bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective platelet function in Niemann‐Pick disease type C1
Authors: Chen Oscar C. W. , Colaco Alexandria , Davis Lianne C. , Kiskin Fedir N. , Farhat Nicole Y. , Speak Anneliese O. , Smith David A. , Morris Lauren , Eden Emily , Tynan Patricia , Churchill Grant C. , Galione Antony , Porter Forbes D. , Platt Frances M.
Published: September 2020

Niemann‐Pick disease type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in either NPC1 (95% of cases) or NPC2. Reduced late endosome/lysosome calcium (Ca2+) levels and the accumulation of unesterified cholesterol and sphingolipids within the late endocytic system characterize this disease. We previously reported impaired lysosome‐related organelle (LRO) function in Npc1−/− Natural Killer cells; however, the potential contribution of impaired acid compartment Ca2+ flux and LRO function in other cell types has not been determined. Here, we investigated LRO function in NPC1 disease platelets. We found elevated numbers of circulating platelets, impaired platelet aggregation and prolonged bleeding times in a murine model of NPC1 disease. Electron microscopy revealed abnormal ultrastructure in murine platelets, consistent with that seen in a U18666A (pharmacological inhibitor of NPC1) treated megakaryocyte cell line (MEG‐01) exhibiting lipid storage and acidic compartment Ca2+ flux defects. Furthermore, platelets from NPC1 patients across different ages were found to cluster at the lower end of the normal range when platelet numbers were measured and had platelet volumes that were clustered at the top of the normal range. Taken together, these findings highlight the role of acid compartment Ca2+ flux in the function of platelet LROs.
Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts
Authors: Stingl Josef , Zach Petr , Sach Josef , Vranova Jana , Suchomel Zdenek , Kudrna Vaclav , Mrzilkova Jana , Kachlik David , Musil Vladimir
Published: September 2020

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well‐developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.
In Vivo Proton Exchange Rate (kex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients
Authors: Ye Haiqi , Shaghaghi Mehran , Chen Qianlan , Zhang Yan , Lutz Sarah E. , Chen Weiwei , Cai Kejia
Published: September 2020

Background

Currently available radiological methods do not completely capture the diversity of multiple sclerosis (MS) lesion subtypes. This lack of information hampers the understanding of disease progression and potential treatment stratification. For example, inflammation persists in some lesions after gadolinium (Gd) enhancement resolves. Novel metabolic and molecular imaging methods may improve the current assessments of MS pathophysiology.

Purpose

To compare the in vivo proton exchange rate (kex) MRI with Gd‐enhanced MRI for characterizing MS lesions.

Study Type

Retrospective.

Subjects

Sixteen consecutively diagnosed relapsing‐remitting multiple sclerosis (RRMS) patients.

Field Strength/Sequence

3.0T MRI with T2‐weighted imaging, postcontrast T1‐weighted imaging, and single‐slice chemical exchange saturation transfer imaging.

Assessment

MS lesions in white matter were assessed for Gd enhancement and kex elevation compared to normal‐appearing white matter (NAWM).

Statistical Tests

Student's t‐test was used for analyzing the difference of kex values between lesions and NAWM, with statistical significance set at 0.05.

Results

Of all 153 MS lesions, 78 (51%) lesions were Gd‐enhancing and 75 (49%) were Gd‐negative. Without exception, all 78 Gd‐enhancing lesions showed significantly elevated kex values compared to NAWM (924 ± 130 s–1 vs. 735 ± 61 s–1, P < 0.05). Of 75 Gd‐negative lesions, 18 lesions (24%) showed no kex elevation (762 ± 29 s–1 vs. 755 ± 28 s–1, P = 0.47) and 57 (76%) showed significant kex elevation (950 ± 124 s–1 vs. 759 ± 48 s–1, P < 0.05) compared to NAWM. MS lesions with kex elevation appeared nodular (118, 87.4%), ring‐like (15, 11.1%), or irregular‐shaped (2, 1.5%).

Data Conclusion

For Gd‐enhancing lesions, kex MRI is highly consistent with Gd‐enhanced images by showing 100% of elevated kex. For all Gd‐negative lesions, the discrepancy on kex MRI may further differentiate active slowly expanding lesions or chronic inactive lesions, supporting kex as an imaging biomarker for tissue oxidative stress and inflammation.

