bluuebunny/crossref_metadata_2025 huggingface dataset:
HydroShoot: a functional-structural plant model for simulating hydraulic structure, gas and energy exchange dynamics of complex plant canopies under water deficit—application to grapevine (Vitis vinifera)
Authors: Albasha R , Fournier C , Pradal C , Chelle M , Prieto J A , Louarn G , Simonneau T , Lebon E
Published: June 2019

This paper presents HydroShoot, a leaf-based functional-structural plant model (FSPM) that simulates gas exchange rates of complex plant canopies under water deficit conditions. HydroShoot is built assuming that simulating both the hydraulic structure of the shoot together with the energy budget of individual leaves is the asset for successfully scaling-up leaf to canopy gas exchange rates. HydroShoot includes three interacting modules: hydraulic, which calculates the distribution of xylem water potential across shoot hydraulic segments; energy, which calculates the complete energy budget of individual leaves; and exchange, which calculates net carbon assimilation and transpiration rates of individual leaves. HydroShoot was evaluated on virtual and real grapevines having strongly contrasted canopies, under well-watered and water deficit conditions. It captured accurately the impact of canopy architecture and soil water status on plant-scale gas exchange rates and leaf-scale temperature and water potential. Both shoot hydraulic structure and leaf energy budget simulations were, as postulated, required to adequately scaling-up leaf to canopy gas exchange rates. Notwithstanding, simulating shoot hydraulic structure was found more necessary to adequately performing this scaling task than simulating leaf energy budget. That is, the intra-canopy variability of leaf water potential was a better predictor of the reduction of whole plant gas exchange rates under water deficit than the intra-canopy variability of leaf temperature. We conclude that simulating the shoot hydraulic structure is a prerequisite if FSPMs are to be used to assess gas exchange rates of complex plant canopies as those of grapevines. Finally, HydroShoot is available through the OpenAlea platform (https://github.com/openalea/hydroshoot) as a set of reusable modules.
Web Content Analysis of University Forestry and Related Natural Resources Landing Webpages in the United States in Relation to Student and Faculty Diversity
Authors: Bal Tara L , Sharik Terry L
Published: June 2019

Under-representation of minorities and women in natural resources (NR)-related fields is common, both as students and as professionals. The perception of a predominantly white, male student body and workforce is a potential barrier to recruiting women and minorities to Forestry and related-NR fields. The images of “forestry” and “natural resources-related” fields were examined as they would be from a potential student’s perspective looking at university and college websites with these degree program majors at the 80 National Association of University Forest Resource Programs member institutions during in 2016. Results suggest the percentage of women and minorities enrolled explains little variation in a program’s website image content, whereas there is significant image under-representation of minorities in all NR fields and of women on forestry-major webpages. In addition, women and minorities are more likely to be portrayed in a passive image, such as posing on campus, rather than in an active image, such as measuring a tree. Potential students are also less likely to see diverse faculty online. A lack of diversity image inclusion in Forestry and related NR will not help students see themselves in these fields or enhance society’s view of these critical fields for future employment and economic growth.
The steps until surgery in the management of Baastrup’s Disease (kissing spine syndrome)
Authors: Kerroum Axel , Laudato Pietro Aniello , Suter Marc R
Published: June 2019

Baastrup’s disease is a rare condition of the vertebral column often misdiagnosed and wrongly treated due to poor knowledge, characterized by low back pain arising from the close approximation of adjacent posterior spinous processes and resultant degenerative changes. Diagnosis rests on clinical examination and detailed imaging studies. Proposed therapies include conservative treatment, percutaneous infiltrations or surgical therapies. We present the case of a 31-year-old man with persistent chronic lumbago for several years. In whom, the diagnosis of Baastrup’s disease was high suspected clinically, with a final surgical treatment despite the absence of inflammation on imaging studies, which allowed the diagnostic confirmation and the return to a normal social and professional life. We wish through this case, to expose the different steps of interventional diagnostic/therapeutical procedures until the surgical management in a clinical suspicion of Baastrup’s diseases with unclear radiological findings.
Antibiotic and antifungal treatment among persons with confirmed coccidioidomycosis — Southern California, 2011
Authors: Chi Gloria C , Benedict Kaitlin , Beer Karlyn D , Jackson Brendan R , McCotter Orion , Xie Fagen , Lawrence Jean M , Tartof Sara Y
Published: June 2019

We investigated coccidioidomycosis testing and treatment patterns among persons in an integrated healthcare delivery system to identify gaps in diagnosis and treatment. Coccidioidomycosis diagnosis delays were common. Among persons who tested positive, 70% were prescribed antibiotics before positive coccidioidomycosis tests. Antibiotic treatment decreased and antifungal treatment increased after positive testing.
Repurposing the thrombopoietin receptor agonist eltrombopag as an anticryptococcal agent
Authors: Ko Hao-Tai , Hsu Li-Hang , Yang Sheng-Yung , Chen Ying-Lien
Published: June 2019

