bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative action as skilled affordance‐responsiveness: An embodied‐mind approach
Authors: Yakhlef Ali , Rietveld Erik
Published: December 2019

Innovative action has often been regarded as the preserve of the deliberate mind and the outcome of individual explicit thought processes. In this regard, the material context within which innovative action occurs is considered as a passive container or at best a modifier of innovative action. Although recent studies have witnessed an interest in relating innovation to issues of embodiment, space and materiality, mainstream research remains largely grounded in a cognitivist, psychological idiom. The present paper takes an embodied‐mind perspective and focuses on the individual–environment system as a whole to suggest that innovative action emerges from an agent's skilful responses to unconventional environmental affordances (or action possibilities). Rather than viewing innovation as occurring within material contexts, we offer a new understanding of context as a rich landscape of affordances that is partly constitutive of innovation. The paper concludes with discussions of the proposed approach, its implications for studying innovative action and suggestions for further enquiry.
Potential mechanism of primary resistance to icotinib in patients with advanced non–small cell lung cancer harboring uncommon mutant epidermal growth factor receptor: A multi‐center study
Authors: Lei Lei , Wang Wen‐xian , Zhu You‐cai , Li Jin‐luan , Fang Yong , Wang Hong , Zhuang Wu , Zhang Yin‐bin , Wang Li‐ping , Fang Mei‐yu , Xu Chun‐wei , Wang Xiao‐jia , Lv Tang‐feng , Song Yong
Published: December 2019

The incidence of epidermal growth factor receptor uncommon mutation (EGFRum) is relatively low and patients harboring EGFRum are resistant to the first‐generation tyrosine kinase inhibitors (TKI). However, the mechanism of primary resistance remains unclear. Medical records of 98 patients who had never been treated by TKI and who accepted icotinib treatment were collected and followed. The circulating tumor DNA (ctDNA) were detected and analyzed using the next‐generation sequencing (NGS) platform after progression on icotinib. The potential primary resistance mechanism of icotinib was explored. A total of 21 (21.4%) and 48 (49%) patients developed primary and acquired resistance to icotinib, respectively. The median progression‐free survival (PFS) of primary resistance patients was 1.8 months (0.5‐2.3, 95% CI = 1.50‐2.10). Before treatment, 52.4% (11/21) of patients carried S768I, 23.8% (5/21) L861Q, 14.3% (3/21) G719X and 14.3% (3/21) exon 20‐ins mutations. Approximately 23.8% (5/21) of patients harbored the combined pattern mutations and 76.2% (16/21) of patients harbored the single pattern mutations. The combined pattern with EGFR classical mutation (EGFRcm) had worse PFS than the combined with EGFRum and single pattern (P < .05). There were 6 (28.57%) patients with acquired EGFR extracellular domain mutation, 5 (23.81%) with BCL2L11 loss (BIM deletion polymorphism), 3 (14.29%) with MET amplification, 1 (4.76%) with ERBB2 amplification, 1 (4.76%) with MYC amplification, 1 (4.76%) with PTEN mutation, 1 (4.76%) with PIK3CA mutation and 3 (14.29%) with unknown status. EGFR extracellular domain mutation, BCL2L11 loss, PI3K‐AKT‐mTOR signaling pathway (PTEN and PIK3CA mutations), MET amplification, ERBB2 amplification or MYC amplification might contribute to molecular mechanisms of primary resistance to icotinib in patients with advanced non‐small cell lung cancer harboring uncommon mutant epidermal growth factor receptor. Combined targeted therapy or chemotherapy should be considered in this population.
TIGIT as an emerging immune checkpoint
Authors: Harjunpää H , Guillerey C
Published: December 2019

T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes that was recently propelled under the spotlight as a major emerging target in cancer immunotherapy. TIGIT interacts with CD155 expressed on antigen-presenting cells or tumour cells to down-regulate T cell and natural killer (NK) cell functions. TIGIT has emerged as a key inhibitor of anti-tumour responses that can hinder multiple steps of the cancer immunity cycle. Pre-clinical studies indicated that TIGIT blockade may protect against various solid and haematological cancers. Several monoclonal antibodies (mAbs) that block the inhibitory activity of human TIGIT have been developed. Clinical trials are ongoing, investigating TIGIT blockade as a monotherapy or in combination with anti-PD1/PD-L1 mAbs for the treatment of patients with advanced solid malignancies. In this review, we cover our current knowledge on TIGIT, from its discovery in 2009 to its current status as a clinical target.
Shopping Streets and Neighborhood Identity: Retail Theming as Symbolic Ownership in New York
Authors: Martucci Sara
Published: December 2019