Level of Evidence 2

Technical Efficacy Stage 3

J. MAGN. RESON. IMAGING 2021;53:408–415.
Evaluating mRNA expression of tax, B chain of PDGF and PDGF‐β receptors as well as HTLV‐I proviral load in ATL patients and healthy carriers
Authors: Atabati Hadi , Esmaeili Seyed‐Alireza , Allahyari Abolghasem , Shirdel Abbas , Rahimi Hossein , Rezaee Seyed Abdolrahim , Momtazi‐Borojeni Amir A. , Rafatpanah Houshang
Published: September 2020

Adult T‐cell leukemia (ATL) is a life‐threatening malignant neoplasm of CD4+ T cells resulted from human T‐cell leukemia virus type I (HTLV‐I). Tax1 protein of HTLV‐I can induce malignant proliferation of T‐cells by modulating the expression of growth factors such as platelet‐derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV‐I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF‐β receptors in ATL patients and HTLV‐I‐infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll‐Histophaque density centrifugation. The mean of HTLV‐I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557‐75962]) was significantly (p = .01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422‐879], respectively. The HTLV‐I PVL in ATL patients exhibited a significant correlation with PBMC count (R = .495, p = .001). The mRNA expression of Tax, B chain of PDGF, and PDGF‐β receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFβ and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV‐I carriers.
Correlation of pulmonary vein reconnection patterns after cryoballoon and duty‐cycled ablation of atrial fibrillation with the time of arrhythmia recurrence
Authors: Wieczorek Marcus , Sassani Kiarash , Hoeltgen Reinhard
Published: September 2020

Background

Pulmonary vein isolation (PVI) is safe and effective in the treatment of atrial fibrillation (AF). We compare and correlate pulmonary vein (PV) reconnection patterns at repeat ablation in patients with recurrent AF after PVI using duty‐cycled radiofrequency (RF) technology (PVAC) or second‐generation cryoballoon (CB) with the time of AF recurrence.

Methods and Results

In total, 85 PVAC and 66 CB patients undergoing a second ablation were enrolled 9.7 ± 3.4 months after initial PVI. PV reconnections were comparably high between both groups (93% PVAC and 92% CB patients). A mean of 2.79 ± 1.2 PVs/patient were reconnected after PVAC PVI compared with 1.97 ± 0.8 in CB patients, P < .0001. 33% PVAC patients, but no CB patient had 4 reconnected PVs (P < .0001). Early AF recurrences were more frequently observed in PVAC patients with ≥2 reconnected PVs, in CB patients with ≥3 reconnected PVs (both P < .01) and patients without PV reconnection, irrespective of the ablation technique. One reconnected PV was associated with late AF recurrence only in CB patients. The correlation between number of reconnected PVs and time of AF recurrence was −0.32 for PVAC and −0.52 for CB.

Conclusions

CB PVI was associated with greater durability and lesser PV reconnections/patient. There were negative correlations for both devices between extent of PV reconnections and time of AF recurrence. CB patients with early AF recurrences‐ although less frequently observed compared with PVAC patients had more reconnected PVs than PVAC patients, suggesting additional effects for AF prevention after CB PVI.
Assessing context suitability (generalizability, external validity, applicability or transferability) of findings in evidence syntheses in healthcare—An integrative review of methodological guidance
Authors: Weise Alina , Büchter Roland , Pieper Dawid , Mathes Tim
Published: September 2020

Background

Evidence syntheses provide the basis for evidence‐based decision making in healthcare. To judge the certainty of findings for the specific decision context evidence syntheses should consider context suitability (ie, generalizability, external validity, applicability or transferability). Our objective was to determine the status quo and to provide a comprehensive overview of existing methodological recommendations of Health Technology Assessment (HTA) and Systematic Review (SR) producing organizations in assessing context suitability of evidence on effectiveness of health care interventions. Additionally, we analyzed similarities and differences between the recommendations.

Methods

In this Integrative Review we performed a structured search for methods documents from evidence synthesis producing organizations that include recommendations on appraising context suitability in effectiveness assessments. Two reviewers independently selected documents according to predefined eligibility criteria. Data were extracted in standardized and piloted tables by one reviewer and verified by a second reviewer. We performed a thematic analysis to identify and summarize the main themes and categories regarding recommended context suitability assessments.

Results

We included 14 methods documents of 12 organizations in our synthesis. Assessment approaches are very heterogeneous both regarding the general concepts (eg, integration in the evidence synthesis preparation process) and the content of assessments (eg, assessment criteria).

Conclusion

Some heterogeneity seems to be justified because of the need to tailor the assessment to different settings and medical areas. However, most differences were inexplicable. More harmonization is desirable and appears possible.
New film technologies to address limitations in vehicle display ecosystems
Authors: Van Derlofske John , Pankratz Steve , Franey Eileen
Published: September 2020

Since the introduction of the first modern (i.e., digital) vehicle displays, designers and manufacturers have made significant advances in technologies that improve image quality and enhance unit durability. Typically, these advances have been targeted and discrete. For example, to increase brightness, high efficiency light control films were deployed; to reduce nighttime windshield glare, a light‐directing louver film was incorporated into the liquid crystal display (LCD) backlight. While this targeted approach to vehicle display concerns has advanced performance—in many cases impressively—it may have reached the limits of its effectiveness. For displays based on the most common head‐up display (HUD) architecture, shortcomings are often interrelated. As such, they require a holistic or cabin human machine interface (HMI) ecosystem approach that recognizes this interplay and, where possible, addresses multiple issues simultaneously. Several new films, in concert with existing film technologies, show how a cabin ecosystem strategy can be implemented.
The Mediating Role of Alexithymia in the Association Between Adverse Childhood Experiences and Postdeployment Mental Health in Canadian Armed Forces Personnel
Authors: McCuaig Edge Heather J. , Lee Jennifer E. C.
Published: September 2020

