bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved cadmium resistance and removal capacity in Pichia kudriavzevii A16 by sucrose preincubation
Authors: Zhang Dandan , Ma Ning , Guo Zhen , Chen Peng , Ma Ranran , Sun Xiaowen , Wang Dongfeng , Wang Junwei , Xu Ying
Published: July 2019

Removal of heavy metals from food material by growing micro‐organisms is limited by the toxicity to cells. In this study, different preincubation treatments were investigated to analyze their effects on cadmium resistance and removal ability of Pichia kudriavzevii A16 and Saccharomyces cerevisiae CICC1211. Sucrose preincubation improved the cadmium resistance of both yeast cells and increased the cadmium‐removal rate of P. kudriavzevii A16. An evident decrease of intracellular and cell‐surface cadmium accumulation was observed after sucrose preincubation, which may be the primary reason responsible for the improved cadmium resistance. Flow cytometry assay showed that sucrose significantly reduced the production of reactive oxygen species (ROS) and cell death rate of both yeasts under cadmium compared with those normally cultured cells. Under cadmium stress, the content of both protein carbonyls and malonyldialdehyde were also reduced by the addition of sucrose, the results were in accordance with the tendency of ROS, exhibiting a defending function of sucrose. Osmotic regulators as proline and trehalose were increased by sucrose preincubation in P. kudriavzevii A16 in the presence of cadmium. The results suggested that sucrose preincubation could be applied to improve cadmium resistance and removal rate of yeasts.
Raman study of the substrate influence on graphene synthesis using a solid carbon source via rapid thermal annealing
Authors: Bleu Yannick , Bourquard Florent , Loir Anne‐Sophie , Barnier Vincent , Garrelie Florence , Donnet Christophe
Published: July 2019

We report the results of a comparative investigation of graphene films prepared on Si(100) and fused silica (SiO2) combining pulsed laser deposition and rapid thermal annealing using Ni catalyst. The effect of modifying the substrate and/or growth temperature (600–1,000°C) of graphene synthesis was investigated by Raman microspectroscopy mapping. Graphene grown on Si(100) was multilayered, and various nickel silicide phases had formed underneath, revealing dependence on the growth temperature. Films prepared on SiO2 mainly comprised bilayered and trilayered graphene, with no traces of nickel silicide. Analysis of Raman D, G, and 2D peak intensities and positions showed that modifying the growth temperature had different effects when a Si(100) or a SiO2 substrate is used. These findings advance our understanding of how different combinations of substrate and thermal processing parameters affect graphene synthesis from solid carbon source using nickel as a catalyst. This knowledge will enable better control of the properties of graphene film (defects, number of layers, etc.) and will have a high potential impact on the design of graphene‐based devices for scientific or industrial applications.
Random‐effects meta‐analysis of few studies involving rare events
Authors: Günhan Burak Kürsad , Röver Christian , Friede Tim
Published: July 2019

Meta‐analyses of clinical trials targeting rare events face particular challenges when the data lack adequate numbers of events for all treatment arms. Especially when the number of studies is low, standard random‐effects meta‐analysis methods can lead to serious distortions because of such data sparsity. To overcome this, we suggest the use of weakly informative priors (WIPs) for the treatment effect parameter of a Bayesian meta‐analysis model, which may also be seen as a form of penalization. As a data model, we use a binomial‐normal hierarchical model (BNHM) that does not require continuity corrections in case of zero counts in one or both arms. We suggest a normal prior for the log‐odds ratio with mean 0 and standard deviation 2.82, which is motivated (a) as a symmetric prior centered around unity and constraining the odds ratio within a range from 1/250 to 250 with 95% probability and (b) as consistent with empirically observed effect estimates from a set of 37 773 meta‐analyses from the Cochrane Database of Systematic Reviews. In a simulation study with rare events and few studies, our BNHM with a WIP outperformed a Bayesian method without a WIP and a maximum likelihood estimator in terms of smaller bias and shorter interval estimates with similar coverage. Furthermore, the methods are illustrated by a systematic review in immunosuppression of rare safety events following pediatric transplantation. A publicly available R package, MetaStan, is developed to automate a Bayesian implementation of meta‐analysis models using WIPs.
Magnetic solid‐phase extraction of tobacco‐specific N‐nitrosamines using magnetic graphene composite as sorbent
Authors: Pang Yong‐Qiang , Chen Xiao‐Jing , Li Xiang‐Yu , Zhang Hong‐Fei , Jiang Xing‐Yi , Zhu Feng‐Peng , Luo Yan‐Bo
Published: July 2019

