bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifetime Benefits and Harms of Prostate-Specific Antigen–Based Risk-Stratified Screening for Prostate Cancer
Authors: Heijnsdijk Eveline A M , Gulati Roman , Tsodikov Alex , Lange Jane M , Mariotto Angela B , Vickers Andrew J , Carlsson Sigrid V , Etzioni Ruth
Published: January 2020

Background

Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44–50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels.

Methods

PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years.

Results

Compared with biennial screening for ages 45–69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8–47.0% fewer tests (range between models), 0.9–2.1% fewer overdiagnoses, and 3.1–3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8–16.0% fewer tests, 5.0–24.0% fewer overdiagnoses, and 5.0–13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression.

Conclusion

Relative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.
When States Fail: The Politics of Orthodox Churches, Forced Displacement and Humanitarian Structures in Serbia and Ukraine
Authors: Leustean Lucian N
Published: January 2020

In Serbia, during the 2015 European refugee crisis, the Orthodox Church mobilized communities in providing humanitarian aid before local authorities and the government issued an organized response. Two years later, in December 2017, with the support of the Orthodox Church, Ukraine exchanged war prisoners with the separatist authorities in Donbas. In both countries, the social and political involvement of Orthodox Churches in dealing with forced displacement was unprecedented. Drawing on literature review and interviews with 25 representatives of governmental and civil-society bodies, members of the clergy and academics, this article explores the ways in which, in Serbia and Ukraine, when states fail to offer support for populations affected by violence, religious communities have been among the first actors to take over state governance and provide human security. It argues that, by doing so, Orthodox Churches become open to politicization from state authorities. The article contributes to the study of religion and forced displacement by linking the politicization of Orthodox Churches to the concept of state failure.
Subcutaneous emphysema and hypercarbia as a complication of laparoscopic procedure: case report
Authors: Aldakhil Sadal K , Tashkandi Abeer A , Al Harbi Mohammed K , Al Shehri Adel
Published: January 2020

Subcutaneous emphysema (SE) is a rare complication of laparoscopic procedures, with an incidence rate of only 0.43–2.3%. In this report, we present a case of a 28-year-old male who underwent an elective laparoscopic inguinal hernia repair and developed surgical emphysema, hypercarbia and respiratory acidosis intraoperatively. Based on our findings, we concluded that regardless of the low incidence of SE, awareness of the associated risk factors should be ensured to avoid laparoscopic procedure-related complications.
A NuSTAR view of GRS 1716−249 in the hard and intermediate states
Authors: Jiang Jiachen , Fürst Felix , Walton Dominic J , Parker Michael L , Fabian Andrew C
Published: January 2020

We present a detailed analysis of the spectral properties of the black hole transient GRS 1716−249, based on the archival Swift and NuSTAR observations taken during the outburst of this source in 2016–2017. The first six NuSTAR observations show that the source is in a canonical hard state, where the spectrum is dominated by a power-law continuum. The seventh NuSTAR observation is taken during the intermediate state where both a disc thermal component and a power-law continuum are shown. All of our observations show a broad emission-line feature in the iron band and a Compton hump above 10 keV. We model the broad-band spectra using a high-density disc reflection model, where the soft X-ray emission in the hard state is interpreted as part of the disc reflection component. This model enables us to constrain the disc density parameter of GRS 1716−249 in the range of 1019–1020 cm−3. We only obtain an upper limit of the inner disc radius using high-density disc reflection spectroscopy and the results indicate either a non-truncated disc or a slightly truncated disc with Rin ≲ 20 rg.
The VHE SED modelling of Markarian 501 in 2009
Authors: Sahu S , López Fortín C E , Iglesias Martínez M E , Nagataki S , Fernández de Córdoba P
Published: January 2020

The high energy blazar, Markarian 501 was observed as a part of multi-instrument and multiwavelength campaign spanning the whole electromagnetic spectrum for 4.5 months during March 15 to August 1, 2009. On May 1, Whipple 10 m telescope observed a very strong γ-ray flare in a time interval of about 0.5 h. Apart from this flare, high state and low state emissions were also observed by Whipple, VERITAS and MAGIC telescopes. Using the photohadronic model and accounting for the absorption of the extragalactic background light to these very high energy γ-rays, excellent fits are obtained for the observed spectra. We have shown that the intrinsic spectrum for low state emission is flat, however, for high and very high states this is a power-law with slowly increasing exponent.
Unlocking Galactic Wolf–Rayet stars with Gaia DR2 – I. Distances and absolute magnitudes
Authors: Rate Gemma , Crowther Paul A
Published: January 2020

