bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre
Authors: Bröker Mirelle E. E. , Klompenhouwer Anne J. , Gaspersz Marcia P. , Alleleyn Annick M. E. , Dwarkasing Roy S. , Pieters Indra C. , de Man Robert A. , IJzermans Jan N. M.
Published: November 2017

Background

When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management.

Methods

We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics of patients with growing FNH with sequential imaging in a 6‐month interval were compared to non‐growing FNH.

Results

Growth was reported in 19/162 (12%) patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs; histological examination confirmed FNH in all patients. In all 15 conservatively treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes were reported. No differences were found in characteristics and presentation of patients with growing or non‐growing FNH.

Conclusion

This study confirms that FNH may grow significantly without causing symptoms. A significant increase in size should not have any implications on clinical management if confident diagnosis by imaging has been established by a tertiary benign liver multidisciplinary team. Liver biopsy is only indicated in case of doubt after state‐of‐the‐art imaging. Resection is deemed unnecessary if the diagnosis is confirmed by multiple imaging modalities in a tertiary referral centre.
Cost-effectiveness of rule-based immunoprophylaxis against respiratory syncytial virus infections in preterm infants
Authors:   on behalf of the Dutch RSV Neonatal Network, Blanken Maarten O. , Frederix Geert W. , Nibbelke Elisabeth E. , Koffijberg Hendrik , Sanders Elisabeth A. M. , Rovers Maroeska M. , Bont Louis
Published: November 2017

The objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving.

Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available.
Sequential Detection of Compromised Items Using Response Times in Computerized Adaptive Testing
Authors: Choe Edison M. , Zhang Jinming , Chang Hua-Hua
Published: November 2017

Item compromise persists in undermining the integrity of testing, even secure administrations of computerized adaptive testing (CAT) with sophisticated item exposure controls. In ongoing efforts to tackle this perennial security issue in CAT, a couple of recent studies investigated sequential procedures for detecting compromised items, in which a significant increase in the proportion of correct responses for each item in the pool is monitored in real time using moving averages. In addition to actual responses, response times are valuable information with tremendous potential to reveal items that may have been leaked. Specifically, examinees that have preknowledge of an item would likely respond more quickly to it than those who do not. Therefore, the current study proposes several augmented methods for the detection of compromised items, all involving simultaneous monitoring of changes in both the proportion correct and average response time for every item using various moving average strategies. Simulation results with an operational item pool indicate that, compared to the analysis of responses alone, utilizing response times can afford marked improvements in detection power with fewer false positives.
A Case of Glomangiopericytoma at the Nasal Septum
Authors: Anzai Takashi , Saito Tsuyoshi , Tsuyama Sho , Toh Miri , Ikeda Katsuhisa , Ito Shin
Published: November 2017

Glomangiopericytoma (GPC) is a rare sinonasal perivascular tumor that accounts for < 0.5–1% of all sinonasal tumors. GPC is categorized as a low-grade neoplasm with borderline malignancy and a tendency of local recurrence. GPC is a rare mesenchymal neoplasm characterized by the perivascular proliferation of tumor cells, and it requires being distinguished from solitary fibrous tumors. Here, we report a case of GPC in a 68-year-old male patient who presented at the emergency room of our hospital with a complaint of sudden epistaxis. A small, reddish, protruding tumor was observed on the right nasal septum. A biopsy revealed a possible perivascular tumor such as a GPC or solitary fibrous tumor. Thus, we performed complete resection with endoscopic surgery. The size of the resected tumor was 12 × 5 mm, and it showed a uniform proliferation of oval-to-short spindle-shaped cells with slightly branching vascular structures. The tumor cells showed minimal cytologic atypia and there were an average of 3 mitoses in 10 high power fields. Necrosis was not observed. The tumor cells showed strong and diffuse nuclear immunostaining with beta catenin and were negative with STAT6, CD34 and bcl-2. The MIB-1 labeling index was approximately 5%. Genetic testing revealed CTNNB1 mutation (p.S33C). Thus, a diagnosis of low grade GPC was made on the biopsy and the patient could be successfully treated with endoscopic resection.
CoelomycetousDothideomyceteswith emphasis on the familiesCucurbitariaceaeandDidymellaceae
Authors: Valenzuela-Lopez N. , Cano-Lira J.F. , Guarro J. , Sutton D.A. , Wiederhold N. , Crous P.W. , Stchigel A.M.
Published: November 2017

