bluuebunny/crossref_metadata_2025 huggingface dataset:
Insecticide Resistance Status of Aedes aegypti (Diptera: Culicidae) in California by Biochemical Assays
Authors: Yang Fan , Schildhauer Samuel , Billeter Sarah A , Hardstone Yoshimizu Melissa , Payne Robert , Pakingan Mary Joyce , Metzger Marco E , Liebman Kelly A , Hu Renjie , Kramer Vicki , Padgett Kerry A
Published: March 2020

Insecticide resistance in Aedes aegypti mosquitoes poses a major threat to public health worldwide. There are two primary biological mechanisms that can lead to insecticide resistance, target site and metabolic resistance, both of which confer resistance to specific classes of insecticides. Due to the limited number of chemical compounds available for mosquito control, it is important to determine current enzymatic profiles among mosquito populations. This study assessed resistance profiles for three metabolic pathways, α-esterases, β-esterases, and mixed-function oxidases (MFOs), as well as insensitivity of the acetylcholinesterase (iAChE) enzyme in the presence of propoxur, among Ae. aegypti from the Central Valley and southern California. All field-collected Ae. aegypti demonstrated elevated MFOs and iAChE activity, indicating potential development of pyrethroid and organophosphate resistance, respectively. Although regional variations were found among α-esterase and β-esterase activity, levels were generally elevated, further suggesting additional mechanisms for developing organophosphate resistance. Furthermore, mosquito samples from southern California exhibited a higher expression level to all three metabolic enzymes and iAChE activity in comparison to mosquitoes from the central region. These results could help guide future mosquito control efforts, directing the effective use of insecticides while limiting the spread of resistance.
Enzyme-based protein-tagging systems for site-specific labeling of proteins in living cells
Authors: Sueda Shinji
Published: March 2020

Various protein-labeling methods based on the specific interactions between genetically encoded tags and synthetic probes have been proposed to complement fluorescent protein-based labeling. In particular, labeling methods based on enzyme reactions have been intensively developed by taking advantage of the highly specific interactions between enzymes and their substrates. In this approach, the peptides or proteins are genetically attached to the target proteins as a tag, and the various labels are then incorporated into the tags by enzyme reactions with the substrates carrying those labels. On the other hand, we have been developing an enzyme-based protein-labeling system distinct from the existing ones. In our system, the substrate protein is attached to the target proteins as a tag, and the labels are incorporated into the tag by post-translational modification with an enzyme carrying those labels followed by tight complexation between the enzyme and the substrate protein. In this review, I summarize the enzyme-based protein-labeling systems with a focus on several typical methods and then describe our labeling system based on tight complexation between the enzyme and the substrate protein.
Concomitant aortic valve replacement and retrosternal goitre resection via mini-sternotomy: a novel case
Authors: Karsan Rickesh B , Nanjaiah Prakash , Hogan John , Mehta Dheeraj , Stetchman Michael
Published: March 2020

Median sternotomy has been used to aide thyroidectomies demonstrating good outcomes; however no cases have been documented to show the use of mini-sternotomy to perform simultaneous thyroidectomy and valve surgery. We present a novel case of an 83-year-old woman with severe aortic stenosis and retrosternal goitre extending to the aortic arch deemed unsuitable for TAVI. Due to co-morbid status and anatomical position preventing routine thyroidectomy, we elected to perform a combined procedure to excise the goitre and perform an aortic valve replacement through a mini-J sternotomy, utilizing 3D-reconstructed imaging to plan our approach. This case shows that mini-sternotomy is a safe and effective method to perform concomitant thyroidectomy and aortic valve surgery.
Pneumomediastinum following spontaneous vaginal delivery: report of a rare phenomenon
Authors: Badran Dania , Ismail Safiyah , Ashcroft James
Published: March 2020

Pneumomediastinum is the presence of mediastinal air, which raises concern for life-threatening conditions such as esophageal perforation and mediastinitis. Here, we described the case of a young female with no previous past medical history, who developed spontaneous pneumomediastinum following uncomplicated spontaneous vaginal delivery (SVD) giving birth to a healthy newborn at full term. The incidence of benign pneumomediastinum following SVD is estimated at 1 in 100 000 deliveries. This case explores the etiology of this rare presentation, recommends essential investigations and advises on pertinent clinical considerations.
Traumatic Brain Injury, Working Memory, and Violent Crime in a Sample of U.S. Service Members Involved in the Military Justice System
Authors: Umbrasas Karl V
Published: March 2020

Introduction

This study examined working memory impairment following mild traumatic brain injury (mTBI) among active duty service members charged with criminal offenses. The prevalence of mTBI among service members involved in the military justice system is unknown. Impairments associated with mTBI may affect cognitive processes related to psycholegal capacities, and history of mTBI may have a persuasive appeal when explaining questions of culpability. The degree to which mTBI affects psycholegal abilities through cognitive impairment, however, is unknown.

