bluuebunny/crossref_metadata_2025 huggingface dataset:
Status of growth plates can be monitored by MRI
Authors: Wada Hiroaki , Ikoma Kazuya , Oka Yoshinobu , Nishida Atsushi , Onishi Okihiro , Kim Wook‐Choel , Tanida Takashi , Yamada Shunji , Matsuda Ken‐ichi , Tanaka Masaki , Kubo Toshikazu
Published: May 2019

Background

Growth plate injuries and disorders cause premature closure, resulting in shortened or deformed limbs. Quantitative assessment by MRI might monitor the status of the growth plate and may assist in the prediction of these deformations.

Purpose

To investigate whether the status of the growth plate can be monitored by quantitative evaluation using MRI of the noninjured region of the growth plate in a physeal injury model.

Study Type

Prospective, longitudinal.

Animal Model

A 3.0‐mm drill was used to create an injury to the central region of the right proximal tibial growth plate in 5‐week‐old male Japanese white rabbits (N = 18). The left tibia served as the control.

Field Strength/Sequence

7.04T, T2‐weighted imaging, diffusion‐weighted imaging.

Assessment

Eight of 18 rabbits underwent MRI, proton density‐weighted imaging, and T2‐weighted and diffusion‐weighted imaging. T2 and apparent diffusion coefficient (ADC) maps were generated for each image. The growth plate height and the T2 and ADC values of the noninjured region were measured. Two rabbits were sacrificed at 2, 4, 6, 8, and 10 weeks postinjury. Proximal tibial bones were evaluated using microcomputed tomography, histological, and immunohistological methods.

Statistical Tests

Data were compared using repeated‐measures analysis of variance followed by Tukey post‐hoc multiple comparison.

Results

Growth plate height decreased at 10 weeks postinjury (P = 0.018) on the injured side. T2 values were greater at 2 weeks postinjury (P = 0.0478) and decreased at 8 and 10 weeks (P = 0.0226, P = 0.0470, respectively) on the injured side. ADC values increased at 6 weeks on the lateral side (P = 0.0304) and decreased at 8 weeks and 10 weeks postinjury (P < 0.01) on the medial and injured sides, respectively.

Data Conclusion

Quantitative MRI can help monitor the status of the growth plate and capture its changes early.

Level of Evidence: 1

Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:133–143.
Relationship between greenhouse gas emissions and changes in soil gas diffusivity in a field experiment with biochar and lime
Authors: Keller Thomas , Hüppi Roman , Leifeld Jens
Published: May 2019

Reducing greenhouse gas emissions from arable soil while maintaining productivity is a major challenge for agriculture. Biochar is known to reduce N2O emissions from soil, but the underlying mechanisms are unclear. This study examined the impact of green waste biochar (20 Mg ha−1) and lime (CaCO3; 2 Mg ha−1) application on soil gas transport properties and related changes in these to soil N2O and CO2emissions measured using automated chambers in a field experiment cropped with maize. In situ soil water content monitoring was combined with laboratory measurements of relative soil gas diffusion coefficient (Dp/D0) at different matric potentials, to determine changes inDp/D0over time. Cumulative N2O emissions were similar in the control and lime treatment, but much lower in the biochar treatment. Cumulative CO2emissions decreased in the order: lime treatment > biochar treatment > control soil. When N2O emissions were not driven by excess N supply shortly after fertilisation, they were associated withDp/D0changes, whereby decreases inDp/D0corresponded to N2O emissions peaks. No distinct pattern was observed between CO2emissions andDp/D0. Cumulative N2O emissions were positively related to number of days withDp/D0< 0.02, a critical limit for soil aeration. These results indicate that improved soil gas diffusivity, and hence improved soil aeration, may explain the effect of biochar in reducing N2O emissions. They also suggest that knowledge ofDp/D0changes may be key to explaining N2O emissions.
Capabilities of low‐wavenumber Raman spectroscopy for analyzing the mechanism of devitrification of molecular glasses
Authors: Malfait Benjamin , Paccou Laurent , Derollez Patrick , Guinet Yannick , Hedoux Alain
Published: May 2019

The mechanism of devitrification of racemic ibuprofen (RS‐IBP, C13H18O2) was analyzed by low‐wavenumber Raman spectroscopy (LWRS). This study shows the capabilities of LWRS to provide detailed new structural information, with respect to X‐ray diffraction data, on the atypical crystallization process of a molecular material (RS‐IBP) composed of a majority of hydrogen atoms. The conversions of Raman intensity into reduced intensity and Raman susceptibility were presented. The combination of these two types of spectrum representation reflecting the fast relaxational dynamics and the structural organization, respectively, has clearly revealed the high degree of disorder of Phase II. Additionally, Phase II was described as an early transient and metastable step of crystallization toward Phase I, from a deeply quenched liquid state. Analyzing the isothermal and nonisothermal crystallization has revealed two types of conversion of Phase II into Phase I, a solid–solid transformation and a crystallization of Phase I after melting of Phase II, respectively.
Synthesis of Biocompatible Double‐Tailed Nonionic Surfactants and Their Investigation for Niosomal Drug‐Loading Applications
Authors: Ali Imdad , Shah Muhammad Raza , Nadeem Said , Saad Ali Heyam , Saifullah Salim , Ahmed Farid , Imran Muhammad
Published: May 2019

