bluuebunny/crossref_metadata_2025 huggingface dataset:
Mother-offspring conflict for water and its mitigation in the oviparous form of the reproductively bimodal lizard, Zootoca vivipara
Authors: Dupoué Andréaz , Sorlin Mahaut , Richard Murielle , Le Galliard Jean François , Lourdais Olivier , Clobert Jean , Aubret Fabien
Published: January 2020

Parent-offspring conflicts are widespread given that resources are often limited. Recent evidence has shown that availability of water can trigger such conflict during pregnancy in viviparous squamate species (lizards and snakes) and thus questions the role of water in the evolution of reproductive modes. Here, we examined the impact of water restriction during gravidity in the oviparous form of the bimodal common lizard (Zootoca vivipara), using a protocol previously used on the viviparous form. Females were captured in early gravidity from six populations along a 600 m altitudinal gradient to investigate whether environmental conditions (altitude, water access and temperature) exacerbate responses to water restriction. Females were significantly dehydrated after water restriction, irrespective of their reproductive status (gravid vs. non-reproductive), relative reproductive effort (relative clutch mass), and treatment timing (embryonic development stage). Female dehydration, together with reproductive performance, varied with altitude, probably due to long term acclimation or local adaptation. This moderate water-based intergenerational conflict in gravid females contrasts sharply with previous findings for the viviparous form, with implications to the evolutionary reversion from viviparity to oviparity. It is likely that oviparity constitutes a water-saving reproductive mode which might help mitigate intensive temperature-driven population extinctions at low altitudes.
Impact of malnutrition in the embolic–haemorrhagic trade-off of elderly patients with atrial fibrillation
Authors: Raposeiras-Roubín Sergio , Abu-Assi Emad , Paz Rafael Cobas , Rosselló Xavier , Barreiro Pardal Cristina , Piñón Esteban Miguel , Pascual Carlos Rodriguez , García Comesaña Julio , González-Carrero López Alberto , Caneiro-Queija Berenice , Cespón-Fernández María , Muñoz-Pousa Isabel , Domínguez-Erquicia Pablo , Domínguez-Rodríguez Luis Manuel , Carpintero Alberto , García Enrique , Ibáñez Borja , Iñíguez-Romo Andrés
Published: January 2020

Aims

Nutrition is an important determinant of health above the age of 80 years. Malnutrition in the elderly is often underdiagnosed. The aim of this study was to report the prevalence and prognostic value of malnutrition in patients ≥80 years old with atrial fibrillation (AF) with and without anticoagulant therapy.

Methods and results

We assessed the nutritional status of 4724 octogenarian patients with diagnoses of AF in a single centre from Spain between 2014 and 2017 with the CONUT score. Malnutrition was confirmed in 2036 patients (43.1%). Anticoagulation prescription was more frequent in patients with good nutrition than in those malnourished (79.5% vs. 71.7%, P < 0.001). The impact of malnutrition on mortality was evaluated by Cox regression, whereas its association with ischaemic stroke and major bleeding was studied through competing risk analysis. After multivariate adjusting, malnutrition was associated with mortality [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.24–1.49], stroke [sub-distribution HR (sHR) 1.37, 95% CI 1.10–1.69], and major bleeding (sHR 1.29, 95% CI 1.02–1.64). In anticoagulated patients, the embolic–haemorrhagic trade-off event was virtually neutral for those who had normal nutritional status [average daily rates (ADRs) for stroke and bleeding: 4.70 and 4.69 per 100 000 patients/day, respectively; difference = +0.01 per 100 000 patients/day; P = 0.99] and negative for those with malnutrition (ADR for stroke and bleeding: 5.38 and 7.61 per 100 000 patients/day, respectively; difference = −2.23 per 100 000 patients/day; P = 0.07).

Conclusion

Malnutrition is very common in octogenarian patients with AF, being a clinical predictor for poor prognosis. For anticoagulated patients, malnutrition was associated with a negative embolic–haemorrhagic balance.
Prevalence and significance of fragmented QRS complex in lead V1 on the surface electrocardiogram of healthy athletes
Authors: Ollitrault Pierre , Pellissier Arnaud , Champ-Rigot Laure , Junqua Nicolas , Chequel Mathieu , Reboursiere Emmanuel , Saloux Éric , Milliez Paul , Hodzic Amir
Published: January 2020

Aims

Limited data exist concerning fragmented QRS complexes (fQRSs) on the surface electrocardiogram (ECG) of apparently healthy athletes. We aimed to study the prevalence and significance of fQRS in lead V1 (fQRSV1), representing right ventricular (RV) activation, regarding training-induced RV morphological remodelling.