Materials and Methods

This was a retrospective study of U.S. service members who presented for forensic evaluation (n = 80). Completed forensic evaluations (eg, criminal responsibility, competence to stand trial, risk assessment) were the source of data. Working Memory Index (WMI) score of the Wechsler Adult Intelligence Scale, Fourth Edition was used as an index of sequelae after brain injury.

Results

A history of mTBI was present in 20% of the sample. The mean time from mTBI diagnosis to presentation for forensic evaluation was 3.96 years. The mTBI-positive group had a mean WMI = 98 and the mTBI-negative group had a mean WMI = 103. The difference in WMI scores between groups was not statistically significant.

Conclusions

This study suggests that a history of mTBI is common among service members charged with criminal offenses. The findings that working memory scores were in the average range among service members with mTBI history may suggest that history of mTBI does not impair psycholegal relevant cognition. More research is needed to clarify how history of mTBI affects service member psycholegal capacities.
Venturing beyond the ISCO: detecting X-ray emission from the plunging regions around black holes
Authors: Wilkins D R , Reynolds C S , Fabian A C
Published: March 2020

We explore how X-ray reverberation around black holes may reveal the presence of the innermost stable circular orbit (ISCO), predicted by general relativity, and probe the dynamics of the plunging region between the ISCO and the event horizon. Being able to directly detect the presence of the ISCO and probe the dynamics of material plunging through the event horizon represents a unique test of general relativity in the strong field regime. X-ray reverberation off of the accretion disc and material in the plunging region is modelled using general relativistic ray tracing simulations. X-ray reverberation from the plunging region has a minimal effect on the time-averaged X-ray spectrum and the overall lag-energy spectrum, but is manifested in the lag in the highest frequency Fourier components, above $0.01\, c^{3}\, (GM)^{-1}$ (scaled for the mass of the black hole) in the 2–4 keV energy band for a non-spinning black hole or the 1–2 keV energy band for a maximally spinning black hole. The plunging region is distinguished from disc emission not just by the energy shifts characteristic of plunging orbits, but by the rapid increase in ionization of material through the plunging region. Detection requires measurement of time lags to an accuracy of 20 per cent at these frequencies. Improving accuracy to 12 per cent will enable constraints to be placed on the dynamics of material in the plunging region and distinguish plunging orbits from material remaining on stable circular orbits, confirming the existence of the ISCO, a prime discovery space for future X-ray missions.
The star formation histories of z ∼ 1 post-starburst galaxies
Authors: Wild Vivienne , Taj Aldeen Laith , Carnall Adam , Maltby David , Almaini Omar , Werle Ariel , Wilkinson Aaron , Rowlands Kate , Bolzonella Micol , Castellano Marco , Gargiulo Adriana , McLure Ross , Pentericci Laura , Pozzetti Lucia
Published: March 2020

We present the star formation histories of 39 galaxies with high-quality rest-frame optical spectra at 0.5 < z < 1.3 selected to have strong Balmer absorption lines and/or Balmer break, and compare to a sample of spectroscopically selected quiescent galaxies at the same redshift. Photometric selection identifies a majority of objects that have clear evidence for a recent short-lived burst of star formation within the last 1.5 Gyr, i.e. ‘post-starburst’ galaxies, however we show that good quality continuum spectra are required to obtain physical parameters such as burst mass fraction and burst age. Dust attenuation appears to be the primary cause for misidentification of post-starburst galaxies, leading to contamination in spectroscopic samples where only the [O ii] emission line is available, as well as a small fraction of objects lost from photometric samples. The 31 confirmed post-starburst galaxies have formed 40–90 per cent of their stellar mass in the last 1–1.5 Gyr. We use the derived star formation histories to find that the post-starburst galaxies are visible photometrically for 0.5–1 Gyr. This allows us to update a previous analysis to suggest that 25–50 per cent of the growth of the red sequence at z ∼ 1 could be caused by a starburst followed by rapid quenching. We use the inferred maximum historical star formation rates of several 100–1000 M⊙ yr−1 and updated visibility times to confirm that sub-mm galaxies are likely progenitors of post-starburst galaxies. The short quenching time-scales of 100–200 Myr are consistent with cosmological hydrodynamic models in which rapid quenching is caused by the mechanical expulsion of gas due to an acive galactic neucleus.
Stimulated emission–based model of fast radio bursts
Authors: Doğan Mustafa , Ekşi Kazım Yavuz
Published: March 2020