In this study, a Food and Drug Administration (FDA)-approved drug with previously unreported antifungal activity was investigated for suitability for use as an anticryptococcal agent. First, we screened a compound library of 1018 FDA-approved drugs against Cryptococcus neoformans. Of 52 drugs possessing anti-Cryptococcus activity, eltrombopag was chosen due to its novel activity. The susceptibility of Cryptococcus against eltrombopag was then studied by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), while the synergy of eltrombopag with other drugs was tested by fractional inhibitory concentration index (FICI). Eltrombopag had a limited spectrum of antifungal activity against C. neoformans/C. gattii species complex (MICs of 0.125 mg/l), Candida glabrata (MIC, 0.25 mg/l), and Trichophyton rubrum (MIC, 0.5 mg/l). Eltrombopag affected cryptococcal virulence factors, including capsule and biofilm formation, melanin production, and growth ability at 37°C. Further, RNA sequencing and deletion mutant library screening experiments revealed that genes involved in the calcineurin pathway, lipid biosynthesis, membrane component, and transporter genes were associated with eltrombopag. In addition, eltrombopag showed synergism with the calcineurin inhibitor FK506 (FICI < 0.5) against Cryptococcus species. In conclusion, eltrombopag exhibited excellent antifungal activity against Cryptococcus species potentially via a mode of action which interferes with virulence factors and the calcineurin pathway, indicating that eltrombopag might be usefully repurposed as an antifungal agent for treating cryptococcosis.
Probing dark matter structure down to 107 solar masses: flux ratio statistics in gravitational lenses with line-of-sight haloes
Authors: Gilman Daniel , Birrer Simon , Treu Tommaso , Nierenberg Anna , Benson Andrew
Published: June 2019

Strong lensing provides a powerful means of investigating the nature of dark matter as it probes dark matter structure on sub-galactic scales. We present an extension of a forward modelling framework that uses flux ratios from quadruply imaged quasars (quads) to measure the shape and amplitude of the halo mass function, including line-of-sight (LOS) haloes and main deflector subhaloes. We apply this machinery to 50 mock lenses – roughly the number of known quads – with warm dark matter (WDM) mass functions exhibiting free-streaming cut-offs parametrized by the half-mode mass mhm. Assuming cold dark matter (CDM), we forecast bounds on mhm and the corresponding thermal relic particle masses over a range of tidal destruction severity, assuming a particular WDM mass function and mass–concentration relation. With significant tidal destruction, at 2σ we constrain $m_{\rm {hm}}\lt 10^{7.9} \left(10^{8.4}\right) \, \mathrm{M}_{\odot }$, or a 4.4 (3.1) keV thermal relic, with image flux uncertainties from measurements and lens modelling of $2{{\ \rm per\ cent}} \left(6{{\ \rm per\ cent}}\right)$. With less severe tidal destruction we constrain $m_{\rm {hm}}\lt 10^{7} \left(10^{7.4}\right) \, \mathrm{M}_{\odot }$, or an 8.2 (6.2) keV thermal relic. If dark matter is warm, with $m_{\rm {hm}} = 10^{7.7} \, \mathrm{M}_{\odot }$ (5.1 keV), we would favour WDM with $m_{\rm {hm}} \gt 10^{7.7} \, \mathrm{M}_{\odot }$ over CDM with relative likelihoods of 22:1 and 8:1 with flux uncertainties of $2{{\ \rm per\ cent}}$ and $6{{\ \rm per\ cent}}$, respectively. These bounds improve over those obtained by modelling only main deflector subhaloes because LOS objects produce additional flux perturbations, especially for high-redshift systems. These results indicate that ∼50 quads can conclusively differentiate between WDM and CDM.
The magnetic properties of photospheric magnetic bright points with high-resolution spectropolarimetry
Authors: Keys Peter H , Reid Aaron , Mathioudakis Mihalis , Shelyag Sergiy , Henriques Vasco M J , Hewitt Rebecca L , Del Moro Dario , Jafarzadeh Shahin , Jess David B , Stangalini Marco
Published: June 2019