Recent studies showing an association between adverse childhood experiences and the development of alexithymia in military personnel have generated interest regarding the role of alexithymia in the pathway linking childhood trauma exposure to mental health disorders. Accordingly, the current study was conducted to (a) examine the associations among adverse childhood experiences, alexithymia, and symptoms of depression and posttraumatic stress disorder (PTSD) among recently deployed Canadian military personnel and (b) assess the mediating role of alexithymia in these associations. Data collected from 2,927 members of the Canadian Armed Forces at baseline and after their return from an overseas deployment were subjected to a prospective path analysis. The results of the path analysis, R2 = .35, pointed to a significant direct effect of childhood adversity on postdeployment mental health symptoms. Contrary to our expectations, the results also pointed to a negative indirect effect of childhood neglect, suggesting that childhood neglect contributed to lower levels of postdeployment depression and PTSD symptoms through the dimension of alexithymia related to difficulty in describing feelings. These patterns of associations, for the most part, persisted even when accounting for combat exposure during recent deployments, R2 = .42. The present results are discussed in light of study limitations and methodological considerations, and policy and clinical implications are noted.
Application of Coblation Tonsillectomy with Inferior Pole Capsule Preservation in Pediatric Patients
Authors: Li Jingjia , Luo Lixia , Chen Weixiong , Zhang Jianli , Deng Xuequan , Liao Lieqiang , Zeng Xianping , Wang Bin
Published: September 2020

Objectives/Hypothesis

To evaluate the application and advantages of coblation tonsillectomy with inferior pole capsule preservation in pediatric patients with tonsillar hypertrophy and recurrent tonsillitis.

Study Design

Retrospective chart review.

Methods

A total of 726 children who were diagnosed with either tonsillar hypertrophy or recurrent tonsillitis were included. Children were divided into two groups according to the surgical technique: conventional coblation tonsillectomy and coblation tonsillectomy with inferior pole capsule preservation. The duration of surgery, intraoperative hemorrhage volume, and postoperative pain, as well as postoperative hemorrhage data in the format of time, location, and degree were compared between the two groups.

Results

Of the 726 children included, conventional coblation tonsillectomy was performed in 320 children, coblation tonsillectomy with inferior pole capsule preservation was performed in 406 children. There were no significant differences in duration of surgery or intraoperative hemorrhage volume between the two groups. Children who underwent coblation tonsillectomy with inferior pole capsule preservation showed a remarkable improvement in postoperative pain on days 3 and 5 postoperatively. Additionally, the coblation tonsillectomy with inferior pole capsule preservation group exhibited a significantly lower total postoperative hemorrhage rate, secondary hemorrhage rate, and hemorrhage rate in the inferior pole compared with that in the conventional coblation tonsillectomy group. During the 1‐year follow‐up period, no cases of tonsillar re‐hypertrophy or recurrent tonsillitis were observed in either group.

Conclusion

For pediatric tonsillar hypertrophy and recurrent tonsillitis, coblation tonsillectomy with inferior pole capsule preservation is a safe and effective technique, capable of reducing postoperative pain and hemorrhage, especially secondary hemorrhage at the inferior pole.

Level of Evidence

3b Laryngoscope, 131:1157–1162, 2021
Pediatric Tracheal Lobular Capillary Hemangioma: A Case Report and Review of the Literature
Authors: Wang Ray Y. , Quintanilla Norma M. , Chumpitazi Bruno P. , Gitomer Sarah , Chiou Eric H. , Ongkasuwan Julina
Published: September 2020

Chronic cough is a common complaint in the pediatric population and can have many different etiologies. We present a rare case of a tracheal lobular capillary hemangioma (LCH), also known as pyogenic granuloma, causing chronic cough in a child. In this case, the tracheal LCH was managed successfully with laser ablation. A review of the literature reveals only 2 other reported pediatric cases of tracheal LCH. Laryngoscope, 131:1729–1731, 2021
Effect of substrate pre‐treatment on the low cycle fatigue performance of tungsten carbide‐cobalt coated additive manufactured 316 L substrates
Authors: Tillmann W. , Hagen L. , Garthe K.‐U. , Hoyer K.‐P. , Schaper M.
Published: September 2020

