bluuebunny/crossref_metadata_2025 huggingface dataset:
Soft Tissue Metrics in Thyroid Eye Disease: An International Thyroid Eye Disease Society Reliability Study
Authors: Mawn Louise A. , Dolman Peter J. , Kazim Michael , Strianese Diego , Genol Ignacio , Chong Kelvin K. L. , Sullivan Timothy J. , Korn Bobby S. , Naik Milind , Dutton Jonathan , Velasco e Cruz Augusto , Li Chun
Published: February 2018

Purpose:

To determine the reliability of 3 scales for assessing soft tissue inflammatory and congestive signs associated with thyroid eye disease.

Methods:

This was a multicentered prospective observational study, recruiting 55 adults with thyroid eye disease from 9 international centers. Six thyroid eye disease soft tissue features were measured; each sign graded using 3 scales (presence/absence [0–1], 3-point scale [0–2], and percentage [0–100]). Each eye was graded twice by 2 independent raters. Accuracy (fraction of agreement) was calculated between the 2 trials for each rater (intrarater reliability) and between raters for all trials (interrater reliability) to determine the most sensitive scale for each feature that maintained a threshold of agreement greater than 0.70. Trial, intrarater reliability, and interrater reliability were determined by accuracy measurement of agreement for each inflammatory/congestive feature.

Results:

Fifty-five patients had 218 assessments for 6 thyroid eye disease metrics. The intrarater reliability for each feature was consistently better than the interrater reliabilities. Using an agreement of 0.70 or better, for the interrater tests, conjunctival and eyelid edema could be reliably measured using the 0–1 or 0–2 scale while conjunctival and eyelid redness could only be reliably measured with the binary 0–1 scale. Caruncular edema and superior conjunctival redness could not be measured reliably between 2 raters with any scale. The percentage scale had poor agreement unless slippage intervals of >20% were allowed on either side of the measurements.

Conclusions:

Of the specific periocular soft tissue inflammatory features measured between raters in the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance scales, edema of the eyelids and conjunctiva could reliably be measured by both 0–1 and 0–2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be measured only by the 0–1 scale, and the other parameters of superior bulbar erythema and caruncular edema were not reliably measured by any scale.
Noninflammatory Thyroid Eye Disease
Authors: Ugradar Shoaib , Rootman Daniel B.
Published: February 2018

Purpose:

Patients presenting with thyroid eye disease (TED) usually follow a well-defined self-remitting course characterized by an active inflammatory phase followed by an inactive fibrotic phase. We present 3 cases where patients presented primarily with signs of progressive fibrosis and no signs of prior active inflammation.

Methods:

We reviewed the clinical notes and investigations of 3 patients who presented to our center between January 2015 and August 2017.

Results:

All patients included in the study presented primarily with severe, progressive fibrosis without evidence of a previous active inflammatory condition. Although there were no signs of inflammation, each case was progressive, with 2 of the cases developing dysthyroid optic neuropathy that was relatively recalcitrant. We found that these patients were older than the general population of TED patients and that their disease course represents a departure from the common narrative.

Conclusions:

This subgroup of TED patients do not conform to the typical inflammatory natural history of TED. We propose that the heterogeneity of the orbital fibroblast pool and their function may be different in this subgroup. Further work will be required to reveal the pathophysiology of this atypical TED process, potentially revealing links between aging and the inflammatory mediators in TED.
Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity
Authors: Nasser Arafat , Møller Anette Torvin , Hellmund Vibe , Thorborg Sidsel Salling , Jespersgaard Cathrine , Bjerrum Ole J. , Dupont Erik , Nachman Gösta , Lykkesfeldt Jens , Jensen Troels Staehelin , Møller Lisbeth Birk
Published: February 2018

Human studies have demonstrated a correlation between noncoding polymorphisms of “the pain protective” haplotype in the GCH1 gene that encodes for GTP cyclohydrolase I (GTPCH1)—which leads to reduced tetrahydrobiopterin (BH4) production in cell systems—and a diminished perception of experimental and clinical pain. Here, we investigate whether heterozygous mutations in the GCH1 gene which lead to a profound BH4 reduction in patients with dopa-responsive dystonia (DRD) have any effect on pain sensitivity. The study includes an investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of 22 patients with DRD and 36 controls. The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different. A family-specific cohort of 11 patients with DRD and 11 controls were included in this study. The patients with DRD were heterozygous for the pain protective haplotype in cis with the GCH1 disease-causing mutation, c.899T>C. No effect on pain perception was observed for this combined haplotype. In conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing pain sensitivity or evoked pain responses.
The prevalence of unexplained falls and syncope in older adults presenting to an Irish urban emergency department
Authors: Bhangu Jaspreet , Hall Patricia , Devaney Naomi , Bennett Kathleen , Carroll Laura , Kenny Rose-Anne , McMahon C. Geraldine
Published: February 2018

Aim

There is growing evidence of an overlap between unexplained falls and syncope in older adults. Our aim was to examine the prevalence and associated resource utilization of these conditions in an urban emergency department (ED).