Methods and results

Between January 2017 and August 2019, 434 consecutive non-sedentary subjects underwent preparticipation cardiovascular screening, including a 12-lead ECG. Three hundred and ninety-three apparently healthy subjects were included, 119 of them were athletes (defined as performing ≥8 h/week for the last 6 months) and 274 were non-athletes. All athletes underwent two-dimensional transthoracic echocardiography. Fragmented QRS complex in lead V1 pattern was defined as a narrow (<120 ms) and quadriphasic QRS complex in lead V1. Fragmented QRS complex in lead V1 was more frequent in athletes compared with non-athletes (22% vs. 5.1%, P < 0.001) and was independently associated with the athlete status [adjusted odds ratio (aOR) = 4.693, 95% confidence interval (95% CI) 2.299—9.583; P < 0.001], the endurance category (aOR = 2.522, 95% CI 1.176—5.408; P = 0.017), and age (aOR = 0.962, 95% CI 0.934–0.989; P = 0.007) in multivariate analysis. In the subgroup of athletes, fQRSV1 was independently associated with mean RV outflow tract diameter (aOR = 1.458, 95% CI 1.105–1.923; P = 0.008) and age (aOR = 0.941, 95% CI 0.894–0.989; P = 0.017) in multivariate analysis.

Conclusion

Fragmented QRS complex in lead V1 is a newly described, frequent, ECG pattern in young and apparently healthy athletes and is associated with training-induced RV remodelling.
Development and Application of Mass Spectroscopy Assays for Nε-(1-Carboxymethyl)-L-Lysine and Pentosidine in Renal Failure and Diabetes
Authors: O’Grady Katherine L , Khosla Sundeep , Farr Joshua N , Bondar Olga P , Atkinson Elizabeth J , Achenbach Sara J , Eckhardt Brittany A , Thicke Brianne S , Tweed Amanda J , Volkman Tammie L , Drake Matthew T , Hines Jolaine M , Singh Ravinder J
Published: January 2020

Background

Advanced glycation end products (AGEs) are formed via the nonenzymatic glycation of sugars with amino acids. Two AGEs, Nε-(1-carboxymethyl)-L-Lysine (CML) and pentosidine, have been observed to be elevated in subjects suffering from a multitude of chronic disease states, and accumulation of these compounds may be related to the pathophysiology of disease progression and aging.

Methods

We describe here the development and validation of a specific and reproducible LC-MS/MS method to quantify CML and pentosidine in human serum with lower limits of quantitation of 75 ng/mL and 5 ng/mL, respectively. The analyte calibration curve exhibited excellent linearity at a range of 0–10 900 ng/mL for CML and 0–800 ng/mL for pentosidine. High-low linearity of 5 serum pairs was assessed, with a mean recovery of 103% (range 94—116%) for CML, and 104% (range 97—116%) for pentosidine.

Results

Serum concentrations of CML and pentosidine were quantified in 30 control and 30 subjects with chronic renal insufficiency. A significant increase in both analytes was observed in renal failure compared to control subjects (2.1-fold and 8.4-fold, respectively; P < 0.001 for both). In a separate cohort of 49 control versus 95 subjects with type 2 diabetes mellitus (T2DM), serum CML but not serum pentosidine, was significantly elevated in the T2DM patients, and CML was also correlated with glycemic control, as assessed by hemoglobin A1c (r = 0.34, P < 0.001).

Conclusions

These mass spectroscopy-based assays for serum CML and pentosidine should be useful in accurately evaluating circulating levels of these key AGEs in various disease states.
High-performance practical stiffness analysis of high-rise buildings using superfloor elements
Authors: Torky Ahmed A , Rashed Youssef F
Published: January 2020

This study develops a high-performance computing method using OpenACC (Open Accelerator) for the stiffness matrix and load vector generation of shear-deformable plates in bending using the boundary element method on parallel processors. The boundary element formulation for plates in bending is used to derive fully populated displacement-based stiffness matrices and load vectors at degrees of freedom of interest. The computed stiffness matrix of the plate is defined as a single superfloor element and can be solved using stiffness analysis, $Ku = F$, instead of the conventional boundary element method, $Hu = Gt$. Fortran OpenACC code implementations are proposed for the computation of the superfloor element’s stiffness, which includes one serial computing code for the CPU (central processing unit) and two parallel computing codes for the GPU (graphics processing unit) and multicore CPU. As industrial level practical floors are full of supports and geometrical information, the computation time of superfloor elements is reduced dramatically when computing on parallel processors. It is demonstrated that the OpenACC implementation does not affect numerical accuracy. The feasibility and accuracy are confirmed by numerical examples that include real buildings with industrial level structural floors. Engineering computations for massive floors with immense geometrical detail and a multitude of load cases can be modeled as is without the need for simplification.
Mr Eliot’s Christmas Morning Service: Participation, Good Will, and Humility in Murder in the Cathedral
Authors: de Villiers Rick
Published: January 2020

Despite the coy designation of ‘Interlude’, the sermon in T.S. Eliot’s Murder in the Cathedral presents a nexus of tension. On the one hand, it constitutes a crucial dramatic component of a play that balances on the knife-edge between pride and humility. On the other hand, it retraces certain theological assimilations found elsewhere in Eliot’s writing which collectively shape his understanding of Christian humility and good will. In circling around recurring phrases and influences, this article traces a conceptual genealogy behind the play’s sermon and offers a revaluation of Murder in the Cathedral as the creative culmination of Eliot’s ongoing engagement with secular humanism.
Identifying new X-ray binary candidates in M31 using random forest classification
Authors: Arnason R M , Barmby P , Vulic N
Published: January 2020

