bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between pain and frailty among Chinese community-dwelling older adults: depression as a mediator and its interaction with pain
Authors: Tian Xiaoyu , Wang Cuili , Qiao Xiaoxia , Liu Na , Dong Lijuan , Butler Mary , Si Huaxin , Jin Yaru
Published: November 2017

Pain and frailty are both prevalent and have severe health impacts among older adults. We conducted a cross-sectional observational study to examine the association between pain and frailty, and depression as a mediator and its interaction with pain on frailty among 1788 Chinese community-dwelling older adults. Physical frailty, pain intensity, and depressive symptoms were assessed using the Frailty Phenotype, the Faces Pain Scale-revised, and the 5-item Geriatric Depression Scale, respectively. We found that both pain (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.32-1.97) and depressive symptoms (OR = 4.67; 95% CI: 3.36-6.50) were positively associated with physical frailty (OR = 1.61; 95% CI: 1.32-1.97), and depressive symptoms were associated with pain (OR = 1.94; 95% CI: 1.15-3.39), attenuating the association between pain and physical frailty by 56.1%. Furthermore, older adults with both pain and depressive symptoms (OR = 8.13; 95% CI: 5.27-12.53) had a higher risk of physical frailty than those with pain (OR = 1.41; 95% CI: 1.14-1.76) or depressive symptoms (OR = 3.63; 95% CI: 2.25-5.85) alone. The relative excess risk of interaction, the attributable proportion due to interaction, and the synergy index (S) were 4.08, 0.50, and 2.34, respectively. These findings suggest that the positive association of pain with frailty is persistent and partially mediated by depression, and comorbid depression and pain have an additive interaction on physical frailty. It has an implication of multidisciplinary care for frail older adults with pain.
Tactile acuity (dys)function in acute nociceptive low back pain: a double-blind experiment
Authors: Adamczyk Wacław M. , Saulicz Oskar , Saulicz Edward , Luedtke Kerstin
Published: November 2017

Research shows that chronic pain is related to cortical alterations that can be reflected in reduced tactile acuity, but whether acute pain perception influences tactile acuity has not been tested. Considering the biological role of nociception, it was hypothesized that nociceptive pain will lead to a rapid improvement in tactile acuity and that this effect is correlated with pain intensity and pain distribution. In this randomised double-blind controlled experiment (trial no. NCT03021278), healthy participants were exposed to 1 of 3 experimental conditions: acute, nociceptive low back pain induced by saline injection, a sham injection (without piercing the skin) potentially inducing nocebo pain, or no intervention. Tactile acuity was measured by a battery of tests, including two-point discrimination threshold (TPD), before, during the pain experience, and after it subsided. We found that TPD did not improve but deteriorated during pain induction in the experimental group compared with the control group (P < 0.001; η2 = 0.20) and changed from 56.94 mm (95% confidence interval: 53.43-60.44) at baseline to 64.22 mm (95% confidence interval: 60.42-68.02) during the pain experience. Maximum reported pain was a significant predictor (β = 0.55, P = 0.01) and accounted for 26% of the variance in TPD (P < 0.05). Other tests, point-to-point test and two-point estimation task, changed with a similar trend but did not reach significance. We concluded that acute, nociceptive pain does not improve but deteriorates tactile acuity linearly. The biological role of the observed phenomenon is unknown, and therefore, future studies should address this question.
Surgical Management of Tumors Involving Meckel's Cave and Cavernous Sinus: Role of an Extended Middle Fossa and Lateral Sphenoidectomy Approach
Authors: Sun Daniel Q. , Menezes Arnold H. , Howard Matthew A. , Gantz Bruce J. , Hasan David M. , Hansen Marlan R.
Published: November 2017

Objective:

To study the indications and outcomes of lateral sphenoidectomy as part of a combined skull base approach in the treatment of tumors involving Meckel's cave (MC) and cavernous sinus (CS).

Study Design:

Retrospective patient series.

Setting:

Tertiary referral center.

Patients:

Twenty-two consecutive patients (mean age: 45 yr, range: 16–76) who underwent transzygomatic, extended middle fossa approaches for tumors involving MC and CS.

Interventions:

Surgical access to MC and CS was achieved via extended middle fossa, trans-clinoid approach. Lateral sphenoidectomy was defined as drill-out of the greater sphenoid wing lateral to foramen rotundum and ovale, decompression of superior orbital fissure, and removal of anterior clinoid process. Reconstruction was achieved using combination of autologous and synthetic materials. Eleven patients (50%) received adjuvant radiation.

