bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcutaneous Cervical Vagal Nerve Stimulation Reduces Sympathetic Responses to Stress in Posttraumatic Stress Disorder
Authors: Gurel Nil Z. , Wittbrodt Matthew T. , Jung Hewon , Shandhi Md. Mobashir H. , Driggers Emily G. , Ladd Stacy L. , Huang Minxuan , Ko Yi-An , Shallenberger Lucy , Beckwith Joy , Nye Jonathon A. , Pearce Bradley D. , Vaccarino Viola , Shah Amit J. , Inan Omer T. , Bremner J. Douglas
Published: February 2020

Objective

Exacerbated autonomic responses to acute stress are prevalent in posttraumatic stress disorder (PTSD). The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD. The authors hypothesized tcVNS would reduce the sympathetic response to stress compared to a sham device.

Methods

Using a randomized double-blind approach, we studied the effects of tcVNS on physiological responses to stress in patients with PTSD (n=25) using noninvasive sensing modalities. Participants received either sham or active tcVNS after exposure to acute personalized traumatic script stress and mental stress (public speech, mental arithmetic) over a three-day protocol. Physiological parameters related to sympathetic responses to stress were investigated.

Results

Relative to sham, tcVNS paired to traumatic script stress decreased sympathetic function as measured by: decreased heart rate (adjusted ß=-5.7%; 95% CI: ±3.6%, effect size d=0.43, p<0.01), increased photoplethysmogram amplitude (peripheral vasodilation) (30.8%; ±28%, 0.29, p<0.05), and increased pulse arrival time (vascular function) (6.3%; ±1.9%, 0.57, p<0.0001). Similar (p < 0.05) autonomic, cardiovascular, and vascular effects were observed when tcVNS was applied after mental stress or without acute stress.

Conclusion

tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD, with effects persisting throughout multiple traumatic stress and stimulation testing days. These findings show that tcVNS has beneficial effects on the underlying neurophysiology of PTSD. Such autonomic metrics may also be evaluated in daily life settings in tandem with tcVNS therapy to provide closed-loop delivery and measure efficacy.

ClinicalTrials.gov Registration # NCT02992899

Highlights

We studied the effects of tcVNS on physiological responses to stress in patients posttraumatic stress disorder (PTSD).

tcVNS modulates physiologic reactivity to traumatic and mental stress in PTSD, and modulates autonomic tone when applied without acute stress.

Repeated tcVNS enhances resilience in the face of repeated stress in PTSD as quantified by peripheral autonomic measures which potentially could serve as real-time measures to evaluate the therapy response in longitudinal settings.
Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression
Authors: MahmoudianDehkordi Siamak , Ahmed Ahmed T. , Bhattacharyya Sudeepa , Han Xianlin , Baillie Rebecca A. , Arnold Matthias , Skime Michelle K. , St. John-Williams Lisa , Moseley M. Arthur , Thompson J. Will , Louie Gregory , Riva-Posse Patricio , Craighead W. Edward , McDonald William , Krishnan Ranga , Rush A John , Frye Mark A. , Dunlop Boadie W. , Weinshilboum Richard M. ,   The Mood Disorders Precision Medicine Consortium (MDPMC), Kaddurah-Daouk Rima
Published: February 2020

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium- and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines – including arginine, proline, and methionine-sulfoxide – were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17≤7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics – including acylcarnitine metabolism, transport and its link to β-oxidation – and lipid membrane remodeling may play roles in SSRI treatment response.
Metastable GPCR dimers trigger the basal signal by recruiting G-proteins
Authors: Kasai Rinshi S. , Fujiwara Takahiro K. , Kusumi Akihiro
Published: February 2020

G-protein-coupled receptors (GPCRs) constitute the largest family of integral membrane proteins in the human genome and are responsible for various important signaling pathways for vision, olfaction, gustation, emotion, cell migration, etc. A distinct feature of the GPCR-family proteins is that many GPCRs, including the prototypical GPCR, β2-adrenergic receptor (β2AR), elicit low levels of basal constitutive signals without agonist stimulation, which function in normal development and various diseases1–3. However, how the basal signals are induced is hardly known. Another general distinctive feature of GPCRs is to form metastable homo-dimers, with lifetimes on the order of 0.1 s, even in the resting state. Here, our single-molecule-based quantification4determined the dissociation constant of β2AR homo-dimers in the PM (1.6 ± 0.29 copies/μm2) and their lifetimes (83.2 ± 6.4 ms), and furthermore found that, in the resting state, trimeric G-proteins were recruited to both β2AR monomers and homo-dimers. Importantly, inverse agonists, which suppress the GPCR’s basal constitutive activity, specifically blocked the G-protein recruitment to GPCR homo-dimers, without affecting that to monomers. These results indicate that the G-proteins recruited to transient GPCR homo-dimers are responsible for inducing their basic constitutive signals. These results suggest novel drug development strategies to enhance or suppress GPCR homo-dimer formation.
Mechanical scarification, seed origin, and substrate influence on germination ofSamanea tubulosa
Authors: Regnier Leonardo L. P.
Published: February 2020

