bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an imaged capillary isoelectric focusing method for characterizing the surface charge of mRNA lipid nanoparticle vaccines
Authors: Loughney John W. , Minsker Kevin , Ha Sha , Rustandi Richard R.
Published: June 2019

Lipid nanoparticles (LNPs) have been employed for drug delivery in small molecules, siRNA, mRNA, and pDNA for both therapeutics and vaccines. Characterization of LNPs is challenging because they are heterogeneous mixtures of large complex particles. Many tools for particle size characterization, such as dynamic and static light scattering, have been applied as well as morphology analysis using electron microscopy. CE has been applied for the characterization of many different large particles such as liposomes, polymer, and viruses. However, there have been limited efforts to characterize the surface charge of LNPs and CIEF has not been explored for this type of particle. Typically, LNPs for delivery of oligonucleotides contain at least four different lipids, with at least one being an ionizable cationic lipid. Here, we describe the development of an imaged capillary isoelectric focusing method used to measure the surface charge (i.e., pI) of an LNP‐based mRNA vaccine. This method is capable of distinguishing the pI of LNPs manufactured with one or more different ionizable lipids for the purpose of confirming LNP identity in a manufacturing setting. Additionally, the method is quantitative and stability‐indicating making it suitable for both process and formulation development.
Optimization of background electrolyte composition for simultaneous contactless conductivity and fluorescence detection in capillary electrophoresis of biological samples
Authors: Lačná Júlia , Přikryl Jan , Teshima Norio , Murakami Hiroya , Esaka Yukihiro , Foret František , Kubáň Petr
Published: June 2019

In this article, optimization of BGE for simultaneous separation of inorganic ions, organic acids, and glutathione using dual C4D‐LIF detection in capillary electrophoresis is presented. The optimized BGE consisted of 30 mM 2‐[4‐(2‐hydroxyethyl)piperazin‐1‐yl]ethanesulfonic acid, 15 mM 2‐amino‐2‐hydroxymethyl‐propane‐1,3‐diol, and 2 mM 18‐crown‐6 at pH 7.2 and allowed simultaneous separation of ten inorganic anions and cations, three organic acids and glutathione in 20 min. The samples were injected hydrodynamically from both capillary ends using the double‐opposite end injection principle. Sensitive detection of anions, cations, and organic acids with micromolar LODs using C4D and simultaneously glutathione with nanomolar LODs using LIF was achieved in a single run. The developed BGE may be useful in analyses of biological samples containing analytes with differing concentrations of several orders of magnitude that is not possible with single detection mode.
Hydration index and hydrated constitutive model of clay shale using acoustic frequency spectrum
Authors: Liu Xiangjun , Ding Yi , Ranjith P G , Luo Pingya
Published: June 2019

Clay shale is frequently encountered in drilling. With strong hydration capacity, when clay shale contacts with drilling fluid, rock structural and mechanical property will be affected, causing wellbore instability. Acoustic frequency spectrum is a significant parameter in geophysical logging. The influence of hydration on clay shale can be reflected in acoustic logging. Therefore, in order to identify hydration damage and have precise evaluation for hydration damage, a novel hydration damage index has been built on the basis of acoustic frequency spectrum. Meanwhile, considering the influence of hydration, hydrated constitutive model has been proposed using this new index. Results demonstrate that acoustic frequency spectrum has clear modification due to hydration damage. In the hydration evolutionary process, fracture initiation and propagation happen, decreasing acoustic amplitude and dominant frequency. The whole hydration evolutionary process exhibits S curve with clear three stages. In the initial stage, changing ranges of acoustic amplitude and frequency are small. In the middle stage, clear fracture propagation can be noticed and fracture network is formed, boosting the change of acoustic frequency spectrum. Finally, acoustic frequency spectrum becomes stable, meaning hydration damage has reached its limitation. Hydration damage degree is variable with different conditions, but the tendency still remains typical S curve. Stress‐strain curves simulated from hydrated constitutive model are in good agreement with results of uniaxial compressive test, indicating this model can be used to express shale mechanical property in hydration evolutionary process. Findings of this paper can offer theoretical reference for evaluating hydration damage and are advantageous for drilling operation in clay shale formation.
Petrogenesis of Middle Devonian diorite at the Xierqu Fe–Cu deposit in the Kalatag district, eastern Tianshan, NW China
Authors: Chen Lei , Deng Xiao‐Hua , Bagas Leon , Wu Xiang‐Bin , Zou Hai‐Yang , Zhang Hui‐Qiong , Sun Yan , Lv Xiao‐Qiang , Wang Jing‐Bin
Published: June 2019

Xierqu is a skarn Fe–Cu deposit associated with porphyritic diorite, in the Kalatag district of eastern Tianshan, China. The diorite yields a sensitive high‐resolution ion microprobe U–Pb zircon date of 391 ± 3 Ma interpreted as its age of emplacement. Major element geochemistry shows that the diorite is a calc‐alkaline assaying 16.7–19 wt.% of Al2O3, with Mg# values of 56.8–67.1, and Al2O3/(CaO + Na2O + K2O) (A/CNK) values of 0.55–0.94. Trace element characteristics of the diorite show that it is enriched in Ba, K, and Sr and depleted in Nb, Ta, and Ti, with a positive Eu (1.18–1.44) anomaly and high Sr/Y and La/Yb ratios. Sr–Nd isotopic analyses yielded positive εNd(t) values ranging from 7.1 to 9.8 with low initial 87Sr/86Sr ratios of 0.703806 to 0.703856. These geochemical and isotopic characteristics indicate that the diorite is adakite‐like emplaced in an island‐arc setting and resulted from partial melting of subducted oceanic crust in a mantle wedge during the Devonian.
Computational fluid dynamic and thermal stress analysis of coatings for high‐temperature corrosion protection of aerospace gas turbine blades
Authors: Kadir Ali , Bég Anwar O. , El Gendy Mohammed , Bég Tasveer A. , Shamshuddin MD.
Published: June 2019