Identifying X-ray binary (XRB) candidates in nearby galaxies requires distinguishing them from possible contaminants including foreground stars and background active galactic nuclei. This work investigates the use of supervised machine learning algorithms to identify high-probability XRB candidates. Using a catalogue of 943 Chandra X-ray sources in the Andromeda galaxy, we trained and tested several classification algorithms using the X-ray properties of 163 sources with previously known types. Amongst the algorithms tested, we find that random forest classifiers give the best performance and work better in a binary classification (XRB/non-XRB) context compared to the use of multiple classes. Evaluating our method by comparing with classifications from visible-light and hard X-ray observations as part of the Panchromatic Hubble Andromeda Treasury, we find compatibility at the 90 per cent level, although we caution that the number of source in common is rather small. The estimated probability that an object is an XRB agrees well between the random forest binary and multiclass approaches and we find that the classifications with the highest confidence are in the XRB class. The most discriminating X-ray bands for classification are the 1.7–2.8, 0.5–1.0, 2.0–4.0, and 2.0–7.0 keV photon flux ratios. Of the 780 unclassified sources in the Andromeda catalogue, we identify 16 new high-probability XRB candidates and tabulate their properties for follow-up.
Precision angular diameters for 16 southern stars with VLTI/PIONIER
Authors: Rains Adam D , Ireland Michael J , White Timothy R , Casagrande Luca , Karovicova I
Published: January 2020

In the current era of Gaia and large, high signal-to-noise stellar spectroscopic surveys, there is an unmet need for a reliable library of fundamentally calibrated stellar effective temperatures based on accurate stellar diameters. Here, we present a set of precision diameters and temperatures for a sample of 6 dwarf, 5 sub-giant, and 5 giant stars observed with the PIONIER beam combiner at the VLTI. Science targets were observed in at least two sequences with five unique calibration stars each for accurate visibility calibration and to reduce the impact of bad calibrators. We use the standard PIONIER data reduction pipeline, but bootstrap over interferograms, in addition to employing a Monte Carlo approach to account for correlated errors by sampling stellar parameters, limb darkening coefficients, and fluxes, as well as predicted calibrator angular diameters. The resulting diameters were then combined with bolometric fluxes derived from broad-band Hipparcos–Tycho photometry and MARCS model bolometric corrections, plus parallaxes from Gaia to produce effective temperatures, physical radii, and luminosities for each star observed. Our stars have mean angular diameter and temperatures uncertainties of 0.8 per cent and 0.9 per cent, respectively, with our sample including diameters for 10 stars with no pre-existing interferometric measurements. The remaining stars are consistent with previous measurements, with the exception of a single star which we observe here with PIONIER at both higher resolution and greater sensitivity than was achieved in earlier work.
Abnormal uterine inflammation in obstetric syndromes: molecular insights into the role of chemokine decoy receptor D6 and inflammasome NLRP3
Authors: Tersigni Chiara , Vatish Manu , D’Ippolito Silvia , Scambia Giovanni , Di Simone Nicoletta
Published: January 2020

The adaptation of the uterine environment into a favorable immunological and inflammatory milieu is a physiological process needed in normal pregnancy. A uterine hyperinflammatory state, whether idiopathic or secondary to hormonal or organic uterine disorders (polycystic ovary syndromes, endometriosis/adenomyosis and fibroids), negatively influences the interactions between decidua and trophoblast, early in gestation, and between chorion and decidua later in pregnancy. Abnormal activation of uterine inflammatory pathways not only contributes to the pathogenesis of the obstetric syndromes, i.e. recurrent pregnancy loss (RPL), pre-term delivery (PTD) and pre-eclampsia (PE), but also to correlates with severity. In this review, we summarize recent advances in the knowledge of uterine molecular mechanisms of inflammatory modulation in normal pregnancy and obstetric syndromes (RPL, PTD and PE). In particular, we focus on two regulators of uterine/placental inflammation: the NLRP3 inflammasome and the chemokines decoy receptor D6. We performed comprehensive review of the literature in PubMed and Google Scholar databases from 1994 to 2018. The available evidence suggests that: (i) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; (ii) there is a role for abnormal expression and function of D6 decoy receptor at the feto–maternal interface in cases of RPL and PTD and (iii) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets.
Targeted next-generation sequencing of 565 neuro-oncology patients at UCLA: A single-institution experience
Authors: Ji Matthew S , Eldred Blaine S C , Liu Regina , Pianka Sean T , Molaie Donna , Kevan Bryan , Pan Stephanie , Lai Thomas J , Nguyen Nhung T , Chow Frances E , Yong William H , Cox Christopher D , Reeh Devin N , Li Tie , Liau Linda M , Nghiemphu Phioanh L , Cloughesy Timothy F , Li Gang , Lai Albert
Published: January 2020

Background

Targeted next-generation sequencing (NGS) is frequently obtained at the University of California, Los Angeles (UCLA) for clinical characterization of CNS tumors. In this study, we describe the diagnostic reliability of the Foundation Medicine (FM) targeted NGS platform and its ability to explore and identify tumor characteristics of prognostic significance in gliomas.

Methods

Neuro-oncology patients seen at UCLA who have received FM testing between August 2012 and March 2019 were included in this study, and all mutations from FM test reports were recorded. Initial tumor diagnoses and diagnostic markers found via standard clinical methods were obtained from pathology reports. With overall and progression-free survival data, elastic net regularized Cox regression and Cox proportional hazards models were used to determine whether any mutations of unknown significance detected by FM could predict patient outcome in glioblastoma (GBM).