As the economies of production and trade have dwindled in Western cities, urban locales have had to capitalize on other opportunities for growth. Middle and upper class consumers are now sought after resources for cities and neighborhoods once supported by manufacturing. This article considers the role of local retail actors in shifting neighborhood identity towards luxury consumption. Important in this transformation is the process of theming by which business owners rely on cues from the neighborhood's identity and institutions, incorporate these cues into decisions for their own businesses, and thereby reify or change neighborhood identity. By tracing changes on shopping streets in Williamsburg, Brooklyn and Manhattan's Lower East Side, I show how retail theming interacts with neighborhood identity. Interviews with storeowners and archival retail data illuminate how choices made by entrepreneurs or coporations contribute to dramatic aesthetic changes on the street. As the neighborhood identities change, existing long–term residents and less wealthy visitors become excluded from the local shopping streets and lose ownership over neighborhoods.
Older Australians' perceptions of alcohol‐related harms and low‐risk alcohol guidelines
Authors: Chapman Janine , Harrison Nathan , Kostadinov Victoria , Skinner Natalie , Roche Ann
Published: December 2019

Introduction and Aims

Australia has an ageing population. Given the concomitant increase in the numbers and proportion of risky drinkers among older adults, research examining contributory factors is a priority. The current study examined older adults' estimates of the NHMRC low‐risk drinking guidelines, consumption patterns and associated harms and self‐identification of drinking type.

Design and Methods

Data from respondents aged 50+ years (N = 11 886) in the 2016 National Drug Strategy Household Survey were subjected to secondary analyses. Estimates of low‐risk drinking levels, perceived level of harm from current drinking, self‐identification of drinking type and awareness of standard drinks and labelling were included. Data were examined for those aged 50–59 years and 60+.

Results

Seventeen percent of older Australians drank at both long‐term and short‐term risk levels. Approximately 39% of males and 11% of females overestimated the long‐term low‐risk levels and 54% of males and 20% of females overestimated the short‐term low‐risk levels. Overestimation was highest among risky drinkers. Most older risky drinkers were aware of standard drinks and labelling; however, less than half perceived their drinking as harmful, instead identifying as social drinkers.

Discussion and Conclusions

Although substantial gaps are evident in older respondents' estimates of low‐risk drinking, additional public awareness campaigns are likely to be of limited use. Older peoples' engagement with the public health system presents ‘windows of opportunity’ to provide targeted, age‐appropriate harm reduction strategies. Appropriate intervention and policy responses are required to direct resources to this emerging area of concern.
Vanishing islands in the sky? A comparison of correlation‐ and mechanism‐based forecasts of range dynamics for montane salamanders under climate change
Authors: Lyons Marta P. , Kozak Kenneth H.
Published: December 2019

Forecasting the effects of climate change on species and populations is a fundamental goal of conservation biology, especially for montane endemics which seemingly are under the greatest threat of extinction given their association with cool, high elevation habitats. Species distribution models (also known as niche models) predict where on the landscape there is suitable habitat for a species of interest. Correlative niche modeling, the most commonly employed approach to predict species' distributions, relies on correlations between species' localities and current environmental data. This type of model could spuriously forecast less future suitable habitat because species' current distributions may not adequately represent their thermal tolerance, and future climate conditions may not be analogous to current conditions. We compared the predicted distributions for three montane species ofPlethodonsalamanders in the southern Appalachian Mountains of North America using a correlative modeling approach and a mechanistic model. The mechanistic model incorporates species‐specific physiology, morphology and behavior to predict an annual energy budget on the landscape. Both modeling approaches performed well at predicting the species' current distributions and predicted that all species could persist in habitats at higher elevation through 2085. The mechanistic model predicted more future suitable habitat than the correlative model. We attribute these differences to the mechanistic approach being able to model shifts in key range‐limiting biological processes (changes in surface activity time and energy costs) that the correlative approach cannot. Choice of global circulation model (GCM) contributed significantly to distribution predictions, with a tenfold difference in future suitability based on GCM, indicating that GCM variability should be either directly included in models of species distributions or, indirectly, through the use of multi‐model ensemble averages. Our results indicate that correlative models are over‐predicting habitat loss for montane species, suggesting a critical need to incorporate mechanisms into forecasts of species' range dynamics.
Migrations and movements of Atlantic tarpon revealed by two decades of satellite tagging
Authors: Luo Jiangang , Ault Jerald S. , Ungar Bruce T. , Smith Steven G. , Larkin Michael F. , Davidson Thomas N. , Bryan David R. , Farmer Nicholas A. , Holt Scott A. , Alford A. Scott , Adams Aaron J. , Humston Robert , Marton Adam S. , Mangum David , Kleppinger Russell , Requejo Angel , Robertson Julian
Published: December 2019