Tobacco‐specific N‐nitrosamines are carcinogenic components in mainstream cigarette smoke. To explore tobacco‐specific N‐nitrosamine release levels in cigarettes, a magnetic solid‐phase extraction procedure using magnetic graphene composite as sorbent for fast enrichment of tobacco‐specific N‐nitrosamine was developed. Under optimal conditions, a tobacco‐specific N‐nitrosamine determination method was successfully proposed by combining magnetic solid‐phase extraction procedure and high‐performance liquid chromatography coupled with tandem mass spectrometry. The method's limit of detection for tobacco‐specific N‐nitrosamines in mainstream cigarette smoke ranged from 0.018 to 0.057 ng/cigarette. Good linearities were obtained with correlation coefficients above 0.9992. The accuracies of tobacco‐specific N‐nitrosamines in a spiked mainstream cigarette smoke sample were from 89.3 to 109.4%, with a relative standard deviation of less than 11.2%. The proposed method has the merits of rapidity and high sensitivity. Finally, the method was successfully applied to tobacco‐specific N‐nitrosamine analysis in real samples.
Characteristics of American alligator bites on people in Florida
Authors: Woodward Allan R. , Leone Erin H. , Dutton Harry J. , Waller Jason E. , Hord Lindsey
Published: July 2019

Human–American alligator (Alligator mississippiensis) conflict in Florida, USA, has increased since the early 1970s, along with the recovery of the American alligator population. To better understand factors contributing to the risk of people being bitten by free‐ranging alligators in Florida, we evaluated the trend of alligator bites during 1971–2014 and examined characteristics associated with bites on people documented during 1948–2014. We classified 372 bites as either unprovoked or unintentionally provoked and used these in further analyses. Major injuries to victims occurred in 247 bite incidents. The estimated annual number of bites resulting in major injury to the victim increased from 3.5 to 7.0 during 1971–2014. The number of bites per Florida resident did not show a significant trend during 1971–2014. No significant change occurred in the frequency of fatal attacks during 1971–2014. Monthly frequency of bites was positively correlated with both mean maximum and mean minimum air temperatures but was not significantly correlated with testosterone concentration in adult male alligators, suggesting that bites are more likely related to feeding rates associated with seasonal fluctuations in ambient temperature than to aggression by male alligators during the breeding season. A high percentage of bites (41.8%) occurred in unnamed water bodies, which were generally small or man‐made. Most (93.7%) victims were Florida residents, and 58.7% resided close to the incident site. Victims were predominantly male (81.4%), and adults were more frequently victims than were adolescents or children. Most victims (93.9%) were in the water or near the shore when bitten. Victims were more likely to sustain major injuries if the bite occurred in deeper water. Male alligators were more frequently (76.9%) responsible for bites. We found only 1 instance in which a bite was associated with defense of eggs or young by an adult female alligator. Evidence of people feeding alligators before the bite was documented in 34.7% of bite incidents. Twenty‐two fatalities were attributed to alligator attacks, but we could not discern a pattern in the ages of victims. Alligators responsible for severe or fatal bites were predominantly in good condition with few deformities or injuries. Most alligator bites in Florida appeared to be attempts at feeding, although 36.8% of incidents entailed a single bite followed by immediate release, suggesting that alligators were unsure about their prey or were biting in defense. The risk of alligator bites can be reduced by educating people likely to interact with alligators and by selectively removing problem alligators in human residential areas and water bodies used regularly by people for swimming, wading, and shoreline activities. © 2019 The Wildlife Society.
First Use of Optical Coherence Tomography on In Vivo Inflammatory Acne‐Like Lesions: A Murine Model
Authors: Hermsmeier Maiko , Sawant Tanvee , Chowdhury Khadiza , Nagavarapu Usha , Chan Kin F.
Published: July 2019

Background and Objectives

Successful outcomes of clinical studies for acne vulgaris depend greatly on achieving statistically significant reduction in acne lesion count and improvement in Investigator's Global Assessment score of the investigational drug product against its vehicle control. To date, there has not been a validated preclinical acne model to evaluate investigational drug products in order to improve the probability of clinical success. An inflammatory acne‐like lesion mouse model developed in‐house has previously been used for clinical guidance in our drug development program. In this study, we aim to implement and assess the adequacy of swept‐source optical coherence tomography (SS‐OCT) in quantifying the dynamic changes in inflammatory acne‐like lesions.

Study Design/Materials and Methods

Live Propionibacterium acnes bacteria were injected intradermally resulting in inflammatory acne‐like lesions. Topical 1% and 2% minocycline gels were applied to the lesions in separate groups once daily for 2 weeks and compared with vehicle and untreated control groups. The growth of these lesions was monitored and measured with a ruler (height)/microcaliper (width)—an approach previously developed, and with SS‐OCT. The reliability of the two methods were assessed. Acquired OCT images across the apex of these inflammatory lesions were statistically analyzed for lesion volume reduction from baseline as well as between the treatment groups and the control groups.

Results

The OCT technique allowed for reliable lesion volume analysis with varying conic profiles. After 14 days of topical minocycline treatments (1%, 2% minocycline), statistically significant reduction in lesion volume (P ≤ 0.05) based on OCT image analysis was observed compared with untreated and vehicle control groups as well as compared with baseline measurements. Under the right conditions, some morphological aspects of the
P. acnes injection site were discernible within the skin in images captured with OCT.

