bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences from newly created trainee associations in Spain And Macedonia
Authors: Núñez Morales N.I. , Suarez de Venegas N. Gomez-Coronado , Sanchez-Lafuente C. Gomez , Alemany T. Gomez , Montero G. , Almerge J. Cambra , Higueras P. Hervias , Sanchez V. Pereira , de Munain E. Lopez , Roman Uria A. San
Published: March 2020

Until July 2016, Spain was not member of European Forum of Psychiatric Trainees. Why? Because Spain did never have Association of Psychiatric trainees. In July 2015, 2 Spanish trainees were invited to attend EFPT meeting in Porto. There, they connect with other European trainees and with the help of MENTA group they starting the foundation of Spanish Psychiatric Trainees Society, now known as SERP. In just 1 year, SERP has increased in number of members and have successfully developed numerous initiatives such as the establishment of our founding documents, the constitution of a democratic board through an Elective General Assembly, the design and update of a website and profiles in the social networks and the organization of the 1st Meeting for National Psychiatric Trainees, which was held in Vitoria-Gasteiz on March 2015 and had as topic Research on psychiatric training period. Last July, Spain was accepted for first time in history as full member of EFPT and we are actively participating in several working groups, even chairing the Child and Adolescent Psychiatry one. This year, Spain is also participating in international exchanges, offering two destination for European trainees. We must acknowledge that during the foundation process, the support of the Spanish National Psychiatric Associations (SEP and SEPB) and EFPT (specially its ENTA group since the first meeting of some of our now board members in the Annual Forum in Porto in 2015), has been crucial.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
TYOT: Tripadvisor for psychiatry trainees?
Authors: De Picker L.
Published: March 2020

Background

Although guidelines to ensure the quality of postgraduate psychiatric training in Europe are provided both by the statements of the European Federation of Psychiatric Trainees (EFPT) and the UEMS Psychiatry Section's European Training Requirements, actual training conditions in different European countries have been documented to vary widely. Furthermore, most trainees are unaware of the existence of such guidelines.

Objective

The test your own training (TYOT) project set out to create an easy-to-use online tool that allows trainees to assess how their own training compares in relation to the European standards, thereby empowering trainees all over Europe.

Methods

An EFPT Focus Group consisting of psychiatric trainees or early career psychiatrists from eleven European countries created a core survey of key aspects of psychiatry training, such as the duration of the training program, the availability of clinical and educational supervision, access to international professional literature, the use of a national logbook, based on the UEMS European Training Requirements and the EFPT statements. Additional subsets of questions were designed for specific domains such as theoretical training in psychiatry, psychotherapy training and the role of supervisors and training institutions. Next, the questions were transferred to a suitable online hosting platform, which allows to automatically provide feedback in an algorithmic fashion about how the trainee’s experience compares to the European standards.

Results

The TYOT platform will be launched in January 2017 and the first results will be presented at the European Congress of Psychiatry 2017. For more information about the TYOT tool please visit http://efpt.eu/training/tyot/.

Disclosure of interest

The author has not supplied his declaration of competing interest.
Borderline personality disorders in adolescents: Treatment issues and epistemic challenges
Authors: Sibeoni J.
Published: March 2020

Some clinicians are still hesitant to use the diagnosis of borderline personality disorder (BPD) in adolescence whereas numerous studies have shown evidence to support its validity within this population. Yet, many epistemic issues remain. Indeed, the concept of BPD in adolescence has inherited the issues from the adult one, to which is added the complexity of this developmental period. Borderline disorder is a confusing and polymorphic clinical object with two different origins: one psychiatric with a nosographic approach and the other psychanalytical with a structural one. On the one hand, BPD in adolescence is considered as a psychiatric diagnosis based on the same criteria used in adult psychiatry, with many studies describing core symptoms at this period such as repetitive non-suicidal self-injury and suicidal behavior. On the other hand, BPD is also considered as one of many options, a behavioral one, to express an internal “borderline” structure. In line with this statement, the role of social and family factors is to be taken into account. Moreover, within a developmental approach, some authors considered difficult to diagnose a personality disorder before 18 years old, while others considered adolescence as a “borderline” period in itself. In this oral communication, we will try to approach these epistemic challenges raised by this phenomenon in the field of adolescent psychiatry and, in order to do so, we will use data from several qualitative studies.

Disclosure of interest

The author has not supplied his declaration of competing interest.
Neurodevelopment disorders in adolescence and transition into adulthood
Authors: Moscoso A.
Published: March 2020

The transitional period from adolescence into adulthood is an important developmental stage, known to be a risk factor for mental health problems. Neuropsychiatric disorders are the main cause of disability for young people aged 10–24 years and they seem to precede mental health disorders in adults. Since persistence of an adolescent episode is a strong predictor of outcome, giving proper care during critical stages might prevent later life psychiatric morbidity arising from adolescent-onset disorders. Mental health services for adolescents have evolved from non-specific secondary treatment to more extensive treatment goals, where prevention and early diagnosis take place; at the same time, specific therapeutic tools for adolescents are increasing and put into practice. In Europe, both child and adolescent psychiatrists (CAP) and adult psychiatrists treat adolescents, and for a few countries, the specialty of adolescent psychiatry exists. In this symposium, we propose to address new strategies to treat adolescents with defying pathologies that often pose problems; we will do it through the scope of CAP and adult psychiatry.