Numerous studies already identified that the fatigue strength of 316 L parts processed by laser beam melting (LBM) is distinctly affected by the surface integrity. Among others, surface defects as well as residual stresses are of crucial importance. Despite new findings in the field of surface engineering of laser beam melting (LBM) parts, the low cycle fatigue strength of thermally sprayed additively manufactured substrates has not been in the focus of research to date. This study aims at evaluating the effect of different pre‐treatments onto 316 L substrates processed by laser beam melting (LBM) prior to the deposition of a high velocity oxy‐fuel (HVOF) sprayed tungsten carbide‐cobalt coating and their effect on the low cycle fatigue strength. Therefore, 316 L substrates were examined in their as‐built state as well as after grit blasting with regards to the surface roughness, strain hardening effects, and residual stresses. To differentiate between topographical effects and residual stress related phenomena, stress‐relieved 316 L substrates served as reference throughout the investigations. The tungsten carbide‐cobalt coated and differently pre‐treated 316 L substrates were mechanically tested under quasi‐static and dynamic load conditions. Besides the low cycle fatigue strength, the fracture toughness as well as the fracture mechanism were identified based on fracture surface analysis.
Transplantation of a latissimus dorsi flap after nearly 6 hr of extracorporal perfusion: A case report
Authors: Kolbenschlag Jonas , Lescan Mario , Bahrs Christian , Bornemann Antje , Daigeler Adrien , Schäfer Ruth
Published: September 2020

Prolonged ischemia of tissues inevitably leads to their necrosis. This is especially relevant in the case of transplantation or replantation. In such situations, reperfusion in a timely manner might not be possible due to transportation times or other unforeseen complications. Therefore, a readily available and simple method to oxygenate the tissue and thus widen the time frame to reperfusion seems desirable. Here, we present the case of extracorporal perfusion of a latissimus dorsi (LD) flap that was successfully transplanted after nearly 6 hr of ischemia. A 41‐year‐old patient suffered multiple injuries including complete severance of the popliteal artery requiring emergency bypass. After stabilization of the patient and subsequent debridement, a LD flap was performed for soft tissue coverage. However, there was an acute occlusion of the bypass during flap inset. To salvage the free flap, a one‐way extracorporal perfusion of the flap with heparinized isotonic saline solution was performed for a total of 5 hr and 47 min. The flap survived with minimal tip necrosis. This case report describes the application of a simple extracorporal perfusion technique for salvage of a free flap over a prolonged ischemia time and discusses the relevant literature. Due to its ease and quickness of application as well as ubiquitous availability, it might serve as a valuable tool in cases of acute problems with the recipient vessels or other incidents where several hours of ischemia time are to be anticipated.
Improving the performance of NRZ‐DPSK optical fiber networks using adaptive FSR in the receiver
Authors: Haridim Motti , Afrimov Liran , Milgrom Benny , Zalmanovich Evgeny , Gamliel Amir , Juwiler Irit
Published: September 2020

In this work, we consider the impact of spectral narrowing of 43Gb/s NRZ‐DPSK signals on the system performance. NRZ‐DPSK signals passing through reconfigurable optical add/drop multiplexer (ROADM) devices are subject to spectral narrowing due to the narrow bandwidth of ROADMs. For a system level analysis of this phenomenon, we model the ROADM devices as a bandpass filter, the bandwidth of which is deliberately decreased. The dependence of the system performance on the delay time between adjacent bits in the receiver is also investigated. It is shown that the performance of signals passing through ROADM devices can be improved with an appropriate delay line interferometer (DLI) for any amount of devices. These results were obtained by simulating the whole system performance using different values of the BPF bandwidth and FSR. We present a technique for finding the optimal FSR of DLI that allows for improving the performance of NRZ‐DPSK systems in the presence of spectral narrowing of the channel. Improved bit error ratio is achieved by using optimized FSR for each BW.
3‐D printed waveguide attenuators operating at ka‐band (26.5‐40 GHz)
Authors: Wang Yi , Guo Cheng , Shang Xiaobang , Wu Wen
Published: September 2020

In this article, two Ka‐band (26.5‐40 GHz) waveguide attenuators designed for three‐dimensional (3‐D) metal printing are presented. These designs are based on long waveguides with elliptical cross‐sections, so that the waveguide structure can be self‐supported during printing. Bended waveguide and helical waveguide are utilized by the two attenuators, respectively, to achieve reduced overall sizes. The attenuations are fixed, however, these can be altered by varying the length/height of waveguides. The limitation of 3‐D metal printing process on surface roughness is also used to provide attenuation. Therefore, the proposed attenuators can cope with printing process with relatively poor surface finish. The prototype designs are fabricated using a metallic selective laser melting (SLM) process and are measured to have good electrical performance across the full waveguide band. The measured attenuation values are in the range of 3.7 to 6.3 dB for the bended waveguide attenuator and 4.3 to 6.3 dB for the helical waveguide attenuator. Both attenuators are measured to have a good return loss (S11 < −20 dB) across the whole Ka‐band. This demonstrates that 3‐D metal printed attenuators could be an attractive alternative to the conventional designs based on absorbing materials, particularly for applications demanding high powers.
Efficacy of a complex smartphone application for reducing hazardous alcohol consumption: Study protocol for a randomized controlled trial with analysis of in‐app user behavior in relation to outcome
Authors: File Domonkos , Bőthe Beáta , Kapitány‐Fövény Máté , Demetrovics Zsolt
Published: September 2020

Objective

The efficacy of alcohol reduction applications is variable, and the underlying factors are largely unknown. The aim of this study is threefold: evaluate the relationship between user engagement and intervention efficacy, investigate the efficacy of the different functions applied, and investigate the efficacy of the intervention application compared to control groups.

