bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of evolution towards left midventricular obstruction in severe Anderson–Fabry cardiomyopathy
Authors: Graziani Francesca , Lillo Rosa , Panaioli Elena , Spagnoletti Gionata , Pieroni Maurizio , Ferrazzi Paolo , Camporeale Antonia , Verrecchia Elena , Sicignano Ludovico Luca , Manna Raffaele , Crea Filippo
Published: November 2020

Aims

In Fabry cardiomyopathy, left ventricular outflow tract obstruction mimicking hypertrophic cardiomyopathy is a very rare finding, with few cases reported and successfully treated with cardiac surgery. In our population of patients with Fabry disease and severe left ventricular hypertrophy (LVH) at the time of diagnosis, we observed an evolution towards a midventricular obstructive phenotype.

Methods and results

We present a case series of three classically affected Fabry male patients with significant diagnostic delay and severe cardiac involvement (maximal wall thickness >20 mm) at first evaluation. All patients developed midventricular obstructive form over time despite prompt initiation and optimal compliance to enzyme replacement therapy. The extension and distribution of the LVH, involving the papillary muscles, was the main mechanism of obstruction, unlike the asymmetric septal basal hypertrophy and the mitral valve abnormalities commonly seen as substrate of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

Conclusions

Fabry cardiomyopathy can evolve over time towards a midventricular obstructive form due to massive LVH in classically affected men with significant diagnostic delay and severe LVH before enzyme replacement therapy initiation. This newly described cardiac phenotype could represent an adverse outcome of the disease.
An empirical comparison of univariate versus multivariate methods for the analysis of brain–behavior mapping
Authors: Ivanova Maria V. , Herron Timothy J. , Dronkers Nina F. , Baldo Juliana V.
Published: November 2020

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much‐needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.
Dysregulation of tissue and serum microRNAs in organ transplant recipients with cutaneous squamous cell carcinomas
Authors: Geusau Alexandra , Borik‐Heil Liliane , Skalicky Susanna , Mildner Michael , Grillari Johannes , Hackl Matthias , Sunder‐Plassmann Raute
Published: November 2020

Micro RNAs (miRNAs) are considered as promising biomarkers for skin cancer. By next generation sequencing (NGS), we measured and compared miRNA expression profiles of tumor, peri‐lesional, and control tissue of immunosuppressed organ transplant recipients (OTR), suffering from localized cutaneous squamous cell carcinoma (cSCC). Out of 490 miRNAs detected in cSCC tissue, 23 significantly regulated miRNAs were selected for quantitative targeted analysis in serum samples of our patients and control sera from OTR without cSCC. Two onco‐miRNAs (mir‐1290, mir‐1246), previously identified as crucial drivers for tumor initiation and cancer progression, were significantly and exclusively upregulated in both tumor tissue and serum. This finding suggests that miRNA dysregulation in cSCC tissue is reflected in serum even in patients without advanced disease and highly differentiated cSCCs.
Factors affecting connectivity and sediment yields following wildfire and post‐fire salvage logging in California's Sierra Nevada
Authors: Olsen Will H. , Wagenbrenner Joseph W. , Robichaud Peter R.
Published: November 2020

Sediment delivery following post‐fire logging is a concern relative to water quality. While studies have assessed the effect of post‐fire logging on sediment yields at different spatial scales, none have explicitly identified sediment sources. Our goal was to quantify post‐fire and post‐salvage logging sediment yields and use rill patterns to identify sediment sources. We measured the extent and type of logging disturbance, length of rills per unit area or “rill density”, ground cover, and sediment yields in nine logged and five control small catchments or “swales”, 0.09 to 0.81 ha, for 5 years after the 2013 Rim Fire in California's Sierra Nevada. The logged swales had a mean ground disturbance of 31%. After the first wet season following logging, there was no difference in either mean rill density (0.071 and 0.088 m m−2, respectively) or mean transformed, normalized sediment yields between the control and logged swales. Untransformed mean sediment yields across three sites ranged from 0.11–11.8 and 1.1–3.2 Mg ha−1 for the controls and salvage‐logged swales, respectively. Rill density was strongly related to sediment yield and increased significantly with the amount of high‐traffic skid trail disturbance in logged swales. Rill density was not significantly related to the amount of bare soil despite a significant relationship between sediment yields and bare soil. Rills usually initiated in bare soil and frequently connected high traffic skid trails to the drainage network after being diverted by waterbars. Rill connectivity and sediment yields decreased in control and logged swales where vegetation or other surface cover was high, suggesting this cover disconnected rills from the drainage network. Increasing ground cover on skid trails and between areas disturbed by post‐fire logging and stream channels may reduce sediment yields as well as the hydrologic connectivity between hillslopes and the drainage network.
Probiotics for Parkinson's disease: Current evidence and future directions
Authors: Tan Ai Huey , Hor Jia Wei , Chong Chun Wie , Lim Shen‐Yang
Published: November 2020

The gut–brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short‐chain fatty acids in PD. In this regard, microbial‐directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/“normalization” of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo‐controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long‐term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.
Synthesis, Characterization, and Viscosification of Amidosulfobutaine and Zwitterionic Gemini Surfactants
Authors: Mansha Muhammad , Ullah Nisar , Kalgaonkar Rajendra A. , Baqader Nour
Published: November 2020