Disclosure of interest

The author has not supplied his declaration of competing interest.
What makes UK, Switzerland and Sweden attractive to trainees?
Authors: Mogren T. , Holmes K. , Biskup E. , Pinto da Costa M.
Published: March 2020

Introduction

Migration of medical professionals has a global impact on healthcare and services, including on mental health. Exploring the reasons for migration and why psychiatric trainees consider to migrate to certain countries is therefore crucial to understand the decision-making process related to migration of psychiatric trainees as well as of future specialists.

Objectives

The aims of this Brain Drain Survey, was to research which countries most trainees in Europe migrate to (host countries) and for which reasons trainees choose to migrate to these countries (“pull factors”).

Methods

In a multicenter, cross-sectional study, data was collected in 33 countries. As part of the survey, all participants responded to a questionnaire exploring trainees’ experiences and attitudes towards migration.

Results

Our results showed that Sweden, Switzerland and the UK were all significant net hosts. The percentage of immigrants varied between these countries. One of the main contributors as a “pull” factor was unsurprisingly, salary. It is notable that all three-host countries were within the highest wage brackets within our survey.

Conclusions

Psychiatric trainees tend to migrate to countries with higher income.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Getting started: Toolbox for a successful private practice
Authors: Nawka A.
Published: March 2020

Starting a private practice can be on one hand the most exciting step you will take in your career, on the other hand it can be at the same time the most intimidating one. First of all, take the time to really think through what you want your work schedule and surroundings to be like and then set up your office the way it will work best for you. You may not get every item on your wish list right away, but do not be afraid to try to set it up just the way you want. Build a healthy network of collaborative clinicians around your practice. Your colleagues can be a great source of referrals to your practice. And without refferals, it is difficult to maintain sufficient patient turnout. That is also why a big part of private practice is marketing. If you want to establish and develop a successful business, you must sell yourself and your practice. Beside your role as a clinician, you will also be running a business. If you seek out some private-practice coaching, you might save a lot of time. Private practice can be wonderful, it is not for everyone. Some therapists find being in a solo private practice very tiring and lonely. For some psychiatrists, the ideal is actually a group practice that has therapists, counsellors, social workers and psychologists so that supervision can be done from a multidisciplinary perspective.

Disclosure of interest

The author has not supplied his declaration of competing interest.
Effect of vaccination on severity and infectiousness of measles during an outbreak in the Netherlands, 2013–2014
Authors: van Dam A.S.G. , Woudenberg T. , de Melker H.E. , Wallinga J. , Hahné S.J.M.
Published: March 2020

An outbreak of measles in the Netherlands in 2013–2014 provided an opportunity to assess the effect of MMR vaccination on severity and infectiousness of measles.

Measles is notifiable in the Netherlands. We used information on vaccination, hospitalisation, complications, and most likely source(s) of infection from cases notified during the outbreak. When a case was indicated as a likely source for at least one other notified case, we defined it as infectious. We estimated the age-adjusted effect of vaccination on severity and infectiousness with logistic regression.

Of 2676 notified cases, 2539 (94.9%) were unvaccinated, 121 (4.5%) were once-vaccinated and 16 (0.6%) were at least twice-vaccinated; 328 (12.3%) cases were reported to have complications and 172 (6.4%) cases were hospitalised. Measles in twice-vaccinated cases led less often to complications and/or hospitalisation than measles in unvaccinated cases (0% and 14.5%, respectively, aOR 0.1 (95% CI 0–0.89), P = 0.03). Of unvaccinated, once-vaccinated and twice-vaccinated cases, respectively, 194 (7.6%), seven (5.1%) and 0 (0%) were infectious. These differences were not statistically significant (P > 0.05).

Our findings suggest a protective effect of vaccination on the occurrence of complications and/or hospitalisation as a result of measles and support the WHO recommendation of a two-dose MMR vaccination schedule.
Rehabilitation Counsellor Competency Studies: A Review of Praxis in a Human Service Profession
Authors: Biggs Herbert C. , Flett Ross A.
Published: March 2020

Competency research in the rehabilitation profession and that of rehabilitation counselling in particular, has an extensive pedigree. This article reviews the significant research in the field and details several of the instruments used in competency research to date. Issues concerning the current use of competency research and the future role of such research are discussed.
Contribution of Rehabilitation Counsellors in the Rehabilitation of Persons with Acquired Brain Injury
Authors: Crisp Ross
Published: March 2020

