bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethyl Glucuronide as a Long-term Alcohol Biomarker in Fingernail and Hair. Matrix Comparison and Evaluation of Gender Bias
Authors: Paul R , Tsanaclis L , Murray C , Boroujerdi R , Facer L , Corbin A
Published: February 2019

Aims

This work aimed to assess the performance of hair and fingernail ethyl glucuronide (EtG) measurement for use as a biomarker of alcohol consumption in persons with known drinking history across a range of drinking behaviours.

Methods

EtG concentrations were assessed from the hair and fingernails of 50 study participants. Alcohol consumption of the previous 90 days was assessed by participant interview using the alcohol timeline follow-back method. EtG concentration was determined using LC–MS-MS using a method which was validated and accredited to ISO/IEC 17025 standards.

Results

There was significant correlation between alcohol consumption and EtG concentrations found in hair and fingernail samples across the study group (n = 50). From participants testing positive for EtG (male n = 14, female n = 13) no significant difference was found between male and female EtG levels in either hair or fingernails. Across all participants there was no significant difference in hair or fingernail EtG concentration between male (n = 23) and females (n = 27).

Conclusions

Our results support the use of EtG to indicate alcohol consumption over the previous 90 days, or ~3 months as is the normal practice in hair analysis. The results confirm that fingernails can be a useful alternative matrix where hair samples are not available.
Environmental constraints on size-dependent signaling affects mating and rival interactions
Authors: Smit Judith A H , Loning Hugo , Ryan Michael J , Halfwerk Wouter
Published: February 2019

Advertisement signals can convey information about a sender’s characteristics, such as body size. The reliability of signals, however, can be reduced when signal production is partially dependent on the environment. Here, we assess the effect of display-site properties on the production, attractiveness and honesty of sexual signals. We recorded male túngara frogs (Physalaemus pustulosus) while manipulating water levels in order to constrain calling. We found that water level affected male call properties in a size-dependent manner, with call amplitude being less affected in smaller males when forced to call in shallow water. Next, we tested how size-dependent and display-site-dependent signaling affected female choice and rival competition. Both males and females showed the strongest response to the call of a large male when he was calling at the deepest water levels. However, females showed no preference for large over small males when both were recorded in shallow water levels, or, depending on the call rate and timing of calls, even preferred small males. Likewise, males responded equally to large and small rivals recorded calling during shallow water level trials. Our experiments show that display-site properties can influence signal production and attractiveness in a size-dependent manner. These results can have important consequences for the evolution of signaling, as small males may be able to use their size to their advantage when selecting appropriate display sites and thereby outcompete large males.
IGLOSS: iterative gapless local similarity search
Authors: Rabar Braslav , Zagorščak Maja , Ristov Strahil , Rosenzweig Martin , Goldstein Pavle
Published: February 2019

Searching for local sequence patterns is one of the basic tasks in bioinformatics. Sequence patterns might have structural, functional or some other relevance, and numerous methods have been developed to detect and analyze them. These methods often depend on the wealth of information already collected. The explosion in the number of newly available sequences calls for novel methods to explore local sequence similarity. We have developed a new method for iterative motif scanning that will look for ungapped sequence patterns similar to a submitted query. Using careful parameter estimation and an adaptation of a fast string-matching algorithm, the method performs significantly better in this context than the existing software.

Availability and implementation

The IGLOSS web server is available at http://compbioserv.math.hr/igloss/.

Supplementary information

Supplementary data are available at Bioinformatics online.
G4Hunter web application: a web server for G-quadruplex prediction
Authors: Brázda Václav , Kolomazník Jan , Lýsek Jiří , Bartas Martin , Fojta Miroslav , Šťastný Jiří , Mergny Jean-Louis
Published: February 2019

Motivation

Expanding research highlights the importance of guanine quadruplex structures. Therefore, easy-accessible tools for quadruplex analyses in DNA and RNA molecules are important for the scientific community.