The viscoelastic surfactants (VES)‐based acid diverters are frequently used to divert acid flow from high‐permeability layers into low‐permeability for enhanced overall productivity of the treated well. In general, an optimum VES‐based system possesses advantages of decrease in absorption loss, damage of reservoir, and improved adaptability of active agents to high salinity. Herein, we report the synthesis of three new zwitterionic gemini surfactants (1–3) and previously known amidosulfobutaine (C18AMP3SB) has been accomplished for the investigation of diverting acid performance. The synthesis of these surfactants was achieved by the amidation of the acid chlorides of commercially available fatty acids with 3‐(dimethylamino)‐1‐propylamine followed by subsequent reactions with appropriate sultone or ethyl 4‐bromobutanoate. The synthesized surfactants were well characterized by spectroscopic methods including IR and NMR spectroscopy. The thermogravimetric analysis (TGA) results suggested that surfactants (1–3) and C18AMP3SB possess excellent thermal stability, with no appreciable loss of mass up to 300°C. The viscosity measurements of the neat surfactants (1–3) and C18AMP3SB were performed under various temperatures, in the presence of different concentration of calcium chloride salt with the aid shear viscosimetry. The analysis revealed that the viscosity of neat C18AMP3SB increases with increase in concentration of CaCl2. With 10% CaCl2 solution, the viscosity was increased from 7.5 to 33.55 cPs, whereas in 20% CaCl2 the viscosity reached to 102 cPs with rise in temperature from ambient to 90°C. Moreover, the viscosity of neat surfactants (1–3) did not exhibit any appreciable viscosity change under the experimental conditions. However, the mixture of surfactants (1–3) each in combination with C18AMP3SB (1:1) displayed significant upsurge in the viscosity, up to more than 10 folds.
Synthesis and Determination of Critical Micelle Concentration of Betainthioates Surfactants
Authors: Khalfallah Ali , Mazzouzi Salma
Published: November 2020

Two series of monotailed and bolaphiles surfactants having quaternary ammonium bromide polar head have been synthesized and characterized. The critical micelle concentration (CMC) of the synthesized cationic surfactants was determined by conductimetric method. According to CMC values, the increase in alkyl chain length leads to a decrease in CMC and the bola‐type exhibits a higher CMC than their counterpart's monotailed.
Effect of benzothiadiazole treatment on quality and anthocyanin biosynthesis in plum fruit during storage at ambient temperature
Authors: Huan Chen , Xu Qihang , Shuling Shen , Dong Jingxian , Zheng Xiaolin
Published: November 2020

BACKGROUND

Plums tend to experience a reduction in fruit quality due to ripening and they deteriorate quickly during storage at room temperature. Benzothiadiazole (BTH) is a plant elicitor capable of inducing disease resistance in many crops. In this study, the effect of BTH treatment on fruit ripening, fruit quality, and anthocyanin biosynthesis in ‘Taoxingli’ plum was investigated.

RESULTS

The results showed that BTH treatment could accelerate fruit ripening without affecting the incidence of fruit decay or the shelf life. Benzothiadiazole treatment improved the quality and consumer acceptability of ‘Taoxingli’ plums during storage by increasing the sweetness, red color formation, and the concentration of healthy antioxidant compounds. The BTH treatment could also effectively promote the biosynthesis of anthocyanin by enhancing the enzyme activities of phenylalanine ammonia‐lyase (PAL), dihydroflavonol 4‐reductase (DFR), anthocyanidin synthase (ANS), and uridine diphosphate flavonoid 3‐O‐glucosyltransferase (UFGT) and up‐regulating the gene expressions of PsPAL, PsCHI, PsDFR, PsANS, and PsUFGT during storage.

CONCLUSION

Benzothiadiazole treatment could be a potential postharvest technology for improving fruit quality and consumer acceptability in harvested plum fruit. © 2020 Society of Chemical Industry
Polyethyleneimine‐modified magnetic carbon nanotubes as solid‐phase extraction adsorbent for the analysis of multi‐class mycotoxins in milk via liquid chromatography–tandem mass spectrometry
Authors: Li Nan , Qiu Jing , Qian Yongzhong
Published: November 2020

Polyethyleneimine‐modified magnetic multi‐walled carbon nanotubes were developed to extract 10 mycotoxins. Simple modification of polyethyleneimine was achieved on the magnetic substrate by using an epoxy‐containing silane agent as a linker. The resultant magnetic adsorbent was integrated with reverse phase and anion exchange interaction sites. Under optimal extraction conditions, only 20.0 mg adsorbent was used to extract the mycotoxins from 50.0 mL loading solution. The maximum adsorption capacities of the adsorbent toward the mycotoxins ranged from 4.9 to 10.2 mg/g. Adsorption and desorption were completed within 3.0 and 2.0 min, respectively. The adsorbent could be used for six repeated runs without evident change in extraction performance. The adsorbent combined with liquid chromatography–tandem mass spectrometry was applied further to analyze the mycotoxins in milk. The absolute recoveries of the 10 mycotoxins ranged from 88.3 to 103.5% with relative standard deviations that ranged from 2.4 to 6.5%, and their limits of detection were 0.003 to 0.442 μg/kg. The proposed adsorbent has great potential in the routine analysis of mycotoxins in ordinary analytical chemistry laboratory.
Long‐Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease
Authors: Pagan Fernando L. , Wilmarth Barbara , Torres‐Yaghi Yasar , Hebron Michaeline L. , Mulki Sanjana , Ferrante Dalila , Matar Sara , Ahn Jaeil , Moussa Charbel
Published: November 2020

Background

Nilotinib is US Food and Drug Administration–approved for leukemia, and this open‐label study investigated the safety, tolerability, and potential clinical effects of nilotinib in medically optimized patients with Parkinson's disease.