Results

Six hundred and three samples tested by FM from 565 distinct patients were identified. Concordance of diagnostic markers was high between standard clinical testing methods and FM. Oligodendroglial markers detected via FM were highly correlated with 1p19q codeletion in IDH mutated gliomas. FM testing of multiple tumor samples from the same patient demonstrated temporal and spatial mutational heterogeneity. Mutations in BCORL1, ERBB4, and PALB2, which are mutations of unknown significance in GBM, were shown to be statistically significant in predicting patient outcome.

Conclusions

In our large cohort, we found that targeted NGS can both reliably and efficiently detect important diagnostic markers in CNS tumors.
Cutaneous sensitization to aziridine preceding the onset of occupational asthma
Authors: Mason P , Liviero F , Crivellaro M , Maculan P , Maestrelli P , Guarnieri G
Published: January 2020

We describe a 47-year-old non-atopic woman, working as a spray painter in a tannery for 23 years, with a 16-year history of cutaneous symptoms and a subsequent 2-year history of asthmatic symptoms after exposure to aerosol and vapour of polyfunctional aziridine (PFA) at work. To confirm the occupational origin of the dermatitis and asthma we performed a skin prick test with PFA and a specific inhalation challenge (SIC) with PFA. Prick test with PFA elicited an immediate positive skin reaction. She developed an immediate asthmatic reaction upon SIC with PFA. The onset of occupational dermatitis before asthma is consistent with the hypothesis that the sensitization to PFA was triggered in the skin. The observation that the reactions elicited in skin and airways upon exposure to PFA exhibited the same time course, suggests a similar mechanism at both sites. Thus, the avoidance of both skin and airway exposure to PFA should be recommended in workplace hygiene practice.
Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting
Authors: Derington Catherine G , Benavides Nancy , Delate Thomas , Fish Douglas N
Published: January 2020

Background

Few published studies exist to describe the off-label use of multiple-dose fosfomycin for outpatient treatment of complicated urinary tract infections (UTI). The purpose of this study was to characterize the patients, infections, drug susceptibilities, and outcomes of multiple-dose fosfomycin episodes for outpatient UTI treatment.

Methods

This retrospective study evaluated patients who received an outpatient prescription for multiple-dose fosfomycin between July 1999 and June 2018. Multiple-dose fosfomycin prescriptions dispensed for UTI prophylaxis were excluded. The primary outcome was clinical resolution (complete resolution of signs and symptoms) of infection within 30 days. Secondary outcomes included descriptions of antibiotics and cultures before and after treatment, 30-day bacteriologic resolution (posttreatment urine culture <103 colony-forming units of the original pathogen), and 90-day healthcare utilizations for UTI or pyelonephritis. Data were analyzed using descriptive statistics.

Results

Of 171 multiple-dose fosfomycin treatment episodes, the most common regimen was 1 dose every 3 days, mean duration of 6.1 days. Clinical resolution occurred in 115 of 171 (67.3%) episodes, and bacteriologic resolution occurred in 37 of 76 (48.7%) episodes with posttreatment cultures. Most patients used antibiotics or had urine cultures before treatment (81.9% and 97.7%, respectively). Additional antibiotic use, urine cultures, and healthcare utilizations within 90 days posttreatment occurred in 51.5%, 66.1%, and 24.6% of patients, respectively.

Conclusions

For treating complicated UTI with multiple-dose fosfomycin, clinical resolution occurred in 2 of 3 treatment episodes and bacteriologic resolution occurred in one-half of treatment episodes. Future research is necessary to determine the relative efficacy and safety and optimal dosing regimen, duration, and population for UTI treatment with multiple-dose fosfomycin.
The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature
Authors: Sirucek Laura , Jutzeler Catherine Ruth , Rosner Jan , Schweinhardt Petra , Curt Armin , Kramer John Lawrence Kipling , Hubli Michèle
Published: January 2020

Objective

Descending pain modulation can be experimentally assessed by way of testing conditioned pain modulation. The application of tonic heat as a test stimulus in such paradigms offers the possibility of observing dynamic pain responses, such as adaptation and temporal summation of pain. Here we investigated conditioned pain modulation effects on tonic heat employing participant-controlled temperature, an alternative tonic heat pain assessment. Changes in pain perception are thereby represented by temperature adjustments performed by the participant, uncoupling this approach from direct pain ratings. Participant-controlled temperature has emerged as a reliable and sex-independent measure of tonic heat.

Methods

Thirty healthy subjects underwent a sequential conditioned pain modulation paradigm, in which a cold water bath was applied as the conditioning stimulus and tonic heat as a test stimulus. Subjects were instructed to change the temperature of the thermode in response to variations in perception to tonic heat in order to maintain their initial rating over a two-minute period. Two additional test stimuli (i.e., lower limb noxious withdrawal reflex and pressure pain threshold) were included as positive controls for conditioned pain modulation effects.

Results

Participant-controlled temperature revealed conditioned pain modulation effects on temporal summation of pain (P = 0.01). Increased noxious withdrawal reflex thresholds (P = 0.004) and pressure pain thresholds (P < 0.001) in response to conditioning also confirmed inhibitory conditioned pain modulation effects.