Conclusions

We demonstrated the first use of SS‐OCT in evaluating in vivo inflammatory acne‐like lesions in a murine model. Our findings support the use of OCT in assessing lesion size and evolution of P. acnes injection sites non‐invasively in preclinical in vivo studies, which could potentially lead to more consistent and predictable outcomes in clinical development. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Composite of Peptide‐Supramolecular Polymer and Covalent Polymer Comprises a New Multifunctional, Bio‐Inspired Soft Material
Authors: Chakraborty Priyadarshi , Ghosh Moumita , Schnaider Lee , Adadi Nofar , Ji Wei , Bychenko Darya , Dvir Tal , Adler‐Abramovich Lihi , Gazit Ehud
Published: July 2019

Peptide‐based supramolecular hydrogels are utilized as functional materials in tissue engineering, axonal regeneration, and controlled drug delivery. The Arg‐Gly‐Asp (RGD) ligand based supramolecular gels have immense potential in this respect, as this tripeptide is known to promote cell adhesion. Although several RGD‐based supramolecular hydrogels have been reported, most of them are devoid of adequate resilience and long‐range stability for in vitro cell culture. In a quest to improve the mechanical properties of these tripeptide‐based gels and their durability in cell culture media, the Fmoc‐RGD hydrogelator is non‐covalently functionalized with a biocompatible and biodegradable polymer, chitosan, resulting in a composite hydrogel with enhanced gelation rate, mechanical properties and cell media durability. Interestingly, both Fmoc‐RGD and Fmoc‐RGD/chitosan composite hydrogels exhibit thixotropic properties. The utilization of the Fmoc‐RGD/chitosan composite hydrogel as a scaffold for 2D and 3D cell cultures is demonstrated. The composite hydrogel is found to have notable antibacterial activity, which stems from the inherent antibacterial properties of chitosan. Furthermore, the composite hydrogels are able to produce ultra‐small, mono‐dispersed, silver nanoparticles (AgNPs) arranged on the fiber axis. Therefore, the authors' approach harnesses the attributes of both the supramolecular‐polymer (Fmoc‐RGD) and the covalent‐polymer (chitosan) component, resulting in a composite hydrogel with excellent potential.
Distinct Subthalamic Coupling in the ON State Describes Motor Performance in Parkinson's Disease
Authors: Ozturk Musa , Abosch Aviva , Francis David , Wu Jianping , Jimenez‐Shahed Joohi , Ince Nuri F.
Published: July 2019

Objective

Cross‐frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross‐frequency interactions across three consecutive cycles over unique 24‐hour‐long recordings.

Background

Identifying neurobiomarkers for PD can drive the development of novel personalized treatments by providing objective assessment of impairment. In particular, distinct frequency bands in LFP recordings and their interaction with one another have been shown to modulate with dopaminergic medication and thus, proposed as such biomarkers.

Methods

We recorded local field potentials 3 weeks postoperatively from externalized leads in 9 patients and correlated the neural patterns with improvements in motor signs over three medication intake cycles. We used two modalities to assess symptoms in the unmedicated OFF and the l‐dopa–induced motor ON state: a subsection of the UPDRS and a keyboard tapping score measuring bradykinesia.

Results

In the OFF state, the amplitude of high‐frequency oscillations in the 200‐ to 300‐Hz range was coupled with the phase of low‐beta (13–22 Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high‐beta (22–30 Hz) and high‐frequency oscillations in the 300‐ to 400‐Hz range had significantly greater improvement in bradykinesia, according to the keyboard scores.

Conclusion

Observing diminished coupling in the ON state, previous studies have hypothesized that the sole existence of coupling in STN has an “impeding” effect on normal processes, and thus it was considered to be pathological. In contrast, our observation of ON state coupling at distinct frequencies associated with the improvements in motor features suggest that the underlying mechanism of coupling might have impeding or enhancing effects depending on the coupled frequencies. © 2019 International Parkinson and Movement Disorder Society
Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription
Authors: Di Stolfo Giuseppe , Accadia Maria , Mastroianno Sandra , Leone Maria P. , Palumbo Orazio , Palumbo Pietro , Potenza Domenico , Maccarone Pasquale , Sacco Michele , Russo Aldo , Carella Massimo
Published: July 2019

Background

The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations.

Methods

We describe a 6‐year‐old child with a 12‐Mb deletion of the region 7q35q36.3.

Results

Among the deleted genes, two genes have cardiac implications: PRKAG2 (OMIM #602743), associated with hypertrophic cardiomyopathy, cardiac conduction disease, and sudden death, and KCNH2 (OMIM #152427), coding for a cardiac potassium channel involved in long QT syndrome, unmasked by the chlorpheniramine treatment. At same time, the SHH gene (OMIM #600725), encoding sonic hedgehog, a secreted protein that is involved in the embryonic development, is deleted.

Conclusion

Our report underlines potential cardiac complications linked to the common pharmacological treatment in this rare multiorgan and proteiform disease.
Differing disease phenotypes of Duchenne muscular dystrophy and Moyamoya disease in female siblings of a Korean family
Authors: Park Joonhong , Jang Woori , Han Ji Yoon
Published: July 2019

Background

Variable disease phenotypes can be influenced by several factors such as allelic variation, environmental factors, genetic modifiers, and genotype–environment interaction. Herein to the best of our knowledge, this is the first report of the coexistence of DMD and RNF213 gene mutations in a Korean family with differing disease phenotypes of Duchenne muscular dystrophy (DMD) and Moyamoya disease (MMD) in each female sibling.