Nonionic surfactants are capable of self‐assembling and thus are of vital importance for designing various drug‐delivery systems. This study reports the synthesis, characterization, biocompatibility, and drug‐loading potential of sulfanilamide‐based novel nonionic surfactants. These surfactants were synthesized in a single‐step reaction and characterized using nuclear magnetic resonance (NMR), electron impact mass spectroscopy, and fourier‐transforminfrared spectroscopy (FTIR). Critical micelle concentration (CMC) of the synthesized nonionic surfactants was determined using a ultraviolet–visible (UV) spectrophotometer. The surfactant potential for niosomal vesicles was explored using simvastatin as a model drug. The drug‐loaded vesicles were screened for shape, size, size distribution, and percent drug entrapment efficiency (EE%) using atomic force microscopy (AFM), zeta potential, and UV–visible spectrophotometry. Biocompatibility of the synthesized surfactants was investigated through blood hemolysis and cell toxicity assays. Synthesized nonionic surfactants revealed lower CMC values of 0.045–0.095 mM and entrapped an improved amount of drug upon self‐simplifying in niosomal vesicles. Findings of the study confirm these nonionic surfactants as hemocompatible and nontoxic candidates for vesicular drug‐delivery applications.
Esophageal pepsin and proton pump synthesis in barrett's esophagus and esophageal adenocarcinoma
Authors: Samuels Tina L. , Altman Kenneth W. , Gould Jon C. , Kindel Tammy , Bosler Matthew , MacKinnon Alexander , Hagen Catherine E. , Johnston Nikki
Published: May 2019

Objectives/Hypothesis

Gastroesophageal reflux disease and associated metaplasia of the esophagus (Barrett's esophagus [BE]) are primary risk factors for esophageal adenocarcinoma (EAC). Widespread use of acid suppression medications has failed to stem the rise of EAC, suggesting that nonacid reflux may underlie its pathophysiology. Pepsin is a tumor promoter in the larynx and has been implicated in esophageal carcinogenesis. Herein, specimens from the esophageal cancer spectrum were tested for pepsin presence. Pepsin‐induced carcinogenic changes were assayed in an esophageal cell culture model.

Study Design

Laboratory analysis.

Methods

Pepsin was assayed in reflux and cancer free esophagi, BE, EAC, and esophageal cancer lacking association with reflux (squamous cell carcinoma [SCC]). Refluxed or locally synthesized pepsin was assayed by Western blot. Local synthesis of pepsin and proton pumps was assayed via reverse transcription–polymerase chain reaction. The effect of pepsin on BE and EAC markers was investigated via enzyme‐linked immunosorbent assay and quantitative polymerase chain reaction in human esophageal epithelial cells treated with pepsin or control diluent.

Results

Pepsinogen and proton pump mRNA were observed in BE (3/5) and EAC (4/4) samples, but not in normal adjacent specimens, SCC (0/2), or reflux and cancer‐free esophagi. Chronic pepsin treatment (0.1–1 mg/mL, 4 weeks) of human esophageal cells in vitro induced BE and EAC markers interleukin 8 andKRT8and depleted normal esophageal markerKRT10(P< .05) expression.

Conclusions

Local synthesis of pepsin and proton pumps in BE and EAC is not uncommon. Absence of these molecules in normal (noncancer) esophagi, SCC, and in vitro data support a role for pepsin in reflux‐attributed carcinogenic changes in the esophagus.

Level of Evidence

NALaryngoscope, 129:2687–2695, 2019
Patient‐reported outcomes for dental health, shoulder‐neck dysfunction, and overall quality of life after treatment with radiation for head and neck cancer
Authors: Verma Neha , Tan Xianming , Knowles Mary , Bernard Stephen , Chera Bhishamjit
Published: May 2019

Objectives

The current exploratory cross‐sectional study was designed to examine and characterize survivorship issues among patients treated with radiation for head and neck cancer with regard to dental health, shoulder‐neck dysfunction, and overall quality of life (QOL).

Methods

Patients (N = 58) being seen for follow‐up at a radiation oncology clinic at least 1 year beyond the end of treatment completed three survey questionnaires regarding general QOL as well as dental health issues and shoulder‐neck dysfunction. The questionnaires were scored and univariate analyses were performed using the variables of age, radiation dosage, definitive radiation + neck dissection versus definitive surgery + postoperative radiation, and chemotherapy.

Results

Median follow‐up was 2.5 years. Of 58 patients, 35% reported having more problems with their general dental health as compared to before treatment and 38% reported having pain at night in the neck/shoulder after treatment. With regard to pretreatment counseling, 79% of patients reported being counseled about their dental health prior to treatment, while 31% reported being counseled about possible shoulder‐neck dysfunction. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation reported more functional and symptomatic issues.

Conclusion

Patients treated with radiation for head and neck cancer face a number of survivorship issues, including problems with dental health and shoulder‐neck dysfunction, and are not necessarily thoroughly counseled about these issues prior to treatment. Patients younger than 65, patients receiving higher doses of radiation, and patients undergoing definitive surgery + postoperative radiation may experience more survivorship issues.