Fast radio bursts (FRBs) are bright, short-duration radio transients with very high brightness temperatures implying highly coherent emission. We suggest that the FRBs are caused by the self-focusing of an electron beam interacting with an ambient plasma right beyond the light cylinder radius of a neutron star. The magnetic field at the light cylinder radius is relatively high that can accommodate both young Crab-like systems and old millisecond pulsars addressing the diverse environments of FRBs. At the first stage, the intense pulsed-beam passing through the background plasma causes instabilities such that the trapped particles in local Buneman-type cavitons saturate the local field. The beam is then radially self-focused due to the circular electric field developed by the two-stream instability that leads to Weibel instability in the transverse direction. Finally, the non-linear saturation of the Weibel instability results in the self-modulational formation of solitons due to plasmoid instability. The resonant solitary waves are the breather-type solitons hosting relativistic particles with self-excited oscillations. The analytical solutions obtained for non-linear dispersion and solitons suggest that, near the current sheets, the relativistic bunches are accelerated/amplified by klystron-like structures due to self-excited oscillations by the induced local electric field. Boosted coherent radio emission propagates through a narrow cone with strong focusing due to radial electric field and magnetic pinching. The non-linear evolution of solitons and the stimulated emission are associated with the Buneman instability and the possibility of the presence of nanosecond shots in FRBs are investigated.
Evidence for cosmic acceleration with next-generation surveys: a model-independent approach
Authors: Bengaly Carlos A P
Published: March 2020

We quantify the evidence for cosmic acceleration using simulations of H(z) measurements from SKA- and Euclid-like surveys. We perform a non-parametric reconstruction of the Hubble parameters and its derivative to obtain the deceleration parameter q(z) using the Gaussian Processes method. This is a completely model-independent approach, so we can determine whether the Universe is undergoing accelerated expansion regardless of any assumption of a dark energy model. We find that Euclid-like and SKA-like band 1 surveys can probe cosmic acceleration at over 3 and 5σ confidence level, respectively. By combining them with an SKA-like band 2 survey, which reaches lower redshift ranges, the evidence for a current accelerated phase increases to over 7σ. This is a significant improvement from current H(z) measurements from cosmic chronometers and galaxy redshift surveys, showing that these surveys can underpin cosmic acceleration in a model-independent way.
The explosion energy of the type IIP supernova SN 2013fs with a confined dense circumstellar shell
Authors: Chugai N N
Published: March 2020

The recent study of the SN 2013fs flash spectrum suggests an enormous explosion energy for SNe IIP, far beyond the possibilities of the neutrino mechanism. The issue of the explosion energy of SN 2013fs is revisited, making use of the effects of the early supernova interaction with the dense circumstellar shell. The velocity of the cold dense shell between reverse and forward shocks is inferred from the analysis of the broad He ii 4686 Å on day 2.4. This velocity, alongside other observables, provides us with an alternative energy estimate of ∼1.8 × 1051 erg for the preferred mass of ∼10 M⊙. The inferred value is within the range of neutrino-driven explosions.
Barking Up the Wrong Tree: On Control, Transformative Experiences, and Turning Over a New Leaf
Authors: Herdova Marcela
Published: March 2020

I argue that we do not intentionally and rationally shape our character and values in major ways. I base this argument on the nature of transformative experiences, that is, those experiences which are transformative from personal and epistemological points of view. The argument is roughly this. First, someone who undergoes major changes in her character or values thereby undergoes a transformative experience. Second, if she undergoes such an experience, her reasons for changing in a major way are inaccessible to her beforehand. Third, if such reasons are inaccessible beforehand, she cannot act on them and thus cannot rationally and intentionally shape her character or values. I also explore some consequences of my argument, especially those related to control and responsibility.
Cancer-specific mutation of GATA3 disrupts the transcriptional regulatory network governed by Estrogen Receptor alpha, FOXA1 and GATA3
Authors: Takaku Motoki , Grimm Sara A , De Kumar Bony , Bennett Brian D , Wade Paul A
Published: March 2020

Estrogen receptors (ER) are activated by the steroid hormone 17β-estradiol. Estrogen receptor alpha (ER-α) forms a regulatory network in mammary epithelial cells and in breast cancer with the transcription factors FOXA1 and GATA3. GATA3 is one of the most frequently mutated genes in breast cancer and is capable of specifying chromatin localization of FOXA1 and ER-α. How GATA3 mutations found in breast cancer impact genomic localization of ER-α and the transcriptional network downstream of ER-α and FOXA1 remains unclear. Here, we investigate the function of a recurrent patient-derived GATA3 mutation (R330fs) on this regulatory network. Genomic analysis indicates that the R330fs mutant can disrupt localization of ER-α and FOXA1. Loci co-bound by all three factors are enriched for genes integral to mammary gland development as well as epithelial cell biology. This gene set is differentially regulated in GATA3 mutant cells in culture and in tumors bearing similar mutations in vivo. The altered distribution of ER-α and FOXA1 in GATA3-mutant cells is associated with altered chromatin architecture, which leads to differential gene expression. These results suggest an active role for GATA3 zinc finger 2 mutants in ER-α positive breast tumors.
Selective targeting of mutually exclusive DNA G-quadruplexes: HIV-1 LTR as paradigmatic model
Authors: Tassinari Martina , Zuffo Michela , Nadai Matteo , Pirota Valentina , Sevilla Montalvo Adriana Carolina , Doria Filippo , Freccero Mauro , Richter Sara N
Published: March 2020