The current investigation presents detailed finite‐element simulations of coating stress analysis for a three‐dimensional, three‐layered model of a test sample representing a typical gas turbine component. Structural steel, titanium alloy, and silicon carbide are selected for main inner, middle, and outermost layers respectively. ANSYS is used to conduct three types of analysis—static structural, thermal stress analysis, and also computational fluid dynamic erosion (via ANSYS FLUENT). The specified geometry, which corresponds to corrosion test samples exactly, is discretized using a body‐sizing meshing approach, comprising mainly of tetrahedron cells. Refinements were concentrated at the connection points between the layers to shift the focus toward the static effects dissipated between them. A detailed grid independence study is conducted to confirm the accuracy of the selected mesh densities. The momentum and energy equations were solved, and the viscous heating option was applied to represent the improved thermal physics of heat transfer between the layers of the structures. A discrete phase model (DPM) in ANSYS FLUENT was used, which allows for the injection of continuous uniform air particles onto the model, thereby enabling an option for calculating the corrosion factor caused by hot air injection. Extensive visualization of results is provided. The simulations show that ceramic (silicon carbide) when combined with titanium clearly provide good thermal protection; however, the ceramic coating is susceptible to cracking and the titanium coating layer on its own achieves significant thermal resistance. Higher strains are computed for the two‐layer model than the single layer model (thermal case). However even with titanium only present as a coating the maximum equivalent elastic strain is still dangerously close to the lower edge. Only with the three‐layer combined ceramic and titanium coating model is the maximum equivalent strain pushed deeper towards the core central area. Here the desired effect of restricting high stresses to the strongest region of the gas turbine blade model is achieved, whereas in the other two models, lower strains are produced in the core central zones. Generally, the CFD analysis reveals that maximum erosion rates are confined to a local zone on the upper face of the three‐layer system which is in fact the sacrificial layer (ceramic coating). The titanium is not debonded or damaged which is essential for creating a buffer to the actual blade surface and mitigating penetrative corrosive effects. The present analysis may further be generalized to consider three‐dimensional blade geometries and corrosive chemical reaction effects encountered in gas turbine aero‐engines.
How important is early home environment in the prediction of attention‐deficit hyperactivity disorder in adolescence? The protective role of early cognitive stimulation
Authors: Einziger Tzlil , Zilberman‐Hayun Yael , Atzaba‐Poria Naama , Auerbach Judith G. , Berger Andrea
Published: June 2019

Attention‐deficit hyperactivity disorder (ADHD) is highly heritable; however, an adequate home environment may moderate its development. This study examined the early home environment of 70 male adolescents (M age = 13.5 years, SD = 0.95) participating in a prospective high‐risk longitudinal study. Results demonstrated that adolescents who were eventually diagnosed with ADHD tended to have higher home chaos and less enriched home environments in early childhood. Within the different aspects of enriched home environment, less cognitive stimulation—but not less emotional/physical support—was found between diagnosed and nondiagnosed adolescents. This effect was also found among the subgroup of those who, a priori, were at familial risk for ADHD. Early cognitive stimulation longitudinally predicted both ADHD diagnosis and ADHD symptom domains, above and beyond parental ADHD symptoms and other aspects of the early home environment. Results suggest the possible protective role of early cognitive stimulation in the development of ADHD.

Highlights

This study examined the aspects of early childhood home environment that serve as risk/protective factors in the developmental course of ADHD.

Early cognitive stimulation, but not home chaos and emotional/physical environment, longitudinally predicted both ADHD symptoms and diagnosis in adolescence.

Early cognitive stimulation might have a protective role in the developmental course of ADHD.
Integrating Aquatic Designated Use Protection and Restoration Strategies Using an Ecosystem Goods and Services Framework
Authors: Diamond Jerome , Tonning Barry , Parry Kristen , Boschen Clint
Published: June 2019

Water quality standards programs in the United States and other countries are based on designated uses (DUs), which are linked to criteria that specify maximum pollutant levels and other characteristics that are thresholds for waterbody compliance with regulatory goals. Most DUs are similar to certain provisioning ecosystem goods and services (EGS), such as drinking water supply and recreation (e.g., boating, fishing). Absent in the DU concept are supporting or regulating services, which results in disjointed and often ineffective aquatic ecosystem protection and restoration strategies. The focus on discrete sets of water quality parameters in the DU concept can often result in the appearance of conflicting DUs, resulting in poor provisioning of certain DUs. We present a framework that uses EGS to provide a more holistic assessment of DUs and to help inform best management practices that could result in fuller attainment of DUs while providing greater provisioning of desired goods and services. Two case studies are discussed, demonstrating some of the issues with the DU concept, how it is implemented in the United States, and how the EGS framework can provide a crosswalk between the DU paradigm and stakeholder goals for a watershed. A process is presented that could help regulatory agencies and stakeholders make better use of the EGS framework in DU decisions, including watershed protection and restoration. The EGS framework presented here, coupled with a watershed stakeholder process focused on developing an integrative management strategy based on the framework, could help achieve multiple beneficial uses in an aquatic system. Integr Environ Assess Manag 2019;15:808–818. © 2019 SETAC.
Producing mands in concurrent operant environments
Authors: Seaver Jonathan P. , Bourret Jason C.
Published: June 2019