Methods

A randomized controlled trial will be conducted to determine the efficacy of a newly developed smartphone application compared to the controls in reducing alcohol consumption at a 30, 60, 90, 120, 150, and 180 days follow‐up. Hazardous drinkers, aged 18 years or older, will be recruited through web articles and will be randomized (blinded to their allocation), to receive one of the two versions of the application (educational or control application) for 30 days, or will be allocated to a wait‐list control group. Function usage times will be recorded on a single‐user level to determine the association between application usage and efficacy.

Results

Data collection will be completed by July 2020, and follow‐up will be completed by January 2021.

Conclusions

The evaluation of intervention efficacy as a function of user behavior will hopefully contribute to the science of developing more efficient alcohol intervention applications in the future.
Differences in pharmacokinetic behaviors of two lipophilic 3‐substituted 2,2,5,5‐tetramethylpyrrolidine‐N‐oxyl radicals, in vivo probes to assess the redox status in the brain using magnetic resonance techniques
Authors: Takeshita Keizo , Okazaki Hana , Tsukamoto Megumi , Okazaki Shoko
Published: September 2020

Purpose

The pharmacokinetics of 3‐methoxycarbonyl‐ and 3‐hydroxymethyl‐2,2,5,5‐tetramethylpyrrolidine‐N‐oxyl radicals (MCP and HMP, respectively), magnetic resonance probes to assess the brain redox status, were examined in healthy mouse brains.

Methods

The time course of the concentration of the radical form of the probe in the brain was examined by signal enhancements on T1‐weighted MR image after an intravenous injection. The distribution of the total probe (sum of radical and reduced forms) was investigated using brain homogenates.

Results

MCP distributed to the brain more than HMP. MCP exhibited biphasic decay with fast and slow components, whereas HMP exhibited monophasic decay with a similar rate constant to the slow component of MCP. Similar profiles were observed in various regions of the brain. The total probe for MCP exhibited monophasic decay at a similar rate constant to the slow component of the radical form; however, the initial content of the total probe was similar to its radical form. For HMP, decay of the total probe coincided with that of the radical form.

Conclusion

The decay of MCP needs to consider the reduction of the probe in and its elimination from the brain, while the decay of HMP may mainly result from its elimination from the brain.
Flexible MEGA editing scheme with asymmetric adiabatic pulses applied for measurement of lactate in human brain
Authors: Dacko Michael , Lange Thomas
Published: September 2020

Purpose

A flexible MEGA editing scheme which decouples the editing efficiency from TE is proposed and the utility of asymmetric adiabatic pulses for this new technique is explored. It is demonstrated that the method enables robust
measurement of lactate in healthy human brain.

Methods

The proposed variation of the MEGA scheme applies editing pulses in both acquired spectra, ensuring that the difference in J‐evolution of the target resonance leads to maximal signal yield in the difference spectrum for arbitrary TE. A MEGA‐sLASER sequence is augmented with asymmetric adiabatic editing pulses for enhanced flexibility and immunity to
miscalibration and inhomogeneities. The technique is validated and optimized for flexible lactate editing via a simple analytical model, numerical simulations and in vitro experiments. The
relaxation constant of lactate is determined in vivo via multiple‐TE measurements with the proposed method and a dedicated postprocessing and quantification approach.

Results

Asymmetric adiabatic editing pulses improve robustness and facilitate efficient J‐editing in sequences or protocols with strong timing constraints. Single voxel measurements using the proposed MEGA scheme in the occipital cortex of six healthy subjects yield a relaxation constant of
 ms for the methyl resonance of lactate at a field strength of 3T.

Conclusions

The proposed MEGA editing scheme allows for novel kinds of J‐editing experiments and promises to be an asset to robust
measurement of lactate and potentially other J‐coupled metabolites in vivo.
Home‐Prepared Enteral Tube Feeding: Evaluation of Microbiological Contamination, Hygiene, and the Profile of the Food Handler
Authors: Galindo Caroline de Oliveira , Beux Marcia Regina , da Costa Rayane Luizi , Uniat Kelly Cristina , Leobet Jaqueline , Ferreira Sila Mary Rodrigues , Medeiros Caroline Opolski , Schieferdecker Maria Eliana Madalozzo , Stangarlin‐Fiori Lize
Published: September 2020

Background

Little is known about the risk to patients’ health when using home‐prepared enteral tube feeding. The objective of this study was to explore the differences in hygiene conditions and microbial load of different types of home‐prepared enteral tube feeding and explore associations between those differences and food handlers’ characteristics.

Methods

We evaluated 96 enteral formulations, considering 3 types used by adult patients: homemade enteral preparations (HEPs), blended enteral preparations (BEPs), and commercial enteral formulas (CEFs). Enteral formulations were collected from homes and microbiologically analyzed. Hygiene criteria were assessed using a checklist, applied during the handling stages. The profile of the food handler was reviewed using a questionnaire.

