bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of frequent users of the emergency department with chronic pain
Authors: Shergill Yaadwinder , Rice Danielle , Smyth Catherine , Tremblay Steve , Nelli Jennifer , Small Rebecca , Hebert Guy , Singer Lesley , Rash Joshua A. , Poulin Patricia A.
Published: March 2020

Objectives

To identify the proportion of high-frequency users of the emergency department (ED) who have chronic pain.

Methods

We reviewed medical records of adult patients with ≥ 12 visits to a tertiary-care, academic hospital ED in Canada in 2012-2013. We collected the following demographics: 1) patient age and sex; 2) visit details – number of ED visits, inpatient admissions, length of inpatient admissions, diagnosis, and primary location of pain; 3) current and past substance abuse, mental health and medical conditions. Charts were reviewed independently by two reviewers. ED visits were classified as either “chronic pain” or “not chronic pain” related.

Results

We analyzed 4,646 visits for 247 patients, mean age was 47.2 years (standard deviation = 17.8), and 50.2% were female. This chart review study found 38% of high-frequency users presented with chronic pain to the ED and that women were overrepresented in this group (64.5%). All high-frequency users presented with co-morbidities and/or mental health concerns. High-frequency users with chronic pain had more ED visits than those without and 52.7% were prescribed an opioid. Chronic abdominal pain was the primary concern for 54.8% of high-frequency users presenting with chronic pain.

Conclusions

Chronic pain, specifically chronic abdominal pain, is a significant driver of ED visits among patients who frequently use the ED. Interventions to support high-frequency users with chronic pain that take into account the complexity of patient's physical and mental health needs will likely achieve better clinical outcomes and reduce ED utilization.
Outcomes in the age of competency-based medical education: Recommendations for emergency medicine training in Canada from the 2019 symposium of academic emergency physicians
Authors: Chan Teresa M. , Paterson Quinten S. , Hall Andrew K. , Zaver Fareen , Woods Robert A. , Hamstra Stanley J. , Stefan Alexandra , Ting Daniel K. , Thoma Brent
Published: March 2020

Objectives

The national implementation of competency-based medical education (CBME) has prompted an increased interest in identifying and tracking clinical and educational outcomes for emergency medicine training programs. For the 2019 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, we developed recommendations for measuring outcomes in emergency medicine training in the context of CBME to assist educational leaders and systems designers in program evaluation.

Methods

We conducted a three-phase study to generate educational and clinical outcomes for emergency medicine (EM) education in Canada. First, we elicited expert and community perspectives on the best educational and clinical outcomes through a structured consultation process using a targeted online survey. We then qualitatively analyzed these responses to generate a list of suggested outcomes. Last, we presented these outcomes to a diverse assembly of educators, trainees, and clinicians at the CAEP Academic Symposium for feedback and endorsement through a voting process.

Conclusion

Academic Symposium attendees endorsed the measurement and linkage of CBME educational and clinical outcomes. Twenty-five outcomes (15 educational, 10 clinical) were derived from the qualitative analysis of the survey results and the most important short- and long-term outcomes (both educational and clinical) were identified. These outcomes can be used to help measure the impact of CBME on the practice of Emergency Medicine in Canada to ensure that it meets both trainee and patient needs.
Isolation and identification of lactic acid bacteria in fresh plants and in silage from Opuntia and their effects on the fermentation and aerobic stability of silage
Authors: Pereira G. A. , Santos E. M. , Araújo G. G. L. , Oliveira J. S. , Pinho R. M. A. , Zanine A. de M. , Souza A. F. N. , Macedo A. J. S. , Neto J. M. C. , Nascimento T. V. C.
Published: March 2020

The current study aimed to select the strains of lactic acid bacteria (LAB) isolated from forage cactus plants and silage and assess their effects on silage fermentation and aerobic stability. Forty wild isolates from plant and cactus silage, classified as LAB, were evaluated for metabolite production and identified by 16S ribosomal DNA sequencing. These wild isolates were identified asLactobacillus plantarum,Weissella cibaria,Weissella confusaandWeissella paramesenteroidesand the LAB populations differed among the silage. The use of microbial inoculants did not influence gas or effluent losses in forage cactus silage. The silage inoculated with the microbial strain GP15 showed the highest number of LAB populations. The amounts of water-soluble carbohydrates (WSC) and ammonia nitrogen differed among the silage. The silage inoculated with the GP1 strain presented the highest WSC. Populations of enterobacteria and yeasts and moulds were below the minimum detection limit (<2.0 log cfu/g silage) in all the silage studied. The predominant action of inoculants was to maximize dry matter recovery of the silage, which could be the criterion adopted to select the strains of LAB for use as inoculants inOpuntiasilage.
Instructional strategies and linguistic features of kindergarten teachers’ shared book reading: The case of Singapore
Authors: Sun He , Toh Weimin , Steinkrauss Rasmus
Published: March 2020