The taxonomy of the coelomycetes has undergone dramatic changes in recent years, but remains controversial due to the high number of taxa involved, their poor morphological differentiation, the rare occurrence of the sexual morphs, and rapid loss of fertilityin vitro. In the present study, we revisited the familiesCucurbitariaceaeandDidymellaceae(Pleosporales, Dothideomycetes), which include numerous plant pathogens, endophytic species associated with a wide host range, and saprobes. The taxonomy of two of the most relevant genera, i.e.PhomaandPyrenochaeta, remains ambiguous after several phylogenetic studies, and needs further revision. We have studied a total of 143 strains of coelomycetes from clinical or environmental origin, by combining the LSU, ITS,tub2 andrpb2 sequences for a multi-locus analysis and a detailed morphological comparison. The resulting phylogenetic tree revealed that some fungi previously considered as members ofCucurbitariaceaerepresented five different families, and four of them,Neopyrenochaetaceae,Parapyrenochaetaceae,PseudopyrenochaetaceaeandPyrenochaetopsidaceae, are proposed here as new. Furthermore, 13 new genera, 28 new species, and 20 new combinations are proposed within thePleosporineae. Moreover, four new typifications are introduced to stabilise the taxonomy of these fungi.
Citation Counts and More Citation Counts: Useful? Interesting? or Counterproductive?
Authors: Campbell John P.
Published: November 2017

In their focal article, Aguinis et al. (2017) categorized the 6,654 unique citations, summed across the six introductory industrial and organizational (I-O) psychology texts, in various ways. They then suggested how such data could be used to (a) infer the “state” of the scientist–practitioner divide; (b) document the extent of the movement of I-O psychologists to management schools; (c) evaluate the future prospects of I-O psychology as a field; and (d) provide guidance in how to define, measure, and reward “scholarly impact” (quotation marks added). This crosses the line from interesting toverycounterproductive.
When Are Models of Technology in Psychology Most Useful?
Authors: Landers Richard N. , Behrend Tara S.
Published: November 2017

In industrial-organizational (I-O) psychology, much like in the organizational sciences more broadly (Hambrick, 2007), we have a bit of an addiction to theoretical models. It is commonly assumed that developing new theory is the most valuable way to solve pressing research problems and to drive our field forward (Mathieu, 2016). However, this assumption is untested, and there is growing awareness among organizational scientists that this hardline approach, which is unusual among both the natural sciences and other social sciences, may even be damaging the reputation and influence of our field (Antonakis, 2017; Ones, Kaiser, Chamorro-Premuzic, & Svensson, 2017). As Hambrick (2007) describes, the requirement for theory first “takes an array of subtle, but significant, tolls on our field” (p. 1348). As we will describe in this article, Morelli, Potosky, Arthur, and Tippins’ (2017) suggestions, if taken at face value, will likely create such tolls by encouraging the creation of new theories of dubious value. To be clear, we agree with Morelli et al. that better theory is needed for technology's impact on I-O psychology broadly and talent assessment in particular. We disagree, however, that creating new technology theories using the approaches that I-O psychology typically employs is likely to accomplish this broader goal. Rather, it will ultimately only isolate research on I-O technologies even further from both mainstream I-O research and technology research. Given that we are already quite isolated, this would be a disastrous path.
The Need for Conceptual Models of Technology in Training and Development: How Immersive Does Training Need to Be?
Authors: Cox Cody B. , House Andrew , Lopez Alex , Pool Gregory J.
Published: November 2017