Results

82.3% (79/96) exceeded acceptable bacterial counts, which was 10³ colony‐forming units per gram for aerobic mesophilic microorganisms and for total coliforms (35 °C), Escherichia coli, Staphylococcus sp, and Staphylococcus coagulase‐positive, if present in the enteral formulations. The number of inadequate samples was higher in HEPs and BEPs than in CEFs. Considering the hygiene criteria, the home‐prepared enteral tube feedings did not differ significantly. There was a significant difference among hygiene conditions considering the variables “monthly family income” and “food training.”

Conclusion

Regardless of the type of enteral formulations used by patients, when handled at home, there was a risk of contamination. However, contaminants present in enteral formulations can be easily controlled with improvements in hygiene measures as well as with greater guidance and control during the handling stages.
Why do participants in voluntary organizations leave? Exploring the relationship between value congruence and length of stay
Authors: Ihm Jennifer , Baek Young Min
Published: September 2020

Recognizing the importance of values and the specific characteristics of participants and situations in voluntary organizations, we examine how value congruence—the fit or compatibility of values between participants and the organization, or among participants—interacts with personal and situational factors to predict participants' length of stay in their organizations. Introducing the case of a voluntary organization that offers shared housing, we measure value congruence through textual similarity in the self‐introduction documents of 49 participants and the organization's mission statement. This approach differs from the self‐reported measures based on participants' perceptions or recalled interactions used in previous studies. In line with expectation‐disconfirmation theory, participants with the strongest beliefs in organizational values had shorter lengths of stay. The amount of intraorganizational communication also moderated the relationship between value congruence and length of stay. This study provides theoretical and methodological implications for nonprofit management by considering personal and situational factors and evaluating value congruence by textual similarity.
Functional imaging of RAS pathway targeting in malignant peripheral nerve sheath tumor cells and xenografts
Authors: Butler Erin , Schwettmann Blake , Geboers Sophie , Hao Guiyang , Kim Jiwoong , Nham Kien , Sun Xiankai , Laetsch Theodore W. , Xu Lin , Williams Noelle S. , Skapek Stephen X.
Published: September 2020

Background

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive form of soft‐tissue sarcoma (STS) in children. Despite intensive therapy, relatively few children with metastatic and unresectable disease survive beyond three years. RAS pathway activation is common in MPNST, suggesting MEK pathway inhibition as a targeted therapy, but the impact on clinical outcome has been small to date.

Procedure

We conducted preclinical pharmacokinetic (PK) and pharmacodynamic studies of two MEK inhibitors, trametinib and selumetinib, in two MPNST models and analyzed tumors for intratumor drug levels. We then investigated 3′‐deoxy‐3′‐[18F]fluorothymidine (18F‐FLT) PET imaging followed by 18F‐FDG PET/CT imaging of MPNST xenografts coupled to short‐term or longer‐term treatment with selumetinib focusing on PET‐based imaging as a biomarker of MEK inhibition.

Results

Trametinib decreased pERK expression in MPNST xenografts but did not prolong survival or decrease Ki67 expression. In contrast, selumetinib prolonged survival of animals bearing MPNST xenografts, and this correlated with decreased pERK and Ki67 staining. PK studies revealed a significantly higher fraction of unbound selumetinib within a responsive MPNST xenograft model. Thymidine uptake, assessed by 18F‐FLT PET/CT, positively correlated with Ki67 expression in different xenograft models and in response to selumetinib.

Conclusion

The ability of MEK inhibitors to control MPNST growth cannot simply be predicted by serum drug levels or drug‐induced changes in pERK expression. Tumor cell proliferation assessed by 18F‐FLT PET imaging might be useful as an early response marker to targeted therapies, including MEK inhibition, where a primary effect is cell‐cycle arrest.
Extraction of naturally occurring cannabinoids: an update
Authors: Nahar Lutfun , Uddin Shaikh Jamal , Alam Md. Ashraful , Sarker Satyajit D.
Published: September 2020

Introduction

Organic molecules that interact with the cannabinoid receptors are called cannabinoids, which can be endogenous, natural or synthetic compounds. They possess similar pharmacological properties as produced by the plant, Cannabis sativa L. Before cannabinoids can be analysed, they need to be extracted from the matrices.

Objective

To review literature on the methods and protocols for the extraction of naturally occurring cannabinoids.

Methodology

An extensive literature search was performed incorporating several databases, notably, Web of Knowledge, PubMed and Google Scholar, and other relevant published materials. The keywords used in the search, in various combinations, with cannabinoids and extraction being present in all combinations, were Cannabis, hemp, cannabinoids, Cannabis sativa, marijuana, and extraction.