Teachers’ language practice during shared book reading may significantly affect the rate and outcome of early language proficiency. The current study has focused on 37 kindergarten teachers and 440 4- to 5-year-old kindergartners during their shared book reading sessions in Singapore, exploring teachers’ variation in instructional strategies and linguistic features, and its relations with children’s language development and teacher’s background. Results demonstrated that teacher’s language strategies and linguistic features varied considerably. Instructional strategies with a medium level of cognitive load were found to be positively related to children’s growth in receptive vocabulary and word reading skills. Teacher’s lexical sophistication was found to be positively associated with children’s vocabulary size. Years of teaching experience was revealed to predict teacher’s variation in medium-level instructions.
Drug and Alcohol Related Patient Presentations to Emergency Departments during Sporting Mass-Gathering Events: An Integrative Review
Authors: Delany Catherine , Crilly Julia , Ranse Jamie
Published: March 2020

Background:

Drug and alcohol consumption at sporting mass-gathering events (MGEs) has become part of the spectator culture in some countries. The direct and indirect effects of drug and alcohol intoxication at such MGEs has proven problematic to in-event health services as well as local emergency departments (EDs). With EDs already under significant strain from increasing patient presentations, resulting in access block, it is important to understand the impact of sporting and other MGEs on local health services to better inform future planning and provision of health care delivery.

Aim:

The aim of this review was to explore the impact of sporting MGEs on local health services with a particular focus on drug and alcohol related presentations.

Method:

A well-established integrative literature review methodology was undertaken. Six electronic databases and the Prehospital and Disaster Medicine (PDM) journal were searched to identify primary articles related to the aim of the review. Articles were included if published in English, from January 2008 through July 2019, and focused on a sporting MGE, mass-gathering health, EDs, as well as drug and alcohol related presentations.

Results:

Seven papers met the criteria for inclusion with eight individual sporting MGEs reported. The patient presentation rate (PPR) to in-event health services ranged from 0.18/1,000 at a rugby game to 41.9/1,000 at a recreational bicycle ride. The transport to hospital rate (TTHR) ranged from 0.02/1,000 to 19/1,000 at the same events. Drug and alcohol related presentations from sporting MGEs contributed up to 10% of ED presentations. Alcohol was a contributing factor in up to 25% of cases of ambulance transfers.

Conclusions:

Drug and alcohol intoxication has varying levels of impact on PPR, TTHR, and ED presentation numbers depending on the type of sporting MGE. More research is needed to understand if drug and alcohol intoxication alone influences PPR, TTHR, and ED presentations or if it is multifactorial. Inconsistent data collection and reporting methods make it challenging to compare different sporting MGEs and propose generalizations. It is imperative that future studies adopt more consistent methods and report drug and alcohol data to better inform resource allocation and care provision.
Feeding and developmental outcomes of infants in a South African community
Authors: Eales Bronwyn , Krüger Esedra , Graham Marien , van der Linde Jeannie
Published: March 2020

Background:

Prevalent environmental risk factors place infants in lower-middle-income countries (LMICs) at an increased risk for feeding and developmental difficulties.

Aim:

This study aimed to determine the relationship between feeding and developmental outcomes in infants, as early feeding difficulties may have a cascading effect on developmental outcomes and vice versa.

Methods:

Data on 144 infants’ feeding and development [mean age (standard deviation) = 8.8 months (2.2)] from a primary health care clinic in Gauteng, South Africa were retrospectively analysed.

Results:

Early introduction of cup feeding was found to be a predictor of possible expressive language and articulation difficulties. Gagging, spitting, or vomiting, pocketing, the use of force feeding, and poor sucking and chewing abilities were significantly associated with behavioural and social–emotional difficulties. Breastfeeding was found to be a protective factor for language development. The results emphasise the importance of primary prevention and early identification of risks in late infancy in LMIC.
The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience
Authors: Konno Hiroko , Murakoshi Takeshi , Miura Kiyonori , Masuzaki Hideaki
Published: March 2020

Dichorionic diamniotic (DCDA) twin pregnancies after single blastocyst embryo transfer have been reported recently, although a blastocyst ovum is generally believed to divide into monochorionic twin pregnancy. We investigated the incidence of DCDA twin pregnancy after single blastocyst embryo transfer and their zygosity. This prospective cohort study included 655 consecutive twin pregnancies that were managed from 2006 to 2014 at our institution. Chorionicity and amnionicity were determined using first-trimester ultrasonography and/or placental pathology. Zygosity was analyzed if the cases were DCDA twins after single blastocyst embryo transfer. Among 655 twin pregnancies, there were 348 DCDA cases, 295 monochorionic diamniotic (MCDA) cases and 12 monochorionic monoamniotic cases. Single blastocyst embryo transfer was performed in 43 cases. Six out of the 43 (14%) cases involved DCDA twin pregnancies and the other 37 cases involved MCDA twin pregnancies. Three DCDA twins born after single blastocyst embryo transfer, wherein frozen embryo transfer (FET) was performed in the natural cycle, were dizygotic, and the other three cases, wherein FET with hormone replacement therapy was performed, were monozygotic. DCDA twin pregnancy occurred in 14% (7% for monozygotic and 7% for dizygotic) of twin pregnancies after single blastocyst embryo transfer cases.
Long-Term Stability of Cortisol Production and Metabolism Throughout Adolescence: Longitudinal Twin Study
Authors: van Keulen Britt J. , Dolan Conor V. , Andrew Ruth , Walker Brian R. , Hulshoff Pol Hilleke E. , Boomsma Dorret I. , Rotteveel Joost , Finken Martijn J. J.
Published: March 2020

