bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Marketing on Twitter and Instagram: Evidence of Directly Advertising to Youth/Adolescents
Authors: Barry Adam E. , Bates Austin M. , Olusanya Olufunto , Vinal Cystal E. , Martin Emily , Peoples Janiene E. , Jackson Zachary A. , Billinger Shanaisa A. , Yusuf Aishatu , Cauley Daunte A. , Montano Javier R.
Published: November 2015

Aims

Assess whether alcohol companies restrict youth/adolescent access, interaction, and exposure to their marketing on Twitter and Instagram.

Methods

Employed five fictitious male and female Twitter (n = 10) and Instagram (n = 10) user profiles aged 13, 15, 17, 19 and/or 21. Using cellular smartphones, we determined whether profiles could (a) interact with advertising content—e.g. retweet, view video or picture content, comment, share URL; and/or (b) follow and directly receive advertising material updates from the official Instagram and Twitter pages of 22 alcohol brands for 30 days.

Results

All user profiles could fully access, view, and interact with alcohol industry content posted on Instagram and Twitter. Twitter's age-gate, which restricts access for those under 21, successfully prevented underage profiles from following and subsequently receiving promotional material/updates. The two 21+ profiles collectively received 1836 alcohol-related tweets within 30 days. All Instagram profiles, however, were able to follow all alcohol brand pages and received an average of 362 advertisements within 30 days. The quantity of promotional updates increased throughout the week, reaching their peak on Thursday and Friday. Representatives/controllers of alcohol brand Instagram pages would respond directly to our underage user's comments.

Conclusion

The alcohol industry is in violation of their proposed self-regulation guidelines for digital marketing communications on Instagram. While Twitter's age-gate effectively blocked direct to phone updates, unhindered access to post was possible. Everyday our fictitious profiles, even those as young as 13, were bombarded with alcohol industry messages and promotional material directly to their smartphones.
Quasar clustering in a galaxy and quasar formation model based on ultra high-resolution N-body simulations
Authors: Oogi Taira , Enoki Motohiro , Ishiyama Tomoaki , Kobayashi Masakazu A. R. , Makiya Ryu , Nagashima Masahiro
Published: November 2015

We investigate clustering properties of quasars using a new version of our semi-analytic model of galaxy and quasar formation with state-of-the-art cosmological N-body simulations. In this study, we assume that a major merger of galaxies triggers cold gas accretion on to a supermassive black hole and quasar activity. Our model can reproduce the downsizing trend of the evolution of quasars. We find that the median mass of quasar host dark matter haloes increases with cosmic time by an order of magnitude from z = 4 (a few 1011 M⊙) to z = 1 (a few 1012 M⊙), and depends only weakly on the quasar luminosity. Deriving the quasar bias through the quasar–galaxy cross-correlation function in the model, we find that the quasar bias does not depend on the quasar luminosity, similar to observed trends. This result reflects the fact that quasars with a fixed luminosity have various Eddington ratios and thus have various host halo masses that primarily determine the quasar bias. We also show that the quasar bias increases with redshift, which is in qualitative agreement with observations. Our bias value is lower than the observed values at high redshifts, implying that we need some mechanisms that make quasars inactive in low-mass haloes and/or that make them more active in high-mass haloes.
Aviremia 10 Years Postdiscontinuation of Antiretroviral Therapy Initiated During Primary Human Immunodeficiency Virus-1 Infection and Association With Gag-Specific T-Cell Responses
Authors: Kinloch-de Loes Sabine , Dorrell Lucy , Yang Hongbing , Hardy Gareth A. D. , Yerly Sabine , Cellerai Cristina , Vandekerckhove Linos , De Spielgelaere Ward , Malatinkova Eva , Wee Lee Koh Willie , Johnson Margaret A.
Published: November 2015