Magnetic bright points (MBPs) are small-scale magnetic elements ubiquitous across the solar disc, with the prevailing theory suggesting that they form due to the process of convective collapse. Employing a unique full Stokes spectropolarimetric data set of a quiet Sun region close to disc centre obtained with the Swedish Solar Telescope, we look at general trends in the properties of magnetic bright points. In total we track 300 MBPs in the data set and we employ NICOLE inversions to ascertain various parameters for the bright points such as line-of-sight magnetic field strength and line-of-sight velocity, for comparison. We observe a bimodal distribution in terms of maximum magnetic field strength in the bright points with peaks at ∼480 G and ∼1700 G, although we cannot attribute the kilogauss fields in this distribution solely to the process of convective collapse. Analysis of muram simulations does not return the same bimodal distribution. However, the simulations provide strong evidence that the emergence of new flux and diffusion of this new flux play a significant role in generating the weak bright point distribution seen in our observations.
Driver mutations in USP8 wild-type Cushing’s disease
Authors: Sbiera Silviu , Perez-Rivas Luis Gustavo , Taranets Lyudmyla , Weigand Isabel , Flitsch Jörg , Graf Elisabeth , Monoranu Camelia-Maria , Saeger Wolfgang , Hagel Christian , Honegger Jürgen , Assie Guillaume , Hermus Ad R , Stalla Günter K , Herterich Sabine , Ronchi Cristina L , Deutschbein Timo , Reincke Martin , Strom Tim M , Popov Nikita , Theodoropoulou Marily , Fassnacht Martin
Published: June 2019

Background

Medical treatment in Cushing’s disease (CD) is limited due to poor understanding of its pathogenesis. Pathogenic variants of ubiquitin specific peptidase 8 (USP8) have been confirmed as causative in around half of corticotroph tumors. We aimed to further characterize the molecular landscape of those CD tumors lacking USP8 mutations in a large cohort of patients.

Methods

Exome sequencing was performed on 18 paired tumor–blood samples with wild-type USP8 status. Candidate gene variants were screened by Sanger sequencing in 175 additional samples. The most frequent variant was characterized by further functional in vitro assays.

Results

Recurrent somatic hotspot mutations in another deubiquitinase, USP48, were found in 10.3% of analyzed samples. Several possibly damaging variants were found in TP53 in 6 of 18 samples. USP48 variants were associated with smaller tumors and trended toward higher frequency in female patients. They also changed the structural conformation of USP48 and increased its catalytic activity toward its physiological substrates histone 2A and zinc finger protein Gli1, as well as enhanced the stimulatory effect of corticotropin releasing hormone (CRH) on pro-opiomelanocortin production and adrenocorticotropic hormone secretion.

Conclusions

USP48 pathogenic variants are relatively frequent in USP8 wild-type tumors and enhance CRH-induced hormone production in a manner coherent with sonic hedgehog activation. In addition, TP53 pathogenic variants may be more frequent in larger CD tumors than previously reported.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Pediatric Myelomeningocele: Executive Summary
Authors: Mazzola Catherine A , Assassi Nadege , Baird Lissa C , Bauer David F , Beier Alexandra D , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Paul , McClung-Smith Catherine , Nikas Dimitrios C , Rehring Patricia , Tamber Mandeep S , Tyagi Rachana
Published: June 2019

BACKGROUND

The incidence of spina bifida (SB) in the developing world is higher than in the United States because of malnutrition and folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible.

OBJECTIVE

The objective of the guidelines are, (1) To create clinical recommendations for best practices, based on a systematic review and analysis of available literature, (2) to obtain multi-disciplinary endorsement of these guidelines from relevant organizations, and (3) to disseminate the educational content to physicians to improve the care of infants with MM.

METHODS

The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review.

RESULTS

Guidelines authors aimed to systematically review the literature and make evidence based recommendations about the timing of closure after birth, hydrocephalus, the impact of prenatal closure, and the effect of prenatal closure on ambulation ability and tethered spinal cord. Evidence concerning persistent ventriculomegaly and cognitive impairment was also evaluated. Hundreds of abstracts were identified and reviewed for each of the 5 topics. A total of 14 studies met stringent inclusion criteria.

CONCLUSION

Based on a comprehensive systematic review, a total of 5 clinical practice recommendations were developed, with 1 Level I, 2 Level II and 2 Level III recommendations.

The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-1.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Tethered Cord Syndrome in Infants With Myelomeningocele With Prenatal Versus Postnatal Repair
Authors: Mazzola Catherine A , Tyagi Rachana , Assassi Nadege , Bauer David F , Beier Alexandra D , Blount Jeffrey P , Durham Susan R , Flannery Ann Marie , Klimo Jr Paul , McClung-Smith Catherine , Nikas Dimitrios C , Rehring Patricia , Tamber Mandeep S
Published: June 2019

BACKGROUND

The incidence of spina bifida (SB) is higher in the developing world as compared to the United States because of folic acid deficiency during pregnancy. Advances in technology have made prenatal repair of myelomeningocele (MM) possible.

OBJECTIVE

The objective of this guideline was to determine if there is a difference in the rate of development of tethered cord syndrome (TCS) in infants who had prenatal closure compared to infants who had MM repair after birth.

METHODS

The Guidelines Task Force developed search terms and strategies to search PubMed and Embase for the relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used. Full text articles were reviewed and, when appropriate, included as evidence.

RESULTS

A total of 261 abstracts were reviewed. Fifty-four full-text articles were selected for further analysis. Three studies met inclusion criteria.