Objectives

Safety and tolerability were the primary objectives, and clinical outcomes were exploratory.

Methods

A total of 63 patients completed a 15‐month phase 2, double‐blind, placebo‐controlled study and were rerandomized 1:1 into an open‐label study of nilotinib 150 mg versus 300 mg for 12 months.

Results

Nilotinib was safe and tolerated, and no adverse effects seemed to be related to the drug, and no differences in adverse events were observed between groups. Exploratory clinical outcomes showed that nilotinib 300 mg was remarkably stable from baseline to 27 months using partial and total Unified Parkinson's Disease Scale (UPDRS). Nilotinib 150 mg versus 300 mg, significantly declined using partial or the sum of UPDRS Parts I and II. There was no significant difference in nilotinib 150 mg versus 300 mg using UPDRS Part III (on levodopa) and total UPDRS Parts I to III. Subgroup analysis showed that late‐start nilotinib 150 mg significantly worsened using the sum of UPDRS Parts II + III and total UPDRS Parts I to III compared with late‐start nilotinib 300 mg. Quality of life using the Parkinson's Disease Questionnaire in nilotinib 150 mg significantly declined between 15 and 27 months compared with nilotinib 300 mg, and there was no change in cognition using the Montreal Cognitive Assessment between groups.

Conclusions

This study provides evidence that nilotinib is safe and tolerated in Parkinson's disease. The exploratory clinical data will inform an adequately powered larger study to evaluate the efficacy of nilotinib 300 mg in Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Fasciculation frequency at the biceps brachii and brachialis muscles is associated with amyotrophic lateral sclerosis disease burden and activity
Authors: Avidan Reuven , Fainmesser Yaara , Drory Vivian E. , Bril Vera , Abraham Alon
Published: November 2020

Introduction

Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we have explored the association between fasciculation frequency in a single location—biceps brachii and brachialis muscles (BB), and disease burden and activity.

Methods

Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow‐up. The association between fasciculations frequency at the BB and ALS Functional Rating Scale—Revised (ALSFRS‐R) and manual muscle testing (MMT) scores was determined.

Results

High fasciculation frequency at the BB, where detection rate was the highest, was associated with shorter disease duration, greater muscle thickness, higher MMT scores, and faster rate of decline in ALSFRS‐R initially, and MMT subsequently.

Discussion

High fasciculation frequency at the BB as determined by sonography, is associated with less impairment at time of examination, and a more active disease with a more rapid progression.
The Media as a Source of Weight Stigma for Pregnant and Postpartum Women
Authors: Nippert Kathryn E. , Tomiyama A. Janet , Smieszek Stephanie M. , Incollingo Rodriguez Angela C.
Published: November 2020

Objective

The media often contain weight‐stigmatizing material. However, little is known about pregnant and postpartum women’s experiences with media‐based weight stigma.

Methods

Two studies investigated weight stigma in the media from multiple perspectives. Study 1 analyzed open‐response examples of weight‐stigmatizing experiences coming from the media, broadly defined, from 123 pregnant and postpartum women (from a larger sample of 501). Study 2 identified online news‐media articles about pregnancy and weight published during the study 1 data collection period (August to November 2017).

Results

Study 1 revealed that weight stigma was common and frequent in media, manifesting across three themes: (1) ideal appearance of pregnant bodies, (2) pressure to quickly “bounce back” after birth to a prepregnancy appearance, and (3) media praising celebrities for achieving either of the previous themes. Study 2 identified 33 articles. A content analysis revealed that women with overweight or obesity were rarely portrayed in images. Additionally, discussion of weight was often negative, focusing on adverse maternal–child health consequences. Finally, media‐communicated ideals for weight and weight loss were often unrealistic and did not reference medical guidelines.