Targeting of G-quadruplexes, non-canonical conformations that form in G-rich regions of nucleic acids, has been proposed as a novel therapeutic strategy toward several diseases, including cancer and infections. The unavailability of highly selective molecules targeting a G-quadruplex of choice has hampered relevant applications. Herein, we describe a novel approach, based on naphthalene diimide (NDI)-peptide nucleic acid (PNA) conjugates, taking advantage of the cooperative interaction of the NDI with the G-quadruplex structure and hybridization of the PNA with the flanking region upstream or downstream the targeted G-quadruplex. By biophysical and biomolecular assays, we show that the NDI-PNA conjugates are able to specifically recognize the G-quadruplex of choice within the HIV-1 LTR region, consisting of overlapping and therefore mutually exclusive G-quadruplexes. Additionally, the conjugates can induce and stabilize the least populated G-quadruplex at the expenses of the more stable ones. The general and straightforward design and synthesis, which readily apply to any G4 target of choice, together with both the red-fluorescent emission and the possibility to introduce cellular localization signals, make the novel conjugates available to selectively control G-quadruplex folding over a wide range of applications.
Small circRNAs with self-cleaving ribozymes are highly expressed in diverse metazoan transcriptomes
Authors: Cervera Amelia , de la Peña Marcos
Published: March 2020

Ribozymes are catalytic RNAs present in modern genomes but regarded as remnants of a prebiotic RNA world. The paradigmatic hammerhead ribozyme (HHR) is a small self-cleaving motif widespread from bacterial to human genomes. Here, we report that most of the classical type I HHRs frequently found in the genomes of animals are contained within a novel family of non-autonomous non-LTR retrotransposons of the retrozyme class. These retroelements are expressed as abundant linear and circular RNAs of ∼170-400 nt in different animal tissues. Bioinformatic and in vitro analyses indicate an efficient self-cleavage of the HHRs harboured in most invertebrate retrozymes, whereas HHRs in retrozymes of vertebrates, such as the axolotl and other amphibians, require to act as dimeric motifs to reach higher self-cleavage rates. Ligation assays of retrozyme RNAs with a protein ligase versus HHR self-ligation indicate that, most likely, tRNA ligases and not the ribozymes are involved in the step of RNA circularization. Altogether, these results confirm the existence of a new and conserved pathway in animals and, likely, eukaryotes in general, for the efficient biosynthesis of RNA circles through small ribozymes, which opens the door for the development of new tools in the emerging field of study of circRNAs.
MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence
Authors: Mathur Radhika , Zhang Yalan , Grimmer Matthew R , Hong Chibo , Zhang Michael , Bollam Saumya , Petrecca Kevin , Clarke Jennifer , Berger Mitchel S , Phillips Joanna J , Oberheim-Bush Nancy Ann , Molinaro Annette M , Chang Susan M , Costello Joseph F
Published: March 2020

Background

Emerging data suggest that a subset of patients with diffuse isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. It is currently unclear why some TMZ-treated LGG patients recur with hypermutation while others do not. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we hypothesize that epigenetic silencing of MGMT by promoter methylation facilitates TMZ-induced mutagenesis in LGG patients and contributes to development of hypermutation at recurrence.

Methods

We utilize a quantitative deep sequencing assay to characterize MGMT promoter methylation in 109 surgical tissue specimens from initial tumors and post-treatment recurrences of 37 TMZ-treated LGG patients. We utilize methylation arrays to validate our sequencing assay, RNA sequencing to assess the relationship between methylation and gene expression, and exome sequencing to determine hypermutation status.

Results

Methylation level at the MGMT promoter is significantly higher in initial tumors of patients that develop hypermutation at recurrence relative to initial tumors of patients that do not (45.7% vs 34.8%, P = 0.027). Methylation level in initial tumors can predict hypermutation at recurrence in univariate models and multivariate models that incorporate patient age and molecular subtype.

Conclusions

These findings reveal a mechanistic basis for observed differences in patient susceptibility to TMZ-driven hypermutation. Furthermore, they establish MGMT promoter methylation level as a potential biomarker to inform clinical management of LGG patients, including monitoring and treatment decisions, by predicting risk of hypermutation at recurrence.
A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma
Authors: Puduvalli Vinay K , Wu Jing , Yuan Ying , Armstrong Terri S , Vera Elizabeth , Wu Jimin , Xu Jihong , Giglio Pierre , Colman Howard , Walbert Tobias , Raizer Jeffrey , Groves Morris D , Tran David , Iwamoto Fabio , Avgeropoulos Nicholas , Paleologos Nina , Fink Karen , Peereboom David , Chamberlain Marc , Merrell Ryan , Penas Prado Marta , Yung W K Alfred , Gilbert Mark R
Published: March 2020

Background

Bevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab.

Methods

This multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and clinical outcomes assessment (MD Anderson Symptom Inventory Brain Tumor module [MDASI-BT]). Eligible patients were adults (≥18 y) with histologically confirmed GBM recurrent after prior radiation therapy, with adequate organ function, KPS ≥60, and no prior bevacizumab or HDAC inhibitors.