Combination antiretroviral therapy during primary human immunodeficiency virus-1 infection may enable long-term drug-free virological control in rare individuals. We describe a female who maintained aviremia and a normal CD4+/CD8+ T cell ratio for 10 years after stopping therapy, despite a persistent viral reservoir. Cellular immune responses may have contributed to this outcome.
Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery
Authors: Kertai Miklos D. , Zhou Shan , Karhausen Jörn A. , Cooter Mary , Jooste Edmund , Li Yi-Ju , White William D. , Aronson Solomon , Podgoreanu Mihai V. , Gaca Jeffrey , Welsby Ian J. , Levy Jerrold H. , Stafford-Smith Mark , Mathew Joseph P. , Fontes Manuel L.
Published: November 2015

AbstractAbstract

The authors performed a retrospective observational study of the association between postoperative nadir platelet counts, acute kidney injury, and mortality in coronary artery bypass grafting (CABG) surgery. The authors found a significant independent association between postoperative nadir platelet counts, acute kidney injury, and mortality after CABG surgery. The work suggests that the potential platelet-related ischemic events during the CABG surgery warrant further investigation.

Supplemental Digital Content is available in the text.

Background

Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery.

Methods

The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality.

Results

The median postoperative nadir platelet count was 121 × 109/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 109/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001).

Conclusion

The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.
Case Scenario: Perioperative Management of a Young Woman with Fontan Repair for Major Gynecologic Surgery
Authors: Dell’Anna Antonio Maria , Grieco Domenico Luca , Russo Andrea , Marana Elisabetta , Antonelli Massimo
Published: November 2015

Effective treatment for many congenital heart diseases diagnosed before birth has become available since the last three decades. Continuous improvements in surgical knowledge and techniques have allowed patients born with severe heart defects to survive through adulthood. However, palliative surgery often implies profound modifications of classical circulatory physiology, which must be taken into account particularly when general anesthesia is needed for major noncardiac surgery. Among the palliative surgeries, Fontan repair is an intervention aiming at excluding the right heart chambers with a total cavopulmonary conduit, which directs blood flow from both inferior and superior vena cavae directly to the right pulmonary artery. In such condition, patients are very sensitive to both preload reduction and pulmonary vascular resistances increase, so that a careful monitoring during anesthesia is required. Unfortunately, standard monitoring with a pulmonary artery catheter is not possible because of altered anatomy of right sections. In this case scenario, the authors report the perioperative management of a young woman who underwent major gynecologic surgery, who was managed using a transpulmonary thermodilution technique that was deemed more accurate than noncalibrated pulse-contour method and also able to provide more information regarding preload status. The authors adopted an integrated approach merging together hemodynamic and functional data (ScvO2 and venoarterial CO2 difference) to assess the appropriateness of hemodynamic management. The authors describe also pathophysiologic changes during such condition and also potential drawbacks of chosen technique.
Allograft Bone Use in Pediatric Subaxial Cervical Spine Fusions
Authors: Murphy Robert F. , Glotzbecker Michael P. , Hresko Michael T. , Hedequist Daniel
Published: November 2015

Background:

The use of freeze-dried allograft as a bone graft substitute for pediatric spine surgery is safe and efficacious in the thoracic and lumbar spines. Allograft bone use in segmental instrumented fusions in the subaxial cervical spine has not been well reported in the literature. We sought to describe our experience with allograft bone in this patient cohort, and to compare union rates to patients treated with autograft.

Methods:

Medical records were queried over a 10-year time period (2004 to 2014). Inclusion criteria were all pediatric patients (18 y old and below) who underwent subaxial cervical spine fusion with minimum follow-up of 24 months. Variables queried included demographics, type of graft material used, diagnosis, approach (anterior, posterior, combined), levels instrumented, placement of postoperative halo, surgical-related complications, and achievement of fusion.

Results:

A total of 26 patients qualified for inclusion (18 allograft, 8 autograft). No differences existed between the 2 groups regarding age, sex, or number of fused levels. In the allograft cohort, average age at initial surgery was 13.3 years (range, 5 to 18 y). The most common reasons for surgery included trauma (6), tumor (3), and syndrome-associated kyphosis (3). The average number of instrumented levels was 4 (range, 2 to 13). Four patients (22%) developed a postoperative surgical complication. There were 2 asymptomatic pseudarthroses not requiring revision. At a minimum of 24-month follow-up (average, 45 mo; range, 24 to 121 mo), the allograft group demonstrated a fusion rate of 88%, which was comparable with a fusion rate of 87% in the autograft group.