Conclusions

The measured interaction between conditioned pain modulation and temporal summation of pain supports the participant-controlled temperature approach as a promising method to explore dynamic inhibitory and facilitatory pain processes previously undetected by rating-based approaches.
Assessing Arm Volume in People During and After Treatment for Breast Cancer: Reliability and Convergent Validity of the LymphaTech System
Authors: Binkley Jill M , Weiler Michael J , Frank Nathan , Bober Lauren , Dixon J Brandon , Stratford Paul W
Published: January 2020

Background

There are challenges related to the accurate and efficient measurement of lymphedema in people with breast cancer. The LymphaTech 3D Imaging System (LymphaTech, Atlanta, GA, USA) is a mobile, noninvasive platform that provides limb geometry measurements.

Objective

The objective of this study was to estimate the reliability and validity of the LymphaTech for measuring arm volume in the context of women seeking care in a specialty breast cancer rehabilitation clinic.

Design

This was a cross-sectional reliability and convergent validity study.

Methods

People who had stage I to IV breast cancer with lymphedema or were at risk for it were included. Arm volume was measured in 66 participants using the LymphaTech and perometer methods. Test-retest reliability for a single measure, limb volume difference, and agreement between methods was analyzed for 30 participants. A method-comparison analysis was also used to assess convergent validity between methods.

Results

Both LymphaTech and perometer methods displayed intraclass correlation coefficients (ICCs) of ≥0.99. The standard errors of measurement for the LymphaTech and length-matched perometer measurements were nearly identical. Similar intraclass correlation coefficients (0.97) and standard errors of measurement (38.0–40.7 mL) were obtained for the between-limb volume difference for both methods. The convergent validity analyses demonstrated no systematic difference between methods.

Limitations

The sample size was not based on a formal sample size calculation. LymphaTech measurements included interrater variance, and perometer measurements contained intrarater variance.

Conclusions

The LymphaTech had excellent test-retest reliability, and convergent validity was supported. This technology is efficient and portable and has a potential role in prospective surveillance and management of lymphedema in clinical, research, and home settings.
Comparing three models of arousal in the human brain
Authors: Haj-Ali Hadeel , Anderson Adam K , Kron Assaf
Published: January 2020

The bipolar valence–arousal model is assumed by many to be an underlying structure of conscious experience of core affect and emotion. In this work, we compare three versions of the bipolar valence–arousal model at the neural domain, using functional magnetic resonance imaging (fMRI). Specifically, we systematically contrast three models of arousal: model 1—‘arousal as a separate quale from valence’, model 2—‘arousal as intensity of bipolar valence’ and model 3—‘arousal as a linear combination of unipolar pleasant and unpleasant’. Using parametric modulation analysis, we estimated the ability of each model to predict activation in arousal-related brain regions, in response to affective stimuli. The results suggest that arousal is not separable from valence in its ability to predict arousal-related neural activity. The relevance of the results to the theory of conscious affect is discussed.
Traversing the Muddy Waters—Legality, Tenability, and Reliability of Co-defendant’s Confession under the Indian Evidence Act
Authors: Yadav Prabhakar
Published: January 2020

This article critiques the Indian jurisprudence on section 30 of the Indian Evidence Act, 1872. Under the present legal framework, a confession of a co-defendant in a joint criminal trial may be utilized by the Courts to corroborate other pieces of evidence, in order to determine the guilt of non-confessing defendants, also. However, this article argues that the ‘original meaning’ of section 30 makes the confession of a testifying defendant, admissible as against its maker—alone. And not against the other co-defendants. This position is supported by the drafting history behind section 30, and further, is the tradition and practice across common law jurisdictions. In this connection, the author argues that in the absence of any cross-examination or oath, admitting such a confession under section 30 prejudices the fair trial right of non-confessing co-defendants. Hence, it must be excluded altogether by the Courts—as a bright-line rule—while the guilt of those non-confessing co-defendants is determined. Conversely, the author argues that the interpretation of section 30 in light of its original meaning, which makes confession admissible against its maker alone, would automatically safeguard constitutional due process guarantees and the fair trial right of the non-confessing defendants.
Effects of Electrical Stimulation on hiPSC-CM Responses to Classic Ion Channel Blockers
Authors: Wei Feng , Pourrier Marc , Strauss David G , Stockbridge Norman , Pang Li
Published: January 2020