Morelli, Potosky, Arthur, and Tippins (2017) articulate a strong need for industrial and organizational (I-O) psychologists to develop a more theory-based understanding of the role of technology in employee selection and assessment. We agree with their concerns but argue that this issue should include examination of how technology impacts training also. Researchers have noted that training is increasingly important for firms, and technology-enhanced training can improve learning and transfer (Ford & Meyer, 2013). However, the arguments that the authors make about the need for a theory-driven approach for examining the impact of technology on selection applies to training outcomes as well. Although considerable evidence exists that workplace training is effective and that technology can impact the success of training, there has been less theory-driven research exploring how technology can enhance or detract from training success. Researchers have already identified several variables related to technology that promote learning, but one variable that remains consistently unexplored in the organizational literature is immersion. This research is particularly important given how increasingly accessible immersive technology, such as virtual reality (VR), is becoming. Thus, we argue that as virtual training environments become more widely available, the variable of “immersion” in training environments is a particularly important one that warrants additional research.
Epigenetic correlates of neonatal contact in humans
Authors: Moore Sarah R. , McEwen Lisa M. , Quirt Jill , Morin Alex , Mah Sarah M. , Barr Ronald G. , Boyce W. Thomas , Kobor Michael S.
Published: November 2017

Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.
Positive maternal mental health during pregnancy associated with specific forms of adaptive development in early childhood: Evidence from a longitudinal study
Authors: Phua Desiree Y. , Kee Michelle K. Z. L. , Koh Dawn X. P. , Rifkin-Graboi Anne , Daniels Mary , Chen Helen , Chong Yap Seng , Broekman Birit F. P. , Magiati Iliana , Karnani Neerja , Pluess Michael , Meaney Michael J. ,   The Growing Up In Singapore Towards Healthy Outcomes Study Group
Published: November 2017

The quality of prenatal maternal mental health, from psychological stress and depressive symptoms to anxiety and other nonpsychotic mental disorders, profoundly affects fetal neurodevelopment. Despite the evidence for the influence of positive mental well-being on health, there is, to our knowledge, no research examining the possible effects of positive antenatal mental health on the development of the offspring. Using exploratory bifactor analysis, this prospective study (n = 1,066) demonstrated the feasibility of using common psychiatric screening tools to examine the effect of positive maternal mental health. Antenatal mental health was assessed during 26th week of pregnancy. The effects on offspring were assessed when the child was 12, 18, and 24 months old. Results showed that positive antenatal mental health was uniquely associated with the offspring's cognitive, language and parentally rated competences. This study shows that the effects of positive maternal mental health are likely to be specific and distinct from the sheer absence of symptoms of depression or anxiety.
Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression
Authors: Silveira Patrícia P. , Pokhvisneva Irina , Parent Carine , Cai Shirong , Rema Anu Sathyan Sathyapalan , Broekman Birit F. P. , Rifkin-Graboi Anne , Pluess Michael , O'Donnell Kieran J. , Meaney Michael J.
Published: November 2017

While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.
Exploring longitudinal associations between neighborhood disadvantage and cortisol levels in early childhood
Authors: Finegood Eric D. , Rarick Jason R. D. , Blair Clancy ,   The Family Life Project Investigators
Published: November 2017

Children who grow up in poverty are more likely to experience chronic stressors that generate “wear” on stress regulatory systems including the hypothalamus–pituitary–adrenal (HPA) axis. This can have long-term consequences for health and well-being. Prior research has examined the role of proximal family and home contributions to HPA axis functioning. However, there is evidence to suggest that more distal levels of context, including neighborhoods, also matter. Prior evidence has primarily focused on adolescents and adults, with little evidence linking the neighborhood context with HPA activity in infancy and toddlerhood. We tested whether neighborhood disadvantage (indexed by US Census data) was associated with basal salivary cortisol levels at 7, 15, and 24 months of child age in a large sample of families (N= 1,292) residing in predominately low-income and rural communities in the United States. Multilevel models indicated that neighborhood disadvantage was positively associated with salivary cortisol levels and that this effect emerged across time. This effect was moderated by the race/ethnicity of children such that the association was only observed in White children in our sample. Findings provide preliminary evidence that the neighborhood context is associated with stress regulation during toddlerhood, elucidating a need for future work to address possible mechanisms.
Methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), in maltreated and nonmaltreated children: Associations with behavioral undercontrol, emotional lability/negativity, and externalizing and internalizing symptoms
Authors: Cicchetti Dante , Handley Elizabeth D.
Published: November 2017

