bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse model of imiquimod-induced psoriatic itch
Authors: Sakai Kent , Sanders Kristen M. , Youssef Marina R. , Yanushefski Kevin M. , Jensen Liselotte , Yosipovitch Gil , Akiyama Tasuku
Published: July 2016

Itch is a major indicator of psoriasis, but the underlying mechanisms behind this symptom are largely unknown. To investigate the neuronal mechanisms of psoriatic itch, we tested whether mice subjected to the imiquimod-induced psoriasis model exhibit itch-associated behaviors. Mice received daily topical applications of imiquimod to the rostral back skin for 7 days. Imiquimod-treated mice exhibited a significant increase in spontaneous scratching behavior directed to the treated area as well as touch-evoked scratching (alloknesis). To characterize this model, we measured the mRNA expression levels of pruritogens and itch-relevant receptors/channels using real-time reverse transcription PCR. The mRNA expression of MrgprA3, MrgprC11, and MrgprD decreased gradually over time in the dorsal root ganglion (DRG) cells. There was no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells. TRPV4 mRNA expression was transiently increased in the DRG cells, whereas TRPM8 mRNA was significantly decreased. The mRNA expression levels of histidine decarboxylase and tryptophan hydroxylase 1, as well as the intensity of histamine and serotonin immunoreactivity, were transiently increased in the skin on day 2, returning to baseline by day 7. Histamine H1-receptor antagonists, chlorpheniramine and olopatadine, significantly inhibited spontaneous scratching on day 2, but not day 7. Neither chlorpheniramine nor olopatadine affected alloknesis on day 2 or day 7. These results may reflect the limited antipruritic effects of histamine H1-receptor antagonists on human psoriasis. The imiquimod-induced psoriasis model seems to be useful for the investigation of itch and its sensitization in psoriasis.
How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment
Authors: Rubio-Abadal Elena , Del Cacho Núria , Saenz-Navarrete Gerard , Arranz Belen , Cambra Rosa-Maria , Cuadras Daniel , Rodante Demián , Fehér Csaba , Roca Mercedes , Barneda Vanessa , Usall Judith
Published: July 2016

Objective

We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship.

Method

A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire—short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed.

Results

A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor.

Conclusions

In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.
Clinical Trial of 1000 Subjects Randomized to 5 Low-Volume Bowel Preparations for Colonoscopy and Their Acceptance of Split-Dose Bowel Preparations
Authors: Gerard David P. , Foster Diane B. , Holden John L. , Kang Jieun , Raiser Manfred W.
Published: July 2016

Background:

We assessed the efficacy and tolerability of 5 low-volume bowel preparations for colonoscopy.

Study:

We performed an investigator-blinded, randomized trial of 5 bowel preparations: 64 ounces of Gatorade and 306 or 357 g of PEG, both given the day prior; Gatorade and 306 g PEG, 2 L PEG-electrolyte solution with ascorbic acid, and sulfate solution, all 3 given as a split dose. One thousand outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago Bowel Preparation Scale (BPS). Tolerability was assessed using a subject questionnaire. Another primary endpoint was patient acceptance of a split-dose bowel preparation assessed using a subject questionnaire.

Results:

No statistically significant differences in the modified Chicago BPS were found among Gatorade and 357 g of PEG given as a day-prior dose and the 3 split-dose arms with 98.5% of colons cleansed adequately. The Gatorade and 357 g of PEG had significantly lower Chicago BPS fluid scores and Chicago BPS total scores (indicating dryer colons that required more irrigation) than the 3 split-dose arms. The Gatorade and PEG preparations were better tolerated. Many subjects are unwilling to consume a split-dose preparation and the majority of subjects would prefer a day-prior preparation with this preference highly dependent on the type of preparation they just consumed.

Conclusions:

The cleanliness of the colons was not significantly different among the 3 split-dose preparations. Day-prior dosing of Gatorade and 357 g of PEG allowed the mucosa to be visualized as well as did the split-dose preparations.
High prevalence of chronic hepatitis B and C virus infection in a population of a German metropolitan area: a prospective survey including 10 215 patients of an interdisciplinary emergency unit
Authors: Bert Florian , Rindermann Andreas , Abdelfattah Murad A. , Stahmeyer Jona T. , Rossol Siegbert
Published: July 2016

Purpose

The prevalence of chronic hepatitis B virus- and hepatitis C virus-infections in the general German population has been estimated to be 0.6–0.7 and 0.3–0.4%, respectively. The population of Frankfurt/Main is multicultural and marked by different risks of chronic viral hepatitis. The aim of this prospective study was to define epidemiologic data for hepatitis B and C from consecutive patients of an interdisciplinary emergency unit in Frankfurt.