Main Outcome Measures and Results:

Tumor pathologies included meningioma (16 patients), epidermoid cyst (2), trigeminal schwannoma (2), invasive pituitary adenoma (1), and chondrosarcoma (1). Mean (range) preoperative tumor size was 4.0 cm (1.3–9). Mean (range) length of follow-up was 4 years (range 0.1–10). Overall tumor control and gross total resection were achieved in 95 and 23% of patients, respectively. Lateral sphenoidectomy was performed in 16 patients (73%) for enhanced surgical access and/or tumor extension to the infratemporal fossa (6 patients). Postoperatively, cranial nerve deficits occurred in 12 (55%) patients (V–9 patients; III, IV, or VI–4; VII–2; VIII–2). Cerebrospinal fluid leak and hydrocephalus occurred in two and four patients, respectively.

Conclusion:

In combination with middle fossa-based approaches to tumors involving MC and CS, lateral sphenoidectomy may play a viable role in tumor access and control.
Whole-body computed tomography in severely injured patients
Authors: Huber-Wagner Stefan , Kanz Karl-Georg , Hanschen Marc , van Griensven Martijn , Biberthaler Peter , Lefering Rolf
Published: November 2017

Purpose of review

To provide an update on the relevant and recent studies on whole-body computed tomography (WBCT) imaging of severely injured patients.

Recent findings

The advantages of WBCT in time saving, diagnostic accuracy and even in survival have been proven in numerous studies. WBCT can also be beneficial in haemodynamically unstable major trauma patients. The CT scanner should be located close to the emergency department or even in the trauma room. The issue of radiation is still quite important, however, iterative as well as split-bolus protocols can nowadays reduce radiation significantly. The question: which trauma patient should receive WBCT and which not is not yet solved sufficiently. Postmortem WBCT has a promising potential to promptly define the definitive cause of death of trauma victims comparably to traditional autopsy.

On account of the recent advances, whole-body CT has become a crucial part of the initial in-hospital assessment of severely injured patients. It is recommended as the standard radiological tool for the emergency diagnostic work-up in major trauma patients.
Carcinoid-syndrome: recent advances, current status and controversies
Authors: Ito Tetsuhide , Lee Lingaku , Jensen Robert T.
Published: November 2017

Purpose of review

To review recent advances and controversies in all aspects of carcinoid-syndrome.

Recent findings

Over the last few years there have been a number of advances in all aspects of carcinoid syndrome as well as new therapies. These include new studies on its epidemiology which demonstrate it is increasing in frequency; increasing insights into the pathogenesis of its various clinical manifestations and into its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history and management of carcinoid heart disease. These advances have generated several controversies and these are also reviewed.

There have been numerous advances in all aspects of the carcinoid-syndrome, which is the most common functional syndrome neuroendocrine tumors produce. These advances are leading to new approaches to the management of these patients and in some cases to new controversies.
Genomic Profiles of Neuroblastoma Associated With Opsoclonus Myoclonus Syndrome
Authors: Hero Barbara , Clement Nathalie , Øra Ingrid , Pierron Gaelle , Lapouble Eve , Theissen Jessica , Pasqualini Claudia , Valteau-Couanet Dominique , Plantaz Dominique , Michon Jean , Delattre Olivier , Tardieu Marc , Schleiermacher Gudrun
Published: November 2017

Opsoclonus myoclonus syndrome (OMS), often called “dancing eyed syndrome,” is a rare neurological condition associated with neuroblastoma in the majority of all childhood cases. Genomic copy number profiles have shown to be of prognostic significance for neuroblastoma patients. The aim of this retrospective multicenter study was to analyze the genomic copy number profiles of tumors from children with neuroblastoma presenting with OMS at diagnosis. In 44 cases of neuroblastoma associated with OMS, overall genomic profiling by either array-comparative genomic hybridization or single nucleotide polymorphism array proved successful in 91% of the cases, distinguishing tumors harboring segmental chromosome alterations from those with numerical chromosome alterations only. A total of 23/44 (52%) tumors showed an segmental chromosome alterations genomic profile, 16/44 (36%) an numerical chromosome alterations genomic profile, and 1 case displayed an atypical profile (12q amplicon). No recurrently small interstitial copy number alterations were identified. With no tumor relapse nor disease-related deaths, the overall genomic profile was not of prognostic impact with regard to the oncological outcome in this series of patients. Thus, the observation of an excellent oncological outcome, even for those with an unfavorable genomic profile of neuroblastoma, supports the hypothesis that an immune response might be involved in tumor control in these patients with OMS.
Reliability of translation of the RAND 36-item health survey in a post-rehabilitation population
Authors: Krops Leonie A. , Wolthuizen Linda , Dijkstra Pieter U. , Jaarsma Eva A. , Geertzen Jan H.B. , Dekker Rienk
Published: November 2017