Patients and methods

A single-centre, prospective, observational study was carried out over a 6-month period. Consecutive patients older than 50 years who presented to the ED because of a fall, collapse or syncope were included. Univariate analysis of demographic data is presented as percentages, mean (SD), 95% confidence intervals (CIs) and medians (interquartile range). Logistic regression modelling was used to examine the association between falls and resource utilization.

Results

A total of 561 patients fulfilled the inclusion criteria during the study period. Unexplained fallers accounted for 14.3% (n=80; 95% CI: 13.3–15.3) and syncope for 12.7% (n=71; 95% CI: 11.7–13.6) of all fall presentations. Overall, 50% (n=282; 95% CI: 48.20–52.34) of patients required admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45–4.23], and unexplained falls (OR=2.36, 95% CI: 1.37–4.08) were more likely to require admission than those with an explained falls. Unexplained fallers were nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89–8.56).

Conclusion

One in four older fallers presenting to ED have symptoms suggestive of syncope or an unexplained fall. There are significant biological consequences of recurrent falls including greater rates of cognitive decline, gait and mobility disturbances, depression and frailty. Recognition that syncope can present as an unexplained fall in older adults is important to ensure that appropriate early modifiable interventions are initiated.
Molecular and Metabolic Basis of Clear Cell Carcinoma of the Kidney
Authors: Akhtar Mohammed , Al-Bozom Issam A. , Al Hussain Turki
Published: February 2018

Renal cell carcinoma (RCC) is a heterogenous group of tumors, >70% of which belong to the category of clear cell carcinoma. In recent years, crucial advances have been made in our understanding of the molecular and metabolic basis of clear cell carcinoma. This tumor manifests significant alterations in the cellular metabolism, so that the tumor cells preferentially induce the hypoxia response pathway using aerobic glycolysis, rather than the normal oxidative phosphorylation for energy. Most of the clear cell carcinomas (sporadic as well as familial) have mutations and deletions in the VHL gene located at 3p (p3.25). Normally, pVHL plays a crucial role in the proteasomal degradation of hypoxia-inducible factors (HIF)1 and HIF2. Lack of a functioning pVHL owing to genetic alterations results in stabilization and accumulation of these factors, which promotes cell growth, cell proliferation, and angiogenesis, contributing to a neoplastic phenotype. Several other genes normally located adjacent to VHL (BAP1, SETD2, PBRM1) may also be lost. These are tumor suppressor genes whose loss not only plays a role in carcinogenesis but may also influence the clinical course of these neoplasms. In addition, interaction among a variety of other genes located at several different chromosomes may also play a role in the genesis and progression of clear cell carcinoma.
Hypofibrinogenemia Is Associated With Poor Outcome and Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in Pediatric Severe Sepsis*
Authors: Signoff Jessica K. , Fitzgerald Julie C. , Teachey David T. , Balamuth Fran , Weiss Scott L.
Published: February 2018

Objectives:

Some children with sepsis exhibit a sustained hyperinflammatory response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a biomarker to identify children with sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome and has utility as a screening biomarker for this sepsis phenotype.

Design:

A retrospective cohort study of patients less than or equal to 21 years treated for severe sepsis from January 2012 to December 2014.

Setting:

Emergency department and PICU at a single academic children’s hospital.

Patients:

Consecutive patients with greater than or equal to one episode of hypofibrinogenemia (serum fibrinogen < 150 mg/dL) within 7 days of sepsis were compared with a random sample of patients without hypofibrinogenemia using an a priori sample size target of 190. Thirty-eight patients with hypofibrinogenemia were compared with 154 without hypofibrinogenemia.

Interventions:

None.

Measurements and Main Results:

The primary outcome was “complicated course” (composite of 28-d mortality or ≥ two organ failures at 7 d). Secondary outcomes were 28-day mortality and fulfillment of diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. We used Wilcoxon rank-sum, Fisher exact test, and multivariable logistic regression to compare patients with versus without hypofibrinogenemia. Patients with hypofibrinogenemia were more likely to have a complicated course (73.7% vs 29.2%; p < 0.001), 28-day mortality (26.3% vs 7.1%, p = 0.002), and meet diagnostic criteria for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (21.1% vs 1.3%; p < 0.001). After controlling for confounders, hypofibrinogenemia remained associated with complicated course (adjusted odds ratio, 8.8; 95% CI, 3.5–22.4), mortality (adjusted odds ratio, 6.0; 95% CI, 2.0–18.1), and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (adjusted odds ratio, 27.6; 95% CI, 4.4–173).

Conclusions:

Hypofibrinogenemia was independently associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric sepsis. Measurement of fibrinogen may provide a pragmatic biomarker to identify children with possible sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome overlap for whom further diagnostic testing and consideration of adjunctive immunomodulatory therapies should be considered.
Outcome Trends of Adult Cancer Patients Receiving Inpatient Rehabilitation
Authors: Gallegos-Kearin Vanessa , Knowlton Sasha E. , Goldstein Richard , Mix Jacqueline , Zafonte Ross , Kwan Michael , Silver Julie , Schneider Jeffrey C.
Published: February 2018

Objective

This study describes characteristics and trends of inpatient rehabilitation among cancer patients within the United States over a 13-yr period.