Understanding large‐scale migratory behaviours, local movement patterns and population connectivity are critical to determining the natural processes and anthropogenic stressors that influence population dynamics and for developing effective conservation plans. Atlantic tarpon occur over a broad geographic range in the Atlantic Ocean where they support valuable subsistence, commercial and recreational fisheries. From 2001 through 2018, we deployed 292 satellite telemetry tags on Atlantic tarpon in coastal waters off three continents to document: (a) seasonal migrations and regional population connectivity; (b) freshwater and estuarine habitat utilization; (c) spawning locations; and (d) shark predation across the south‐eastern United States, Gulf of Mexico and northern Caribbean Sea. These results showed that some mature tarpon make long seasonal migrations over thousands of kilometres crossing state and national jurisdictional borders. Others showed more local movements and habitat use. The tag data also revealed potential spawning locations consistent with those inferred in other studies from observations of early life stage tarpon leptocephalus larvae. Our analyses indicated that shark predation mortality on released tarpon is higher than previously estimated, especially at ocean passes, river mouths and inlets to bays. To date, there has been no formal stock assessment of Atlantic tarpon, and regional fishery management plans do not exist. Our findings will provide critical input to these important efforts and assist the multinational community in the development of a stock‐wide management information system to support informed decision‐making for sustaining Atlantic tarpon fisheries.
RBM10 regulates centriole duplication in HepG2 cells by ectopically assembling PLK4‐STIL complexes in the nucleus
Authors: Kunimoto Hiroyuki , Inoue Akira , Kojima Hirotada , Yang Junhao , Zhao Hong , Tsuruta Daisuke , Nakajima Koichi
Published: December 2019

RNA‐binding motif protein 10 (RBM10) primarily regulates alternative splicing of certain genes. Loss‐of‐function mutations in RBM10 have been frequently reported in patients with various cancers. However, how RBM10 levels affect cell proliferation and tumorigenesis remains unknown. To elucidate the role of RBM10 in cell proliferation, we established HepG2‐RBM10 knockout cell lines and derivative doxycycline‐inducible RBM10‐expressing cells. RBM10 over‐expression caused growth arrest in the M phase with a monopolar spindle because of impaired centriole duplication. Two RBM10 splicing mutants, one with F345A/F347A and the other with only the C‐terminal half (401–930), were sufficient to cause growth arrest, whereas an RBM10 mutant with cytoplasmic localization forced by an NES did not show growth arrest. RBM10 over‐expression induced the formation of many large nuclear domains containing RBM10, PLK4, STIL and SAS6, which are the regulatory proteins involved in centriole duplication. Consistently, the centrioles in the RBM10‐over‐expressing HepG2 cells lost PLK4 and STIL, accounting for the unsuccessful centriole duplication. In contrast, RBM10 depletion resulted in elevated levels of cytoplasmic PLK4 with a concomitant increase in the number of centrioles in HepG2 cells but not in A549 cells. Thus, nuclear RBM10 regulates normal chromosomal division in a cell‐type‐specific manner, independent of alternative RNA splicing.
Inhibitor epidemiology and genetic‐related risk factors in people with haemophilia from Côte d’Ivoire
Authors: Lambert Catherine , Lannoy Nathalie , Meité N’Dogomo , Sanogo Ibrahima , Eeckhoudt Stéphane , Hermans Cedric
Published: December 2019

Introduction

In Sub‐Saharan Africa, inhibitor prevalence data in people with haemophilia (PWH) are scarce, as are data on genetic or treatment‐related risk factors.

Aims and methods

We performed a prospective study on PWH from Côte d’Ivoire to collect data into inhibitor prevalence, create a database of haemophilia genotypes, establish correlations between inhibitor presence and genetic variants identified amongst Ivoirian PWHs and evaluate exposure to CFCs.

Results

The study included 54 unrelated participants (43 severe, four moderate, two mild haemophilia A and five severe haemophilia B). PWH were treated on‐demand with various product types for short periods, non‐intensively, and using low‐dose regimens. We reported similar distributions of intron 22 inversions (39.5%), point pathogenic variants (32.6%) and rearrangements in Ivoirian severe haemophilia A patients versus non‐African ethnic groups. The haplotypes H1 (29.6%), H2 (36.3%) and H3 (34.1%) frequencies in haemophilia A were consistent with results published on African populations. We identified eight new causal variants. An inhibitor was found in 12% of haemophilia A patients previously exposed to replacement therapies. Among PWH with inhibitors, 66.7% had a positive intron 22 inversion and 50% the H1 haplotype.