The aim of this study is to evaluate the reliability of the RAND 36-item Health survey as a measure of health-related quality of life in a general Dutch post-rehabilitation population. A total of 752 ex-rehabilitation patients were invited to complete the Dutch RAND 36-item health survey. After 2 weeks, the people who responded to the first questionnaire were asked to complete the same questionnaire again. Internal consistency of the questionnaire was expressed as Cronbach’s α. Test–retest reliability was expressed as intraclass correlation coefficient (ICC) and presented in Bland–Altman plots. Internal consistency was found acceptable for all subscales (n=276; Cronbach’s α ranged from 0.81 to 0.95). Test–retest reliability was found acceptable for research and group comparisons for all subscales (n=184; ICC ranged from 0.71 to 0.88). Overall, test–retest reliability of the physical functioning (ICC=0.86), pain (ICC=0.87), and general health (ICC=0.88) subscale was relatively high, and that of health change (ICC=0.71) was relatively low. Reliability of the questionnaire did not notably differ between participants who indicated stable health and participants who indicated health change during the past weeks. In conclusion, the Dutch translation of the RAND 36-item health survey is reliable for research and group comparisons in a general post-rehabilitation population. However, the RAND 36-item health survey is not sufficiently reliable for individual comparisons within this population.
High-Stakes Testing in Nursing Education
Authors: Hunsicker Jamie , Chitwood Tara
Published: November 2017

In an aim to improve first-time NCLEX-RN pass rates, some nursing programs have instituted high-stakes testing. This literature review investigated nursing faculty understanding of and student experiences with high-stakes testing. High-stakes testing is an assessment used to make decisions about student progression or completion of a nursing program. The literature revealed both negative and positive consequences associated with high-stakes testing. Literature from state boards of nursing and professional nursing organizations was also reviewed for recommendations.
Verification of the Optimal Chest Compression Depth for Children in the 2015 American Heart Association Guidelines: Computed Tomography Study
Authors: Kim Yong Hwan , Lee Jun Ho , Cho Kwang Won , Lee Dong Woo , Kang Mun Ju , Lee Kyoung Yul , Byun Joung Hun , Lee Young Hwan , Hwang Seong Youn , Lee Na Kyoung
Published: November 2017

Objective:

The 2015 American Heart Association guidelines recommended pediatric rescue chest compressions of at least one-third the anteroposterior diameter of the chest, which equates to approximately 5 cm. This study evaluated the appropriateness of these two types by comparing their safeties in chest compression depth simulated by CT.

Design:

Retrospective study with data analysis conducted from January 2005 to June 2015

Setting:

Regional emergency center in South Korea.

Patients:

Three hundred forty-nine pediatric patients 1–9 years old who had a chest CT scan.

Interventions:

Simulation of chest compression depths by CT.

Measurements and Main Results:

Internal and external anteroposterior diameter of the chest and residual internal anteroposterior diameter after simulation were measured from CT scans. The safe cutoff levels were differently applied according to age. One-third external anteroposterior diameters were compared with an upper limit of chest compression depth recommended for adults. Primary outcomes were the rates of overcompression to evaluate safety. Overcompression was defined as a negative value of residual internal anteroposterior diameter—age-specific cutoff level. Using a compression of 5-cm depth simulated by chest CT, 16% of all children (55/349) were affected by overcompression. Those 1–3 years old were affected more than those 4–9 years old (p < 0.001). Upon one-third compression of chest anteroposterior depth, only one subject (0.3%) was affected by overcompression. Rate of one-third external anteroposterior diameter greater than 6 cm in children 8 and 9 years old was 16.1% and 33.3%, respectively.

Conclusions:

A chest compression depth of one-third anteroposterior might be more appropriate than the 5-cm depth chest compression for younger Korean children. But, one-third anteroposterior depth chest compression might induce deep compressions greater than an upper limit of compression depth for adults in older Korean children.
Risk Factors for Ventilator-Associated Events in a PICU*
Authors: Guess Raeley , Vaewpanich Jarin , Coss-Bu Jorge A. , Phongjitsiri Siriporn , Kennedy Curtis , Starke Jeffrey , Thammasitboon Satid
Published: November 2017

Objective:

The term ventilator-associated events includes ventilator-associated condition, infection-related ventilator-associated complication, and ventilator-associated pneumonia. We sought to identify potential new risk factors for ventilator-associated condition and infection-related ventilator-associated complication in the PICU population.

Design:

Matched case control study.

Setting:

Children’s hospital at a tertiary care academic medical center.

Patients:

During the study period, 606 patients were admitted to PICU and ventilated more than 48 hours; 70 children met ventilator-associated condition criteria.

Interventions:

None.