Patients and methods

Over a period of 12 months, 10 215 patients of an interdisciplinary emergency unit in Frankfurt/Main were screened for hepatitis B surface-antigen (HBsAg) and hepatitis C virus-antibodies (HCV-Ab). In case of positive HBsAg or HCV-Ab, a quantitative PCR analysis of virus was carried out.

Results

The prevalence of HBsAg and HCV-Ab in the study population was 1.32% (n=135; group 1) and 2.70% (n=276; group 2), respectively, with a sex ratio close to 1. Quantitative PCR tests of virus load were performed in 72.59% (group 1) and in 82.61% (group 2), with confirmed viremia in 54.08% (group 1) and 41.67% (group 2), and correlated to elevated liver enzymes in 49.05% (group 1) and in 75.78% (group 2) of the cases. The ethnic distribution was 87.09% White (n=8897; group A) versus 12.90% other ethnic groups (n=1318; group B), with a prevalence of HBsAg-positive and HCV-Ab-positive cases of 1.08 and 2.76% (group A) and 2.96 and 2.28% (group B).

Conclusion

The results show that in multicultural areas, the prevalence of chronic viral hepatitis is increased. Because of the potential of progressive liver damage in viral hepatitis, field screening in specific populations at high risk for hepatitis should be performed.
Molecular basis of inherited thrombocytopenias: an update
Authors: Savoia Anna
Published: July 2016

Purpose of review

Inherited thrombocytopenias are a heterogeneous group of diseases caused by mutations in many genes. They account for approximately only 50% of cases, suggesting that novel genes have yet to be identified for a comprehensive understanding of platelet biogenesis defects. This review provides an update of the last year of discoveries on inherited thrombocytopenias focusing on the molecular basis and potential pathogenic mechanisms affecting megakaryopoiesis and platelet production.

Recent findings

Most of the novel discoveries are related to identification of mutations in novel inherited thrombocytopenia genes using a next-generation sequencing approach. They include MECOM, DIAPH1, TRPM7, SRC, FYB, and SLFN14, playing different roles in megakaryopoiesis and platelet production. Moreover, it is worth mentioning data on hypomorphic mutations of FLI1 and the association of single nucleotide polymorphisms, such as that identified in ACTN1, with thrombocytopenia.

Thanks to the application of next-generation sequencing, the number of inherited thrombocytopenia genes is going to increase rapidly. Considering the wide genetic heterogeneity (more than 30 genes), these technologies can also be used for diagnostic purpose. Whatever is the aim, extreme caution should be taken in interpreting data, as inherited thrombocytopenias are mainly autosomal dominant diseases caused by variants of apparent unknown significance.
New views on global child health: global solutions for care of vulnerable children in the United States
Authors: Uwemedimo Omolara T. , Arora Gitanjli , Russ Christiana M.
Published: July 2016

Purpose of review

This paper provides a brief overview of the current landscape of global child health and the impact of social determinants on the world's children. In the United States (US), global child health (GCH) has increasingly been highlighted as a priority area by national organizations, such as the National Academy of Medicine and American Academy of Pediatrics, as well as individual pediatricians committed to ensuring the health of all children regardless of geographic location. Although GCH is commonly used to refer to the health of children outside of the US, here, we highlight the recent call for GCH to also include care of US vulnerable children. Many of the lessons learned from abroad can be applied to pediatrics domestically by addressing social determinants that contribute to health disparities.

Recent findings

Using the ‘three-delay’ framework, effective global health interventions target delays in seeking, accessing, and/or receiving adequate care. In resource-limited, international settings, novel health system strengthening approaches, such as peer groups, community health workers, health vouchers, cultural humility training, and provision of family-centered care, can mitigate barriers to healthcare and improve access to medical services.