Conclusions:

The use of allograft bone for pediatric subaxial instrumented cervical spine fusions is safe in a variety of conditions, with the same rate of fusion as autograft. Rates of complications are acceptable. To avoid donor-site morbidity from autogenous graft harvest, we recommend considering allograft bone in subaxial cervical spine fusions with modern segmental instrumentation.

Level of Evidence:

Level IV—case series; therapeutic.
Long-term Results of Combined Epiphysiodesis and Imhauser Intertrochanteric Osteotomy in SCFE: A Retrospective Study on 53 Hips
Authors: Trisolino Giovanni , Pagliazzi Gherardo , Di Gennaro Giovanni L. , Stilli Stefano
Published: November 2015

Background:

The management of moderate and severe slipped capital femoral epiphysis is still an issue. The main concern is represented by the choice of an intra-articular or an extra-articular osteotomy to correct the deformity. Theoretically, the intra-articular osteotomy allows the best correction, but it is technically demanding and involves a higher risk of avascular necrosis (AVN); conversely, an extra-articular intertrochanteric osteotomy (ITO) is easier and involves a lower risk of early complications, but may lead to femoroacetabular impingement, resulting in early osteoarthritis and the need for total hip replacement (THR).

The aim of this study was to analyze the long-term survivorship free from THR after combined epiphysiodesis and Imhauser ITO.

Methods:

From 1975 to 2000, 45 patients (53 hips) underwent a combined epiphysiodesis and Imhauser ITO. There were 27 male and 18 female patients with an average age of 12.8±1.9 years. All cases showed a posterior sloping angle >40 degrees (mean, 69±16 degrees). The cumulative survivorship was determined according to Kaplan and Meier, with the end point defined as conversion to THR.

Results:

A total of 6 patients (6 hips; 11%) had a follow-up <2 years. Among them, no postoperative complications occurred. For the remaining 39 patients (47 hips, 89%), the mean follow-up was 21±11 years. Four early postoperative complications were reported (2 AVN, 2 chondrolysis). The cumulative 39 years’ survivorship free from THR was 68.5% (95% confidence interval, 42.4%-84.7%). The age at surgery (hazard ratio=1.849 per year older, P=0.017) and the postoperative onset of AVN or chondrolysis (hazard ratio=10.146, P=0.010) affected the long-term prognosis significantly.

Conclusions:

The combined epiphysiodesis and Imhauser ITO is a valid surgical option in moderate to severe slipped capital femoral epiphysis, preserving the natural hip for at least 39 years in the majority of the patients. Care must be taken to avoid AVN or chondrolysis. The age at surgery affects the prognosis negatively.

Level of Evidence:

Level III—a retrospective study.
Comparison of Surgical Outcomes, Narcotics Utilization, and Costs After an Anterior Cervical Discectomy and Fusion
Authors: Tabaraee Ehsan , Ahn Junyoung , Bohl Daniel D. , Collins Michael J. , Massel Dustin H. , Aboushaala Khaled , Singh Kern
Published: November 2015

Study Design:

Retrospective cohort analysis of a prospectively maintained registry.

Objective:

To compare the surgical outcomes, narcotic utilization, and costs between a stand-alone (SA) cage and anterior plating (AP) with an interbody device for 1-level anterior cervical discectomy and fusion (ACDF).

Background Data:

ACDF with a SA cage has gained popularity as a potential alternative to anterior cervical plating. Few studies have compared the surgical outcomes, narcotic utilization, and costs of ACDF utilizing a SA cage versus AP with an interbody device.

Methods:

Patients who underwent a primary 1-level ACDF for degenerative spinal pathology between 2010 and 2013 were analyzed. Patients were stratified on the basis of the type of implant system (SA cage vs. AP) and assessed with regard to demographics, comorbidities, smoking, visual analogue scale (VAS) scores (preoperative/postoperative), procedural time, estimated blood loss (EBL), length of hospitalization, complications, reoperations, narcotic consumption, and total costs. Statistical analysis was performed with independent sample T tests for continuous variables and χ2 analysis for categorical data. An α level of <0.05 denoted statistical significance.