Measurements and Main Results:

We applied the definition for ventilator-associated condition (i.e., a sustained increase in ventilator settings after a period of stable or decreasing support) to our database. Within ventilator-associated condition cases, 40 cases were infection-related ventilator-associated complication and 30 cases were noninfectious-related ventilator-associated condition. We identified 140 controls and matched to ventilator-associated condition cases with regard to age, immunocompromised status, and ventilator days to event. Patients with ventilator-associated condition had longer ICU stay versus controls; 24 days median (12–43 interquartile range) versus 7 days (4–14); (p < 0.01), respectively, and longer duration of ventilatory support 17 days (10–32) versus 6 days (3–10); p < 0.01, respectively. Mortality was 22.8% in the ventilator-associated condition versus 9% in the control group (p < 0.01). A multivariate regression analysis adjusted for Pediatric Index of Mortality 2 identified mean peak inspiratory pressure and acute kidney injury to be associated with ventilator-associated condition (odds ratio, 1.12 [95% CI, 1.02–1.22] and odds ratio, 2.85 [1.43–5.66], respectively). Acute kidney injury and neuromuscular blockade in a multivariate regression analysis adjusted for Pediatric Index of Mortality 2 were associated with infection-related ventilator-associated complication (odds ratio, 2.36 [1.03–5.40] and 3.19 [1.17–8.68], respectively).

Conclusions:

There is an association between ventilator-associated condition and infection-related ventilator-associated complication in critically ill children with acute kidney injury, ventilatory support, and neuromuscular blockade. Attention should be given by clinical practitioners to recognize these modifiable risk factors and to implement strategies to decrease the prevalence of ventilator-associated events.
High-risk Human Papillomavirus Determination in Formalin-fixed, Paraffin-embedded Cervical Tissue Using the Roche Cobas 4800 System: A Comparative Study With Liquid-based Cytology
Authors: Tardío Juan C. , Cambero Olivia , Sánchez-Estévez Carolina , Sánchez-García Ana B. , Angulo Fernando , Moreno Amalia
Published: November 2017

Roche cobas 4800 human papillomavirus (HPV) test is an automated real-time polymerase chain reaction–based system that allows the simultaneous detection of 14 human papillomavirus high-risk (HR-HPV) genotypes. This test is Food and Drug Administration approved since 2011 for HPV determination in liquid-based cytologic samples, but a clinically validated technique for formalin-fixed, paraffin-embedded (FFPE) tissue specimens is presently not commercially available. In our laboratory, we have developed an HPV detection procedure in FFPE tissue by cobas 4800 HPV test. In order to validate our method, we retrospectively studied 165 FFPE cervical biopsy and conization specimens with varied diagnoses from our files. In 50 of them, we contrasted the results with those obtained from simultaneous liquid-based cytologies from the same patients. Finally, seeking the possible complementary clinical usefulness of the procedure, we compared the HPV genotypes detected in cervical intraepithelial neoplasia grade 1 (CIN1)-diagnosed biopsies from 20 patients with a subsequent high-grade CIN (CIN2+) diagnosis with those from another group of 20 patients without a subsequent CIN2+ diagnosis. Eighty-seven percent of the assays provided informative results. HR-HPV was detected in 28 of 32 (88%) invasive cervical squamous carcinomas. Coincidental HR-HPV genotypes were obtained in 32 of 50 (64%) cases with simultaneous cervical biopsy and liquid-based cytologic samples. A significant higher risk of progression to CIN2+ was found when HPV16 (P=0.022) or any HR-HPV genotype (P=0.037) was detected in CIN1 biopsies. The reported procedure provides an automated, technically time-saving, easy to integrate into laboratory routine, and reliable method of HR-HPV determination in FFPE specimens.
Atypical Placental Site Nodule Arising in a Postcesarean Section Scar: Case Report and Review of the Literature
Authors: McCarthy Whitney A. , Paquette Cherie , Colavita Mauro , Lawrence W. Dwayne
Published: November 2017

The distinction between benign and malignant trophoblastic lesions often presents a diagnostic challenge, even in entities with defined morphologic and immunohistochemical criteria. Lesions arising from chorionic-type intermediate trophoblast, namely placental site nodule (PSN) and epithelioid trophoblastic tumor (ETT), can be distinguished by existing criteria. However, a putative intermediate lesion termed “atypical placental site nodule” (APSN) has been described in the literature but is not well-classified. We present a case of APSN, along with a brief literature review, and we propose more definitive morphologic and immunohistochemical criteria for this entity, in order to facilitate easier diagnosis and gather more information regarding outcomes.
Quantitative Computed Tomography Metrics From the Transplanted Lung can Predict Forced Expiratory Volume in the First Second After Lung Transplantation
Authors: Mortani Barbosa Eduardo J. , Shou Haochang , Simpsom Scott , Gee James , Tustison Nicholas , Lee James C.
Published: November 2017

Purpose:

Bronchiolitis obliterans syndrome after lung transplantation (LTx) manifests as a sustained decline in forced expiratory volume in the first second (FEV1). Quantitative computed tomography (QCT) metrics may predict FEV1 better than semiquantitative scores (SQSs), and the transplanted lung may provide better information than the native lung in unilateral LTx.

