bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaginal Birth After Previous Cesarean Birth: A Comparison of 3 National Guidelines
Authors: Tsakiridis Ioannis , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: October 2018

Importance

Vaginal birth after previous cesarean birth (VBAC) is a reasonable option for many women with previous cesarean delivery.

Objective

The aim of this study was to summarize evidence and compare recommendations from national guidelines regarding VBAC.

Evidence Acquisition

A descriptive review of 3 national guidelines on VBAC was conducted: Royal College of Obstetricians and Gynaecologists on “Birth After Previous Caesarean Birth,” American College of Obstetricians and Gynecologists on “Vaginal Birth After Cesarean Delivery,” and Society of Obstetricians and Gynaecologists of Canada on “Guidelines for Vaginal Birth After Previous Caesarean Birth.” These guidelines were summarized and compared in terms of the recommended antenatal and intrapartum care of women. Recommendations and strength of evidence were also reviewed based on method of reporting.

Results

The variations mentioned on the different guidelines reflect the heterogeneity of the published data on the management of VBAC during the antenatal and intrapartum care.

Conclusions

Evidence-based medicine could support the conception of international recommendations for VBAC, which may improve both safety and efficacy of this procedure.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to (1) examine all the aspects of vaginal birth after cesarean birth: indications and contradictions; (2) summarize antenatal care recommendations in cases of vaginal birth after cesarean delivery; and (3) propose the necessary intrapartum care in cases of vaginal birth after cesarean birth.
Case Report: Importance of B-scan Ultrasonography for the Detection of Choroidal Melanoma
Authors: Wilczek Margaret A. , Gold Aaron S. , Ehlies Fiona J. , Murray Timothy G.
Published: October 2018

SIGNIFICANCE

This case highlights the importance of using ultrasonography to evaluate an eye that has no clear view of the fundus.

PURPOSE

Uveal melanoma stems from melanocytes found in the iris, ciliary body, and choroid, and it is the most common primary intraocular malignancy found in adults. The lesion is identified predominantly via fundus biomicroscopy and binocular indirect ophthalmoscopy. The authors present a unique case where visual evaluation of the fundus was not possible, and ultrasonography was used to assess the retina and choroid.

CASE REPORT

A 38-year-old Hispanic man with prior ocular trauma presented with an eye that could not be clinically examined owing to complete pupil occlusion. The diagnosis of presumed uveal melanoma was made exclusively based on the outcome of ocular ultrasonography. Further histologic, antibody, and genetic testing was completed once the patient had undergone treatment of the affected eye and uveal melanoma was confirmed.

CONCLUSIONS

In this rare instance, B-scan ultrasonography provided a finding that required the patient to undergo enucleation in an eye without visual potential. Genetic testing was then used to appropriately categorize the tumor as a class 1B melanoma, indicating that there is a risk of metastasis. Consequently, the patient is being monitored by a medical oncologist.
Factors Associated With First Medication Time for Children Treated in the Emergency Department for Asthma
Authors: Jang Hoon , Ozkaynak Mustafa , Ayer Turgay , Sills Marion R.
Published: October 2018

Objectives

Acute asthma exacerbations are among the most common reasons for childhood emergency department (ED) visits and hospitalizations. Although early ED administration of asthma medication has been shown to decrease hospitalizations, studies of factors associated with early ED asthma medication delivery have been limited. The objective of our study was to identify patient- and ED-related factors associated with early medication delivery among children treated in the ED for asthma exacerbations.

Methods

This retrospective study used electronic health record data from all encounters for a primary diagnosis of asthma in an academic children's hospital ED during the study period 2009 to 2013. Using multivariate logistic regression, we identified the association between patient- and ED-related factors and the time to first medication defined as a binary outcome using a threshold of 1 hour from ED arrival. We then stratified our analysis by triage level (Emergency Severity Index [ESI]).

Results

Of the 4846 encounters during the study period, 62% were male, mean age was 7.30 years, 76% had public insurance, and 57% had an ESI level of 3. Medication was administered within 1 hour of arrival in 2236 encounters (46%). After adjusting for covariates, multivariate logistic regression revealed that patients were less likely to have medications within 1 hour when they had less severe ESI (ESI 2 vs ESI 4: odds ratio [OR], 0.139; confidence interval [CI], 0.114–0.170), arrived via non–emergency medical services (OR, 0.525; CI, 0.413–0.665), or arrived to a crowded ED (OR, 0.574; CI, 0.505–0.652). Age, sex, and insurance type were not associated with timeliness of initial medication administration. Stratified analyses demonstrated that the crowding effect was larger for less severely ill patients.

Conclusions

Our study found that patient severity (acuity level, arrival mode) and level of ED crowing—but not demographic factors—are associated with the administration of medication in the first hour to pediatric patients with asthma. Our findings may be helpful in redesigning asthma care management strategies.
Biased Competition Favoring Physical Over Emotional Pain: A Possible Explanation for the Link Between Early Adversity and Chronic Pain
Authors: Lane Richard D. , Anderson Frances Sommer , Smith Ryan
Published: October 2018

Background

Early adversity predisposes to chronic pain, but a mechanistic explanation is lacking. Survivors of early adversity with chronic pain often seem impaired in their ability to be aware of, understand, and express distressing emotions such as anger and fear in social contexts. In this context, it has been proposed that pain may at times serve as a “psychic regulator” by preventing awareness of more intolerable emotions.