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great potential for personalized cardiac safety prediction, particularly for that of drug-induced proarrhythmia. However, hiPSC-CMs fire spontaneously and the variable beat rates of cardiomyocytes can be a confounding factor that interferes with data interpretation. Controlling beat rates with pacing may reduce batch and assay variations, enable evaluation of rate-dependent drug effects, and facilitate the comparison of results obtained from hiPSC-CMs with those from adult human cardiomyocytes. As electrical stimulation (E-pacing) of hiPSC-CMs has not been validated with high-throughput assays, herein, we compared the responses of hiPSC-CMs exposed with classic cardiac ion channel blockers under spontaneous beating and E-pacing conditions utilizing microelectrode array technology. We found that compared with spontaneously beating hiPSC-CMs, E-pacing: (1) reduced overall assay variabilities, (2) showed limited changes of field potential duration to pacemaker channel block, (3) revealed reverse rate dependence of multiple ion channel blockers on field potential duration, and (4) eliminated the effects of sodium channel block on depolarization spike amplitude and spike slope due to a software error in acquiring depolarization spike at cardiac pacing mode. Microelectrode array optogenetic pacing and current clamp recordings at various stimulation frequencies demonstrated rate-dependent block of sodium channels in hiPSC-CMs as reported in adult cardiomyocytes. In conclusion, pacing enabled more accurate rate- and concentration-dependent drug effect evaluations. Analyzing responses of hiPSC-CMs under both spontaneously beating and rate-controlled conditions may help better assess the effects of test compounds on cardiac electrophysiology and evaluate the value of the hiPSC-CM model.
Patrick Mollison CBE. 17 March 1914—26 November 2011
Authors: Craft Alan W.
Published: January 2020

Patrick Mollison was a pioneer in blood transfusion, playing a major role in changing it from a risky procedure to one which is now extremely safe. The urgent need for blood during World War II provided a stimulus for the development of this important lifesaving measure. His first major contribution was to devise a mechanism whereby blood could be stored for more than just short periods. Mixing donated blood with acid–citrate–dextrose (ACD) became a standard procedure for almost 30 years and was used worldwide. He later took a special interest in haemolytic disease of the newborn (HDN), which was largely due to Rhesus incompatibility between mother and baby. He was also involved with work which eventually led to HDN becoming preventable with the use of anti-D treatment of mothers. He wrote the first standard textbook on blood transfusion; almost 70 years later it is in its eleventh edition and still bears his name in the title. He spent his working life in blood transfusion and the study of the scientific aspects of this subject, developing a university department at Hammersmith Hospital and publishing almost 200 scientific papers as well as the textbook. He was very much a clinical scientist rather than a front-line clinician, although he was physician to Her Majesty Queen Elizabeth and was present at the birth of all four of her children.
Mindreading in the balance: adults' mediolateral leaning and anticipatory looking foretell others’ action preparation in a false-belief interactive task
Authors: Zani Giovanni , Butterfill Stephen A. , Low Jason
Published: January 2020

Anticipatory looking on mindreading tasks can indicate our expectation of an agent's action. The challenge is that social situations are often more complex, involving instances where we need to track an agent's false belief to successfully identify the outcome to which an action is directed. If motor processes can guide how action goals are understood, it is conceivable—where that kind of goal ascription occurs in false-belief tasks—for motor representations to account for someone's belief-like state. Testing adults (
N
= 42) in a real-time interactive helping scenario, we discovered that participants' early mediolateral motor activity (leftwards–rightwards leaning on balance board) foreshadowed the agent's belief-based action preparation. These results suggest fast belief-tracking can modulate motor representations generated in the course of one's interaction with an agent. While adults' leaning, and anticipatory looking, revealed the contribution of fast false-belief tracking, participants did not correct the agent's mistake in their final helping action. These discoveries suggest that adults may not necessarily use another's belief during overt social interaction or find reflecting on another's belief as being normatively relevant to one's own choice of action. Our interactive task design offers a promising way to investigate how motor and mindreading processes may be variously integrated.
Distinguishing between parallel and serial processing in visual attention from neurobiological data
Authors: Li Kang , Kadohisa Mikiko , Kusunoki Makoto , Duncan John , Bundesen Claus , Ditlevsen Susanne
Published: January 2020

Serial and parallel processing in visual search have been long debated in psychology, but the processing mechanism remains an open issue. Serial processing allows only one object at a time to be processed, whereas parallel processing assumes that various objects are processed simultaneously. Here, we present novel neural models for the two types of processing mechanisms based on analysis of simultaneously recorded spike trains using electrophysiological data from prefrontal cortex of rhesus monkeys while processing task-relevant visual displays. We combine mathematical models describing neuronal attention and point process models for spike trains. The same model can explain both serial and parallel processing by adopting different parameter regimes. We present statistical methods to distinguish between serial and parallel processing based on both maximum likelihood estimates and decoding the momentary focus of attention when two stimuli are presented simultaneously. Results show that both processing mechanisms are in play for the simultaneously recorded neurons, but neurons tend to follow parallel processing in the beginning after the onset of the stimulus pair, whereas they tend to serial processing later on.
Low-cost, open-access quantitative phase imaging of algal cells using the transport of intensity equation
Authors: Grant Stephen D. , Richford Kyle , Burdett Heidi L. , McKee David , Patton Brian R.
Published: January 2020

Phase microscopy allows stain-free imaging of transparent biological samples. One technique, using the transport of intensity equation (TIE), can be performed without dedicated hardware by simply processing pairs of images taken at known spacings within the sample. The resulting TIE images are quantitative phase maps of unstained biological samples. Therefore, spatially resolved optical path length (OPL) information can also be determined. Using low-cost, open-source hardware, we applied the TIE to living algal cells to measure their effect on OPL. We obtained OPL values that were repeatable within species and differed by distinct amounts depending on the species being measured. We suggest TIE imaging as a method of discrimination between different algal species and, potentially, non-biological materials, based on refractive index/OPL. Potential applications in biogeochemical modelling and climate sciences are suggested.
Non-normal origin of modal instabilities in rotating plane shear flows
Authors: Jose Sharath , Govindarajan Rama
Published: January 2020