Recent rehabilitation counselling literature has pointed to major developments in the contribution of rehabilitation counsellors to acquired brain injury (ABI) rehabilitation. Rehabilitation counsellors have widened their skill base in case management, vocational evaluation, and in the therapeutic relationship between counsellor and client. It is evident, however, that better methods of ABI rehabilitation service delivery, including those services provided by rehabilitation counsellors, continue to be sought. Strategies needed to ensure the advancement of rehabilitation counselling practice and research in ABI rehabilitation are discussed, and involve the adoption of a systems approach, a shift away from dominant clinical psychological analyses in favour of psychosocial frameworks, and the co-participation of persons with ABI in the rehabilitation process.
Failures in Occupational Rehabilitation: A Case Study Analysis
Authors: Kenny Dianna T.
Published: March 2020

Forty-nine injured workers were selected from a study population of 3,041 injured workers using a critical case sampling technique, to explore characteristics of workplaces and worker perceptions and attributions related to return to work status following workplace injury. The only significant differences between those who returned and those who did not return to work were satisfaction with pre-injury pay and provision of training in occupational health and safety procedures. From the in-depth structured interviews of 49 injured workers, 5 workers who failed to return to work were selected for detailed case study to further explicate the factors which contributed to unsuccessful rehabilitation. Worker characteristics, the timing and meaning of the injury to individual workers, and conflicting and unstated agendas in the occupational rehabilitation process, were all identified as critical factors which impact on return to work outcomes.
Is Counselling a Health Hazard to Counsellors? Occupational Stress and Occupational Health for Counsellors
Authors: Chinnery Darien , Campbell Angela , Churches Sara , Houston Doris , King Tania , Prophet Gael
Published: March 2020

A questionnaire survey of 85 counsellors investigated potential contributors to stress in the workplace and valued coping strategies. The sample consisted of three groups: a Government group, a Private group and a Religious group, which represented three different types of work organisation. Recent research suggests that organisational factors contribute to occupational stress, and that personal coping strategies may not alleviate stress appreciably. The results of the study indicated that the most stressed group was the Government group of counsellors, that the most highly rated contributor to stress was management attitudes and that the most valued coping strategies were organisational in nature rather than personal.
Whole grain and cereal fibre intake in the Australian Health Survey: associations to CVD risk factors
Authors: Barrett Eden M , Batterham Marijka J , Beck Eleanor J
Published: March 2020

Objective:

To explore associations of whole grain and cereal fibre intake to CVD risk factors in Australian adults.

Design:

Cross-sectional analysis. Intakes of whole grain and cereal fibre were examined in association to BMI, waist circumference (WC), blood pressure (BP), serum lipid concentrations, C-reactive protein, systolic BP, fasting glucose and HbA1c.

Setting:

Australian Health Survey 2011–2013.

Participants:

A population-representative sample of 7665 participants over 18 years old.

Results:

Highest whole grain consumers (T3) had lower BMI (T0 26·8 kg/m2, T3 26·0 kg/m2, P < 0·0001) and WC (T0 92·2 cm, T3 90·0 cm, P = 0·0005) compared with non-consumers (T0), although only WC remained significant after adjusting for dietary and lifestyle factors, including cereal fibre intake (P = 0·03). Whole grain intake was marginally inversely associated with fasting glucose (P = 0·048) and HbA1c (P = 0·03) after adjusting for dietary and lifestyle factors, including cereal fibre intake. Cereal fibre intake was inversely associated with BMI (P < 0·0001) and WC (P < 0·0008) and tended to be inversely associated with total cholesterol, LDL-cholesterol and apo-B concentrations, although associations were attenuated after further adjusting for BMI and lipid-lowering medication use.

Conclusions:

The extent to which cereal fibre is responsible for the CVD-protective associations of whole grains may vary depending on the mediators involved. Longer-term intervention studies directly comparing whole grain and non-whole grain diets of similar cereal fibre contents (such as through the use of bran or added-fibre refined grain products) are needed to confirm independent effects.
Modeling the emergence of North African knapweed (Centaurea diluta), an increasingly troublesome weed in Spain
Authors: Sousa-Ortega Carlos , Royo-Esnal Aritz , DiTommaso Antonio , Izquierdo Jordi , Loureiro Iñigo , Marí Ana I. , Cordero Fernando , Vargas Manuel , Saavedra Milagros , Paramio José A. , Fernández José L. , Torra Joel , Urbano José M.
Published: March 2020

