bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distance and Colour-based Scores for Blood Test Risk Stratification
Authors: Zenil Hector , Hernández-Quiroz Francisco , Hérnandez-Orozco Santiago , Saeb-Parsy Kourosh , Hernández De la Cerda Héctor , Riedel Jürgen 
Published: February 2020

AbstractWe introduce a numerical and a colour-based risk stratification score to quantify abnormal blood analyte values. The score indicates how removed values of an individual are from considered healthy ranges from the literature or derived from empirical data such as medical surveys. The scores’ behaviour can be adjusted to incorporate medical knowledge by assigning multipliers or ‘weights’ to individual components and is rooted on a numerical and a colour-based scheme. We test the score against real and synthetic data from medically relevant cases, extremes cases, and empirical blood cell count data from the CDC NHANES survey spanning 13 years, from 2003 to 2016. We find that both the numerical and colour-based scores are informative in distinguishing healthy individuals from those with diseases manifested with abnormal blood results.
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

AbstractObjectiveExacerbated 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.MethodsUsing 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.ResultsRelative 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.ConclusiontcVNS 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 # NCT02992899HighlightsWe 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

AbstractSelective 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.
Mechanical scarification, seed origin, and substrate influence on germination ofSamanea tubulosa
Authors: Regnier Leonardo L. P. 
Published: February 2020

ABSTRACTSamanea 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

AbstractThe 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

AbstractBoth 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 statementAchilles 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

ABSTRACTS-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

ABSTRACTVentricular 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.SUMMARYThe 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

ABSTRACTFacilitation 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

SUMMARYChromosome 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

AbstractWhile 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.
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

PurposeThis 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/approachThis 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.FindingsThe 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/valueThis article contributed ideas for the concept and aspect of health messages to be incorporated into health education materials for drowning prevention and water safety.