CONCLUSION

There was Class II evidence from 1 study and Class III evidence from another 2 studies demonstrating that TCS develops in infants with prenatal MM closure at an equal or higher rate than with postnatal closure. There was an increased risk of development of inclusion cysts in infants who underwent in utero closure. Continued surveillance for TCS and/or the development of inclusion cysts in children with prenatal and postnatal closure of MM is indicated (Level II). Differences between prenatal and postnatal repair with respect to the development of TCS and/or inclusion cysts should be considered alongside other relevant maternal and fetal outcomes when deciding upon a preferred method for MM closure.

The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-6.
Quantile regression for survival data in modern cancer research: expanding statistical tools for precision medicine
Authors: Hong Hyokyoung G , Christiani David C , Li Yi
Published: June 2019

Quantile regression links the whole distribution of an outcome to the covariates of interest and has become an important alternative to commonly used regression models. However, the presence of censored data such as survival time, often the main endpoint in cancer studies, has hampered the use of quantile regression techniques because of the incompleteness of data. With the advent of the precision medicine era and availability of high throughput data, quantile regression with high-dimensional predictors has attracted much attention and provided added insight compared to traditional regression approaches. This paper provides a practical guide for using quantile regression for right censored outcome data with covariates of low- or high-dimensionality. We frame our discussion using a dataset from the Boston Lung Cancer Survivor Cohort, a hospital-based prospective cohort study, with the goals of broadening the scope of cancer research, maximizing the utility of collected data, and offering useful statistical alternatives. We use quantile regression to identify clinical and molecular predictors, for example CpG methylation sites, associated with high-risk lung cancer patients, for example those with short survival.
Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine
Authors: Bilotta Anthony J , Cong Yingzi
Published: June 2019

The gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD). Diet is critical in the development and maintenance of a healthy microbiome, where dietary fiber (found in the highest amounts in fruits, vegetables, and legumes) is metabolized by the microbiome. In turn, the bacterial metabolites of dietary fiber, short chain fatty acids (SCFAs), regulate gut homeostasis. SCFAs engage G-protein coupled receptors (GPRs) and act as histone deacetylase inhibitors (HDACi) to module epithelial and immune cell functions in the intestines, where they generally promote an anti-inflammatory state. This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.
Linking Persistent Pain and Frailty in Older Adults
Authors: Guerriero Fabio , Reid M C
Published: June 2019

Objective

In older adults, the impact of persistent pain goes beyond simple discomfort, often contributing to worsening functional outcomes and ultimately frailty. Frailty is a geriatric syndrome that, like persistent pain, increases in prevalence with age and is characterized by a decreased ability to adapt to common stressors such as acute illness, thereby increasing risk for multiple adverse health outcomes. Evidence supports a relationship between persistent pain and both the incidence and progression of frailty, independent of health, social, and lifestyle confounders.

Design and Setting

In this article, we synthesize recent evidence linking persistent pain and frailty in an effort to clarify the nature of the relationship between these two commonly occurring geriatric syndromes.

Setting

We propose an integration of the frailty phenotype model by considering the impact of persistent pain on vulnerability toward external stressors, which can ultimately contribute to frailty in older adults.

Results and Conclusions

Incorporating persistent pain into the frailty construct can help us better understand frailty and ultimately improve care for patients with, as well as those at increased risk for, pain and frailty.
Simultaneous determination of the cosmic birefringence and miscalibrated polarization angles from CMB experiments
Authors: Minami Yuto , Ochi Hiroki , Ichiki Kiyotomo , Katayama Nobuhiko , Komatsu Eiichiro , Matsumura Tomotake
Published: June 2019

We show that the cosmic birefringence and miscalibrated polarization angles can be determined simultaneously by cosmic microwave background (CMB) experiments using the cross-correlation between $E$- and $B$-mode polarization data. This is possible because the polarization angles of the CMB are rotated by both the cosmic birefringence and miscalibration effects, whereas those of the Galactic foreground emission are rotated only by the latter. Our method does not require prior knowledge of the $E$- and $B$-mode power spectra of the foreground emission, but uses only the knowledge of the CMB polarization spectra. Specifically, we relate the observed $EB$ correlation to the difference between the observed$E$- and $B$-mode spectra in the sky, and use different multipole dependences of the CMB (given by theory) and foreground spectra (given by data) to derive the likelihood for the miscalibration angle $\alpha$ and the birefringence angle $\beta$. We show that a future satellite mission similar to LiteBIRD can determine $\beta$ with a precision of 10 arcmin.
Epigenetically quantified immune cells in salivary glands of Sjögren’s syndrome patients: a novel tool that detects robust correlations of T follicular helper cells with immunopathology
Authors: Blokland Sofie L M , van Vliet-Moret Fréderique M , Hillen Maarten R , Pandit Aridaman , Goldschmeding Roel , Kruize Aike A , Bouma Gerben , van Maurik André , Olek Sven , Hoffmueller Ulrich , van Roon Joel A G , Radstake Timothy R D J
Published: June 2019

Objective

To investigate whether epigenetic cell counting represents a novel method to quantify immune cells in salivary glands of patients with different forms of Sjögren’s and sicca syndrome and to capture immunopathology and potentially aid in diagnosis.