Samanea tubulosais an important species mainly to its uses in reforestation projects and as a wood and fruit resource. This species seed dormancy and other scarce germination information have been limiting the adequate seedling production process. Thus, this study tried to understand how seed origin, mechanical scarification, and substrate could influence the seedling production process. The population affected the time required for germination and germination speed, probably due to high genetic variability. Whereas mechanical scarification did not present statistical differences in the control treatment, with seeds in the natural condition, indicating that seed dormancy could be variable. Substrate promoted significant differences in germination rate. The population seems to affect, but not preclude seedling production. Mechanical scarification did not provide a relevant enhancement of germination. Vermiculite presented a significantly higher germination rate than the organic-based substrate.
A whole-brain connectivity map of mouse insular cortex
Authors: Gehrlach Daniel A. , Gaitanos Thomas N. , Klein Alexandra S. , Weiand Caroline , Hennrich Alexandru A. , Conzelmann Karl-Klaus , Gogolla Nadine
Published: February 2020

The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly reciprocal, the IC connectivity with subcortical structures was often unidirectional, revealing prominent top-down and bottom-up pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.
Achilles tendon stiffness minimizes the energy cost in simulations of walking in older but not in young adults
Authors: Delabastita Tijs , De Groote Friedl , Vanwanseele Benedicte
Published: February 2020

Both Achilles tendon stiffness and walking patterns influence the energy cost of walking, but their relative contributions remain unclear. These independent contributions can only be investigated using simulations. We created models for 16 young (24±2 years) and 15 older (75±4 years) subjects, with individualized (using optimal parameter estimations) and generic triceps surae muscle-tendon parameters. We varied Achilles tendon stiffness and calculated the energy cost of walking. Both in young and older adults, Achilles tendon stiffness independently contributed to the energy cost of walking. However, overall, a 25% increase in Achilles tendon stiffness increased the triceps surae and whole-body energy cost of walking with approximately 7% and 1.5%, respectively. Therefore, the influence of Achilles tendon stiffness is rather limited. Walking patterns also independently contributed to the energy cost of walking because the plantarflexor (including, but not limited to the triceps surae) energy cost of walking was lower in older than in young adults. Hence, training interventions should probably rather target specific walking patterns than Achilles tendon stiffness to decrease the energy cost of walking. However, based on the results of previous experimental studies, we expected that the calculated hip extensor and whole-body energy cost of walking would be higher in older than in young adults. This was not confirmed in our results. Future research might therefore assess the contribution of the walking pattern to the energy cost of walking by individualizing maximal isometric muscle force and by using three-dimensional models of muscle contraction.

Summary statement

Achilles tendon stiffness and walking patterns independently contribute to the energy cost in simulations of walking in young and older adults. The influence of Achilles tendon stiffness is rather small.
Regulation of T cell receptor signaling by protein acyltransferase DHHC21
Authors: Fan Ying , Shayahati Bieerkehazhi , Tewari Ritika , Boehning Darren , Akimzhanov Askar M.
Published: February 2020

S-acylation – reversible post-translational lipidation of cysteine residues – is emerging as an important regulatory mechanism in T cell signaling. Dynamic S-acylation is critical for protein recruitment into the T cell receptor complex and initiation of the subsequent signaling cascade. However, the enzymatic control of protein S-acylation in T cells remains poorly understood. Here, we report a previously uncharacterized role of DHHC21, a member of the mammalian family of DHHC protein acyltransferases, in regulation of the T cell receptor pathway. We found that loss of DHHC21 prevented S-acylation of key T cell signaling proteins, resulting in disruption of the early signaling events and suppressed expression of T cell activation markers. Furthermore, downregulation of DHHC21 prevented activation and differentiation of naïve T cells into effector subtypes. Together, our study provides the first direct evidence that DHHC protein acyltransferases can play an essential role in regulation of T cell-mediated immunity.
Gain-of-function mutation inGli3causes ventricular septal defects
Authors: Wiegering Antonia , Adibi Paniz , Rüther Ulrich , Gerhardt Christoph
Published: February 2020

Ventricular septal defects (VSDs) are developmental disorders, characterised by a gap in the septum between the right and the left ventricle, that lead to life-threatening heart defects. At present, the only curative treatment of VSDs is surgical closure. Since these surgeries comprise several severe risks, the development of alternative therapies against VSDs is urgently needed. To develop such therapies, the current knowledge of the molecular factors and mechanisms underlying VSDs has to be increased. Based on our previous data, we analysed the relevance of the HH signalling pathway mediator GLI3 in ventricular septum (VS) formation. GLI3 functions as both a transcriptional activator (GLI3-A) and repressor (GLI3-R). By analysing two different mouseGli3mutants, we revealed that the lack of GLI3-A with simultaneous presence of GLI3-R impairs cilia-mediated PDGFRα signalling causing reduced cell proliferation and in consequence the development of VSDs. Moreover, we showed that the rescue of PDGFRα signalling restores cell proliferation. Since VSDs are also appear in humans with comparable gain-of-function mutations inGLI3, our findings propose activators of PDGFRα signalling as potential agents against the development of VSDs.