Results

In addition to classical maceration with organic solvents, e.g. ethanol, pressurised solvent extraction, solvent heat reflux, Soxhlet extraction, supercritical fluid extraction, ultrasound‐assisted extraction and microwave‐assisted extraction, are routinely used nowadays for the extraction of cannabinoids from plant materials and cannabis consumer products. For the extraction of cannabinoids from biological samples, e.g. human blood, and also from food and beverages, and wastewater, solid‐phase extraction and its variants, as well as liquid–liquid extraction are commonly used. Parameters for extraction can be optimised by response surface methodology or other mathematical modelling tools. There are at least six US patents on extraction of cannabinoids available to date.

Conclusions

Irrespective of the extraction method, extraction temperature, extraction time and extraction pressure play a vital role in overall yield of extraction. Solvent polarity can also be an important factor in some extraction methods.
Risk of common infections among individuals with psoriasis in Sweden: A nationwide cohort study comparing secukinumab to ustekinumab
Authors: Srinivas Chaitra , Odsbu Ingvild , Linder Marie
Published: September 2020

Purpose

To determine risk of respiratory tract infections, urinary tract infections and candidiasis in secukinumab users compared to ustekinumab users among individuals with psoriasis in Sweden.

Methods

This was a Swedish population‐based register‐linked new‐user cohort study on individuals with psoriasis and psoriasis arthritis treated with secukinumab (2015‐2017) and ustekinumab (2009‐2017). Ever‐never exposure definition was used, that is, each individual's follow‐up time was attributed to the drug they were first exposed to. Risk of severe respiratory and urinary tract infections and candidiasis (diagnosis codes from out‐patient specialist visits and in‐patient hospitalisations) and respiratory and urinary tract infections treated in primary care (proxied by dispensation of antibiotics) was determined by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression. We also give crude incidence rates and rate ratios.

Results

In total, 1955 new users of secukinumab (n = 848) and ustekinumab (n = 1107) were identified. There was a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users (HR: 1.22, 95% CI: 1.03‐1.43). Non‐significant differences in estimated risk of severe respiratory and urinary tract infections (HR: 0.96, 95% CI: 0.57‐1.61) and candidiasis (HR: 1.80, 95% CI: 0.84‐3.84) treated in the hospital setting were observed.

Conclusion

We observed a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users. Larger studies with longer follow‐up are needed to draw conclusions on relative safety.
Synthesis and characterization of new proton exchange membrane deriving from sulfonated polyether sulfone using ionic crosslinking for electrodialysis applications
Authors: Mabrouk Walid , Lafi Ridha , Charradi Khaled , Ogier Lionel , Hafiane Amor , Fauvarque Jean François , Sollogoub Cyrille
Published: September 2020

In this research work, the synthesis and characterization of new ion exchange membranes made from sulfonated polyether sulfone (SPES) crosslinked by aminated PES (NH2PES) crosslinking reagent have been investigated for electrodialysis (ED) applications. Sulfonated and aminated PES have similar chemical structures that allow a good compatibility, the only difference between them is their functional groups. This membrane (called HNH2) has been obtained by reaction between SPES with 1.3 SO3H groups per monomer unit and the calculated equivalent amount of NH2PES. Three HNH2 membranes have been fabricated with different degrees of sulfonation. The HNH2 membranes properties have been evaluated using different characterization analysis. The results have shown that HNH2 membranes appear to be very promising candidates for electrochemical applications.
Low‐crystallinity to highly amorphous copolyesters with high glass transition temperatures based on rigid carbohydrate‐derived building blocks
Authors: Chen Jingying , Lin Yiming , Chen Yong , Koning Cor E , Wu Jing , Wang Huaping
Published: September 2020

The current trend of developing novel biobased polymeric materials is focused more on utilizing the unique structural/physical properties of renewable building blocks towards niche market applications. In this work, with the aim of developing low‐crystallinity to amorphous polyesters with enhanced thermal properties, a series of copolyesters based on rigid and structurally asymmetric carbohydrate‐derived building blocks, namely furan‐2,5‐dicarboxylic acid and isosorbide, and 1,4‐butanediol were successfully synthesized using melt polycondensation. The copolyesters were obtained with varied chemical compositions and rather high molecular weights (Mn = 24 000–31 000 g mol−1) and intrinsic viscosities ([η] = 0.56–0.72 dL g−1). Incorporation of both building blocks significantly enhances the glass transition temperatures (Tg = 38–107 °C) of polyesters, and also efficiently inhibits the crystallization of the copolyesters. A low content of isosorbide (ca 10 mol%) leads to complete transition of the homopolyester to nearly fully amorphous materials. Detailed characterizations of the chemical structures and thermal properties of the synthesized copolyesters were conducted using various analytical techniques. In addition, hydrolytic and enzymatic degradations of the copolymers in the presence of porcine pancreatic lipase and cutinase were also investigated. © 2020 Society of Industrial Chemistry
AC–DC electropenetrography: fundamentals, controversies, and perspectives for arthropod pest management
Authors: Backus Elaine A , Guedes Raul Narciso C , Reif Kathryn E
Published: September 2020