Results

Ninety patients (bevacizumab + vorinostat: 49, bevacizumab: 41) were enrolled, of whom 74 were evaluable for PFS (bevacizumab + vorinostat: 44, bevacizumab: 30). Median PFS (3.7 vs 3.9 mo, P = 0.94, hazard ratio [HR] 0.63 [95% CI: 0.38, 1.06, P = 0.08]), median OS (7.8 vs 9.3 mo, P = 0.64, HR 0.93 [95% CI: 0.5, 1.6, P = 0.79]) and clinical benefit were similar between the 2 arms. Toxicity (grade ≥3) in 85 evaluable patients included hypertension (n = 37), neurological changes (n = 2), anorexia (n = 2), infections (n = 9), wound dehiscence (n = 2), deep vein thrombosis/pulmonary embolism (n = 2), and colonic perforation (n = 1).

Conclusions

Bevacizumab combined with vorinostat did not yield improvement in PFS or OS or clinical benefit compared with bevacizumab alone or a clinical benefit in adults with recurrent GBM. This trial is the first to test a Bayesian adaptive design with adaptive randomization and Bayesian continuous monitoring in patients with primary brain tumor and demonstrates the feasibility of using complex Bayesian adaptive design in a multicenter setting.
Associations of maternal stress and/or depressive symptoms with diet quality during pregnancy: a narrative review
Authors: Boutté Alycia K , Turner-McGrievy Gabrielle M , Wilcox Sara , Liu Jihong , Eberth Jan M , Kaczynski Andrew T
Published: March 2020

Background

Pregnancy can be a stressful time for many women; however, it is unclear if higher stress and depressive symptoms are associated with poorer diet quality during pregnancy.

Objective

The aims for this narrative review were to (1) synthesize findings of original, peer-reviewed studies that examined associations of stress and/or depressive symptoms with diet quality during pregnancy; (2) review the measurement tools used to assess stress, depressive symptoms, and diet quality; (3) identify current gaps in the extant literature; and (4) offer recommendations for future research.

Methods

A search strategy was used to identify peer-reviewed manuscripts published between January 1997 and October 2018, using the following databases: PubMed, CINAHL Complete, PsycINFO, Academic Search Complete, and Psychology & Behavioral Sciences Collection. The search was updated December 2019. Two reviewers independently assessed title, abstract, and full-text of the studies that met the inclusion criteria. Data were extracted and a quality assessment was conducted.

Results

Twenty-seven observational studies were identified in this review (21 cross-sectional and 6 longitudinal). In 22 studies, higher stress and/or depressive symptoms were associated with poorer diet quality or unhealthy dietary patterns; 5 studies found no association. Findings are mixed and inconclusive regarding the relationship among stress, depressive symptoms, and food groups related to diet quality and frequency of fast-food consumption.

Conclusions

The current data suggest stress and depressive symptoms may be a barrier to proper diet quality during pregnancy; however, variability in the assessment tools, timing of assessments, and use of covariates likely contribute to the inconsistency in study findings. Gaps in the literature include limited use of longitudinal study designs, limited use of comprehensive diet-quality indices, underrepresentation of minority women, and lack of multilevel theoretical frameworks. Studies should address these factors to better assess associations of stress and/or depressive symptoms with diet quality during pregnancy.
J. Laurence Laughlin versus Irving Fisher on the quantity theory of money, 1894 to 1913
Authors: Dimand Robert W
Published: March 2020

In the controversy leading to the Federal Reserve Act of 1913, J. Laurence Laughlin of the University of Chicago and Irving Fisher of Yale were the leading opponent and proponent, respectively, of the quantity theory of money as the theoretical basis for reorganizing the US monetary system. Laughlin identified the quantity theory with bimetallist claims that monetizing silver would have lasting real benefits. Laughlin offered a cost of production theory of the value of gold as an alternative to the quantity theory, while his students published empirical critiques of the quantity theory. Fisher upheld the quantity theory as explaining price movements while distancing the theory from assertions of long-run non-neutrality of money. Laughlin and Fisher vigorously debated monetary theory and monetary reform, notably at American Economic Association meetings. Their confrontations illuminate the monetary controversies preceding the Federal Reserve Act, which reflected the views of Laughlin and Willis (adviser to Congressman Carter Glass) while rejecting the mandate to stabilize the price level proposed by Senator Owen and his adviser Fisher.
Clinical practice guidelines and recommendations for the management of patients with systemic lupus erythematosus: a critical comparison
Authors: Oliveira Margarida , Palacios-Fernandez Sergio , Cervera Ricard , Espinosa Gerard
Published: March 2020

Objective

SLE has a great clinical heterogeneity and low prevalence, thus making the development of recommendations or clinical practice guidelines (CPG) based on high-quality evidence difficult. In the last few years, several CPG appeared addressing the management of the disease. The aim of this review is to critically compare the recommendations made in the most recent CPG and to analyse and compare their methodological quality.

Methods

The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool was used to compare the methodological quality of each of the CPG.