We obtain distances to 383 Galactic Wolf–Rayet (WR) stars from Gaia DR2 parallaxes and Bayesian methods, with a prior based on H ii regions and dust extinction. Distances agree with those from Bailer-Jones et al. for stars up to 2 kpc from the Sun, though deviate thereafter due to differing priors, leading to modest reductions in luminosities for recent WR spectroscopic results. We calculate visual and K-band absolute magnitudes, accounting for dust extinction contributions and binarity, and identify 187 stars with reliable absolute magnitudes. For WR and O stars within 2 kpc, we find a WR/O ratio of 0.09. The distances are used to generate absolute magnitude calibrations and obtain the Gaia colour–magnitude diagram for WR stars. Average vWR-band absolute magnitudes for WN stars range from –3.6 mag (WN3–4) to –7.0 mag (WN8–9ha), and –3.1 (WO2–4) to –4.6 mag (WC9), with standard deviations of ∼0.6 mag. Using H ii region scale heights, we identify 31 WR stars at large (3σ, |z| ≥ 156 pc) distances from the mid-plane as potential runaways accounting for the Galactic warp, of which only four involve WN8–9 stars, contrary to previous claims.
Age demographics of the Milky Way disc and bulge
Authors: Grady J , Belokurov V , Evans N W
Published: January 2020

We exploit the extensive Gaia Data Release 2 set of long-period variables to select a sample of O-rich Miras throughout the Milky Way disc and bulge for study. Exploiting the relation between Mira pulsation period and stellar age/chemistry, we slice the stellar density of the Galactic disc and bulge as a function of period. We find that the morphology of both components evolves as a function of stellar age/chemistry with the stellar disc being stubby at old ages, becoming progressively thinner and more radially extended at younger stellar ages, consistent with the picture of inside-out and upside-down formation of the Milky Way’s disc. We see evidence of a perturbed disc, with large-scale stellar overdensities visible both in and away from the stellar plane. We find that the bulge is well modelled by a triaxial boxy distribution with an axial ratio of ∼1:0.4:0.3. The oldest of the Miras (∼9–10 Gyr) show little bar-like morphology, while the younger stars appear inclined at a viewing angle of ∼21° to the Sun–Galactic Centre line. This suggests that bar formation and buckling took place 8–9 Gyr ago, with the older Miras being hot enough to avoid being trapped by the growing bar. We find the youngest Miras to exhibit a strong peanut morphology, bearing the characteristic X-shape of an inclined bar structure.
Effects of Social Media on Adolescents’ Willingness and Intention to Use E-Cigarettes: An Experimental Investigation
Authors: Vogel Erin A , Ramo Danielle E , Rubinstein Mark L , Delucchi Kevin L , Darrow Sabrina M , Costello Caitlin , Prochaska Judith J
Published: January 2020

Introduction

This study examined the effects of experimentally manipulated social media exposure on adolescents’ willingness and intention to use e-cigarettes.

Aims and Methods

Participants were 135 adolescents of age 13–18 (52.6% female, mean age = 15.3) in California. Participants viewed six social media posts online in a 2 (post source: peer or advertisement) × 2 (e-cigarette content exposure: heavy or light) between-subjects design. Analyses were weighted to population benchmarks. We examined adolescents’ beliefs, willingness, and intention to use e-cigarettes in association with social media use intensity in daily life and with experimentally manipulated exposure to social media posts that varied by source (peer or advertisement) and content (e-cigarette heavy or light).

Results

Greater social media use in daily life was associated with greater willingness and intention to use e-cigarettes and more positive attitudes, greater perceived norms, and lower perceived danger of e-cigarette use (all p-values <.01). In tests of the experimental exposures, heavy (vs. light) e-cigarette content resulted in greater intention (p = .049) to use e-cigarettes and more positive attitudes (p = .019). Viewing advertisements (vs. peer-generated posts) resulted in greater willingness and intention (p-values <.01) to use e-cigarettes, more positive attitudes (p = .003), and greater norm perceptions (p = .009). The interaction effect of post source by post content was not significant for any of the outcomes (all p-values >.529).

Conclusions

Greater social media use and heavier exposure to advertisements and e-cigarette content in social media posts are associated with a greater risk for e-cigarette use among adolescents. Regulatory action is needed to prohibit sponsored e-cigarette content on social media platforms used by youth.

Implications

Adolescents who use social media intensely may be at higher risk for e-cigarette use. Even brief exposure to e-cigarette content on social media was associated with greater intention to use and more positive attitudes toward e-cigarettes. Regulatory action should be taken to prohibit sponsored e-cigarette content on social media used by young people, including posts by influencers who appeal to young people.
The Effect of Cigarette Packaging and Illness Sensitivity on Attention to Graphic Health Warnings: A Controlled Study
Authors: Hardardottir Agnes , Al-Hamdani Mohammed , Klein Raymond , Hurst Austin , Stewart Sherry H
Published: January 2020

Introduction

The social and health care costs of smoking are immense. To reduce these costs, several tobacco control policies have been introduced (eg, graphic health warnings [GHWs] on cigarette packs). Previous research has found plain packaging (a homogenized form of packaging), in comparison to branded packaging, effectively increases attention to GHWs using UK packaging prototypes. Past studies have also found that illness sensitivity (IS) protects against health-impairing behaviors. Building on this evidence, the goal of the current study was to assess the effect of packaging type (plain vs. branded), IS level, and their interaction on attention to GHWs on cigarette packages using proposed Canadian prototypes.

Aims and Methods

We assessed the dwell time and fixations on the GHW component of 40 cigarette pack stimuli (20 branded; 20 plain). Stimuli were presented in random order to 50 smokers (60.8% male; mean age = 33.1; 92.2% daily smokers) using the EyeLink 1000 system. Participants were divided into low IS (n = 25) and high IS (n = 25) groups based on scores on the Illness Sensitivity Index.