North African knapweed (Centaurea diluta Aiton) is an annual weed that is widespread in southern Spain and is of increasing concern in dryland cropping systems. Despite its expanding range in Spain, there is limited information on the emergence timing and pattern of this species, knowledge of which is critical for developing more timely and effective management strategies. Therefore, there is a need to develop simple and reliable models to predict the timing and emergence of this annual weed under dryland conditions. A multi-location field experiment was established across Spain in 2016 to 2017 to assess the emergence of C. diluta. At each of 11 locations, seeds were sown in the fall, and emergence was recorded. Overall emergence averaged 39% in the first year across all sites and 11% in the second year. In both years, the main emergence flush occurred at the beginning of the growing season. A three-parameter Weibull function best described seedling emergence of C. diluta. Emergence models were developed based on thermal time (TT) and hydrothermal time (HTT) and showed high predictability, as evidenced by root mean-square error prediction values of 10.8 and 10.7, respectively. Three cardinal points were established for TT and HHT at 0.5, 10, and 35 C for base, optimal, and ceiling temperatures, respectively, while base water potential was estimated at −0.5 MPa.
Grounding Line Retreat of Denman Glacier, East Antarctica, Measured With COSMO‐SkyMed Radar Interferometry Data
Authors: Brancato V. , Rignot E. , Milillo P. , Morlighem M. , Mouginot J. , An L. , Scheuchl B. , Jeong S. , Rizzoli P. , Bueso Bello J. L. , Prats‐Iraola P.
Published: March 2020

Denman Glacier, East Antarctica, holds an ice volume equivalent to a 1.5 m rise in global sea level. Using satellite radar interferometry from the COSMO‐SkyMed constellation, we detect a 5.4 ± 0.3 km grounding line retreat between 1996 and 2017–2018. A novel reconstruction of the glacier bed topography indicates that the retreat proceeds on the western flank along a previously unknown 5 km wide, 1,800 m deep trough, deepening to 3,400 m below sea level. On the eastern flank, the grounding line is stabilized by a 10 km wide ridge. At tidal frequencies, the grounding line extends over a several kilometer‐wide grounding zone, enabling warm ocean water to melt ice at critical locations for glacier stability. If warm, modified Circumpolar Deep Water reaches the sub‐ice‐shelf cavity and continues to melt ice at a rate exceeding balance conditions, the potential exists for Denman Glacier to retreat irreversibly into the deepest, marine‐based basin in Antarctica.
Trends and Variability in Stratospheric NOx Derived From Merged SAGE II and OSIRIS Satellite Observations
Authors: Dubé Kimberlee , Randel William , Bourassa Adam , Zawada Daniel , McLinden Chris , Degenstein Doug
Published: March 2020

Nitrogen oxides (NOx) in the stratosphere are produced from N2O, which is the dominant emission contributing to stratospheric ozone depletion in the 21st century and an important anthropogenic greenhouse gas. Decades worth of observations are required in order to quantify the variability and trends in stratospheric NOx so that we can better understand their impact on climate. Here we use the Stratospheric Aerosol and Gas Experiment (SAGE) II, a solar occultation instrument that measured NO2 from 1984 to 2005, and the Optical Spectrograph and InfraRed Imager System (OSIRIS), a limb‐scattering instrument that began measuring NO2 in 2001. By taking advantage of the 4‐year overlap between these instruments it was possible to produce a merged data set of stratospheric NO2, spanning over 34 years. In order to merge the data a photochemical correction was applied to account for the different times of day at which the instruments measure, and to convert the NO2 to NOx. A linear regression model was applied to the merged, deseasonalized data set to identify variability associated with long‐term trends, the quasi‐biennial oscillation (QBO), and volcanic aerosols. High levels of aerosol associated with large volcanic eruptions were found to greatly influence the calculated trend; when volcanic periods are excluded the trend in NOx is around 10% per decade in the tropical lower stratosphere. In this case, the observed trends and variability from the satellite measurements show overall good agreement with simulations from the whole atmosphere community climate model (WACCM).
Numerically Relevant Timescales in the MG2 Microphysics Model
Authors: Santos Sean Patrick , Caldwell Peter M. , Bretherton Christopher S.
Published: March 2020

Climate models rely on parameterizations of a variety of processes in the atmospheric physics, but a common concern is that the temporal resolution is too coarse to consistently resolve the behavior that individual parameterizations are designed to capture. This study examines timescales numerically derived from the Morrison‐Gettelman (MG2) microphysics as implemented within the Energy Exascale Earth System Model, version 1 (E3SMv1). Numerically relevant timescales in MG2 are derived by computing the eigenspectrum of its Jacobian. These timescales are found to often be smaller than the default 5 min time step used for MG2. The fast timescales are then heuristically connected to individual microphysics processes. By substepping a few particular rain processes within MG2, the time discretization error for those processes was considerably reduced with minimal additional expense to the overall microphysics. While this improvement has a substantial effect on the target processes and on the vertical distribution of stratiform‐derived rain within E3SMv1, the overall model climate is found to not be sensitive to MG2 time step. We hypothesize that this is because the surface climate does not depend strongly on certain process rates, especially MG2's rain evaporation rate.
E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
Authors: Parolo Claudio , Greenwood Ava S. , Ogden Nathan E. , Kang Di , Hawes Chase , Ortega Gabriel , Arroyo-Currás Netzahualcóyotl , Plaxco Kevin W.
Published: March 2020