Level of Evidence

IV
Pressure‐Controlled Structural Symmetry Transition in Layered InSe
Authors: Su Huimin , Liu Xuan , Wei Chengrong , Li Junning , Sun Zeyuan , Liu Qiye , Zhou Xuefeng , Deng Junhong , Yi Huan , Hao Qiaoyan , Zhao Yusheng , Wang Shanmin , Huang Li , Wu Shiwei , Zhang Wenjing , Li Guixin , Dai Jun‐Feng
Published: May 2019

Structural symmetry of crystals plays important roles regarding the physical properties of two‐dimensional (2D) materials, particularly in the nonlinear optics regime. There has been a long‐term exploration of the physical properties in 2D materials with various stacking structures, which correspond to different structural symmetries. Usually, the manipulation of rotational alignment between layers in 2D heterostructures is realized at the synthetic stage through artificial stacking like assembling building blocks. However, the reconfigurable control of translational symmetry of crystalline structure is still challenging. High pressure, as a powerful external control knob, provides a very promising route to circumvent this constraint. Here, a pressure‐controlled symmetry transition in layered InSe is experimentally demonstrated. The continuous and reversible evolution of structural symmetries can be in situ monitored by using polarization‐resolved second‐harmonic‐generation (SHG) spectroscopy. As pressure changes, the reconfigurable symmetry transition of the SHG pattern from threefold rotational symmetry to mirror symmetry is experimentally observed in layered InSe samples and successfully explained by the proposed interlayer‐translation model. This opens new routes toward potential applications of manipulating crystal symmetry of 2D materials.
Refractory Plasmonic Metal Nitride Nanoparticles for Broadband Near‐Infrared Optical Switches
Authors: Xian Yuehui , Cai Yu , Sun Xiaoyu , Liu Xiaofeng , Guo Qiangbing , Zhang Zuxing , Tong Limin , Qiu Jianrong
Published: May 2019

Ultrafast laser‐induced thermalization‐cooling of carriers in plasmonic nanostructures has been extensively explored in the development of high‐speed photonic switches with a broad operating bandwidth. However, potential laser damage arising from the strong light–matter interaction remains a tremendous obstacle for practical applications of most colloidal processed plasmonic nanoparticles (NPs). Here, it is demonstrated that titanium nitride (TiN) NPs, with a broadband localized surface plasmon resonance in the near infrared (NIR) region, can be exploited as an ultrafast optical switch based on transient photo‐bleaching, which manifests as a saturable absorption behavior with strong optical nonlinearity. The developed TiN‐based optical switches exhibit high robustness against laser damage (up to peak power of 557 GW cm−2) and enable both Q‐switched and transform‐limited mode‐locked pulse generation in the NIR spectral region in either fiber or solid‐state lasers with pulse duration down to 763 fs. The results may stimulate further exploration of metal nitride materials for applications in nonlinear optics and ultrafast photonic devices.
Under‐Oil Superhydrophilic Poly(vinyl alcohol)/Silica Hybrid Nanofibrous Aerogel for Gravity‐Driven Separation of Surfactant‐Stabilized Water‐in‐Oil Emulsions
Authors: Zheng Xie , Liu Xiaoyun , Zha Liusheng
Published: May 2019

For efficient and green separation of surfactant‐stabilized water‐in‐oil (W/O) emulsions, under‐oil superhydrophilic poly(vinyl alcohol) (PVA)/silica hybrid nanofibrous aerogel is fabricated by freeze‐drying the dispersion of shortened PVA/tetraethyl orthosilicate composite electrospun nanofibers in t‐butanol, followed by heat‐treatment. Its hierarchical porous structure, observed by scanning electron microscope, consists of major and minor pores with an average diameter of 15.9 and 1.0 µm, respectively. The silica‐based crosslinking structure inside the nanofibers and the chemical linkage between them, evidenced by infrared spectroscopy, endows the nanofibrous aerogel with desirable stability in water and compression recoverability. When it is used for gravity‐driven separation of Span80 stabilized water‐in‐n‐hexane emulsion, the flux is 2083 L m−2 h−1 and the purity of the separated n‐hexane reaches 99.997%, corresponding to the separation efficiency of 99.79%. The nanofibrous aerogel after use is readily recycled by rinsing and freeze‐drying, without using any organic solvent, as it possesses under‐oil superhydrophilicity and prominent oil antifouling property. Differing from the previously reported separation materials, PVA/silica hybrid nanofibrous aerogel simultaneously acts as gravity‐driven filtration material and adsorption material to both absorb their coalesced water droplets and allow the separated oil to penetrate in the separation process.
Time to invest in corporate social responsibility and the value of CSR operations: The case of environmental externalities
Authors: Braouezec Yann , Joliet Robert
Published: May 2019

The radical restructuring of the German utility giants RWE and E.ON in the wake of Germany's shift to renewable energy motivates the need of a formal model of corporate social responsible (CSR) investment appraisal with environmental externalities. We offer in this paper a model that uses the tools of decision analysis to value the option to postpone the project. We show that adding a CSR dimension to projects generating negative environmental externalities can induce the firm to invest immediately, whereas it always postpones projects without CSR activities. According to the project's attributes, the paper also determines the optimal level of effort in CSR.
MDS evidence‐based review of treatments for essential tremor
Authors: Ferreira Joaquim J. , Mestre Tiago A. , Lyons Kelly E. , Benito‐León Julián , Tan Eng‐King , Abbruzzese Giovanni , Hallett Mark , Haubenberger Dietrich , Elble Rodger , Deuschl Günther ,   on behalf of MDS Task Force on Tremor and the MDS Evidence Based Medicine Committee
Published: May 2019

Background

Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor.

Objectives

To conduct an evidence‐based review of current pharmacological and surgical treatments for essential tremor, using standardized criteria defined a priori by the International Parkinson and Movement Disorder Society.