The creative use of limited resources for pediatric care internationally may offer insight into effective strategies to address health challenges that children face here in the US. The growing number of child health providers with clinical experience in resource-limited, low-income countries can serve as an unforeseen yet formidable resource for improving pediatric care in underserved US communities.
Comparison of the effects of mirror therapy and electromyography-triggered neuromuscular stimulation on hand functions in stroke patients: a pilot study
Authors: Amasyali Saliha Y. , Yaliman Ayşe
Published: July 2016

To determine the effectiveness of mirror therapy and electromyography (EMG)-triggered neuromuscular stimulation on improvement of functions of the upper extremity in patients with subacute stroke in comparison with conventional therapy as well as to evaluate the advantage of each treatment over another, we conducted a prospective, randomized, and controlled trial involving 24 patients with ischemic stroke. The mean age and mean time since stroke of the patients were 58.79±11.49 years and 5.25±2.25 months. Patients were assigned randomly to a mirror therapy group (MT group, n=9), which consisted of therapy with a mirror box 5 days/week, 30 min/day, for 3 weeks, an electrostimulation group (ES group, n=7), which consisted of therapy with EMG-triggered stimulation (EMG-stim) of similar duration and frequency of treatment as the MT group, and a control group (n=8). All the groups received conventional physiotherapy for the same period as the MT group. Patients in the MT group practiced their therapy at home after supervised sessions. The Fugl-Meyer scores of the upper extremity, grip force, wrist extension, and Box and Block Test were evaluated at baseline, after treatment, and at 3 months after the treatment. All of these measures were evaluated by a blinded researcher. We found that there was no significant improvement in wrist extension range and grip force in control group. The MT and EMG-stim were effective in increasing the Fugl-Meyer motor scale for upper extremity (MT group: P<0.01), increasing wrist extension range, grip force, and hand dexterity determined by the Box and Block Test (MT group and ES group P<0.05). Furthermore, hand skills were increased significantly in the MT group compared with the ES group at the follow-up assessment (P<0.05). This pilot study suggested that MT was more efficient in improving motor performance than physiotherapy alone. Also, MT may be more useful in improving the hand skills compared with EMG-stim. We assume that this difference might be related to the feasibility of maintenance of MT at home.
Active music therapy approach in amyotrophic lateral sclerosis: a randomized-controlled trial
Authors: Raglio Alfredo , Giovanazzi Elena , Pain Debora , Baiardi Paola , Imbriani Chiara , Imbriani Marcello , Mora Gabriele
Published: July 2016

This randomized controlled study assessed the efficacy of active music therapy (AMT) on anxiety, depression, and quality of life in amyotrophic lateral sclerosis (ALS). Communication and relationship during AMT treatment were also evaluated. Thirty patients were assigned randomly to experimental [AMT plus standard of care (SC)] or control (SC) groups. AMT consisted of 12 sessions (three times a week), whereas the SC treatment was based on physical and speech rehabilitation sessions, occupational therapy, and psychological support. ALS Functional Rating Scale-Revised, Hospital Anxiety and Depression Scale, McGill Quality of Life Questionnaire, and Music Therapy Rating Scale were administered to assess functional, psychological, and music therapy outcomes. The AMT group improved significantly in McGill Quality of Life Questionnaire global scores (P=0.035) and showed a positive trend in nonverbal and sonorous-music relationship during the treatment. Further studies involving larger samples in a longer AMT intervention are needed to confirm the effectiveness of this approach in ALS.
Debriefing as a Supportive Component for Registered Nurses in Transition
Authors: Shinners Jean , Africa Larissa , Hawkes Beth
Published: July 2016

Debriefing is considered a positive approach used to evaluate learning, support communication, and explore emotions following simulation or a clinical experience. This article discusses the use of debriefing as an evolving strategy for new graduate nurses and focuses on the importance of structured clinical debriefing as a component to relieve stress while providing periods of reflection and cohesion.
Postmortem Body and Organ Measurements in Neonates and Infants
Authors: Evetts Audrey-Ann Marie , Shkrum Michael J. , Tugaleva Elena
Published: July 2016