Results

Overall, plain packaging relative to branded packaging increased fixations (but not dwell time) on GHWs. Moreover, low IS (but not high IS) smokers showed more fixations to GHWs on plain versus branded packages.

Conclusions

These findings demonstrate that plain packaging is a promising intervention for daily smokers, particularly those low in IS, and contribute evidence in support of impending implementation of plain packaging in Canada.

Implications

Our findings have three important implications. First, our study provides controlled experimental evidence that plain packaging is a promising intervention for daily smokers. Second, the findings of this study contribute supportive evidence for the impending plain packaging policy in Canada, and can therefore aid in defense against anticipated challenges from the tobacco industry upon its implementation. Third, given its effects in increasing attention to GHWs, plain packaging is an intervention likely to provide smokers enhanced incentive for smoking cessation, particularly among those low in IS who may otherwise be less interested in seeking treatment for tobacco dependence.
An Internally-Consistent Database for Oxygen Isotope Fractionation Between Minerals
Authors: Vho Alice , Lanari Pierre , Rubatto Daniela
Published: January 2020

The knowledge of the fractionation behaviour between phases in isotopic equilibrium and its evolution with temperature is fundamental to assist the petrological interpretation of measured oxygen isotope compositions. We report a comprehensive and updated internally consistent database for oxygen isotope fractionation. Internal consistency is of particular importance for applications of oxygen isotope fractionation that consider mineral assemblages rather than individual mineral couples. The database DBOxygen is constructed from a large dataset of published experimental, semi-empirical and natural data, which were weighted according to type. It includes fractionation factors for 153 major and accessory mineral phases and a pure H2O fluid phase in the temperature range of 0–900°C, with application recommended for temperatures of 200–900°C. Multiple primary data for each mineral couple were discretized and fitted to a model fractionation function. Consistency between the models for each mineral couple was achieved by simultaneous least square regression. Minimum absolute uncertainties based on the spread of the available data were calculated for each fractionation factor using a Monte Carlo sampling technique. The accuracy of the derived database is assessed by comparisons with previous oxygen isotope fractionation calculations based on selected mineral/mineral couples. This database provides an updated internally consistent tool for geochemical modelling based on a large set of primary data and including uncertainties. For an effective use of the database for thermometry and uncertainty calculation we provide a MATLAB©-based software ThermoOx. The new database supports isotopic modelling in a thermodynamic framework to predict the evolution of δ18O in minerals during metamorphism.
Experimenter- and Infrared Thermography–Derived Measures of Capsaicin-Induced Neurogenic Flare Among Non-Hispanic White and Black Adults
Authors: Fulton Brook A , Burton Emily F , Nance Sabrina , Letzen Janelle E , Campbell Claudia M
Published: January 2020

Objective

Capsaicin is a widely utilized experimental pain stimulus; however, few studies have reported on ethnic differences in pain responses to capsaicin. The present study used infrared thermography to 1) measure differences in capsaicin-induced neurogenic flare between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults and 2) determine the association between neurogenic flare and secondary hyperalgesia.

Methods

Fifty-four participants (NHB N = 28) underwent heat/capsaicin sensitization model procedures. Neurogenic flare was examined using experimenter (i.e., subjective) and thermography (i.e., objective) measurements. A typically nonpainful mechanical punctate probe was used to measure secondary hyperalgesia.

Results

Ethnic groups did not significantly differ in age, sex, marital status, or personal income. Although experimenters rated a significantly wider area of capsaicin-related neurogenic flare among NHW compared with NHB participants (F1, 52 = 8.33, P = 0.006), thermography results showed no differences between groups in neurogenic flares (F1, 52 = 0.01, P = 0.93). Further, although NHB individuals reported greater average pain during the capsaicin procedures compared with NHW individuals (NHB = 58.57 [3.67], NHW = 46.46 [3.81]; F2, 51 = 5.19, P = 0.03), the groups did not differ in secondary hyperalgesia (F2, 51 = 0.03, P = 0.86), and ethnicity did not moderate the association between neurogenic flare and secondary hyperalgesia (F3, 50 = 0.24, P = 0.87).

Conclusions

Findings cautiously support the use of infrared thermography over subjective experimenter report when measuring neurogenic inflammation in diverse samples. However, infrared thermography should not be used as a diagnostic tool for pain, given the lack of association between these factors. Future research is warranted to replicate these findings in a larger and more diverse sample to determine accurate neurogenic inflammation measures across other ethnic minority populations.
Sleep duration over 28 years, cognition, gray matter volume, and white matter microstructure: a prospective cohort study
Authors: Zitser Jennifer , Anatürk Melis , Zsoldos Enikő , Mahmood Abda , Filippini Nicola , Suri Sana , Leng Yue , Yaffe Kristine , Singh-Manoux Archana , Kivimaki Mika , Ebmeier Klaus , Sexton Claire
Published: January 2020

Study Objectives

To examine the association between sleep duration trajectories over 28 years and measures of cognition, gray matter volume, and white matter microstructure. We hypothesize that consistently meeting sleep guidelines that recommend at least 7 hours of sleep per night will be associated with better cognition, greater gray matter volumes, higher fractional anisotropy, and lower radial diffusivity values.