Methods

We followed the recommendations of the International Parkinson and Movement Disorder Society Evidence Based Medicine Committee.

Results

Sixty‐four studies of pharmacological and surgical interventions were included in the review. Propranolol and primidone were classified as clinically useful, similar to Topiramate, but only for doses higher than 200 mg/day. Alprazolam and botulinum toxin type A were classified as possibly useful. Unilateral Ventralis intermedius thalamic DBS, radiofrequency thalamotomy, and MRI‐guided focused ultrasound thalamotomy were considered possibly useful. All the above recommendations were made for limb tremor in essential tremor. There was insufficient evidence for voice and head tremor as well as for the remaining interventions.

Conclusion

Propranolol, primidone, and topiramate (>200 mg/day) are the pharmacological interventions in which the data reviewed robustly supported efficacy. Their safety profile and patient preference may guide the prioritization of these interventions in clinical practice. MRI‐guided focused ultrasound thalamotomy was, for the first time, assessed and was considered to be possibly useful. There is a need to improve study design in essential tremor and overcome the limitation of small sample sizes, cross‐over studies, short‐term follow‐up studies, and use of nonvalidated clinical scales. © 2019 International Parkinson and Movement Disorder Society
Prepulse inhibition of the blink reflex is abnormal in functional movement disorders
Authors: Hanzlíková Zuzana , Kofler Markus , Slovák Matěj , Věchetová Gabriela , Fečíková Anna , Kemlink David , Sieger Tomáš , Růžička Evžen , Valls‐Solé Josep , Edwards Mark J. , Serranová Tereza
Published: May 2019

Background

Patients with functional movement disorders also typically have functional somatic symptoms, including pain, fatigue, and sensory disturbance. A potentially unifying mechanism for such symptoms is a failure in processing of sensory inputs. Prepulse inhibition is a neurophysiological method that allows for the study of preconscious somatosensory processing.

Objective

The objective of this study was to assess prepulse inhibition in patients with functional movement disorders and healthy control subjects.

Methods

We analyzed the effect of a weak electrical stimulus to the index finger (prepulse) on the magnitude of the R2 response of the blink reflex induced by electrical stimuli delivered to the supraorbital nerve in 22 patients with clinically established functional movement disorders and 22 matched controls. Pain, depression, anxiety, and obsessive‐compulsive symptoms were assessed using self‐rated questionnaires. In addition, in patients we assessed motor symptom severity.

Results

Prepulses suppressed the R2 response of the blink reflex in both groups, by 36.4% (standard deviation: 25.6) in patients and by 67.3% (standard deviation: 16.4) in controls. This difference was significant (P < 0.001). There was no significant correlation between motor and nonmotor symptom measures and prepulse inhibition size.

Conclusions

Impaired prepulse inhibition of the blink reflex suggests an abnormal preconscious processing of somatosensory inputs, which can be interpreted within predictive coding accounts of both functional movement disorders and functional somatic syndromes. Our results, along with previous findings of a reduced prepulse inhibition in fibromyalgia syndrome, support a possible unified pathophysiology across functional neurological and somatic syndromes with noteworthy implications for diagnostic classification and development of novel biomarkers and treatments. © 2019 International Parkinson and Movement Disorder Society
Clinical and methodological challenges for assessing freezing of gait: Future perspectives
Authors: Mancini Martina , Bloem Bastiaan R. , Horak Fay B. , Lewis Simon J.G. , Nieuwboer Alice , Nonnekes Jorik
Published: May 2019

Freezing of gait, defined as sudden and usually brief episodes of inability to produce effective stepping, often results in falls and is both disabling and common in parkinsonism. In this narrative review, sprung from the 2nd International Workshop on freezing of gait in Leuven, we summarize the latest insights into clinical and methodological challenges for assessing freezing of gait. We also highlight the role of emerging wearable technology to improve the management of this debilitating symptom. © 2019 International Parkinson and Movement Disorder Society
Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene
Authors: Lundin Johanna , Markljung Ellen , Baranowska Körberg Izabella , Hofmeister Wolfgang , Cao Jia , Nilsson Daniel , Holmdahl Gundela , Barker Gillian , Anderberg Magnus , Vukojević Vladana , Lindstrand Anna , Nordenskjöld Agneta
Published: May 2019

Background

The bladder exstrophy‐epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases.

Methods

We performed array comparative genomic hybridization (array‐CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies.

Results

We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10−4). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut, indicating a potential functional effect of the LZTR1mut.

Conclusion

Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.
Long noncoding RNA NEAT1 regulates the development of osteosarcoma through sponging miR‐34a‐5p to mediate HOXA13 expression as a competitive endogenous RNA
Authors: Ji Shaolin , Wang Shunsheng , Zhao Xiaodan , Lv Li
Published: May 2019

Background

Long noncoding RNA (lncRNA) exerts a potential regulatory role in tumorigenesis. LncRNA NEAT1 expression remains high in osteosarcoma tissues. However, its biological mechanism in osteosarcoma remains unknown.

Methods

In this study, NEAT1 expression in osteosarcoma cells was detected by qRT‐PCR. Proliferative and apoptosis potentials of osteosarcoma cells were determined by CCK‐8 assay and Flow Cytometry, respectively. We identified the potential target of NEAT1 through bioinformatics and dual‐luciferase reporter gene assay. Furthermore, their interaction and functions in regulating the development of osteosarcoma were clarified by Western blot and RIP assay.