Design

This was a retrospective study of data from the Uniform Data System for Medical Rehabilitation from 2002 to 2014. Patients older than 17 yrs admitted to inpatient rehabilitation facilities with a diagnosis of malignant cancer were included. Trends of rehabilitation outcomes including length of stay, Functional Independence Measure (FIM) Instrument scores, and discharge location were examined.

Results

Data from 115,570 cancer patients were evaluated. Mean age was 66 ± 14 yrs and 49% were women. Mean length of stay decreased over time (2002: 14 days to 2014: 13 days; P < 0.0005). Patient's admission total FIM scores decreased over time (2002: 68 ± 18 to 2014: 61 ± 16; P < 0.0005). The FIM change score increased over time (2002: 19 ± 16 to 2014: 25 ± 17; P < 0.0005). The greatest significant functional gains occurred in self care and transfers. Most patients (>70%) were discharged to the community.

Conclusions

Cancer patients receiving acute inpatient rehabilitation demonstrated significant improvements in functional outcomes from admission to discharge. Cancer patients became more independent in important activities of daily living, thereby potentially reducing caregiver burden and ensuring safer discharges back to the community. This study suggests potential benefit of inpatient rehabilitation for appropriate cancer patients.
Hypercholesterolemia Is Associated with the Subjective Evaluation of Postoperative Outcomes in Patients with Idiopathic Carpal Tunnel Syndrome Who Undergo Surgery: A Multivariate Analysis
Authors: Yano Koichi , Kawabata Akira , Ikeda Mikinori , Suzuki Keisuke , Kaneshiro Yasunori , Egi Takeshi
Published: February 2018

Background:

Carpal tunnel syndrome is a compression neuropathy of the median nerve at the wrist; its symptoms include neuropathic pain and sensory and motor disturbance distributed by the median nerve. Carpal tunnel syndrome and hypercholesterolemia have similar backgrounds, but the effect of these similarities on postoperative outcomes has not been reported. Using multivariate analysis, the authors analyzed the relationship between prognostic factors, including the presence of hypercholesterolemia, and subjective postoperative outcomes of patients with idiopathic carpal tunnel syndrome.

Methods:

Of 168 hands with carpal tunnel syndrome that were treated surgically, 141 that were followed up and assessed 1 year postoperatively or thereafter were included. The mean postoperative follow-up period was 40.8 months. Surgery was performed through a small palmar skin incision under local anesthesia. The outcomes were postoperative symptoms, including pain and numbness, and overall Kelly assessment.

Results:

Preoperative numbness and pain resolved and alleviated in 94 of 141 hands and was diminished in 59 of 64 hands. Univariate analysis showed that postoperative numbness and Kelly assessment were significantly associated with hypercholesterolemia. Multivariate analysis showed that postoperative numbness was significantly associated with smoking and hypercholesterolemia, and Kelly assessment was significantly associated with smoking (adjusted OR, 3.3; 95 percent CI, 1.1 to 10; p = 0.04) and hypercholesterolemia (adjusted OR, 2.9; 95 percent CI, 1.4 to 6.3; p = 0.01).

Conclusion:

Hypercholesterolemia, usually a systemic condition in sites other than the hand, is associated with the subjective evaluation of postoperative symptoms in patients with idiopathic carpal tunnel syndrome.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Asthmatic Exacerbation as a Cause of False-Positive Whole-Body Iodine Scan in a Patient With Treated Papillary Thyroid Carcinoma
Authors: Chaussé Guillaume , Kader Tina , Abikhzer Gad , Probst Stephan
Published: February 2018

A 44-year-old woman was found to have new diffuse lung uptake on a follow-up whole-body 131I scan 1 year after being treated with surgery and radioactive iodine for papillary thyroid cancer. However, subsequent CT thorax and thyroglobulin levels were both unremarkable. Shortly after, she presented with respiratory symptoms, exhibiting end-expiratory wheezing on auscultation. Metacholine challenge test confirmed asthma. Symptoms improved under inhaled corticosteroids and beta-2 agonists. Resolution of lung uptake was confirmed on a second 131I imaging 6 months later.
Improving Quality of Dynamic Airway Computed Tomography Using an Expiratory Airflow Indicator Device
Authors: Hahn Lewis D. , Sung Arthur W. , Shafiq Majid , Guo Haiwei Henry
Published: February 2018

Purpose:

Dynamic computed tomography (CT) of the airways is increasingly used to evaluate patients with suspected expiratory central airway collapse, but current protocols are susceptible to inadequate exhalation caused by variable patient compliance with breathing instructions during the expiratory phase. We developed and tested a low-cost single-use expiratory airflow indicator device that was designed to improve study quality by providing a visual indicator to both patient and operator when adequate expiratory flow was attained.