Studying the intimate association of arthropods with their physical substrate is both important and challenging. It is important because substrate is a key determinant for organism fitness; challenging because the intricacies of this association are dynamic, and difficult to record and resolve. The advent of electropenetrography (EPG) and subsequent developments allowed researchers to overcome this challenge. Nonetheless, EPG research has been historically restricted to piercing–sucking hemipteran plant pests. Recently, its potential use has been greatly broadened for additional pests with instrument advances. Thus, blood‐feeding arthropods and chewing feeders, as well as non‐feeding behaviors like oviposition by both pests and parasitoids, are novel new targets for EPG research, with critical consequences for integrated pest management. EPG can explain mechanisms of crop damage, plant or animal pathogen transmission, and the effects of insecticides, antifeedants, repellents, or transgenic plants and animals, on specific behaviors of damage or transmission. This review broadly covers the principles and development of EPG technology, emphasizing controversies and challenges remaining with suggested research to overcome them. In addition, it summarizes 60+ years of basic and applied EPG research, and previews future directions for pest management. The goal is to stimulate new applications for this unique enabling technology. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.
Many‐Body Effects in Suspended Graphene Probed through Magneto‐Phonon Resonances
Authors: Berciaud Stéphane , Potemski Marek , Faugeras Clément
Published: September 2020

Micro‐magneto‐Raman scattering spectroscopy is made use of to probe magneto‐phonon resonances (MPR) in suspended mono‐ to pentalayer graphene. MPR correspond to avoided crossings between zone‐center optical phonons (G‐mode) and optically active inter‐Landau level (LL) transitions and provide a tool to perform LL spectroscopy at a fixed energy (≈197 meV) set by the G‐mode phonon. Using a single‐particle effective bilayer model, the velocity parameter associated with each MPR is readily extracted. A single velocity parameter slightly above the bulk graphite value suffices to fit all MPR for N ≥ 2 layer systems. In contrast, in monolayer graphene, it is found that the velocity parameter increases significantly from (1.23 ± 0.01) × 106 m s−1 up to (1.45 ± 0.02) × 106 m s−1 as the first to third optically active inter‐LL transitions couple to the G‐mode phonon. This result is understood as a signature of enhanced many‐body effects in unscreened graphene.
Flash desorption of low‐volatility compounds deposited on a heated solid substrate (90°C) by dripping liquid methanol
Authors: Usmanov Dilshadbek T. , Ninomiya Satoshi , Hiraoka Kenzo
Published: September 2020

Rationale

Desorption of low‐volatility compounds deposited on a solid substrate by dripping a methanol drop was explored.

Methods

Low‐volatility compounds such as drugs and explosives were deposited/dried on the substrate at 35°C. After increasing the temperature to 90°C, 5 μL methanol was dripped onto the substrate. The desorbed analytes were ionized by alternating current corona discharge and analyzed by mass spectrometry.

Results

Flash desorption for drugs and explosives was observed accompanied by the rapid evaporation of methanol. However, saccharides, fullerene, cholesterol, and gramicidin S were not detected by the present method.

Conclusions

It was suggested that surface‐active compounds were desorbed at the peripheral front region of the spreading liquid methanol accompanied by rapid evaporation of methanol.
Fitness of influenza A and B viruses with reduced susceptibility to baloxavir: A mini‐review
Authors: Abed Yacine , Saim‐Mamoun Amel , Boivin Guy
Published: September 2020

Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu®), zanamivir (Relenza®), peramivir (Rapivab®) and laninamivir (Inavir®), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti‐influenza agents. Baloxavir marboxil (BXM), an inhibitor of the cap‐dependent endonuclease activity of the influenza PA protein, was approved in the United States and Japan in 2018. Baloxavir acid (BXA), the active compound of BXM, demonstrated a potent in vitro activity against different types/subtypes of influenza viruses including seasonal influenza A/B strains as well as avian influenza A viruses with a pandemic potential. A single oral dose of BXM provided virological and clinical benefits that were respectively superior or equal to those displayed by the standard (5 days, twice daily) oseltamivir regimen. Nevertheless, BXM‐resistant variants have emerged at relatively high rates in BXM‐treated children and adults. Consequently, there is a need to study the fitness (virulence and transmissibility) characteristics of mutants with a high potential to emerge as such variants can compromise the clinical usefulness of BXM. The purpose of this manuscript is to review the fitness properties of influenza A and B isolates harbouring mutations of reduced susceptibility to BXA.
Realizations in feedforward forms of nonlinear input‐output equations with time‐delays
Authors: Kaldmäe Arvo , Kawano Yu , Kotta Ülle
Published: September 2020

The article studies possibilities to find realization of nonlinear retarded control system with constant commensurable delays, described by higher order input‐output equation, in a set of first‐order equations, which is in the so‐called feedforward form. Necessary and sufficient conditions are found for solvability of the problem when the realization is assumed to be strongly observable, that is, when the states of the feedforward form can be represented as functions of system output, input, their time‐derivatives and delays. Though the extension follows, in general, the polynomial approach of the delay‐free case, it is nontrivial. For instance, polynomial division is not, in general, possible for polynomials, defined over ring. Three examples illustrate the results.