This study examined strategies designed to increase the rate of targeted, low‐probability mands in a concurrent operant environment. We examined the effects of schedule manipulations, prompt manipulations, motivating operation manipulations, and combined behavioral process manipulations. Increases in target mands were produced for all 8 participants. Schedule manipulations were effective in producing increased rates of targeted mands for 3 of 8 participants, whereas prompt manipulations were effective for 4 of 8 participants. Motivating operation manipulations were effective in producing increased rates of targeted mands for 2 of 8 participants and combined behavioral process manipulations were effective for the single participant exposed to the combination.
Web‐based stimulus preference assessment and reinforcer assessment for videos
Authors: Curiel Hugo , Poling Alan
Published: June 2019

This study replicated and extended the use of a web‐based multiple‐stimulus‐without‐replacement preference assessment (Curiel, Curiel, Li, Deochand, & Poling, 2018) by adding a web‐based single‐operant reinforcer assessment. Five adults diagnosed with autism spectrum disorder participated in this study. The web‐based program identified preference hierarchies for 4 of the 5 participants, and the single‐operant reinforcer assessment confirmed that the highly preferred videos functioned as reinforcers. Advantages of computer‐based stimulus preference and reinforcer assessments are discussed.
Evaluating preference for and reinforcing efficacy of fruits and vegetables compared with salty and sweet foods
Authors: Kronfli Faris R. , Vollmer Timothy R. , Fernand Jonathan K. , Bolívar Hypatia A.
Published: June 2019

Children diagnosed with autism spectrum disorder are often more selective in their food preferences than their typically developing peers. Additionally, many preferred food selections have minimal nutritional value. We evaluated the preference for, and reinforcing efficacy of, fruits and vegetables compared with salty and sweet foods, which are often used as edible reinforcers. Multiple‐stimulus preference assessments were conducted to identify preferred foods, and reinforcer assessments were conducted to determine the reinforcing efficacy of more preferred foods. Fruits and vegetables were sometimes preferred over salty or sweet foods and often functioned as reinforcers. Future research should incorporate fruits and vegetables into preference assessments when identifying putative reinforcers.
The use of polymeric meshes for pelvic organ prolapse: Current concepts, challenges, and future perspectives
Authors: Mancuso Elena , Downey Candice , Doxford‐Hook Elizabeth , Bryant Michael G , Culmer Peter
Published: June 2019

Pelvic organ prolapse (POP) is one of the most common chronic disorders in women, impacting the quality of life of millions of them worldwide. More than 100 surgical procedures have been developed over the decades to treat POP. However, the failure of conservative strategies and the number of patients with recurrence risk have increased the need for further adjuvant treatments. Since their introduction, surgical synthetic meshes have dramatically transformed POP repair showing superior anatomic outcomes in comparison to traditional approaches. Although significant progress has been attained, among the meshes in clinical use, there is no single mesh appropriate for every surgery. Furthermore, due to the risk of complications including acute and chronic infection, mesh shrinkage, and erosion of the tissue, the benefits of the use of meshes have recently been questioned. The aim of this work is to review the evolution of POP surgery, analyzing the current challenges, and detailing the key factors pertinent to the design of new mesh systems. Starting with a description of the pelvic floor anatomy, the article then presents the traditional treatments used in pelvic organ disorders. Next, the development of synthetic meshes is described with an insight into how their function is dependent on both mesh design variables (i.e., material, structure, and functional treatment) and surgical applications. These are then linked to common mesh‐related complications, and an indication of current research aiming to address these issues.
The Effect of a Screening and Treatment Program for the Prevention of Fractures in Older Women: A Randomized Pragmatic Trial
Authors: Merlijn Thomas , Swart Karin MA , van Schoor Natasja M , Heymans Martijn W , van der Zwaard Babette C , van der Heijden Amber A , Rutters Femke , Lips Paul , van der Horst Henriëtte E , Niemeijer Christy , Netelenbos J Coen , Elders Petra JM
Published: June 2019