The article reports how a gain-of-function mutation ofGli3causes ventricular septal defects and paves the way for therapies tackling these congenital heart defects.
Determining which mechanisms underlie facilitation by tussocks in tropical high mountains and their relative importance
Authors: Pedraza Fernando , García-Meza Diego , Tovar Hugo , Martorell Carlos
Published: February 2020

Facilitation by tussocks is common in high-altitude tropical environments. It is thought that facilitation results from stress amelioration, but it is unclear which of the many stressors acting in these environments is ameliorated. We aimed at determining the relative importance of different stressors as drivers of facilitation by the tussockFestuca tolucensisin Mexico. We manipulated five stressors in the field: minimum temperatures by using electric radiators that kept plants warm; maximum temperatures by means of reflective sand that precluded temperature build-up during the day; UV radiation by using screens opaque to UV; poor soil properties by comparing soils from beneath tussocks and from bare ground; and low water availability by adding vermiculite to the soil. The performance (survival and growth) ofMexerion sarmentosum(a plant usually associated withFestuca) in these treatments was compared to that recorded under tussocks and in bare ground. Amelioration of extreme temperatures had the largest positive effects onMexerionsurvival. UV radiation and increased soil humidity did not affect survival, although humidity increased growth rates. Nevertheless, tussocks reduced the growth ofMexerion, which is consistent with observations of competition between plants and soil microorganisms favoured by tussocks. Our results highlight the importance of the extreme daily fluctuations in temperature that characterise tropical mountains as fundamental drivers of their dynamics.
sciCNV: High-throughput paired profiling of transcriptomes and DNA copy number variations at single cell resolution
Authors: Mahdipour-Shirayeh Ali , Erdmann Natalie , Leung-Hagesteijn Chungyee , Tiedemann Rodger E.
Published: February 2020

Chromosome copy number variations (CNVs) are a near-universal feature of cancer however their effects on cellular function are incompletely understood. Single cell RNA sequencing (scRNA-seq) can reveal cellular gene expression however cannot directly link this to CNVs. Here we report new normalization methods (RTAM1 and −2) for scRNA-seq that improve gene expression alignment between cells, enhancing gene expression comparisons and the application of scRNA-seq to CNV detection. We also report sciCNV, a pipeline for inferring CNVs from RTAM-normalized data. Together, these tools provide dual profiling of transcriptomes and CNVs at single-cell resolution, enabling exploration of the effects of cancer CNVs on cellular programs. We apply these tools to multiple myeloma (MM) and examine the cellular effects of cancer CNVs +8q. Consistent with prior reports, MM cells with +8q22-24 upregulate MYC, MYC-target genes, mRNA processing and protein synthesis, verifying the approach. Overall, we provide new tools for scRNA-seq that enable matched profiling of the CNV landscape and transcriptome of single cells, facilitate deconstruction of the effects of cancer CNVs on cellular reprogramming within single samples.
Temperature-Induced Uncoupling of Cell Cycle Regulators
Authors: Falahati Hanieh , Hur Woonyung , Di Talia Stefano , Wieschaus Eric F.
Published: February 2020

While feedback loops are essential for robustness in signaling systems, they make discerning the role of individual components challenging. Here we introduce temperature as a powerful perturbation method for uncoupling enzymatic processes, by exposing the differential sensitivity of limiting reactions to temperature due to their activation energies. Using this method, we study the sensitivity to temperature of different cell cycle events of early fly embryos. While the subdivision of cell cycle steps is conserved across a wide range of temperatures (5-35°C), the transition into prometaphase exhibits the most sensitivity, arguing that it has a different mechanism of regulation. Using a biosensor, we quantify the activity of Cdk1 and show that the activation of Cdk1 drives entry into prometaphase but is not required for earlier events. In fact, chromosome condensation can still occur when Cdk1 is inhibited pharmacologically. These results demonstrate that different kinases are rate-limiting for different steps of mitosis.
Crystal structure of 1,4,8,11-tetramethyl-1,4,8,11-tetraazoniacyclotetradecane bis(perchlorate) dichloride from synchrotron X-ray data
Authors: Moon Dohyun , Choi Jong-Ha
Published: February 2020