Materials and Methods:

Paired inspiratory-expiratory CT scans and pulmonary function testing of 178 LTx patients were analyzed retrospectively. SQS were graded (absent, mild, moderate, severe) for features including mosaic attenuation and bronchiectasis. QCT included lung volumes and air-trapping volumes, by lobe. Multivariate Pearson correlation and multivariate linear least squares regression analyses were performed.

Results:

Multivariate linear least squares regression models using FEV1 as the outcome variable and SQS or QCT metrics as predictor variables demonstrated SQS to be a weak predictor of FEV1 (adjusted R
2, 0.114). QCT metrics were much stronger predictors of FEV1 (adjusted R
2, 0.654). QCT metrics demonstrated stronger correlation (r) with FEV1 than SQS. In bilateral LTx, whole lung volume difference (r=0.69), left lung volume difference (r=0.69), and right lung volume difference (r=0.65) were better than the sum of SQS (r=−0.54). Interestingly, in left LTx we obtained r=0.81, 0.86, 0.25, and −0.39, respectively. In right LTx, we obtained r=0.69, 0.49, 0.68, and −0.31, respectively.

Conclusions:

QCT metrics demonstrate stronger correlations with FEV1 and are better predictors of pulmonary function than SQS. SQS performs moderately well in bilateral LTx, but poorly on unilateral LTx. In unilateral LTx, QCT metrics from the transplanted lung are better predictors of FEV1 than QCT metrics from the nontransplanted lung.
Visual snow syndrome: what we know so far
Authors: Puledda Francesca , Schankin Christoph , Digre Kathleen , Goadsby Peter J.
Published: November 2017

Purpose of review

We provide an overview of the neurological condition known as visual snow syndrome. Patients affected by this chronic disorder suffer with a pan-field visual disturbance described as tiny flickering dots, which resemble the static noise of an untuned television.

Recent findings

The term ‘visual snow’ has only appeared in the medical literature very recently. The clinical features of the syndrome have now been reasonably described and the pathophysiology has begun to be explored. This review focuses on what is currently known about visual snow.

Recent evidence suggests visual snow is a complex neurological syndrome characterized by debilitating visual symptoms. It is becoming better understood as it is systematically studied. Perhaps the most important unmet need for the condition is a sufficient understanding of it to generate and test hypotheses about treatment.
Coarse-graining as a downward causation mechanism
Authors: Flack Jessica C.
Published: November 2017

Downward causation is the controversial idea that ‘higher’ levels of organization can causally influence behaviour at ‘lower’ levels of organization. Here I propose that we can gain traction on downward causation by being operational and examining how adaptive systems identify regularities in evolutionary or learning time and use these regularities to guide behaviour. I suggest that in many adaptive systems components collectively compute their macroscopic worlds through coarse-graining. I further suggest we move from simple feedback to downward causation when components tune behaviour in response to estimates of collectively computed macroscopic properties. I introduce a weak and strong notion of downward causation and discuss the role the strong form plays in the origins of new organizational levels. I illustrate these points with examples from the study of biological and social systems and deep neural networks.

This article is part of the themed issue ‘Reconceptualizing the origins of life’.
Exploring astrobiology using
in silico
molecular structure generation
Authors: Meringer Markus , Cleaves H. James
Published: November 2017

The origin of life is typically understood as a transition from inanimate or disorganized matter to self-organized, ‘animate’ matter. This transition probably took place largely in the context of organic compounds, and most approaches, to date, have focused on using the organic chemical composition of modern organisms as the main guide for understanding this process. However, it has gradually come to be appreciated that biochemistry, as we know it, occupies a minute volume of the possible organic ‘chemical space’. As the majority of abiotic syntheses appear to make a large set of compounds not found in biochemistry, as well as an incomplete subset of those that are, it is possible that life began with a significantly different set of components. Chemical graph-based structure generation methods allow for exhaustive
in silico
enumeration of different compound types and different types of ‘chemical spaces’ beyond those used by biochemistry, which can be explored to help understand the types of compounds biology uses, as well as to understand the nature of abiotic synthesis, and potentially design novel types of living systems.

This article is part of the themed issue ‘Reconceptualizing the origins of life’.
Subsumed complexity: abiogenesis as a by-product of complex energy transduction
Authors: Adam Z. R. , Zubarev D. , Aono M. , Cleaves H. James
Published: November 2017

The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry calledsubsumed complexity, organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification.