Methods

We studied 613 participants (age 42.3 ± 5.03 years at baseline) who self-reported sleep duration at five time points between 1985 and 2013, and who had cognitive testing and magnetic resonance imaging administered at a single timepoint between 2012 and 2016. We applied latent class growth analysis to estimate membership into trajectory groups based on self-reported sleep duration over time. Analysis of gray matter volumes was carried out using FSL Voxel-Based-Morphometry and white matter microstructure using Tract Based Spatial Statistics. We assessed group differences in cognitive and MRI outcomes using nonparametric permutation testing.

Results

Latent class growth analysis identified four trajectory groups, with an average sleep duration of 5.4 ± 0.2 hours (5%, N = 29), 6.2 ± 0.3 hours (37%, N = 228), 7.0 ± 0.2 hours (45%, N = 278), and 7.9 ± 0.3 hours (13%, N = 78). No differences in cognition, gray matter, and white matter measures were detected between groups.

Conclusions

Our null findings suggest that current sleep guidelines that recommend at least 7 hours of sleep per night may not be supported in relation to an association between sleep patterns and cognitive function or brain structure.
Adapting the Diabetes Prevention Program for low- and middle-income countries: preliminary implementation findings from lifestyle Africa
Authors: Catley Delwyn , Puoane Thandi , Goggin Kathy , Tsolekile Lungiswa P , Resnicow Ken , Fleming Kandace , Smyth Joshua M , Hurley Emily A , Schlachter Sarah , Vitolins Mara Z , Lambert Estelle V , Hassen Mariam , Muhali Kenneth , Schoor Rachel
Published: January 2020

Rates of cardiovascular disease and diabetes are rising in low- and middle-income countries (LMIC), but there is a dearth of research devoted to developing and evaluating chronic disease interventions in these settings, particularly in Africa. Lifestyle Africa is a novel, culturally adapted version of the Diabetes Prevention Program (DPP) being evaluated in an ongoing community-based cluster-randomized trial in an underresourced urban community in South Africa. The purpose of this study is to describe the adaptations and adaptation process used to develop the program and to report preliminary implementation findings from the first wave of groups (n = 11; 200 individuals) who participated in the intervention. The RE-AIM model and community advisory boards guided the adaptation process. The program was designed to be delivered by community health workers (CHWs) through video-assisted sessions and supplemented with text messages. Participants in the trial were overweight and obese members of existing chronic disease “support groups” served via CHWs. Implementation outcomes included completion of sessions, session attendance, fidelity of session delivery, and participant satisfaction. Results indicated that 10/11 intervention groups completed all 17 core sessions. Average attendance across all sessions and groups was 54% and the percentage who attended at least 75% of sessions across all groups was 35%. Fidelity monitoring indicated a mean of 84% of all required procedures were completed while overall communication skills were rated as “good" to “excellent”. These preliminary results support the feasibility of culturally adapting the DPP for delivery by CHWs in underresourced settings in LMIC.
Hypoxia, hypercarbia, and mortality reporting in studies of anaesthesia-related neonatal neurodevelopmental delay in rodent models
Authors: Floyd Thomas F. , Khmara Kseniya , Lamm Ryan , Seidman Peggy
Published: January 2020

BACKGROUND

The concept of anaesthesia-related neonatal neurotoxicity originated in neonatal rodent models, yet prospective clinical studies have largely not supported this concern.

OBJECTIVES

To determine the frequency and magnitude of hypercarbia, hypoxia and death in rodent models of neonatal anaesthetic toxicity and neurodevelopmental delay.

DESIGN

Systematic review of published rodent studies of neonatal anaesthesia neurotoxicity. We documented anaesthetic, route, dose, frequency and duration of exposures. We further report ventilation method, documentation of adequacy of ventilation [arterial blood gas (ABG), other], mortality and the reporting of mortality.

DATA SOURCES

A PubMed literature search from 2003 to 2017 was conducted to identify studies on neurotoxicity in neonatal rodent models.

ELIGIBILITY

Studies were included when at least one group of animals fell within the postnatal age range of 3 to 15 days. Only English language original studies published as full-length articles in peer reviewed journals were included in the final analysis.

RESULTS

One hundred and three manuscripts were included. Ninety-eight percent of studies were conducted using spontaneous ventilation (101/103), with ABG monitoring used in only 33% of studies and visual monitoring alone for respiratory distress or cyanosis was employed in 60%. Of the 33% who reported ABG results, there were widely divergent values, with most reporting modest-to-severe hypercarbia. Mortality (median 11%, range of 0 to 40%), which infers severe hypoxia, was documented in only 36/103 (35%) reports.

CONCLUSION

Hypoxia and hypercarbia have known apoptotic effects on developing brains. Hence, the inadequate control of hypercarbia and hypoxia in neonatal rodent models of anaesthetic exposure during spontaneous ventilation suggests that the evidence for developmental delay and neurotoxicity attributed to anaesthesia may not be valid in humans.
A single-dose of stellate ganglion block for the prevention of postoperative dysrhythmias in patients undergoing thoracoscopic surgery for cancer
Authors: Wu Cai-Neng , Wu Xin-Hai , Yu Dong-Nan , Ma Wu-Hua , Shen Chun-Hui , Cao Ying
Published: January 2020

BACKGROUND

New-onset arrhythmias and sleep disturbances are frequently observed during the postoperative period in patients undergoing thoracic surgery.