Methods

Deletion or duplication of the exon in DMD was screened using multiplex ligation‐dependent probe amplification (MLPA). Subsequently, single exon deletion or duplication identified by MLPA was confirmed by Sanger sequencing. On the other hand, a common missense mutation [NM_001256071.2:c.14429G>A (p.Arg4810Lys)] related to MMD in exon 60 of RNF213 was also identified by Sanger sequencing.

Results

Three female family members carried the same disease‐causing mutations, c.9953_9954delAG of DMD and c.14429G>A of RNF213. Two (II‐2 and II‐3) of these siblings suffer from the disease but exhibited different DMD or MMD symptoms, while the mother (I‐2) seemed almost unaffected.

Conclusion

This report illustrates the difficulty that might be encountered in the interpretation of complex clinical manifestations when different genetic defects affecting neuromuscular and vascular diseases coexist.
Five novel NF1 gene pathogenic variants in 10 different Chinese families with neurofibromatosis type 1
Authors: Chen Linlin , Xue Feng , Xu Jia , He Jinwei , Fu Wenzhen , Zhang Zhenlin , Kang Qinglin
Published: July 2019

Background

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with equal sex incidence that is characterized by neurofibromas, café‐au‐lait macules, axillary freckling, optic pathway tumor, distinctive osseous lesion, and iris Lisch nodules. Inactivating variants in the NF1 gene have been identified to be correlated with NF1. This tumor suppressor gene is located at 17q11.2.

Methods

Ten affected NF1 probands and their available relatives from 10 unrelated Chinese families with neurofibromatosis type 1 were clinically studied. All of these probands mainly complained of osseous lesions. PCR was used to analyze and sequence the variants. We collected both laboratory and radiological information.

Results

We detected five novel pathogenic variants including two de novo variants in these 10 families: one missense variant, p.Cys709Arg(c.2125T>C), in exon 18 and four frameshift variants: p.Leu1459Profs*2(c.4436dupT) in exon 34; p.Lys99Argfs*4(c.296delA) in exon 4; p.Leu762Cysfs*2(c.2283delA) in exon 19; and p.Leu1522Ilefs*53(c.4562_4563dupAT) in exon 34.

Conclusion

Novel pathogenic variants in the NF1 gene in these families correlated with the phenotype and genotype and explained the clinical manifestations of these patients. The results help us to understand the genetic basis of patients with neurofibromatosis type 1 in China. Our study expands the pathogenic variant spectrum of the NF1 gene and may be helpful in genetic counseling and prenatal genetic diagnosis.
Design of MIMO antenna to interference inherent for ultra wide band systems using defected ground structure
Authors: Babu K Vasu , Anuradha Bhuma
Published: July 2019

A compact monopole ultra wide band (UWB) antenna is analyzed and described with defect in ground plane. By introducing four arcs at the edges of square patch is achieved an UWB antenna ranging from 3.1 to 10 GHz. Arranging the antenna elements in close proximity of spatial diversity is introduced without establishing the strong mutual coupling. The measured IBW's (impedance bandwidth's) are 3.0 to 4.0 GHz (1000 MHz), 5.6 to 4.3 GHz (1300 MHz), and 9.5 to 8.4 GHz (1100 MHz) occupied the bandwidth from 2.0 to 10.0 GHz which covers Bluetooth, WLAN, and ultra wideband for VSWR ≤2. The average value of the gain in antenna is 5.04 dBi with a small variation of ±1.20 dBi for the whole entire IBW. This antenna shows better radiation patterns like an omnidirectional with a narrow compact size having an area of 2100 mm2 (60 × 35 mm) and spacing between the two square patches is 0.05 λ0.
Technical Note: Quality assurance of proton central axis pencil‐beam spread‐out Bragg peak using large‐diameter multilayer ionization chambers
Authors: Wang Peng , Zhu Mingyao , Langen Katja
Published: July 2019

Purpose

The aim of this work is to describe a method of machine quality assurance (QA) by measuring proton spread‐out Bragg peak constructed by the integrated depth dose via a large‐diameter (12‐cm) multilayer ionization chamber (LD‐MLIC).

Methods

Two types of contours are used to create the nominal plan. The final nominal plan is composed of mixed‐energy proton pencil‐beam spots located close to the central axis. The integrated depth dose (IDD) curve contains a flat SOBP region. The LD‐MLIC–measured IDD was compared to the IDD curve exported from the treatment planning system (TPS). In addition, three plans with intentionally modified energy layers to simulate wrong‐delivered energy layers were created and measured by the LD‐MLIC. The water equivalent thickness (WET) difference between the inserted and replaced energies was 0.2 cm. Six weeks of measurements were analyzed. A low‐pass filter was introduced to mitigate the high‐frequency noise in the IDD signal ratios. The filtered IDD signal ratios between the modified plans in different weeks and the baseline were used to check the energy accuracy.