Results

We developed a web version of the G4Hunter application. This new web-based server is a platform-independent and user-friendly application for quadruplex analyses. It allows retrieval of gene/nucleotide sequence entries from NCBI databases and provides complete characterization of localization and quadruplex propensity of quadruplex-forming sequences. The G4Hunter web application includes an interactive graphical data representation with many useful options including visualization, sorting, data storage and export.

Availability and implementation

G4Hunter web application can be accessed at: http://bioinformatics.ibp.cz.

Supplementary information

Supplementary data are available at Bioinformatics online.
MicroRNAs in endometriosis: biological function and emerging biomarker candidates†
Authors: Bjorkman Sarah , Taylor Hugh S
Published: February 2019

MicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.
Genetic transformation of Coniochaeta sp. 2T2.1, key fungal member of a lignocellulose-degrading microbial consortium
Authors: Nichols Nancy N , Hector Ronald E , Frazer Sarah E
Published: February 2019

Coniochaeta sp. strain 2T2.1 is a key member of a microbial consortium that degrades lignocellulosic biomass. Due to its ecological niche and ability to also grow in pure culture on wheat straw, protocols for transformation and antibiotic selection of the strain were established. Hygromycin was found to be a reliable selectable transformation marker, and the mammalian codon-optimized green fluorescent protein was expressed and used to visualize fluorescence in transformed cells of strain 2T2.1.
Biventricular repair after the hybrid Norwood procedure
Authors: Sojak Vladimir , Bokenkamp Regina , Kuipers Irene , Schneider Adriaan , Hazekamp Mark
Published: February 2019

OBJECTIVES

We analysed the outcomes of patients undergoing biventricular repair (BVR) after an initial hybrid Norwood approach as a salvage procedure in extremely sick infants; or as the initial palliation in patients with uncertain feasibility of single-stage BVR due to severe left ventricular outflow tract obstruction; or as part of a left ventricle (LV) recruitment strategy in patients with borderline LVs.

METHODS

Between September 2010 and July 2018, 26 patients underwent BVR after initial hybrid palliation at a median age of 13 days. The rationale for the hybrid approach was to promote the growth of the LV in 10 patients and that of the left ventricular outflow tract and/or aortic valve in 12 patients and to be a salvage procedure in 4 patients. Significant growth of the LV was noted during the interstage period, which had a median length of 65 days (P = 0.008). Fourteen patients underwent aortic arch repair, ventricular septal defect closure and relief of subaortic stenosis; 5 patients underwent the Yasui procedure; 4 patients had the Ross–Konno procedure; 2 patients had an arterial switch operation; and 1 patient had truncus arteriosus repair.

RESULTS

Twenty-two patients (84.6%) are alive at a median follow-up period of 1.8 (range 0.04–6.2) years. There were 2 early and 2 late deaths. Nineteen catheter-based reinterventions and 15 reoperations were performed after BVR.

CONCLUSIONS

The hybrid Norwood procedure permits stabilization of critical infants. It allows for growth of left ventricular structures in some patients with borderline left hearts and in those with severe left ventricular outflow tract obstruction. More patients may eventually have BVR than was thought during the newborn period.
Competition experiments betweenBrettanomyces bruxellensisstrains reveal specific adaptation to sulfur dioxide and complex interactions at intraspecies level
Authors: Avramova Marta , Grbin Paul , Borneman Anthony , Albertin Warren , Masneuf-Pomarède Isabelle , Varela Cristian
Published: February 2019