Results:

Of the 93 patients included, 52 (55.9%) underwent an ACDF with a SA cage system. Patient demographics, comorbidity burden, body mass index, smoking status, and preoperative VAS score were similar between cohorts. The SA cohort incurred a significantly lower EBL (P<0.001) than the AP cohort. However, none required a transfusion and the procedural time, length of hospitalization, postoperative VAS score, complication rates, 1-year arthrodesis rate, and reoperation rates were similar between cohorts. Postoperative narcotics consumption and total costs were also similar between groups.

Conclusions:

Our findings suggest that the SA cage may be associated with a significantly lower EBL, which may not be clinically relevant. Perioperative outcomes, complications, reoperation rates, narcotics consumption in the immediate postoperative period, and total costs may be similar regardless of the instrumentation utilized in a 1-level ACDF.
Antinociceptive effects of imidazoline I2 receptor agonists in the formalin test in rats
Authors: Thorn David A. , Qiu Yanyan , Jia Shushan , Zhang Yanan , Li Jun-Xu
Published: November 2015

The imidazoline I2 receptor is an emerging drug target for analgesics. This study extended previous studies by examining the antinociceptive effects of three I2 receptor agonists (2-BFI, BU224, and CR4056) in the formalin test. The receptor mechanisms and anatomical mediation of I2 receptor agonist-induced antinociception were also examined. Formalin-induced flinching responses (2%, 50 μl) were quantified after treatment with I2 receptor agonists alone or in combination with the I2 receptor antagonist idazoxan. Anatomical mediation was studied by locally administering 2-BFI into the plantar surface or into the right lateral ventricle through cannulae (intracerebroventricular). The locomotor activity was also examined after central (intracerebroventricular) administration of 2-BFI. 2-BFI (1–10 mg/kg, intraperitoneal) and BU224 (1–10 mg/kg, intraperitoneal) attenuated the spontaneous flinching response observed during 10 min (phase 1) and 20–60 min (phase 2) following formalin treatment, whereas CR4056 (1–32 mg/kg, intraperitoneal) decreased only phase 2 flinching response. The I2 receptor antagonist idazoxan attenuated the antinociceptive effects of 2-BFI and BU224 during phase 1, but not phase 2. Peripheral administration of 2-BFI (1–10 mg/kg, intraplantar) to the hind paw of rats had no antinociceptive effect. In contrast, centrally delivered 2-BFI (10–100 µg, intracerebroventricular) dose-dependently attenuated phase 1 and phase 2 flinching at doses that did not reduce the locomotor activity. Together, these data revealed the differential antinociceptive effects of I2 receptor agonists and the differential antagonism profiles by idazoxan, suggesting the involvement of different I2 receptor subtypes in reducing different phases of formalin-induced pain-like behaviors. In addition, the results also suggest the central mediation of I2 receptor agonist-induced antinociceptive actions.
Insulin Resistance Predicts Virological Response to Interferon-α in Chronic Hepatitis B Patients
Authors: Wang Xin , Zhao Ying-Ren , Liu Hong-Li , Ma Xiao-Hua , Zhang Yu , Yi Rui-Tian
Published: November 2015

Goals:

To elucidate impact of insulin resistance (IR) on the response to interferon-α (IFN-α) therapy in chronic hepatitis B (CHB) patients.

Background:

Metabolic factors influencing the virological response of CHB patients on IFN-α treatment are still unexplored.

Study:

Eighty CHB patients were treated with IFN-α for 48 weeks. The IR was evaluated by homeostasis model assessment of IR (HOMA-IR) before treatment. Viral load and biochemical parameters were measured at 12, 24, and 48 weeks after starting treatment, and then 24 weeks after the end of treatment. IFN-γ and tumor necrosis factor-α were tested at baseline and 12 weeks of treatment.