It is common practice in pediatric autopsies to compare the body and organ measurements of the deceased child against the existing reference data. Although a number of resources are available, many are outdated and have significant limitations. The goal of this study was to assess the reference sources currently used by the Ontario pathologists in pediatric autopsies. A survey of 14 Ontario pathologists, who do coroners' pediatric autopsies, identified 20 publications commonly referenced for body and organ measurements. Of all the cited sources, only a few had all the features regarded by the pathologists as ideal for a reference source. These features included accessibility to the source, large sample size, defined control populations, statistical analyses, and sex distinctions. The results of this study will be used to guide the development of a new reference, based on Ontario data, that will enhance measurement standards in pediatric autopsy practice.
A Limited Immunohistochemical Panel to Distinguish Basal Cell Carcinoma of Cutaneous Origin From Basaloid Squamous Cell Carcinoma of the Head and Neck
Authors: Villada Gabriel , Kryvenko Oleksandr N. , Campuzano-Zuluaga German , Kovacs Christina , Chapman Jennifer , Gomez-Fernandez Carmen
Published: July 2016

Head and neck carcinomas with basaloid features can be diagnostically challenging. A common diagnostic issue is the distinction between a basaloid squamous cell carcinoma (bSCC) and a basal cell carcinoma (BCC) of cutaneous origin. This is particularly true in small biopsy specimens where classic architectural and histologic features may be difficult to appreciate. A specific diagnosis is essential because of significant differences in clinical outcome and therapeutic management. Ten resection cases of bSCC and BCC of the head and neck were selected based on primary location and the classic morphologic features that characterize these 2 entities. The following immunohistochemical markers were evaluated: epithelial membrane antigen (EMA), Ber-EP4, CD44, Bcl2, androgen receptor, SOX2, and p16. The strongest statistically significant differences in staining patterns were for EMA, p16, and SOX2. EMA was positive in all bSCCs and negative in all BCCs. SOX2 was positive in all bSCCs and in only 3 out of 10 BCCs. Staining was weak and peripheral in the SOX2-positive BCCs. p16 was positive in 8 out of 10 bSCCs and negative in all BCCs. We conclude that bSCC and BCC of the head and neck can be readily distinguished by a limited panel consisting primarily of EMA, and supported by SOX2 and p16.
PTEN Expression in Mucinous Prostatic Adenocarcinoma, Prostatic Adenocarcinoma With Mucinous Features, and Adjacent Conventional Prostatic Adenocarcinoma: A Multi-institutional Study of 92 Cases
Authors: Bertsch Elizabeth C. , Magi-Galluzzi Cristina , Cheng Liang , Osunkoya Adeboye O.
Published: July 2016

Recent studies have demonstrated that most patients with mucinous prostatic adenocarcinoma may have a better prognosis than those with conventional prostatic adenocarcinoma; however, the mechanism remains unclear. Loss of phosphatase and tensin homolog (PTEN) expression is known to occur in aggressive high-grade prostatic adenocarcinoma, but expression in mucinous prostatic adenocarcinoma has not been well characterized. In this study, we sought to analyze PTEN expression in mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma. Cases were obtained from the Urologic Pathology files of 3 major academic institutions. Ninety-two cases were identified. PTEN expression was positive in the mucinous component of 79/92 (86%) cases. Concordant positive expression of PTEN between mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma was present in 60/79 (76%) cases. The fact that 86% of cases of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were positive for PTEN despite relatively high Gleason scores is in keeping with the fact that these tumors may be less aggressive than conventional prostatic adenocarcinoma without associated extraluminal mucinous components. In 76% of cases, the expression profiles (PTEN positive or negative) of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were similar to those of the adjacent conventional prostatic adenocarcinoma, implying that they may likely be clonal from a molecular standpoint. In addition, it is highly conceivable that the subset of PTEN-negative mucinous tumors may still have a relatively good prognosis due to a different/PTEN-independent protective pathway or mechanism.
A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype
Authors: Valente Kari , Blackham Aaron U. , Levine Edward , Russell Greg , Votanopoulos Konstantinos I. , Stewart John H. , Shen Perry , Geisinger Kim R. , Sirintrapun Sahussapont J.
Published: July 2016

Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype.
Improving Depression Among HIV-Infected Adults: Transporting the Effect of a Depression Treatment Intervention to Routine Care
Authors: Bengtson Angela M. , Pence Brian W. , Gaynes Bradley N. , Quinlivan E. Byrd , Heine Amy D. , O'Donnell Julie K. , Crane Heidi M. , Mathews W. Christopher , Moore Richard D. , Westreich Daniel , O'Cleirigh Conall , Christopoulos Katerina , Mimiaga Matthew J. , Mugavero Michael J.
Published: July 2016

Background:

Depression affects 20%–30% of people with HIV. Randomized controlled trials (RCTs) have demonstrated the effectiveness of interventions to improve depression among HIV-infected adults, but typically have highly selected populations which may limit generalizability. Inverse probability of sampling weights (IPSW) is a recently proposed method to transport (or standardize) findings from RCTs to a specific external target population.

