noninvasive estimation of lung vascular permeability.
Does oxidative stress shorten telomeres
in vivo
? A review
Authors: Reichert Sophie , Stier Antoine
Published: December 2017

The length of telomeres, the protective caps of chromosomes, is increasingly used as a biomarker of individual health state because it has been shown to predict chances of survival in a range of endothermic species including humans. Oxidative stress is presumed to be a major cause of telomere shortening, but most evidence to date comes from
in vitro
cultured cells. The importance of oxidative stress as a determinant of telomere shortening
in vivo
remains less clear and has recently been questioned. We, therefore, reviewed correlative and experimental studies investigating the links between oxidative stress and telomere shortening
in vivo
. While correlative studies provide equivocal support for a connection between oxidative stress and telomere attrition (10 of 18 studies), most experimental studies published so far (seven of eight studies) partially or fully support this hypothesis. Yet, this link seems to be tissue-dependent in some cases, or restricted to particular categories of individual (e.g. sex-dependent) in other cases. More experimental studies, especially those decreasing antioxidant protection or increasing pro-oxidant generation, are required to further our understanding of the importance of oxidative stress in determining telomere length
in vivo
. Studies comparing growing versus adult individuals, or proliferative versus non-proliferative tissues would provide particularly important insights.
Heterothermy is associated with reduced fitness in wild rabbits
Authors: Maloney Shane K. , Marsh Maija K. , McLeod Steven R. , Fuller Andrea
Published: December 2017

An increase in variation in the 24 h pattern of body temperature (heterothermy) in mammals can be induced by energy and water deficits. Since performance traits such as growth and reproduction also are impacted by energy and water balance, we investigated whether the characteristics of the body temperature rhythm provide an indication of the reproductive success of an individual. We show that the amplitude of the daily rhythm of body temperature in wild rabbits (
Oryctolagus cuniculus
) prior to breeding is inversely related to the number of pregnancies in the subsequent seven months, while the minimum daily body temperature is positively correlated to the number of pregnancies. Because reproductive output could be predicted from characteristics of the core body temperature rhythm prior to the breeding season, we propose that the pattern of the 24 h body temperature rhythm could provide an index of animal fitness in a given environment.
Graph-facilitated resonant mode counting in stochastic interaction networks
Authors: Adamer Michael F. , Woolley Thomas E. , Harrington Heather A.
Published: December 2017

Oscillations in dynamical systems are widely reported in multiple branches of applied mathematics. Critically, even a non-oscillatory deterministic system can produce cyclic trajectories when it is in a low copy number, stochastic regime. Common methods of finding parameter ranges for stochastically driven resonances, such as direct calculation, are cumbersome for any but the smallest networks. In this paper, we provide a systematic framework to efficiently determine the number of resonant modes and parameter ranges for stochastic oscillations relying on real root counting algorithms and graph theoretic methods. We argue that stochastic resonance is a network property by showing that resonant modes only depend on the squared Jacobian matrix
J
2
, unlike deterministic oscillations which are determined by
J
. By using graph theoretic tools, analysis of stochastic behaviour for larger interaction networks is simplified and stochastic dynamical systems with multiple resonant modes can be identified easily.
The interaction between electromagnetic fields at megahertz, gigahertz and terahertz frequencies with cells, tissues and organisms: risks and potential
Authors: Romanenko Sergii , Begley Ryan , Harvey Alan R. , Hool Livia , Wallace Vincent P.
Published: December 2017

Since regular radio broadcasts started in the 1920s, the exposure to human-made electromagnetic fields has steadily increased. These days we are not only exposed to radio waves but also other frequencies from a variety of sources, mainly from communication and security devices. Considering that nearly all biological systems interact with electromagnetic fields, understanding the affects is essential for safety and technological progress. This paper systematically reviews the role and effects of static and pulsed radio frequencies (100–109Hz), millimetre waves (MMWs) or gigahertz (109–1011Hz), and terahertz (1011–1013Hz) on various biomolecules, cells and tissues. Electromagnetic fields have been shown to affect the activity in cell membranes (sodium versus potassium ion conductivities) and non-selective channels, transmembrane potentials and even the cell cycle. Particular attention is given to millimetre and terahertz radiation due to their increasing utilization and, hence, increasing human exposure. MMWs are known to alter active transport across cell membranes, and it has been reported that terahertz radiation may interfere with DNA and cause genomic instabilities. These and other phenomena are discussed along with the discrepancies and controversies from published studies.
Membrane capacitance of thousands of single white blood cells
Authors: Wang Ke , Chang Chun-Chieh , Chiu Tzu-Keng , Zhao Xiaoting , Chen Deyong , Chou Wen-Pin , Zhao Yang , Wang Hung-Ming , Wang Junbo , Wu Min-Hsien , Chen Jian
Published: December 2017