Results

Our results demonstrated a high expression of NEAT1 in osteosarcoma tissues and cells. Overexpression of NEAT1 markedly accelerated proliferative and reduced apoptosis potentials of osteosarcoma cells. Besides, NEAT1 could positively regulate the expression of HOXA13 by competing with miR‐34a‐5p.

Conclusion

These results indicated that NEAT1 participated in the development of osteosarcoma as a ceRNA to competitively bind to miR‐34a‐5p and thus mediate HOXA13 expression.
A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276
Authors: Yu Xiaobo , Wei Bajin , Su Rong , Yao Jia , Feng Xiaowen , Jiang Guoping , Xie Haiyang , Wu Jian , Xu Xiao , Zhang Min , Zheng Shusen , Zhou Lin
Published: May 2019

Background

Liver transplantation is an effective therapy for end‐stage liver diseases and acute liver failure. After the operation, however, recipients may suffer grafts loss induced by alloimmune reaction, which is termed as acute allograft rejection. The interaction between costimulatory molecules, CD276, and its ligand, TREML2, promotes T cell‐mediated immune response, as well as acute or chronic allograft rejection. Our research aimed at correlating genetic polymorphisms of CD276/TREML2 with acute rejection, and evaluating its prognostic value of acute rejection after liver transplantation.

Methods

The study enrolled a total of 388 recipients. Among them, acute allograft rejection was observed in 54 cases. We performed single nucleotide polymorphism genotyping of CD276, including rs11072431, rs11574495, rs12593558, rs12594627, rs2127015, rs3816661 and rs7176654, and TREML2, including rs4714431, rs6915083, rs7754593, and rs9394767 from preoperative peripheral blood genome DNA.

Results

We found rs2127015 of CD276, rs6915083 and rs7754593 of TREML2, and HBV infection as well were associated with acute rejection. And, rs2127015 influences CD276 expression. Moreover, we established a risk assessment model, composited by statistically proved risk factors.

Conclusion

By integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.
FANCC Dutch founder mutation in a Mennonite family from Tamaulipas, México
Authors: García‐de Teresa Benilde , Frias Sara , Molina Bertha , Villarreal María Teresa , Rodriguez Alfredo , Carnevale Alessandra , López‐Hernández Gerardo , Vollbrechtshausen Lilia , Olaya‐Vargas Alberto , Torres Leda
Published: May 2019

Background

Fanconi anemia (FA) (OMIM #227650) is a rare hereditary disease characterized by genomic instability. The clinical phenotype involves malformations, bone marrow failure, and cancer predisposition. Genetic heterogeneity is a remarkable feature of FA; at least 22 FANC genes are known to cooperate in a unique FA/BRCA repair pathway. A common rule on the mutations found in these genes is allelic heterogeneity, except for mutations known to have arisen from a founder effect like the FANCC c.67delG in the Dutch Mennonite Community. Here, we present an 11‐year‐old male patient, member of the Mennonite Community of Tamaulipas México, with a clinical and cytogenetic diagnosis of FA.

Method

Chromosome fragility test was performed in all siblings. Genomic DNA was obtained from peripheral blood samples. Sanger sequencing was used to identify the FANCC c.67delG mutation (NC_000009.11(NM_000136.2):c.67delG p.(Asp23IlefsTer23)) and its accompanying haplotype.

Results

The FANCC c.67delG mutation in 13 members of his family confirmed a FA diagnosis in two of his siblings and identified heterozygous carriers. Haplotype analysis supports that in this family, FA is caused by the founder mutation that initially appeared in Mennonite Dutch and followed this population's migrations through Canada and further to Mexico.

Conclusion

The identification of the FANCC c.67delG mutation in this family not only allows proper genetic counseling, but it also grants the possibility to raise awareness of FA risk among the Mennonite community living in Mexico.
Production of highly polarized [1‐13C]acetate by rapid decarboxylation of [2‐13C]pyruvate – application to hyperpolarized cardiac spectroscopy and imaging
Authors: Steinhauser Jonas , Wespi Patrick , Kwiatkowski Grzegorz , Kozerke Sebastian
Published: May 2019

Purpose

The objective of the present work was to develop and implement an efficient approach to hyperpolarize [1‐13C]acetate and apply it to in vivo cardiac spectroscopy and imaging.

Methods

Rapid hydrogen peroxide induced decarboxylation was used to convert hyperpolarized [2‐13C]pyruvate into highly polarized [1‐13C]acetate employing an additional step following rapid dissolution of [2‐13C]pyruvate in a home‐built multi‐sample dissolution dynamic nuclear polarization system. Phantom dissolution experiments were conducted to determine optimal parameters of the decarboxylation reaction, retaining polarization and T1 of [1‐13C]acetate. In vivo feasibility of detecting [1‐13C]acetate metabolism is demonstrated using slice‐selective spectroscopy and multi‐echo imaging of [1‐13C]acetate and [1‐13C]acetylcarnitine in the healthy rat heart.

Results

The first in vivo signal was observed ~23 s after dissolution. At the corresponding time point in the phantom experiments, 97.9 ± 0.4% of [2‐13C]pyruvate were converted into [1‐13C]acetate by the decarboxylation reaction. T1 and polarization of [1‐13C]acetate was determined to be 29.7 ± 1.9% and a 47.7 ± 0.5 s. Polarization levels of [2‐13C]pyruvate and [1‐13C]acetate were not significantly different after transfer to the scanner. In vivo, [1‐13C]acetate and [1‐13C]acetylcarnitine could be detected using spectroscopy and imaging.