Results:

Pretreatment HOMA-IR proved to be the only independent predictor of primary nonresponse, as well as the pretreatment HOMA-IR, viral load and primary nonresponse were independently associated with virological response at 24, 48 weeks of treatment and at the follow-up endpoint. The significant higher virological relapse rate in patients with IR was observed in patients with virological response at 48 weeks of treatment. The mean HOMA-IR was significantly lower in virological responders than in virological nonresponders. The secretion of IFN-γ and tumor necrosis factor-α was not induced in patients with IR at 12 weeks after IFN-α treatment.

Conclusions:

Our data suggest that IR is strongly associated with virological response, thus reflecting the important role played by metabolic factors in the viral kinetics during IFN-α treatment. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.
A Short Screening Tool to Identify Victims of Child Sex Trafficking in the Health Care Setting
Authors: Greenbaum V. Jordan , Dodd Martha , McCracken Courtney
Published: November 2015

Objectives

The aim of this study was to describe characteristics of commercial sexual exploitation of children/child sex trafficking (CSEC/CST) victims and to develop a screening tool to identify victims among a high-risk adolescent population.

Methods

In this cross-sectional study, patients aged 12 to 18 years who presented to 1 of 3 metropolitan pediatric emergency departments or 1 child protection clinic and who were identified as victims of CSEC/CST were compared with similar-aged patients with allegations of acute sexual assault/sexual abuse (ASA) without evidence of CSEC/CST. The 2 groups were compared on variables related to medical and reproductive history, high-risk behavior, mental health symptoms, and injury history. After univariate analysis, a subset of candidate variables was subjected to multivariable logistic regression to identify an optimum set of 5 to 7 screening items.

Results

Of 108 study participants, 25 comprised the CSEC/CST group, and 83 comprised the ASA group. Average (SD) age was 15.4 (1.8) years for CSEC/CST patients and 14.8 (1.6) years for ASA patients; 100% of the CSEC/CST and 95% of the ASA patients were female. The 2 groups differed significantly on 16 variables involving reproductive history, high-risk behavior, sexually transmitted infections, and previous experience with violence. A 6-item screen was constructed, and a cutoff score of 2 positive answers had a sensitivity of 92%, specificity of 73%, positive predictive value of 51%, and negative predictive value of 97%.

Conclusions

Adolescent CSEC/CST victims differ from ASA victims without evidence of CSEC/CST across several domains. A 6-item screen effectively identifies CSEC/CST victims in a high-risk adolescent population.
Primary Endometrial Yolk Sac Tumor With Endodermal-Intestinal Differentiation Masquerading as Metastatic Colorectal Adenocarcinoma
Authors: Damato Stephen , Haldar Krishnayan , McCluggage W. Glenn
Published: November 2015

Yolk sac tumors (YSTs) with a somatic glandular pattern can be difficult to recognize histologically because they reproduce developing intestinal, hepatic, or lung tissue and can express markers such as CDX2 and TTF1. We report an unusual case of a primary endometrial YST showing florid endodermal-intestinal differentiation in a 63-yr-old woman with a history of colorectal adenocarcinoma. Histologically, the tumor exhibited a glandular and papillary architecture and showed widespread immunoreactivity for CDX2 and focal staining for CK20 and CEA, mimicking metastatic colorectal carcinoma on biopsy. The presence of subnuclear cytoplasmic clearing and positive staining for germ cell markers, however, pointed toward a diagnosis of primary endometrial YST, and this was supported by the radiologic and the subsequent pathologic finding of a primary endometrial-based lesion. YSTs in this age group usually arise in association with somatic tumors and in this case a small focus of coexistent endometrioid adenocarcinoma was identified within the uterus. Despite surgery and adjuvant chemotherapy, the patient showed disease progression with liver and lung metastases 6 mo postoperatively.
Primary Extranodal Marginal Cell Lymphoma, MALT Type, of the Endometrium Arising in a Patient With Rheumatoid Arthritis: Report of a Case
Authors: Magnoli Francesca , Cimetti Laura , Bernasconi Barbara , Sahnane Nora , Redaelli Isabella , Riva Cristina , Uccella Silvia
Published: November 2015