Recent studies have suggested a strong niche adaptation for Brettanomyces bruxellensis strains according to human-related fermentation environments, including beer, wine and bioethanol. This is further supported by a correlation between B. bruxellensis genetic grouping and tolerance to SO2, the main antimicrobial used in wine. The allotriploid AWRI1499-like cluster, in particular, shows high SO2 tolerance suggesting that the genetic configuration observed for these strains may confer a selective advantage in winemaking conditions. To test this hypothesis, we evaluated the relative selective advantage of representatives of the three main B. bruxellensis genetic groups in presence of SO2. As a proof-of-concept and using recently developed transformation cassettes, we compared strains under different SO2 concentrations using pairwise competitive fitness experiments. Our results showed that AWRI1499 is specifically adapted to environments with high SO2 concentrations compared to other B. bruxellensis wine strains, indicating a potential correlation between allotriploidisation origin and environmental adaptation in this species. Additionally, our findings suggest different types of competition between strains, such as coexistence and exclusion, revealing new insights on B. bruxellensis interactions at intraspecies level.
Hospitalization-Associated Change in Gait Speed and Risk of Functional Limitations for Older Adults
Authors: Duan-Porter Wei , Vo Tien N , Ullman Kristen , Langsetmo Lisa , Strotmeyer Elsa S , Taylor Brent C , Santanasto Adam J , Cawthon Peggy M , Newman Anne B , Simonsick Eleanor M , Waters Teresa M , Ensrud Kristine E
Published: February 2019

Background

Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs).

Methods

We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70–79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. Gait speed, and new self-reported limitations in mobility and ADLs were assessed annually. Selected participants (n = 2,963) had no limitations at the beginning of each 1-year interval. Hospitalizations were self-reported every 6 months and verified with medical record data. Generalized estimating equations were used to examine hospitalization-associated change in gait speed and odds of new limitations over each 1-year interval. Fully adjusted models included demographics, hospitalization within the past year, health conditions, symptoms, body mass index, and health-related behaviors.

Results

In fully adjusted models, any hospitalization was associated with decrease in gait speed (−0.04 m/s; 95% confidence interval [CI]: −0.05 to −0.03) and higher odds of new limitations in mobility or ADLs (odds ratio = 1.97, 95% CI: 1.70–2.28), and separately with increased odds of new mobility limitation (odds ratio = 2.22, 95% CI: 1.90–2.60) and new ADL limitations (odds ratio = 1.84, 95% CI: 1.53–2.21). Multiple hospitalizations within a year were associated with gait speed decline (−0.06 m/s; 95% CI: −0.08 to −0.04) and greater odds of new limitations in mobility or ADLs (odds ratio = 2.96, 95% CI: 2.23–3.95).

Conclusions

Functionally independent older adults experienced hospitalization-associated declines in gait speed and new limitations in mobility and ADLs.
Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease
Authors: Breton Jessica , Kastl Arthur , Hoffmann Natalie , Rogers Rachel , Grossman Andrew B , Mamula Petar , Kelsen Judith R , Baldassano Robert N , Albenberg Lindsey
Published: February 2019

Background

Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn’s colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center.

Methods

Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis.

Results

Sixty-three patients with refractory UC, Crohn’s colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2–16.5] years; median disease duration [IQR], 1.2 [0.41–4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21–58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti–tumor necrosis factor alpha (anti-TNFα) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40–65) to 10 (0–40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNFα therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08–0.76) and PUCAI ≥65 at baseline (OR, 0.2; 95% CI, 0.05–0.74).

Conclusions

Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic.
Preexposure Prophylaxis for Mitigating Risk of HIV Transmission During HIV Cure–Related Clinical Trials With a Treatment Interruption
Authors: Lelièvre Jean-Daniel
Published: February 2019

Analytical treatment interruption performed during human immunodeficiency virus (HIV) cure–related clinical trials exposes sex partners of participants in these trials to a risk of HIV transmission. Preexposure prophylaxis (PrEP), which emerged in recent years as a key strategy for preventing HIV transmission, is often considered a useful tool to prevent this risk. This article supports offering PrEP to the stable sex partners of participants in these trials but also notes limitations that must be addressed. It concludes that PrEP cannot on its own eliminate the risk of secondary transmission in this context.
Asylum-seeking Parents’ Reports of Health Deterioration in Their Children since Fleeing Their Home Country
Authors: De Montgomery Christopher Jamil , Stathopoulou Theoni , Eikemo Terje Andreas
Published: February 2019