Life-course experiences have been postulated to program hypothalamus–pituitary–adrenal (HPA) axis activity, suggesting that HPA axis activity is, at least partially, stable over time. Yet, there is paucity of data on the long-term stability of cortisol production and metabolism. We performed a prospective follow-up study in twins recruited from a nationwide register to estimate the stability of cortisol production and metabolism over time, and the contribution of genetic and environmental factors to this stability. In total, 218 healthy mono- and dizygotic twins were included. At the ages of 9, 12 and 17 years, morning urine samples were collected for assessment (by gas chromatography-tandem mass spectrometry) of cortisol metabolites, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolism activity. Our results showed a low stability for both cortisol metabolite excretion rate (with correlations <.20) and cortisol metabolism activity indices (with correlations of .25 to .46 between 9 and 12 years, −.02 to .15 between 12 and 17 years and .09 to .28 between 9 and 17 years). Because of the low stability over time, genetic and environmental contributions to this stability were difficult to assess, although it seemed to be mostly determined by genetic factors. The low stability in both cortisol production and metabolism between ages 9 and 17 years reflects the dynamic nature of the HPA axis.
Effects of competition from California weedy rice (Oryza sativa f. spontanea) biotypes on a cultivated rice variety
Authors: Karn Elizabeth , De Leon Teresa , Espino Luis , Al-Khatib Kassim , Brim-DeForest Whitney
Published: March 2020

Weedy rice is an emerging problem of cultivated rice in California. Infestations of weedy rice in cultivated rice result in yield loss and reduced grain quality. In this study, we aimed to evaluate growth and yield components of a widely grown cultivated rice variety in California in response to weedy rice competition. Greenhouse competition experiments in an additive design were conducted in 2017 and 2018 to determine the growth and yield components of ‘M-206’ rice and five weedy rice biotypes found in California at varying weed densities. M-206 rice initially grew at a faster relative growth rate of 0.53 cm−1 wk−1 under competitive conditions compared with 0.47 cm−1 wk−1 in the absence of weedy rice, but absolute and relative growth rates declined more rapidly under competitive conditions as plants approached maturity. At harvest, M-206 plant height was reduced 13% under competitive conditions, and M-206 tiller number was reduced 23% to 49%, depending on the weedy rice biotype it was competing with. Except for 100-grain weight, the growth traits and grain yield components of M-206 rice were reduced with increasing density of weedy rice. At the highest weed density measured, 40 plants m−2, M-206 rice had yield losses of 69% grain yield plant−1, 69% panicle weight, 59% fresh and dry biomass, 55% grain yield panicle−1, and 54% panicle number. The five evaluated weedy rice biotypes varied widely in early growth rates, height, biomass production, and grain yield, indicating differing competitive strategies. Most weedy rice biotypes produce plants with greater plant height, tiller number, panicle number, and above- and below-ground biomass compared with cultivated rice. Weedy rice biotypes produced 45% to 57% higher grain yield per plant than M-206 rice under competitive conditions.
Future Directions
Authors: Arensman Ella , De Leo Diego , Pirkis Jane
Published: March 2020

Abstract. This final chapter focuses on the progress made so far in the area of suicide prevention and calls attention to considerations for future work. Recommendations for the implementation of national suicide prevention strategies are proposed, including close collaboration between countries within the same geographic region, as well as guidance from countries wherein national strategies have successfully implemented, such as the sharing of effective strategy templates. In addition, the value of accurate surveillance data in overcoming barriers, informing actions and responding to real time trends in suicide and self-harm is emphasized. The need for more systematic research into the efficacy of intervention and prevention approaches is also highlighted. Furthermore, the provision of governmental support to ensure long-term sustainability of national suicide prevention strategies is endorsed. Approaches to enhance the evaluation of the efficacy of national suicide prevention strategies and interdisciplinary partnerships and collaborations are discussed. Finally, recommended resources to assist in implementing and evaluating key components of national suicide prevention strategies are listed.
Pulsated Global Hydrogen and Methane Flux at Mid‐Ocean Ridges Driven by Pangea Breakup
Authors: Merdith Andrew S. , del Real Pablo García , Daniel Isabelle , Andreani Muriel , Wright Nicky M. , Coltice Nicolas
Published: March 2020