This article is part of the themed issue ‘Reconceptualizing the origins of life’.
Differential and defective expression of Koala Retrovirus indicate complexity of host and virus evolution
Authors: Tarlinton R.E , Legione A.R. , Sarker N. , Fabijan J. , Meers J. , McMichael L. , Simmons G. , Owen H. , Seddon J.M. , Dick G. , Ryder J.S. , Hemmatzedah F. , Trott D.J. , Speight N. , Holmes N. , Loose M. , Emes R.D.
Published: November 2017

Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus free or to have only exogenous variants of KoRV with low rates of KoRV induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV induced disease such as lymphoma. This paper uses a combination of sequencing technologies, Illumina RNA sequencing of “southern” (south Australian) and “northern” (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of “southern” (South Australian and Victorian animals) to retrieve full length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication competent KoRV, are not in fact KoRV free but harbour defective, presumably endogenous, “RecKoRV” variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV induced disease.
Diallel analysis revealsMx1-dependent andMx1-independent effects on response to influenza A virus in mice
Authors: Maurizio Paul L. , Ferris Martin T. , Keele Gregory R. , Miller Darla R. , Shaw Ginger D. , Whitmore Alan C. , West Ande , Morrison Clayton R. , Noll Kelsey E. , Plante Kenneth S. , Cockrell Adam S. , Threadgill David W. , Pardo-Manuel de Villena Fernando , Baric Ralph S. , Heise Mark T. , Valdar William
Published: November 2017

1.

Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but this host genetic architecture is not well understood. Here we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8×8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 days post-infection. Heritable effects in aggregate explained about 57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 post-infection and was consistent with previous reports of anti-influenza myxovirus resistance 1 (Mx1) polymorphisms segregating between these strains; the additive effects largely recapitulated haplotype effects observed at theMx1locus in a previous study of the incipient CC (pre-CC), and are also replicated here in a CC recombinant intercross (CC-RIX) population. Genetic dominance of protectiveMx1haplotypes was observed to differ by subspecies origin: relative to thedomesticusnullMx1allele,musculusacts dominantly whereascastaneusacts additively. After controlling forMx1, heritable effects, though less distinct, accounted for about 34% of the phenotypic variance. Implications for future mapping studies are discussed.
The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea
Authors: Deeg Christoph M. , Chow Cheryl-Emiliane T. , Suttle Curtis A.
Published: November 2017

Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant giant viruses in the oceans, and the first klosneuvirus isolate, a subgroup of theMimiviridaeproposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastidBodo saltans. Its 1.39 Mb genome is the largest described for theMimiviridaeand encodes 1227 predicted ORFs, including pathways for host-independent replication. Yet, much of its translational machinery has been lost, including all tRNAs. Essential genes are invaded by homing endonuclease-encoding self-splicing introns that may defend against competing viruses. Putative anti-host factors show extensive gene duplication via a genomic accordion indicating an ongoing evolutionary arms race and highlighting the rapid evolution and genomic plasticity that has led to genome gigantism and the enigma that is giant viruses.
Butterflyfishes as a System for Investigating Pair Bonding
Authors: Nowicki Jessica P. , O’Connell Lauren A. , Cowman Peter F. , Walker Stefan P. W. , Coker Darren J. , Pratchett Morgan S.
Published: November 2017

For many animals, affiliative relationships such as pair bonds form the foundation of society, and are highly adaptive. Animal systems amenable for comparatively studying pair bonding are important for identifying underlying biological mechanisms, but mostly exist in mammals. Better establishing fish systems will enable comparison of pair bonding mechanisms across taxonomically distant lineages that may reveal general underlying principles. We examined the utility of wild butterflyfishes (f: Chaetodontidae; g:Chaetodon) for comparatively studying pair bonding. Stochastic character mapping inferred that within the family, pairing is ancestral, with at least seven independent transitions to group formation and seven transition to solitary behavior from the late Miocene to recent. In six sympatric and wide-spread species representing a clade with one ancestrally reconstructed transition from paired to solitary grouping, we then verified social systems at Lizard Island, Australia.In situobservations confirmed thatChaetodon baronessa, C. lunulatus, andC. vagabundusare predominantly pair bonding, whereasC. rainfordi, C. plebeius, andC. trifascialisare predominantly solitary. Even in the predominantly pair bonding species,C. lunulatus, a proportion of adults (15 %) are solitary. Importantly, inter- and intra-specific differences in social systems do not co-vary with other previously established attributes (geographic occurrence, parental care, diet, or territoriality). Hence, the proposed butterflyfish populations are promising for comparative analyses of pair bonding and its mechanistic underpinnings. Avenues for further developing the system are proposed, including determining whether the utility of these species applies across their geographic disruptions.
Uncovering cell-free protein expression dynamics by a promoter library with diverse strengths
Authors: Galiñanes Reyes Sabrina , Kuruma Yutetsu , Tsuda Soichiro
Published: November 2017