OBJECTIVE

We evaluated the effectiveness of a single-dose stellate ganglion block (SGB) to prevent the occurrence of arrhythmias in patients undergoing thoracic surgery for cancer.

DESIGN

Randomised controlled double-blind study.

SETTING

Single university hospital.

PATIENTS

Ninety patients with lung cancer or oesophagal cancer scheduled for elective video-assisted thoracoscopic surgery were randomly randomised into one of two equal groups (the SGB group and control group, n = 40 each).

INTERVENTIONS

Patients received a single dose of 5 ml of 0.5% ropivacaine during ultrasound-guided SGB before induction of general anaesthesia in the SGB group.

MAIN OUTCOME MEASURES

Holter ECG was continuously monitored during the first 48 postoperative hours, and sleep state was monitored during the first two postoperative nights.

RESULTS

The incidences of postoperative supraventricular tachycardias were lower in the SGB group compared with the control group during the first 48 postoperative hours; 11.6 (5/43) vs. 31.8% (14/44), respectively, P = 0.023 (odds ratio 0.28, 95% confidence interval 0.09 to 0.87). The SGB also prolonged the total sleep time and increased the sleep efficiency during the first two postoperative nights. The duration of stage N2 sleep was longer in the SGB group compared with the control group [28 (interquartile range, 14 to 58) to 94 (interquartile range, 69 to 113) min, P = 0.016] on the first postoperative night. There were no differences in the duration of stage N1 and N3 sleep (P = 0.180, 0.086, respectively) on the first postoperative night, and the duration of stage N1, N2 and N3 sleep (P = 0.194, 0.057, 0.405, respectively) on the second postoperative night between the groups.

CONCLUSION

A pre-operative SGB effectively prevented the occurrence of postoperative supraventricular tachycardias and improves the objective sleep quality in patients undergoing thoracic surgery for cancer.

TRIAL REGISTRATION NUMBER

ChiCTR-1900023064.
Simulated patient-based teaching of medical students improves pre-anaesthetic assessment
Authors: Berger-Estilita Joana M. , Greif Robert , Berendonk Christoph , Stricker Daniel , Schnabel Kai P.
Published: January 2020

BACKGROUND

Pre-anaesthetic assessment of patients is a complex competency that needs to be taught during anaesthesia clerkships.

OBJECTIVES

We aimed to improve student teaching and investigated the effectiveness of trained ‘simulated patients’ (lay persons or actors trained to portray specific roles or symptoms) in the teaching of medical students to perform routine pre-anaesthetic assessments. We hypothesised that the intervention of one 30-min teaching sequence with a simulated patient will improve the performance of year 4 medical students in pre-anaesthesia assessment of elective surgical patients, compared with the control of standard apprentice-based teaching.

DESIGN

Randomised controlled trial.

SETTING/PARTICIPANTS

One hundred and forty-four year 4 medical students at the University of Bern.

INTERVENTION

These students were randomised to either the standard clinician-supervised learning in the operating theatre (n=71; control group) or a single teaching session with a simulated patient (nonhealthcare provider, as a trained layperson) (n=73; intervention group). Both groups of students then performed pre-anaesthetic patient visits. The student performances during these visits were assessed according to the mini-Clinical Evaluation Exercise tool by trained anaesthesiologists blinded to randomisation. The 71 students in the standard clinical supervision group also underwent the simulated patient teaching session on the day following the assessments.

RESULTS

The students in the intervention group of simulated patient teaching scored significantly higher in both their mini-Clinical Evaluation Exercise overall impression scores (8.8 ± 0.8 vs. 8.3 ± 0.9; P = 0.004) and mean domain scores (8.7 ± 0.8 vs. 8.3 ± 0.9; P = 0.01), compared with those of the control group with the standard clinical supervision.

CONCLUSION

The current single teaching encounter with a trained layperson acting as a simulated patient improved medical student performances in their pre-anaesthetic clinical assessment of surgical patients. This might be a suitable alternative to reduce the teaching burden for busy and costly clinicians.
Extracorporeal cardiopulmonary resuscitation at the emergency department
Authors: Poppe Michael , Schriefl Christoph , Steinacher Anna , Clodi Christian , Warenits Alexandra-Maria , Nürnberger Alexander , Hubner Pia , Holzer Michael , Horvat Johann , Wiedemann Dominik , Weiser Christoph
Published: January 2020

BACKGROUND

There is an increasing use of extracorporeal life support in refractory cardiac arrest. Recent studies highlighted the importance of an early and accurate patient selection for this invasive procedure.

OBJECTIVES

The aim of this study was to retrospectively validate a six-criteria-screening-checklist (witnessed collapse, bystander-cardiopulmonary resuscitation/first medical contact <5 min, shockable, age <70 years, end tidal carbon dioxide >14 mmHg and pupils not anisocoric/distorted/mydriatic) as an early screening tool in patients treated with extracorporeal cardiopulmonary resuscitation (eCPR) at the emergency department.