Methods:

We used IPSW to transport the 6-month effect of the Measurement-Based Care (MBC) intervention on depression from the SLAM DUNC trial to a population of HIV-infected, depressed adults in routine care in the United States between 2010 and 2014.

Results:

In the RCT, MBC was associated with an improvement in depression at 6 months of 3.6 points on the Hamilton Depression Rating scale [95% confidence interval (CI): −5.9 to −1.3]. When IPSW were used to standardize results from the trial to the target population, the intervention effect was attenuated by 1.2 points (mean improvement 2.4 points; 95% CI: −6.1 to 1.3).

Conclusions:

If implemented among HIV-infected, depressed adults in routine care, MBC may be less effective than in the RCT but can still be expected to reduce depression. Attenuation of the intervention effect among adults in routine care reflects the fact that the trial enrolled a larger proportion of individuals for whom the intervention was more effective. Given the burden of depression among HIV-infected adults, more effective interventions to improve depression are urgently needed. However, examining the transportability of trial findings is essential to understand whether similar effects can be expected if interventions are scaled-up.
Comparison of Routine Knee Magnetic Resonance Imaging at 3 T and 7 T
Authors: Springer Elisabeth , Bohndorf Klaus , Juras Vladimir , Szomolanyi Pavol , Zbýň Štefan , Schreiner Markus M. , Schmitt Benjamin , Trattnig Siegfried
Published: July 2016

Objective

The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR] and diagnostic confidence) from a standard knee magnetic resonance imaging (MRI) examination with comparable sequence protocols and acquisition times at 3 T and at 7 T.

Materials and Methods

Forty patients experiencing knee pain of unknown etiology underwent comparable MR protocols with standard turbo-spin echo and short tau inversion recovery sequences of the knee joint (5 sequences) at 3 T and 7 T. For quantitative analysis, SNR was determined using these 5 sequences and 3 additional morphological sequences. For a semiquantitative assessment of diagnostic confidence, a diagnostic confidence score (DCS) was assigned, using a 10-point scale. Two experienced radiologists who specialized in musculoskeletal imaging and who were blinded to the field-strength independently assessed 22 potential pathological findings, in total, in 4 anatomically defined areas in the knee joint and rated their diagnostic confidence.

Results

In quantitative analysis, all sequences provided higher voxel-volume-adjusted SNR values at 7 T compared with that at 3 T. In semiquantitative analysis, summed DCS values for potential pathological findings in each of the 4 anatomically defined areas were higher at 7 T compared with that at 3 T. There was a statistically significant improvement in the DCS for both readers at 7 T for the diagnosis and exclusion of focal or diffuse grade I or II cartilage defects in the patellar cartilage. For 8 potential pathological findings, a statistically significant difference between the 2 field-strengths could be observed for 1 reader only. For the residual 13 potential pathological findings, there was no statistically significant difference observed. The percentage of concordant ratings was 84.6% at 3 T and 85.4% at 7 T.

Conclusions

Ultra-high-field MRI at 7 T improved the overall diagnostic confidence in routine MRI of the knee joint compared with that at 3 T. This is especially true for small joint structures and subtle lesions. Higher spatial resolution was identified as the main reason for this improvement.
Percutaneous Pancreatic Biopsies—Still an Effective Method for Histologic Confirmation of Malignancy
Authors: Bhatti Imran , Ojo Dotun , Dennison Ashley R. , Rees Yvonne , Elabassy Mosheir , Garcea Giuseppe
Published: July 2016

Purpose:

To determine the accuracy and safety of the percutaneous biopsy of pancreatic mass lesions.

Materials and Methods:

Over a 12-year period clinical parameters, imaging, pathologic results, and complications were assessed in patients undergoing percutaneous biopsies pancreatic lesions.

Results:

One hundred fifty-three patients underwent pancreatic biopsy. The preferred modality for performing the biopsy was ultrasound (93%, n=143) followed by computerized tomography (7%, n=10). Histologic diagnosis was achieved in 147 patients, of which 3 (2%) were benign and 144 (94%) were malignant. Complications included a single death from overwhelming hemorrhage and 2 patients with morbidity (hematoma and cerebrovascular accident). The sensitivity and specificity of percutaneous biopsies was 90% and 95%, respectively.