More than 50,000 asylum seekers scattered across Greece were waiting to have their cases processed in February 2016. Using unique survey data collected in six Greek refugee camps at the time, this article explores the health of asylum-seeking children as assessed by their parents. More than half of the parents reported that children’s health had deteriorated considerably or greatly since commencing their flight and the longer the time spent in Greece, the larger the share. The same tendency was found in a logistic regression model adjusting for educational level, sex and origin country. Feeling safe at the current location and access to basic amenities were alleviating factors. The results call for increased attention to the needs of asylum-seeking children in the Greek refugee camps and urgent action to alleviate potentially long-term impacts of the process of seeking asylum on these children.
Predicting multiple planet stability and habitable zone companions in the TESS era
Authors: Agnew Matthew T , Maddison Sarah T , Horner Jonathan , Kane Stephen R
Published: February 2019

We present an approach that is able to both rapidly assess the dynamical stability of multiple planet systems, and determine whether an exoplanet system would be capable of hosting a dynamically stable Earth-mass companion in its habitable zone (HZ). We conduct a suite of numerical simulations using a swarm of massless test particles (TPs) in the vicinity of the orbit of a massive planet, in order to develop a predictive tool which can be used to achieve these desired outcomes. In this work, we outline both the numerical methods we used to develop the tool, and demonstrate its use. We find that the TPs survive in systems either because they are unperturbed due to being so far removed from the massive planet, or due to being trapped in stable mean-motion resonant orbits with the massive planet. The resulting unexcited TP swarm produces a unique signature in (a, e) space that represents the stable regions within the system. We are able to scale and translate this stability signature, and combine several together in order to conservatively assess the dynamical stability of newly discovered multiple planet systems. We also assess the stability of a system’s HZ and determine whether an Earth-mass companion could remain on a stable orbit, without the need for exhaustive numerical simulations.
Delivering SaCas9 mRNA by lentivirus-like bionanoparticles for transient expression and efficient genome editing
Authors: Lu Baisong , Javidi-Parsijani Parisa , Makani Vishruti , Mehraein-Ghomi Farideh , Sarhan Walaa Mohamed , Sun Dongjun , Yoo Kyung Whan , Atala Zachary P , Lyu Pin , Atala Anthony
Published: February 2019

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system discovered using bacteria has been repurposed for genome editing in human cells. Transient expression of the editor proteins (e.g. Cas9 protein) is desirable to reduce the risk of mutagenesis from off-target activity. Using the specific interaction between bacteriophage RNA-binding proteins and their RNA aptamers, we developed a system able to package up to 100 copies of Staphylococcus aureus Cas9 (SaCas9) mRNA in each lentivirus-like bionanoparticle (LVLP). The SaCas9 LVLPs mediated transient SaCas9 expression and achieved highly efficient genome editing in the presence of guide RNA. Lower off-target rates occurred in cells transduced with LVLPs containing SaCas9 mRNA, compared with cells transduced with adeno-associated virus or lentivirus expressing SaCas9. Our LVLP system may be useful for efficiently delivering Cas9 mRNA to cell lines and primary cells for in vitro and in vivo gene editing applications.
Microbial Correlates ofFusariumLoad and Deoxynivalenol Content in Individual Wheat Kernels
Authors: Bakker Matthew G. , McCormick Susan P.
Published: February 2019

Characteristics or constituents of plant-associated microbiomes may assist in constraining disease development. To investigate this possibility for the wheat–Fusarium head blight pathosystem, we assessed seed weight, pathogen load, deoxynivalenol content, and microbiome profiles for individual wheat kernels collected over 2 years from a disease-conducive environment. We found that the microbiomes of individual, hulled wheat kernels consist of dozens to greater than a hundred bacterial taxa and up to several dozen fungal taxa, and that year-to-year variation in microbiome structure was large. Measures of microbial community diversity were negatively correlated with measures of disease severity, and had significant power to explain variation in pathogen load among seeds. Several operational taxonomic units belonging to the genus Sphingomonas demonstrated particularly strong negative relationships with pathogen load. This study illuminates the composition of microbiomes associated with wheat kernels under disease-conducive field conditions, and suggests relationships between microbiome characteristics and Fusarium head blight that warrant further study.
Effectiveness of Cryopreserved Amniotic Membrane Transplantation in Corneal Ulceration: A Meta-Analysis
Authors: Liu Jinghua , Li Linghan , Li Xuan
Published: February 2019

Purpose:

To evaluate the effectiveness of cryopreserved amniotic membrane transplantation (AMT) in corneal ulceration.