The crystal structure of title salt, C14H36N4
4+·2ClO4
−·2Cl−, has been determined using synchrotron radiation at 220 K. The structure determination reveals that protonation has occurred at all four amine N atoms. The asymmetric unit contains one half-cation (completed by crystallographic inversion symmetry), one perchlorate anion and one chloride anion. A distortion of the perchlorate anion is due to its involvement in hydrogen-bonding interactions with the cations. The crystal structure is consolidated by intermolecular hydrogen bonds involving the 1,4,8,11-tetramethyl-1,4,8,11-tetraazoniacyclotetradecane N—H and C—H groups as donor groups, and the O atoms of the perchlorate and chloride anion as acceptor groups, giving rise to a three-dimensional network.
Telecenters and the expansion of human capabilities among rural women
Authors: Lwoga Edda Tandi , Chigona Wallace
Published: February 2020

Purpose

This study aims to assess the contribution of telecenters in expanding the capabilities of rural women to achieve their development outcomes in three rural districts in Tanzania.

Design/methodology/approach

The study conducted 12 focus group discussions with 37 rural women users and 36 rural women non-users of telecenters and semi-structured interviews with telecenter managers in the selected districts. The framework for the study is based on Sen’s capability approach.

Findings

The study noted that telecenters may enable rural women to build some capabilities (social, financial, human and political capabilities), and inhibit others, resulting in diverse development outcomes, based on the choices made and conversion factors. These conversion factors included institutional factors (inadequate computers, space and personnel, unreliable electrical power and slow internet connectivity) and individual factors (multiple responsibilities, status, low-level of education, language barrier, lack of information and communication technology (ICT) skills and technology efficacy and inability to afford ICT short courses). Other conversion factors (e.g. availability of affordable ICTs) enabled rural women to build their capabilities.

Originality/value

This is a comprehensive study that provides findings for rural telecenters to plan and allow rural women to expand their capabilities and achieve their development goals in Tanzania or other settings with similar conditions.
Exploring IKEA effect in self-expressive mass customization: underlying mechanism and boundary conditions
Authors: Ling I-Ling , Liu Yi-Fen , Lin Chien-Wei (Wilson) , Shieh Chih-Hui
Published: February 2020

Purpose

This study aims to understand the underlying mechanism and boundary conditions of the IKEA effect in self-expressive mass customization (MC). It examines the effect of the extent of choice in MC toolkits in terms of perceived value of self-designed products, as well as how self-expression mediates this effect and what kind of consumers are more inclined to experience such effect.

Design/methodology/approach

Two experiments were conducted, using online MC toolkits. In total, 393 consumers participated in the experiments. Data collected were analyzed using t-tests, analyses of variance, path analyses, bootstrap analyses and spotlight tests.

Findings

The results show that offering a greater extent of choice in MC toolkits to consumers provides a greater opportunity for self-expression, resulting in higher product valuation. Further, consumers who have high romanticism in aesthetic preference and high self-esteem are more inclined to influences associated with this effect.

Originality/value

This research adds to the literature on the IKEA effect in self-expressive MC by identifying a key antecedent (extent of choice), its underlying mechanism (self-expression), and two boundary conditions (aesthetic preference and self-esteem). The results of this study provide firms with a better understanding of how they can improve their self-expressive MC strategies.
Development and validation of a health educational booklet
Authors: Farizan Noor Hamzani , Sutan Rosnah , Hod Rozita , KC Mani Kulanthayan
Published: February 2020

Purpose

This study aimed to develop and validate a health education booklet (Be SAFE booklet) as a guide to improving knowledge, attitude, and practice toward drowning prevention and water safety among parents of primary school children in a local community in Selangor.

Design/methodology/approach

This methodological study was conducted in two phases: the development of the content, and validation of the educational material. Booklet development involved content survey and design development. These steps consisted of a content analysis method, information from current literature, document analysis from the stakeholder, and input from parents or guardians and children. The validation by nine panel experts and 15 parents/guardians involved both review, content validity, and face validity.

Findings

The booklet was developed by emphasizing on four main aspects related to drowning prevention and water safety; namely, supervision, alertness, first aid, and education. The assessment rated by the content validity index (CVI), resulted in an I-CVI ranging from 0.78 to 1 and S-CVI of 0.94; the face validity achieved a level of agreement with an average of 94 percent. The results indicated that the Be SAFE booklet was validated and could be considered useful in helping to promote drowning prevention and water safety among primary school pupils' parents.