Results

The differences between the LD‐MLIC–measured and TPS‐exported IDDs of the nominal plan were within 2% in most parts of the curve. Bumps/dips (~1%) were noted in the filtered IDD ratio between the modified plans and the baseline.

Conclusions

The LD‐MLIC can be used to check the accuracy of multiple energies Bragg peak locations quickly in proton machine QA. The LD‐MLIC was sensitive in identifying an erroneous energy with 0.2 cm in WET.
Undernutrition and hyperandrogenism during pregnancy: Role in programming of cardiovascular disease and infertility
Authors: Mossa Francesca , Latham Keith E. , Ireland James J. , Veiga‐Lopez Almudena
Published: July 2019

Maternal nutritional status programs the development of several systems in female offspring, with effects that depend on the severity, duration, and window of development when the nutritional perturbation is imposed. On the basis of the developmental origins of health and disease concept, we hypothesize that gestational low caloric intake may induce maternal subclinical hyperandrogenism during early pregnancy and compromise cardiovascular health and fertility in the female offspring. To examine this possibility, a literature search for human and animal studies was conducted using two electronic databases, PubMed and Cochrane until April 2019 to address the following questions: (a) Do androgens have a developmental role in cardiovascular and ovarian development? (b) Is excess maternal testosterone linked to cardiovascular disease and infertility? and (c) Could early pregnancy undernutrition enhance maternal androgen production and compromise health and fertility in female offspring? The observations reviewed, establish a potential causative link between maternal undernutrition and subclinical hyperandrogenism with hypertension and reduced ovarian reserve in the progeny. Further studies in appropriate models are needed to better understand whether low energy intake and subclinical maternal hyperandrogenism during early pregnancy can negatively affect the health of the female offspring.
Longitudinal follow‐up of biopsy‐proven small fiber neuropathy
Authors: MacDonald Steven , Sharma Tara L. , Li Jianbo , Polston David , Li Yuebing
Published: July 2019

Introduction

Little is published on the prognosis of small fiber neuropathy (SFN).

Methods

A retrospective analysis of 101 patients with biopsy proven SFN.

Results

Study participants included 87 patients with length‐dependent SFN and 14 patients with non–length‐dependent SFN. The average duration of symptoms was 3.2 years prior to SFN diagnosis, and the average follow‐up duration after diagnosis was 6.2 years. Neuropathic pain was present in 98% of patients and in 84.2% of patients at the final visit. The average total number of pain medications ever used was 4.4 per patient. Signs of autonomic dysfunction were initially present in 24.8% of patients, but improved in most. Large fiber involvement was seen in 11.9% of patients. Small fiber neuropathy affected employment and ambulation status in 5.3% and 6.3% of patients, respectively.

Discussion

Small fiber neuropathy tends to be stable and rarely affects ambulation and employment status. Effective pain control remains a challenge.
Experience and expectations of patients on weight loss: The Learning Health System Network Experience
Authors: DeJesus R. S. , Bauer K. W. , Bradley D. P. , Haller I. , Bradley S. M. , Schroeder D. R. , St. Sauver J. , Phelan S. M. , Croghan I. T.
Published: July 2019

Objective

Weight perception and degree of confidence in achieving healthy lifestyle can be determinants of engagement in obesity interventions. This study explored patients' perceived need for weight loss and the degree of self‐confidence in ability to lose weight and sought to identify factors associated with patients' self‐confidence in ability to lose weight.

Methods

The authors analysed data from a survey mailed to primary care patients within five sites of the Learning Health Systems Network that explored participants' prior experience with weight management.

Results

Among the 2,263 participants who completed the survey section on ‘Patients’ Experience with Weight Management’, perceived need to lose 51 lb or more was statistically significant among those with class III obesity compared with other body mass index (BMI) groups (p value < 0.001). Reported desire to lose weight was also significantly higher among those with the highest BMI than those who were overweight (p value < 0.001). However, this same group had the lowest belief in ability to lose weight (p value < 0.001). In a multiple regression analysis, female gender, higher BMI and need to lose >10 lb were each independently associated with less belief in being able to lose weight.

Conclusions

Patients had varying perceptions on weight loss; those with category III obesity had the highest desire to lose weight but had the least confidence in ability to lose weight. Higher BMI, female gender and need to lose >10 lb were associated with decreased self‐confidence in ability to lose weight.
Second malignancies in patients treated for Ewing sarcoma: A systematic review
Authors: Caruso Jennifer , Shulman David S. , DuBois Steven G.
Published: July 2019

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.
Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia
Authors: Hecht Anna , Meyer Julia , Chehab Farid F. , White Kristie L. , Magruder Kevin , Dvorak Christopher C. , Loh Mignon L. , Stieglitz Elliot
Published: July 2019

Background

Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre‐HCT therapy has an effect on the molecular burden of disease and how this affects outcome post‐HCT.

Procedure

Twenty‐one patients with JMML who received pre‐HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre‐HCT therapy, using custom amplicon next‐generation sequencing.

Results

Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate‐intensity chemotherapy, one patient received only azacitidine. The 5‐year progression‐free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high‐intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre‐HCT therapy.