The present study examined the effect of various dimensions of child maltreatment (i.e., developmental timing of maltreatment, number of maltreatment subtypes, and chronicity of maltreatment) on methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), and investigated the associations betweenNR3C1methylation and child outcomes. Participants included 534 children who attended a research summer camp program for school-aged maltreated (53.4%) and nonmaltreated (46.6%) children from low socioeconomic backgrounds. Results show that children with early onset maltreatment evidence significant hypermethylation compared to nonmaltreated children. Moreover, more maltreatment subtypes experienced and more chronic maltreatment are both related to greaterNR3C1hypermethylation. Findings also indicate that hypermethylation ofNR3C1is linked with a number of negative child outcomes including greater emotional lability–negativity, higher levels of ego undercontrol, more externalizing behavior, and greater depressive symptoms. Together, results highlight the role of methylation ofNR3C1in the effects of child maltreatment on the development of emotion dysregulation and psychopathology.
In the eye of the beholder: Perceptions of neighborhood adversity and psychotic experiences in adolescence
Authors: Newbury Joanne B. , Arseneault Louise , Caspi Avshalom , Moffitt Terrie E. , Odgers Candice L. , Baldwin Jessie R. , Zavos Helena M. S. , Fisher Helen L.
Published: November 2017

Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.
Altered ventral striatal–medial prefrontal cortex resting-state connectivity mediates adolescent social problems after early institutional care
Authors: Fareri Dominic S. , Gabard-Durnam Laurel , Goff Bonnie , Flannery Jessica , Gee Dylan G. , Lumian Daniel S. , Caldera Christina , Tottenham Nim
Published: November 2017

Early caregiving adversity is associated with increased risk for social difficulties. The ventral striatum and associated corticostriatal circuitry, which have demonstrated vulnerability to early exposures to adversity, are implicated in many aspects of social behavior, including social play, aggression, and valuation of social stimuli across development. Here, we used resting-state functional magnetic resonance imaging to assess the degree to which early caregiving adversity was associated with altered coritocostriatal resting connectivity in previously institutionalized youth (n = 41) relative to youth who were raised with their biological families from birth (n = 47), and the degree to which this connectivity was associated with parent-reported social problems. Using a seed-based approach, we observed increased positive coupling between the ventral striatum and anterior regions of medial prefrontal cortex (mPFC) in previously institutionalized youth. Stronger ventral striatum–mPFC coupling was associated with parent reports of social problems. A moderated-mediation analysis showed that ventral striatal–mPFC connectivity mediated group differences in social problems, and more so with increasing age. These findings show that early institutional care is associated with differences in resting-state connectivity between the ventral striatum and the mPFC, and this connectivity seems to play an increasingly important role in social behaviors as youth enter adolescence.
Childhood adversity moderates the influence of proximal episodic stress on the cortisol awakening response and depressive symptoms in adolescents
Authors: Starr Lisa R. , Dienes Kimberly , Stroud Catherine B. , Shaw Zoey A. , Li Y. Irina , Mlawer Fanny , Huang Meghan
Published: November 2017

Childhood adversity (CA) is known to predict sensitization to proximal stressors. Researchers have suggested that disruptions in hypothalamus–pituitary–adrenal axis functioning may be a biological mechanism. If so, CA may predict altered associations between proximal life stress and markers of cortisol secretion. We examined whether CA moderates associations between recent episodic stress and (a) the cortisol awakening response (CAR), and (b) depressive symptoms, in 241 adolescents aged 14–17 years (cortisoln= 196). Salivary cortisol was sampled at 0, 30, and 60 min postawakening for 2 days. The CAR was calculated as the area under the curve with respect to increase and waking cortisol. CA and episodic stress were assessed using contextual-threat-method-coded objective interviews. CA significantly interacted with episodic stress to predict both the CAR and depression. Among those with low CA, episodic stress predicted increased CAR but did not predict depression. For adolescents with high CA, episodic stress predicted lower CAR and higher depression. These interactions were found only for independent (uncontrollable, fateful) events, and not for dependent (self-generated) stress. Increased allostatic load resulting from CA exposure may interfere with adolescents' ability to optimally regulate their CAR in relation to recent stress, contributing to increased depression risk.
Childhood abuse and neglect and physical health at midlife: Prospective, longitudinal evidence
Authors: Johnson William F. , Huelsnitz Chloe O. , Carlson Elizabeth A. , Roisman Glenn I. , Englund Michelle M. , Miller Gregory E. , Simpson Jeffry A.
Published: November 2017