Materials and Methods:

A total of 56 patients undergoing dynamic airway CT were evaluated, 35 of whom were scanned before introduction of the indicator device (control group), with the rest comprising the intervention group. Lung volumes and tracheal cross-sectional areas on inspiratory/expiratory phases were computed using automated lung segmentation and quantitative software analysis. Inadequate exhalation was defined as absolute volume change of <500 mL during the expiratory phase.

Results:

Fewer patients in the intervention group demonstrated inadequate exhalation. The average change in volume was higher in the intervention group (P=0.004), whereas the average minimum tracheal cross-sectional area was lower (P=0.01).

Conclusions:

The described expiratory airflow indicator device can be used to ensure adequate exhalation during the expiratory phase of dynamic airway CT. A higher frequency of adequate exhalation may improve reliability and sensitivity of dynamic airway CT for diagnosis of expiratory central airway collapse.
Opioid addiction, diversion, and abuse in chronic and cancer pain
Authors: Kata Vijay , Novitch Matthew B. , Jones Mark R. , Anyama Best O. , Helander Erik M. , Kaye Alan D.
Published: February 2018

Purpose of review

The primary cause of overdose death in the United States is related to pharmaceutical opioids. A few particular populations that struggle with adverse outcomes related to opioid abuse are those in palliative care, those with chronic pain, and those receiving pain treatments secondary to cancer or chemotherapy.

Recent findings

There have been massive efforts to decrease the use of opioid abuse in patient care in a gestalt manner, but palliative care provides unique challenges in applying these reduction tactics used by other specialties.

We explore behavioral interventions, provider education, alternative pain management techniques, postmarketing surveillance, and abuse-deterrent formulas as emerging methods to counteract opioid abuse in these populations.
Poor Survival After Retransplantation in NASH Cirrhosis
Authors: Thuluvath Avesh J. , Chen Po-Hung , Thuluvath Paul J. , Kantsevoy Sergey , Savva Yulia
Published: February 2018

Background

Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the United States. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH.

Methods

We queried the United Network for Organ Sharing data sets from 2002 to 2016 to analyze the outcomes of adults with NASH (n = 128) and compared them with groups that received re-LT for cryptogenic cirrhosis (n = 189), alcoholic cirrhosis (n = 300) or autoimmune hepatitis cirrhosis (n = 118) after excluding multiple-organ re-LT and individuals with hepatocellular carcinoma. We estimated survival probabilities using a Kaplan-Meier estimator, and a relative risk of patient and graft mortality using proportional hazards regression.

Results

The NASH group was older and had a higher prevalence of obesity, type II diabetes mellitus, renal insufficiency, portal vein thrombosis, and poor performance status. The median interval between the first and the second LT was shorter in the NASH group (27 days). The graft and patient 5-year survival rates were lower for the NASH group after re-LT compared with the other 3 groups. After adjusting for demographic and disease complication factors, the factors that increased a risk of patient or graft failure were a poor performance status (hazard ratio [HR], 1.64; 1.19-2.26), Donor Risk Index (HR, 1.51; 1.08-2.12), and a high Model for End-stage Liver Disease score (HR, 1.02; 1.00-1.04).

Conclusions

Despite the comparable outcomes reported for initial LT among the various etiologies, the outcome of re-LT is significantly worse for NASH cirrhosis.
Distance-dependent aposematism and camouflage in the cinnabar moth caterpillar (Tyria jacobaeae, Erebidae)
Authors: Barnett James B. , Cuthill Innes C. , Scott-Samuel Nicholas E.
Published: February 2018

Defended prey often use distinctive, conspicuous, colours to advertise their unprofitability to potential predators (aposematism). These warning signals are frequently made up of salient, high contrast, stripes which have been hypothesized to increase the speed and accuracy of predator avoidance learning. Limitations in predator visual acuity, however, mean that these patterns cannot be resolved when viewed from a distance, and adjacent patches of colour will blend together (pattern blending). We investigated how saliency changes at different viewing distances in the toxic and brightly coloured cinnabar moth caterpillar (Tyria jacobaeae). We found that although the caterpillars' orange-and-black stripes are highly salient at close range, when viewed from a distance the colours blend together to match closely those of the background. Cinnabar caterpillars therefore produce a distance-dependent signal combining salient aposematism with targeted background matching camouflage, without necessarily compromising the size or saturation of their aposematic signal.
Isotopic niche reflects stress-induced variability in physiological status
Authors: Karlson Agnes M. L. , Reutgard Martin , Garbaras Andrius , Gorokhova Elena
Published: February 2018