Cell-free protein expression systems have been widely used for synthetic biology and metabolic engineering applications in recent years. Yet little is known about protein expression in the cell-free systems. Here we take a systems approach to uncover underlying dynamics of cell-free protein expression. We construct a set of T7 promoter variants to express proteins at different transcription rates in a reconstituted andE. coliextract-based cell-free systems. We find that the maximum expression level and the rate of protein synthesis as responses to the transcription rate change are different in the two cell-free systems, suggesting they are driven by different expression dynamics. We confirm this by constructing a simple mathematical model for each cell-free system, which well reproduce the experimental results and also identify different limiting factors for better protein expression in the two cell-free systems. In particular, they revealed there is a negative feedback effect in the mRNA-protein translation by the PURE system and also identified different limiting factors for better protein expression in the two cell-free systems.
Multidimensional quantitative analysis of mRNA expression within intact vertebrate embryos
Authors: Trivedi Vikas , Choi Harry M.T. , Fraser Scott E. , Pierce Niles A.
Published: November 2017

For decades, in situ hybridization methods have been essential tools for studies of vertebrate development and disease, as they enable qualitative analyses of mRNA expression in an anatomical context. Quantitative mRNA analyses typically sacrifice the anatomy, relying on embryo microdissection, dissociation, cell sorting, and/or homogenization. Here, we eliminate the tradeoff between quantitation and anatomical context, using multiplexed in situ hybridization chain reaction (HCR) to perform accurate and precise relative quantitation of mRNA expression with subcellular resolution within whole-mount vertebrate embryos. Gene expression can be queried in two directions: read-out from anatomical space to expression space reveals co-expression relationships in selected regions of the specimen; conversely, read-in from multidimensional expression space to anatomical space reveals those anatomical locations in which selected gene co-expression relationships occur. As we demonstrate by examining gene circuits underlying somitogenesis, quantitative read-out and read-in analyses provide the strengths of flow cytometry expression analyses, but by preserving subcellular anatomical context, they enable iterative bi-directional queries that open a new era for in situ hybridization.

Multiplexed in situ hybridization chain reaction (HCR) enables quantitative multidimensional analyses of developmental gene expression with subcellular resolution in an anatomical context.
Pair bond endurance promotes cooperative food defense and inhibits conflict in coral reef butterflyfishes
Authors: Nowicki Jessica P. , Walker Stefan P. W. , Coker Darren J. , Hoey Andrew S. , Nicolet Katia J. , Pratchett Morgan S.
Published: November 2017

Pair bonding is generally linked to monogamous mating systems, where the reproductive benefits of extended mate guarding and/or of bi-parental care are considered key adaptive functions. However, in some species, including coral reef butterflyfishes (f. Chaetodonitidae), pair bonding occurs in sexually immature and homosexual partners, and in the absence of parental care, suggesting there must be non-reproductive adaptive benefits of pair bonding. Here, we examined whether pair bonding butterflyfishes cooperate in defense of food, conferring direct benefits to one or both partners. Pairs ofChaetodon lunulatusandC. baronessause contrasting cooperative strategies. InC. lunulatus,both partners mutually defend their territory, while inC. baronessa,males prioritize territory defence; conferring improvements in feeding and energy reserves in both sexes relative to solitary counterparts. We further demonstrate that partner fidelity contributes to this function by showing that re-pairing invokes intra-pair conflict and inhibits cooperatively-derived feeding benefits, and that partner endurance is required for these costs to abate. Overall, our results suggest that in butterflyfishes, pair bonding enhances cooperative defense of prey resources, ultimately benefiting both partners by improving food resource acquisition and energy reserves.
Early-exposure to new sex pheromone blend alters mate preference in female butterflies and in their offspring
Authors: Dion Emilie , Pui Li Xian , Monteiro Antónia
Published: November 2017

Insects use species-specific sex pheromone blends to attract members of the opposite sex which express the corresponding molecular receptors. Given this lock and key mechanism used for species identification and mate choice, it is currently not well understood how pheromone blends or receptor systems evolve. One possibility is that insects develop preferences for new sex pheromone blends via the process of learning, and that these learned preferences may be passed on to the next generation. We tested these hypotheses by exposing newly emerged Bicyclus anynana female butterflies to either wild type or to modified male sex pheromone blends. A few days later, we scored female mating outcome in a choice trial involving both male types. We also assessed the mating outcome of naïve offspring of females that underwent distinct odor learning trials to test for a potential inheritance of learned odor preferences. Naïve (parental) females mated preferentially with Wt-blend males, but females pre-exposed to new blends either shifted their preference to new-blend males, or mated equally with males of either blend type; the response depending on the new blend they were introduced to. Naïve daughters of females who were exposed to new-blend males behaved similarly to their experienced mothers. We demonstrate that females are able to learn preferences for novel pheromone blends in response to a short social experience, and pass that learned preference down to the next generation. This suggests that learning can be a key factor in the evolution of sex pheromone blend recognition and in chemosensory speciation.