Conclusions

Despite the myelodysplastic nature of JMML, patients treated with pre‐HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post‐HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.
Nitrosatable drug exposure during pregnancy and risk of stillbirth
Authors: Thomsen Anne Marie L. , Liew Zeyan , Riis Anders Hammerich , Stayner Leslie Thomas , Ramlau‐Hansen Cecilia Høst , Sigsgaard Torben , Olsen Jørn
Published: July 2019

Purpose

Nitrosatable drugs can react with nitrite in the stomach and form N‐nitroso compounds. Exposure to nitrosatable drugs has been associated with congenital malformations and preterm birth, but use during pregnancy as a cause of fetal death is not well‐known. We examined if prenatally nitrosatable drug use is associated with risk of stillbirth.

Methods

A nationwide cohort was conducted using 554 844 women with singleton and first recorded pregnancies regardless of previous pregnancy history from the Danish Medical Birth Register from 1996 to 2015. Exposure was recorded by use of the Danish National Prescription Register and defined as women who had redeemed a prescribed nitrosatable drug in the first 22 weeks of pregnancy. The reference group was women with no redeemed prescribed nitrosatable drug in this time period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for stillbirth.

Results

Among the 84 720 exposed women, 348 had a stillbirth compared with 1690 stillbirths among the 470 124 unexposed women. Women who used any prescribed nitrosatable drug were more likely to have a stillbirth compared with unexposed women (aHRs 1.24; 95% CI, 1.03‐1.49).

Conclusion

Nitrosatable drug use during the first 22 weeks of pregnancy might increase risk of stillbirth. The findings should be interpreted cautiously because of important unmeasured factors that might influence the observed association, including maternal vitamin C intake, dietary, and other sources of nitrate/nitrite intake.
Barrier properties and abrasion resistance of biopolymer‐based coatings on biodegradable poly(lactic acid) films
Authors: Mohd Aris Zarif Farhana , Bavishi Vishal , Sharma Rashmi , Nagarajan Ramaswamy
Published: July 2019

Coated polylactic acid (PLA) films consisting of crosslinked‐chitosan/beeswax layer were prepared to improve barrier properties and abrasion resistance of the base substrate. The effect of crosslinking the chitosan layer on durability and barrier properties of the coatings was investigated. Crosslinked samples exhibited lower degree of swelling compared to uncrosslinked samples and 50% reduction in water vapor transmission rate (WVTR) compared to neat PLA films. The beeswax coating decreased the WVTR of chitosan‐coated PLA films significantly (by 100%). However, it had a marginal effect on the oxygen transmission rate. Water vapor transmission was less affected by abrasion than oxygen transmission for both uncrosslinked and crosslinked samples. The WVTR of crosslinked samples were retained even after being subjected to abrasion, whereas WVTR of uncrosslinked samples dropped by 50%. Results obtained using the Taber test method also show that the weight loss of crosslinked coatings are about 75% less than that of uncrosslinked samples and can withstand a greater number of cycles before rupture. These translucent‐coated films retained good barrier and mechanical properties along with providing improved abrasion resistance after crosslinking. This approach provides exciting new possibilities for expanding the use of biodegradable polymers in packaging applications. POLYM. ENG. SCI., 59:1874–1881, 2019. © 2019 Society of Plastics Engineers
Lentil aspiration leading to likely hypersensitivity pneumonitis
Authors: Dhochak Nitin , Jat Kana R. , Lodha Rakesh , Kabra Sushil K.
Published: July 2019

Rationale

A variety of inhaled antigens have been implicated to cause hypersensitivity pneumonitis (HP). We observed that children force‐fed with lentil‐based weaning food had persistent respiratory symptoms and radiology similar to HP.

Objectives

To describe the clinical features of lentil HP.

Methods

We conducted a retrospective review of records of children with lentil HP attending Pediatric Chest Clinic at a tertiary care hospital in North India from 2008‐2018. We included case records with elevated immunoglobulin G (IgG) specific for lentil antigen.

Measurements and Main Results

Nine children (seven boys) were identified with median (IQR) age of onset of symptoms and diagnosis at 9 (6, 12) and 11 (10, 16) months, respectively. Chronic cough (100%), shortness of breath (89%), fever (78%), vomiting (56%), and wheezing (33%) were common symptoms. Fine crackles were heard in 33% of children, none had clubbing. CT scans showed nodular opacities and consolidation in 78% and 67% children, respectively. Bronchoalveolar lavage showed increased neutrophils and lymphocytes (67% and 33%, respectively). All children showed rapid remission with systemic steroids (prednisolone), starting at a median dose of 1 (1, 1.1) mg kg−1 day−1. One child had a clinical relapse which was treated with oral steroids again. IgG specific to lentil antigens was elevated in children with lentil HP (21‐>200 mgA/L) compared with children with other chronic respiratory illnesses (n = 7, <2‐11.4 mgA/L).