DESIGN

Retrospective observational study.

SETTING/PATIENTS

All patients at least 18 years of age with nontraumatic cardiac arrest and without return of spontaneous circulation before eCPR treatment at our department between January 2013 and December 2018 were included in this retrospective observational study.

INTERVENTION

No specific intervention was set in this observational study.

MAIN OUTCOME MEASURES

Primary outcome was the rate of patients who fulfilled all criteria, secondary outcome was 30-day and 6-month survival in accordance with the criteria.

RESULTS

Overall, data from a total of 92 patients were eligible for analyses. Out of these, 27 patients (29%) met all criteria. Patients, who fulfilled all criteria, showed significantly higher odds for 30-day survival [OR 6.0 (95% CI 1.78 to 20.19)] P 
= 0.004. Patients, who did not fulfil all criteria, showed significantly higher rates of early mortality after eCPR initiation [OR 4.57 (95% CI 1.69 to 12.37)] P 
= 0.003.

CONCLUSION

Patients fulfilling all inclusion criteria showed higher rates of survival after eCPR. Our results affirm that there is a possibility and even an obvious necessity for early patient selection based on standardised criteria before eCPR treatment. Large randomised trials are urgently needed to answer this question accurately.
Mariana serpentinite mud volcanism exhumes subducted seamount materials: implications for the origin of life
Authors: Fryer Patricia , Wheat C. Geoffrey , Williams Trevor , Kelley Christopher , Johnson Kevin , Ryan Jeffrey , Kurz Walter , Shervais John , Albers Elmar , Bekins Barbara , Debret Baptiste , Deng Jianghong , Dong Yanhui , Eickenbusch Philip , Frery Emanuelle , Ichiyama Yuji , Johnston Raymond , Kevorkian Richard , Magalhaes Vitor , Mantovanelli Simone , Menapace Walter , Menzies Catriona , Michibayashi Katsuyoshi , Moyer Craig , Mullane Kelli , Park Jung-Woo , Price Roy , Sissmann Olivier , Suzuki Shino , Takai Ken , Walter Bastien , Zhang Rui , Amon Diva , Glickson Deborah , Pomponi Shirley
Published: January 2020

The subduction of seamounts and ridge features at convergent plate boundaries plays an important role in the deformation of the overriding plate and influences geochemical cycling and associated biological processes. Active serpentinization of forearc mantle and serpentinite mud volcanism on the Mariana forearc (between the trench and active volcanic arc) provides windows on subduction processes.  Here, we present (1) the first observation of an extensive exposure of an undeformed Cretaceous seamount currently being subducted at the Mariana Trench inner slope; (2) vertical deformation of the forearc region related to subduction of Pacific Plate seamounts and thickened crust; (3) recovered Ocean Drilling Program and International Ocean Discovery Program cores of serpentinite mudflows that confirm exhumation of various Pacific Plate lithologies, including subducted reef limestone; (4) petrologic, geochemical and paleontological data from the cores that show that Pacific Plate seamount exhumation covers greater spatial and temporal extents; (5) the inference that microbial communities associated with serpentinite mud volcanism may also be exhumed from the subducted plate seafloor and/or seamounts; and (6) the implications for effects of these processes with regard to evolution of life.

This article is part of a discussion meeting issue ‘Serpentine in the Earth system’.
Habitability of the marine serpentinite subsurface: a case study of the Lost City hydrothermal field
Authors: Lang Susan Q. , Brazelton William J.
Published: January 2020

The Lost City hydrothermal field is a dramatic example of the biological potential of serpentinization. Microbial life is prevalent throughout the Lost City chimneys, powered by the hydrogen gas and organic molecules produced by serpentinization and its associated geochemical reactions. Microbial life in the serpentinite subsurface below the Lost City chimneys, however, is unlikely to be as dense or active. The marine serpentinite subsurface poses serious challenges for microbial activity, including low porosities, the combination of stressors of elevated temperature, high pH and a lack of bioavailable ∑CO
2
. A better understanding of the biological opportunities and challenges in serpentinizing systems would provide important insights into the total habitable volume of Earth's crust and for the potential of the origin and persistence of life in Earth's subsurface environments. Furthermore, the limitations to life in serpentinizing subsurface environments on Earth have significant implications for the habitability of subsurface environments on ocean worlds such as Europa and Enceladus. Here, we review the requirements and limitations of life in serpentinizing systems, informed by our research at the Lost City and the underwater mountain on which it resides, the Atlantis Massif.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth System’.
Fluviispira multicolorata gen. nov., sp. nov. and Silvanigrella paludirubra sp. nov., isolated from freshwater habitats
Authors: Pitt Alexandra , Koll Ulrike , Schmidt Johanna , Hahn Martin W.
Published: January 2020

Strain 33A1-SZDPT was isolated from a small creek located in Puch, Austria. Strain SP-Ram-0.45-NSY-1T was obtained from a small pond located in Schönramer Moor, Germany. 16S rRNA gene sequence similarities between the type strain of