Conclusions:

Ultrasound-guided and computerized tomographic-guided percutaneous biopsy of pancreatic lesions is an effective and safe method to confirm or refute malignancy in suspicious pancreatic lesions. Endoscopic ultrasound-guided Tru-Cut may have the added advantage of avoiding the risk of peritoneal soiling.
Some mechanistic requirements for major transitions
Authors: Schuster Peter
Published: July 2016

Major transitions in nature and human society are accompanied by a substantial change towards higher complexity in the core of the evolving system. New features are established, novel hierarchies emerge, new regulatory mechanisms are required and so on. An obvious way to achieve higher complexity is integration of autonomous elements into new organized systems whereby the previously independent units give up their autonomy at least in part. In this contribution, we reconsider the more than 40 years old hypercycle model and analyse it by the tools of stochastic chemical kinetics. An open system is implemented in the form of a flow reactor. The formation of new dynamically organized units through integration of competitors is identified with transcritical bifurcations. In the stochastic model, the fully organized state is quasi-stationary whereas the unorganized state corresponds to a population with natural selection. The stability of the organized state depends strongly on the number of individual subspecies,n, that have to be integrated: two and three classes of individuals,and, readily form quasi-stationary states. The four-membered deterministic dynamical system,, is stable but in the stochastic approach self-enhancing fluctuations drive it into extinction. In systems with five and more classes of individuals,, the state of cooperation is unstable and the solutions of the deterministic ODEs exhibit large amplitude oscillations. In the stochastic system self-enhancing fluctuations lead to extinction as observed with. Interestingly, cooperative systems in nature are commonly two-membered as shown by numerous examples of binary symbiosis. A few cases of symbiosis of three partners, calledthree-way symbiosis, have been found and were analysed within the past decade. Four-way symbiosis is rather rare but was reported to occur in fungus-growing ants. The model reported here can be used to illustrate the interplay between competition and cooperation whereby we obtain a hint on the role that resources play in major transitions. Abundance of resources seems to be an indispensable prerequisite of radical innovation that apparently needs substantial investments. Economists often claim that scarcity is driving innovation. Our model sheds some light on this apparent contradiction. In a nutshell, the answer is: scarcity drives optimization and increase in efficiency but abundance is required for radical novelty and the development of new features.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Generating minimal living systems from non-living materials and increasing their evolutionary abilities
Authors: Rasmussen Steen , Constantinescu Adi , Svaneborg Carsten
Published: July 2016

We review lessons learned about evolutionary transitions from a bottom-up construction of minimal life. We use a particular systemic protocell design process as a starting point for exploring two fundamental questions: (i) how may minimal living systems emerge from non-living materials? and (ii) how may minimal living systems support increasingly more evolutionary richness? Under (i), we present what has been accomplished so far and discuss the remaining open challenges and their possible solutions. Under (ii), we present a design principle we have used successfully both for our computational and experimental protocellular investigations, and we conjecture how this design principle can be extended for enhancing the evolutionary potential for a wide range of systems.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Viruses and mobile elements as drivers of evolutionary transitions
Authors: Koonin Eugene V.
Published: July 2016

The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of ‘public goods’. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host–parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Stabilizing multicellularity through ratcheting
Authors: Libby Eric , Conlin Peter L. , Kerr Ben , Ratcliff William C.
Published: July 2016

The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary ‘ratchets’, limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Epigenetic inheritance systems contribute to the evolution of a germline
Authors: Lachmann Michael , Libby Eric
Published: July 2016

Differentiation within multicellular organisms is controlled by epigenetic markers transmitted across cell division. The process of differentiation will modify these epigenetic markers so that information that one cell type possesses can be lost in the transition to another. Many of the systems that encode these markers also exist in unicellular organisms but do not control differentiation. Thus, during the evolution of multicellularity, epigenetic inheritance systems were probably exapted for their current use in differentiation. We show that the simultaneous use of an information carrier for differentiation and transmission across generations can lead to the evolution of cell types that do not directly contribute to the progeny of the organism and ergo a germ–soma distinction. This shows that an intrinsic instability during a transition from unicellularity to multicellularity may contribute to widespread evolution of a germline and its maintenance, a phenomenon also relevant to the evolution of eusociality. The difference in epigenetic information contents between different cell lines in a multicellular organism is also relevant for the full-success cloning of higher animals, as well as for the maintenance of single germlines over evolutionary timescales.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Energy and time determine scaling in biological and computer designs
Authors: Moses Melanie , Bezerra George , Edwards Benjamin , Brown James , Forrest Stephanie
Published: July 2016