Conclusion

Decarboxylation of hyperpolarized [2‐13C]pyruvate enables the efficient production of highly polarized [1‐13C]acetate that is applicable to study short‐chain fatty acid metabolism in the in vivo heart.
Compressed Sensing 3D‐GRASE for faster High‐Resolution MRI
Authors: Cristobal‐Huerta A. , Poot D.H.J. , Vogel M.W. , Krestin G.P. , Hernandez‐Tamames J.A.
Published: May 2019

Purpose

High‐resolution three‐dimensional (3D) structural MRI is useful for delineating complex or small structures of the body. However, it requires long acquisition times and high SAR, limiting its clinical use. The purpose of this work is to accelerate the acquisition of high‐resolution images by combining compressed sensing and parallel imaging (CSPI) on a 3D‐GRASE sequence and to compare it with a (CS)PI 3D‐FSE sequence. Several sampling patterns were investigated to assess their influence on image quality.

Methods

The proposed k‐space sampling patterns are based on two undersampled k‐space grids, variable density (VD) Poisson‐disc, and VD pseudo‐random Gaussian, and five different trajectories described in the literature. Bloch simulations are performed to obtain the transform point spread function and evaluate the coherence of each sampling pattern. Image resolution was assessed by the full‐width at half‐maximum (FWHM). Prospective CSPI 3D‐GRASE phantom and in vivo experiments in knee and brain are carried out to assess image quality, SNR, SAR, and acquisition time compared to PI 3D‐GRASE, PI 3D‐FSE, and CSPI 3D‐FSE acquisitions.

Results

Sampling patterns with VD Poisson‐disc obtain the lowest coherence for both PD‐weighted and ‐weighted acquisitions. VD pseudo‐random Gaussian obtains lower FWHM, but higher sidelobes than VD Poisson‐disc. CSPI 3D‐GRASE reduces acquisition time (43% for PD‐weighted and 40% for ‐weighted) and SAR (∼45% for PD‐weighted and ‐weighted) compared to CSPI 3D‐FSE.

Conclusions

CSPI 3D‐GRASE reduces acquisition time compared to a CSPI 3DFSE acquisition, preserving image quality. The design of the sampling pattern is crucial for image quality in CSPI 3D‐GRASE image acquisitions.
Development of a GPGPU‐parallelized hybrid finite‐discrete element method for modeling rock fracture
Authors: Fukuda Daisuke , Mohammadnejad Mojtaba , Liu Hongyuan , Dehkhoda Sevda , Chan Andrew , Cho Sang‐Ho , Min Gyeong‐Jo , Han Haoyu , Kodama Jun‐ichi , Fujii Yoshiaki
Published: May 2019

The hybrid finite‐discrete element method (FDEM) is widely used for engineering applications, which, however, is computationally expensive and needs further development, especially when rock fracture process is modeled. This study aims to further develop a sequential hybrid FDEM code formerly proposed by the authors and parallelize it using compute unified device architecture (CUDA) C/C++ on the basis of a general‐purpose graphics processing unit (GPGPU) for rock engineering applications. Because the contact detection algorithm in the sequential code is not suitable for GPGPU parallelization, a different contact detection algorithm is implemented in the GPGPU‐parallelized hybrid FDEM. Moreover, a number of new features are implemented in the hybrid FDEM code, including the local damping technique for efficient geostatic stress analysis, contact damping, contact friction, and the absorbing boundary. Then, a number of simulations with both quasi‐static and dynamic loading conditions are conducted using the GPGPU‐parallelized hybrid FDEM, and the obtained results are compared both quantitatively and qualitatively with those from either theoretical analysis or the literature to calibrate the implementations. Finally, the speed‐up performance of the hybrid FDEM is discussed in terms of its performance on various GPGPU accelerators and a comparison with the sequential code, which reveals that the GPGPU‐parallelized hybrid FDEM can run more than 128 times faster than the sequential code if it is run on appropriate GPGPU accelerators, such as the Quadro GP100. It is concluded that the GPGPU‐parallelized hybrid FDEM developed in this study is a valuable and powerful numerical tool for rock engineering applications.
Efficient and accurate stress recovery procedure and a posteriori error estimator for the stable generalized/extended finite element method
Authors: Lins Rafael , Proença Sergio Persival , Duarte C. Armando
Published: May 2019

This paper presents a new stress recovery technique for the generalized/extended finite element method (G/XFEM) and for the stable generalized FEM (SGFEM). The recovery procedure is based on a locally weighted L2 projection of raw stresses over element patches; the set of elements sharing a node. Such projection leads to a block‐diagonal system of equations for the recovered stresses. The recovery procedure can be used with GFEM and SGFEM approximations based on any choice of elements and enrichment functions. Here, the focus is on low‐order 2D approximations for linear elastic fracture problems. A procedure for computing recovered stresses at re‐entrant corners of any internal angle is also presented. The proposed stress recovery technique is used to define a Zienkiewicz‐Zhu (ZZ) a posteriori error estimator for the G/XFEM and the SGFEM. The accuracy, computational cost, and convergence rate of recovered stresses together with the quality of the ZZ estimator, including its effectivity index, are demonstrated in problems with smooth and singular solutions.
Struggling to be seen and understood as a person – Chronic back pain patients’ experiences of encounters in health care: An interview study
Authors: Allvin Renée , Fjordkvist Erika , Blomberg Karin
Published: May 2019

Aim

The aim of this study was to describe how patients with chronic back pain experience encounters with health care. Persons with chronic back pain are a stigmatized group often treated based on stereotypes, which may lead to misunderstandings and create frustrated patients and healthcare personnel. Few studies have examined the generic aspects of quality of care in this context.