Methods:

The following electronic databases were searched: PubMed, EMBASE, and Cochrane Library. We evaluated the corneal epithelium healing rate (CEHR) and vision improvement rate (VIR) after AMT in the treatment of corneal ulceration. We analyzed the differences in the CEHR and VIR between the 2 groups of infective and noninfective corneal ulcerations. Subgroup analysis for the CEHR and VIR was performed based on the surgical methods. There were 3 subgroups: single-layered inlay, multilayered inlay, and sandwich (SAN). The differences were tested by referring to the Cochrane Handbook. Pooled estimates were determined with STATA software, version 15.

Results:

Eighteen eligible studies reporting the outcomes in 390 eyes of 385 patients were included. The results of the meta-analysis showed that the pooled CEHR was 97% (I2 = 37.9%, 95% confidence interval: 0.94–0.99, P = 0.089). The pooled VIR was 53% (I2 = 68.1%, 95% confidence interval: 0.42–0.65, P < 0.001). There were no significant differences in either the CEHR or the VIR between the 2 groups of infective and noninfective corneal ulcerations. Among the 3 subgroups of single-layered inlay, multilayered inlay, and SAN, the differences in both CEHR and VIR were statistically significant.

Conclusions:

Consistent with many published reports, this meta-analysis also concluded that AMT was effective in the treatment of corneal ulceration. The curative effect of AMT was not different between the infective and noninfective corneal ulcerations. The differences in both CEHR and VIR were statistically significant among the subgroups.
Effect of Anti–Vascular Endothelial Growth Factor Therapy on Corneal Nerves
Authors: Goldhardt Raquel , Batawi Hatim Ismail M. , Rosenblatt Mark , Lollett Ivonne V. , Park Jasmine J. , Galor Anat
Published: February 2019

Purpose:

Vascular endothelial growth factor (VEGF) is a trophic factor for corneal nerves (CNs). Despite its widespread use to treat a variety of retinal diseases, the effect of repetitive intravitreal (IV) anti-VEGF injections on CN is not known.

Methods:

Retrospective case–control study. CN parameters were compared between eyes in 39 individuals who received anti-VEGF injections in one eye only. Next, we compared CN parameters between 50 eyes of 50 individuals with a history of IV anti-VEGF injections and 80 eyes of 80 individuals without a history of injection. In vivo confocal microscopic examination was conducted using the ConfoScan 4. Images were analyzed by the Corneal Nerve Analysis tool. Paired and independent t test methodologies were used to compare nerve parameters, and multivariable linear regression analysis was performed to control for potential confounders.

Results:

In 39 patients (own controls), eyes with a history of IV injection had lower CN length density, total length, nerve fibers, bifurcations, and branches (P < 0.005) compared to the fellow eyes without injection. Similar findings were seen in the eyes of 50 individuals with a history of injection compared to 80 individuals without injection. A history of IV injections and ethnicity remained significantly associated with the CN length density and explained 32% of the variability (R = 0.56).

Conclusions:

We found decreased CN parameters in eyes with a history of anti-VEGF injections compared to eyes without such a history.
Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials
Authors: Giannaccare Giuseppe , Pellegrini Marco , Sebastiani Stefano , Bernabei Federico , Roda Matilde , Taroni Leonardo , Versura Piera , Campos Emilio C.
Published: February 2019

Purpose:

To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease.

Methods:

We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I2 tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity.