The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid “scaffold” attached on one end to an electrode and presenting both a redox reporter and an epitope on the other. In the absence of antibody, the reporter efficiently transfers electrons when interrogated electrochemically. Binding-induced steric hindrance limits movement, reducing electron transfer in a manner that is both easily measured and quantitatively related to target concentration. Previously we have used monoclonal antibodies to explore the analytical performance of E-DNA sensors, showing that they support the rapid, single-step, quantitative detection of multiple antibodies in small volume samples. Here, in contrast, we employ authentic human samples to better explore the platform’s clinical potential. Specifically, we developed E-DNA sensors targeting three HIV-specific antibodies and then compared the analytical and clinical performance of these against those of gold standard serological techniques. Doing so we find that, although the multistep amplification of an ELISA leads to a lower detection limits, the clinical sensitivity of ELISAs, E-DNA sensors and lateral-flow dipsticks are indistinguishable across our test set. It thus appears that, by merging the quantitation and multiplexing of ELISAs with the convenience and speed of dipsticks, E-DNA scaffold sensors could significantly improve on current serological practice.
Wafer-scale 3D shaping of high aspect ratio structures by multistep plasma etching and corner lithography
Authors: Ni Shu , Berenschot Erwin J. W. , Westerik Pieter J. , de Boer Meint J. , Wolf René , Le-The Hai , Gardeniers Han J. G. E. , Tas Niels R.
Published: March 2020

The current progress of system miniaturization relies extensively on the development of 3D machining techniques to increase the areal structure density. In this work, a wafer-scale out-of-plane 3D silicon (Si) shaping technology is reported, which combines a multistep plasma etching process with corner lithography. The multistep plasma etching procedure results in high aspect ratio structures with stacked semicircles etched deep into the sidewall and thereby introduces corners with a proper geometry for the subsequent corner lithography. Due to the geometrical contrast between the gaps and sidewall, residues are left only inside the gaps and form an inversion mask inside the semicircles. Using this mask, octahedra and donuts can be etched in a repeated manner into Si over the full wafer area, which demonstrates the potential of this technology for constructing high-density 3D structures with good dimensional control in the bulk of Si wafers.
Burkholderia insecticola triggers midgut closure in the bean bug Riptortus pedestris to prevent secondary bacterial infections of midgut crypts
Authors: Kikuchi Yoshitomo , Ohbayashi Tsubasa , Jang Seonghan , Mergaert Peter
Published: March 2020

In addition to abiotic triggers, biotic factors such as microbial symbionts can alter development of multicellular organisms. Symbiont-mediated morphogenesis is well-investigated in plants and marine invertebrates but rarely in insects despite the enormous diversity of insect-microbe symbioses. The bean bug Riptortus pedestris is associated with Burkholderia insecticola which are acquired from the environmental soil and housed in midgut crypts. To sort symbionts from soil microbiota, the bean bug develops a specific organ called the “constricted region” (CR), a narrow and symbiont-selective channel, located in the midgut immediately upstream of the crypt-bearing region. In this study, inoculation of fluorescent protein-labeled symbionts followed by spatiotemporal microscopic observations revealed that after the initial passage of symbionts through the CR, it closes within 12–18 h, blocking any potential subsequent infection events. The “midgut closure” developmental response was irreversible, even after symbiont removal from the crypts by antibiotics. It never occurred in aposymbiotic insects, nor in insects infected with nonsymbiotic bacteria or B. insecticola mutants unable to cross the CR. However, species of the genus Burkholderia and its outgroup Pandoraea that can pass the CR and partially colonize the midgut crypts induce the morphological alteration, suggesting that the molecular trigger signaling the midgut closure is conserved in this bacterial lineage. We propose that this drastic and quick alteration of the midgut morphology in response to symbiont infection is a mechanism for stabilizing the insect-microbe gut symbiosis and contributes to host-symbiont specificity in a symbiosis without vertical transmission.
Correction: PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes
Authors: Jeong Myong-Ho , Jeong Hyeon-Ju , Ahn Byeong-Yun , Pyun Jung-Hoon , Kwon Ilmin , Cho Hana , Kang Jong-Sun
Published: March 2020

A correction to this paper has been published and can be accessed via a link at the top of the paper.
CD73 promotes tumor metastasis by modulating RICS/RhoA signaling and EMT in gastric cancer
Authors: Xu Zhijun , Gu Chuncai , Yao Xingxing , Guo Weihong , Wang Huanan , Lin Tian , Li Fengping , Chen Da , Wu Jianhua , Ye Gengtai , Zhao Liying , Hu Yanfeng , Yu Jiang , Shi Jiaolong , Li Guoxin , Liu Hao
Published: March 2020