Conclusions

This work is the first to document that online news media are a pervasive and potentially distressing source of pregnancy‐related weight stigma, suggesting much‐needed reform in media guidelines.
‘Post‐NPM’ by force or fiat? A comparison of administrative reform trajectories in Brazil and Mexico1
Authors: Donadelli Flavia , Cunha Bruno Q. , Dussauge‐Laguna Mauricio I.
Published: November 2020

‘New Public Management’ (NPM) ideas gained widespread acceptance all over the world in the 1980s and 1990s. In developing countries, notable examples of its influence include the Brazilian ‘Master Plan for Reforming Public Administration’, launched in 1995 by president Cardoso, and the Mexican ‘Federal Public Administration Modernisation Programme’ created in the same year by president Zedillo. Both reflected NPM doctrine and advanced changes for the organisation of the Executive. This article explores the evolution of these two countries' managerial reforms and the extent to which they eventually continued converging (or not) around similar principles, such as those often referred to as ‘Post‐New Public Management’ (Post‐NPM). By applying quantitative textual analysis of official documents and an analysis of self‐reported institutional changes, the article concludes that despite their governing parties' strong political differences Mexico and Brazil did converge during the 2000s, improving controls from the centre, and prioritising the adoption of transparency and participation tools. The comparison of the trajectories of the administrative reforms of these countries between 1995 and 2016 contributes to international debates on policy convergence and Post‐NPM reforms.
Structural, thermal, and dielectric properties of porous PVDF/Li4Ti5O12 nanocomposite membranes for high‐power lithium‐polymer batteries
Authors: Nasrallah Doaa A. , El‐Metwally Essam G. , Ismail Ahmed M.
Published: November 2020

Polymer nanocomposites consisting of materials such as ionic polymers and nano‐ceramic fillers are widely used in high‐power lithium‐polymer batteries because of their high ionic conductivity, good mechanical strength, electrothermal stability, and better compatibility with electrodes. Nanocomposite films of polyvinylidene fluoride (PVDF)/lithium titanium oxide Li4Ti5O12 (LTO) with different volume fractions of LTO nanoparticles (NPs) are prepared via casting method. The DSC thermograms revealed a slight decrease in the melting temperature Tm and a noticeable reduction in the degree of crystallinity with increasing the volume fraction of LTO. This decrease is confirmed by the increment in the relative fraction of β‐phase in the PVDF matrix calculated from both XRD and FTIR. SEM images indicated the growth of porous globular structures in the presence of LTO NPs. Besides, the hydrophilicity of PVDF is improved by incorporating LTO NPs. The dielectric constant ε′(ω), loss ε″(ω), ac conductivity σac(ω), complex impedance Z*(ω), and Nyquist plots of PVDF/LTO nanocomposites are investigated in the temperature range from 303 to 413 K and frequency range from 100 Hz to 1 MHz. The σac(ω) and frequency exponent s are found to obey the correlated barrier hopping model. Values of the frequency exponent s and the charge carriers binding energy Wm for the studied nanocomposite films decrease with rising temperature and LTO addition. Furthermore, dielectric constant ε′(ω), loss ε″(ω), and ac electrical conductivity σac(ω) of films are found to be strongly frequency and temperature dependent. The localized states density N(EF) at the Fermi level increase with increasing temperature and LTO NPs volume fraction, resulting in the Wm decrease and the enhancement of the ac electrical conductivity σac(ω). The impedance spectrum and Nyquist plots provide an insight into the influence of LTO vol% in the resistive and capacitive characteristics of PVDF/LTO films. These results recommend the choice of LTO NPs as dopants to enhance the electrical properties of the PVDF matrix to be used in high‐power lithium‐ion batteries and electronic devices.
A quality improvement project to increase palliative care team involvement in pediatric oncology patients
Authors: Farooki Sana , Olaiya Oluwaseun , Tarbell Lisa , Clark Nicholas A. , Linebarger Jennifer S. , Stroh John , Ellis Kelstan , Lewing Karen
Published: November 2020

Background

Pediatric palliative care (PPC) for oncology patients improves quality of life and the likelihood of goal‐concordant care. However, barriers to involvement exist.

Objectives

We aimed to increase days between PPC consult and death for patients with refractory cancer from a baseline median of 13.5 days to ≥30 days between March 2019 and March 2020.

Methods

Outcome measure was days from PPC consult to death; process measure was days from diagnosis to PPC consult. The project team surveyed oncologists to identify barriers. Plan‐do‐study‐act cycles included establishing target diagnoses, offering education, standardizing documentation, and sending reminders.

Results

The 24‐month baseline period included 30 patients who died and 25 newly diagnosed patients. The yearlong intervention period included six patients who died and 16 newly diagnosed patients. Interventions improved outcome and process measures. Targeted patients receiving PPC ≥30 days prior to death increased from 43% to 100%; median days from consult to death increased from 13.5 to 159.5. Targeted patients receiving PPC within 30 days of diagnosis increased from 28% to 63%; median days from diagnosis to consult decreased from 221.5 to 14. Of those without PPC consult ≤ 30 days after diagnosis, 17% had template documentation of the rationale.