Method

This narrative review builds on the premise that physical pain and emotional pain are conscious experiences that can compete for selective attention. We highlight mechanisms whereby the consequences of early adversity may put emotional pain at a competitive disadvantage. A case history, supportive research findings, and an evidence-based neurobiological model are presented.

Results

Arising from abuse or neglect in childhood, impairments in the adult capacity to attend to and/or conceptualize the emotional meaning of felt distress may be associated with impaired engagement of the default network and impaired top-down modulation of affective response generation processes. Persistent and poorly conceptualized affective distress may be associated with reduced emotion regulation ability, reduced vagal tone, increased inflammation, and amplified nociceptive signals. Attention to physical pain may be reinforced by the temporary reduction in negative emotions that it causes.

Conclusions

These processes jointly promote biased competition favoring attention to physical pain and away from one's own emotions. They may constitute an unintentional analog of the phenomenon of self-injury in patients with borderline personality disorder in whom the intentional infliction of physical pain serves to downregulate intense emotional distress. Attending to, expressing, and understanding previously unacknowledged psychological distress unrelated to pain may facilitate recovery from chronic pain after early adversity. Mechanistic studies that can validate this clinically derived neurobiological hypothesis are urgently needed.
Resilience From a Stakeholder Perspective: The Role of Next of Kin in Cancer Care
Authors: Bergerød Inger Johanne , Braut Geir S. , Wiig Siri
Published: October 2018

Objective

The aim of this article was to provide new knowledge on how next of kin are co-creators of resilient performance, as seen from the viewpoint of the healthcare personnel and managers. The following research question guided the study: How are next of kin involved in shaping resilience within cancer care in hospitals?

Methods

The design of the study is a case study of cancer departments in two Norwegian hospitals. Data collection included a total of 32 qualitative semistructured interviews at two organizational levels (managers and staff). The data were analyzed by ways of a directed content analysis according to Hollnagel's Resilience in Health Care framework of resilience potentials (anticipate, monitor, respond, learn).

Results

Next of kin are involved in creating and maintaining resilience in cancer care by different kind of activities and in-depth insight into the patient's condition, which strengthen all resilience potentials of responding, anticipation, monitoring, and learning. We have identified nine areas in which next of kin are co-creators in shaping resilience. Next of kin are important stakeholders, both as safety experts and as safety resources, helping healthcare professionals provide quality and safety in the patient care process under difficult conditions. Next of kin's knowledge of the patient's history, their observation of the patient over time within the hospital, at home, and across care transitions are key elements of their contribution.

Conclusions

Next of kin complement healthcare professionals in all four potentials for resilient performance. The study suggests that the Resilience in Health Care framework takes into account the role of next of kin, as a stakeholder potential, because this has not previously been sufficiently considered.
Targeting Fallible Men: Communication Strategies and Moral Issues in a Pre-exposure Prophylaxis Trial
Authors: Trachman Mathieu , Girard Gabriel
Published: October 2018

Based on the analysis of a French pre-exposure prophylaxis trial (Ipergay), and focusing on the communication strategies used to recruit volunteers, this article explores the figure who serves to justify the trial and who shapes the way in which populations concerned by this prevention tool are targeted. We show that this figure is that of the fallible man, a classic in moral philosophy: while aware of what is good or right for him, he is unable to put this knowledge into practice. The targeting of fallible men makes sense in the context of a resurgence of high-risk behaviors objectified in the late 1990s: qualifying gays who take risks as fallible individuals create a distance with respect to the “barebacker” who risks his life deliberately and has no intention of changing his behavior. Recognizing that certain gays are vulnerable to risk also provides justification for a preventive strategy that acknowledges the inadequacy of behavioral prevention, without giving up on prevention altogether. All in all, this analysis shows that the technological and epidemiological realism often highlighted in pre-exposure prophylaxis interventions is not without a moral dimension, attentive to individuals' contradictions and singularities, doubts and uncertainties, and to the risk of stigmatization inherent to the acknowledgement of risk-taking.
Being “False Positive”: An “Inconvenience”? Debates and Questions Regarding the Notion of Vaccine-Induced Seropositivity (VISP) in the Recruitment of Healthy Volunteers for a Preventive Anti-HIV Vaccine Trial
Authors: Couderc Mathilde
Published: October 2018

This article considers a stage in the clinical trial process seldom documented in social sciences: recruitment of healthy volunteers for an HIV preventive vaccine trial through a media campaign. It analyzes one of the consequences of participating in such a clinical trial: the development of vaccine-induced seropositivity (VISP) and how this biomedical notion is mobilized both in recruitment procedures' normative discourses and from the volunteers' points of view, and its consequences on their decision to participate. The interpretations of VISP by volunteers depend on several factors: socialization, itinerary into the recruitment procedure, sexuality, etc., and generates diverse feelings such as indifference, doubt, or even fear. Fear of VISP represents the principal refusal reason for those who interrupted their participating step, just before inclusion stage. Addressing VISP phenomenon is important because it represents a major challenge for the information and the communication procedures for the next anti-HIV prophylactic trials recruitment campaigns.
Current Update on Desmoid Fibromatosis
Authors: Ganeshan Dhakshinamoorthy , Amini Behrang , Nikolaidis Paul , Assing Matthew , Vikram Raghunandan
Published: October 2018

Objective

The purpose of this article is to review the etiopathogenesis, molecular cytogenetics, histopathology, clinical features, and multimodality imaging features of desmoid fibromatosis. Recent advances in the management of desmoid fibromatosis will also be discussed.