Molecular hydrogen production occurs through the serpentinization of mantle peridotite exhumed at mid‐ocean ridges. Hydrogen is considered essential to sustain microbial life in the subsurface; however, estimates of hydrogen flux through geological time are unknown. Here we present a model of the primary, abiotic production of molecular hydrogen from the serpentinization of oceanic lithosphere using full‐plate tectonic reconstructions for the last 200 Ma. We find significant variability in hydrogen fluxes (1–70 • 1016 mol/Ma or 0.2–14.1 • 105 Mt/Ma), which are a function of the sensitivity of evolving ocean basins to spreading rates and can be correlated with the opening of key ocean basins during the breakup of Pangea. We suggest that the primary driver of this hydrogen flux is the continental reconfiguration during Pangea breakup, as this produces ocean basins more conducive to exhuming and exposing mantle peridotite at slow and ultraslow spreading ridges. Consequently, present‐day flux estimates are ~7 • 1017 mol/Ma (1.4 • 106 Mt/Ma), driven primarily by the slow and ultraslow spreading ridges in the Atlantic, Indian, and Arctic oceans. As methane has also been sampled alongside hydrogen at hydrothermal vents, we estimate the methane flux using methane‐to‐hydrogen ratios from present‐day hydrothermal vent fluids. These ratios suggest that methane flux ranges between 10 and 100% of the total hydrogen flux, although as the release of methane from these systems is still poorly understood, we suggest a lower estimate, equivalent to around 7–12 • 1016 mol/Ma (1.1–1.9 • 106 Mt/Ma) of methane.
Seismic P Wave Velocity Model From 3‐D Surface and Borehole Seismic Data at the Alpine Fault DFDP‐2 Drill Site (Whataroa, New Zealand)
Authors: Lay V. , Buske S. , Bodenburg S. B. , Townend J. , Kellett R. , Savage M. K. , Schmitt D. R. , Constantinou A. , Eccles J. D. , Bertram M. , Hall K. , Lawton D. , Gorman A. R. , Kofman R. S.
Published: March 2020

The New Zealand Alpine Fault is a major plate boundary that is expected to be close to rupture, allowing a unique study of fault properties prior to a future earthquake. Here we present 3‐D seismic data from the DFDP‐2 drill site in Whataroa to constrain valley structures that were obscured in previous 2‐D seismic data. The new data consist of a 3‐D extended vertical seismic profiling (VSP) survey using three‐component and fiber optic receivers in the DFDP‐2B borehole and a variety of receivers deployed at the surface. The data set enables us to derive a detailed 3‐D P wave velocity model by first‐arrival traveltime tomography. We identify a 100–460 m thick sediment layer (mean velocity 2,200 ± 400 m/s) above the basement (mean velocity 4,200 ± 500 m/s). Particularly on the western valley side, a region of high velocities rises steeply to the surface and mimics the topography. We interpret this to be the infilled flank of the glacial valley that has been eroded into the basement. In general, the 3‐D structures revealed by the velocity model on the hanging wall of the Alpine Fault correlate well with the surface topography and borehole findings. As a reliable velocity model is not only valuable in itself but also crucial for static corrections and migration algorithms, the Whataroa Valley P wave velocity model we have derived will be of great importance for ongoing seismic imaging. Our results highlight the importance of 3‐D seismic data for investigating glacial valley structures in general and the Alpine Fault and adjacent structures in particular.
Quantifying the Impact of Excess Moisture From Transpiration From Crops on an Extreme Heat Wave Event in the Midwestern U.S.: A Top‐Down Constraint From Moderate Resolution Imaging Spectroradiometer Water Vapor Retrieval
Authors: Souri Amir H. , Wang Huiqun , González Abad Gonzalo , Liu Xiong , Chance Kelly
Published: March 2020

The primary focus of this study is to understand the contribution from excess moisture from crop transpiration to the severity of a heat wave episode that hit the Midwestern U.S. from 16 to 20 July 2011. To elucidate this, we first provide an optimal estimate of the transpiration water vapor flux using satellite total column water vapor retrievals whose accuracy and precision are characterized using independent observations. The posterior transpiration flux is estimated using a local ensemble transform Kalman filter that employs a mesoscale weather model as the forward model. The new estimation suggests that the prior values of transpiration flux from crops are biased high by 15%. We further use the constrained flux to examine the sensitivity of meteorology to the contributions from crops. Over the agricultural areas during daytime, elevated moisture (up to 40%) from crops not only increases humidity (thus the heat index) but also provides a positive radiative forcing by increasing downward longwave radiation (13 ± 4 W m−2) that results in even higher surface air temperature (+0.4 °C). Consequently, we find that the elevated moisture generally provides positive feedback to aggravate the heat wave, with daytime enhancements of heat index by as large as 3.3 ± 0.8 °C. Due to a strong diurnal cycle in the transpiration, the feedback tends to be stronger in the afternoon (up to 5 °C) and weaker at night. Results offer a potential basis for designing mitigation strategies for the effect of transpiration from agriculture in the future, in addition to improving the estimation of canopy transpiration.
Adherence to the WCRF/AICR 2018 recommendations for cancer prevention and risk of cancer: prospective cohort studies of men and women
Authors: Kaluza Joanna , Harris Holly R. , Håkansson Niclas , Wolk Alicja
Published: March 2020

Background

In 2018, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) issued revised recommendations for cancer prevention. We examined the relation between adherence to these recommendations and risk of total cancer in two population-based Swedish prospective cohorts (29,451 men and 25,349 women).