Results

Most CPG agreed in the general management and first-line treatment recommendations where there is higher quality evidence and disagreed in refractory disease treatment where there is lack of quality evidence. Also, the CPG are agreed in whether a patient should be treated regarding the most severe clinical manifestation or taking into account the treatment that best serves all clinical manifestations. The majority of the appraised CPG scored high-quality ratings, especially for scope and purpose and clarity of presentation, while they were of less quality when assessing applicability of each CPG.

Conclusion

CPG should aid, but not replace, the health professional’s clinical judgment in daily clinical patient management.
Stachybotriaceae on Cucurbits Demystified: Genetic Diversity and Pathogenicity of Ink Spot Pathogens
Authors: Rennberger Gabriel , Keinath Anthony P.
Published: March 2020

Recently, the incidence of Myrothecium leaf spot, a foliar disease of watermelon, has increased in South Carolina. However, the identity of the fungal species responsible for outbreaks of this disease has not been determined. Sequence data from four partial gene regions were used to conduct Bayesian inference in order to identify 95 isolates of Stachybotriaceae. Isolates were collected in South Carolina between July 2015 and May 2018. In total, six species of Stachybotriaceae were identified on watermelon and two other cucurbits: Albifimbria verrucaria, Gregatothecium humicola, Paramyrothecium foliicola, P. humicola, Xenomyrothecium tongaense, and Xepicula leucotricha. Two species, G. humicola and P. foliicola, were the predominant species found. Within these two species, genetic differences within small spatial scales were detected. Five species (all except Xenomyrothecium tongaense) were tested in experiments to determine their pathogenicity and relative virulence on three hosts grown in rotation in South Carolina. Southern pea plants were less susceptible than watermelon and tomato plants, which were equally susceptible. This constitutes the first reliable report of pathogenicity of any of the five tested species of Stachybotriaceae on these three vegetable crops. Another important finding was that none of the isolates were identified as P. roridum, the species considered to be the only causal agent of Myrothecium leaf spot on cucurbits. We propose the common name “ink spot” for the foliar phase of diseases caused by genera within the family Stachybotriaceae. This name is descriptive and likely to be accepted by growers. To prevent further loss incurred by ink spot, watermelon and tomato crops should be monitored for this disease.
Therapeutic targeting of the DNA damage response in prostate cancer
Authors: Marshall Catherine H. , Antonarakis Emmanuel S.
Published: March 2020

Purpose of review

The present article highlights the most common DNA repair gene mutations, using specific examples of individual genes or gene classes, and reviews the epidemiology and treatment implications for each one [with particular emphasis on poly-ADP-ribose polymerase (PARP) inhibition and PD-1 blockade].

Recent findings

Genetic and genomic testing have an increasingly important role in the oncology clinic. For patients with prostate cancer, germline genetic testing is now recommended for all men with high-risk and metastatic disease, and somatic multigene tumor testing is recommended for men with metastatic castration-resistant disease. The most common mutations that are present in men with advanced prostate cancer are in genes coordinating DNA repair and the DNA damage response.

Although much of what is discussed currently remains investigational, it is clear that genomically-targeted treatments will become increasingly important for patients with prostate cancer in the near future and beyond.
Pelvic floor disorders in women with premature ovarian insufficiency: a cross-sectional study
Authors: Fante Júlia Ferreira , Machado Helymar da Costa , Juliato Cassia Raquel Teatin , Benetti-Pinto Cristina Laguna , Brito Luiz Gustavo Oliveira
Published: March 2020

Objectives:

This study aimed to investigate the prevalence of self-reported main pelvic floor disorders (PFD) (urinary incontinence [UI], pelvic organ prolapse [POP], and fecal incontinence [FI]) and its associated factors in women with premature ovarian insufficiency (POI) and a control group.

Methods:

This was a cross-sectional study wherein two groups were interviewed from August, 2017 to November, 2018—women with POI (n = 150) and a control group matched for age and body weight (n = 150). Sociodemographic variables and two questionnaires validated in Brazilian Portuguese language for PFD (Kings Health Questionnaire [KHQ] and Pelvic Floor Distress Inventory—20 [PFDI-20]) were used. Laycock's power, endurance, repetitions, fast contractions, every contraction timed (PERFECT) scale for pelvic floor muscle assessment was used in both groups.

Results:

The prevalence of self-reported UI was 27.33% and 37.33% for POI and control groups (P > 0.05), respectively. There was no perceived difference regarding the prevalence of POP (9.33% POI group vs 8% control group; P = 0.682) and FI (8% POI vs 4% control group; P = 0.145). The P (power) (P = 0.46), E (endurance) (P = 0.91), R (repetitions) (P = 0.88), and F (fast contractions) (P = 0.19) values were statistically similar in both the groups. Multivariate analysis (n = 141) showed that higher weight (odds ratio [OR] 1.047 [1.018-1.076]; P < 0.001) and gravidity rates (OR 1.627 [1.169-2.266]; P < 0.01) were risk factors for UI and higher weight (OR 1.046 [1.010-1.084]; P = 0.01), and presence of comorbidities (OR 8.75 [1.07-71.44]; P < 0.01) were risk factors for POP in the POI group; there was no variable that was associated with FI.