Population screening for fracture risk may reduce the fracture incidence. In this randomized pragmatic trial, the SALT Osteoporosis Study (SOS), we studied whether screening for fracture risk and subsequent treatment in primary care can reduce fractures compared with usual care. A total of 11,032 women aged 65 to 90 years with ≥1 clinical risk factor for fractures were individually randomized to screening (n = 5575) or usual care (n = 5457). Participants in the screening group underwent a screening program, including bone densitometry and vertebral fracture assessment. Participants with a high 10-year fracture probability (FRAX) or a vertebral fracture were offered treatment with anti-osteoporosis medication by their general practitioner. Incident fractures as reported by questionnaires were verified with medical records. Follow-up was completed by 94% of the participants (mean follow-up = 3.7 years). Of the 5575 participants in the screening group, 1417 (25.4%) had an indication for anti-osteoporosis medication. Screening and subsequent treatment had no statistically significant effect on the primary outcome fracture (hazard ratio [HR] = 0.97; 95% confidence interval [CI] 0.87–1.08), nor on the secondary outcomes osteoporotic fractures (HR = 0.91; 95% CI 0.81–1.03), major osteoporotic fractures (HR = 0.91; 95% CI 0.80–1.04), hip fractures (HR = 0.91; 95% CI 0.71–1.15), falls (odds ratio [OR] = 0.91; 95% CI 0.72–1.15), or mortality (HR = 1.03; 95% CI 0.91–1.17). Post hoc explorative finding suggested that screening might be most effective after a recent fracture (HR = 0.65; 95% CI 0.44–0.96 for major osteoporotic fractures and HR = 0.38; 95% CI 0.18–0.79 for hip fractures). The results of this study might have been compromised by nonparticipation and medication nonadherence in the screening group. Overall, this study does not provide sufficient indications to consider screening for fracture prevention. However, we cannot exclude its clinical relevance to reduce (major) osteoporotic fractures and hip fractures because of the relatively small number of women with a treatment indication in the intervention group. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Aerobic training induces differential expression of genes involved in lipid metabolism in skeletal muscle and white adipose tissues
Authors: de Souza Cordeiro Letícia Maria , Mario Érica Guilhen , Moreira Carolina Campos Lima , Rodrigues Angélica Heringer , Wanner Samuel Penna , Soares Danusa Dias , Botion Leida Maria , Ferreira Adaliene Versiani Matos
Published: June 2019

Aerobic training induces adaptive responses in skeletal muscles and white adipose tissues, thus facilitating lipid utilization as energy substrates during a physical exercise session. However, the effects of training on cytokines levels and on transcription factors involved in lipid metabolism in muscle and different white adipose depots are still unclear; therefore, these were the aims of the present study. Nineteen adult male Wistar rats were randomly assigned to a trained group or a control, non‐trained group. The 10‐week training protocol consisted of running on a treadmill, during 1 hour per day, 5 days per week, at 75% of maximum aerobic speed. As expected, trained rats improved their aerobic performance and had augmented citrate synthase activity in the soleus, while the control rats did not. Although body weight was not different between groups, the adiposity index and white adipose depots (ie, epididymal and retroperitoneal) were reduced in trained rats. Training reduced serum concentration of insulin, but failed to change serum concentrations of glucose, triacylglycerol, total cholesterol, and nonesterified fatty acids. Training increased sterol regulatory element‐binding protein‐1c expression in the gastrocnemius and epididymal adipose tissue, and reduced peroxisome proliferator‐activated receptor γ (PPARγ) expression in most of the tissues analyzed. The expression of PPARα and carnitine palmitoyltransferase 1 increased in the gastrocnemius and mesenteric adipose tissue but reduced in epididymal adipose tissue. Triacylglycerol content and tribbles 3 expression reduced in the gastrocnemius of trained rats. Tumor necrosis factor‐α and interleukin‐6 were increased in all adipose depots evaluated. Collectively, our data indicate that the 10‐week aerobic training changed gene expression to improve muscle oxidative metabolism and facilitate lipid degradation in adipose tissues. Our data also highlight the existence of adaptive responses that are distinct between the skeletal muscle and white adipose tissue and between different adipose depots.
MicroRNA‐329 upregulation impairs the HMGB2/β‐catenin pathway and regulates cell biological behaviors in melanoma
Authors: Mo You , Fang Rui‐Hua , Wu Jiang , Si Yuan , Jia Shu‐Qing , Li Qun , Bai Jing‐Zhu , She Xi‐Ning , Wang Jian‐Qin
Published: June 2019

Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA‐329 (miR‐329) has been seen in several human cancers. In this study, we identify whether miR‐329 serves as a candidate regulator in melanoma. Melanoma‐related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR‐329 and high‐mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR‐329 on HMGB2 and the β‐catenin pathway in melanoma cell activities, miR‐329 mimics, miR‐329 inhibitors, and siRNA‐HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR‐329 was predicted to influence melanoma by targeting HMGB2 via the β‐catenin pathway. High level of HMGB2 and low miR‐329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR‐329. In melanoma cells transfected with miR‐329 mimics or siRNA‐HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of β‐catenin, cyclin D1, and vimentin and increased levels of GSK3β and E‐cadherin. Collectively, our results show that miR‐329 can suppress the melanoma progression by downregulating HMGB2 via the β‐catenin pathway.
Expression and activity of key lipases during the larval development of walking catfish (Clarias magur)
Authors: Mir Ishfaq Nazir , Srivastava P. P. , Bhat Irfan Ahmad , Dar Showkat Ahmad , Sushila Ngairangbam , Varghese Tincy , Muralidhar A. P. , Jain K. K.
Published: June 2019