Methods

Standardized-WCRF/AICR 2018 and simplified-WCRF/AICR 2018 adherence scores were constructed based on the WCRF/AICR recommendations for body weight, physical activity, diet, alcohol consumption and dietary supplement use. Data were collected using a self-administered questionnaire.

Results

During the 15.4 years of follow-up, 12,693 incident cancers were ascertained. The multivariable HR between extreme categories of the Standardized-WCRF/AICR 2018 score (4.1–7 vs. 0–2) was 0.88 (95% CI = 0.82–0.95) and for the Simplified score (5–8 vs. 0–2) was 0.85 (95% CI = 0.80–0.90); each 1-score increment in recommendation adherence was associated with 3% (95% CI = 1–5%) and 4% (95% CI = 2–5%) decreased risk, respectively. Based on the Simplified scoring, most participants (>90%) did not meet WCRF/AICR 2018 recommendations regarding consumption of plant foods, limited consumption of red/processed meat and ‘fast food’/processed food, and <50% of participants met the weight and physical activity recommendations.

Conclusions

Adherence to the 2018WCRF/AICR recommendations substantially reduced the risk of total cancer. Given that many people do not meet the recommendations, there is a great potential for cancer prevention.
A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo
Authors: Xing Panfei , Niu Yiming , Mu Ruoyu , Wang Zhenzhen , Xie Daping , Li Huanling , Dong Lei , Wang Chunming
Published: March 2020

Near-infrared (NIR) fluorescent probes are among the most attractive chemical tools for biomedical imaging. However, their in vivo applications are hindered by albumin binding, generating unspecific fluorescence that masks the specific signal from the analyte. Here, combining experimental and docking methods, we elucidate that the reason for this problem is an acceptor (A) group-mediated capture of the dyes into hydrophobic pockets of albumin. This pocket-capturing phenomenon commonly applies to dyes designed under the twisted intramolecular charge-transfer (TICT) principle and, therefore, represents a generic but previously unidentified backdoor problem. Accordingly, we create a new A group that avoids being trapped into the albumin pockets (pocket-escaping) and thereby construct a NIR probe, BNLBN, which effectively prevents this backdoor problem with increased imaging accuracy for liver fibrosis in vivo. Overall, our study explains and overcomes a fundamental problem for the in vivo application of a broad class of bioimaging tools.
Rigidity enhances a magic-number effect in polymer phase separation
Authors: Xu Bin , He Guanhua , Weiner Benjamin G. , Ronceray Pierre , Meir Yigal , Jonikas Martin C. , Wingreen Ned S.
Published: March 2020

Cells possess non-membrane-bound bodies, many of which are now understood as phase-separated condensates. One class of such condensates is composed of two polymer species, where each consists of repeated binding sites that interact in a one-to-one fashion with the binding sites of the other polymer. Biologically-motivated modeling revealed that phase separation is suppressed by a “magic-number effect” which occurs if the two polymers can form fully-bonded small oligomers by virtue of the number of binding sites in one polymer being an integer multiple of the number of binding sites of the other. Here we use lattice-model simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one of the polymer species has a rigid shape that allows for multiple distinct bonding conformations. Moreover, if one species is rigid, the effect is robust over a much greater range of relative concentrations of the two species.
Incorporation of clinical and biological factors improves prognostication and reflects contemporary clinical practice
Authors: Murthy Rashmi K. , Song Juhee , Raghavendra Akshara S. , Li Yisheng , Hsu Limin , Hess Kenneth R. , Barcenas Carlos H. , Valero Vicente , Carlson Robert W. , Tripathy Debu , Hortobagyi Gabriel N.
Published: March 2020

We developed prognostic models for breast cancer-specific survival (BCSS) that consider anatomic stage and other important determinants of prognosis and survival in breast cancer, such as age, grade, and receptor-based subtypes with the intention to demonstrate that these factors, conditional on stage, improve prediction of BCSS. A total of 20,928 patients with stage I–III invasive primary breast cancer treated at The University of Texas MD Anderson Cancer Center between 1990 and 2016, who received surgery as an initial treatment were identified to generate prognostic models by Fine-Gray competing risk regression model. Model predictive accuracy was assessed using Harrell’s C-index. The Aalen–Johansen estimator and a selected Fine–Gray model were used to estimate the 5-year and 10-year BCSS probabilities. The performance of the selected model was evaluated by assessing discrimination and prediction calibration in an external validation dataset of 29,727 patients from the National Comprehensive Cancer Network (NCCN). The inclusion of age, grade, and receptor-based subtype in addition to stage significantly improved the model predictive accuracy (C-index: 0.774 (95% CI 0.755–0.794) vs. 0.692 for stage alone, p < 0.0001). Young age (<40), higher grade, and TNBC subtype were significantly associated with worse BCSS. The selected model showed good discriminative ability but poor calibration when applied to the validation data. After recalibration, the predictions showed good calibration in the training and validation data. More refined BCSS prediction is possible through a model that has been externally validated and includes clinical and biological factors.
Electron microscopy dataset for the recognition of nanoscale ordering effects and location of nanoparticles
Authors: Boiko Daniil A. , Pentsak Evgeniy O. , Cherepanova Vera A. , Ananikov Valentine P.
Published: March 2020