Results:

Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554–1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043–0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India.

Conclusions:

This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.
Why Suicide Risk Assessment Still Matters
Authors: WORTZEL HAL S. , NAZEM SARRA , BAHRAINI NAZANIN H. , MATARAZZO BRIDGET B.
Published: February 2019

Both public awareness of suicide and professional efforts directed at suicide prevention have increased considerably in recent years. Unfortunately, rates of death by suicide have remained relatively stable over the past decade despite these enhanced efforts. Some have argued that “suicide risk assessment doesn’t work” and have called into question the utility of devoting clinical time and energy to risk assessment. In this column, the authors first present an overview of the argument against suicide risk assessment and the data supporting that argument, followed by an alternate argument as to why suicide risk assessment still matters. When properly performed in concert with patient-centered mental health care, suicide risk assessment and management may add to the therapeutic and recovery-oriented benefits of care, independent of the ability to predict death by suicide.
Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling
Authors: KAHN DAVID A.
Published: February 2019

Objective:

The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum.

Methods:

A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data.

Results:

Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity.

Conclusions:

The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.
Psychosis Risk Syndrome: What Now?
Authors: SENTISSI OTHMAN , ANDREOU MARIA A. , MOEGLIN CLOTILDE , CURTIS LOGOS , SANTOS BROSCH MICAELA
Published: February 2019

Background:

Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify “high-risk” patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce “psychosis risk syndrome” as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, “attenuated psychosis syndrome” was included in section III of the newly published manual as a condition for further studies.

Objective:

The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms (“prodrome” and “psychosis-risk syndrome”) and concerning available therapeutic options, both psychosocial and pharmacological.

Conclusions:

“Attenuated psychosis syndrome” is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.
Experience-related alterations in white matter structure and gene expression in adult rats
Authors: Vallès Astrid , Sampaio-Baptista Cassandra , Khrapitchev Alexandre A. , Akkermans Guus , Winkler Anderson , Foxley Sean , Sibson Nicola R. , Roberts Mark , Miller Karla , Diamond Mathew E. , Martens Gerard J.M. , Weerd Peter De , Johansen-Berg Heidi
Published: February 2019

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI). However, it remains unclear which mechanisms drive or underlie WM plasticity in adulthood. Here, we combined DTI and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. Somatosensory experience resulted in differences in WM and grey matter structure. C-FOS mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the structural WM measures, suggesting that WM plasticity is activity-dependent. Analysis of myelin-related genes revealed higher myelin basic protein expression in WM, while genome-wide RNA sequencing analysis identified 134 differentially-expressed genes regulating proteins involved in functions related to cell proliferation and differentiation, neuronal activity modulation and regulation of myelination. In conclusion, the macroscale measures of WM differences identified in response to somatosensory experience are supported by molecular evidence, which strongly suggest myelination as, at least, one of the underlying mechanisms.
Transfer learning of deep neural network representations for fMRI decoding
Authors: Svanera Michele , Savardi Mattia , Benini Sergio , Signoroni Alberto , Raz Gal , Hendler Talma , Muckli Lars , Goebel Rainer , Valente Giancarlo
Published: February 2019

Background

Deep neural networks have revolutionised machine learning, with unparalleled performance in object classification. However, in brain imaging (e.g. fMRI), the direct application of Convolutional Neural Networks (CNN) to decoding subject states or perception from imaging data seems impractical given the scarcity of available data.

New method

In this work we propose a robust method to transfer information from deep learning (DL) features to brain fMRI data with the goal of decoding. By adopting Reduced Rank Regression with Ridge Regularisation we establish a multivariate link between imaging data and the fully connected layer (fc7) of a CNN. We exploit the reconstructed fc7 features by performing an object image classification task on two datasets: one of the largest fMRI databases, taken from different scanners from more than two hundred subjects watching different movie clips, and another with fMRI data taken while watching static images,

Results

The fc7 features could be significantly reconstructed from the imaging data, and led to significant decoding performance.