Originality/value

This article contributed ideas for the concept and aspect of health messages to be incorporated into health education materials for drowning prevention and water safety.
Prevalence of infectious diseases in patients with autoimmune blistering diseases
Authors: Ujiie Inkin , Ujiie Hideyuki , Yoshimoto Norihiro , Iwata Hiroaki , Shimizu Hiroshi
Published: February 2020

A long‐term immunosuppressive treatment can provoke latent infections. Autoimmune blistering diseases (AIBD) are mostly treated with systemic immunosuppressive agents. To prevent the reactivation or exacerbation of existing latent infections, patients must be screened for infectious diseases before immunosuppressive treatments are initiated. However, the prevalence of infectious diseases in AIBD remains to be elucidated. To evaluate the necessity of screening infectious diseases in AIBD, we retrospectively reviewed the clinical records of 215 patients at a single center with AIBD for hepatitis B virus (HBV), hepatitis C virus (HCV), Mycobacterium tuberculosis, Treponema pallidum, human T‐cell leukemia virus type 1 (HTLV‐1) and HIV infections. Approximately 40% of patients were infected with HBV. During systemic corticosteroid treatment, HBV DNA became positive in 3.4% of cases. Antibodies to HCV, interferon‐γ release assays for M. tuberculosis and the T. pallidum latex agglutination test were positive in 0.6%, 6.6% and 1.2% cases, respectively. Neither HTLV‐1 nor HIV infections were detected. In conclusion, checks for HBV and M. tuberculosis infections should be made before immunosuppressive treatments are started, because of the high prevalence of these potentially life‐threatening infections. Other infections should be tested for depending on the patient’s risk factors.
High contrast yellow mosaic patterns are prey attractants for orb‐weaving spiders
Authors: Peng Po , Stuart‐Fox Devi , Chen Szu‐Wei , Tan Eunice J. , Kuo Guan‐Lin , Blamires Sean J. , Tso I‐Min , Elgar Mark A.
Published: February 2020

Many animals improve their foraging success by producing signals that exploit the sensory biases of potential prey, but the specific properties that make these sensory traps effective remain unclear.

We combine field experiments with phylogenetic comparative analyses to investigate the visual luring properties of different signal designs in web‐building spiders. Our field experiments used cardboard spider models to examine the effects of area of colour patches, colour and pattern on the foraging success of the colourful giant wood spider, Nephila pilipes. These experiments revealed that both the colour (yellow) and pattern (yellow and black mosaic) are essential for luring prey in a high ambient light environment.

We subsequently used phylogenetic comparative analyses to demonstrate an evolutionary association between prey viewing environment and spider ventral signal among 63 species of orb‐weavers from 53 genera.

Combined, our data show that (a) the colour of the bright body parts of orb‐weavers is essential for both diurnal and nocturnal prey attraction, whereas the pattern and area of colour patches are important for diurnal foraging and (b) the evolution of these visual lures is associated with the viewing environment, specifically ambient light intensity.

We conclude that the effectiveness of colour luring might be a major driver of the convergent evolution of yellow mosaic patterns in phylogenetically divergent orb‐weavers.

Our discoveries indicate that prey colour preferences and signal efficacy play a significant role in the evolution of visually mediated prey‐luring systems.

A free Plain Language Summary can be found within the Supporting Information of this article.
Enhancing imaging of the Sub‐Andean Foothills geology using magnetotellurics: A case history of a 3D survey in southern Bolivia
Authors: Pezzoli Mauro , Lazaro Evanz , Cuevas Nestor , Burga Sergio
Published: February 2020

A magnetotelluric acquisition and modelling campaign, comprising 400 full tensor soundings, was carried out in the Sub‐Andean Foothills in the area located south of Santa Cruz de la Sierra, Bolivia. The objective of the survey was to improve the imaging of the Paleozoic section and provide insight to the overall structure of the Devonian Silurian complex. The acquired data were inverted assuming both two‐dimensional and three‐dimensional dimensionality of the subsurface structure, adopting a multi‐step iterative workflow, which began applying unconstrained inversion and introduced increasing constraints determined at each following step based on the interpretation of the latest inversion results. The geological interpretation of the final inversion results allowed to better image the expected complexity in the structures, particularly highlighting several different levels of detachment, mainly in the area of Kirusillas Formation. Furthermore, an oblique sense was identified of the main tendency of N‐S deformation, related to a dextral transgressional movement that generates discrete dislocations, at a length scale of the order of a few kilometres.
Tissue factor pathway inhibitor 2 suppresses the growth of thyroid cancer cells through by induction of apoptosis
Authors: Yang Yan , Zhang Chen , Li Shu , Liu Jialun , Qin Yiyu , Ge Anxing
Published: February 2020

Background

Tissue factor pathway inhibitor 2 (TFPI‐2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear.

Methods

The TFPI‐2 protein level in thyroid cancer tissues and cell lines (8305C and B‐CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI‐2 promoter methylation was examined using methylation‐specific polymerase chain reaction (MSP). Lentivirus containing TFPI‐2 cDNA (Lenti‐TFPI‐2) was constructed to elevate TFPI‐2 expression in 8305C and B‐CPAP cells. The effects of Lenti‐TFPI‐2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti‐TFPI‐2 on cell apoptosis.