Design

A descriptive design with a qualitative approach was used.

Methods

Nine individual interviews were conducted with chronic back pain patients after admission to an orthopaedic hospital ward. Data were analysed using content analysis.

Results

The patients’ experiences of healthcare encounters can be described by the theme “Struggling to be seen and understood as a person,” comprising the categories “Lack of access and trust to care,” “A desire to be taken care of and listened to” and “Own strength to handle healthcare situations.”
Vanillin: The Case for Greener Production Driven by Sustainability Megatrend
Authors: Ciriminna Rosaria , Fidalgo Alexandra , Meneguzzo Francesco , Parrino Francesco , Ilharco Laura M. , Pagliaro Mario
Published: May 2019

Approaching the end of the second decade of the 21st century, almost the whole demand of vanillin is met by the synthetic product obtained either via a petrochemical process starting from phenol and glyoxylic acid or from energy intensive alkaline oxidative depolymerization of lignin. Only a minor fraction is comprised of natural vanillin obtained from ferulic acid fermentation, and even less of highly valued Vanilla planifolia extracts. Are there alternative green production methods? And, if yes, are they suitable to find practical application?
Integrated psychology support and comprehensive cognitive evaluation improves access to special education services for children with sickle cell disease
Authors: Ghafuri Djamila Labib , Sanger Maureen , Rodeghier Mark , DeBaun Michael Rutledge
Published: May 2019

Background

Children with sickle cell disease (SCD) are at risk for cognitive deficits. Limited data describe whether comprehensive cognitive evaluation improves education resources and whether caregivers perceive the assessment as beneficial. We tested our two hypotheses: (a) an integrated comprehensive cognitive evaluation program in children with SCD results in increased special education services allocation; and (b) caregivers will value comprehensive cognitive evaluation services provided.

Procedure

In a tertiary care medical facility, as part of quality improvement project, in a before‐and‐after evaluation between March 2011 and July 2014, we examined the impact of targeted comprehensive cognitive evaluation on change in special education services. We also evaluated the caregiver's perception regarding the utility of the provided services.

Results

A total of 21% (42 of 196) students (median age 11 years, range 3‐18) with SCD were referred for cognitive assessment due to overt stroke (n = 11), silent stroke (n = 14), or concerns about cognitive or academic functioning without evidence of strokes (n = 17). At baseline, 45.2% received special education services and after the comprehensive cognitive evaluation 86.7% received special education services (P < 0.001). Among 33 caregivers who completed the survey, 97% reported that the assessment was helpful and 60% indicated that assessment led to beneficial changes for their children at school.

Conclusion

Education advocacy coupled with comprehensive cognitive assessment in students with SCD improved access to special education services, and caregivers uniformly endorse this service as having added value.
Impact of a transition program with navigator on loss to follow‐up, medication adherence, and appointment attendance in hemoglobinopathies
Authors: Allemang Brooke , Allan Kate , Johnson Colleen , Cheong Melina , Cheung Patrina , Odame Isaac , Ward Richard , Williams Suzan , Mukerji Geetha , Kuo Kevin H.M.
Published: May 2019

Background

Transition from pediatric to adult care is a period of high risk for loss to follow‐up, morbidity, and mortality in adolescents and young adults (AYA) with hemoglobinopathies. The purpose of this study was to determine whether a transition program with transition navigator (TN) reduced loss to follow‐up and hospitalizations and improved medication adherence and appointment attendance compared with an unstructured transfer.

Procedure

A retrospective observational study compared all AYA with hemoglobinopathies who turned 18 one year prior to (n = 51) and one year after (n = 61) the initiation of the transition program. Data from one year prior to last pediatric appointment and one year following first adult appointment were collected from each patient.

Results

The transition program with TN reduced loss to follow‐up from 29% to 7% (P = 0.034). A greater proportion of patients in the transition cohort maintained or improved adherence to hydroxyurea or iron chelation to ≥4 days/week; exposure to the program was independently associated with such improvement (P = 0.047). A trend toward improvement or maintenance of ≥90% attendance to appointments was observed (P = 0.096). Frequency of hospitalization was not significantly different between the two cohorts (P = 0.985).

Conclusions

A transition program with TN significantly reduced loss to follow‐up, and significantly improved and maintained fair to good medication adherence. Further analysis of economic benefit and patient satisfaction will be conducted.
Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis
Authors: Boscolo Elisa , Pastura Patricia , Glaser Kathryn , Goines Jillian , Hammill Adrienne M. , Adams Denise M. , Dickie Peter , Hsi Dickie Belinda , Le Cras Timothy D.
Published: May 2019

Background

Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly with significant morbidity and mortality. KLA is characterized by diffuse multifocal lesions comprised of focal areas of “kaposiform” spindled cells accompanying malformed lymphatic channels. The goal of this study was to identify activated signaling pathways in cells isolated from three KLA patients for the purpose of testing new therapies.

Procedure

Cells were obtained from the lungs of one patient isolated at autopsy and the spleen of two patients removed in surgery due to disease complications. A protein kinase array was performed on the KLA cell lysates and normal lymphatic endothelial cells.