The study was conducted to investigate the expression and activity of key lipolytic enzymes during the ontogenetic development of Clarias magur. After partial characterization, the messenger RNA (mRNA) expression analysis of lipoprotein lipase (LPL), pancreatic triacylglycerol lipase (PL), and bile salt‐activated lipase (BAL) genes along with the specific lipase activity were performed in larvae from Day 1 after hatching till 34‐day posthatch (dph). Heterogeneous patterns of mRNA expression were shown by the important lipolytic enzymes and were detected before first exogenous feeding during the yolk‐sac stage. LPL started increasing from 13 dph and peaked at 16 dph followed by a declining trend till 34 dph. However, the PL observed to be peaking at 9, 22, and 30 dph. Similarly, BAL showed an increasing trend from 11 to 22 dph with a significantly high level of mRNA expression at 16 dph. Later, the specific lipase activity was evaluated which appears at Day 1 after hatching with a progressive increase from 7 to 16 dph and a further declining trend afterwards with a peak at 22 dph. The results indicated the development of exocrine pancreas at 16 dph. Furthermore, the transcript levels and the activity of lipases were regulated with the age. Hence, the present study can be helpful in devising different strategies containing optimum lipid levels at a suitable stage of development for improving the survival during larval rearing. Furthermore, the study could be a baseline for elucidating the optimized dietary lipid levels of this catfish during its larval rearing.
Role of surgical resection in the era of FOLFIRINOX for advanced pancreatic cancer
Authors: Byun Yoonhyeong , Han Youngmin , Kang Jae Seung , Choi Yoo Jin , Kim Hongbeom , Kwon Wooil , Kim Sun‐Whe , Oh Do‐Youn , Lee Sang Hyub , Ryu Ji Kon , Kim Yong‐Tae , Jang Jin‐Young
Published: June 2019

Background

The introduction of FOLFIRINOX regimen greatly changed the treatment for advanced pancreatic cancers. However, detailed studies on the clinical effects and factors affecting the prognosis are insufficient. We performed this study to evaluate the effects of FOLFIRINOX and the surgical resection in advanced pancreatic cancer.

Methods

Three hundred and thirty‐seven patients with advanced pancreatic cancer who initially received FOLFIRINOX, from January 2011 to December 2017, were retrospectively reviewed. Patients were evaluated according to the National Comprehensive Cancer Network guideline, responses after four to six cycles of FOLFIRINOX were re‐evaluated according to the response evaluation criteria in solid tumors, and further treatment was decided in the multidisciplinary meeting.

Results

Sixty‐seven (19.9%) patients had borderline resectable pancreatic cancer, 135 (40.1%) locally advanced pancreatic cancer, and 135 (40.1%) metastatic pancreatic cancer. The median survival period was significantly longer in the surgical group than in the nonsurgical group in each clinical stage, even in metastatic pancreatic cancer (32 vs. 14, P = 0.012). In multivariate analysis, metastatic status at diagnosis, progressive disease after FOLFIRINOX, surgical resection, and declined CA19‐9 after FOLFIRINOX were significant prognostic factors.

Conclusions

Surgical treatment greatly affects survival outcomes in advanced pancreatic cancer treated with FOLFIRINOX. Further studies on the optimal indication of operation and the protocol are needed.
Endolysosomal compartments as platforms for orchestrating innate immune and metabolic sensors
Authors: Miyake Kensuke , Saitoh Shin-ichiroh , Sato Ryota , Shibata Takuma , Fukui Ryutaro , Murakami Yusuke
Published: June 2019

TLRs respond to a variety of microbial products and initiate defense responses against bacteria and viruses. A variety of pathogens invade into and control the endosomal compartment to survive in host cells. On the other hand, host cells deploy cell surface and endosomal TLRs to pathogen-containing vesicles to mount defense responses. The endosomal compartment is a site for pathogen-sensing. As TLR-dependent defense responses are accompanied with a shift to the anabolic state, TLR responses need to be under metabolic control. Cellular metabolic state is monitored by sensing lysosomal metabolites by the mammalian target of rapamycin complex 1 (mTORC1). Type I IFN production induced by endosomal TLRs requires mTORC1. Recent studies have demonstrated that the interaction between TLRs and mTORC1 depends on their anterograde movement to the cell periphery. In a nutrient-sufficient state, a molecular complex called Ragulator recruits and activates mTORC1 in lysosomes. In parallel, Ragulator allows the small GTPase Arl8b to drive lysosomes to the cell periphery. Nutrient-activated mTORC1 in peripheral lysosomes is constitutively associated with type I IFN signaling molecules such as TRAF3 and IKKα. On the other hand, TLR7 and TLR3 are activated in the endosomal compartment and induce trafficking of TLR-containing vesicles to the cell periphery in a manner dependent on Arl8b or another GTPase Rab7a, respectively. Lysosomal trafficking helps TLR7 and TLR3 to interact with nutrient-activated mTORC1 and type I IFN signaling molecules. The endosomal compartments serve as platforms where metabolic sensing machinery licenses TLRs to initiate type I IFN responses.
Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease
Authors: Bakermans Adrianus J. , Wessel Chang Ho , Zheng Kang H. , Groot Paul F.C. , Stroes Erik S.G. , Nederveen Aart J.
Published: June 2019

Background

Clinical assessments of peripheral artery disease (PAD) severity are insensitive to pathophysiological changes in muscle tissue oxygenation and energy metabolism distal to the affected artery.

Purpose

To quantify the blood oxygenation level‐dependent (BOLD) response and phosphocreatine (PCr) recovery kinetics on a clinical MR system during a single exercise‐recovery session in PAD patients.

Study Type

Case–control study.

Subjects

Fifteen Fontaine stage II patients, and 18 healthy control subjects

Field Strength/Sequence

Interleaved dynamic multiecho gradient‐echo 1H T2* mapping and adiabatic pulse‐acquire 31P‐MR spectroscopy at 3T.