Metabolic rate in animals and power consumption in computers are analogous quantities that scale similarly with size. We analyse vascular systems of mammals and on-chip networks of microprocessors, where natural selection and human engineering, respectively, have produced systems that minimize both energy dissipation and delivery times. Using a simple network model that simultaneously minimizes energy and time, our analysis explains empirically observed trends in the scaling of metabolic rate in mammals and power consumption and performance in microprocessors across several orders of magnitude in size. Just as the evolutionary transitions from unicellular to multicellular animals in biology are associated with shifts in metabolic scaling, our model suggests that the scaling of power and performance will change as computer designs transition to decentralized multi-core and distributed cyber-physical systems. More generally, a single energy–time minimization principle may govern the design of many complex systems that process energy, materials and information.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Agent-based models for the emergence and evolution of grammar
Authors: Steels Luc
Published: July 2016

Human languages are extraordinarily complex adaptive systems. They feature intricate hierarchical sound structures, are able to express elaborate meanings and use sophisticated syntactic and semantic structures to relate sound to meaning. What are the cognitive mechanisms that speakers and listeners need to create and sustain such a remarkable system? What is the collective evolutionary dynamics that allows a language to self-organize, become more complex and adapt to changing challenges in expressive power? This paper focuses on grammar. It presents a basic cycle observed in the historical language record, whereby meanings move from lexical to syntactic and then to a morphological mode of expression before returning to a lexical mode, and discusses how we can discover and validate mechanisms that can cause these shifts using agent-based models.

This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation
Authors: Chan Shiu-Wan
Published: July 2016

We have previously shown that physio/pathological levels of hydrogen peroxide (H2O2) stimulate translation from the hepatitis C virus (HCV) internal ribosome entry site (IRES) element in tissue-cultured cells. Here, using in vitro translation, we further show that H2O2 upregulates HCV IRES-dependent mRNA translation and correlates with an increase in intracellular oxidant level. Using Western blotting, immunocytochemistry, microscopy and affinity pulldown, we show that H2O2 stimulates HCV IRES-dependent translation and correlates with nuclear–cytoplasmic shuttling of the La autoantigen, resulting in enhanced binding of cytoplasmic La to HCV IRES RNA. The role of the La protein in H2O2-stimulated IRES-dependent translation is further confirmed by the ability of an anti-La antibody to suppress H2O2-activated IRES-dependent translation in vitro. This is further supported by the ability of an ectopically expressed dominant, negative La mutant protein to suppress H2O2-inducible IRES-mediated translation in Huh7 cells, transiently transfected with a bicistronic reporter and in a sub-genomic replicon cell line resembling a persistent infection. On the other hand, translation from the encephalomyocarditis virus IRES is diminished in the presence of H2O2, suggesting that H2O2 translational responsiveness is a specific property of the HCV IRES and is not a general phenomenon for all viral IRESs. Altogether, these results suggest that HCV adapts to physio/pathological oxidative stress in the host cell by mediating La cytoplasmic shuttling to enhance its IRES-dependent translation.
Functional Cliques in Developmentally Correlated Neural Networks
Authors: Luccioli S. , Barzilai A. , Ben-Jacob E. , Bonifazi P. , Torcini A.
Published: July 2016

We consider a sparse random network of excitatory leaky integrate-andfire neurons with short-term synaptic depression. Furthermore to mimic the dynamics of a brain circuit in its first stages of development we introduce for each neuron correlations among in-degree and out-degree as well as among excitability and the corresponding total degree, We analyze the influence of single neuron stimulation and deletion on the collective dynamics of the network. We show the existence of a small group of neurons capable of controlling and even silencing the bursting activity of the network. These neurons form afunctional cliquesince only their activation in a precise order and within specific time windows is capable to ignite population bursts.
FEELnc: A tool for Long non-coding RNAs annotation and its application to the dog transcriptome
Authors: Wucher V , Legeai F , Hédan B , Rizk G , Lagoutte L , Leeb T , Jagannathan V , Cadieu E , David A , Lohi H , Cirera S , Fredholm M , Botherel N , Leegwater P , Le Béguec C , Fieten H , Johansson C , Johnsson J ,   LUPA consortium, Alifoldi J , André C , Lindblad-Toh K , Hitte C , Derrien T
Published: July 2016