Conclusions

Desmoid fibromatosis is a rare soft tissue neoplasm with a high incidence of local recurrence. Imaging plays an important role in the diagnosis and management of this disease.
Accuracy of Quantification of Iodine and Hounsfield Unit Values on Virtual Monochromatic Imaging Using Dual-Energy Computed Tomography: Comparison of Dual-Layer Computed Tomography With Fast Kilovolt-Switching Computed Tomography
Authors: Washio Hayate , Ohira Shingo , Karino Tsukasa , Nitta Yuya , Hayashi Masaaki , Miyazaki Masayoshi , Teshima Teruki
Published: October 2018

Objective

The aim of the study was to compare the accuracy of quantification of iodine and Hounsfield unit (HU) values on virtual monochromatic imaging (VMI) using dual-layer computed tomography (DLCT) and fast kilovolt-switching computed tomography (FKSCT).

Materials and Methods

This study was performed in 2 phantoms (large and small) using 16 rods representing different materials (iodine, calcium, blood, and adipose tissue) with different dimensions and concentrations. The absolute percentage errors (absolute ratio of measurement error to true iodine concentration) for iodine concentration and HU value on VMI at 50, 70, and 100 keV were compared between DLCT and FKSCT. The Mann–Whitney U test was used to assess statistical significance.

Results

Overall, the absolute percentage errors for iodine concentration and HU value on VMI were smaller for DLCT than for FKSCT.

Conclusions

Overall, the accuracy of iodine and HU values was higher for DLCT than for FKSCT.
Prevalence and Natural History of Coronary Ostial Aneurysms in Marfan Patients
Authors: Haroun Reham R. , Chu Linda C. , Fishman Elliot K.
Published: October 2018

Objective

The aim of this study was to determine the prevalence and natural history of coronary ostial aneurysms in Marfan patients with aortic root replacement.

Methods

Thirty-one Marfan patients (mean age, 33.7 ± 11.8 years) who underwent aortic root replacement and postoperative electrocardiogram-gated computed tomographic (CT) angiograms between January 2007 and December 2015 were retrospectively identified. A subset of 15 patients underwent follow-up CT angiograms. Computed tomographic angiograms were postprocessed on 3-dimensional software to measure maximal coronary ostial diameter. Coronary ostial aneurysm was defined as diameter of greater than 10 mm.

Results

Right coronary ostial aneurysms were present in 45.2% (14/31) of patients, and left main coronary ostial aneurysms were present in 51.6% (16/31) of patients. Mean ostial diameter was 10.1 ± 1.9 mm for the right coronary artery and 10.0 ± 1.8 mm for the left coronary artery. In a subset of patients with follow-up CT angiograms, there was no significant change in coronary ostial diameter on follow-up examinations (P > 0.05).

Conclusions

Coronary ostial aneurysms were common in Marfan patients after aortic root replacement. These findings remain stable over time and may have little clinical consequence.
The Added Value of Computer-aided Detection of Small Pulmonary Nodules and Missed Lung Cancers
Authors: Cai Jiali , Xu Dongming , Liu Shiyuan , Cham Matthew D.
Published: October 2018

Lung cancer at its earliest stage is typically manifested on computed tomography as a pulmonary nodule, which could be detected by low-dose multidetector computed tomography technology and the use of thinner collimation. Within the last 2 decades, computer-aided detection (CAD) of pulmonary nodules has been developed to meet the increasing demand for lung cancer screening computed tomography with a larger set of images per scan. This review introduced the basic techniques and then summarized the up-to-date applications of CAD systems in clinical and research programs and in the low-dose lung cancer screening trials, especially in the detection of small pulmonary nodules and missed lung cancers. Many studies have already shown that the CAD systems could increase the sensitivity and reduce the false-positive rate in the diagnosis of pulmonary nodules, especially for the small and isolated nodules. Further improvements to the current CAD schemes are needed to detect nodules accurately, particularly for subsolid nodules.
Myocardial Electrical Remodeling and the Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart: Anti-Arrhythmogenic Effect of Liposome-Encapsulated Hemoglobin (HbV) on the Myocardium
Authors: Takase Bonpei , Higashimura Yuko , Hashimoto Kenichi , Asahina Haruka , Ishihara Masayuki , Sakai Hiromi
Published: October 2018

Introduction:

Prolonged low blood pressure <40 mmHg in hemorrhagic shock (HS) causes irreversible heart dysfunction, ‘Shock Heart Syndrome’ (SHS), which is associated with lethal arrhythmias (ventricular tachycardia or ventricular fibrillation [VT/VF]) leading to a poor prognosis.