As label-free biomarkers, the electrical properties of single cells are widely used for cell type classification and cellular status evaluation. However, as intrinsic cellular electrical markers, previously reported membrane capacitances (e.g. specific membrane capacitance
C
spec
and total membrane capacitance
C
mem
) of white blood cells were derived from tens of single cells, lacking statistical significance due to low cell numbers. In this study, white blood cells were first separated into granulocytes and lymphocytes by density gradient centrifugation and were then aspirated through a microfluidic constriction channel to characterize both
C
spec
and
C
mem
. Thousands of granulocytes (
n
cell
= 3327) and lymphocytes (
n
cell
= 3302) from 10 healthy blood donors were characterized, resulting in
C
spec
values of 1.95 ± 0.22 µF cm
−2
versus 2.39 ± 0.39 µF cm
−2
and
C
mem
values of 6.81 ± 1.09 pF versus 4.63 ± 0.57 pF. Statistically significant differences between granulocytes and lymphocytes were located for both
C
spec
and
C
mem
. In addition, neural network-based pattern recognition was used to classify white blood cells, producing successful classification rates of 78.1% for
C
spec
and 91.3% for
C
mem
, respectively. These results indicate that as intrinsic bioelectrical markers, membrane capacitances may contribute to the classification of white blood cells.
Large-scale molecular dynamics simulation of coupled dynamics of flow and glycocalyx: towards understanding atomic events on an endothelial cell surface
Authors: Jiang Xi Zhuo , Gong Haipeng , Luo Kai Hong , Ventikos Yiannis
Published: December 2017

The glycocalyx has a prominent role in orchestrating multiple biological processes occurring at the plasma membrane. In this paper, an all-atom flow/glycocalyx system is constructed with the bulk flow velocity in the physiologically relevant ranges for the first time. The system is simulated by molecular dynamics using 5.8 million atoms. Flow dynamics and statistics in the presence of the glycocalyx are presented and discussed. Complex dynamic behaviours of the glycocalyx, particularly the sugar chains, are observed in response to blood flow. In turn, the motion of the glycocalyx, including swing and swirling, disturbs the flow by altering the velocity profiles and modifying the vorticity distributions. As a result, the initially one-dimensional forcing is spread to all directions in the region near the endothelial cell surface. Furthermore, the coupled dynamics exist not only between the flow and the glycocalyx but also within the glycocalyx molecular constituents. Shear stress distributions between one-dimer and three-dimer cases are also conducted. Finally, potential force transmission pathways are discussed based on the dynamics of the glycocalyx constituents, which provides new insight into the mechanism of mechanotransduction of the glycocalyx. These findings have relevance in the pathologies of glycocalyx-related diseases, for example in renal or cardiovascular conditions.
Evidence for a sex effect during overimitation: boys copy irrelevant modelled actions more than girls across cultures
Authors: Frick Aurélien , Clément Fabrice , Gruber Thibaud
Published: December 2017

Children are skilful at acquiring tool-using skills by faithfully copying relevant and irrelevant actions performed by others, but poor at innovating tools to solve problems. Five- to twelve-year-old urban French and rural Serbian children (N = 208) were exposed to aHook task; a jar containing a reward in a bucket and a pipe cleaner as potential recovering tool material. In both countries, few children under the age of 10 made a hook from the pipe cleaner to retrieve the reward on their own. However, from five onward, the majority of unsuccessful children succeeded after seeing an adult model manufacturing a hook without completing the task. Additionally, a third of the children who observed a similar demonstration including an irrelevant action performed with a second object, a string, replicated this meaningless action. Children's difficulty with innovation and early capacity for overimitation thus do not depend on socio-economic background. Strikingly, we document a sex difference in overimitation across cultures, with boys engaging more in overimitation than girls, a finding that may result from differences regarding explorative tool-related behaviour. This male-biased sex effect sheds new light on our understanding of overimitation, and more generally, on how human tool culture evolved.
Acoustic monitoring of coastal dolphins and their response to naval mine neutralization exercises
Authors: Lammers Marc O. , Howe Marian , Zang Eden , McElligott Megan , Engelhaupt Amy , Munger Lisa
Published: December 2017