Conclusion

This study provides original data on molecular diagnosis of haemophilia, inhibitor prevalence and risk factors for inhibitor development previously associated with inhibitors in Côte d’Ivoire. The low inhibitor prevalence likely reflects the limited exposure to replacement therapy in Côte d’Ivoire. Further larger, multicentric and international studies are needed to gain more insight on inhibitor incidence and risk factors in African PWH.
Update on the pathology, genetics and somatic landscape of sebaceous tumours
Authors: Ferreira Ingrid , Wiedemeyer Katharina , Demetter Pieter , Adams David J , Arends Mark J , Brenn Thomas
Published: December 2019

Cutaneous sebaceous neoplasms show a predilection for the head and neck area of adults and include tumours with benign behaviour, sebaceous adenoma and sebaceoma, and sebaceous carcinoma with potential for an aggressive disease course at the malignant end of the spectrum. The majority of tumours are solitary and sporadic, but a subset of tumours may be associated with Lynch syndrome, also known as hereditary non‐polyposis colon cancer (HNPCC) and previously referred to as Muir‐Torre syndrome (now known to be part of Lynch syndrome). This review provides an overview of the clinical and histological features of cutaneous sebaceous neoplasia with an emphasis on differentiating features and differential diagnosis. It also offers insights into the recently described molecular pathways involved in the development of sebaceous tumours and their association with Lynch syndrome.
Magnesium‐dependent activated partial thromboplastin time assay—Simple method for lupus anticoagulant detection
Authors: Tokutake Takayoshi , Ieko Masahiro , Naito Sumiyoshi , Yoshida Mika , Baba Hisami , Kobayashi Hikaru , Ishida Fumihiro
Published: December 2019

Introduction

Detection of lupus anticoagulant (LA), an antiphospholipid (aPL) antibody, in a clotting time test is an important finding for diagnosis of antiphospholipid syndrome (APS). However, confirmation of LA requires several different testing procedures, some of which can be difficult and require time. We report here a simple and highly specific method for detecting LA.

Materials and Methods

We examined 66 plasma samples obtained from LA‐positive (LA) and 75 from LA‐negative (non‐LA) subjects, which included patients with acquired hemophilia and coagulation disorders, as well as from 43 healthy volunteer samples as normal controls. Activated partial thromboplastin time (APTT) was determined by adding 20 mmol of CaCl2 (Ca‐APTT) or 25 mmol of a mixture of Mg and Ca (Mg‐APTT). The ratio of Mg‐APTT/Ca‐APTT was then calculated and used as the Mg/Ca Index.

Results

The Mg/Ca Index value for the LA group was significantly lower than that for the non‐LA and normal control groups (P < .0001). When the cutoff value of the Mg/Ca Index was less than 1.00, the sensitivity of LA determination using the Mg‐APTT assay was 80.3%, while specificity was 100%.

Conclusion

Our findings indicate that the present Mg‐APTT assay is a simple yet highly specific method for LA detection.
Blocking inflammation to improve immunotherapy of advanced cancer
Authors: Macciò Antonio , Madeddu Clelia
Published: December 2019

The ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T‐cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer.
Uppåkra. A Central Site in South Scandinavian Iron Age
Authors: Larsson Lars
Published: December 2019

In the 1930s, during the construction of a house south of Lund in south-western Scania (southern Sweden), a thick occupation layer was discovered. The layer formed as a result of settlement during the Early Iron Age as a small-scale excavation demonstrated. The article is a presentation of recent investigations of the site in 1996-2014. The occupation layer, which covers an area of some 40 hectares, contained traces of settlements from the late Pre-Roman Iron Age to the Viking Age. Of particular significance are the remains of a small timber structure interpreted as a ceremonial building. It was reconstructed seven times during the 1st millennium AD and used for around seven hundred years. On each side of the ceremonial building were depositions of weapons combined with animal bones from large feasts. Besides the ceremonial building, several large halls were excavated, dating from the Roman Iron Age to the Viking Age. These produced evidence of repeated and deliberate arson. Several years of metal detector surveys have resulted in 14,000 registered finds that give a good foundation for interpreting the significance of the site in local, regional and international perspectives as an important religious, political and economic centre in southern Sweden. Contributions by a large number of scholars have helped to provide a well-based insight into different crafts and sources of artistic inspiration.
Identification of dynamic signatures associated with smoking‐related squamous cell lung cancer and chronic obstructive pulmonary disease
Authors: Sun Xiaoru , Shang Jingzhe , Wu Aiping , Xia Jingyan , Xu Feng
Published: December 2019

Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer. The aim of this study was to identify early diagnosis biomarkers for lung squamous cell carcinoma (SQCC) in COPD patients and to determine the potential pathogenetic mechanisms. The GSE12472 data set was downloaded from the Gene Expression Omnibus database. Differentially co‐expressed links (DLs) and differentially expressed genes (DEGs) in both COPD and normal tissues, or in both SQCC + COPD and COPD samples were used to construct a dynamic network associated with high‐risk genes for the SQCC pathogenetic process. Enrichment analysis was performed based on Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used the gene expression data and the clinical information to identify the co‐expression modules based on weighted gene co‐expression network analysis (WGCNA). In total, 205 dynamic DEGs, 5034 DLs and one pathway including CDKN1A, TP53, RB1 and MYC were found to have correlations with the pathogenetic progress. The pathogenetic mechanisms shared by both SQCC and COPD are closely related to oxidative stress, the immune response and infection. WGCNA identified 11 co‐expression modules, where magenta and black were correlated with the “time to distant metastasis.” And the “surgery due to” was closely related to the brown and blue modules. In conclusion, a pathway that includes TP53, CDKN1A, RB1 and MYC may play a vital role in driving COPD towards SQCC. Inflammatory processes and the immune response participate in COPD‐related carcinogenesis.
Inhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia
Authors: Carrà Giovanna , Nicoli Paolo , Lingua Marcello Francesco , Maffeo Beatrice , Cartellà Antonio , Circosta Paola , Brancaccio Mara , Parvis Guido , Gaidano Valentina , Guerrasio Angelo , Saglio Giuseppe , Taulli Riccardo , Morotti Alessandro
Published: December 2019

The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.
Editorial Perspective: Childhood maltreatment – the problematic unisex assumption
Authors: White Jordon D. , Kaffman Arie
Published: December 2019

Childhood maltreatment (CM) is a heterogeneous group of childhood adversities that can range from different forms of abuse (physical, sexual, emotional) or neglect (physical, emotional, cognitive), to severe bullying by peers. With an annual estimated cost of $500 billion in the United States alone, CM is recognized as one of the most significant risk factors for a range of psychiatric and medical conditions (White and Kaffman, 2019). Further, rates of numerous psychiatric, neurological, and medical conditions differ significantly between males and females (Gillies and McArthur, 2010), inspiring decades of research on how sex moderates consequences of CM (Gershon et al., 2008). Although vulnerability to CM has been reported to vary by sex, very few findings have been consistent across studies. Moreover, most work to date has focused on how sex alters the frequencies of different psychopathologies in maltreated individuals, with little attention to whether different developmental processes may underlie these psychopathologies in males and females (White and Kaffman, 2019). The primary goal of this editorial was to advocate for more effective research strategies to address these questions. We first examine the rationale for studying sex as an important moderator of consequences of CM, briefly summarize some of the most consistent clinical findings, and discuss the implications of sex in treatment response. We then highlight important obstacles that contribute to the large number of inconsistent findings and make five recommendations on how to move forward.
Proteomic and metabolomic profiling underlines the stage‐ and time‐dependent effects of high temperature on grape berry metabolism
Authors: Lecourieux David , Kappel Christian , Claverol Stéphane , Pieri Philippe , Feil Regina , Lunn John E. , Bonneu Marc , Wang Lijun , Gomès Eric , Delrot Serge , Lecourieux Fatma
Published: December 2019

Climate change scenarios predict an increase in mean air temperatures and in the frequency, intensity, and length of extreme temperature events in many wine‐growing regions worldwide. Because elevated temperature has detrimental effects on berry growth and composition, it threatens the economic and environmental sustainability of wine production. Using Cabernet Sauvignon fruit‐bearing cuttings, we investigated the effects of high temperature (HT) on grapevine berries through a label‐free shotgun proteomic analysis coupled to a complementary metabolomic study. Among the 2,279 proteins identified, 592 differentially abundant proteins were found in berries exposed to HT. The gene ontology categories “stress,” “protein,” “secondary metabolism,” and “cell wall” were predominantly altered under HT. High temperatures strongly impaired carbohydrate and energy metabolism, and the effects depended on the stage of development and duration of treatment. Transcript amounts correlated poorly with protein expression levels in HT berries, highlighting the value of proteomic studies in the context of heat stress. Furthermore, this work reveals that HT alters key proteins driving berry development and ripening. Finally, we provide a list of differentially abundant proteins that can be considered as potential markers for developing or selecting grape varieties that are better adapted to warmer climates or extreme heat waves.
The Digital Divide: Couple and Family Therapy Programs’ Integration of Teletherapy Training and Education
Authors: Pickens Jaclyn Cravens , Morris Neli , Johnson David J.
Published: December 2019

The mental health field is increasingly integrating and growing a teletherapy presence, and couple and family therapists are uniquely situated to offer these services based on our history of innovative approaches to therapeutic services. To do so successfully, careful consideration of training and education must occur. To evaluate current teletherapy training and education opportunities of COAMFTE accredited couple, marriage, and family therapy programs, an inductive qualitative content analysis was conducted on the responses of 95 faculty at COAMFTE accredited programs. Findings indicate that more than two thirds of the participants were in favor of teletherapy integration in training programs; however, most programs currently do not offer such opportunities. Barriers that prevent such integration were highlighted as well as existing concerns to training graduate students in teletherapy. Implications for training programs, policies, and regulations are discussed.
Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks
Authors: Djemil Sarra , Chen Xin , Zhang Ziyue , Lee Jisoo , Rauf Mikael , Pak Daniel T. S. , Dzakpasu Rhonda
Published: December 2019