A unique ordering effect has been observed in functional catalytic nanoscale materials. Instead of randomly arranged binding to the catalyst surface, metal nanoparticles show spatially ordered behavior resulting in formation of geometrical patterns. Understanding of such nanoscale materials and analysis of corresponding microscopy images will never be comprehensive without appropriate reference datasets. Here we describe the first dataset of electron microscopy images comprising individual nanoparticles which undergo ordering on a surface towards the formation of geometrical patterns. The dataset developed in this study spans three levels of nanoscale organization: (i) individual nanoparticles (1–5 nm) and arrays of nanoparticles (5–20 nm), (ii) ordering effects (20–200 nm) and (iii) complex patterns (from nm to μm scales). The described dataset for the first time provides a possibility for the development of machine learning algorithms to study the unique phenomena of nanoparticles ordering and hierarchical organization.
Processing citizen science- and machine-annotated time-lapse imagery for biologically meaningful metrics
Authors: Jones Fiona M. , Arteta Carlos , Zisserman Andrew , Lempitsky Victor , Lintott Chris J. , Hart Tom
Published: March 2020

Time-lapse cameras facilitate remote and high-resolution monitoring of wild animal and plant communities, but the image data produced require further processing to be useful. Here we publish pipelines to process raw time-lapse imagery, resulting in count data (number of penguins per image) and ‘nearest neighbour distance’ measurements. The latter provide useful summaries of colony spatial structure (which can indicate phenological stage) and can be used to detect movement – metrics which could be valuable for a number of different monitoring scenarios, including image capture during aerial surveys. We present two alternative pathways for producing counts: (1) via the Zooniverse citizen science project Penguin Watch and (2) via a computer vision algorithm (Pengbot), and share a comparison of citizen science-, machine learning-, and expert- derived counts. We provide example files for 14 Penguin Watch cameras, generated from 63,070 raw images annotated by 50,445 volunteers. We encourage the use of this large open-source dataset, and the associated processing methodologies, for both ecological studies and continued machine learning and computer vision development.
Oxytocin Receptors Regulate Social Preference in Zebrafish
Authors: Landin Jenny , Hovey Daniel , Xu Bo , Lagman David , Zettergren Anna , Larhammar Dan , Kettunen Petronella , Westberg Lars
Published: March 2020

With a strong tendency to socialise, the zebrafish is a useful model to study social behaviour, with implications for better treatments of social impairments, for instance in autism spectrum disorders. Although oxytocin is crucial for social behaviour in mammals, the importance of the fish orthologue – isotocin or zebrafish oxytocin (zOT) – for social behaviour in zebrafish is unclear. The aims of this study were firstly, to elucidate the receptor specificity of zOT and the related vasotocin or zebrafish vasopressin (zVP; the orthologue of mammalian vasopressin) and the nonpeptidergic oxytocin receptor antagonist L-368,899, and secondly to investigate if L-368,899 inhibits social preference in zebrafish. The potencies of ligands were evaluated for zOT/zVP family receptors in HEK293 cells. Adult and larval zebrafish were treated with L-368,899 or vehicle and subsequently assessed for social behaviour and anxiety (adults only). The antagonist L-368,899 specifically inhibited the two zOT receptors, but not the two zVP-1 receptors. The antagonist decreased social preference in adult and larval zebrafish. It did not affect anxiety in adults. These results indicate that endogenous zOT, and possibly zVP, is involved in social behaviour in zebrafish via either or both of the two zOT receptors, and show promise for future explorations of the anatomy and evolution of networks underlying social behaviour.
25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments
Authors: Ting Daniel S. W. , Foo Valencia H. X. , Tan Tien-En , Sie Nicole M. , Wong Chee Wai , Tsai Andrew S. H. , Tan Gavin S. W. , Lim Laurence S. , Yeo Ian Y. S. , Wong Doric W. K. , Ong Sze Guan , Wong Edmund Y. M. , Ang Chong Lye , Lee Shu Yen
Published: March 2020

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients’ demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups – Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991–2005 and 2006–2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.
A high-resolution polarimeter formed from inexpensive optical parts
Authors: Harvie A. J. , Phillips T. W. , deMello J. C.
Published: March 2020

We describe a high resolution laser polarimeter built from commodity optical components. The optical rotation angle is determined by measuring the phase difference between two harmonically modulated polarised laser beams – an ‘object beam’ that passes through the sample under test and a ‘reference beam’ that bypasses the sample. The complete polarimeter may be assembled from low cost off-the-shelf parts for less than £300 (UK Sterling). Data acquisition and analysis are carried out on a microcontroller running an efficient algorithm based on the sliding Discrete Fourier Transform. Despite its low cost, the polarimeter is a fully automatic, research-grade instrument with an accuracy of ±0.0013° and a precision of ±0.0028° – comparable to far costlier commercial instruments. The polarimeter’s ease of use, compact size, fast measurement times and high angular resolution make it a capable and versatile tool for analytical science, while its low cost means it is ideally suited for use in resource-constrained environments and process monitoring. The polarimeter is released here as open hardware, with technical diagrams, a full parts list, and source code for its firmware included as Supplementary Information.
Hypoplasia of cerebellar afferent networks in Down syndrome revealed by DTI-driven tensor based morphometry
Authors: Lee Nancy Raitano , Nayak Amritha , Irfanoglu M. Okan , Sadeghi Neda , Stoodley Catherine J. , Adeyemi Elizabeth , Clasen Liv S. , Pierpaoli Carlo
Published: March 2020