Small variations introduced in shear flows are known to affect stability dramatically. Rotation of the flow system is one example, where the critical Reynolds number for exponential instabilities falls steeply with a small increase in rotation rate. We ask whether there is a fundamental reason for this sensitivity to rotation. We answer in the affirmative, showing that it is the non-normality of the stability operator in the absence of rotation which triggers this sensitivity. We treat the flow in the presence of rotation as a perturbation on the non-rotating case, and show that the rotating case is a special element of the pseudospectrum of the non-rotating case. Thus, while the non-rotating flow is always modally stable to streamwise-independent perturbations, rotating flows with the smallest rotation are unstable at zero streamwise wavenumber, with the spanwise wavenumbers close to that of disturbances with the highest transient growth in the non-rotating case. The instability critical rotation number scales inversely as the square of the Reynolds number, which we demonstrate is the same as the scaling obeyed by the minimum perturbation amplitude in non-rotating shear flow needed for the pseudospectrum to cross the neutral line. Plane Poiseuille flow and plane Couette flow are shown to behave similarly in this context.
Mice tune out not in: violation of prediction drives auditory saliency
Authors: Rogalla Meike M. , Rauser Inga , Schulze Karsten , Osterhagen Lasse , Hildebrandt K. Jannis
Published: January 2020

Successful navigation in complex acoustic scenes requires focusing on relevant sounds while ignoring irrelevant distractors. It has been argued that the ability to track stimulus statistics and generate predictions supports the choice of what to attend and what to ignore. However, the role of these predictions about future auditory events in drafting decisions remains elusive. While most psychophysical studies in humans indicate that expected stimuli are more easily detected, most work studying physiological auditory processing in animals highlights the detection of unexpected, surprising stimuli. Here, we tested whether in the mouse, high target probability results in enhanced detectability or whether detection is biased towards low-probability deviants using an auditory detection task. We implemented a probabilistic choice model to investigate whether a possible dependence on stimulus statistics arises from short-term serial correlations or from integration over longer periods. Our results demonstrate that target detectability in mice decreases with increasing probability, contrary to humans. We suggest that mice indeed track probability over a timescale of at least several minutes but do not use this information in the same way as humans do: instead of maximizing reward by focusing on high-probability targets, the saliency of a target is determined by surprise.
Disentangling the mechanisms underpinning disturbance-mediated invasion
Authors: Lear Luke , Hesse Elze , Shea Katriona , Buckling Angus
Published: January 2020

Disturbances can play a major role in biological invasions: by destroying biomass, they alter habitat and resource abundances. Previous field studies suggest that disturbance-mediated invader success is a consequence of resource influxes, but the importance of other potential covarying causes, notably the opening up of habitats, have yet to be directly tested. Using experimental populations of the bacteriumPseudomonas fluorescens, we determined the relative importance of disturbance-mediated habitat opening and resource influxes, plus any interaction between them, for invader success of two ecologically distinct morphotypes. Resource addition increased invasibility, while habitat opening had little impact and did not interact with resource addition. Both invaders behaved similarly, despite occupying different ecological niches in the microcosms. Treatment also affected the composition of the resident population, which further affected invader success. Our results provide experimental support for the observation that resource input is a key mechanism through which disturbance increases invasibility.
Methylobacterium crusticola sp. nov., isolated from biological soil crusts
Authors: Jia Li juan , Zhang Kai shuai , Tang Kai , Meng Jian yu , Zheng Chao , Feng Fu ying
Published: January 2020

A pink-pigmented, Gram-negative, rod-shaped, obligate aerobic bacterial strain, MIMD6T, was isolated from biological soil crusts in PR China. Cells grew at 20–37 °C (optimum, 30 °C), at pH 6–8 (optimum, pH 7) and with 0–1 % (w/v) NaCl (optimum, 0 %). Strain MIMD6T could use methanol or formate as a sole carbon source to grow, and carried methanol dehydrogenase genes mxaF and xoxF, supporting its methylotrophic metabolism. The respiratory quinone was ubiquinone Q-10, the major fatty acids were C18 : 1ω7c (87.3 %), and the major polar lipids were diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unknown aminolipid and one unidentified glycolipid. The results of phylogenetic analyses based on the sequences of the 16S rRNA gene, seven housekeeping genes (dnaK, recA, rimO, rpIK, rpmG, rpsR and rpoB) and methanol dehydrogenase genes indicated that strain MIMD6T formed a phylogenetic linage with members of the genus

Methylobacterium

. Strain MIMD6T was most closely related to

Methylobacterium isbiliense

DSM 17168T and

Methylobacterium nodulans

LMG 21967T with 16S rRNA gene sequence similarities of 95.7 and 95.2 %, respectively. The genomic DNA G+C content calculated via draft genome sequencing was 73.0 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain MIMD6T and the type strains of other

Methylobacterium

species were 70.7–82.0 and 24.6–30.0 %, respectively. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain MIMD6T represents a novel species of the genus

Methylobacterium

, for which the name Methylobacterium crusticola sp. nov. is proposed. The type strain is MIMD6T (=KCTC 52305T=MCCC 1K01311T).
Artificial Intelligence Assisted Early Warning System for Acute Kidney Injury Driven by Multi-Center ICU Database
Authors: Huang Sai , Chen Li , Wang Lili , Cui Xiang , Feng Cong , Zhang Zhengbo , Li Tanshi
Published: January 2020

Background

To improve the performance of early acute kidney injury (AKI) prediction in intensive care unit (ICU), we developed and externally validated machine learning algorithms in two large ICU databases.