Results

Higher activation of key signaling pathways in the KLA cells, including PRAS40, AKT1/2/3, and ERK‐1/2, was identified by protein kinase array and confirmed by Western blot analysis. This indicated a role for highly activated PI3K–AKT and MAPK–ERK‐1/2 signaling pathways in KLA cells. Cell proliferation studies assessed PI3K inhibitors (LY294002; BYL719), AKT inhibitor ARQ092, mTOR inhibitor rapamycin, and MAPK inhibitor U0126. These studies demonstrated that PI3K–AKT–mTOR and MAPK signaling are important mediators of KLA cell proliferation. BYL719 and rapamycin were more effective at inhibiting KLA cell proliferation than U0126.

Conclusions

Our studies using cells from KLA patient lesions demonstrate that these cells are highly proliferative and the PI3K–AKT–mTOR and MAPK pathways are promising therapeutic targets. Development and clinical trials of PI3K, AKT, and MAPK inhibitors for cancer treatment and the data in this study lend support for early clinical trials assessing the efficacy of these inhibitors in KLA patients.
Outcomes of hypoplastic left heart syndrome and fetal aortic valvuloplasty in a country with suboptimal postnatal management
Authors: Cruz‐Lemini Mónica , Alvarado‐Guaman Monica , Nieto‐Castro Belen , Luna‐Garcia Jonathan , Martínez‐Rodríguez Miguel , Juarez‐Martínez Israel , Palacios‐Macedo Alexis , Cruz‐Martínez Rogelio
Published: May 2019

What is already known about this topic?

Fetal aortic valvuloplasty may prevent progression to hypoplastic left heart syndrome (HLHS) in utero and, thus, decrease postnatal morbidity

Despite the high survival rate of HLHS in developed countries, many studies suggest that the risks of this fetal intervention may outweigh the benefits.

What does this study add?

Fetal aortic valvuloplasty is associated with ≈50% long‐term survival, while HLHS currently carries more than 95% risk of perinatal death in countries with suboptimal postnatal management, with little or no experience regarding surgical palliation, and with the vast majority of cases receiving comfort measures.
Variation of clinical manifestations according to culprit drugs in DRESS syndrome
Authors: Sim Da Woon , Yu Ji Eun , Jeong Jiung , Jung Jae‐Woo , Kang Hye‐Ryun , Kang Dong Yoon , Ye Young Min , Jee Young‐Koo , Kim Sujeong , Park Jung‐Won , Kang Min Gyu , Kim Sae Hoon , Park Hye‐Kyung , Yang Min‐Suk , Hur Gyu‐Young , Lee Jun Kyu , Choi Jeong‐Hee , Kwon Yong Eun , Koh Young‐Il ,   Korean Severe Cutaneous Adverse Reactions Consortium
Published: May 2019

Purpose

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T‐cell–mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs.

Methods

We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization‐Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti‐tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti‐inflammatory drugs.

Results

Differences were observed among culprit drugs regarding the frequencies of hepatitis (P < 0.01), renal dysfunction (P < 0.0001), lymphadenopathy (P < 0.01), and atypical lymphocyte (P < 0.01). Latency period differed among culprit drugs (P < 0.0001), being shorter in vancomycin and cephalosporin. In terms of clinical severity, admission duration (P < 0.01) and treatment duration (P < 0.05) differed among culprit drugs, being longer in vancomycin and anti‐tuberculosis drugs, respectively.

Conclusions

Based on the findings, clinical manifestations, including latency period and clinical severity, may differ according to culprit drugs in DRESS syndrome.
Genug Platz an der Sonne
Authors: Stierstadt Klaus
Published: May 2019

Eine Frage, die beim Ausbau erneuerbarer Energieerzeugung immer wieder aufkommt, ist die nach dem Flächenbedarf. Eine Abschätzung auf Basis heutiger Daten zeigt: Grundsätzlich ist mehr als genug Platz in Deutschland für eine hundertprozentige Umstellung der Stromproduktion auf Sonne, Wasser und Wind. Global gesehen gilt dies sogar für eine auf zehn Milliarden angewachsene Menschheit. Dabei muss allerdings die Solarenergie einen wesentlichen Anteil übernehmen.
Optisch konfigurierbarer, organischer Transistor
Authors: Herder Martin , Pätzel Michael , Hecht Stefan
Published: May 2019

Die Kombination von organischen Halbleitern mit molekularen Fotoschaltern erlaubt es, den Stromfluss in elektronischen Bauelementen durch Bestrahlung mit Licht reversibel zu modulieren. Die so erhaltenen multifunktionalen Transistoren können als flexible Speichermedien sowie als hochauflösende Displayelemente verwendet werden.
Elektrische Stromkreise per Drag‐and‐Drop mit iCircuit
Authors: Weatherby Thomas , Burde Jan‐Philipp , Wilhelm Thomas , Kuhn Jochen
Published: May 2019

Elektrische Größen sind bei einfachen Stromkreisen messbar, aber nicht direkt beobachtbar. Die App iCircuit ermöglicht es, auf einfache Art und Weise elektrische Stromkreise zu simulieren und dabei alle gewünschten Größen darzustellen.
Poesie und Mikroskopie
Authors: Rückelt Miriam
Published: May 2019

Die Anthologie „Science meets Fiction“ betrachtet die Welt durch das Mikroskop und erzählt in poetischer Sprache von den Wundern der Nanowelten.