Primary marginal zone B-cell MALT-type lymphomas of the uterine corpus are exceedingly rare entities, with only 6 cases reported in the literature to date. We present the additional case of a 70-yr-old white woman who underwent a laparoscopic total hysterectomy with bilateral salpingo-oophorectomy for an asymptomatic ovarian cyst. At microscopic examination, endometrial samples showed a dense, nodular lymphocytic infiltrate, suggestive of a lymphoproliferative disorder. Morphology, immunohistochemistry, and molecular analysis supported the diagnosis of MALT-type lymphoma of the endometrium. Benign reactive conditions, such as endometritis and other small B-cell lymphomas were ruled out. Moreover, we investigated the pathogenesis of our case, focusing on Chlamydia trachomatis infection, chromosomal translocations affecting the NF-kB pathway, and discussing the role of autoimmunity in the development of MALT-type lymphomas.
Assessing Residents’ Frozen Section Skills for Endometrial Cancer
Authors: Selove William , Bradford Leslie S. , Liu Yuxin
Published: November 2015

Intraoperative frozen section (IFS) on endometrial cancer is an invaluable skill for pathologists-in-training to master. Within limited time constraints, pathologists are expected to determine tumor type, grade, and depth of myometrial invasion. During their training, pathology residents gradually gain experience in handling the majority of cases. However, significant errors can still be seen among senior level trainees. We aimed to improve training effectiveness by evaluating our trainees’ performance, identifying common errors, and recommending focused curriculum. Twenty-two residents [postgraduate year (PGY)-1–PGY-4] performed 260 IFS during a 4-yr period. We compared their independent IFS diagnoses with final diagnoses. Overall resident IFS accuracy was 73%. Accuracy for tumor type and depth of myometrial invasion was 80% and 93%, respectively. Two thirds of errors were due to sampling with the rest because of interpretation. Major deficiencies lay in recognizing high-risk histologic types (serous, clear cell, sarcoma) and unconventional myometrial invasion patterns (MELF, adenoma malignum, and adenomyosis-like). Resident IFS errors would theoretically result in suboptimal staging for 32 (12%) patients and unnecessary staging for 1 (0.4%). Overall IFS performance improved as training level increased (76% accuracy for PGY-1 accompanied by PGY-5; 59% for PGY-2; 74% for PGY-3; and 86% for PGY-4). We recommend a dedicated curriculum targeting these difficult yet clinically important entities through review literature and a collection of classic cases demonstrating the diverse morphology variations. Implementing such focused training would greatly improve our trainees’ competence on IFS, preparing them to handle a wide variety of cases and situations in future practice.
Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome
Authors: Mhawech-Fauceglia Paulette , Ramzan Amin , Walia Saloni , Pham Huyen Q. , Yessaian Annie
Published: November 2015

A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal.
Introduction to ‘Homology and convergence in nervous system evolution’
Authors: Strausfeld Nicholas J. , Hirth Frank
Published: November 2015

The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso–ventral and anterior–posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the ‘Cambrian explosion’ arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss homology and convergence in nervous system evolution. By integrating knowledge ranging from evolutionary theory and palaeontology to comparative developmental genetics and phylogenomics, the meeting covered disparities in nervous system origins as well as correspondences of neural circuit organization and behaviours, all of which allow evidence-based debates for and against the proposition that the nervous systems and brains of animals might derive from a common ancestor.
Homology, convergence and parallelism
Authors: Ghiselin Michael T.
Published: November 2015

Homology is a relation of correspondence between parts of parts of larger wholes. It is used when tracking objects of interest through space and time and in the context of explanatory historical narratives. Homologues can be traced through a genealogical nexus back to a common ancestral precursor. Homology being a transitive relation, homologues remain homologous however much they may come to differ. Analogy is a relationship of correspondence between parts of members of classes having no relationship of common ancestry. Although homology is often treated as an alternative to convergence, the latter is not a kind of correspondence: rather, it is one of a class of processes that also includes divergence and parallelism. These often give rise to misleading appearances (homoplasies). Parallelism can be particularly hard to detect, especially when not accompanied by divergences in some parts of the body.
Xenacoelomorpha: a case of independent nervous system centralization?
Authors: Gavilán Brenda , Perea-Atienza Elena , Martínez Pedro
Published: November 2015