Tumor microenvironment plays vital roles in shaping cancer diversity, and CD73 (ecto-5′-nucleotidase; NT5E) is an emerging immune checkpoint in modulating cancer progression via conversion of immunostimulatory ATP into immunosuppressive adenosine. However, how the CD73 is regulated and how it functions in the progression of cancer are largely unknown. Here, we showed that CD73 was overexpressed and correlated with poor prognosis of gastric cancer. CD73 links adenosinergic signaling in microenvironment switching to induction of epithelial-to-mesenchymal transition phenotype in gastric cancer during metastasis. Further pathway and gene set enrichment analysis of transcriptome data revealed the modulation role of CD73 in RICS/RhoA signaling by its extracellular function in adenosinergic pathway, which subsequently inhibited phosphorylation of LIMK/cofilin and promoted β-catenin activation. Pharmacological inhibition of CD73 adenosinergic signaling was found to induce RICS dysfunction. Dissemination and hematogenous metastasis model showed that targeting CD73 in gastric cancer could suppress experimental metastasis. To conclude, it substantiates CD73 as a target for treatment of gastric cancer metastasis and verifies RICS as an intracellular functional molecule linking CD73/adenosinergic signaling switching to RhoA/LIMK/cofilin pathway.
8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer
Authors: Dupont William D. , Breyer Joan P. , Plummer W. Dale , Chang Sam S. , Cookson Michael S. , Smith Joseph A. ,   University of Washington Center for Mendelian Genomics, Blue Elizabeth , Bamshad Michael , Chong Jessica , Nickerson Deborah , Blue Elizabeth E. , Bamshad Michael J. , Smith Jeffrey R.
Published: March 2020

The 8q24 genomic locus is tied to the origin of numerous cancers. We investigate its contribution to hereditary prostate cancer (HPC) in independent study populations of the Nashville Familial Prostate Cancer Study and International Consortium for Prostate Cancer Genetics (combined: 2,836 HPC cases, 2,206 controls of European ancestry). Here we report 433 variants concordantly associated with HPC in both study populations, accounting for 9% of heritability and modifying age of diagnosis as well as aggressiveness; 183 reach genome-wide significance. The variants comprehensively distinguish independent risk-altering haplotypes overlapping the 648 kb locus (three protective, and four risk (peak odds ratios: 1.5, 4, 5, and 22)). Sequence of the near-Mendelian haplotype reveals eleven causal mutation candidates. We introduce a linkage disequilibrium-based algorithm discerning eight independent sentinel variants, carrying considerable risk prediction ability (AUC = 0.625) for a single locus. These findings elucidate 8q24 locus structure and correlates for clinical prediction of prostate cancer risk.
Universal three-dimensional crosslinker for all-photopatterned electronics
Authors: Kim Min Je , Lee Myeongjae , Min Honggi , Kim Seunghan , Yang Jeehye , Kweon Hyukmin , Lee Wooseop , Kim Do Hwan , Choi Jong-Ho , Ryu Du Yeol , Kang Moon Sung , Kim BongSoo , Cho Jeong Ho
Published: March 2020

All-solution processing of large-area organic electronics requires multiple steps of patterning and stacking of various device components. Here, we report the fabrication of highly integrated arrays of polymer thin-film transistors and logic gates entirely through a series of solution processes. The fabrication is done using a three-dimensional crosslinker in tetrahedral geometry containing four photocrosslinkable azide moieties, referred to as 4Bx. 4Bx can be mixed with a variety of solution-processable electronic materials (polymer semiconductors, polymer insulators, and metal nanoparticles) and generate crosslinked network under exposure to UV. Fully crosslinked network film can be formed even at an unprecedentedly small loading, which enables preserving the inherent electrical and structural characteristics of host material. Because the crosslinked electronic component layers are strongly resistant to chemical solvents, micropatterning the layers at high resolution as well as stacking the layers on top of each other by series of solution processing steps is possible.
Structural insights into catalytic mechanism and product delivery of cyanobacterial acyl-acyl carrier protein reductase
Authors: Gao Yu , Zhang Hongmei , Fan Minrui , Jia Chenjun , Shi Lifang , Pan Xiaowei , Cao Peng , Zhao Xuelin , Chang Wenrui , Li Mei
Published: March 2020

Long-chain alk(a/e)nes represent the major constituents of conventional transportation fuels. Biosynthesis of alkanes is ubiquitous in many kinds of organisms. Cyanobacteria possess two enzymes, acyl-acyl carrier protein (acyl-ACP) reductase (AAR) and aldehyde-deformylating oxygenase (ADO), which function in a two-step alkane biosynthesis pathway. These two enzymes act in series and possibly form a complex that efficiently converts long chain fatty acyl-ACP/fatty acyl-CoA into hydrocarbon. While the structure of ADO has been previously described, structures of both AAR and AAR–ADO complex have not been solved, preventing deeper understanding of this pathway. Here, we report a ligand-free AAR structure, and three AAR–ADO complex structures in which AARs bind various ligands. Our results reveal the binding pattern of AAR with its substrate/cofactor, and suggest a potential aldehyde-transferring channel from AAR to ADO. Based on our structural and biochemical data, we proposed a model for the complete catalytic cycle of AAR.
Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions
Authors: Thompson Oliver , von Meyenn Ferdinand , Hewitt Zoe , Alexander John , Wood Andrew , Weightman Richard , Gregory Sian , Krueger Felix , Andrews Simon , Barbaric Ivana , Gokhale Paul J. , Moore Harry D. , Reik Wolf , Milo Marta , Nik-Zainal Serena , Yusa Kosuke , Andrews Peter W.
Published: March 2020