Methods

DNA from frozen salivary gland tissue sections of sicca patients was used for bisulphite conversion of demethylated DNA cytosine residues, followed by cell-specific quantitative PCR to calculate cell percentages in relation to total tissue cell numbers as quantified by housekeeping gene demethylation. The percentages of epigenetically quantified cells were correlated to RNA expression of matched salivary gland tissue and histological and clinical parameters.

Results

The percentages of epigenetically quantified CD3, CD4, CD8, T follicular helper (Tfh) cells, FoxP3+ regulatory T cells and B cells were significantly increased in the salivary glands of patients with SS. Unsupervised clustering using these percentages identified patient subsets with an increased lymphocytic focus score and local B cell hyperactivity and classifies patients different from conventional classification criteria. In particular, Tfh cells were shown to strongly correlate with the expression of CXCL13, lymphocytic focus scores, local B cell hyperactivity and anti-SSA positivity.

Conclusion

Epigenetic cell counting is a promising novel tool to objectively and easily quantify immune cells in the labial salivary gland of sicca patients, with a relatively small amount of tissue needed. In view of the potential of this technique to include a huge number of (cell-specific) biomarkers, this opens up new standardized ways of salivary gland analysis with high relevance for patient classification, understanding of immunopathology and monitoring of drug responses in clinical trials.
THERMOLUMINESCENCE SPECTRA AND DOSE RESPONSES OF SrSO4 PHOSPHORS DOPED WITH RARE EARTHS (Eu, Dy, Tm) AND PHOSPHORUS
Authors: Tang Qiang , Tang Huaming , Luo Daling , Zhang Chunxiang , Guo Jingyuan , Wu Huiping
Published: June 2019

The thermoluminescence (TL) spectra and dose responses of strontium sulphate doped with rare earth ions show that the SrSO4:Eu2+ phosphor might reasonably be assumed a isoelectronic trap sample which has unique TL characteristics: there is only one obvious glow peak at 385 nm, 489 K in the TL 3D emission spectra and its TL dose response is linear-sublinear. However, there are several elementary glow peaks in the TL 3D emission spectra and their TL dose responses are linear-supralinear for SrSO4:RE3+ (RE = Dy, Tm). These TL peaks occurred from low to high temperature indicate that the traps are distributed in different energy levels. When a suitable amount of other impurities co-doped into these SrSO4:RE3+, such as phosphorus, the relative intensities of these elementary glow peaks are changed significantly, especially the TL peak ~500 K is enhanced while the peaks at lower temperature are suppressed. The enhanced peak of SrSO4:RE3+,P is attributed to the deep traps. Their dose responses remain in nonlinearity when co-doped phosphorus. The above results and the luminescence properties of other sulphate doped rare earths impurities illustrate that the TL characteristics depend on the structure of defect complexes which can be assumed the basic elements in the TL multi-stage processes.
Medical Surveillance and Medical Confidentiality in an Age of Transition: The Debate over Cancer Registration in West Germany
Authors: Frohman Larry
Published: June 2019

In the 1970s, cancer registries emerged as an essential tool in West Germany’s efforts to control cancer. However, they assumed this new importance at the very moment when the West German public was becoming increasingly concerned about personal privacy and the potential harms resulting from the collection and use of personal information, and the ensuing debate over information access and privacy became one of the central axes for a broader rethinking of medical confidentiality between the 1970s and the early 1990s. Although this debate explored the complex relationship between patient privacy, patient treatment and the public interest as it spiralled across the 1980s, in the prevailing political climate, it proved impossible to devise an acceptable compromise. The conflict was not resolved until the turn of the 1990s, when technological and administrative innovation made it possible to sidestep the issue of consent with regard to cancer registration.
Bacillus thuringiensis cry1C expression from the plastid genome of poplar leads to high mortality of leaf-eating caterpillars
Authors: Wu Yuyong , Xu Letian , Chang Ling , Ma Meiqi , You Lili , Jiang Chunmei , Li Shengchun , Zhang Jiang
Published: June 2019