Conclusions

Lentil aspiration is an important cause of HP in infants of weaning age with force‐feeding practices. Further studies are needed to identify aspirated antigens which cause HP in aspiration prone children.
Formulation of CL‐20‐Based Explosive Ink and Its Detonating Transfer Performance in Micro‐Size Charge
Authors: Li Qianbing , An Chongwei , Peng Jinyu , Xu Chuanhao , Guo Hao , Wang Shuang , Ye Baoyun , Wang Jingyu
Published: July 2019

Explosive ink in the micro‐size charges of explosive circuits for energetic devices has attracted considerable interest. Herein, explosive ink with 90 wt.% of energetic solid was selected by testing the rheological properties of formulations with different CL‐20 concentrations. Explosive ink suspensions with sub‐micro CL‐20 (2,4,6,8,10,12‐hexanitro‐2,4,6,8,10,12‐hexaazaisowurtzitane) as main explosive and fluorine‐containing rubber/polyvinyl alcohol (PVA) emulsion as binder system were prepared. Direct ink writing (DIW) technology was used for the printing of the sample and for the loading of the explosive ink in a micro‐size groove. The morphology and crystal type of the CL‐20‐based composite samples were characterized by SEM and XRD, and its detonating transfer performance in the micro‐size groove were tested. Results show that the CL‐20‐based composite has a good molding effect, and the crystal type has not changed. The critical detonation thickness is around 11 μm at 1.0 mm fixed width in the wedge tests, and the critical detonation size (cross section) is about 0.3 mm×0.3 mm. The detonation wave could continue to propagate around multiple 90° corners. The maximum corner turning ability of the detonation wave is 140° and the CL‐20‐based composite can detonate completely in a complex charge circuit.
Detonation Characteristics of an Aluminized Explosive Added with Boron and Magnesium Hydride
Authors: Cao Wei , Song Qingguan , Gao Dayuan , Han Yong , Xu Sen , Lu Xiaojun , Guo Xiangli
Published: July 2019

Investigation of the detonation characteristics of an aluminized explosive added with boron (B) and magnesium hydride (MgH2) were undertaken and compared with the aluminized explosive of similar formulation. Firstly, the explosion heat was measured in a vacuumed calorimetric bomb, then the detonation pressure was determined by the interface velocity experiment, and finally the cylinder expansion test was performed. From the calorimetric data, the addition of B and MgH2 into an aluminized explosive increases the heat of explosion slightly. From the detonation pressure data, the addition of B and MgH2 appears to have no significant influence to the detonation pressure. From the cylinder test data, the detonation velocity, wall velocity, Gurney energy and detonation energy were determined. The aluminized explosive added with B and MgH2 shows weak acceleration ability, but exhibits a stronger afterburning potential. Finally the equation of state of the detonation products was determined for different casing conditions. Conclusions about how to use B and MgH2 in aluminized explosives to generate optimal effects are drawn.
Structures of the Neisseria meningitides methionine‐binding protein MetQ in substrate‐free form and bound to l‐ and d‐methionine isomers
Authors: Nguyen Phong T. , Lai Jeffrey Y. , Kaiser Jens T. , Rees Douglas C.
Published: July 2019

The bacterial periplasmic methionine‐binding protein MetQ is involved in the import of methionine by the cognate MetNI methionine ATP binding cassette (ABC) transporter. The MetNIQ system is one of the few members of the ABC importer family that has been structurally characterized in multiple conformational states. Critical missing elements in the structural analysis of MetNIQ are the structure of the substrate‐free form of MetQ, and detailing how MetQ binds multiple methionine derivatives, including both l‐ and d‐methionine isomers. In this study, we report the structures of the Neisseria meningitides MetQ in substrate‐free form and in complexes with l‐methionine and with d‐methionine, along with the associated binding constants determined by isothermal titration calorimetry. Structures of the substrate‐free (N238A) and substrate‐bound N. meningitides MetQ are related by a “Venus‐fly trap” hinge‐type movement of the two domains accompanying methionine binding and dissociation. l‐ and d‐methionine bind to the same site on MetQ, and this study emphasizes the important role of asparagine 238 in ligand binding and affinity. A thermodynamic analysis demonstrates that ligand‐free MetQ associates with the ATP‐bound form of MetNI ∼40 times more tightly than does liganded MetQ, consistent with the necessity of dissociating methionine from MetQ for transport to occur.
A novel fluorescent probe for the early detection of prostate cancer based on endogenous zinc sensing
Authors: Fu Shibo , Wan Xiang , Du Chenchen , Wang Hongyu , Zhou Juan , Wang Zhong
Published: July 2019

Background

The early detection of prostate cancer can significantly optimize the prognosis, prolong patient lifespan, and improve quality of life. It has been well documented that prostate cancer tissues have lower zinc content than normal prostate tissues due to an impairment of the zinc accumulation mechanism.

Methods

A novel diketopyrrolopyrrole (DPP)‐based fluorescent zinc ion probe named DPP‐C2 was prepared. The fluorescent intensity of this novel molecule is in direct proportion to environmental zinc concentration. Malignant (DU145 and PC3 cells) and normal prostate epithelial RWPE‐1 cells were tested. Prostate cancer tissues were also cultured and observed as tissue sections. The probe was also intravenously administered to tumor‐bearing (DU145 and PC3 cells) nude mice and observed under a whole‐body fluorescence live‐imaging system.