The isotopic niche has become an established concept in trophic ecology. However, the assumptions behind this approach have rarely been evaluated. Evidence is accumulating that physiological stress can affect both magnitude and inter-individual variability of the isotopic signature in consumers via alterations in metabolic pathways. We hypothesized that stress factors (inadequate nutrition, parasite infestations, and exposure to toxic substances or varying oxygen conditions) might lead to suboptimal physiological performance and altered stable isotope signatures. The latter can be misinterpreted as alterations in isotopic niche. This hypothesis was tested by inducing physiological stress in the deposit-feeding amphipod
Monoporeia affinis
exposed to either different feeding regimes or contaminated sediments. In the amphipods, we measured body condition indices or reproductive output to assess growth status and δ
13
C and δ
15
N values to derive isotope niche metrics. As hypothesized, greater isotopic niche estimates were derived for the stressed animals compared to the control groups. Moreover, the δ
15
N values were influenced by body size, reproductive status and parasite infestations, while δ
13
C values were influenced by body size, oxygen conditions and survival. Using regression analysis with isotope composition and growth variables as predictors, we were able to discriminate between the amphipods exposed to nutritionally or chemically stressful conditions and those in the control groups. Thus, interpretation of isotopic niche can be confounded by natural or anthropogenic stressors that may induce an apparent change in isotopic niche. These findings stress the importance of including measures of growth and health status when evaluating stable isotope data in food web studies.
Shared periodic performer movements coordinate interactions in duo improvisations
Authors: Eerola Tuomas , Jakubowski Kelly , Moran Nikki , Keller Peter E. , Clayton Martin
Published: February 2018

Human interaction involves the exchange of temporally coordinated, multimodal cues. Our work focused on interaction in the visual domain, using music performance as a case for analysis due to its temporally diverse and hierarchical structures. We made use of two improvising duo datasets—(i) performances of a jazz standard with a regular pulse and (ii) non-pulsed, free improvizations—to investigate whether human judgements of moments of interaction between co-performers are influenced by body movement coordination at multiple timescales. Bouts of interaction in the performances were manually annotated by experts and the performers’ movements were quantified using computer vision techniques. The annotated interaction bouts were then predicted using several quantitative movement and audio features. Over 80% of the interaction bouts were successfully predicted by a broadband measure of the energy of the cross-wavelet transform of the co-performers’ movements in non-pulsed duos. A more complex model, with multiple predictors that captured more specific, interacting features of the movements, was needed to explain a significant amount of variance in the pulsed duos. The methods developed here have key implications for future work on measuring visual coordination in musical ensemble performances, and can be easily adapted to other musical contexts, ensemble types and traditions.
Letting the ‘cat’ out of the bag: pouch young development of the extinct Tasmanian tiger revealed by X-ray computed tomography
Authors: Newton Axel H. , Spoutil Frantisek , Prochazka Jan , Black Jay R. , Medlock Kathryn , Paddle Robert N. , Knitlova Marketa , Hipsley Christy A. , Pask Andrew J.
Published: February 2018

The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was an iconic Australian marsupial predator that was hunted to extinction in the early 1900s. Despite sharing striking similarities with canids, they failed to evolve many of the specialized anatomical features that characterize carnivorous placental mammals. These evolutionary limitations are thought to arise from functional constraints associated with the marsupial mode of reproduction, in which otherwise highly altricial young use their well-developed forelimbs to climb to the pouch and mouth to suckle. Here we present the first three-dimensional digital developmental series of the thylacine throughout its pouch life using X-ray computed tomography on all known ethanol-preserved specimens. Based on detailed skeletal measurements, we refine the species growth curve to improve age estimates for the individuals. Comparison of allometric growth trends in the appendicular skeleton (fore- and hindlimbs) with that of other placental and marsupial mammals revealed that despite their unique adult morphologies, thylacines retained a generalized early marsupial ontogeny. Our approach also revealed mislabelled specimens that possessed large epipubic bones (vestigial in thylacine) and differing vertebral numbers. All of our generated CT models are publicly available, preserving their developmental morphology and providing a novel digital resource for future studies of this unique marsupial.
Information theory, predictability and the emergence of complex life
Authors: Seoane Luís F. , Solé Ricard V.
Published: February 2018

Despite the obvious advantage of simple life forms capable of fast replication, different levels of cognitive complexity have been achieved by living systems in terms of their potential to cope with environmental uncertainty. Against the inevitable cost associated with detecting environmental cues and responding to them in adaptive ways, we conjecture that the potential for predicting the environment can overcome the expenses associated with maintaining costly, complex structures. We present a minimal formal model grounded in information theory and selection, in which successive generations of agents are mapped into transmitters and receivers of a coded message. Our agents are guessing machines and their capacity to deal with environments of different complexity defines the conditions to sustain more complex agents.
Pairwise approximation for
SIR
-type network epidemics with non-Markovian recovery
Authors: Röst G. , Vizi Z. , Kiss I. Z.
Published: February 2018

We present the generalized mean-field and pairwise models for non-Markovian epidemics on networks with arbitrary recovery time distributions. First we consider a hyperbolic partial differential equation (PDE) system, where the population of infective nodes and links are structured by age since infection. We show that the PDE system can be reduced to a system of integro-differential equations, which is analysed analytically and numerically. We investigate the asymptotic behaviour of the generalized model and provide an implicit analytical expression involving the final epidemic size and pairwise reproduction number. As an illustration of the applicability of the general model, we recover known results for the exponentially distributed and fixed recovery time cases. For gamma- and uniformly distributed infectious periods, new pairwise models are derived. Theoretical findings are confirmed by comparing results from the new pairwise model and explicit stochastic network simulation. A major benefit of the generalized pairwise model lies in approximating the time evolution of the epidemic.
Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe
Authors: Gordon Stephen V. , Parish Tanya
Published: February 2018