Assessment

Blood pressure in the arms and ankles were measured to determine the ankle‐brachial index (ABI). Subjects performed a plantar flexion exercise‐recovery protocol. The gastrocnemius and soleus muscle BOLD responses were characterized using the T2* maps. High‐energy phosphate metabolite concentrations were quantified by fitting the series of 31P‐MR spectra. The PCr recovery time constant (τPCr) was derived as a measure of in vivo mitochondrial oxidative capacity.

Statistical Tests

Comparisons between groups were performed using two‐sided Mann–Whitney U‐tests. Relations between variables were assessed by Pearson's r correlation coefficients.

Results

The amplitude of the functional hyperemic BOLD response in the gastrocnemius muscle was higher in PAD patients compared with healthy subjects (–3.8 ± 1.4% vs. –1.4 ± 0.3%; P < 0.001), and correlated with the ABI (r = 0.79; P < 0.001). PCr recovery was slower in PAD patients (τPCr = 52.0 ± 13.5 vs. 30.3 ± 9.7 sec; P < 0.0001), and correlated with the ABI (r = –0.64; P < 0.001). Moreover, τPCr correlated with the hyperemic BOLD response in the gastrocnemius muscle (r = –0.66; P < 0.01).

Data Conclusion

MR readouts of calf muscle tissue oxygenation and high‐energy phosphate metabolism were acquired essentially simultaneously during a single exercise‐recovery session. A pronounced hypoxia‐triggered vasodilation in PAD is associated with a reduced mitochondrial oxidative capacity.

Level of Evidence: 2

Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:98–107.
Hantavirus infection in Iranian patients suspected to viral hemorrhagic fever
Authors: Salehi‐Vaziri Mostafa , Kaleji Azadeh Salarian , Fazlalipour Mehdi , Jalali Tahmineh , Mohammadi Tahereh , Khakifirouz Sahar , Baniasadi Vahid , Pouriayevali Mohammad Hassan , Mahmoudi Ahmad , Tordo Noel , Mostafavi Ehsan
Published: June 2019

Background: Hantaviruses are a group of emerging pathogens causing hemorrhagic fever with renal syndrome and Hantavirus cardiopulmonary syndrome in human. This study was conducted to investigate Hantavirus infection among Iranian viral hemorrhagic fever suspected patients.

Methods: From April 2014 to June 2016, 113 cases from 25 different provinces of Iran were analyzed for Hantavirus infection by IgM/IgG ELISA and pan‐Hantavirus RT‐PCR tests.

Results: Although, viral genome was detected in none of the subjects, IgM and IgG antibodies were detected in 19 and 4 cases, respectively. Differentiation of the anti‐Hantavirus antibodies according to virus species by EUROLINE Anti‐Hantavirus Profile Kit revealed three Puumala virus IgM positive, one Hantaan virus IgM positive, one Hantaan virus IgM borderline, and two Puumala virus IgG borderline cases.

Conclusions: This study demonstrates the circulation of Hantaviruses in Iran and calls for further investigations of these life‐threatening viruses in the country.
Multiple‐pass‐enhanced Raman spectroscopy for long‐term monitoring of hydrogen isotopologues
Authors: Wen Chengwei , Huang Xin , Wang Weiwei , Shen Chunlei , Li Hairong
Published: June 2019

We report a variant of multiple‐pass Raman spectroscopy with enhanced sensitivity for engineering applications. A four‐mirror multiple pass cell is introduced and compared with the conventional two (concave)‐mirror configuration. With this system, gas samples in static cells are measured and monitored. The results show that the noise equivalent detection limit (3σn) close to 100 ppm for hydrogen isotopologues can be achieved within two seconds with a 1.5‐W red laser. The relative precision is characterized by long‐term measurement, and the results indicate high system stability. The signal‐to‐noise ratio (SNR) in different configurations are investigated, and results show that high (greater than nine) SNR gain is achieved in the configuration of 12 passes. This newly designed Raman system is highly stable and suitable for fast and precise in‐line monitoring of hydrogen isotopologue mixtures, as well as other (hazardous) gas samples.
Effect of treatment sequence on survival in stage IV rectal cancer with synchronous and potentially resectable liver metastases
Authors: Ghiasloo Mohammad , Kahya Hasan , Van Langenhove Samuel , Grammens Julien , Vierstraete Maaike , Berardi Giammauro , Troisi Roberto I. , Ceelen Wim
Published: June 2019

Background and Objectives

The optimal treatment sequence in stage IV rectal cancer (RC) with synchronous liver metastases (SLM) remains undefined. Here, we compared outcomes between patients treated with the bowel‐first approach (BFA) or the liver‐first approach (LFA).

Methods

Consecutive patients diagnosed with stage IV RC with SLM and who underwent complete resection were included. Both groups were matched using propensity scores. Differences in postoperative outcome, local control, and long‐term survival were studied. In addition, a decision analysis (DA) model was built using TreeAge Pro to define the approach that results in the highest treatment completion rate.

Results

During a 12‐year period, 52 patients were identified, 21 and 31 of whom underwent the BFA and the LFA, respectively. Twenty‐eight patients were matched; patients treated with the BFA experienced a longer median OS (50.0 vs 33.0 months; P = .40) and higher 5‐year OS (42.9% vs 28.6%). The DA defined the BFA to be superior when the failure threshold (ie, no R0 resection, treatment discontinuation regardless of cause) for colectomy is less than 28.6%.