Conclusions:

Women with POI did not have significant differences when compared with the control group regarding the prevalence of PFD and pelvic floor muscle assessment. Having higher weight and gravidity rates were associated with self-reported UI, while the presence of comorbidities and higher weight were risk factors for POP in the POI group.

Video Summary:
http://links.lww.com/MENO/A555.
The many flavors of monocyte/macrophage--endothelial cell interactions
Authors: Hernandez Gloria E. , Iruela-Arispe M. Luisa
Published: March 2020

Purpose of review

The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages originated directly from embryonic progenitors, populate and establish residency in all tissues examined so far. This review aims to summarize our current understanding on the diversity of monocyte/macrophage subtypes associated with the vasculature, their specific origins, and nature of their cross-talk with the endothelium.

Recent findings

Taking stock of the many interactions between the endothelium and monocytes/macrophages reveals a far more intricate and ever-growing depth. In addition to circulating and surveilling the endothelium, monocytes can specifically be differentiated into patrolling cells that crawl on the surface of the endothelium and promote homeostasis. The conversion of classical to patrolling is endothelium-dependent uncovering an important functional link. In addition to patrolling cells, the endothelium also recruits and harbor an intimal-resident myeloid population that resides in the tunica intima in the absence of pathological insults. Moreover, the adventitia is populated with resident macrophages that support blood vessel integrity and prevent fibrosis.

The last few years have witnessed a significant expansion in our knowledge of the many subtypes of monocytes and macrophages and their corresponding functional interactions with the vascular wall. In addition to surveying the endothelium for opportunities of diapedeses, monocyte and macrophages take residence in both the intima (as patrolling or resident) and in the adventitia. Their contributions to vascular function are broad and critical to homeostasis, regeneration, and expansion.
Small molecule therapeutics to treat the β-globinopathies
Authors: Yu Lei , Myers Greggory , Engel James D.
Published: March 2020

Purpose of review

The current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies.

Recent findings

Recent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies.

We summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target for therapeutic purposes, we next address the contributions of protein complexes associated with these HPFH mutation-affected transcription factors with the aim of defining proteins that might provide additional targets for chemical molecules to inactivate the corepressors. Among the enzymes associated with the transcription factor complexes, a group of corepressors with currently available inhibitors were initially thought to be good candidates for potential therapeutic purposes. We discuss possibilities for pharmacological inhibition of these corepressor enzymes that might significantly reactivate fetal γ-globin gene expression. Finally, we summarize the current clinical trial data regarding the inhibition of select corepressor proteins for the treatment of sickle cell disease and β-thalassemia.
Reasons for worldwide decline in male fertility
Authors: Mann Uday , Shiff Benjamin , Patel Premal
Published: March 2020

Purpose of review

To review the evidence regarding a decrease in worldwide sperm parameters and discuss potential causative factors.

Recent findings

The topic of worldwide decline in sperm parameters is contentious; however, recent high-quality studies have demonstrated that there is indeed a decline in sperm parameters. Several retrospective and basic science studies have shown possible links for this decline in sperm parameters such as obesity, diet, and environmental toxins.

There exist substantial data to suggest a decline in sperm counts over time. Although causative factors have yet to be fully elucidated, potential causes include, increased rates of obesity, poor diet, and exposure to environmental toxins. How this decline in sperm counts reflects fertility has yet to be determined. As such, further studies are necessary to evaluate whether this decline in sperm count correlates with decreased fecundity and how to identify and mitigate potential causative factors.
Desmoplasia and Biophysics in Pancreatic Ductal Adenocarcinoma
Authors: Di Maggio Francesco , El-Shakankery Karim Hussien
Published: March 2020

Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.
Clinical Practice Guidelines for Pancreatic Cancer 2019 From the Japan Pancreas Society
Authors: Okusaka Takuji , Nakamura Masafumi , Yoshida Masahiro , Kitano Masayuki , Uesaka Katsuhiko , Ito Yoshinori , Furuse Junji , Hanada Keiji , Okazaki Kazuichi
Published: March 2020

Objectives

Clinical Practice Guidelines for Pancreatic Cancer were first published in 2006 by the Japan Pancreas Society, and they were revised in 2009, 2013, and 2016. In July 2019, the Clinical Practice Guidelines for Pancreatic Cancer 2019 were newly revised in Japanese.

Methods

For this version, we developed the new guidelines according to the Minds Manual for Guideline Development 2017, which includes the concepts of GRADE (Grading Recommendations Assessment, Development, and Evaluation), to enable a better understanding of the current guidelines.

Results

The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive and palliative medicine. They include 56 clinical questions and 84 statements. There are statements corresponding to clinical questions, evidence levels, recommendation strengths, and agreement rates.