Previous research suggests that the experience of abuse and neglect in childhood has negative implications for physical health in adulthood. Using data from the Minnesota Longitudinal Study of Risk and Adaptation (N= 115), the present research examined the predictive significance of childhood physical abuse, sexual abuse, and physical/cognitive neglect for multilevel assessments of physical health at midlife (age 37–39 years), including biomarkers of cardiometabolic risk, self-reports of quality of health, and a number of health problems. Analyses revealed that childhood physical/cognitive neglect, but not physical or sexual abuse, predicted all three health outcomes in middle adulthood, even when controlling for demographic risk factors and adult health maintenance behaviors. We discuss possible explanations for the unique significance of neglect in this study and suggest future research that could clarify previous findings regarding the differential impact of different types of abuse and neglect on adult health.
Richard J. O’Connell (1941–2015)
Authors: Manga Michael , Becker Thorsten
Published: November 2017

This son of a Montana sheriff discovered the fundamental rules underlying complex geophysical phenomena, and he taught others to do the same.
Divergent Republican Tax Plans Blur Future for Grad Students
Authors: Cartier Kimberly
Published: November 2017

The U.S. House of Representatives aims to tax tuition waivers as income, whereas the Senate does not. This new tax would undermine graduate students across all fields, experts say.
Dissipative quantum error correction and application to quantum sensing with trapped ions
Authors: Reiter F. , Sørensen A. S. , Zoller P. , Muschik C. A.
Published: November 2017

Quantum-enhanced measurements hold the promise to improve high-precision sensing ranging from the definition of time standards to the determination of fundamental constants of nature. However, quantum sensors lose their sensitivity in the presence of noise. To protect them, the use of quantum error-correcting codes has been proposed. Trapped ions are an excellent technological platform for both quantum sensing and quantum error correction. Here we present a quantum error correction scheme that harnesses dissipation to stabilize a trapped-ion qubit. In our approach, always-on couplings to an engineered environment protect the qubit against spin-flips or phase-flips. Our dissipative error correction scheme operates in a continuous manner without the need to perform measurements or feedback operations. We show that the resulting enhanced coherence time translates into a significantly enhanced precision for quantum measurements. Our work constitutes a stepping stone towards the paradigm of self-correcting quantum information processing.
Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells
Authors: Ito Shoko , Okuda Satoru , Abe Masako , Fujimoto Mari , Onuki Tetsuo , Nishimura Tamako , Takeichi Masatoshi
Published: November 2017

Normal epithelial cells are stably connected to each other via the apical junctional complex (AJC). AJCs, however, tend to be disrupted during tumor progression, and this process is implicated in cancer dissemination. Here, using colon carcinoma cells that fail to form AJCs, we investigated molecular defects behind this failure through a search for chemical compounds that could restore AJCs, and found that microtubule-polymerization inhibitors (MTIs) were effective. MTIs activated GEF-H1/RhoA signaling, causing actomyosin contraction at the apical cortex. This contraction transmitted force to the cadherin-catenin complex, resulting in a mechanosensitive recruitment of vinculin to cell junctions. This process, in turn, recruited PDZ-RhoGEF to the junctions, leading to the RhoA/ROCK/LIM kinase/cofilin-dependent stabilization of the junctions. RhoGAP depletion mimicked these MTI-mediated processes. Cells that normally organize AJCs did not show such MTI/RhoA sensitivity. Thus, advanced carcinoma cells require elevated RhoA activity for establishing robust junctions, which triggers tension-sensitive reorganization of actin/adhesion regulators.
Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer
Authors: Zhang Jingsong , Cunningham Jessica J. , Brown Joel S. , Gatenby Robert A.
Published: November 2017

Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka–Volterra equations with three competing cancer “species”: androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.
Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance
Authors: Brenachot Xavier , Ramadori Giorgio , Ioris Rafael M. , Veyrat-Durebex Christelle , Altirriba Jordi , Aras Ebru , Ljubicic Sanda , Kohno Daisuke , Fabbiano Salvatore , Clement Sophie , Goossens Nicolas , Trajkovski Mirko , Harroch Sheila , Negro Francesco , Coppari Roberto
Published: November 2017