To investigate the potential impacts of naval mine neutralization exercises (MINEX) on odontocete cetaceans, a long-term passive acoustic monitoring study was conducted at a US Navy training range near Virginia Beach, USA. Bottom-moored acoustic recorders were deployed in 2012–2016 near the epicentre of MINEX training activity and were refurbished every 2–4 months. Recordings were analysed for the daily presence/absence of dolphins, and dolphin acoustic activity was quantified in detail for the hours and days before and after 31 MINEX training events. Dolphins occurred in the area year-round, but there was clear seasonal variability, with lower presence during winter months. Dolphins exhibited a behavioural response to underwater detonations. Dolphin acoustic activity near the training location was lower during the hours and days following detonations, suggesting that animals left the area and/or reduced their signalling. Concurrent acoustic monitoring farther away from the training area suggested that the radius of response was between 3 and 6 km. A generalized additive model indicated that the predictors that explained the greatest amount of deviance in the data were the day relative to the training event, the hour of the day and circumstances specific to each training event.
Quantifying team cooperation through intrinsic multi-scale measures: respiratory and cardiac synchronization in choir singers and surgical teams
Authors: Hemakom Apit , Powezka Katarzyna , Goverdovsky Valentin , Jaffer Usman , Mandic Danilo P.
Published: December 2017

A highly localized data-association measure, termed intrinsic synchrosqueezing transform (ISC), is proposed for the analysis of coupled nonlinear and non-stationary multivariate signals. This is achieved based on a combination of noise-assisted multivariate empirical mode decomposition and short-time Fourier transform-based univariate and multivariate synchrosqueezing transforms. It is shown that the ISC outperforms six other combinations of algorithms in estimating degrees of synchrony in synthetic linear and nonlinear bivariate signals. Its advantage is further illustrated in the precise identification of the synchronized respiratory and heart rate variability frequencies among a subset of bass singers of a professional choir, where it distinctly exhibits better performance than the continuous wavelet transform-based ISC. We also introduce an extension to the intrinsic phase synchrony (IPS) measure, referred to as nested intrinsic phase synchrony (N-IPS), for the empirical quantification of physically meaningful and straightforward-to-interpret trends in phase synchrony. The N-IPS is employed to reveal physically meaningful variations in the levels of cooperation in choir singing and performing a surgical procedure. Both the proposed techniques successfully reveal degrees of synchronization of the physiological signals in two different aspects: (i) precise localization of synchrony in time and frequency (ISC), and (ii) large-scale analysis for the empirical quantification of physically meaningful trends in synchrony (N-IPS).
Neutral genetic variation in adult Chinook salmon (
Oncorhynchus tshawytscha
) affects brain-to-body trade-off and brain laterality
Authors: Wiper Mallory L. , Lehnert Sarah J. , Heath Daniel D. , Higgs Dennis M.
Published: December 2017

Low levels of heterozygosity can have detrimental effects on life history and growth characteristics of organisms but more subtle effects such as those on trade-offs of expensive tissues and morphological laterality, especially of the brain, have not been explicitly tested. The objective of the current study was to investigate how estimated differences in heterozygosity may potentially affect brain-to-body trade-offs and to explore how these heterozygosity differences may affect differential brain growth, focusing on directional asymmetry in adult Chinook salmon (
Oncorhynchus tshawytscha
) using the laterality and absolute laterality indices. Level of inbreeding was estimated as mean microsatellite heterozygosity resulting in four ‘inbreeding level groups’ (Very High, High, Medium, Low). A higher inbreeding level corresponded with a decreased brain-to-body ratio, thus a decrease in investment in brain tissue, and also showed a decrease in the laterality index for the cerebellum, where the left hemisphere was larger than the right across all groups. These results begin to show the role that differences in heterozygosity may play in differential tissue investment and in morphological laterality, and may be useful in two ways. Firstly, the results may be valuable for restocking programmes that wish to emphasize brain or body growth when crossing adults to generate individuals for release, as we show that genetic variation does affect these trade-offs. Secondly, this study is one of the first examinations to test the hypothesized relationship between genetic variation and laterality, finding that in Chinook salmon there is potential for an effect of inbreeding on lateralized morphology, but not in the expected direction.
Manganese molybdate nanoflakes on silicon microchannel plates as novel nano energetic material
Authors: Zhang Chi , Wu Dajun , Shi Liming , Zhu Yiping , Xiong Dayuan , Xu Shaohui , Huang Rong , Qi Ruijuan , Zhang Wenchao , Wang Lianwei , Chu Paul K.
Published: December 2017