Centralized nervous systems (NSs) and complex brains are among the most important innovations in the history of life on our planet. In this context, two related questions have been formulated: How did complex NSs arise in evolution, and how many times did this occur? As a step towards finding an answer, we describe the NS of several representatives of the Xenacoelomorpha, a clade whose members show different degrees of NS complexity. This enigmatic clade is composed of three major taxa: acoels, nemertodermatids and xenoturbellids. Interestingly, while the xenoturbellids seem to have a rather ‘simple’ NS (a nerve net), members of the most derived group of acoel worms clearly have ganglionic brains. This interesting diversity of NS architectures (with different degrees of compaction) provides a unique system with which to address outstanding questions regarding the evolution of brains and centralized NSs. The recent sequencing of xenacoelomorph genomes gives us a privileged vantage point from which to analyse neural evolution, especially through the study of key gene families involved in neurogenesis and NS function, such as G protein-coupled receptors, helix-loop-helix transcription factors and Wnts. We finish our manuscript proposing an adaptive scenario for the origin of centralized NSs (brains).
Loss of neurogenesis inHydraleads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells
Authors: Wenger Y. , Buzgariu W. , Galliot B.
Published: November 2015

Hydracontinuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory–motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis inHydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx,Dlx1,DMBX1/Manacle,Ets1,Gli3,KLF11,LMX1A,ZNF436,Shox1), epitheliopeptides (Arminins,PW peptide), neurosignalling components (CAMK1D,DDCl2,Inx1), ligand-ion channel receptors (CHRNA1,NaC7),G-Protein Coupled ReceptorsandFMRFRL.Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.
Independent origins of neurons and synapses: insights from ctenophores
Authors: Moroz Leonid L. , Kohn Andrea B.
Published: November 2015

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses suggest that both electrical and chemical synapses evolved more than once.
Phototaxis and the origin of visual eyes
Authors: Randel Nadine , Jékely Gáspár
Published: November 2015

Vision allows animals to detect spatial differences in environmental light levels. High-resolution image-forming eyes evolved from low-resolution eyes via increases in photoreceptor cell number, improvements in optics and changes in the neural circuits that process spatially resolved photoreceptor input. However, the evolutionary origins of the first low-resolution visual systems have been unclear. We propose that the lowest resolving (two-pixel) visual systems could initially have functioned in visual phototaxis. During visual phototaxis, such elementary visual systems compare light on either side of the body to regulate phototactic turns. Another, even simpler and non-visual strategy is characteristic of helical phototaxis, mediated by sensory–motor eyespots. The recent mapping of the complete neural circuitry (connectome) of an elementary visual system in the larva of the annelidPlatynereis dumeriliisheds new light on the possible paths from non-visual to visual phototaxis and to image-forming vision. We outline an evolutionary scenario focusing on the neuronal circuitry to account for these transitions. We also present a comprehensive review of the structure of phototactic eyes in invertebrate larvae and assign them to the non-visual and visual categories. We propose that non-visual systems may have preceded visual phototactic systems in evolution that in turn may have repeatedly served as intermediates during the evolution of image-forming eyes.
Animal–microbe interactions and the evolution of nervous systems
Authors: Eisthen Heather L. , Theis Kevin R.
Published: November 2015

Animals ubiquitously interact with environmental and symbiotic microbes, and the effects of these interactions on animal physiology are currently the subject of intense interest. Nevertheless, the influence of microbes on nervous system evolution has been largely ignored. We illustrate here how taking microbes into account might enrich our ideas about the evolution of nervous systems. For example, microbes are involved in animals' communicative, defensive, predatory and dispersal behaviours, and have likely influenced the evolution of chemo- and photosensory systems. In addition, we speculate that the need to regulate interactions with microbes at the epithelial surface may have contributed to the evolutionary internalization of the nervous system.
Genealogical correspondence of a forebrain centre implies an executive brain in the protostome–deuterostome bilaterian ancestor
Authors: Wolff Gabriella H. , Strausfeld Nicholas J.
Published: November 2015