Obesity-induced inflammation engenders insulin resistance and type 2 diabetes mellitus (T2DM) but the inflammatory effectors linking obesity to insulin resistance are incompletely understood. Here, we show that hepatic expression of Protein Tyrosine Phosphatase Receptor Gamma (PTPR-γ) is stimulated by inflammation in obese/T2DM mice and positively correlates with indices of inflammation and insulin resistance in humans. NF-κB binds to the promoter of Ptprg and is required for inflammation-induced PTPR-γ expression. PTPR-γ loss-of-function lowers glycemia and insulinemia by enhancing insulin-stimulated suppression of endogenous glucose production. These phenotypes are rescued by re-expression of Ptprg only in liver of mice lacking Ptprg globally. Hepatic PTPR-γ overexpression that mimics levels found in obesity is sufficient to cause severe hepatic and systemic insulin resistance. We propose hepatic PTPR-γ as a link between obesity-induced inflammation and insulin resistance and as potential target for treatment of T2DM.
The power of monitoring: optimizing survey designs to detect occupancy changes in a rare amphibian population
Authors: Barata Izabela M. , Griffiths Richard A. , Ridout Martin S.
Published: November 2017

Biodiversity conservation requires reliable species assessments and rigorously designed surveys. However, determining the survey effort required to reliably detect population change can be challenging for rare, cryptic and elusive species. We used a tropical bromeliad-dwelling frog as a model system to explore a cost-effective sampling design that optimizes the chances of detecting a population decline. Relatively few sampling visits were needed to estimate occupancy and detectability with good precision, and to detect a 30% change in occupancy with 80% power. Detectability was influenced by observer expertise, which therefore also had an effect on the sampling design – less experienced observers require more sampling visits to detect the species. Even when the sampling design provides precise parameter estimates, only moderate to large changes in occupancy will be detected with reliable power. Detecting a population change of 15% or less requires a large number of sites to be surveyed, which might be unachievable for range-restricted species occurring at relatively few sites. Unless there is high initial occupancy, rare and cryptic species will be particularly challenging when it comes to detecting small population changes. This may be a particular issue for long-term monitoring of amphibians which often display low detectability and wide natural fluctuations.
Function of capric acid in cyclophosphamide-induced intestinal inflammation, oxidative stress, and barrier function in pigs
Authors: Lee Sang In , Kang Kyung Soo
Published: November 2017

The small intestine is not only critical for nutrient absorption, but also serves as an important immune organ. Medium-chain fatty acids have nutritional and metabolic effects and support the integrity of the intestinal epithelium. However, their roles in intestinal immunity in pigs are not fully understood. We investigated the effects of a medium-chain fatty acid, capric acid, on intestinal oxidative stress, inflammation, and barrier function in porcine epithelial cells and miniature pigs after treatment with the immune suppressant cyclophosphamide. Capric acid alleviated inflammatory cytokine production (TNF-α and IL-6) and related gene expression (NF-κB, TNF-α, IFN-γ), alleviated oxidative stress (GSSG/GSH ratio, H2O2, and malondialdehyde), and increased oxidative stress-related gene expression (SOD1 and GCLC) in cyclophosphamide-treated IPEC-J2 cells. The permeability of FD-4 and expression of ZO-1 and OCLN in cyclophosphamide-treated IPEC-J2 cells were reduced by capric acid. Dietary capric acid reduced TNF-α, IL-6, and MDA levels and increased SOD, GPx, and the expression of genes related to pro-inflammatory, oxidative stress, and intestinal barrier functions in cyclophosphamide-treated miniature pigs. These results revealed that capric acid has protective effects against cyclophosphamide-induced small intestinal dysfunction in pigs.
All-trans retinoic acid enhances cytotoxicity of CIK cells against human lung adenocarcinoma by upregulating MICA and IL-2 secretion
Authors: Fan Xiao-yan , Wang Peng-yu , Zhang Chao , Zhang Yu-long , Fu Yun , Zhang Cong , Li Qiao-xia , Zhou Jie-na , Shan Bao-en , He Dong-wei
Published: November 2017