Methods:

To investigate whether the liposome-encapsulated human hemoglobin oxygen carrier (HbV) is comparable in effectiveness to autologous washed red blood cells (wRBCs) for improving arrhythmogenic properties in SHS, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed in Sprague-Dawley rat hearts obtained from rats subjected to acute HS by withdrawing 30% of total blood volume. After acute HS, the rats were immediately resuscitated by transfusing exactly the same amount of saline (SAL), 5% albumin (5% ALB), HbV, or wRBCs. After excising the heart, OMP and EPS were performed in Langendorff-perfused hearts.

Results:

OMP showed a tendency for abnormal conduction and significantly impaired action potential duration dispersion (APDd) in both ventricles with SAL and 5% ALB. In contrast, myocardial conduction and APDd were substantially preserved with HbV and wRBCs. Sustained VT/VF was easily provoked by a burst pacing stimulus to the left ventricle with SAL and 5% ALB. No VT/VF was induced with HbV and wRBCs. Pathology showed myocardial structural damage characterized by worse myocardial cell damage and Connexin43 with SAL and 5% ALB, whereas it was attenuated with HbV and wRBCs.

Conclusions:

Ventricular structural remodeling after HS causes VT/VF in the presence of APDd. Transfusion of HbV prevents VT/VF, similarly to transfusion of wRBCs, by preventing electrical remodeling and preserving myocardial structures in HS-induced SHS.
Late Peaks of HMGB1 and Sepsis Outcome: Evidence For Synergy With Chronic Inflammatory Disorders
Authors: Karakike Eleni , Adami Maria-Evangelia , Lada Malvina , Gkavogianni Theologia , Koutelidakis Ioannis M. , Bauer Michael , Giamarellos-Bourboulis Evangelos J. , Tsangaris Iraklis
Published: October 2018

High mobility group box 1 (HMGB1) is released from macrophages as a late biomarker of sepsis. Conditions associated with pre-existing macrophage activation may modify HMGB1 expression. This study aimed to assess the impact of HMGB1 kinetics on 28-day mortality. In a sub-study of a previous randomized clinical trial among patients with systemic inflammatory response syndrome and gram-negative infections, patients were classified in early and late HMGB1 peak groups. Serial measurements of HMGB1, ferritin and interferon-gamma (IFNγ) were performed in all available sera. Two hundred ten patients were included; 118 (46.5%) had at least one inflammatory disease (diabetes, chronic obstructive pulmonary disease, chronic heart failure, or chronic renal disease). Mortality after 28 days was higher among patients with a late peak of HMGB1 (OR 2.640; P = 0.026). Co-existence of late peak and inflammatory disease synergistically impacted mortality (odds ratio of logistic regression analysis 3.17; P: 0.027). Late peak was concomitantly associated with higher values of ferritin (P = 0.035), and IFNγ (P = 0.002) among patients with hyperferritinemia. It is concluded that late HMGB1 peak was associated with worse prognosis, especially in patients with underlying chronic inflammatory conditions.
Intracellular RNA-tracking methods
Authors: George Logan , Indig Fred E. , Abdelmohsen Kotb , Gorospe Myriam
Published: October 2018

RNA tracking allows researchers to visualize RNA molecules in cells and tissues, providing important spatio-temporal information regarding RNA dynamics and function. Methods such as fluorescentin situhybridization (FISH) and molecular beacons rely on complementary oligonucleotides to label and view endogenous transcripts. Other methods create artificial chimeric transcripts coupled with bacteriophage-derived coat proteins (e.g. MS2, λN) to tag molecules in live cells. In other approaches, endogenous RNAs are recognized by complementary RNAs complexed with noncatalytic Cas proteins. Each technique has its own set of strengths and limitations that must be considered when planning an experiment. Here, we discuss the mechanisms, advantages, and weaknesses ofin situhybridization, molecular beacons, MS2 tagging and Cas-derived systems, as well as how RNA tracking can be employed to study various aspects of molecular biology.
The time geography of segregation during working hours
Authors: Dannemann Teodoro , Sotomayor-Gómez Boris , Samaniego Horacio
Published: October 2018

While segregation is usually evaluated at the residential level, the recent influx of large streams of data describing urbanites’ movement across the city allows to generate detailed descriptions of spatio-temporal segregation patterns across the activity space of individuals. For instance, segregation across the activity space is usually thought to be lower compared with residential segregation given the importance of social complementarity, among other factors, shaping the economies of cities. However, these new dynamic approaches to segregation convey important methodological challenges. This paper proposes a methodological framework to investigate segregation during working hours. Our approach combines three well-known mathematical tools: community detection algorithms, segregation metrics and random walk analysis. Using Santiago (Chile) as our model system, we build a detailed home–work commuting network from a large dataset of mobile phone pings and spatially partition the city into several communities. We then evaluate the probability that two persons at their work location will come from the same community. Finally, a randomization analysis of commuting distances and angles corroborates the strong segregation description for Santiago provided by the sociological literature. While our findings highlights the benefit of developing new approaches to understand dynamic processes in the urban environment, unveiling counterintuitive patterns such as segregation at our workplace also shows a specific example in which the exposure dimension of segregation is successfully studied using the growingly available streams of highly detailed anonymized mobile phone registries.
Metabolism studies of paeoniflorin in rat liver microsomes by ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)
Authors: Zhu L. J. , Sun S. S. , Hu Y. X. , Liu Y. F.
Published: October 2018