Nano energetic materials have attracted great attention recently owing to their potential applications for both civilian and military purposes. By introducing silicon microchannel plates (Si-MCPs) three-dimensional (3D)-ordered structures, monocrystalline MnMoO4with a size of tens of micrometres and polycrystalline MnMoO4nanoflakes are produced on the surface and sidewall of nickel-coated Si-MCP, respectively. The MnMoO4crystals ripen controllably forming polycrystalline nanoflakes with lattice fringes of 0.542 nm corresponding to the(1¯11)plane on the sidewall. And these MnMoO4nanoflakes show apparent thermite performance which is rarely reported and represents MnMoO4becoming a new category of energetic materials after nanocrystallization. Additionally, the nanocrystallization mechanism is interpreted by ionic diffusion caused by 3D structure. The results indicate that the Si-MCP is a promising substrate for nanocrystallization of energetic materials such as MnMoO4.
The genus
Gennadas
(Benthesicymidae: Decapoda): morphology of copulatory characters, phylogeny and coevolution of genital structures
Authors: Vereshchaka Alexander L. , Lunina Anastasia A. , Olesen Jørgen
Published: December 2017

Species within
Gennadas
differ from each other largely only in male (petasma) and female (thelycum) copulatory characters, which were restudied in scanning electron microscopy and used as a basis for phylogenetic analyses. Twenty-six petasma characters and 49 thelycum characters were identified. All 16 recognized species of
Gennadas
and
Aristaeomorpha foliacea
(outgroup) were included as terminals. Four robust monophyletic clades were retrieved, described and diagnosed as new species groups. The thelycum characters had greater impact on tree topology and supported deeper nodes than did the petasma characters. We hypothesize that features of the thelycum evolved first followed by aspects of the petasma. Relatively more conservative characters include parts of the sternites of the thelycum and of the petasma, while the scuti and protuberances on the thelycum and the shape and subdivisions of the petasma lobes are evolutionarily plastic. We identified two groups of copulatory characters, which are likely coupled functionally and interlinked evolutionarily: (i) the external part of the petasma and the posterior part of the thelycum and (ii) the internal part of the petasma and anterior part of the thelycum. We reconstruct possible mating position during copulation for each of the new species groups presented here. We also present an updated key to genera of Benthesicymidae and key to species of
Gennadas
.
On the characterization of vortex configurations in the steady rotating Bose–Einstein condensates
Authors: Kevrekidis P. G. , Pelinovsky D. E.
Published: December 2017

Motivated by experiments in atomic Bose–Einstein condensates (BECs), we compare predictions of a system of ordinary differential equations (ODEs) for dynamics of one and two individual vortices in the rotating BECs with those of the Gross–Pitaevskii mean-field model written as a partial differential equation (PDE). In particular, we characterize orbitally stable vortex configurations in a symmetric harmonic trap due to a cubic repulsive interaction and a steady rotation. The ODE system is analysed in detail and the PDE model is approximated numerically. Good agreement between the two models is established in the semi-classical (Thomas–Fermi) limit that corresponds to the BECs at large values of the chemical potential.
Condition-dependent female preference for male genitalia length is based on male reproductive tactics
Authors: Hernandez-Jimenez Armando , Rios-Cardenas Oscar
Published: December 2017

There is extensive morphological variation of male genitalia across animals with internal fertilization, even among closely related species. Most studies attempting to explain this extraordinary diversity have focused on processes that occur post-copula (e.g. sperm competition, cryptic female choice). Only a few studies have focused on the pre-copula process of female preference. In addition, the extent to which this variation could be associated with the use of different reproductive tactics has yet to be explored. Here, we show that female preference for male genitalia length in two livebearing fishes depends on the type of reproductive tactic of the males being evaluated as well as the body condition of the female. In a species where all males coax females to acquire matings (courters), females preferred males with short genitalia. In a species with genetically influenced alternative reproductive tactics (courter males that only court and produce courter sons, sneaker males that use the coercive tactic of sneak chase and produce sneaker sons), female preference depended on an interaction between male tactic and female condition: females in good condition preferred courter males with short genitalia, and sneaker males with long genitalia. Our results suggest that female preference for male traits favourable to their sons may be an important factor contributing to the diversification of male genitalia. Despite the contrasting selection for genitalia length that our female preference tests suggest, we found no significant differences in genitalia length between coaxing (courters) and coercive (sneakers) males. Our study represents a starting point to more clearly understand the role of alternative reproductive tactics and variation in female mate preference in the evolution of male genitalia.
Aging and neurodegeneration are associated with increased mutations in single human neurons
Authors: Lodato Michael A. , Rodin Rachel E. , Bohrson Craig L. , Coulter Michael E. , Barton Alison R. , Kwon Minseok , Sherman Maxwell A. , Vitzthum Carl M. , Luquette Lovelace J. , Yandava Chandri , Yang Pengwei , Chittenden Thomas W. , Hatem Nicole E. , Ryu Steven C. , Woodworth Mollie B. , Park Peter J. , Walsh Christopher A.
Published: December 2017