To determine the growth inhibition capability of all-trans retinoic acid (ATRA) with cytokine-induced killer cells (CIKs), we evaluated their effects, alone and in combination, on human lung carcinoma A549 cells. CIKs treated with ATRA significantly inhibited cell growth. Additionally, CIK with ATRA synergistically inhibited migration and invasiveness, colony formation of A549 and NCI-H520 cells. Furthermore, analysis of apoptosis markers Bcl-2, Bax, Survivin and cleaved Caspase-3 showed that Bcl-2 and Survivin mRNA levels significantly decreased, and that Bax mRNA significantly increased, in the CIK + ATRA-treated cells, with corresponding effects on their respective proteins. The involved mechanisms may be associated with upregulated expression of MHC class I-Related Chain (MICA) and interleukin (IL)-2. These results suggest that administration of combined CIK and ATRA is a potentially novel treatment for lung carcinoma.
Association between antibodies against group B Streptococcus surface proteins and recto-vaginal colonisation during pregnancy
Authors: Dzanibe Sonwabile , Kwatra Gaurav , Adrian Peter V. , Kimaro-Mlacha Sheila Z. , Cutland Clare L. , Madhi Shabir A.
Published: November 2017

Group B Streptococcus (GBS) recto-vaginal colonisation in pregnant women is the major risk factor for early-onset invasive GBS disease in their newborns. We aimed to determine the association between serum antibody levels against 11 GBS surface proteins and recto-vaginal acquisition of GBS colonisation during pregnancy. Sera collected from pregnant women at 20–25 weeks and ≥37 weeks of gestation age were measured for IgG titres against GBS surface proteins using  a multiplex immunoassay. Women were evaluated for recto-vaginal colonisation every 4–5 weeks. We observed that the likelihood of becoming colonised with GBS during pregnancy was lower in women with IgG titres ≥200 U/mL against gbs0233 (adjusted OR = 0.47 [95% CI: 0.25–0.89], p = 0.021) and ≥85 U/mL for gbs1539 (adjusted OR = 0.44 [95% CI: 0.24–0.82], p = 0.01) when comparing between women who acquired GBS colonisation and those that remained free of GBS colonisation throughout pregnancy. IgG titres (U/mL) specific to BibA and Sip were higher in pregnant women colonised with GBS (380.19 and 223.87, respectively) compared to women with negative GBS cultures (234.42 and 186.21, respectively; p < 0.01) at ≥37 weeks gestation. Antibodies induced by gbs0233 and gbs1539 were associated with a reduced likelihood of recto-vaginal GBS acquisition during pregnancy and warrant further investigation as vaccine targets.
An efficient electrode for simultaneous determination of guanine and adenine using nano-sized lead telluride with graphene
Authors: Pradhan Susmita , Biswas Sudip , Das Dipak K. , Bhar Radhaballabh , Bandyopadhyay Rajib , Pramanik Panchanan
Published: November 2017

Herein, lead telluride (PbTe) nanocrystals were chemically synthesized at room temperatureviareduction of homogeneous mixtures of tartrate complexes of Pb2+and Te4+with sodium borohydride.
A green route for the synthesis of pyrrolo[2,3-d]pyrimidine derivatives catalyzed by β-cyclodextrin
Authors: Yadav Vijay B. , Rai Pragati , Sagir Hozeyfa , Kumar Akhilesh , Siddiqui I. R.
Published: November 2017

The disclosed synthetic method for pyrrolo[2,3-d]pyrimidine derivatives offers several advantages such as non-toxic catalyst and aqueous reaction medium.
“Snorkelling” vs. “diving” in mixed micelles probed by means of a molecular bathymeter
Authors: Rodriguez-Muñiz Gemma M. , Gomez-Mendoza Miguel , Nuin Edurne , Andreu Inmaculada , Marin M. Luisa , Miranda Miguel A.
Published: November 2017

A molecular bathymeter based on a carboxylic acid linked to a signalling fluorophore proves “snorkelling” vs. “diving” in mixed micelles.
Dynamical properties of heterogeneous nucleation of parallel hard squares
Authors: González-Pinto Miguel , Martínez-Ratón Yuri , Velasco Enrique
Published: November 2017

The dynamical relaxation of heterogeneous crystal nucleation in fluids of parallel hard squares confined in square cavities has been investigated using dynamic density functional theory.
Non-labeled lensless micro-endoscopic approach for cellular imaging through highly scattering media
Authors: Wagner Omer , Pandya Aditya , Chemla Yoav , Pinhas Hadar , Schelkanova Irina , Shahmoon Asaf , Mandel Yossi , Douplik Alexandre , Zalevsky Zeev
Published: November 2017