Mycobacterium tuberculosis is an expert and deadly pathogen, causing the disease tuberculosis (TB) in humans. It has several notable features: the ability to enter non-replicating states for long periods and cause latent infection; metabolic remodelling during chronic infection; a thick, waxy cell wall; slow growth rate in culture; and intrinsic drug resistance and antibiotic tolerance. As a pathogen, M. tuberculosis has a complex relationship with its host, is able to replicate inside macrophages, and expresses diverse immunomodulatory molecules. M. tuberculosis currently causes over 1.8 million deaths a year, making it the world’s most deadly human pathogen.
Enhanced instructed fear learning in delusion-proneness
Authors: Louzolo Anaïs , Almeida Rita , Guitart-Masip Marc , Björnsdotter Malin , Ingvar Martin , Olsson Andreas , Petrovic Predrag
Published: February 2018

Psychosis is characterized by distorted perceptions and deficient low-level learning, including reward learning and fear conditioning. This has been interpreted as reflecting imprecise priors in a predictive coding system. However, this idea is not compatible with formation of overly strong beliefs and delusions in psychosis-associated states. A reconciliation of these paradoxical observations is that these individuals actively develop and use higher-order beliefs in order to interpret a chaotic environment. In the present behavioural and fMRI study, we compared delusion-prone individuals (n=20), a trait related to psychotic disorders, with controls (n=23; n=20 in fMRI-part) to study the effect of beliefs on fear learning. We show that instructed fear learning, involving explicit change of beliefs and an associated activation of lateral orbitofrontal cortex, is expressed to a higher degree in delusion-prone subjects. Our results suggest that strong high-level top-down learning co-exists with previously reported weak low-level bottom-up learning in psychosis-associated states.
Dual-layer transposon repression in heads of Drosophila melanogaster
Authors: van den Beek Marius , da Silva Bruno , Pouch Juliette , Ali Chaouche Mohammed el amine , Carré Clément , Antoniewski Christophe
Published: February 2018

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of heritable mutations caused by their transposition in the genome. It is not clear whether the piRNA pathway plays a functional role in adult, non-gonadal tissues in Drosophila melanogaster. To address this question, we first analyzed the small RNA content of adult Drosophila melanogaster heads. We found that varying amount of piRNA-sized, ping-pong positive molecules in heads correlates with contamination by gonadal tissue during RNA extraction, suggesting that most of piRNAs detected in head sequencing libraries originate from gonads. We next sequenced the heads of wild type and piwi mutants to address whether piwi loss of function would affect the low amount of piRNA-sized, ping-pong negative molecules that are still detected in heads hand-checked to avoid gonadal contamination. We find that loss of piwi does not affect significantly these 24-28 RNA molecules. Instead, we observe increased siRNA levels against the majority of Drosophila transposable element families. To determine the effect of this siRNA level change on transposon expression, we sequenced the transcriptome of wild type, piwi, dicer-2 and piwi, dicer-2 double-mutant fly heads. We find that RNA expression levels of the majority of TE families in piwi or dicer-2 mutants remain unchanged and that TE transcript abundance increases significantly only in piwi, dicer-2 double-mutants. These results lead us to suggest a dual-layer model for TE repression in adult somatic tissues. Piwi-mediated transcriptional gene silencing (TGS) established during embryogenesis constitutes the first layer of TE repression whereas Dicer-2-dependent siRNA-mediated post-transcriptional gene silencing (PTGS) provide a backup mechanism to repress TEs that escape silencing by piwi-mediated TGS.
Borderline personality disorder with cocaine dependence: impulsivity, emotional dysregulation and amygdala functional connectivity
Authors: Balducci Thania , Gonzalez-Olvera Jorge J , Angeles-Valdez Diego , Espinoza-Luna Isabel , Garza-Villarreal Eduardo A
Published: February 2018

Objective: Borderline personality disorder (BPD) is present in 19% of cocaine dependence (CD) cases; however, this dual pathology (DP) is poorly understood. We assessed impulsivity, emotional dysregulation (ED) and amygdala functional connectivity in this DP.

Methods. We recruited 69 participants divided into 4 groups: DP (n = 20), CD without BPD (n = 19), BPD without CD (n = 10) and healthy controls (HC, n = 20). We used self-reported instruments to measure impulsivity and ED. We acquired resting state fMRI and performed seed-based analyses of functional connectivity (FC) of bilateral amygdalas.

Results. BPD and CD factors had opposing effects in impulsivity and ED, as well as on FC between left amygdala and medial prefrontal cortex. For the FC between right amygdala and left insula, the effect of having both disorders was additive, reducing FC strength. Significant FC clusters were correlated with impulsivity and ED.