Conclusion

Interventions utilized met the global aim, outcome, and process measures. Use of QI methodology empowered providers to involve PPC. Poor template use was a barrier to identifying further drivers. Future directions for this project relate to expanding the target list, creating long‐term sustainability, formalizing standards, and surveying patients and families.
A Correlation between Structural Parameters and Electrical Conductivity of Calcium‐Modified Ba(Zr0.05Ti0.95)O3 Ceramic
Authors: Selvamani Rachna , Singh Gurvinderjit , Tiwari Vidya Sagar , Karnal Ashwani K.
Published: November 2020

Lead‐free (Ba1–xCax)(Zr0.05Ti0.95)O3 (x = 0.03, 0.05, 0.08, 0.10, 0.12, and 0.15) (BCZTx) ceramics are fabricated using the solid state reaction method. The ionic conductivity of the ceramic samples is investigated by complex impedance spectroscopy. The impedance measurements suggest that doubly charged oxygen vacancies ( are responsible for conduction and relaxation. The impedance measurements show that with increase in calcium content the ionic conductivity increases till x = 0.10 and thereafter it decreases gradually. This anomaly in the conductivity is discussed on the basis of structural parameters such as lattice free volume, tolerance factors, and number of equivalent oxygen sites. The presence of the anomaly at x = 0.10 is attributed to a balance between the number of equivalent oxygen sites increasing and the lattice free volume reducing with calcium content.
Polyamine pathway is associated with muscle anabolic effects by androgen receptor ligand
Authors: Kanou Masanobu , Nakamura Katsuyuki , Horie Kyohei , Sakai Hiroshi , Yanagihara Yuta , Sakakibara Iori , Yamana Kei , Imai Yuuki
Published: November 2020

Background

Muscle wasting is a common condition concomitant with aging. Androgens significantly increase skeletal muscle mass, but the role of the androgen receptor (AR) in skeletal muscle is not well established. TEI‐SARM2, a novel selective androgen receptor modulator (SARM), was developed as a pharmaceutical candidate for the treatment of muscle wasting diseases.

Methods

The efficacy and specificity of TEI‐SARM2 were analysed in vitro assays, and efficacy was also evaluated in vivo using orchiectomized male rats, rat tail‐suspension, rat and mice cancer‐induced muscle atrophy models, and female cynomolgus monkeys. Male myofibre‐specific AR‐knockout (mARKO) mice were orchiectomized to investigate the role of AR in muscle using TEI‐SARM2. RNA‐seq analysis of bulbocavernosus muscle was performed. The effects of spermidine were evaluated in C2C12 myoblasts.

Results

Selective, potent anabolic effects of TEI‐SARM2 in muscle were detected in rats and monkeys. TEI‐SARM2 inhibited muscle loss and promoted muscle recovery in a model of muscle disuse and prevented muscle wasting and improved survival rate in cancer models. In vivo and RNA‐seq analyses revealed that AR regulates skeletal muscle mass in myofibres and extra‐myofibres, both directly and indirectly. Among them, polyamine synthesis‐related genes were focused, and spermidine treatment could induce C2C12 cell proliferation.

Conclusions

TEI‐SARM2 exhibited potent and selective anabolic effects in muscles, as well as tissue specificity in various animal models. The results support that TEI‐SARM2 is a promising drug candidate for muscle wasting diseases. TEI‐SARM2 induced anabolic effects on skeletal muscle via AR in myofibres as well as other androgen target cells.
Assisted reproductive technology in Japan: A summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology
Authors: Ishihara Osamu , Jwa Seung Chik , Kuwahara Akira , Katagiri Yukiko , Kuwabara Yoshimitsu , Hamatani Toshio , Harada Miyuki , Osuga Yutaka
Published: November 2020

Purpose

Since 2007, the Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle‐based data for assisted reproductive technology (ART) in an online registry. Here, we present the characteristics and treatment outcomes of ART cycles registered during 2018.

Methods

The Japanese ART registry consists of cycle‐specific information for all ART treatment cycles implemented at 621 participating facilities. We conducted descriptive analyses for such cycles registered for 2018.

Results

In total, 454 893 treatment cycles and 56 979 neonates were reported in 2018: both increased from 2017. The mean maternal age was 38.0 years (standard deviation ± 4.7). Of 247 402 oocyte retrievals, 118 378 (47.8%) involved freeze‐all‐embryos cycles; fresh embryo transfer (ET) was performed in 50 463 cycles: a decreasing trend since 2015. A total of 199 914 frozen‐thawed ET cycles were reported, resulting in 69 357 pregnancies and 49 360 neonates born. Single ET (SET) was performed in 82.2% of fresh transfers and 83.4% of frozen‐thawed cycles, with singleton pregnancy/live birth rates of 97.2%/97.2% and 97.0%/97.2%, respectively.

Conclusions

Total ART cycles and subsequent live births increased in 2018. SET was performed in over 80% of cases, and the mode of ET has shifted continuously from using fresh embryos to frozen‐thawed ones compared with previous years.
Comparison of machine learning approaches used to identify the drivers of Bakken oil well productivity
Authors: Attanasi Emil D. , Freeman Philip A. , Coburn Timothy C.
Published: November 2020