Conclusions

These guidelines represent the most standard clinical and practical management guidelines at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2019 in Japanese and is an attempt to disseminate the Japanese guidelines worldwide for introducing the Japanese approach for clinical management of pancreatic cancer.
The “Far Left” of the Morphologic Spectrum of Ovarian High-grade Serous Carcinoma: Case Report of a Purely Noninvasive High-grade Serous Carcinoma Mimicking an Ovarian Serous Borderline Tumor
Authors: Katsakhyan Levon , Baraban Ezra G. , Dumoff Kimberly L. , Burger Robert A. , Parikh Rupal , Cooper Kumarasen
Published: March 2020

High-grade serous carcinoma has a variety of different growth patterns, but is typically easily recognizable to pathologists and rarely confused with serous borderline tumors. We report a case of a 71-yr-old woman with a unilateral 5.1 cm ovarian cyst with small papillary projections on contrast-enhanced magnetic resonance imaging of the pelvis. Histologic examination showed a noninvasive papillary neoplasm with hierarchical branching and epithelial proliferation, and thus, at low magnification, bearing a striking resemblance to a serous borderline tumor. However, a more careful examination demonstrated high-grade cytologic features, nuclear pleomorphism, and abundant mitotic activity, suggestive of high-grade serous carcinoma. The morphology and immunohistochemical profile of this lesion is consistent with a rare, purely noninvasive growth pattern of high-grade serous carcinoma. This lesion represents the “far left” of the high-grade ovarian serous carcinoma morphologic spectrum and can mimic a serous borderline tumor.
Decolourization of crystal violet using nano-sized novel fluorite structure Ga2Zr2−xWxO7photocatalyst under visible light irradiation
Authors: Abbas H. A. , Nasr Rabab A. , Abu-Zurayk Rund , Al Bawab Abeer , Jamil Tarek S.
Published: March 2020

Fluorite-type Zr-based oxides with the composition Ga2Zr2−xWxO7(x= 0, 0.05, 0.1, 0.15 and 0.2) were prepared using the citrate technique. Appropriate characterizations of all prepared materials were carried out. X-ray diffraction clarified that the undoped and W-doped Ga2Zr2O7samples were crystallized in the cubic fluorite phase structure. The average particle size of the samples was in the range of 3–8 nm. The lowest band gap (1.7 eV) and the highest surface area (124.3 m2g−1) were recorded for Ga2Zr0.85W0.15O7.The photocatalytic impacts of the prepared systems were studied by removal of crystal violet (CV) dye employing visible light illumination and taking into consideration the initial dye concentrations, duration of visible irradiation treatment, catalysts dose and the dopant concentration. The obtained results showed higher dye removal with the boost of the catalyst dosage. W doping shifted the absorption to the visible light range by decreasing the band gap from 4.95 eV for parent Ga2Zr2O7to 1.7 eV for 15 mol% tungsten-doped Ga2Zr2O7enhancing the photocatalytic decolourization of CV from 4.2% to 83.6% for undoped and 15 mol% W-doped Ga2Zr2O7, respectively, at optimum operating conditions (pH 9, 1 g l−1catalyst dose and 300 min) while heavily doped W sample containing 20 mol% W showed lower removal than 15 mol% W-doped Ga2Zr2O7. Complete CV degradation using 15 mol% W-doped Ga2Zr2O7was attained with the assistance of 25 mmol l−1hydrogen peroxide. The reaction is aligned to pseudo-first-order kinetics. Different scavengers were introduced to decide the significance of the reactive species in CV degradation.O2−∙and h+had the major role in the degradation of CV by Ga2Zr2−xWxO7system compared with HO•.
Cracking failure of curved hollow tree trunks
Authors: Huang Yan-San , Chiang Pei-Lin , Kao Ying-Chuan , Hsu Fu-Lan , Juang Jia-Yang
Published: March 2020

Understanding the failure modes of curved hollow tree trunks is essential from both safety and conservation perspectives. Despite extensive research, the underlying mechanism that determines the cracking failure of curved hollow tree trunks remains unclear due to the lack of theoretical analysis that considers both the initial curvature and orthotropic material properties. Here we derive new mathematical expressions for predicting the bending moment,
M
crack
, at which the cracking failure occurs. The failure mode of a tree species is then determined, as a function of
t
/
R
and
cR
, by comparing
M
crack
with
M
bend
, where
t
,
R
and
c
are, respectively, the trunk wall thickness, outer radius and initial curvature;
M
bend
is the bending moment for conventional bending failure. Our equation shows that
M
crack
is proportional to the tangential tensile strength of wood

σ
T

, increases with
t
/
R
, and decreases with the final
cR
. We analyse 11 tree species and find that hardwoods are more likely to fail in conventional bending, whereas softwoods tend to break due to cracking. This is due to the softwoods' much smaller tangential tensile strength, as observed from the data of 66 hardwoods and 43 softwoods. For larger
cR
, cracking failure is easier to occur in curvature-decreasing bending than curvature-increasing due to additional normal tensile force
F
acting on the neutral cross-section; on the other hand, for smaller
cR
, bending failure is easier to occur due to decreased final curvature. Our formulae are applicable to other natural and man-made curved hollow beams with orthotropic material properties. Our findings provide insights for those managing trees in urban situations and those managing for conservation of hollow-dependent fauna in both urban and rural settings.