To explore metabolism mechanism of paeoniflorin in the liver and further understand intact metabolism process of paeoniflorin, a rapid, convenient and effective assay is described using ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). The strategy was confirmed in the following primary processes: firstly, different concentration of paeoniflorin, rat liver microsomes, coenzymes and different incubated conditions were optimized to build a biotransformation model of rat liver microsomes
in vitro
by high performance liquid chromatography with diode array detection (HPLC-DAD); secondly, the metabolites of paeoniflorin in rat liver microsomes were detected and screened using UPLC-Q-TOF-MS/MS by comparing the total ion chromatogram (TIC) of the experimental group with those of control groups; finally, the molecular formulae and corresponding chemical structures of paeoniflorin metabolites were identified by comparing the MS and MS/MS spectra with the self-constructed database and simulation software. Based on this analytical strategy, 20 metabolites of paeoniflorin were found and 6 metabolites (including four new compounds) were tentatively identified. It was shown that hydrolysis and oxidation were the major metabolic pathways of paeoniflorin in rat liver microsomes, and the main metabolic sites were the structures of pinane and the ester bond. These findings were significant for a better understanding of the metabolism of paeoniflorin in rat liver microsomes and the proposed metabolic pathways of paeoniflorin might provide fundamental support for the further research in the pharmacological mechanism of Paeoniae Radix Rubra (PRR).
Fluorine-doped graphene with an outstanding electrocatalytic performance for efficient oxygen reduction reaction in alkaline solution
Authors: Guo Jiahao , Zhang Jianguo , Zhao Hanqing , Fang Yongshuang , Ming Kun , Huang Hao , Chen Junming , Wang Xuchun
Published: October 2018

Doping carbon materials have proved to be the front runners to substitute for Pt as oxygen reduction reaction (ORR) catalysts. Fluorine-doped graphene (FG) has rarely been used as ORR catalyst because of the difficulty in preparation. Herein, we report FG sheets prepared by a thermal pyrolysis graphene oxide (GO) process in the presence of zinc fluoride (ZnF
2
) as an efficient electrocatalyst for ORR in the alkaline medium. The results show that the pyrolysis temperature seriously affected the doped fluoride amount and morphology of catalyst. It is found that the FG-1100 catalyst possesses a more positive onset potential, higher current density and better four-electron process for ORR than other FG samples. FG-1100 displays an outstanding ORR catalytic activity that is comparable to that of the commercial Pt/C catalyst. Also, its durability and methanol tolerance ability are superior to those of the commercial Pt/C. The excellent ORR catalytic performance is closely related to its higher doped fluorine amount and wrinkle morphology. The FG catalyst can be developed as a low-cost, efficient and durable catalyst as a viable replacement for the Pt/C catalyst, promoting the commercialization of fuel cells.
Preparation and properties of hydrochars from macadamia nut shell via hydrothermal carbonization
Authors: Fan Fangyu , Yang Zongling , Li Han , Shi Zhengjun , Kan Huan
Published: October 2018

Macadamia nut shell (MNS) is a type of waste lignocellulose obtained from macadamia nut production processing. Large MNS wastes caused serious resource waste and environmental pollution. So, preparation of hydrochars from MNS via hydrothermal carbonization (HTC) is of great significance. HTC of MNS was conducted to study the effect of process parameters, including HTC temperature (180–260°C) and residence time (60–180 min) on the properties of hydrochars. Results showed that the increase in HTC temperature and residence time decreased the mass yield of hydrochars and increased the high heating value of hydrochars. Furthermore, the C content of hydrochars increased, whereas the H and O contents decreased. Mass yield of hydrochar is 46.59%, energy yield is 64.55% and the higher heating value is 26.02 MJ kg
−1
at a temperature of 260°C and time of 120 min. The surface structure of hydrochars was rougher compared with that of MNS as observed via scanning electron microscopy. The chemical and combustion behaviour of MNS and hydrochars was analysed by Fourier transform infrared spectroscopy, and thermogravimetric analysis indicated that decarboxylation and dehydration reactions were the predominant pathways during the HTC process. Results showed that HTC can facilitate the transformation of MNS into solid fuel.
Proton tunnelling in hydrogen bonds and its implications in an induced-fit model of enzyme catalysis
Authors: Pusuluk Onur , Farrow Tristan , Deliduman Cemsinan , Burnett Keith , Vedral Vlatko
Published: October 2018