Geologists and petroleum engineers have struggled to identify the mechanisms that drive productivity in horizontal hydraulically fractured oil wells. The machine learning algorithms of Random Forest (RF), gradient boosting trees (GBT) and extreme gradient boosting (XGBoost) were applied to a dataset containing 7311 horizontal hydraulically fractured wells drilled into the middle member of the Bakken Formation from 2010 through 2017. The initial goal is to use these data‐driven machine learning algorithms to identify the most important explanatory predictors of well productivity within nine subareas and the composite area. Predictor variables representing initial gas production, the initial 180‐day water cut, and vertical depth vary spatially and are identified with geologically favorable areas. Well‐completion predictors include the well lateral length, number of fracture stages, volume of proppant per stage, and the volume of injected fluids per stage. The performance of methods is compared based on a common test sample. The analysis then examines the comparative predictive performance of the three algorithms for 1330 wells that had initiated production after the initial 7311 well sample had been producing. The computations of predictor importance identified the initial 180‐day water cut and the 30‐day initial gas production predictors as having a dominant influence in most subareas and for the composite area. The relative importance of well completion predictor variables, that is, the number of fracture stages per well, volume of injected proppant per stage, volume of injected fluids per stage, and lateral length, varied considerably across the subareas. For the common test or holdout sample, the models calibrated with the XGBoost algorithm had superior predictive power. The predictive power of all the algorithms trained on the data from the original sample suffered some loss when tested with a sample of wells that had started production after the end of that period. Implications of the empirical findings and strategies to mitigate loss of predictive power are discussed in the concluding section.
Complex Morphogenesis by a Model Intrinsically Disordered Protein
Authors: González‐Obeso Constancio , González‐Pérez Miguel , Mano João F. , Alonso Matilde , Rodríguez‐Cabello José Carlos
Published: November 2020

The development of intricate and complex self‐assembling structures in the micrometer range, such as biomorphs, is a major challenge in materials science. Although complex structures can be obtained from self‐assembling materials as they segregate from solution, their size is usually in the nanometer range or requires accessory techniques. Previous studies with intrinsically disordered proteins (IDPs) have shown that the active interplay of different molecular interactions provides access to new and more complex nanostructures. As such, it is hypothesized that enriching the variety of intra‐ and intermolecular interactions in a model IDP will widen the landscape of sophisticated intermediate structures that can be accessed. In this study, a model silk‐elastin‐like recombinamer capable of interacting via three non‐covalent interactions, namely hydrophobic, ion‐pairing, and H‐bonding is built. This model material is shown to self‐assemble into complex stable micrometer‐sized biomorphs. Variation of the block composition, pH, and temperature demonstrates the necessary interplay of all three interactions for the formation of such complex structures.
Ultrasound assisted extraction and solvent partition for polyhydroxylated and polymethoxylated flavones and phenolic acids from Orthosiphon aristatus
Authors: Chan Hui Peng , Chua Lee Suan , Abdullah Farah Izana
Published: November 2020

The technique of ultrasound‐assisted extraction was used to recover polyhydroxylated and polymethoxylated flavones, and phenolic acids from Orthosiphon aristatus. The compounds were then partitioned in different solvents such as hexane, chloroform, ethyl acetate, and acetone with increasing polarity. This workflow would reduce the complexity of chemical composition in crude extract to ease phytochemical profiling using a high throughput analytical tool of liquid chromatography with tandem mass spectrometry. Several newly reported flavone derivatives such as velutin, tricin, 3,7‐dimethylquercetin, 4′,7′‐dimethoxyluteolin, 4′,7′‐dimethoxyluteolin‐dimethyl ether, and 5‐hydroxy‐3,4′,7‐trimethoxyflavone, in addition to previously reported compounds were detected. The recovered flavone derivatives were mostly lipophilic in nature because they were partitioned in hexane and chloroform, particularly the dimer and trimer of sinensetin. Meanwhile, phenolic acids such as rosmarinic acid and salvianolic acid were detected in the ethyl acetate and acetone fractions, as well as in the remaining aqueous residue. These phenolic acids rich fractions were also found to have higher antioxidant capacity than crude extract. The combination of ultrasound‐assisted extraction and solvent partition provided insights into the profile of polyhydroxylated and polymethoxylated flavones, and phenolic acids from the highly complex herbal plant of O. aristatus. The detection of the phytochemicals may explain the previously reported pharmacological properties of the herb.
Development of New Radical‐Mediated Selective Reactions Promoted by Hypervalent Iodine(III) Reagents
Authors: Matsumoto Akira , Lee Hyo‐Jun , Maruoka Keiji
Published: November 2020

In this account, we describe our recent developments on the four‐types of hypervalent iodine(III)‐mediated radical reactions in organic synthesis. Firstly, the activation of aldehydic C−H bonds can be successfully effected with hypervalent iodine(III) reagents, thereby allowing the synthesis of various ketones with high efficiency. Secondly, the site‐selective oxidation of unactivated C(sp3)−H bonds of hydrocarbon substrates was realized with designer hypervalent iodine(III) reagents. Thirdly, various perfluoroalkyl and α‐aminoalkyl radicals can be generated from sodium perfluoroalkanesulfinates and sodium α‐aminoalkanesulfinates, respectively, under the influence of hypervalent iodine(III) reagents. Finally, the efficient generation of difluoromethyl radical from hypervalent difluoroacetoxyliodine(III) reagent was realized by photolysis. These four different strategies are illustrated by using various selective radical approaches.
Shocks, superconvergence, and a stringy equivalence principle
Authors: Koloğlu Murat , Kravchuk Petr , Simmons-Duffin David , Zhiboedov Alexander
Published: November 2020