Conclusions

In stage IV rectal cancer with SLM, either the BFA or the LFA result in similar long‐term outcomes. Treatment should be tailored according to clinicopathological variables.
Construction of a comprehensive beer proteome map using sequential filter‐aided sample preparation coupled with liquid chromatography tandem mass spectrometry
Authors: Sun Zhen , Yu Xinhe , Zhang Yanrong , Xu Jiuxiang , Li Xianzhen
Published: June 2019

The quality traits of beer, which include flavor, texture, foam stability, gushing, and haze formation, rely on contributions from beer proteins and peptides. Large‐scale proteomic analysis of beer is gaining importance, not only with respect to authenticity of raw material in beer but also to improve quality control during beer production. In this work, foam proteins were first isolated from beer by virtue of their high hydrophobicity. Then sequential filter‐aided sample preparation coupled with liquid chromatography and tandem mass spectrometry was used to analyze both beer protein and foam protein. Finally, 4692 proteins were identified as beer proteins, and 3906 proteins were identified as foam proteins. In total, 7113 proteins were identified in the beer sample. Several proteins contributing to beer quality traits, including lipid transfer protein, serpin, hordein, gliadin, and glutenin, were detected in our proteins list. This work constructed a comprehensive beer proteome map that may help to evaluate potential health risks related to beer consumption in celiac patients.
Measuring the impact of dysphonia on quality of life using health state preferences
Authors: Naunheim Matthew R. , Goldberg Leanne , Dai Jennifer B. , Rubinstein Benjamin J. , Courey Mark S.
Published: June 2019

Objectives

Formal evaluation of health states related to dysphonia have not been rigorously evaluated in affected patients. The objective of this project was to evaluate the health states of mild, moderate, and severe dysphonia using formal health state preference evaluation, and to compare these outcomes with the degree of voice handicap.

Design

Prospective health state preference assessment.

Methods

A convenience sample of patients presenting with voice complaints were enrolled from an academic voice center. Demographic and voice handicap index (VHI‐10) data were obtained, and an assessment of preference for five health states (monocular blindness, binocular blindness, mild dysphonia, moderate dysphonia, and severe dysphonia) was performed. Utility scores were calculated on a scale from 0 (death) to 1 (perfect health). Analysis was performed with ANOVA testing with post‐hoc comparisons and correlation statistics.

Results

Of 209 assessments, 149 (75.6%) met quality criteria. Relative to monocular blindness (score 0.61 [CI 0.57–0.64]), moderate dysphonia (0.58 [0.54–0.62]) was rated equivalently, with severe dysphonia (0.33 [0.29–0.37]) ranking significantly worse and mild dysphonia (0.96 [0.95–0.98]) significantly better. Binocular blindness (0.18 [0.15–0.21]) was the worst‐ranked health state. There was a weak inverse correlation of VHI‐10 with dysphonia‐related preference scores; with worsening reported voice handicap, scores decreased.

Conclusion

This study demonstrated that dysphonia had a significant impact of quality of life, with moderate dysphonia ranking equivalently with monocular blindness. These numerical estimates may be used for ongoing research into the value and cost‐effectiveness of medical, therapeutic, and surgical interventions for voice disorders.

Level of Evidence

2c (outcomes research)

Laryngoscope, 130:E177–E182, 2020
Prenatal cytogenomic identification and molecular refinement of compound heterozygous STRC deletion breakpoints
Authors: Shi Lisong , Bai Yan , Kharbutli Yara , Oza Andrea M. , Amr Sami S. , Edelmann Lisa , Mehta Lakshmi , Scott Stuart A.
Published: June 2019

Here, we report the prenatal detection of a compound heterozygous deletion at chromosome 15q15.3 by clinical chromosomal microarray (CMA) testing that included the CATSPER2 male infertility gene. However, given the low resolution of CMA at this homologous locus, it was unclear if the neighboring STRC hearing loss gene was also affected. Therefore, we developed a novel allele‐specific PCR strategy, which narrowed the proximal breakpoint of the maternally inherited deletion to a 310 bp interval that was 440 bp upstream from the STRC transcription start site.
Effect of a general body force on a 2D generalized thermoelastic body with a cylindrical cavity
Authors: Sherief Hany H. , El‐Maghraby Nasser M. , Zaky Mohamed F.
Published: June 2019

We consider a 2D problem for an infinite body with a cylindrical cavity formed of a thermoelastic substance. The body is under the action of a nonsolenoidal body force. The theory used is that of Generalized Thermoelasticity. The surface is assumed to be traction free and subjected to an asymmetrical thermal shock. Laplace transform is used. The inversion process is carried out numerically. All the relevant functions are represented graphically.
Diet‐Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort
Authors: Low Dorrain Yanwen , Lefèvre‐Arbogast Sophie , González‐Domínguez Raúl , Urpi‐Sarda Mireia , Micheau Pierre , Petera Melanie , Centeno Delphine , Durand Stephanie , Pujos‐Guillot Estelle , Korosi Aniko , Lucassen Paul J , Aigner Ludwig , Proust‐Lima Cécile , Hejblum Boris P , Helmer Catherine , Andres‐Lacueva Cristina , Thuret Sandrine , Samieri Cécilia , Manach Claudine
Published: June 2019

Scope

Untargeted metabolomics may reveal preventive targets in cognitive aging, including within the food metabolome.