Quantitative magnetic resonance imaging (MRI) investigations of brain anatomy in children and young adults with Down syndrome (DS) are limited, with no diffusion tensor imaging (DTI) studies covering that age range. We used DTI-driven tensor based morphometry (DTBM), a novel technique that extracts morphometric information from diffusion data, to investigate brain anatomy in 15 participants with DS and 15 age- and sex-matched typically developing (TD) controls, ages 6–24 years (mean age ~17 years). DTBM revealed marked hypoplasia of cerebellar afferent systems in DS, including fronto-pontine (middle cerebellar peduncle) and olivo-cerebellar (inferior cerebellar peduncle) connections. Prominent gray matter hypoplasia was observed in medial frontal regions, the inferior olives, and the cerebellum. Very few abnormalities were detected by classical diffusion MRI metrics, such as fractional anisotropy and mean diffusivity. Our results highlight the potential importance of cerebro-cerebellar networks in the clinical manifestations of DS and suggest a role for DTBM in the investigation of other brain disorders involving white matter hypoplasia or atrophy.
Publisher Correction: α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility
Authors: Arcos Alexis , de Paola Matilde , Gianetti Diego , Acuña Diego , Velásquez Zahady D. , Miró María Paz , Toro Gabriela , Hinrichsen Bryan , Muñoz Rosa Iris , Lin Yimo , Mardones Gonzalo A. , Ehrenfeld Pamela , Rivera Francisco J. , Michaut Marcela A. , Batiz Luis Federico
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis
Authors: Hsu Wei-Fan , Chen Chi-Yi , Tseng Kuo-Chih , Lai Hsueh-Chou , Kuo Hsing-Tao , Hung Chao-Hung , Tung Shui-Yi , Wang Jing-Houng , Chen Jyh-Jou , Lee Pei-Lun , Chien Rong-Nan , Lin Chun-Yen , Yang Chi-Chieh , Lo Gin-Ho , Tai Chi-Ming , Lin Chih-Wen , Kao Jia-Horng , Liu Chun-Jen , Liu Chen-Hua , Yan Sheng-Lei , Bair Ming-Jong , Su Wei-Wen , Chu Cheng-Hsin , Chen Chih-Jen , Lo Ching-Chu , Cheng Pin-Nan , Chiu Yen-Cheng , Wang Chia-Chi , Cheng Jin-Shiung , Tsai Wei-Lun , Lin Han-Chieh , Huang Yi-Hsiang , Tsai Pei-Chien , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung , Peng Cheng-Yuan
Published: March 2020

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17–0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.
Mid- to long-wave infrared computational spectroscopy with a graphene metasurface modulator
Authors: Shrestha Vivek Raj , Craig Benjamin , Meng Jiajun , Bullock James , Javey Ali , Crozier Kenneth B.
Published: March 2020

In recent years there has been much interest concerning the development of modulators in the mid- to long-wave infrared, based on emerging materials such as graphene. These have been frequently pursued for optical communications, though also for other specialized applications such as infrared scene projectors. Here we investigate a new application for graphene modulators in the mid- to long-wave infrared. We demonstrate, for the first time, computational spectroscopy in the mid- to long-wave infrared using a graphene-based metasurface modulator. Furthermore, our metasurface device operates at low gate voltage. To demonstrate computational spectroscopy, we provide our algorithm with the measured reflection spectra of the modulator at different gate voltages. We also provide it with the measured reflected light power as a function of the gate voltage. The algorithm then estimates the input spectrum. We show that the reconstructed spectrum is in good agreement with that measured directly by a Fourier transform infrared spectrometer, with a normalized mean-absolute-error (NMAE) of 0.021.
Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1
Authors: Lukovic Dunja , Artero Castro Ana , Kaya Koray Dogan , Munezero Daniella , Gieser Linn , Davó-Martínez Carlota , Corton Marta , Cuenca Nicolás , Swaroop Anand , Ramamurthy Visvanathan , Ayuso Carmen , Erceg Slaven
Published: March 2020

Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is a photoreceptor-specific chaperone that stabilizes the effector enzyme of phototransduction, cGMP phosphodiesterase 6 (PDE6). Mutations in the AIPL1 gene cause a severe inherited retinal dystrophy, Leber congenital amaurosis type 4 (LCA4), that manifests as the loss of vision during the first year of life. In this study, we generated three-dimensional (3D) retinal organoids (ROs) from human induced pluripotent stem cells (hiPSCs) derived from an LCA4 patient carrying a Cys89Arg mutation in AIPL1. This study aimed to (i) explore whether the patient hiPSC-derived ROs recapitulate LCA4 disease phenotype, and (ii) generate a clinically relevant resource to investigate the molecular mechanism of disease and safely test novel therapies for LCA4 in vitro. We demonstrate reduced levels of the mutant AIPL1 and PDE6 proteins in patient organoids, corroborating the findings in animal models; however, patient-derived organoids maintained retinal cell cytoarchitecture despite significantly reduced levels of AIPL1.
Optical coherence tomography angiography as a novel approach to contactless evaluation of sublingual microcirculation: A proof of principle study
Authors: Hessler Michael , Nelis Pieter , Ertmer Christian , Alnawaiseh Maged , Lehmann Florian , Schmidt Christina , Kampmeier Tim-Gerald , Rehberg Sebastian Willy , Arnemann Philip-Helge , Rovas Alexandros
Published: March 2020

Microcirculatory disorders are crucial in pathophysiology of organ dysfunction in critical illness. Evaluation of sublingual microcirculation is not routinely conducted in daily practice due to time-consuming analysis and susceptibility to artifacts. We investigated the suitability of optical coherence tomography angiography (OCTA) for contactless evaluation of sublingual microcirculation. Sublingual microcirculation was imaged in 10 healthy volunteers, using an OCTA device and an incident dark field (IDF) illumination microscopy (current gold standard). OCTA images were analyzed with regard to flow density and perfused vessel density (PVDbyOCTA). IDF videos were analyzed following current recommendations. Flow density was automatically extracted from OCTA images (whole en face 48.9% [43.2; 54.5]; central ring 52.6% [43.6; 60.6]). PVDbyOCTA did not differ from the PVD calculated from IDF videos (PVDbyOCTA 18.6 mm/mm² [18.0; 21.7]) vs. PVDbyIDF 21.0 mm/mm² [17.5; 22.9]; p = 0.430). Analysis according to Bland-Altman revealed a mean bias of 0.95 mm/mm² (95% Confidence interval −1.34 to 3.25) between PVDbyOCTA and PVDbyIDF with limits of agreement of −5.34 to 7.24 mm/mm². This study is the first to demonstrate the suitability of OCTA for evaluating sublingual microcirculation. Comparison of the perfused vessel density between methods showed a plausible level of agreement.
Fungal Cell Wall and Methyl-β–Cyclodextrin Synergistically Enhance Paclitaxel Biosynthesis and Secretion in Corylus avellana Cell Suspension Culture
Authors: Farhadi Siamak , Moieni Ahmad , Safaie Naser , Sabet Mohammad Sadegh , Salehi Mina
Published: March 2020

Paclitaxel is the top-selling chemotherapeutic drug used for the treatment of lung, ovarian and breast cancer as well as Kaposi’s sarcoma. Cell suspension culture (CSC) of Corylus avellana has been addressed as a promising alternative for producing paclitaxel. In this study, endophytic fungus strain YEF33 was isolated from Taxus baccata and identified as Coniothyrium palmarum. The effects of the elicitors derived from this fungus including cell extract, culture filtrate and cell wall (CW) and also chitin, alone or in combination with Methyl-β-Cyclodextrin (MBCD), on paclitaxel biosynthesis in C. avellana CSC were assayed for the first time. CW of C. palmarum was the most efficient fungal elicitor for paclitaxel biosynthesis in C. avellana CSC. The results revealed that MBCD affected paclitaxel biosynthesis differently depending on fungal elicitor type and vice versa. MBCD, either alone or in combination with fungal elicitors, induced a high secretion of paclitaxel, suggesting the decrement of toxicity and retro-inhibition processes of paclitaxel for cells. The joint effects of C. palmarum CW (2.5% (v/v) on 17th day) and 50 mM MBCD synergistically enhanced paclitaxel biosynthesis (402.4 µg l−1; 5.8-fold), 78.6% of which (316.5 µg l−1) were secreted into culture medium, a level 146% higher than that in control.
Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo
Authors: Fiedorowicz M. , Khan M. I. , Strzemecki D. , Orzeł J. , Wełniak-Kamińska M. , Sobiborowicz A , Wieteska M. , Rogulski Z. , Cheda L. , Wargocka-Matuszewska W. , Kilian K. , Szczylik C. , Czarnecka A. M.
Published: March 2020

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Prognosis for ccRCC is generally poor since it is largely resistant to chemo- and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/TICs isolated from established RCC cell lines – basic ccRCC research model – has never been investigatedin vivo. CD105+, CD105−, CD44+ and CD44− as well as CD44−/CD105− CD44+/CD105+ and CD44−/CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into NOD SCID mice and tumor growth was monitored with MRI and PET/CT. Tumor growth was observed after implantation of CD105+, CD44+, CD44−, CD44−/CD105+ and CD44−/CD105− but not CD105− or CD44+/CD105+. Implantation of CD44−/CD105− cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44− tumors expresses Nanog and Oct-4, while CD44− tumors additionally expressed endothelial cell marker - CD31.