Results

TFPI‐2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI‐2 protein level is positively associated with survival time. The promoter of TFPI‐2 is hypermethylated in cancer tissues. TFPI‐2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy‐ori 3‐1 cells, whereas they were decreased in 8305C and B‐CPAP cells. pcDNA‐TFPI‐2 elevated TFPI‐2 mRNA and protein in 8305C and B‐CPAP cells. TFPI‐2 overexpression suppressed proliferation and induced apoptosis of 8305C and B‐CPAP cells.

Conclusions

TFPI‐2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI‐2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI‐2 may serve as a novel and effective target for thyroid cancer therapy.
Safety, tolerability, pharmacokinetics and pharmacodynamics of the anti‐CD38 cytolytic antibody TAK‐079 in healthy subjects
Authors: Fedyk Eric R. , Zhao Lin , Koch Annelize , Smithson Glennda , Estevam Jose , Chen Grace , Lahu Gezim , Roepcke Stefan , Lin Jianchang , Mclean Lachy
Published: February 2020

Aims

This investigation characterised tolerability, pharmacokinetics and pharmacodynamics of the anti‐CD38 antibody TAK‐079.

Methods

A randomised, double‐blind, placebo‐controlled trial of a single intravenous (i.v.) infusion or subcutaneous (s.c.) injection of TAK‐079 at escalating doses in healthy subjects (n = 74), who were followed for 92 days postexposure.

Results

TAK‐079 was well tolerated. All adverse events were mild or moderate. There were no withdrawals, infusion, or injection site reactions over the tested i.v. and s.c. doses up to 0.06 and 0.6 mg kg−1, respectively. At higher doses, transient cytokine level increases, following i.v. administration, coincided with reduction in CD38‐expressing cells; clinical symptoms included mild pyrexia, headache, and postural hypotension. Following an i.v. infusion of 0.06 mg kg−1 TAK‐079, maximum observed serum concentration (Cmax) was 100.4 (%CV: 52) ng mL−1, time to Cmax was the end of infusion and natural killer (NK_ cells were reduced 93.8 (±8.5) % from baseline levels. Following a s.c. injection of 0.6 mg kg−1 TAK‐079, Cmax was 23.0 (%CV: 67) ng mL−1 with time to Cmax of 24 (range 7.98–96.02) hours, and plasmablasts were subsequently reduced 93.4 (±8.8) % from predose levels. Serum immunoglobulin (Ig)M, IgA and IgG levels were reduced by 15–60% and had not returned to baseline levels within 78 days after administration at ≥0.3 mg kg−1 s.c. Reductions in NK cells at 0.6 mg kg−1 s.c. were approximately 2–3 times more durable than at 0.06 mg kg−1 i.v.

Conclusions

TAK‐079 was well tolerated and s.c. administration elicited more durable reductions in plasmablasts and NK cells. This plasmacytolytic profile could be useful for treating disorders caused by plasma or NK cells, malignant counterparts, and/or pathogenic antibodies.
Fostering highly engaged knowledge building communities in socioemotional and sociocognitive hybrid learning spaces
Authors: Hod Yotam , Katz Shir
Published: February 2020

With the aim of understanding sociocognitive and socioemotional hybridity in learning spaces, we examined a semester‐long learning community where students were given the freedom to advance their epistemological and social agendas across face‐to‐face and online settings. We collected and analyzed 1,780 online notes written by students throughout the semester and coded them based on their sociocognitive or socioemotional values. We then examined the conversation chains that students engaged in vis‐a‐vis their developments as a group. In addition to showing how the group developmental stages served as a macro‐level context for the socioemotional and sociocognitive spaces, the analysis highlighted how deep, rapid, community knowledge building conversations spontaneously emerged in relation to the timing of socioemotional developments. This study elucidates an important dimension of hybrid spaces, emphasizing the need to design activities to support both sociocognitive and socioemotional spaces in technology‐enhanced learning communities.
Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals
Authors: Jeremias Guilherme , Gonçalves Fernando J. M. , Pereira Joana L. , Asselman Jana
Published: February 2020

Epigenetic mechanisms have gained relevance in human health and environmental studies, due to their pivotal role in disease, gene × environment interactions and adaptation to environmental change and/or contamination. Epigenetic mechanisms are highly responsive to external stimuli and a wide range of chemicals has been shown to determine specific epigenetic patterns in several organisms. Furthermore, the mitotic/meiotic inheritance of such epigenetic marks as well as the resulting changes in gene expression and cell/organismal phenotypes has now been demonstrated. Therefore, epigenetic signatures are interesting candidates for linking environmental exposures to disease as well as informing on past exposures to stressors. Accordingly, epigenetic biomarkers could be useful tools in both prospective and retrospective risk assessment but epigenetic endpoints are currently not yet incorporated into risk assessments. Achieving a better understanding on this apparent impasse, as well as identifying routes to promote the application of epigenetic biomarkers within environmental risk assessment frameworks are the objectives of this review. We first compile evidence from human health studies supporting the use of epigenetic exposure‐associated changes as reliable biomarkers of exposure. Then, specifically focusing on environmental science, we examine the potential and challenges of developing epigenetic biomarkers for environmental fields, and discuss useful organisms and appropriate sequencing techniques to foster their development in this context. Finally, we discuss the practical incorporation of epigenetic biomarkers in the environmental risk assessment of chemicals, highlighting critical data gaps and making key recommendations for future research within a regulatory context.
The Bangladesh Cerebral Palsy Register: the value of surveillance
Authors: Bedard Tanya
Published: February 2020