Comparison with existing methods

The decoding based on reconstructed fc7 outperformed the decoding based on imaging data alone.

Conclusion

In this work we show how to improve fMRI-based decoding benefiting from the mapping between functional data and CNN features. The potential advantage of the proposed method is twofold: the extraction of stimuli representations by means of an automatic procedure (unsupervised) and the embedding of high-dimensional neuroimaging data onto a space designed for visual object discrimination, leading to a more manageable space from dimensionality point of view.
HABIT – a webserver for interactive T cell neoepitope discovery
Authors: Martins Joana , Magalhães Carlos , Vieira Vítor , Rocha Miguel , Osório Nuno S.
Published: February 2019

Neoepitopes generated by amino acid variants specifically found in pathogens or cancer cells are gaining momentum in immunotherapy development. HABIT (HLA Binding InTelligence) is a web platform designed to generate and analyse machine learning-based T cell epitope predictions for improved neoepitope discovery.

Availability and Implementation

HABIT is available at http://habit.evobiomed.com. Peptide-HLA binding predictions by NetMHCpan 4.0 and NetMHCIIpan 3.1 were implemented in a web application for interactive data exploration using shiny package powered by RStudio.

Contact

nosorio@med.uminho.pt

Supplementary information

Supplementary data and video tutorials are available online.
New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania
Authors:   Malaria Genomic Epidemiology Network
Published: February 2019

We conducted a genome-wide association study of host resistance to severePlasmodium falciparummalaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association inATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.
Global phylogenomics of multidrug resistant Salmonella enterica serotype Kentucky ST198
Authors: Hawkey Jane , Le Hello Simon , Doublet Benoît , Granier Sophie , Hendriksen Rene , Fricke W. Florian , Ceyssens Pieter-Jan , Gomart Camille , Billman-Jacobe Helen , Holt Kathryn E , Weill François-Xavier
Published: February 2019

Salmonella enterica serotype Kentucky (S. Kentucky) can be a common causative agent of salmonellosis, usually associated with consumption of contaminated poultry. Antimicrobial resistance (AMR) to multiple drugs, including ciprofloxacin, is an emerging problem within this serotype. We used whole-genome sequencing (WGS) to investigate the phylogenetic structure and AMR content of 121 S. Kentucky ST198 isolates from five continents. Population structure was inferred using phylogenomic analysis and whole genomes were compared to investigate changes in gene content, with a focus on acquired AMR genes. Our analysis showed that multidrug resistant (MDR) S. Kentucky isolates belonged to a single lineage, which we estimate emerged circa 1989 following the acquisition of the AMR-associated Salmonella genomic island 1 (variant SGI1-K) conferring resistance ampicillin, streptomycin, gentamicin, sulfamethoxazole, and tetracycline. Phylogeographic analysis indicates this clone emerged in Egypt before disseminating into Northern, Southern and Western Africa, then to the Middle East, Asia and the European Union. The MDR clone has since accumulated various substitution mutations in the quinolone resistance determining regions (QRDR) of DNA gyrase (gyrA) and DNA topoisomerase (parC), such that most strains carry three QRDR mutations which together confer resistance to ciprofloxacin. The majority of AMR genes in the S. Kentucky genomes were carried either on plasmids or SGI structures. Remarkably, each genome carried a different SGI1-K derivative structure; this variation could be attributed to IS26-mediated insertions and deletions, which appear to have hampered previous attempts to trace the clone's evolution using sub-WGS resolution approaches. Several different AMR plasmids were also identified, encoding resistance to chloramphenicol, third-generation cephalosporins, carbapenems, and/or azithromycin. These results indicate that most MDR S. Kentucky circulating globally result from the clonal expansion of a single lineage that acquired chromosomal AMR genes 30 years ago, and has continued to diversify and accumulate additional resistances to last-line oral antimicrobials.
Bacterial Glycogen as a Durable Energy Reserve Contributing to Persistence: An Updated Bibliography and Mathematical Model
Authors: Wang Liang , Liu Qinghua , Tan Xinle , Yang Ting , Tang Daoquan , Wang Wei , Wise Michael J.
Published: February 2019