Plastid transformation technology has several attractive features compared with traditional nuclear transformation technology. However, only a handful of species are able to be successfully transformed. Here, we report an efficient and stable plastid transformation protocol for poplar, an economically important tree species grown worldwide. We transformed the Bacillus thuringiensis cry1C gene into the poplar plastid genome, and homoplasmic transplastomic poplar was obtained after two to three rounds of regeneration under antibiotic selection for 7–12 months. The transplastomic poplar expressing Cry1C insecticidal protein showed the highest accumulation level in young leaves, which reached up to 20.7 μg g-1 fresh weight, and comparatively low levels in mature and old leaves, and hardly detectable levels in non-green tissues, such as phloem, xylem and roots. Transplastomic poplar showed high toxicity to Hyphantria cunea and Lymantria dispar, two notorious forest pests worldwide, without affecting plant growth. These results are the first successful examples of insect-resistant poplar generation by plastid genome engineering and provide a new avenue for future genetic improvement of poplar plants.
Novel hepatitis D-like agents in vertebrates and invertebrates
Authors: Chang Wei-Shan , Pettersson John H-O , Le Lay Callum , Shi Mang , Lo Nathan , Wille Michelle , Eden John-Sebastian , Holmes Edward C
Published: June 2019

Hepatitis delta virus (HDV) is the smallest known RNA virus, encoding a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians, and invertebrates, with PCR and Sanger sequencing confirming the presence of the invertebrate HDV-like viruses. Notably, the novel viruses identified here share genomic features characteristic of HDV, such as a circular genome of only approximately 1.7 kb in length, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions, and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human viruses. Importantly, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV–HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV, but also shed light on its origin and evolutionary history.
Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases
Authors: Metintas Muzaffer , Ak Güntülü , Metintas Selma , Yildirim Huseyin , Dündar Emine , Rahman Najib
Published: June 2019

Background:

This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.

Methods:

Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan–guided Abrams’ needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan–guided Abrams’ needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.

Results:

A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.

Conclusion:

Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.
Coronary artery tortuosity: a narrative review
Authors: Kahe Farima , Sharfaei Sadaf , Pitliya Anmol , Jafarizade Mehrian , Seifirad Soroush , Habibi Shaghayegh , Chi Gerald
Published: June 2019

Coronary artery tortuosity (CAT) is a prevalent angiographic finding commonly associated with aging, hypertension, atherosclerosis and other conditions. Preliminary evidence suggests that degradation of elastin, a key component of extracellular matrix in the vascular wall, may be responsible for the development of CAT. The clinical significance of CAT should be considered in several aspects. First, coronary flow alteration associated with CAT may result in myocardial ischemia owing to reduced perfusion pressure distal to the tortuous segment. Second, increased and oscillatory shear stress in the tortuous vessel may promote atherosclerotic plaque formation and acute coronary syndrome. Third, as one of the criteria for coronary lesion complexity, the presence of severe tortuosity proximal to the culprit lesion may pose a challenge to wiring and stent or balloon delivery, thereby increasing the risk of periprocedural complications. Last, the presence of CAT may serve as a diagnostic clue of concurrent vasculopathy such as fibromuscular dysplasia or spontaneous coronary artery dissection. In general, CAT represents a benign entity that does not require specific treatment or intervention. Further research is warranted to elucidate the pathogenesis and prognostic effect of coronary tortuosity.
Effect of Patent Ductus Arteriosus on Splanchnic Oxygenation at Enteral Feeding Introduction in Very Preterm Infants
Authors: Martini Silvia , Corvaglia Luigi , Aceti Arianna , Vitali Francesca , Faldella Giacomo , Galletti Silvia
Published: June 2019

Because of its possible effect on mesenteric blood flow, the presence of a hemodynamically significant patent ductus arteriosus (PDA) is often of concern for the introduction of enteral feeds in preterm neonates. Near‐infrared spectroscopy allows a continuous monitoring of splanchnic oxygenation (SrSO2) and may provide useful hemodynamic information. This observational study evaluated SrSO2 patterns in response to first feed administration in 50 preterm infants <32 weeks’ gestation with different ductal status. According to their echocardiographic characteristics, the enrolled infants were divided into the following groups: pulsatile PDA with hemodynamically significant features, restrictive PDA, and no evidence of PDA. The presence of PDA, either with restrictive or hemodynamically significant characteristics, does not significantly affect SrSO2 response to enteral feeding introduction and is not associated with increased rates of gut complications. This finding may provide encouraging evidence in support of early enteral nutrition in very preterm infants with PDA.
Computed Tomography for 4-Dimensional Angiography and Perfusion Imaging of the Prostate for Embolization Planning of Benign Prostatic Hyperplasia
Authors: Kobe Adrian , Puippe Gilbert , Klotz Ernst , Alkadhi Hatem , Pfammatter Thomas
Published: June 2019

Objectives

The aim of this study was to evaluate the feasibility of a computed tomography (CT) protocol enabling the visualization of the prostatic artery (PA) before prostatic artery embolization (PAE) in benign prostatic hyperplasia, which provides quantitative perfusion information of the prostate gland.