This commentary is on the original article by Manlongat et al. on pages 463–469 of this issue.
Validity of the Ages and Stages Questionnaire to identify young children with gross motor difficulties who require physiotherapy assessment
Authors: Fauls John R , Thompson Bronwyn L , Johnston Leanne M
Published: February 2020

Aim

To determine if the Ages and Stages Questionnaire, Third Edition Gross Motor domain (ASQ‐3‐GM) score is predictive of motor performance on the Alberta Infant Motor Scale (AIMS) and/or Neurological, Sensory, Motor, Developmental Assessment (NSMDA).

Method

This was a cross‐sectional study involving analysis of a 1‐year consecutive clinical sample of data obtained from children attending a specialist public outpatient service. Participants were 84 children aged 0 to 5 years (mean age 24.9mo, SD 18.4mo; 50 males, 34 females) referred for physiotherapy assessment of gross motor skills in a tertiary child development service. Parents completed the ASQ‐3 questionnaire and children were assessed using the AIMS (if aged 0–18mo) and/or NSMDA (all children). To determine possible relationships between ASQ‐3‐GM scores with AIMS and NSMDA scores, we calculated Spearman’s rank correlation coefficients. To determine validity of the ASQ‐3‐GM ‘refer for further assessment’ (‘refer’) cut‐off score to identify gross motor difficulties we calculated frequency distributions and crosstab analyses.

Results

ASQ‐3‐GM scores correlated with AIMS centile rank (r=0.697, p<0.001) and NSMDA motor performance classification (r=–0.548, p<0.001). The ASQ‐3‐GM ‘refer’ cut‐off had 77% sensitivity, 91% specificity, and 95% positive predictive value (PPV) to identify children that scored ≤10th centile on the AIMS and 57% sensitivity, 92% specificity, and 97% PPV to identify children with at least minimal dysfunction on the NSMDA.

Interpretation

The ASQ‐3‐GM ‘refer’ cut‐off score is a valid predictor of gross motor difficulties in young children.

What this paper adds

The Ages and Stages Questionnaire, Third Edition Gross Motor domain (ASQ‐3‐GM) score is valid to identify gross motor difficulties in young children.

The ASQ‐3‐GM ‘refer’ cut‐off had 95% positive predictive value (PPV) for children that scored ≤10th centile on the Alberta Infant Motor Scale.

The ASQ‐3‐GM ‘refer’ cut‐off had 97% PPV for at least minimal dysfunction on the Neurological, Sensory, Motor, Developmental Assessment.
Psychosocial adjustment of young offspring in the context of parental type 1 and type 2 diabetes: a systematic review
Authors: Landi G. , Andreozzi M. S. , Pakenham K. I. , Grandi S. , Tossani E.
Published: February 2020

Aims

To identify all available research on psychosocial outcomes in young people who have a parent with type 1 or type 2 diabetes.

Methods

Embase, PsychInfo, Scopus, Web of Science, PubMed and ProQuest Social Sciences databases were searched according to a registered study protocol (PROSPERO CRD42019125301). Quality assessment, data extraction and data synthesis were carried out.

Results

The initial search yielded 11 599 articles, 10 of which met the criteria for this review: six for type 1 diabetes and four for type 2 diabetes. Through thematic analysis, five categories emerged related to offspring psychosocial adjustment: offspring mental health, offspring physical health, offspring personal resources, parental illness characteristics and offspring caregiving. Overall, there were few studies focusing solely on the effects of parental type 1 and type 2 diabetes on young people. From the limited available research, there is weak evidence suggesting both parental types of diabetes can adversely impact young offspring. Illness‐related variables were only explored in parental type 1 diabetes studies, while offspring caregiving was only examined in parental type 2 diabetes studies.

Conclusions

Research on the effects of parental diabetes on young people is scarce; however, there was weak evidence to suggest some young people are at risk of adverse psychosocial impacts. Given the rise in the incidence of diabetes globally, there is a pressing public health need to conduct more rigorously designed studies to ascertain the extent to which young people are at risk of mental and physical health problems and to identify risk and protective factors associated with youth adjustment in the context of parental diabetes.
Effect of brief social contact video compared with expert information video in changing knowledge and attitude towards psychosis patients among medical students
Authors: Tsoi Ottilia Y. Y. , Chan Sherry K. W. , Chui Aretha H. C. , Hui Christy L. M. , Chang Wing C. , Lee Edwin H. M. , Henderson Claire , Chen Eric Y. H.
Published: February 2020

Objective

Direct contact interventions are known to reduce stigma. Effects of both filmed and direct social contact were found similar in reducing stigma. This study aims to understand the effect of video intervention, especially the effects between patient‐sharing video and expert information video, among the medical students.