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of fifteen normal individuals (aged 4 months to 82 years) as well as nine individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and Xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures, and may be important in other human age-associated conditions.

One-Sentence Summary

Somatic single-nucleotide variants accumulate in human neurons in aging with regional specificity and in progeroid diseases.
Loss of the intellectual disability and autism gene Cc2d1a and its homolog Cc2d1b differentially affect spatial memory, anxiety, and hyperactivity
Authors: Zamarbide Marta , Oaks Adam W. , Pond Heather L. , Adelman Julia S. , Manzini M. Chiara
Published: December 2017

Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1A cause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a-deficient mice present with cognitive and social deficits, hyperactivity and anxiety. In Drosophila loss of the only ortholog of Cc2d1a, lgd, is embryonic lethal, while in vertebrates Cc2d1a has a homolog Cc2d1b which appears to be compensating, indicating that Cc2d1a and Cc2d1b have redundant function in humans and mice. Here, we generate an allelic series of Cc2d1a and Cc2d1b loss of function to determine the relative role of these genes during behavioral development. We generated Cc2d1b knockout (KO), Cc2d1a/1b double heterozygous and double KO mice, then performed behavioral studies to analyze learning and memory, social interactions, anxiety, and hyperactivity. We found that Cc2d1a and Cc2d1b have partially overlapping roles. Overall, loss of Cc2d1b is less severe than loss of Cc2d1a, only leading to cognitive deficits, while Cc2d1a/1b double heterozygous animals are similar to Cc2d1a-deficient mice. These results will help us better understand the deficits in individuals with CC2D1A mutations, suggesting that recessive CC2D1B mutations and trans-heterozygous CC2D1A and CC2D1B mutations could also contribute to the genetics of ID.
Detecting cancer vulnerabilities through gene networks under purifying selection in 4,700 cancer genomes
Authors: Gupta Anika , Horn Heiko , Razaz Parisa , Kim April , Lawrence Michael , Getz Gad , Lage Kasper
Published: December 2017

Large-scale cancer sequencing studies have uncovered dozens of mutations critical to cancer initiation and progression. However, a significant proportion of genes linked to tumor propagation remain hidden, often due to noise in sequencing data confounding low frequency alterations. Further, genes in networks under purifying selection (NPS), or those that are mutated in cancers less frequently than would be expected by chance, may play crucial roles in sustaining cancers but have largely been overlooked. We describe here a statistical framework that identifies genes that have a first order protein interaction network significantly depleted for mutations, to elucidate key genetic contributors to cancers. Not reliant on and thus, unbiased by, the gene of interest’s mutation rate, our approach has identified 685 putative genes linked to cancer development. Comparative analysis indicates statistically significant enrichment of NPS genes in previously validated cancer vulnerability gene sets, while further identifying novel cancer-specific candidate gene targets. As more tumor genomes are sequenced, integrating systems level mutation data through this network approach should become increasingly useful in pinpointing gene targets for cancer diagnosis and treatment.
Experimental assay of a fitness landscape on a macroevolutionary scale
Authors: Pokusaeva Victoria O. , Usmanova Dinara R. , Putintseva Ekaterina V. , Espinar Lorena , Sarkisyan Karen S. , Mishin Alexander S. , Bogatyreva Natalya S. , Ivankov Dmitry N. , Akopyan Arseniy V. , Avvakumov Sergey Ya. , Povolotskaya Inna S. , Filion Guillaume J. , Carey Lucas B. , Kondrashov Fyodor A.
Published: December 2017

Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, substitutions are under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. Sign epistasis affected few genotypes but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.