Results

The probe showed minimal cytotoxicity to malignant and normal prostate cells. The RWPE‐1 cells showed not only stronger baseline fluorescence but also a significant increase in signal intensity after culturing in a zinc‐supplemented medium. In human prostate sections, the pathologically confirmed cancer tissues exhibited weaker fluorescence signals than normal and benign hyperplastic tissues. With proper excitation, prostate tissues revealed more intense fluorescence signals than tumor tissues, whereas other surrounding tissues showed almost no fluorescence.

Conclusions

The novel zinc ion fluorescent probe DPP‐C2 is low toxic and showed potential application for the early detection of prostate cancer based on endogenous zinc sensing.
Robust finite‐time stabilization of a class of high‐order stochastic nonlinear systems subject to output constraint and disturbances
Authors: Fang Liandi , Ma Li , Ding Shihong , Zhao Dean
Published: July 2019

In this paper, the robust stabilization problem is addressed for a class of high‐order stochastic nonlinear systems with output constraints and disturbances by using finite‐time control technique. One of the features of the considered stochastic systems is that the fractional powers are allowed to be any positive odd rational numbers, rather than grater than or equal to one. By constructing a novel tan‐type barrier Lyapunov function and using the adding a power integrator technique, the explicit steps on how to construct a backstepping‐like finite‐time controller have been developed to handle the robust stabilization and output constraint. Rigorous mathematical proof shows that the system states will finite‐time converge to a small region of the origin and the output constraint can be kept. Finally, a simulation example is given to illustrate the effectiveness of the proposed approach.
Odd ideas about learning science: A response to Osborne
Authors: Hammer David , Manz Eve
Published: July 2019

Osborne (2019, this issue) raises several issues in his response to Furtak and Penuel (2019, Sci Edu, 103, 167–186). He challenges the primacy of phenomena, argues that commonsense is not productive for science, and maintains that the primary goal of science instruction is students’ understanding the canon. To us, the import of Osborne's response, and what moved us to accept the editors’ invitation to comment, is in how it reflects the ongoing complexity and instability of views within the community of scholarship in science education. We reflect on these ongoing tensions.
Science‐as‐practice and the status of knowledge: A response to Osborne
Authors: Penuel William R. , Furtak Erin Marie
Published: July 2019

In this response to Osborne's commentary, we clarify the bases for our case for drawing on both scientific studies and learning research to guide current reforms in science education. While acknowledging “the constructivist's dilemma,” we assert the fundamental importance of positioning students as knowledge builders in science classrooms.
Chemotherapy-Induced Neuropathy and Drug Discovery Platform Using Human Sensory Neurons Converted Directly from Adult Peripheral Blood
Authors: Vojnits Kinga , Mahammad Saleemulla , Collins Tony J. , Bhatia Mickie
Published: July 2019

Chemotherapy-induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life-saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34+ hematopoietic cells, but was limited to a small-scale product of SNs and derived exclusively from less abundant allogenic sources of cord or drug mobilized peripheral blood (PB). To address this shortcoming, we have developed and report detailed procedures toward the generation of human SN directly converted from conventionally drawn PB of adults that can be used in a high-content screening platform for discovery-based studies of chemotherapy agents on neuronal biology. In the absence of mobilization drugs, cryogenically preserved adult human PB could be induced to (i)SN via development through expandable neural precursor differentiation. iSNs could be transferable to high-throughput procedures suitable for high-content screening applicable to neuropathy for example, alterations in neurite morphology in response to chemotherapeutics. Our study provides the first reported platform using adult PB-derived iSNs to study peripheral nervous system-related neuropathies as well as target and drug screening potential for the ability to prevent, block, or repair chemotherapy-induced PN damage. Stem Cells Translational Medicine  2019;8:1180–1191
Unexpected Size Effect: The Interplay between Different‐Sized Nanoparticles in Their Cellular Uptake
Authors: Li Ling , Xi Wen‐Song , Su Qianqian , Li Yang , Yan Gui‐Hua , Liu Yuanfang , Wang Haifang , Cao Aoneng
Published: July 2019

The size effect on the cellular uptake of nanoparticles (NPs) has been extensively studied, but it is still not well understood. Herein, a reductionist approach is used to minimize all influencing factors except the particle size, and co‐exposure of different‐sized silica nanoparticles (SNPs) is adopted instead of the common single exposure. SNPs are found being internalized by Hela cells in serum‐free medium mainly via clathrin‐dependent endocytosis, thus simplifying the data analysis for reliable attribution to size effects. Remarkably, even though at conditions that the size effects seem very small or even undetectable in the common single exposure experiments, the co‐exposure experiments reveal significant size effects due to an unexpected interplay between two different‐sized SNPs. Namely, the bigger SNPs significantly promote the cellular uptake of the smaller ones, while the smaller SNPs inhibit the internalization of the bigger ones, with a total uptake increase of the particle number of SNPs in the cells. This strong interplay between different‐sized NPs might unavoidably exist within most “single‐sized” NP products, whose sizes actually distribute in certain ranges, thus urging reconsideration of the size effect on the cellular uptake of NPs, for the benefits of both bioapplications and safety assessment of nanomaterials.