Methods

Using eICU® Collaborative Research Database (eICU) and MIMIC-III databases, we selected all adult patients (age ≥ 18). The detection of AKI was based on both the oliguric and serum creatinine criteria of the KDIGO (Kidney Disease Improving Global Outcomes). We developed an early warning system for forecasting the onset of AKI within the first week of ICU stay, by using 6- or 12-hours as the data extraction window and make a prediction within a 1-hour window after a gap window of 6- or 12-hours. We used 52 features which are routinely available ICU data as predictors. eICU was used for model development, and MIMIC-III was used for externally validation. We applied and experimented on eight machine learning algorithms for the prediction task.

Results

3,816 unique admissions in multi-center eICU database were selected for model development, and 5,975 unique admissions in single-center MIMIC-III database were selected for external validation. The incidence of AKI within the first week of ICU stay in eICU and MIMIC-III cohorts was 52.1% (n=1,988) and 31.3% (n=1,870), respectively. In eICU cohort, the performance of AKI prediction is better with shorter extraction window and gap window. We found that the AdaBoost algorithm yielded the highest AUC (0.8859) on the model with 6-hours data extraction window and 6-hours gap window (model 6-6) rather than other prediction models. In MIMIC-III cohort, AdaBoost also performed well.

Conclusions

We developed the machine learning-based early AKI prediction model, which considered clinical important features and has been validated in two datasets.
MAPK-induced miR-29 targets MAFG and suppresses melanoma development
Authors: Vera Olga , Bok Ilah , Jasani Neel , Nakamura Koji , Xu Xiaonan , Mecozzi Nicol , Angarita Ariana , Wang Kaizhen , Tsai Kenneth Y. , Karreth Florian A.
Published: January 2020

The tumor suppressive miR-29 family of microRNAs is encoded by two clusters, miR-29b1∼a and miR-29b2∼c, and is regulated by several oncogenic and tumor suppressive stimuli. Here we investigated whether oncogenic MAPK hyperactivation regulates miR-29 abundance and how this signaling axis impacts melanoma development. Using mouse embryonic fibroblasts and human melanocytes, we found that oncogenic MAPK signaling stimulates p53-independent and p53-dependent transcription of pri-miR-29b1∼a and pri-miR-29b2∼c, respectively. Expression analyses revealed that while pri-miR-29a∼bl remains elevated, pri-miR-29b2∼c levels decrease during melanoma progression. Using a rapid mouse modeling platform, we showed that inactivation of miR-29 in vivo accelerates melanoma development and decreases overall survival. We identified the transcription factor MAFG as abona fidemiR-29 target that has oncogenic potential in melanocytes and is required for growth of melanoma cells. Our findings suggest that MAPK-induced miR-29 contributes to a tumor suppressive barrier by targeting MAFG, which is overcome by attenuation of miR-29b2∼c expression.
The increase in paraoxonase-1 is associated with a decrease in left ventricular volume in kidney transplant recipients
Authors: Connelly Philip W. , Yan Andrew T. , Nash Michelle M. , Wald Rachel , Lok Charmaine , Gunaratnam Lakshman , Kirpalani Anish , Prasad G.V. Ramesh
Published: January 2020

Background

Patients on dialysis have impaired cardiac function, in part due to increased fluid volume and ventricular stress. Restored kidney function through transplantation reduces left ventricular volume in both systole and diastole. Paraoxonase 1 (PON1) is reduced in patients on dialysis, which may be related to their impaired cardiac function. We tested the hypothesis that change in PON1 is associated with changes in left ventricular (LV) end-volume and LV mass after kidney transplantation.

Methods

Patients were studied before and 12 months after kidney transplantation. The control group was patients on dialysis not expected to receive a transplant in the next 12 months. Cardiac magnetic resonance imaging was used to measure LV end-diastolic and end-systolic volume and LV mass. PON1 was measured by arylesterase activity and by mass.

Results

PON1 mass and activity were not different between the groups at baseline. Both PON1 mass and activity were increased post-kidney transplantation (p<0.0001 for change). The change in PON1 mass (p=0.0062) and PON1 arylesterase activity (p=0.0254) were inversely correlated with the change in NT-proBNP for patients receiving a kidney transplant. However, only the change in the PON1 mass, but not the change in PON1 arylesterase, was inversely correlated with the change in left ventricular volume (ml/m2.7) (p=0.0146 and 0.0114 for diastolic and systolic, respectively) and with the change in hemoglobin (p=0.0042).

Conclusions

PON1 mass and activity increase after kidney transplantation. The increase in PON1 mass is consistent with a novel relationship to the increase in hemoglobin and the decrease in LV end-systolic and end-diastolic volume.