Methods and results

A case‐control study nested in the prospective Three‐City study includes participants aged ≥65 years and initially free of dementia. A total of 209 cases of cognitive decline and 209 controls (matched for age, gender, education) with slower cognitive decline over up to 12 years are contrasted. Using untargeted metabolomics and bootstrap‐enhanced penalized regression, a baseline serum signature of 22 metabolites associated with subsequent cognitive decline is identified. The signature includes three coffee metabolites, a biomarker of citrus intake, a cocoa metabolite, two metabolites putatively derived from fish and wine, three medium‐chain acylcarnitines, glycodeoxycholic acid, lysoPC(18:3), trimethyllysine, glucose, cortisol, creatinine, and arginine. Adding the 22 metabolites to a reference predictive model for cognitive decline (conditioned on age, gender, education and including ApoE‐ε4, diabetes, BMI, and number of medications) substantially increases the predictive performance: cross‐validated Area Under the Receiver Operating Curve = 75% [95% CI 70–80%] compared to 62% [95% CI 56–67%].

Conclusions

The untargeted metabolomics study supports a protective role of specific foods (e.g., coffee, cocoa, fish) and various alterations in the endogenous metabolism responsive to diet in cognitive aging.
Intracranial simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MRA: Analyzation, optimization, and extension for dynamic MRA
Authors: Xiong Yuhui , Zhang Zhe , He Le , Ma Yu , Han Hualu , Zhao Xihai , Guo Hua
Published: June 2019

Purpose

Simultaneous noncontrast angiography and intraplaque (SNAP) imaging, as a noncontrast‐enhanced MRA technique, may not provide consistent vessel visualization for intracranial artery imaging among subjects. This study aims to investigate the underlying mechanism and extend SNAP to dynamic MRA.

Methods

The cause of the instability of intracranial SNAP‐MRA was investigated through theoretical analysis and simulations. The scan parameters, including TI and flip angle, were optimized for reliable imaging. In vivo experiments were conducted to validate the simulation results. The simulation results were correlated with real intracranial blood flow by introducing the concept of blood travel time, and intracranial SNAP‐MRA was revealed to reflect the cerebral blood expanse region in 5 TI. A new noncontrast‐enhanced dynamic MRA technique, termed 4D SNAP‐MRA, was proposed and demonstrated through in vivo scans.

Results

The cause of the instability of intracranial SNAP‐MRA was proved to be the slow or fast blood flow in the imaging slab. This instability can be mitigated by adjusting TI and flip angle in the SNAP sequence. The proposed 4D SNAP‐MRA can provide dynamic visualization of the cerebral blood circulation and cerebral hemodynamic information such as blood travel time.

Conclusion

The 3D SNAP‐MRA with optimal imaging parameters can generate cerebral angiography with hemodynamic information, and the 4D SNAP‐MRA provides dynamic visualization of the cerebral blood circulation.
Effects of Hatchery Broodstock Collection on Adult Muskellunge Populations
Authors: Meerbeek Jonathan R. , Weber Michael J.
Published: June 2019

Stocking programs for Muskellunge Esox masquinongy throughout North America rely on the collection of wild adult Muskellunge to acquire gametes for hatchery propagation. The process of collecting, transporting, confining, handling, and spawning broodstock Muskellunge may cause mortality that could alter Muskellunge density, size structure, and population survival rates. We used long-term Muskellunge capture–recapture data collected from the Iowa Great Lakes and Clear Lake in northern Iowa to estimate the number and proportion of Muskellunge captured annually and the initial mortality rates resulting from broodstock collection. We also evaluated whether Muskellunge apparent survival rates differed between individuals used as broodstock and those that were not captured annually. Finally, we evaluated whether the number of initial mortalities or the number of individuals captured were related to annual population survival estimates. Collectively, 7,010 adult Muskellunge (3,896 males and 3,114 females) captures occurred between 2001 and 2017, and population densities within a system ranged from 0.11 to 0.39 fish/ha. An average of 33% (range = 13–76%) of the population was captured during broodstock operations annually. Between 0 and 28 (0.0000 to 0.0191 fish/ha) Muskellunge died at each hatchery annually, and more males died than females (total of 150 males and 68 females; 3.9% and 2.2% of captured fish, respectively). However, annual mortalities were generally a low proportion of Muskellunge in the lake (<2%; <0.001 fish/ha). There was some evidence of size-selective mortality, particularly for males, where larger individuals (875–975 mm) were more likely to die, but we found no evidence to suggest that broodstock collection affected annual population survival estimates. Muskellunge broodstock mortality appears to act in a compensatory manner with natural mortality, and other sources of population mortality are more likely to have a greater effect on the population.
Tuning into performance and satisfaction in nonprofit orchestras: One link between transformational leadership and satisfaction is through reduction in conflict
Authors: Kammerhoff Jana , Lauenstein Oliver , Schütz Astrid
Published: June 2019

In this study, we tested hypotheses concerning volunteers' not‐for‐profit work, specifically the relations of transformational leadership with performance and satisfaction as well as the question of how task and relationship conflict fit into these relations. We argue that conflicts are detrimental to satisfaction and performance and that the frequency of conflict can be reduced through transformational leadership. We analyzed data from a large sample of lay orchestra musicians (N = 1,535) and found that musicians' perceptions of their conductors' transformational leadership style were positively related to both the performance and satisfaction of the musicians. Furthermore, we found that conflict mediated the relation between transformational leadership and satisfaction to some extent. The mediation occurred via the frequencies of both task and relationship conflicts even though the frequency of conflict was quite low in this sample in general.