Nicotinic acetylcholine receptors (nAChRs) are known to play a role in cognitive functions of the hippocampus, such as memory consolidation. Given that they conduct Ca2+ and are capable of regulating the release of glutamate and γ‐aminobutyric acid (GABA) within the hippocampus, thereby shifting the excitatory‐inhibitory ratio, we hypothesized that the activation of nAChRs will result in the potentiation of hippocampal networks and alter synchronization. We used nicotine as a tool to investigate the impact of activation of nAChRs on neuronal network dynamics in primary embryonic rat hippocampal cultures prepared from timed‐pregnant Sprague‐Dawley rats. We perturbed cultured hippocampal networks with increasing concentrations of bath‐applied nicotine and performed network extracellular recordings of action potentials using a microelectrode array. We found that nicotine modulated network dynamics in a concentration‐dependent manner; it enhanced firing of action potentials as well as facilitated bursting activity. In addition, we used pharmacological agents to determine the contributions of discrete nAChR subtypes to the observed network dynamics. We found that β4‐containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of α7 nAChRs augments nicotine‐mediated network potentiation but is not necessary for its manifestation. We also observed that antagonists of N‐methyl‐D‐aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs) partially blocked the effects of nicotine. Furthermore, nicotine exposure promoted autophosphorylation of Ca2+/calmodulin‐dependent kinase II (CaMKII) and serine 831 phosphorylation of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) subunit GluA1. These results suggest that nicotinic receptors induce potentiation and synchronization of hippocampal networks and glutamatergic synaptic transmission. Findings from this work highlight the impact of cholinergic signaling in generating network‐wide potentiation in the form of enhanced spiking and bursting dynamics that coincide with molecular correlates of memory such as increased phosphorylation of CaMKII and GluA1.

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The impact of surface alteration on epithelial tissue attachment after the mechanical cleaning of titanium or zirconia surface
Authors: Hu Jiangqi , Atsuta Ikiru , Ayukawa Yasunori , Zhou Xudiyang , Dwi Rakhmatia Yunia , Koyano Kiyoshi
Published: December 2019

Objective

Mechanical plaque removal may alter the surface morphology of the gingival penetration part of the implant. We applied an air‐powered abrasive system (AP), titanium curette (TC), stainless curette (SC), ultrasound scaler (US), and titanium brush (TB) which are commonly used to remove plaque, to titanium or zirconia and the changes in surface morphology and the epithelial attach against substrata.

Materials and Methods

(a) The morphological changes of titanium and zirconia after mechanical cleaning were assessed by scanning electron microscopy and a roughness analyser. (b) Oral epithelial cells of rats were inoculated on the surface of the materials after mechanical cleaning, and the adherence of epithelial cells was observed. (c) The maxillary first molars were extracted from the rats and replaced by experimental titanium or zirconia implants. The length of the immunoreactive laminin‐332 band was observed at the implant‐peri‐implant epithelium interface.

Results

(a) The surface roughness increased in experimental groups except the AP group. (b) Among the experimental groups, the AP group showed the highest number of attached cells. (c) The length of the immunoreactive laminin‐332 band was longer in the control group than those in all five experimental groups. Among the experimental groups, the AP group showed the longest band.

Conclusion

All mechanical cleaning methods increased the surface roughness of the materials except AP. AP did not cause distinct implant surface alterations. Surface alteration caused by mechanical cleaning may evoke inferior for epithelial attachment and reduce resistance against foreign infiltration.
The Role of Substance Use and Resiliency Factors on Suicidal Ideation among Middle School Students
Authors: Greene Naomi , Tomedi Laura , Reno Jessica , Green Dan
Published: December 2019

BACKGROUND

Suicidal ideation, an important risk factor for suicide, is strongly associated with substance use. Factors such as family cohesion, connection with friends, and social support can be protective against suicidal behaviors. The purpose of this study was to explore the association between suicidal ideation, substance use, and resiliency factors among middle school students.

METHODS

The 2013 New Mexico Youth Risk and Resiliency Survey provided the data for this analysis. Suicidal ideation was defined as affirmative responses to questions about thoughts of killing oneself and/or making a suicide plan. We used logistic regression to explore the association between suicidal ideation, substance use, and resiliency factors.

RESULTS

Overall, 23% of students reported suicidal ideation. Among girls, having a caring friend was associated with lower odds of suicidal ideation only among those not using other drugs. Among boys, having a caring friend decreased the odds of suicidal ideation regardless of substance use.