Silvanigrella aquatica

, currently the only member of the family

Silvanigrellaceae

, and strains 33A1-SZDPT and SP-Ram-0.45-NSY-1T of 94.1 and 99.1 %, respectively, suggested affiliation of the two strains with this family. Phylogenetic reconstructions with 16S rRNA gene sequences and phylogenomic analyses with amino acid sequences obtained from 103 single-copy genes suggested that the strains represent a new genus and a new species in the case of strain 33A1-SZDPT (=JCM 32978T=DSM 107810T), and a new species within the genus

Silvanigrella

in the case of strain SP-Ram-0.45-NSY-1T (=JCM 32975T=DSM 107809T). Cells of strain 33A1-SZDPT were motile, pleomorphic, purple-pigmented on agar plates, putatively due to violacein, and showed variable pigmentation in liquid media. They grew chemoorganotrophically and aerobically and tolerated salt concentrations up to 1.2 % NaCl (v/w). The genome size of strain 33A1-SZDPT was 3.4 Mbp and the G+C content was 32.2 mol%. For this new genus and new species, we propose the name Fluviispira multicolorata gen. nov., sp. nov. Cells of strain SP-Ram-0.45-NSY-1T were motile, pleomorphic, red-pigmented and grew chemoorganotrophically and aerobically. They tolerated salt concentrations up to 1.1 % NaCl (v/w). The genome size of strain SP-Ram-0.45-NSY-1T was 3.9 Mbp and the G+C content 29.3 mol%. For the new species within the genus

Silvanigrella

we propose the name Silvanigrella paludirubra sp. nov.
NetCombin: An algorithm for optimal level-k network construction from triplets
Authors: Poormohammadi Hadi , Zarchi Mohsen Sardari
Published: January 2020

Phylogenetic networks construction is one the most important challenge in phylogenetics. These networks can present complex non-treelike events such as gene flow, horizontal gene transfers, recombination or hybridizations. Among phylogenetic networks, rooted structures are commonly used to represent the evolutionary history of a species set, explicitly. Triplets are well known input for constructing the rooted networks. Obtaining an optimal rooted network that contains all given triplets is main problem in network construction. The optimality criteria include minimizing the level and the number of reticulation nodes. The complexity of this problem is known to be NP-hard. In this research, a new algorithm called Netcombin is introduced to construct an optimal network which is consistent with input triplets. The innovation of this algorithm is based on binarization and expanding processes. The binarization process innovatively uses a measure to construct a binary rooted treeTconsistent with the maximum number of input triplets. ThenTis expanded in an intellectual process by adding minimum number of edges to obtain final network with the minimum number of reticulation nodes. In order to evaluate the proposed algorithm, NetCombin is compared with four state of the art algorithms, RPNCH, NCHB, TripNet, and SIMPLISTIC. The experimental results on real data indicate that by considering the trade-off between speed and precision, the NetCombin outperforms the others.

Author summary

Hadi Poormohammadi got his PhD in Mathematics, Applied combinatorics from Shahid Beheshti University, Tehran, Iran in 2013. He is now working as an assistant professor at the Faculty of Computer Engineering, Meybod University. His research interests include Combinatorics, Graph theory and Bioinformatics.

Mohsen Sardari Zarchi got his PhD in computer engineering, Artificial Intelligence from University of Isfahan in 2015. He is now working as an assistant professor at the Faculty of Computer Engineering, Meybod University. His research interests include Deep learning, Image processing, Artificial intelligence and Bioinformatics.
An unorthodox mechanism underlying voltage sensitivity of TRPV1 ion channel
Authors: Yang Fan , Xu Lizhen , Lee Bo Hyun , Xiao Xian , Yarov-Yarovoy Vladimir , Zheng Jie
Published: January 2020

While the capsaicin receptor TRPV1 channel is a polymodal nociceptor for heat, capsaicin, and proton, the channel’s responses to each of these stimuli are profoundly regulated by membrane potential, damping or even prohibiting its response at negative voltages and amplifying its response at positive voltages. Though voltage sensitivity plays an important role is shaping pain responses, how voltage regulates TRPV1 activation remains unknown. Here we showed that the voltage sensitivity of TRPV1 does not originate from the S4 segment like classic voltage-gated ion channels; instead, outer pore acidic residues directly partake in voltage-sensitive activation, with their negative charges collectively constituting the observed gating charges. Voltage-sensitive outer pore movement is titratable by extracellular pH and is allosterically coupled to channel activation, likely by influencing the upper gate in the ion selectivity filter. Elucidating this unorthodox voltage-gating process provides a mechanistic foundation for understanding polymodal gating and opens the door to novel approaches regulating channel activity for pain managements.
A deep dive into the ancestral chromosome number and genome size of flowering plants
Authors: Carta Angelino , Bedini Gianni , Peruzzi Lorenzo
Published: January 2020

Chromosome number and genome variation in flowering plants has stimulated a blossoming number of speculations about the ancestral chromosome number of angiosperms, but estimates so far remain equivocal.

We used a probabilistic approach to model haploid chromosome number (n) changes along a phylogeny embracing more than 10 thousands taxa, to reconstruct the ancestral chromosome number of the common ancestor of extant angiosperms and the most recent common ancestor for single angiosperm families. Independently, we carried out an analysis of 1C genome size evolution, including over 5 thousands taxa.