Conclusions. In this preliminary study, we found that clinical scores of DP patients were closer to those of BPD without CD than to those of CD without BPD, while amygdala to medial prefrontal cortex FC patterns in DP patients were closer to HC than expected.
Microbial Treatment of Soil Contaminated with Spent engine Oil / Biotreatment of Soil Contaminated with Spent Engine by Microorganisms
Authors: Ayandele A. A.
Published: February 2018

The potential of six microorganisms (Pseudomonas aeruginosa, Micrococcus sp, Flavobacterium sp, Rhizopus sp, Penicillium sp and Fusarium sp) isolated from hydrocarbon contaminated site were evaluated for their biodegradation ability. The soil samples were contaminated with 5% (w/v) of spent engine oil and the rate of biodegradation of the oil was studied for a period of 10weeks under greenhouse experiment. The total heterotrophic bacteria count (THBC), total hydrocarbon degrading bacteria count (THDBC), physicochemical and heavy metals properties of the soil samples and Total Petroleum Hydrocarbon (TPH) were determined after treatment with test organisms. THBC and THDBC ranged from 0.175 to 0.280 CFUg-1 and 0.47 CFUg-1 respectively for the control plot, while THBC is ranging from 0.197 to 0.275 CFUg-1 and THDBC was 0.180 to 0. 473 CFUg-1 for the contaminated plot. There was a slight increase in the pH value of the contaminated soil sample and the treated soil samples as the experimental weeks increased. The results obtained showed a significant decrease (at p ≤ 0.05) in the nutrients content of the soil samples. There was an increase from 1.09 in the control to 15.5% in the content of organic matter after contamination and from 1.88% to 26.8% in the % of organic matter too. There was a significant reduction (at p ≤ 0.05) in the concentration of Fe, Zn, Pb, Cd, Cu, Cr and Ni after 10 weeks of incubation with the tested organisms. Plant growth in the treated contaminated soil samples ranged from 32.6cm to 38.6cm, while that of the control 1 (Uncontaminated soil) was 51.2cm and 19.7cm high was observed in the Control 2 (contaminated untreated soil) after 22 days of the experiment. The TPH degradation (% loss) ranged from 79.7 to 89. 2% after 10 weeks of treatment. P. aeruginosa had the highest level of degradation (89.2%), while Micrococcus sp and Rhizopus sp had the least degradation at 79.9%.

All the microorganisms used in this study had the abilities to remediating soil contaminated with spent engine oil and the remediated soil samples were able to support the growth of Zea mays at 5% (w/v) level of contamination.
Early lethality of embryos derived from transgenic Xenopus females is associated with reduced ovarian grem1 expression
Authors: Beck Caroline W. , Ward Joanna , Troise Lisa , Brochard Catherine
Published: February 2018

The grem1 gene codes a protein that inhibits the action of multiple members of a growth factor family known as bone morphogenetic proteins (BMPs). Certain members of this BMP family can regulate both fecundity and fertility in mammals via their action on oocyte (egg) development, and grem1 has been identified as a marker of oocyte quality in humans. The model amphibian Xenopus laevis is far more fecund than mammals, producing thousands of eggs in a clutch. However, female transgenic frogs carrying grem1 under the control of a stress inducible hsp70 promoter (“G” frogs) produce very few viable offspring. Here, we show that this is not due to reduced fecundity or fertilization rate, but results from a significant reduction in subsequent survival over the first day of development. Embryos that successfully survive for the first day were found to go on to develop normally when compared to their peers. Both the morphology and stage distribution of oocytes from G females appears normal, and oocytes develop at expected rates, although stage VI oocytes were found to have a lower response to in vitro progesterone treatment. Unexpectedly, levels of grem1 mRNA were found to be consistently lower in the female ovaries from four independent G transgenic lines than in wild type ovaries. Both transgenic and wild type offspring were equally affected, confirming a maternal effect. Our study shows that transgenic females with the lowest levels of grem1 transcripts in the ovary have the lowest rates of survival past the first day of amphibian embryogenesis, equivalent to pre-implantation staged mammalian embryos. The reduced expression of grem1 in the oocytes of transgenic females suggests transgene supression of an endogenous locus may occur in the Xenopus female germline, an unexpected finding.
Understanding 6th-Century Barbarian Social Organization and Migration through Paleogenomics
Authors: Amorim Carlos Eduardo G. , Vai Stefania , Posth Cosimo , Modi Alessandra , Koncz István , Hakenbeck Susanne , La Rocca Maria Cristina , Mende Balazs , Bobo Dean , Pohl Walter , Baricco Luisella Pejrani , Bedini Elena , Francalacci Paolo , Giostra Caterina , Vida Tivadar , Winger Daniel , von Freeden Uta , Ghirotto Silvia , Lari Martina , Barbujani Guido , Krause Johannes , Caramelli David , Geary Patrick J. , Veeramah Krishna R.
Published: February 2018

ABSTARCT

Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early Medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data was consistent with the proposed long-distance migration from Pannonia to Northern Italy.
Making honey bees lie: experimental dissociation of flight experience and dance communication
Authors: Chatterjee Arumoy , Prabhudev M.V. , George Ebi A. , Basu Pallab , Brockmann Axel
Published: February 2018

Honey bees use their dance to communicate flight distance and direction of a food source to their nest mates in the hive. How bees transpose flight information to generate a corresponding walking (dance) behavior is still unknown. We now present a detailed study of the changes in dance duration of individual bees after shifting feeder distance. Our experiments indicated that most bees needed two or more foraging trips to the new position before showing an updated dance duration. In addition, only a few bees significantly changed dance duration immediately, whereas most bees first produced intermediary durations. Double shift experiments showed that under certain conditions bees do not update dance duration but continued to perform dance duration for the previously visited feeder position. We propose that generation of dance information involves two memory contents one for newly acquired and one for previously stored distance information.