Abstract

We study propagation of a probe particle through a series of closely situated gravitational shocks. We argue that in any UV-complete theory of gravity the result does not depend on the shock ordering — in other words, coincident gravitational shocks commute. Shock commutativity leads to nontrivial constraints on low-energy effective theories. In particular, it excludes non-minimal gravitational couplings unless extra degrees of freedom are judiciously added. In flat space, these constraints are encoded in the vanishing of a certain “superconvergence sum rule.” In AdS, shock commutativity becomes the statement that average null energy (ANEC) operators commute in the dual CFT. We prove commutativity of ANEC operators in any unitary CFT and establish sufficient conditions for commutativity of more general light-ray operators. Superconvergence sum rules on CFT data can be obtained by inserting complete sets of states between light-ray operators. In a planar 4d CFT, these sum rules express $$ \frac{a-c}{c} $$

a
−
c

c

in terms of the OPE data of single-trace operators.
The cosmological phonon: symmetries and amplitudes on sub-horizon scales
Authors: Grall Tanguy , Jazayeri Sadra , Stefanyszyn David
Published: November 2020

Abstract

In contrast to massless spinning particles, scalars are not heavily constrained by unitarity and locality. Off-shell, no gauge symmetries are required to write down manifestly local theories, while on-shell consistent factorisation is trivial. Instead a useful classification scheme for scalars is based on the symmetries they can non-linearly realise. Motivated by the breaking of Lorentz boosts in cosmology, in this paper we classify the possible symmetries of a shift-symmetric scalar that is assumed to non-linearly realise Lorentz boosts as, for example, in the EFT of inflation. Our classification method is algebraic; guided by the coset construction and inverse Higgs constraints. We rediscover some known phonon theories within the superfluid and galileid classes, and discover a new galileid theory which we call the extended galileid. Generic galileids correspond to the broken phase of galileon scalar EFTs and our extended galileids correspond to special subsets where each galileon coupling is fixed by an additional symmetry. We discuss the broken phase of theories that also admit a perturbation theory around Poincaré invariant vacua and we show that the so-called exceptional EFTs, the DBI scalar and special galileon, do not admit such a broken phase. Concentrating on DBI we provide a detailed account of this showing that the scattering amplitudes are secretly Poincaré invariant when the theory is expanded around the superfluid background used in the EFT of inflation. We point out that DBI is an exception to the common lore that the residue of the total energy pole of cosmological correlators is proportional to the amplitude. We also discuss the inevitability of poles in 2 → 2 scattering amplitudes when boost are spontaneously broken meaning that such theories do not admit Adler zeros and generalisations even in the presence of a shift symmetry.
Sharp Asymptotics for the Solutions of the Three-Dimensional Massless Vlasov–Maxwell System with Small Data
Authors: Bigorgne Léo
Published: November 2020

This paper is concerned with the asymptotic properties of the small data solutions to the massless Vlasov–Maxwell system in 3d. We use vector field methods to derive almost optimal decay estimates in null directions for the electromagnetic field, the particle density and their derivatives. No compact support assumption in x or v is required on the initial data, and the decay in v is in particular initially optimal. Consistently with Proposition 8.1 of Bigorgne (Asymptotic properties of small data solutions of the Vlasov–Maxwell system in high dimensions. arXiv:1712.09698, 2017), the Vlasov field is supposed to vanish initially for small velocities. In order to deal with the slow decay rate of the solutions near the light cone and to prove that the velocity support of the particle density remains bounded away from 0, we make crucial use of the null properties of the system.
A landing theorem for entire functions with bounded post-singular sets
Authors: Benini Anna Miriam , Rempe Lasse
Published: November 2020

TheDouady-Hubbard landing theoremfor periodic external rays is one of the cornerstones of the study of polynomial dynamics. It states that, for a complex polynomialfwith bounded postcritical set, every periodic external ray lands at a repelling or parabolic periodic point, and conversely every repelling or parabolic point is the landing point of at least one periodic external ray. We prove an analogue of this theorem for an entire functionfwith bounded postsingular set. Iffhas finite order of growth, then it is known that the escaping setI(f) contains certain curves calledperiodic hairs; we show that every periodic hair lands at a repelling or parabolic periodic point, and conversely every repelling or parabolic periodic point is the landing point of at least one periodic hair. For a postsingularly bounded entire functionfof infinite order, such hairs may not exist. Therefore we introduce certain dynamically natural connected subsets ofI(f), calleddreadlocks. We show that every periodic dreadlock lands at a repelling or parabolic periodic point, and conversely every repelling or parabolic periodic point is the landing point of at least one periodic dreadlock. More generally, we prove that every point of a hyperbolic set is the landing point of a dreadlock.
Distribution-Valued Ricci Bounds for Metric Measure Spaces, Singular Time Changes, and Gradient Estimates for Neumann Heat Flows
Authors: Sturm Karl-Theodor
Published: November 2020

We will study metric measure spaces$$(X,\mathsf{d},{\mathfrak {m}})$$(X,d,m)beyond the scope of spaces with synthetic lower Ricci bounds. In particular, we introduce distribution-valued lower Ricci bounds$$\mathsf{BE}_1(\kappa ,\infty )$$BE1(κ,∞)

for which we prove the equivalence with sharp gradient estimates,

the class of which will be preserved under time changes with arbitrary$$\psi \in \mathrm {Lip}_b(X)$$ψ∈Lipb(X), and

which are satisfied for the Neumann Laplacian on arbitrary semi-convex subsets$$Y\subset X$$Y⊂X.