CONCLUSIONS

Suicidal ideation is prevalent among middle school children. Substance abuse is associated with suicidal ideation; however, individual and community support can be protective. Interventions aimed at reducing suicidal behaviors among middle school students should account for the impact of substance use and help strengthen social support.
The importance of considering optimal government policy when social norms matter for the private provision of public goods
Authors: Meunier Guy , Schumacher Ingmar
Published: December 2019

We study optimal government policy in a reference model (Rege, 2004, Journal of Public Economic Theory, 6, 65–77) of public good provision and social approval in a dynamic setting. We show that even if complete adherence to the social norm maximizes social welfare it is by no means necessarily optimal to push society toward it. We stress the different roles of social externality and the public good problem. We discuss the problem with the standard crowding in and out argument and analyze the relationship with Pigouvian taxes. We discuss the role of the cost of public funds and show how it can create path dependency, the multiplicity of both optimal equilibria and optimal paths, and discuss the role of parameter instability.
PXR haplotype clusters will affect the pharmacokinetics of ciclosporin in Chinese renal transplant recipients
Authors: Li Danying , Zhu Huaijun , Luo Xuemei , Ge Weihong
Published: December 2019

Objective

PXR was reported to be the key nuclear receptor regulating the expression of metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of PXR haplotype clusters on ciclosporin concentration in Chinese renal transplant recipients during the early stage after transplantation.

Methods

A total of 98 recipients receiving ciclosporin were genotyped by PCR-RFLP, and the ciclosporin concentration was determined by EMIT.

Key findings

The frequency of IVS2+55A>G, IVS2+78A>G, IVS6-17C>T, 1792A>G, 1944T>C and 2654T>C variant alleles was 0.343, 0.332, 0.378, 0.515, 0.520 and 0.393, which fitted Hardy–Weinberg equilibrium. Only the IVS6-17C>T and 2654T>C were significantly associated with the ciclosporin C2/D during the end of the first month. The mean ciclosporin C2/D level of the PXR*1B haplotype clusters was 1.3-fold and 1.2-fold higher compared with the *1A and *1C. No significant difference was observed in CsA C2/D between the PXR*1A and PXR*1C. We found no difference in C0/D among the six genotypes or the three haplotype clusters.

Conclusions

The PXR*1B in Chinese renal transplant patients was associated with ciclosporin concentration. Genetic polymorphisms and specific haplotype clusters in PXR could have significant contributory roles in affecting interethnic variations in drug disposition in the Chinese population.
Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects
Authors: Huang Min , He Ji-Xiang , Hu Hui-Xin , Zhang Kan , Wang Xiao-Ning , Zhao Bao-Bing , Lou Hong-Xiang , Ren Dong-Mei , Shen Tao
Published: December 2019

Objectives

Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019.

Key findings

Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines.

Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.
A new algorithm for optimization of rate‐adaptive pacing improves exercise tolerance in patients with HFpEF
Authors: Serova Maria , Andreev Denis , Giverts Ilya , Sazonova Yulia , Svet Aleksey , Kuklina Maria , Sedov Vsevolod , Syrkin Abram , Saner Hugo
Published: December 2019

Aim

To develop an algorithm for optimization of rate‐adaptive pacing settings in heart failure patients with preserved ejection fraction (HFpEF) and permanent cardiac pacing.

Methods

This is a prospective randomized controlled study. A total of 54 patients with HFpEF, permanent atrial fibrillation (AF), and VVIR pacing were randomized to an intervention group with optimization of rate‐adaptation parameters by using cardiopulmonary exercise testing (CPET) and pacemaker stress echocardiography (PASE), and to a control group with conventional programming. CPET, 6‐min walk test (6‐mwt), echocardiography (echo), Duke Activity Status Index (DASI), and Minnesota questionnaire (MLHFQ) were performed at baseline and after 3 months. PASE was used to exclude exercise‐induced ischemia and to determine safe upper sensor rate. Pacing parameters were corrected to achieve optimal heart rate increments of 3‐6 bpm for 1 mL/min/kg of VO2 (oxygen uptake).

Results

After 3 months, the intervention group demonstrated significant improvement of VO2 peak by 1.64 ± 1.6 mL/min/kg, anaerobic threshold by 1.33 ± 1.3 mL/min/kg, exercise time by 170 ± 98 s, 6‐mwt distance by 75 ± 63 m (P < .0001 for all), DASI by 5.23 points (P = .009), MLHFQ‐score (reduction by 9 points, P < .0001), and echo parameters (decrease in LA volume from 108 (84; 132) to 95 (85; 130) mL, P = .026; E/e’ from 11.7 ± 3.2 to 10.4 ± 2.9, P = .025; systolic pulmonary artery pressure (SPAP) from 44 ± 14 to 39 ± 12 mm Hg, P = .001) compared to the control group.