One Sentence Summary

Generation of dance information is temporally separated from immediate flight experience and involves two different memory contents.
Dynamic Network Analysis of the 4D Nucleome
Authors: Liu Sijia , Chen Pin-Yu , Hero Alfred , Rajapakse Indika
Published: February 2018

Motivation

For many biological systems, it is essential to capture simultaneously the function, structure, and dynamics in order to form a comprehensive understanding of underlying phenomena. The dynamical interaction between 3D genome spatial structure and transcriptional activity creates a genomic signature that we refer to as the four-dimensional organization of the nucleus, or 4D Nucleome (4DN). The study of 4DN requires assessment of genome-wide structure and gene expression as well as development of new approaches for data analysis.

Results

We propose a dynamic multilayer network approach to study the co-evolution of form and function in the 4D Nucleome. We model the dynamic biological system as a temporal network with node dynamics, where the network topology is captured by chromosome conformation (Hi-C), and the function of a node is measured by RNA sequencing (RNA-seq). Network-based approaches such as von Neumann graph entropy, network centrality, and multilayer network theory are applied to reveal universal patterns of the dynamic genome. Our model integrates knowledge of genome structure and gene expression along with temporal evolution and leads to a description of genome behavior on a system wide level. We illustrate the benefits of our model via a real biological dataset on MYOD1-mediated reprogramming of human fibroblasts into the myogenic lineage. We show that our methods enable better predictions on form-function relationships and refine our understanding on how cell dynamics change during cellular reprogramming.

Availability: The software is available upon request.

Contact

indikar@umich.edu

Supplementary information

See Supplementary Material.
Delineating feedback activity in the MAPK and AKT pathways using feedback-enabled Inference of Signaling Activity
Authors: Thijssen Bram , Jastrzebski Katarzyna , Beijersbergen Roderick L. , Wessels Lodewyk F.A.
Published: February 2018

An important aspect of cellular signaling networks is the existence of feedback mechanisms. However, due to the complexity of signaling networks, as well as the presence of multiple interrelated feedback events, it can be difficult to identify which signaling routes are active in any particular context. We have previously shown that Inference of Signaling Activity (ISA) can be a useful method to study steady-state oncogenic signaling across different cell lines and inhibitor treatments. However, ISA did not explicitly include feedback signaling events. Incorporating feedback will increase the complexity and computational cost of the model, and more data is likely to be needed to infer feedback activities. Here, we developed feedback-ISA (f-ISA), an extension of the ISA modeling approach which incorporates feedback signaling events. It also includes integrated batch correction in order to fit the models to multiple, independent datasets simultaneously. We find that the identifiability of feedback activities can be counter-intuitive, which shows the importance of analyzing the full, joint uncertainty in model parameters. By iteratively adapting the model and including multiple datasets, including both steady state and intervention data, we constructed a model that can explain a large part of the phosphorylation levels of several signaling molecules in the MAPK and AKT pathways, across many breast cancer cell lines and across various conditions. The resulting model delineates which routes in the signaling network are likely to be active in each cell line and condition, given all of the data. Additionally, such models can indicate whether datasets agree with each other, and identify which parts of the data cannot be explained, thereby highlighting gaps in the current knowledge. We conclude that this modeling approach can be useful to quantitatively understand how complex cellular signaling networks behave across different cell lines and conditions.
Precise Slow Oscillation-Spindle Coupling Promotes Memory Consolidation in Younger and Older Adults
Authors: Muehlroth Beate E. , Sander Myriam C. , Fandakova Yana , Grandy Thomas H. , Rasch Björn , Shing Yee Lee , Werkle-Bergner Markus
Published: February 2018

Memory consolidation during sleep relies on the precisely timed interaction of rhythmic neural events. Here, we investigate differences in slow oscillations (SO) and sleep spindles (SP) and their coupling across the adult human lifespan and ask whether observed alterations relate to the ability to retain associative memories across sleep. We demonstrate that the fine-tuned SO–SP coupling that is present in younger adults diffuses with advanced age and shifts both in time and frequency. Crucially, we show that the tight precision of SO–SP coupling promotes memory consolidation in younger and older adults, and that brain integrity in source regions for the generation of SOs and SPs reinforces this beneficial SO–SP coupling in old age. Our results reveal age-related differences in SO–SP coupling in healthy elderly individuals. Furthermore, they broaden our understanding of the conditions and the functional significance of SO–SP coupling across the entire adult lifespan.