The role of proton tunnelling in biological catalysis is investigated here within the frameworks of quantum information theory and thermodynamics. We consider the quantum correlations generated through two hydrogen bonds between a substrate and a prototypical enzyme that first catalyses the tautomerization of the substrate to move on to a subsequent catalysis, and discuss how the enzyme can derive its catalytic potency from these correlations. In particular, we show that classical changes induced in the binding site of the enzyme spreads the quantum correlations among all of the four hydrogen-bonded atoms thanks to the directionality of hydrogen bonds. If the enzyme rapidly returns to its initial state after the binding stage, the substrate ends in a new transition state corresponding to a quantum superposition. Open quantum system dynamics can then naturally drive the reaction in the forward direction from the major tautomeric form to the minor tautomeric form without needing any additional catalytic activity. We find that in this scenario the enzyme lowers the activation energy so much that there is no energy barrier left in the tautomerization, even if the quantum correlations quickly decay.
A Hamiltonian mean field system for the Navier–Stokes equation
Authors: Hochgerner Simon
Published: October 2018

We use a Hamiltonian interacting particle system to derive a stochastic mean field system whose McKean–Vlasov equation yields the incompressible Navier–Stokes equation. Since the system is Hamiltonian, the particle relabeling symmetry implies a Kelvin Circulation Theorem along stochastic Lagrangian paths. Moreover, issues of energy dissipation are discussed and the model is connected to other approaches in the literature.
Molecular archaeoparasitology identifies cultural changes in the Medieval Hanseatic trading centre of Lübeck
Authors: Flammer Patrik G. , Dellicour Simon , Preston Stephen G. , Rieger Dirk , Warren Sylvia , Tan Cedric K. W. , Nicholson Rebecca , Přichystalová Renáta , Bleicher Niels , Wahl Joachim , Faria Nuno R. , Pybus Oliver G. , Pollard Mark , Smith Adrian L.
Published: October 2018

Throughout history, humans have been afflicted by parasitic worms, and eggs are readily detected in archaeological deposits. This study integrated parasitological and ancient DNA methods with a large sample set dating between Neolithic and Early Modern periods to explore the utility of molecular archaeoparasitology as a new approach to study the past. Molecular analyses provided unequivocal species-level parasite identification and revealed location-specific epidemiological signatures. Faecal–oral transmitted nematodes (
Ascaris lumbricoides
and
Trichuris trichiura
) were ubiquitous across time and space. By contrast, high numbers of food-associated cestodes (
Diphyllobothrium latum
and
Taenia saginata
) were restricted to medieval Lübeck. The presence of these cestodes and changes in their prevalence at approximately 1300 CE indicate substantial alterations in diet or parasite availability.
Trichuris trichiura
ITS-1 sequences grouped into two clades; one ubiquitous and one restricted to medieval Lübeck and Bristol. The high sequence diversity of
T.t
.ITS-1 detected in Lübeck is consistent with its importance as a Hanseatic trading centre. Collectively, these results introduce molecular archaeoparasitology as an artefact-independent source of historical evidence.
Carrying a selfish genetic element predicts increased migration propensity in free-living wild house mice
Authors: Runge Jan-Niklas , Lindholm Anna K.
Published: October 2018

Life is built on cooperation between genes, which makes it vulnerable to parasitism. Selfish genetic elements that exploit this cooperation can achieve large fitness gains by increasing their transmission relative to the rest of the genome. This leads to counter-adaptations that generate unique selection pressures on the selfish genetic element. This arms race is similar to host–parasite coevolution, as some multi-host parasites alter the host’s behaviour to increase the chance of transmission to the next host. Here, we ask if, similarly to these parasites, a selfish genetic element in house mice, thethaplotype, also manipulates host behaviour, specifically the host’s migration propensity. Variants of thetthat manipulate migration propensity could increase in fitness in a meta-population. We show that juvenile mice carrying thethaplotype were more likely to emigrate from and were more often found as migrants within a long-term free-living house mouse population. This result may have applied relevance as thethas been proposed as a basis for artificial gene drive systems for use in population control.
Delayed trait development and the convergent evolution of shell kinesis in turtles
Authors: Cordero Gerardo A. , Quinteros Kevin , Janzen Fredric J.
Published: October 2018

Understanding developmental processes is foundational to clarifying the mechanisms by which convergent evolution occurs. Here, we show how a key convergently evolving trait is slowly ‘acquired’ in growing turtles. Many functionally relevant traits emerge late in turtle ontogeny, owing to design constraints imposed by the shell. We investigated this trend by examining derived patterns of shell formation associated with the multiple (at least 8) origins of shell kinesis in small-bodied turtles. Using box turtles as a model, we demonstrate that the flexible hinge joint required for shell kinesis differentiates gradually and via extensive repatterning of shell tissue. Disproportionate changes in shell shape and size substantiate that this transformation is a delayed ontogenetic response (3–5 years post-hatching) to structural alterations that arise in embryogenesis. These findings exemplify that the translation of genotype to phenotype may reach far beyond embryonic life stages. Thus, the temporal scope for developmental origins of adaptive morphological change might be broader than generally understood. We propose that delayed trait differentiation via tissue repatterning might facilitate phenotypic diversification and innovation that otherwise would not arise due to developmental constraints.
Phototrophic co-cultures from extreme environments: community structure and potential value for fundamental and applied research
Authors: Shaw Claire , Brooke Charles , Hawley Erik , Connolly Morgan P. , Garcia Javier A. , Harmon-Smith Miranda , Shapiro Nicole , Barton Michael , Tringe Susannah G. , del Rio Tijana Glavina , Culley David E. , Castenholz Richard , Hess Matthias
Published: October 2018