Our inferences revealed an ancestral haploid chromosome number for angiospermsn= 7, a diploid status, and an ancestral 1C = 1.73 pg. For 160 families, inferred ancestralnare provided for the first time.

Both descending dysploidy and polyploidy played crucial roles in chromosome number evolution. While descending dysploidy is equally distributed early and late across the phylogeny, polyploidy is detected mainly towards the tips. Similarly, also 1C genome size significantly increases (or decreases) in late-branching lineages. Therefore, no evidence exists for a clear link between ancestral chromosome numbers and ancient polyploidization events, suggesting that further insights are needed to elucidate the organization of genome packaging into chromosomes.
Module analysis using single-patient differential expression signatures improve the power of association study for Alzheimer’s disease
Authors: Huang Jialan , Lu Dong , Meng Guofeng
Published: January 2020

The causal mechanism of Alzheimer’s disease is extremely complex. It usually requires a huge number of samples to achieve a good statistical power in association studies. In this work, we illustrated a different strategy to identify AD risk genes by clustering AD patients into modules based on their single-patient differential expression signatures. Evaluation suggested that our method could enrich AD patients with common clinical manifestations. Applying it to a cohort of only 310 AD patients, we identified 175 AD risk loci at a strict threshold of empiricalp< 0.05 while only two loci were identified using all the AD patients. As an evaluation, we collected 23 AD risk genes reported in a recent large-scale meta-analysis and found that 18 of them were re-discovered by association studies using clustered AD patients, while only three of them were re-discovered using all AD patients. Functional annotation suggested that AD associated genetic variants mainly disturbed neuronal/synaptic function. Our results suggested module analysis, even randomly clustering, helped to enrich AD patients affected by the common risk variants.
An ExbD Disordered Domain Peptide Inhibits TonB System Activity
Authors: Kopp Dale R. , Postle Kathleen
Published: January 2020

The TonB system energizes transport of essential nutrients, such as iron siderophores, across unenergized outer membranes of Gram-negative bacteria. The integral cytoplasmic membrane proteins of the TonB system--ExbB, ExbD, and TonB--transduce the protonmotive force of the cytoplasmic membrane to TonB-dependent outer membrane transporters for active transport. ExbD protein is anchored in the cytoplasmic membrane, with the majority of it occupying the periplasm. We previously identified a conserved motif within a periplasmic disordered domain that is essential for TonB system function. Here we demonstrated that export of a peptide derived from that motif into the periplasm prevented TonB system function and inhibited all known ExbD interactions in vivo. Formaldehyde crosslinking captured the ExbD peptide in multiple ExbD and TonB complexes. Furthermore, peptides with mutations in the conserved motif not only had significantly reduced ability to inhibit TonB system activity, but they also altered interactions with ExbD and TonB, indicating the specificity of the interaction. Conserved motif peptide interactions with ExbD and TonB mostly occurred between Stage II and Stage III of the TonB energy transduction cycle, a transition that is characterized by the use of protonmotive force. Taken together, the data suggest that the ExbD disordered domain motif has multiple interactions with TonB and ExbD during between Stage II and III of the TonB energization cycle. Because of the essentiality of the motif, it may be a potential template for design of novel antibiotics that target the TonB system.

IMPORTANCE

Gram-negative bacteria are intrinsically antibiotic-resistant due to the diffusion barrier posed by their outer membranes. The TonB system allows them to circumvent this barrier for their own nutritional needs, including iron. The ability of bacteria to acquire iron is a virulence factor for many Gram-negative pathogens. However, no antibiotics currently target the TonB system. Because TonB and ExbD must interact productively in the periplasm for transport across the outer membrane, they constitute attractive targets for potential antibiotic development where chemical characteristics need not accommodate the need to cross the hydrophobic cytoplasmic membrane. Here we show that a small ExbD-derived peptide can interfere with the TonB-ExbD interaction to inhibit the TonB system in vivo.
Prediction of synonymous corrections by the BE-FF computational tool expands the targeting scope of base editing
Authors: Roy Rabinowitz , Shiran Abadi , Shiri Almog , Daniel Offen
Published: January 2020

Base editing is a genome-editing approach that employs the CRISPR/Cas system to precisely install point mutations within the genome. A cytidine or adenosine deaminase enzyme is fused to a deactivated Cas and converts C to T or A to G, respectively. The diversified repertoire of base editors, varied in their Cas and deaminase proteins, provides a wide range of functionality. However, existing base-editors can only induce transition substitutions in a specified region determined by the base editor, thus, they are incompatible for many point mutations. Here, we present BE-FF (Base Editors Functional Finder), a novel computational tool that identifies suitable base editors to correct the translated sequence erred by a given single nucleotide variation. Even if a perfect correction of the single nucleotide variation is not possible, BE-FF detects synonymous corrections to produce the reference protein. To assess the potential of BE-FF, we analysed a database of human pathogenic point mutations and found suitable base editors for 60.9% of the transition mutations. Importantly, 19.4% of them were made possible only by synonymous corrections. Moreover, we detected 298 cases in which pathogenic mutations caused by transversions were potentially repairable by base editing via synonymous corrections, although it had been thought impractical. The BE-FF tool and the database are available athttps://www.danioffenlab.com/be-ff.

GRAPHICAL ABSTRACT