Materials and Methods

In this institutional review board–approved study, 22 consecutive patients (mean age, 67 ± 7 years) who were planned to undergo PAE underwent a dynamic CT scan of the pelvis (scan range, 22.4 cm; cycle time, 1.5 seconds; scan time, 44 seconds; 25 scan cycles; 70 kVp; 100 mAs) after the administration of 70 mL of iodinated contrast media (flow rate, 6 mL/s; 10 seconds' delay). Image postprocessing consisted of a spatiotemporal, frequency-depending multiband filtering technique with noise reduction, motion correction, resulting in (1) time-resolved, temporal maximum intensity projection (MIP) images from fusion of multiple arterial time points; (2) 4-dimensional (4D) CT angiography images after bone and calcium plaque removal; and (3) parametric perfusion maps of the prostate. Intraprocedural cone-beam CT was performed with a microcatheter in the PA. In both modalities, the contrast-to-noise ratio of the right internal iliac artery or the PA was calculated, respectively. Visibility of the PA was scored using a Likert scale (score 1 = not seen, to score 4 = intraprostatic PA branches seen). Quantitative perfusion analysis of the dynamic pelvic CT included calculation of the blood flow, blood volume, mean transit time, and flow extraction product.

Results

The average volume CT dose index and dose length product of CT was 35.7 ± 6.8 mGy and 737.4 ± 146.3 mGy·cm, respectively. Contrast-to-noise ratio of the pelvic vessels on temporal MIP images and cone-beam CT were 45 ± 19 and 69 ± 27, respectively (P < 0.01). The mean visibility score of the PA was 3.6 ± 0.6 for 4D-CT angiography and 3.97 ± 0.2 for cone-beam CT (P < 0.001). The PA was visualized in 100% of 4D-CT angiography examinations, with one PA being visible only proximally. Prostate CT perfusion analysis showed blood flow, blood volume, mean transit time, and flow extraction product values of 27.9 ± 12.5 mL/100 mL/min, 2.0 ± 0.8 mL/100 mL, 4.5 ± 0.5 second, and 12.6 ± 5.4 mL/100 mL/min, respectively, for the whole prostate gland. About half the patients showed a pronounced difference between the lobes.

Conclusions

We introduced a CT protocol for PAE planning providing excellent visualization of the PA on temporal MIP images and 4D-CT angiography at a reasonable dose and low contrast volume. In addition, quantitative perfusion information is available, which might be useful for outcome prediction after embolization.
Cardiovascular Magnetic Resonance Imaging
Authors: Houbois Christian P. , Thavendiranathan Paaladinesh , Wintersperger Bernd J.
Published: June 2019

The era of modern oncology incorporates an ever-evolving personalized approach to hematological malignancies and solid tumors. As a result, patient survival rates have, in part, substantially improved, depending on the specific type of underlying malignancy. However, systemic therapies may come along with potential cardiotoxic effects resulting in heart failure with increased morbidity and mortality. Ultimately, patients may survive their malignancy but die as a result of cancer treatment. Cardiovascular magnetic resonance imaging has long been in use for the assessment of function and tissue characteristics in patients with various nonischemic cardiac diseases. Besides an introductory overview on the general definition of cardiotoxicity including potential underlying mechanisms, this review provides insight into the application of various cardiovascular magnetic resonance imaging techniques in the setting of cancer therapy–related cardiac and vascular toxicity. Early identification of cardiotoxic effects may allow for on-time therapy adjustment and/or cardioprotective measures to avoid subsequent long-term heart failure with increased mortality.
Derivation of oligodendrocyte precursor cells from human bone marrow stromal cells and use for re-myelination in the congenitally dysmyelinated brain
Authors: Lam Guy , Shea Graham Ka-Hon , Wu Lap Kei , Sui Maximillian Li Tak , Hei Kwok Chun , Kuen Zora Chan Chui , Cheuk Yin Yvonne Wong , Tsui Alex Yat Ping , Shum Daisy Kwok Yan , Chan Ying Shing
Published: June 2019

ABSTRACT/ SUMMARY

Oligodendrocytes (OLs) are the only myelinating glia in the central nervous system (CNS). In congenital myelin disorders, OL dysfunction or death results in loss of myelin. This causes progressive and irreversible impairment to motor and cognitive functions, and is amongst the most disabling neurological disorder.

Neonatal engraftment by glial progenitor cells (GPCs) allows the robust myelination of congenitally dysmyelinated brain, thereby preserving brain function and quality of life of patients. However, endogenous sources of glial progenitors are hard to obtain without causing secondary injury, while use of exogenous sources such as embryonic stem cells and induced-pluripotent stem cells face considerable ethical and safety issues.

To circumvent such hurdles, we asked whether NG2+cells in the bone marrow could be a potential cell source for GPCs. We successfully generated glial progenitor cells (GPCs) from human bone marrow stromal cells (hBMSCs) from 3 donors using a 14- day induction protocol. The generated hBMSC-GPCs were highly enriched in OPC marker expression, including OLIG2, PDGFRα, NG2, SOX10 and O4, and showed efficient differentiation into myelinogenic oligodendrocytes when transplanted into postnatal day 7 (P7) myelin-deficient shiverer mice. Remyelination of the shiverer mouse brain significantly extended lifespan and improved motor function.