We describe an imaging approach based on an optical setup made up of a miniature, lensless, minimally invasive endoscope scanning a sample and matching post processing techniques that enable enhanced imaging capabilities. The two main scopes of this article are that this approach enables imaging beyond highly scattering medium and increases the resolution and signal to noise levels reaching single cell imaging. Our approach has more advantages over ordinary endoscope setups and other imaging techniques. It is not mechanically limited by a lens, the stable but flexible fiber can acquire images over long time periods (unlike current imaging methods such as OCT etc.), and the imaging can be obtained at a certain working distance above the surface, without interference to the imaged object. Fast overlapping scans enlarge the region of interest, enhance signal to noise levels and can also accommodate post-processing, super-resolution algorithms. Here we present that due to the setup properties, the overlapping scans also lead to dramatic enhancement of non-scattered signal to scattered noise. This enables imaging through highly scattering medium. We discuss results obtained from in vitro investigation of weak signals of ARPE cells, rat retina, and scattered signals from polydimethylsiloxane (PDMS) microchannels filled with hemoglobin and covered by intralipids consequently mimicking blood capillaries and the epidermis of human skin. The development of minimally invasive procedures and methodologies for imaging through scattering medium such as tissues can vastly enhance biomedical diagnostic capabilities for imaging internal organs. We thereby propose that our method may be used for such tasks in vivo.
The devil is in the domain: understanding protein recognition of multiple RNA targets
Authors: Gronland Glen R. , Ramos Andres
Published: November 2017

RNA regulation provides a finely tuned and highly co-ordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on a recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. Deconvoluting the molecular complexity of the RNA regulatory network is essential to understanding cell differentiation and function, and requires accurate models for protein–RNA recognition and protein target selectivity. We discuss that the structural and molecular understanding of the key determinant of recognition, together with the availability of methods to examine protein–RNA interactions at the transcriptome level, may provide an avenue to establish these models.
Transcriptional regulators of redox balance and other homeostatic processes with the potential to alter neurodegenerative disease trajectory
Authors: Burnside Scott W. , Hardingham Giles E.
Published: November 2017

Diverse neurodegenerative diseases share some common aspects to their pathology, with many showing evidence of disruption to the brain's numerous homeostatic processes. As such, imbalanced inflammatory status, glutamate dyshomeostasis, hypometabolism and oxidative stress are implicated in many disorders. That these pathological processes can influence each other both up- and downstream makes for a complicated picture, but means that successfully targeting one area may have an effect on others. This targeting requires an understanding of the mechanisms by which homeostasis is maintained during health, in order to uncover strategies to boost homeostasis in disease. A case in point is redox homeostasis, maintained by antioxidant defences co-ordinately regulated by the transcription factor Nrf2, and capable of preventing not only oxidative stress but also inflammation and neuronal loss in neurodegenerative disease models. The emergence of other master regulators of homeostatic processes in the brain controlling inflammation, mitochondrial biogenesis, glutamate uptake and energy metabolism raises the question as to whether they too can be targeted to alter disease trajectory.
Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion
Authors: Rizzotto Andrea , Schirmer Eric C.
Published: November 2017

Nuclear size normally scales with the size of the cell, but in cancer this ‘karyoplasmic ratio’ is disrupted. This is particularly so in more metastatic tumors where changes in the karyoplasmic ratio are used in both diagnosis and prognosis for several tumor types. However, the direction of nuclear size changes differs for particular tumor types: for example in breast cancer, larger nuclear size correlates with increased metastasis, while for lung cancer smaller nuclear size correlates with increased metastasis. Thus, there must be tissue-specific drivers of the nuclear size changes, but proteins thus far linked to nuclear size regulation are widely expressed. Notably, for these tumor types, ploidy changes have been excluded as the basis for nuclear size changes, and so, the increased metastasis is more likely to have a basis in the nuclear morphology change itself. We review what is known about nuclear size regulation and postulate how such nuclear size changes can increase metastasis and why the directionality can differ for particular tumor types.