Conclusion

An algorithm incorporating CPET and PASE for optimal programming of rate‐adaptation parameters is a valuable tool to improve exercise capacity in HFpEF patients with permanent AF and VVIR pacing who remain exercise intolerant after conventional programming.
Photodynamic Therapy for Cancer: What's Past is Prologue
Authors: Hamblin Michael R.
Published: December 2019

Thomas J Dougherty from Roswell Park Cancer Center played a major role in the progress of photodynamic therapy (PDT) from a laboratory science into a real‐world clinical therapy to treat patients with cancer. Nevertheless over the succeeding 45 years, it is fair to say that the overall progress of clinical PDT for cancer has been somewhat disappointing. The goal of this perspective article is to summarize some of the clinical trials run by various companies using photosensitizers with different structures that have been conducted for different types of cancer. While some have been successful, others have failed, and several are now ongoing. I will attempt to touch on some factors, which have influenced this checkered history and look forward to the future of clinical PDT for cancer.
Examination of jackass (Equus asinus) accessory sex glands by B‐mode ultrasound and of testicular artery blood flow by colour pulsed‐wave Doppler ultrasound: Correlations with semen production
Authors: Gacem Sabrina , Papas Marion , Catalan Jaime , Miró Jordi
Published: December 2019

The accessory sex glands play a major role in the production of seminal plasma, and testicular artery blood flow seems to strongly influence testicular function. However, very little ultrasound imaging of these organs has been undertaken in donkeys. The present work reports the results of such examinations in five jackasses along the year. The accessory glands were inspected by B‐mode ultrasound while the testicular artery blood flow was assessed by colour pulsed‐wave Doppler ultrasound. The testicular artery was examined at pampiniform plexus (PPT), supratesticular area (ST) and capsular artery (CA). Values were recorded for the total arterial blood flow (TABF), peak systolic velocity (PSV), end‐diastolic velocity (EDV), resistive index (RI), pulsatility index (PI) and time average maximum velocity (TAMV). Semen was obtained and assessed for sperm concentration, viability, abnormalities and motility using a CASA system. The bulbourethral glands, prostate and ductus deferens ampullae were relatively larger than in the stallion. Bulbourethral glands and ampullae sizes were inversely correlated with sperm motility. An reduction in blood flow between the level the PPP and the CA was observed, helping to reduce testis temperature and oxygen pressure. Blood flow at the CA showed the strongest correlation with semen production. PI and RI were positively correlated with the CASA motility variable STR (p = .02, p = .06) and sperm viability (p = .01), while sperm concentration (p = .05) correlated inversely with PSV, EDV, TAMV and TABF. EDV also correlated negatively with the CASA variables VSL, LIN, STR and VAP (p ≤ .05). PI and RI were also negatively correlated with testis length (p = .0093, p = −.0438).
The Lost Patriarchs Project: Recovering the Greek Fathers in the medieval Latin tradition
Authors: Bruce Scott G.
Published: December 2019

This article calls attention to an important, yet neglected, subset of medieval Latin sources: the dozens upon dozens of works of late antique and early Byzantine Christian Greek authors translated into Latin between the second and the thirteenth centuries. It also introduces a new initiative to study these sources: The Lost Patriarchs Project. The goal of this article is threefold. First, it presents a sample of the deep, virtually untouched reservoir of medieval Latin texts that have Greek origins, including patristics, hagiography, and apocrypha, and marshals evidence for their use among medieval readers. Second, it considers some of the reasons why this corpus of medieval Latin literature has not been subject to critical inquiry. Third, it announces plans for a new instrument of reference tentatively entitled The Lost Patriarchs: A Survey of the Greek Fathers in the Medieval Latin Tradition. A reference tool of this kind would gather all that is known about these texts in current scholarship, allowing future researchers to begin the work of creating critical editions of them and incorporating them into our understanding of medieval thought.
(Dis)Owning Exotic: Navigating Race, Intimacy, and Trans Identity
Authors: Buggs Shantel Gabrieal
Published: December 2019

Despite societal shifts making the United States more inclusive, particularly among younger people, transgender people and people of color remain populations that have labels like “exotic” or “taboo” associated with them. This article explores the racialized dating experiences of an immigrant trans woman of color who uses online dating platforms to facilitate her dating life in Texas. Given that the existing literature on trans people tends to focus on identity development, health concerns, or questions of legality and policy in arenas such as the workplace and in education, there is still limited research on the romantic and sexual lives of trans people. In fact, much of the growing research on trans relationships focuses either on couples where one partner transitioned and the couple maintained a relationship or studies lumping trans experiences under an LGBT umbrella. Using an intersectional theoretical approach, this case study unpacks how race, racism, and transphobia, as well as internalized racial and gender logics, work in tandem to shape desirability and date ability.