Significance statement

While the diversity of sex pheromone communication systems across insects is well documented, the mechanisms that lead to such diversity are not well understood. Sex pheromones constitute a species-specific system of sexual communication that reinforces interspecific reproductive isolation. When odor blends evolve, the efficacy of male-female communication becomes compromised, unless preference for novel blends also evolves. We explore odor learning as a possible mechanism leading to changes in sex pheromone preferences. We show that preferences for new blends can develop following a short learning experience, and that these novel preferences can be transmitted to the next generation. To our knowledge, this is the first investigation of sex pheromone blend preference learning impacting mate choice and being inherited in an insect.
Temporal coupling of field potentials and action potentials in the neocortex
Authors: Watson Brendon O. , Ding Mingxin , Buzsáki György
Published: November 2017

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years investigators have found that action potential firing rates increase during elevations in power high-frequency band oscillations (50-200 Hz range). However action potentials also contribute to the LFP signal itself, making the spike–LFP relationship complex. Here we examine the relationship between spike rates and LFPs in varying frequency bands in rat neocortical recordings. We find that 50-180Hz oscillations correlate most consistently with high firing rates, but that other LFPs bands also carry information relating to spiking, including in some cases anti-correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation-based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.
B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage
Authors: Wong Jason B , Hewitt Susannah L , Heltemes-Harris Lynn M , Mandal Malay , Johnson Kristen , Rajewsky Klaus , Koralov Sergei B , Clark Marcus R , Farrar Michael A , Skok Jane A
Published: November 2017

B-1a cells are long-lived, self-renewing innate like B cells that predominantly inhabit the peritoneal and pleural cavities. In contrast to conventional B-2 cells they have a receptor repertoire that is biased towards bacterial and self-antigens, promoting a rapid response to infection and clearing of apoptotic cells. Although B-1a cells are known to primarily originate from fetal tissues the mechanisms by which they arise has been a topic of debate for many years. Here we show that in the fetal liver (FL) versus bone marrow (BM) environment, reduced IL-7R/STAT5 levels promote immunoglobulin kappa (Igk) recombination at the early pro-B cell stage. As a result, B cells can directly generate a mature B cell receptor (BCR) and bypass the requirement for a pre-BCR and pairing with surrogate light chain (SLC). This ‘alternate pathway’ of development enables the production of B cells with self reactive, skewed specificity receptors that are peculiar to the B-1a compartment. Together our findings connect seemingly opposing models of B-1a cell development and explain how these cells acquire their unique properties.
Network modelling unravels mechanisms of crosstalk between ethylene and salicylate signalling in potato
Authors: Ramšak Živa , Coll Anna , Stare Tjaša , Tzfadia Oren , Baebler Špela , Baebler Špela , Van de Peer Yves , Gruden Kristina
Published: November 2017

To provide means for novel crop breeding strategies, it is crucial to understand the mechanisms underlying the interaction between plants and their pathogens. Network modelling represents a powerful tool that can unravel properties of complex biological systems. Here, we build on a reliable Arabidopsis (Arabidopsis thaliana L.) immune signalling model, extending it with the information from diverse publically available resources. The resulting prior knowledge network (20,012 nodes, 70,091 connections) was then translated to potato (Solanum tuberosum L.) and superimposed with an ensemble network inferred from potato time-resolved transcriptomics data. We used different network modelling approaches to generate specific hypotheses of potato immune signalling mechanisms. An interesting finding was the identification of a string of molecular events, illuminating the ethylene pathway modulation of the salicylic acid pathway through NPR1 gene expression. Functional validations confirmed this modulation, thus confirming the potential of our integrative network modelling approach for unravelling molecular mechanisms in complex systems.

One-sentence summary

Analysis of integrated prior knowledge and ensemble networks highlights a novel connection between ethylene and salicylic acid signalling modules in potato.
Addressing the reliability fallacy: Similar group effects may arise from unreliable individual effects
Authors: Fröhner Juliane H. , Teckentrup Vanessa , Smolka Michael N. , Kroemer Nils B.
Published: November 2017

To cast valid predictions of future behavior or diagnose disorders, the reliable measurement of a “biomarker” such as the brain activation to prospective reward is a prerequisite. Surprisingly, only a small fraction of functional magnetic resonance imaging (fMRI) studies report or cite the reliability of brain activation maps involved in group analyses. Here, using simulations and exemplary longitudinal data of 126 healthy adolescents performing an intertemporal choice task, we demonstrate that reproducing a group activation map over time is not a sufficient indication of reliable measurements at the individual level. Instead, selecting regions based on significant main effects at the group level may yield estimates that fail to reliably capture individual variance in the subjective evaluation of an offer. Collectively, our results call for more attention on the reliability of supposed biomarkers at the level of the individual. Thus, caution is warranted in employing brain activation patterns prematurely for clinical applications such as diagnosis or tailored interventions before their reliability has been conclusively established by large-scale studies. To facilitate assessing and reporting of the reliability of fMRI contrasts in future studies, we provide a toolbox that incorporates common measures of global and local reliability.