Glycogen is conventionally viewed as a transient energy reserve that can be rapidly synthesized for glucose accumulation or mobilized for ATP production and blood glucose homeostasis in higher organisms. However, this understanding is not completely applicable to prokaryotes due to glycogen structural heterogeneity. A number of studies have noted that glycogen with short average chain lengthgcin bacteria has the potential to degrade slowly, which might prolong bacterial survival in the environment and thus enhance potential for transmission to new hosts. This phenomenon has been examined over the past few years and called the durable energy storage mechanism hypothesis (DESM). In this updated bibliography, we summarize recent progress and provide a mathematical model of glycogen as a durable energy reserve.
Learning of Spatial Properties of a Large-scale Virtual City with an Interactive Map
Authors: König Sabine U. , Kakerbeck Viviane , Nolte Debora , Duesberg Laura , Kuske Nicolas , König Peter
Published: February 2019

On the basis of embodied/-enacted theories of the mind, investigations of spatial cognition related to real world environments have become current research interests. How this perspective relates to acquiring spatial knowledge not by active exploration, but through map learning, however, remains unresolved. Therefore, we designed a large virtual city comprised of over 200 houses, suitable for active exploration or spatial learning based on a map. Here, we report our results after single and repeated 30-minute training sessions using an interactive city map. We tested subjects’ knowledge of the orientation of houses towards cardinal north and of two houses relative to each other and the locations of two houses towards each other in a pointing task. Our results revealed that a single training session was sufficient to repeatedly view the majority of houses covering a large area of the city. However, repeated training sessions were necessary to improve the performance level and reveal significant differences between tasks. In contrast to a previous study in a real world city, performance in the two orientation tasks was better than in the pointing task. The lack of distance and the lack of angular difference effects onto task performance suggest the use of a global reference frame. Performance was positively correlated with a self-report on spatial abilities (FRS) in the absolute orientation and pointing task but not the relative orientation task. Overall, our results suggest that training with an interactive city map enhances abstract knowledge, not directly available from an embodied perspective.
SLC19A1 is an importer of the immunotransmitter cGAMP
Authors: Cordova Anthony F. , Ritchie Christopher , Hess Gaelen T. , Bassik Michael C. , Li Lingyin
Published: February 2019

2’3’-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral Stimulator of Interferon Genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.
Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner
Authors: Duarte-Guterman Paula , Hamson Dwayne K. , Wainwright Steven R. , Chow Carmen , Chaiton Jessica , Lieblich Stephanie , Watson Neil V. , Galea Liisa A.M.
Published: February 2019

Androgens (testosterone and dihydrotestosterone) increase adult hippocampal neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone, a potent androgen, on neurogenesis in adult and middle-aged males and females. Rats were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU). The following day rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and new neuron survival (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased new neuron survival in young males but surprisingly not in middle-aged male rats. In females, DHT did not significantly affect adult neurogenesis in young or middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.
A Novel Neoantigen Discovery Approach based on Chromatin High Order Conformation: Mapping the Neoantigen to 3D Genome
Authors: Shang Xueying , Zhang Mingxuan , Meng Luming , Su Xianbin , Li Qingjiao , Lin Mengna , Zou Xin , Luo Qing , Zhai Yangyang , He Kunyan , Wang Lan , Da Lintai , Cai Tom Weidong , Han Ze-guang , Shi Yi
Published: February 2019

The high-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate immune response of the T cells. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Here we retrospect the DNA origins of the immune-positive and non-negative neoantigens in the context of 3D genome and discovered that 1) DNA loci of the immuno-positive neoantigens tend to cluster genome-wise. 2) DNA loci of the immuno-positive neoantigens tend to belong to active chromosomal compartment (compartment A) in some chromosomes. 3). DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We believe that the 3D genome information will help more precise neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.