In the latter case, the distribution-valued Ricci bound will be given by the signed measure$$\kappa = k\,{\mathfrak {m}}_Y + \ell \,\sigma _{\partial Y}$$κ=kmY+ℓσ∂Ywherekdenotes a variable synthetic lower bound for the Ricci curvature ofXand$$\ell $$ℓdenotes a lower bound for the “curvature of the boundary” ofY, defined in purely metric terms. We also present a new localization argument which allows us to pass on the RCD property to arbitrary open subsets of RCD spaces. And we introduce new synthetic notions for boundary curvature, second fundamental form, and boundary measure for subsets of RCD spaces.
Complex Phase Retrieval from Subgaussian Measurements
Authors: Krahmer Felix , Stöger Dominik
Published: November 2020

Phase retrieval refers to the problem of reconstructing an unknown vector$$x_0 \in {\mathbb {C}}^n$$x0∈Cnor$$x_0 \in {\mathbb {R}}^n $$x0∈Rnfrommmeasurements of the form$$y_i = \big \vert \langle \xi ^{\left( i\right) }, x_0 \rangle \big \vert ^2 $$yi=|⟨ξi,x0⟩|2, where$$ \left\{ \xi ^{\left( i\right) } \right\} ^m_{i=1} \subset {\mathbb {C}}^m $$ξii=1m⊂Cmare known measurement vectors. While Gaussian measurements allow for recovery of arbitrary signals provided the number of measurements scales at least linearly in the number of dimensions, it has been shown that ambiguities may arise for certain other classes of measurements$$ \left\{ \xi ^{\left( i\right) } \right\} ^{m}_{i=1}$$ξii=1msuch as Bernoulli measurements or Fourier measurements. In this paper, we will prove that even when a subgaussian vector$$ \xi ^{\left( i\right) } \in {\mathbb {C}}^m $$ξi∈Cmdoes not fulfill a small-ball probability assumption, thePhaseLiftmethod is still able to reconstruct a large class of signals$$x_0 \in {\mathbb {R}}^n$$x0∈Rnfrom the measurements. This extends recent work by Krahmer and Liu from the real-valued to the complex-valued case. However, our proof strategy is quite different and we expect some of the new proof ideas to be useful in several other measurement scenarios as well. We then extend our results$$x_0 \in {\mathbb {C}}^n $$x0∈Cnup to an additional assumption which, as we show, is necessary.
Efficient leave-one-out cross-validation for Bayesian non-factorized normal and Student-t models
Authors: Bürkner Paul-Christian , Gabry Jonah , Vehtari Aki
Published: November 2020

Cross-validation can be used to measure a model’s predictive accuracy for the purpose of model comparison, averaging, or selection. Standard leave-one-out cross-validation (LOO-CV) requires that the observation model can be factorized into simple terms, but a lot of important models in temporal and spatial statistics do not have this property or are inefficient or unstable when forced into a factorized form. We derive how to efficiently compute and validate both exact and approximate LOO-CV for any Bayesian non-factorized model with a multivariate normal or Student-$$t$$tdistribution on the outcome values. We demonstrate the method using lagged simultaneously autoregressive (SAR) models as a case study.
Direct oral anticoagulants (DOAC) for prevention of recurrent arterial or venous thromboembolic events (ATE/VTE) in myeloproliferative neoplasms
Authors: Huenerbein Karlo , Sadjadian Parvis , Becker Tatjana , Kolatzki Vera , Deventer Eva , Engelhardt Carina , Griesshammer Martin , Wille Kai
Published: November 2020

In patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), arterial or venous thromboembolic events (ATE/VTE) are a major burden. In order to control these complications, vitamin K antagonists (VKA) are widely used. There is no robust evidence supporting the use of direct oral anticoagulants (DOAC) in MPN patients. We therefore compared the efficacy and safety of both anticoagulants in 71 cases from a cohort of 782 MPN patients. Seventy-one of 782 MPN patients (9.1%) had ATE/VTE with nine ATE (12.7%) and 62 VTE (87.3%). Forty-five of 71 ATE/VTE (63.4%) were treated with VKA and 26 (36.6%) with DOAC. The duration of anticoagulation therapy (p = 0.984), the number of patients receiving additional aspirin (p = 1.0), and the proportion of patients receiving cytoreductive therapy (p = 0.807) did not differ significantly between the VKA and DOAC groups. During anticoagulation therapy, significantly more relapses occurred under VKA (n = 16) compared to DOAC treatment (n = 0, p = 0.0003). However, during the entire observation period of median 3.2 years (0.1–20.4), ATE/VTE relapse-free survival (p = 0.2) did not differ significantly between the two anticoagulants. For all bleeding events (p = 0.516) or major bleeding (p = 1.0), no significant differences were observed between VKA and DOAC. In our experience, the use of DOAC was as effective and safe as VKA, possibly even potentially beneficial with a lower number of recurrences and no increased risk for bleedings. However, further and larger studies are required before DOAC can be routinely used in MPN patients.