Orthologous genes involved in the formation of proteins associated with memory acquisition are similarly expressed in forebrain centres that exhibit similar cognitive properties. These proteins include cAMP-dependent protein kinase A catalytic subunit (PKA-Cα) and phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKII), both required for long-term memory formation which is enriched in rodent hippocampus and insect mushroom bodies, both implicated in allocentric memory and both possessing corresponding neuronal architectures. Antibodies against these proteins resolve forebrain centres, or their equivalents, having the same ground pattern of neuronal organization in species across five phyla. The ground pattern is defined by olfactory or chemosensory afferents supplying systems of parallel fibres of intrinsic neurons intersected by orthogonal domains of afferent and efferent arborizations with local interneurons providing feedback loops. The totality of shared characters implies a deep origin in the protostome–deuterostome bilaterian ancestor of elements of a learning and memory circuit. Proxies for such an ancestral taxon are simple extant bilaterians, particularly acoels that express PKA-Cα and pCaMKII in discrete anterior domains that can be properly referred to as brains.
Ecological innovations in the Cambrian and the origins of the crown group phyla
Authors: Budd Graham E. , Jackson Illiam S. C.
Published: November 2015

Simulation studies of the early origins of the modern phyla in the fossil record, and the rapid diversification that led to them, show that these are inevitable outcomes of rapid and long-lasting radiations. Recent advances in Cambrian stratigraphy have revealed a more precise picture of the early bilaterian radiation taking place during the earliest Terreneuvian Series, although several ambiguities remain. The early period is dominated by various tubes and a moderately diverse trace fossil record, with the classical ‘Tommotian’ small shelly biota beginning to appear some millions of years after the base of the Cambrian at
ca
541 Ma. The body fossil record of the earliest period contains a few representatives of known groups, but most of the record is of uncertain affinity. Early trace fossils can be assigned to ecdysozoans, but deuterostome and even spiralian trace and body fossils are less clearly represented. One way of explaining the relative lack of clear spiralian fossils until about 536 Ma is to assign the various lowest Cambrian tubes to various stem-group lophotrochozoans, with the implication that the groundplan of the lophotrochozoans included a U-shaped gut and a sessile habit. The implication of this view would be that the vagrant lifestyle of annelids, nemerteans and molluscs would be independently derived from such a sessile ancestor, with potentially important implications for the homology of their sensory and nervous systems.
Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks
Authors: Cichy Radoslaw Martin , Khosla Aditya , Pantazis Dimitrios , Oliva Aude
Published: November 2015

Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative explanation that captures the complexity of scene recognition, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and a novel quantitative model of how spatial layout representations may emerge in the human brain.
Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders
Authors: Skene Nathan G. , Grant Seth G.N.
Published: November 2015

The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE) method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesized that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.
Crystal structure of 4-({(1E,2E)-3-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]allylidene}amino)-1H-1,2,4-triazole-5(4H)-thione
Authors: Kulkarni Ajaykumar D. , Rahman Md. Lutfor , Mohd. Yusoff Mashitah , Kwong Huey Chong , Quah Ching Kheng
Published: November 2015

The asymmetric unit of the titled compound, C22H20FN5S, comprises two independent molecules (AandB), both of which have atransconformation with respect to the methene C=C [1.342 (2) and 1.335 (2) Å] and the acyclic N=C [1.283 (2) and 1.281 (2) Å] bonds. In moleculeA, the triazole ring makes dihedral angles of 55.01 (12) and 18.17 (9)° with the benzene and indole rings, respectively. The corresponding dihedral angles for moleculeBare 54.54 (11) and 14.60 (10)°, respectively. In the crystal, molecules are consolidated into –A–B–A–B– chains along [010]viaN—H...N hydrogen bonds. The chains are further linked into layers parallel to theacplaneviaπ–π interactions involving inversion-related triazole rings [centroid–centroid distances = 3.3436 (11)–3.4792 (13) Å].