Cyanobacteria are found in most illuminated environments and are key players in global carbon and nitrogen cycling. Although significant efforts have been made to advance our understanding of this important phylum, still little is known about how members of the cyanobacteria affect and respond to changes in complex biological systems. This lack of knowledge is in part due to our dependence on pure cultures when determining the metabolism and function of a microorganism. In the work presented here we took advantage of the Culture Collection of Microorganisms from Extreme Environments (CCMEE), a collection of more than 1,000 publicly available photosynthetic co-cultures now maintained at the Pacific Northwest National Laboratory. To highlight some of their scientific potential, we selected 26 of these photosynthetic co-cultures from the CCMEE for 16S rRNA gene sequencing. We assessed if samples readily available from the CCMEE could be used to generate new insights into the role of microbial communities in global and local carbon and nitrogen cycling. Results from this work support the existing notion that culture depositories in general hold the potential to advance fundamental and applied research. If collections of co-cultures can be used to infer roles of the individual organisms remains to be seen and requires further investigation.
Multiplexed biochemical imaging reveals caspase activation patterns underlying single cell fate
Authors: Fries Maximilian W. , Haas Kalina T. , Ber Suzan , Saganty John , Richardson Emma K. , Venkitaraman Ashok R. , Esposito Alessandro
Published: October 2018

The biochemical activities underlying cell-fate decisions vary profoundly even in genetically identical cells. But such non-genetic heterogeneity remains refractory to current imaging methods, because their capacity to monitor multiple biochemical activities in single living cells over time remains limited1. Here, we deploy a family of newly designed GFP-like sensors (NyxBits) with fast photon-counting electronics and bespoke analytics (NyxSense) in multiplexed biochemical imaging, to define a network determining the fate of single cells exposed to the DNA-damaging drug cisplatin. By simultaneously imaging a tri-nodal network comprising the cell-death proteases Caspase-2, -3 and -92, we reveal unrecognized single-cell heterogeneities in the dynamics and amplitude of caspase activation that signify survival versus cell death via necrosis or apoptosis. Non-genetic heterogeneity in the pattern of caspase activation recapitulates traits of therapy resistance previously ascribed solely to genetic causes3,4. Chemical inhibitors that alter these patterns can modulate in a predictable manner the phenotypic landscape of the cellular response to cisplatin. Thus, multiplexed biochemical imaging reveals cellular populations and biochemical states, invisible to other methods, underlying therapeutic responses to an anticancer drug. Our work develops widely applicable tools to monitor the dynamic activation of biochemical networks at single-cell resolution. It highlights the necessity to resolve patterns of network activation in single cells, rather than the average state of individual nodes, to define, and potentially control, mechanisms underlying cellular decisions in health and disease.
Alexidine dihydrochloride has broad spectrum a ctivities against diverse fungal pathogens
Authors: Mamouei Zeinab , Alqarihi Abdullah , Singh Shakti , Xu Shuying , Mansour Michael K. , Ibrahim Ashraf S , Uppuluri Priya
Published: October 2018

Invasive fungal infections due to Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, constitute a substantial threat to hospitalized, immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices, and emergence of drug-resistant fungi such as Candida auris, introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms which increases the chance of infection relapses. Here, we screened a small molecule Prestwick Chemical Library, consisting of 1200 FDA approved off-patent drugs, against C. albicans, C. auris and A. fumigatus, to identify those that inhibit growth of all three pathogens. Inhibitors were further prioritized for their potency against other fungal pathogens, and their ability to kill preformed biofilms. Our studies identified the bis-biguanide Alexidine dihydrochloride (AXD), as a drug with the highest antifungal and anti-biofilm activity against a diverse range of fungal pathogens. Finally, AXD significantly potentiated the efficacy of fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mice central venous catheters in vivo, highlighting its potential as a pan-antifungal drug.

Importance

The prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multi-drug resistant strains such as C. auris. High mortality related to fungal infections point to major limitations of current antifungal therapy, and an unmet need for new antifungal drugs. We screened a library of repurposed FDA approved inhibitors to identify compounds with activities against a diverse range of fungi, in varied phases of growth. The assays identified Alexidine dihydrochloride (AXD) to have pronounced antifungal activity including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro, and prevented biofilm growth in vivo. Thus AXD has the potential to be developed as a pan-antifungal, anti-biofilm drug.
Infiltration of CD8+ T cells into tumor-cell clusters in Triple Negative Breast Cancer
Authors: Li Xuefei , Gruosso Tina , Zuo Dongmei , Omeroglu Atilla , Meterissian Sarkis , Guiot Marie-Christine , Adam Salazar , Park Morag , Levine Herbert
Published: October 2018