Whole transcriptome sequencing (RNA-seq) has become a standard for cataloguing and monitoring RNA populations. Among the plethora of reconstructed transcripts, one of the main bottlenecks consists in correctly identifying the different classes of RNAs, particularly those that will be translated (mRNAs) from the class of long non-coding RNAs (lncRNAs). Here, we present FEELnc (FlExible Extraction of LncRNAs), an alignment-free program which accurately annotates lncRNAs based on a Random Forest model trained with general features such as multik-mer frequencies and relaxed open reading frames. Benchmarking versus five state-of-art tools shows that FEELnc achieves similar or better classification performance on GENCODE and NONCODE datasets. The program also provides several specific modules that enable to fine-tune classification accuracy, to formalize the annotation of lncRNA classes and to annotate lncRNAs even in the absence of training set of noncoding RNAs. We used FEELnc on a real dataset comprising 20 new canine RNA-seq samples produced in the frame of the European LUPA consortium to expand the canine genome annotation and classified 10,374 novel lncRNAs and 58,640 new mRNA transcripts. FEELnc represents a standardized protocol for identifying and annotating lncRNAs and is freely accessible athttps://github.com/tderrien/FEELnc.
Neuronal control of the fingertips is socially configured in touchscreen smartphone users
Authors: Balerna Myriam , Ghosh Arko
Published: July 2016

As a common neuroscientific observation, the more a body part is used, the less variable the corresponding computations become. We here report a more complicated scenario concerning the fingertips of smartphone users. We sorted 21-days histories of touchscreen use of 57 volunteers into social and non-social categories. Sensorimotor variability was measured in a laboratory setting by simple button depressions and scalp electrodes (electroencephalogram, EEG). The ms range trial-to-trial variability in button depression was directly proportional to the number of social touches and inversely proportional to non-social touches. Variability of the early tactile somatosensory potentials was also proportional to the number of social touches, but not to non-social touches. The number of Apps and the speed of touchscreen use also reflected this variability. We suggest that smartphone use affects elementary computations even in tasks not involving a phone and that social activities uniquely reconfigure the thumb to touchscreen use.

Impact Statement

Unconstrained behavior on a smartphone is a powerful predictor of neuronal functions measured in the laboratory and the details of the smartphone-neuronal association challenges the established ideas of brain plasticity.
2-[(5-Amino-1,3,4-thiadiazol-2-yl)sulfanyl]-N-(2,4,5-trichlorophenyl)acetamide
Authors: Madan Kumar S. , Madhu Kumar D. J. , Shivakumar H. P. , Jagadeesha Prasad D. , Byrappa K. , Abdoh M. M. M.
Published: July 2016

In the title compound, C10H7Cl3N4OS2, the dihedral angle between the trichlorobenzene and thiadiazole rings is 29.26 (17)°. In the crystal, molecules are connected by N—H...O and C—H...O hydrogen bonds, forming chains propagating along [001]. The chains are linkedviaN—H...N hydrogen bonds to form slabs parallel to (100).
Threshold concept in intellectual property law
Authors: Azam Monirul
Published: July 2016

Purpose

This paper aims to identify the threshold concept in intellectual property (IP) law.

Design/methodology/approach

It used doctrinal methods for such identification based on the existing pedagogical scholarship in the field of effective teaching and learning.

Findings

It explained how the use of the threshold concept in IP law education could facilitate understanding of IP law from globalised perspectives and validate use of IP in a balanced way.

Research limitations/implications

It is yet to be tested for practical curriculum design in different jurisdictions.

Practical implications

The understanding of threshold concepts in IP law could generate “eureka” moments, when, after a long struggle, students come to a deep understanding of a new concept.

Social implications

This will facilitate social acceptance of IP for balancing global obligation and national developmental and social goals.

Originality/value

Till date, little work has been undertaken on the threshold concepts on IP law. Therefore, this study tried to make a unique contribution by identifying threshold concepts in intellectual property law.