Methods

Seventy‐two medical students were recruited from two consecutive clinical study periods. Students from one period were in the patient‐sharing group, watching a 7‐minute patient‐sharing video. The others were in expert information group watching a 5‐minute psychosis video. Subject's desire of social distance (Reported and Intended Behaviour Scale) knowledge (the Social Contact Intended Learning Outcome) attitude towards mental illness (Clinicians Attitudes Scales version 4) and emotional reactions (the Emotional Reactions to Mental illness Scales) were measured. Assessments were done at baseline, immediately after video watching and at 1 to 2 weeks follow‐up. Within‐group ANOVA was used to assess the difference between time points. Group by time effect was explored.

Results

Significant improvement in knowledge level was found with a significant group by time effect (F = 6.261, P = .004) for PS group and was maintained at follow‐up. Post‐intervention attitude was significantly improved in PS group but not maintained. Only social distance was improved significantly in EX group (F = 8.093, P = 0.003). Both groups had a significant reduction in fear sub‐score.

Conclusion

This study provided evidence on the effect of patient‐sharing video in improving the attitude and knowledge of medical students. Expert information video about psychosis can improve social proximity. Combining these approaches may improve stigma and knowledge among medical students.
Cultural competency in dietetic diabetes care—A qualitative study of the dietician’s perspective
Authors: Jager Mirjam , den Boeft Andrea , Leij‐Halfwerk Susanne , van der Sande Rob , van den Muijsenbergh Maria
Published: February 2020

Introduction

Diabetes type 2 is more prevalent in ethnic minorities in the Netherlands, and outcomes of health care in general are worse compared to other Dutch patients. The purpose of this study is to explore the experiences of dieticians and the knowledge, skills and attitudes they consider to be important for effective dietetic care in migrant patients.

Methods

Semi‐structured interviews were held with 12 dieticians, of various ages, ethnic backgrounds and experience. The interview guide was based on Seeleman's cultural competence model and the Dutch dietetic consultation model. Interviews were transcribed, coded and thematically analysed, revealing 7 main themes.

Results

Dieticians were uncertain whether their care fulfilled their migrant patients’ needs. They experienced language differences as a major barrier for retrieving information and tailoring advice to the patient's needs. Furthermore, dieticians feel they lack cultural knowledge. An open and respectful attitude was considered important for effective care. The communication barrier hindered building a trusting relationship; however, few dieticians mentioned a need for communication training. They expressed a need for cultural competence training, specifically to acquire cultural knowledge.

Conclusion

Dieticians struggle with providing dietetic care for migrant diabetes patients due to communication barriers and difficulty in building a trusting relationship. They are conscious of their lack of cultural knowledge, and acknowledge the need for an open and respectful attitude and essential communication skills in order to collect and convey information. They seem unaware of the impact of low (health) literacy. Cultural competence training is needed for effective dietetic care for migrants.
Factors contributing to the decline of an endangered flightless longhorn beetle: A 20‐year study
Authors: Baur Bruno , Coray Armin , Lenzin Heiner , Schmera Dénes
Published: February 2020

World‐wide decreases of insect abundance and diversity are of major concern because of their importance for ecosystem functioning and the stability of ecosystems. Various studies reported dramatic declines of butterflies, wild bees and beetles in agricultural areas. Yet, evidence for decreasing abundance in cryptic insect species is scarce.

Using a transect‐count technique, we monitored the relative population size of the endangered flightless grassland longhorn beetle Iberodorcardion fuliginator in 13 dry, semi‐natural grassland sites in the border region of Switzerland, France, and Germany at yearly intervals over 20 years (1999–2018). To disentangle potential causes for changes in I. fuliginator abundance over time, we recorded quantitatively the plant communities in all sites in 2004 and 2017 and changes in other habitat characteristics.

We found that the overall abundance of I. fuliginator individuals decreased by 90% over 20 years: at one site the population went extinct, at five sites the populations were critically decreasing, at four sites the populations were decreasing and at only three sites population size remained stable.

Linear models revealed that the factor ‘change in plant species composition’ is the main driver for the decrease in beetle abundance. Alternative models indicated that – in addition to vegetation changes – area of suitable habitat and low heat load affected the probability of decreasing population size.

Our study shows that gradual habitat deterioration measured as reduction in grass cover and change in plant species composition negatively affect the abundance of the highly specialised beetle I. fuliginator.