The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations.
Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans
Authors: Lee Kyung-Tae , Hong Joohyeon , Lee Dong-Gi , Lee Minjae , Cha Suyeon , Lim Yu-Gyeong , Jung Kwang-Woo , Hwangbo Areum , Lee Yelin , Yu Shang-Jie , Chen Ying-Lien , Lee Jong-Seung , Cheong Eunji , Bahn Yong-Sun
Published: March 2020

Cryptococcus neoformans causes fatal fungal meningoencephalitis. Here, we study the roles played by fungal kinases and transcription factors (TFs) in blood-brain barrier (BBB) crossing and brain infection in mice. We use a brain infectivity assay to screen signature-tagged mutagenesis (STM)-based libraries of mutants defective in kinases and TFs, generated in the C. neoformans H99 strain. We also monitor in vivo transcription profiles of kinases and TFs during host infection using NanoString technology. These analyses identify signalling components involved in BBB adhesion and crossing, or survival in the brain parenchyma. The TFs Pdr802, Hob1, and Sre1 are required for infection under all the conditions tested here. Hob1 controls the expression of several factors involved in brain infection, including inositol transporters, a metalloprotease, PDR802, and SRE1. However, Hob1 is dispensable for most cellular functions in Cryptococcus deuterogattii R265, a strain that does not target the brain during infection. Our results indicate that Hob1 is a master regulator of brain infectivity in C. neoformans.
Infrared spectroscopy data- and physics-driven machine learning for characterizing surface microstructure of complex materials
Authors: Lansford Joshua L. , Vlachos Dionisios G.
Published: March 2020

There is a need to characterize complex materials and their dynamics under reaction conditions to accelerate materials design. Adsorbate vibrational excitations are selective to adsorbate/surface interactions and infrared (IR) spectra associated with activating adsorbate vibrational modes are accurate, capture details of most modes, and can be obtained operando. Current interpretation depends on heuristic peak assignments for simple spectra, precluding the possibility of obtaining detailed structural information. Here, we combine data-based approaches with chemistry-dependent problem formulation to develop physics-driven surrogate models that generate synthetic IR spectra from first-principles calculations. Using synthetic IR spectra of carbon monoxide on platinum, we implement multinomial regression via neural network ensembles to learn probability distributions functions (pdfs) that describe adsorption sites and quantify uncertainty. We use these pdfs to infer detailed surface microstructure from experimental spectra and extend this methodology to other systems as a first step towards characterizing complex interfaces and closing the materials gap.
Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer
Authors: Tesch Megan E. , Pater Justin A. , Vandekerkhove Gillian , Wang Gang , Binnington Kristin , So Alan I. , Wyatt Alexander W. , Eigl Bernhard J.
Published: March 2020

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift BAP1 variant, and as expected, immunostaining validated the loss of BAP1 protein in patient-derived tumor specimens. Together, these data provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of the BAP1 TPDS continues to evolve, and may affect future screening and surveillance guidelines.
Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection
Authors: Kazer Samuel W. , Aicher Toby P. , Muema Daniel M. , Carroll Shaina L. , Ordovas-Montanes Jose , Miao Vincent N. , Tu Ang A. , Ziegler Carly G. K. , Nyquist Sarah K. , Wong Emily B. , Ismail Nasreen , Dong Mary , Moodley Amber , Berger Bonnie , Love J. Christopher , Dong Krista L. , Leslie Alasdair , Ndhlovu Zaza M. , Ndung’u Thumbi , Walker Bruce D. , Shalek Alex K.
Published: March 2020

Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell–cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease1,2 and nominating testable therapeutic targets3. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability4. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection5, we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
Draft genomes of two Atlantic bay scallop subspecies Argopecten irradians irradians and A. i. concentricus
Authors: Liu Xiao , Li Chao , Chen Min , Liu Bo , Yan Xiaojun , Ning Junhao , Ma Bin , Liu Guilong , Zhong Zhaoshan , Jia Yanglei , Shi Qiong , Wang Chunde
Published: March 2020