The novel induction protocol described here provides a method for fast, simple and effective glial therapy for myelin disorders, overcoming existent hurdles of cell source restriction and time frame requirement.

Graphical Abstract

Highlights

- Human bone marrow stromal cells (BMSCs) can be programmed to myelinating glia (GPCs, glial progenitor cells), via a novel 14-dayin vitroinduction protocol

- Transplantation of these hBM-GPCs robustly remyelinated myelin deficient shiverer mice.

- hBM-GPC transplant significantly extended lifespan, increased body weight and improved motor function
Bayesian inference of power law distributions
Authors: Grigaityte Kristina , Atwal Gurinder
Published: June 2019

Observed data from many research disciplines, ranging from cellular biology to economics, often follow a particular long-tailed distribution known as a power law. Despite the ubiquity of natural power laws, inferring the exact form of the distribution from sampled data remains challenging. The possible presence of multiple generative processes giving rise to an unknown weighted mixture of distinct power law distributions in a single dataset presents additional challenges. We present a probabilistic solution to these issues by developing a Bayesian inference approach, with Markov chain Monte Carlo sampling, to accurately estimate power law exponents, the number of mixtures, and their weights, for both discrete and continuous data. We determine an objective prior distribution that is invariant to reparameterization of parameters, and demonstrate its effectiveness to accurately infer exponents, even in the low sample limit. Finally, we provide a comprehensive and documented software package, written in Python, of our Bayesian inference methodology, freely available at https://github.com/AtwalLab/BayesPowerlaw.
MiR-9-5p protects from kidney fibrosis by metabolic reprogramming
Authors: Fierro-Fernández Marta , Miguel Verónica , Márquez-Expósito Laura , Nuevo-Tapioles Cristina , Herrero J. Ignacio , Blanco-Ruiz Eva , Tituaña Jessica , Castillo Carolina , Cannata Pablo , Monsalve María , Ruiz-Ortega Marta , Ramos Ricardo , Lamas Santiago
Published: June 2019

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and control biological processes, including fibrogenesis. Kidney fibrosis remains a clinical challenge and miRNAs may represent a valid therapeutic avenue. We show that miR-9-5p protected from renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). This was reflected in reduced expression of pro-fibrotic markers, decreased number of infiltrating monocytes/macrophages and diminished tubular epithelial cell injury and transforming growth factor-beta 1 (TGF-β1)-dependent de-differentiation in human kidney proximal tubular (HKC-8) cells. RNA sequencing (RNA-Seq) studies in the UUO model revealed that this protection was mediated by a global shift in the expression profile of genes related to key metabolic pathways, including mitochondrial dysfunction, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis, preventing their UUO-dependent down-regulation. This effect was mirrored by a prevention in the TGF-β1-induced bioenergetics changes in HKC-8 cells. The expression of the FAO-related axis peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-peroxisome proliferator-activated receptor alpha (PPARα) was reduced by UUO, although preserved by the administration of miR-9-5p. We found that in mice null for the mitochondrial master regulator PGC-1α, miR-9-5p was unable to promote a protective effect in the UUO model. We propose that miR-9-5p elicits a protective response to chronic kidney injury and renal fibrosis by inducing reprogramming of the metabolic derangement and mitochondrial dysfunction affecting tubular epithelial cells.
Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis
Authors: Xu Jianquan , Ma Hongqiang , Ma Hongbin , Jiang Wei , Duan Meihan , Zhao Shimei , Gao Chenxi , Hahm Eun-Ryeong , Lardo Santana M. , Troy Kris , Sun Ming , Pai Reet , Stolz Donna B , Singh Shivendra , Brand Randall E , Hartman Douglas J. , Hu Jing , Hainer Sarah J. , Liu Yang
Published: June 2019

Aberrant chromatin structure is a hallmark in cancer cells and has long been used for clinical diagnosis of cancer. However, underlying higher-order chromatin folding during malignant transformation remains elusive, due to the lack of molecular scale resolution. Using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncovered a gradual decompaction and fragmented higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, even prior to the tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal the functional consequences in enhanced formation of transcription factories, spatial juxtaposition with relaxed nanosized chromatin domains and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin decompaction to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal the gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.

SIGNIFICANCE

Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although much progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the higher-order folding of chromatin structure remains largely unknown. Using optimized super-resolution microscopy, we uncover de-compacted and fragmented chromatin folding in tumor initiation and stepwise progression in multiple tumor types, even prior to the presence of tumor cells. This study underlines the significance of unfolding higher-order chromatin structure as an enabling characteristic to promote tumorigenesis, which may facilitate the development and evaluation of new preventive strategies. The potential of imaging higher-order chromatin folding to improve cancer detection and risk stratification is demonstrated by detecting high-risk precursors that cannot be distinguished by conventional pathology.