Infiltration of CD8+ T lymphocytes into solid tumors is associated with good prognosis in various types of cancer, including Triple Negative Breast Cancers (TNBC). However, the mechanisms underlying different infiltration-levels are largely unknown. Here, we have characterized the spatial profile of CD8+ T cells around tumorcell clusters in the core and margin regions in TNBC. Combining mathematical modeling and data analysis, we propose that there exists a possible chemo-repellent inside tumor-cell clusters, which prevents CD8+ T cells from infiltrating into tumor-cell clusters. Furthermore, investigation into the properties of collagen fibers suggests that variations in desmoplastic elements does not limit infiltration of CD8+ T lymphocytes into tumor-cell clusters. This is consistent with the prediction of our mathematical modeling analysis whereby CD8+ T cells are predicted to infiltrate the fibrotic barrier and their infiltration into tumor clusters is governed by other mechanisms involving a local repellent.
Enhancing biochemical resolution by hyper-dimensional imaging microscopy
Authors: Esposito Alessandro , Venkitaraman Ashok R.
Published: October 2018

Two decades of high-paced innovation have improved the spatial resolution of fluorescence microscopy to enable molecular resolution combined with the low-invasiveness and specificity characteristic of optical microscopy. However, fluorescence microscopy also enables scientists and clinicians to map and quantitate the physico-chemical properties (e.g., analyte concentration, enzymatic activities and protein-protein interactions) of biological samples. But the optimization of the biochemical resolving power in fluorescence microscopy is not as well-developed compared to its spatial resolution. Typical techniques rely on the observation of individual properties of fluorescence thus limiting the opportunities for sensing and multiplexing. Aiming to overcome existing limitations, we demonstrate a new imaging paradigm — Hyper Dimensional Imaging Microscopy (HDIM) — that enables the orthogonal properties of fluorescence emission (excited state lifetime, polarization and spectra) in biological samples to be quantified simultaneously and efficiently. Therefore, akin to how multi-dimensional separation in mass-spectroscopy and multi-dimensional spectra in NMR impacted proteomics and structural biology, we envisage that HDIM spectra of unprecedented dimensionality will impact the fields of systems biology and medical diagnostics by maximizing the biochemical resolving power of fluorescence microscopy.
Checkpoint non-fidelity induces a complex landscape of lineage fitness after DNA damage
Authors: Campbell Callum J. , Venkitaraman Ashok R. , Esposito Alessandro
Published: October 2018

DNA damage in proliferating mammalian cells causes death1, senescence2 or continued survival, via checkpoints that monitor damage and regulate cell cycle progression, DNA repair and fate determination3. Cell cycle checkpoints facilitate tumour suppression by preventing the generation of proliferating mutated cells4, particularly by blocking passage of DNA lesions into replication and mitosis5. While checkpoint non-fidelity permits cells to carry genomic aberrations into subsequent cell cycle phases6, its long-term consequences on lineages descendant from damaged cells remains poorly characterised. Devising methods for microscopy-based lineage tracing, we unexpectedly demonstrate that transient DNA damage to single living cells bearing a negligent checkpoint induces heterogenous cell-fate outcomes in their descendant generations removed from the initial insult. After transiently damaged cells undergo an initial arrest, pairs of descendant cells without obvious cell-cycle abnormalities either divide or die in a seemingly stochastic way. Progeny of transiently damaged cells may die generations afterwards, creating considerable variability of lineage fitness that promotes overall persistence in a mutagenic environment. Descendants of damaged cells frequently form micronuclei, activating immunogenic signalling. Our findings reveal previously unrecognized, heterogenous effects of cellular DNA damage that manifest long afterwards in descendant cells. We suggest that these heterogenous descendant cell-fate responses may function physiologically to ensure the elimination and immune clearance of damaged cell lineages, but pathologically, may enable the prolonged survival of cells bearing mutagenic damage.
Scale-invariant geometric data analysis (SIGDA) provides robust, detailed visualizations of human ancestry specific to individuals and populations
Authors: Robinson Max , Zimmer Anat , Farrah Terry , Mauldin Denise E. , Price Nathan D. , Hood Leroy E. , Glusman Gustavo
Published: October 2018

Scale invariance is a common property of physical laws and a key concept in perspective drawing, which aims to provide a meaningful two-dimensional representation of a more complex, three-dimensional scene. Here we describe Scale Invariant Geometric Data Analysis (SIGDA), a new, general exploratory data analysis (EDA) method based on normalization of data to scale invariance. We discuss similarities and differences between SIGDA and two widely-used EDA methods, Correspondence Analysis (CA) and Principal Components Analysis (PCA). We then illustrate SIGDA’s ability to analyze and visualize population structure relationships within the data that inspired its development: genetic marker data, in which context PCA is considered a standard method. We show that SIGDA provides significant advantages over PCA of the same data, including: (a) robust detection and separation of a larger number of population axes, leading to (b) better separation of annotated populations; (c) separation of an independent allele frequency axis interpretable as a proxy for allele age, (d) visualization of marker flow between populations (populationhistory), and (d) robust detection and visualization of relationships between closely-related individuals and among family groups. Although this illustration focuses on a specific task, SIGDA is a general-purpose EDA method and derives its advantages from its novel approach to fundamental issues in data analysis, rather than clever sampling or other task-specific methodology.

One Sentence Summary

We illustrate the advantages of Scale Invariant Geometric Data Analysis (SIGDA), a new exploratory data analysis method similar to PCA, by applying SIGDA to derive detailed, robust visualizations of the complex history of human population structure from a large sample of single nucleotide variants.