The two subspecies of Atlantic bay scallop (Argopecten irradians), A. i. irradians and A. i. concentricus, are economically important aquacultural species in northern and southern China. Here, we performed the whole-genome sequencing, assembly, and gene annotation and produced draft genomes for both subspecies. In total, 253.17 and 272.97 gigabases (Gb) of raw reads were generated from Illumina Hiseq and PacBio platforms for A. i. irradians and A. i. concentricus, respectively. Draft genomes of 835.7 Mb and 874.82 Mb were assembled for the two subspecies, accounting for 83.9% and 89.79% of the estimated sizes of their corresponding genomes, respectively. The contig N50 and scaffold N50 were 78.54 kb and 1.53 Mb for the A. i. irradians genome, and those for the A. i. concentricus genome were 63.73 kb and 1.25 Mb. Moreover, 26,777 and 25,979 protein-coding genes were predicted for A. i. irradians and A. i. concentricus, respectively. These valuable genome assemblies lay a solid foundation for future theoretical studies and provide guidance for practical scallop breeding.
Detecting small and cryptic animals by combining thermography and a wildlife detection dog
Authors: Karp Denise
Published: March 2020

Small and cryptic species are challenging to detect and study in their natural habitat. Many of these species are of conservation concern, and conservation efforts may be hampered by the lack of basic information on their ecological needs. Brown hare (Lepus europaeus) leverets - one example of such a small, cryptic and endangered animal - are notoriously difficult to detect, and therefore data on wild leverets are virtually non-existent. Novel technologies and methods such as thermal imaging and the use of wildlife detection dogs represent suitable means for the detection of such species by overcoming the problem of camouflage, using heat or scent emission respectively. Our study on brown hare leverets provides information on how to apply these new techniques successfully for the detection of small and cryptic species, thus enabling the collection of data that was previously inaccessible (e.g. behavioural observation, radio tagging). We found that the choice of method should be made according to vegetative structure. While the handheld thermal imaging camera is best used in areas with no or low vegetative cover, the thermal drone can be used up to medium vegetative cover, whereas the detection dog method is best applied where vegetation is very dense and not suitable to be searched using thermography. Being able to search all sort of different vegetation types, our combined approach enables the collection of a balanced and unbiased dataset regarding habitat type and hence selection of study specimen. We hope that the use of these new techniques will encourage research on many cryptic species that formerly have been neglected because they could not be detected using conventional methodologies.
Alcohol pretreatment of stools effect on culturomics
Authors: Afouda Pamela , Hocquart Marie , Pham Thi-Phuong-Thao , Kuete Edmond , Ngom Issa Isaac , Dione Niokhor , Valles Camille , Bellali Sara , Lagier Jean-Christophe , Dubourg Grégory , Raoult Didier
Published: March 2020

Recent studies have used ethanol stool disinfection as a mean of promoting valuable species’ cultivation in bacteriotherapy trials for Clostridium difficile infections (CDI) treatment with a particular focus on sporulating bacteria. Moreover, the culturomic approach has considerably enriched the repertoire of cultivable organisms in the human gut in recent years. This study aimed to apply this culturomic approach on fecal donor samples treated with ethanol disinfection to evidence potential beneficial microbes that could be used in bacteriotherapy trials for the treatment of CDI. Thereby, a total of 254 bacterial species were identified, 9 of which were novel. Of these, 242 have never been included in clinical trials for the treatment of CDIs, representing potential new candidates for bacteriotherapy trials. While non-sporulating species were nevertheless more affected by the ethanol pretreatment than sporulating species, the ethanol disinfection technique did not specifically select bacteria able to sporulate, as suggested by previous studies. Furthermore, some bacteria previously considered as potential candidates for bacteriotherapy have been lost after ethanol treatment. This study, while enriching the bacterial repertoire of the human intestine, would nevertheless require determining the exact contribution of each of species composing the bacterial consortia intended to be administered for CDI treatment.
Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows
Authors: Pascottini O. Bogado , Van Schyndel S. J. , Spricigo J. F. W. , Carvalho M. R. , Mion B. , Ribeiro E. S. , LeBlanc S. J.
Published: March 2020

Systemic inflammation (SI) is increasingly studied in several species because it may be central in many metabolic disturbances and be a risk factor for clinical disease. This proof-of-concept study evaluated the effects of the anti-inflammatory drug meloxicam on markers of SI and energy metabolism, polymorphonuclear neutrophil (PMN) function, and endometritis in clinically healthy postpartum dairy cows. Cows received meloxicam (0.5 mg/kg of body weight; n = 20) once daily for 4 days (10–13 days postpartum) or were untreated (n = 22). Blood samples were collected −7, 1, 3, 5, 7, 10, 11, 12, 13, 14, 18, 21, 28, and 35 days relative to calving to measure serum concentrations of metabolic and inflammatory markers. Function of peripheral blood PMN were evaluated at 5, 10, 14, and 21, and proportion of PMN in endometrial cytology were performed at 5, 10, 14, 21, 28 and 35 days postpartum. Meloxicam decreased serum haptoglobin from the second until the last day of treatment, and improved indicators of energy metabolism (lesser β-hydroxybutyrate and greater insulin-like growth factor-1 during treatment, and greater glucose at the end of treatment than control cows). This improved PMN function at 14 days postpartum, but the endometrial inflammatory status was not affected.