bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the disease itself: A cross‐cutting educational initiative for patients and families with rare diseases
Authors: Rovira‐Moreno Eulàlia , Abuli Anna , Codina‐Sola Marta , Valenzuela Irene , Serra‐Juhe Clara , Cuscó Ivon , Borregán Mar , Cueto‐González Anna , Vendrell Teresa , López‐Grondona Fermina , Brun‐Gasca Carme , Brignani Eduardo , Martínez‐Ribot Laia , Garci‐Espejo Regla , Cruz Jordi , García‐Arumí Elena , Tizzano Eduardo F.
Published: November 2020

Rare diseases (RDs) as a whole affect a huge number of individuals although each specific condition comprises a low number of individuals. As a consequence, funds allocated to expand research to all conditions are often limited. Several initiatives have emerged to invest more resources for research in RDs, but patients express unmet needs regarding educational initiatives, awareness support, and psychosocial resources. We developed an educational training program in the format of weekly sessions covering basic medical scientific knowledge and psychosocial aspects of RDs. The aim of this initiative was to assess its overall impact regarding knowledge, psychological issues, and participant satisfaction. Items were evaluated through surveys before and after the sessions. Here, we report the experience and impact of two editions of this initiative with a total of 37 participants. Our results show improvements in knowledge and better management of the psychological impact. Moreover, participants were able to exchange experiences and concerns, most of which were shared even though the RDs were different. Overall, the program was evaluated by the participants as a highly beneficial experience and all of them were interested in attending advanced editions.
Canonical double covers of generalized Petersen graphs, and double generalized Petersen graphs
Authors: Qin Yan‐Li , Xia Binzhou , Zhou Sanming
Published: November 2020

The canonical double cover of a graph is the direct product of and . If then is called stable; otherwise is called unstable. An unstable graph is said to be nontrivially unstable if it is connected, non‐bipartite and no two vertices have the same neighborhood. In 2008 Wilson conjectured that, if the generalized Petersen graph is nontrivially unstable, then both and are even, and either is odd and , or . In this note we prove that this conjecture is true. At the same time we determine all possible isomorphisms among the generalized Petersen graphs, the canonical double covers of the generalized Petersen graphs, and the double generalized Petersen graphs. Based on these we completely determine the full automorphism group of the canonical double cover of for any pair of integers with .
Design, synthesis, and antifungal evaluation of novel coumarin‐pyrrole hybrids
Authors: Zhang Shuguang , Tan Xin , Liang Chaogen , Zhang Weihua
Published: November 2020

A series of coumarin derivatives bearing a pyrrole scaffold were designed, prepared, and assessed for their in vitro antifungal activities against six phytopathogenic fungi. The antifungal activity screening results suggest that some synthesized hybrids exhibited potential fungicidal activities against the tested fungi. In particular, compounds 6j, 6k, 6o, 6p, and 6r displayed significant antifungal effects against Rhizoctorzia solani, and possessed EC50 values of 3.94, 7.75, 6.38, 6.25, and 7.67 μg/ mL, respectively. The above activities are more potent than the commercialized fungicide Boscalid (11.52 μg/mL) and Osthole (9.79 μg/mL). These results provide a significant reference for further rational design of coumarin‐based fungicides.
An epilepsy‐associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model
Authors: Ahn Lucie Y. , Coatti Giuliana C. , Liu Jingyi , Gumus Evren , Schaffer Ashleigh E. , Miranda Helen C.
Published: November 2020

ACTL6B is a component of the neuronal BRG1/brm‐associated factor (nBAF) complex, which is required for chromatin remodeling in postmitotic neurons. We recently reported biallelic pathogenic variants in ACTL6B in patients diagnosed with early infantile epileptic encephalopathy, subtype 76 (EIEE‐76), presenting with severe, global developmental delay, epileptic encephalopathy, cerebral atrophy, and abnormal central nervous system myelination. However, the pathophysiological mechanisms underlying their phenotype is unknown. Here, we investigate the molecular pathogenesis of ACTL6B p.(Val421_Cys425del) using in silico 3D protein modeling predictions and patient‐specific induced pluripotent stem cell‐derived neurons. We found neurons derived from EIEE‐76 patients showed impaired accumulation of ACTL6B compared to unaffected relatives, caused by reduced protein stability. Furthermore, EIEE‐76 patient‐derived neurons had dysregulated nBAF target gene expression, including genes important for neuronal development and disease. Multielectrode array system analysis unveiled elevated electrophysiological activity of EIEE‐76 patients‐derived neurons, consistent with the patient phenotype. Taken together, our findings validate a new model for EIEE‐76 and reveal how reduced ACTL6B expression affects neuronal function.
Paper‐based surface‐enhanced Raman spectroscopy sensors for field applications
Authors: Tay Li‐Lin , Poirier Shawn , Ghaemi Ali , Hulse John , Wang Shiliang
Published: November 2020

Paper‐based surface‐enhanced Raman spectroscopy (SERS) sensors can be fabricated easily by dropcasting or inkjet printing colloidal Au nanoparticles onto cellulose‐based filter papers. They are flexible, economical, and sensitive and provide the crucial advantage of point‐of‐need sampling for application in the field. In this study, paper‐based SERS sensors are fabricated through inkjet printing of a colloidal Au sol onto a filter paper substrate. We have characterized their SERS performances with benzenethiol and pyridine molecules using a handheld Raman analyzer. Due to the heterogeneous loading of the Au nanoclusters on the paper substrate, we introduce the concept of receiver operating characteristic as an alternate measurand to quantify the performance of these sensors. With their inherent filtration sampling capability, we demonstrate the use of paper SERS sensors for the detection of chemical aerosols. Lastly, we present the use of a precision materials printer to deposit quantifiable amounts of analyte (fentanyl) uniformly across the active sensing area of a paper SERS sensor. This will allow for analyte‐loaded certified references to be prepared and used in the field as standards for comparison.
Automated weak signal extraction of hyperspectral Raman imaging data by adaptive low‐rank matrix approximation
Authors: He Hao , Lin Chun , Zong Cheng , Xu Mengxi , Zheng Peng , Ye Ruiqian , Wang Lei , Ren Bin
Published: November 2020

Hyperspectral Raman imaging has emerged as a promising spectroscopic tool that can provide spatial and molecular information of the sample in a label‐free and noninvasive manner, which is very suitable to the biological and biomedical research. However, the intrinsically weak Raman scattering effect results in the low signal quality of the measured Raman spectra, which has largely limited the application of Raman imaging. In this paper, we develop an adaptive low‐rank matrix approximation method to automatically extract the signal from the noisy hyperspectral Raman imaging data. After spike removal, the hyperspectral Raman imaging data are decomposed into a linear combination of submatrices by singular value decomposition. Next, the submatrices are classified into positive and negative groups according to the SNR contribution. The negative group, reflecting the instrumental noise, is discarded, and the positive group is used to reconstruct the denoised signal. We prove on the simulated data that this algorithm can significantly decrease the normalized mean noise error from 34.35% down to 1.9%. Such a strong denoising performance enables it to efficiently extract the signal from the noisy hyperspectral Raman imaging data, especially under the low SNR condition. We finally apply this algorithm to the fast speed Raman imaging of HeLa cell and surprisingly find that the slight difference of the spectra can be differentiated after signal extraction. This algorithm offers a promising tool in the Raman imaging and also can be extended to other spectroscopic imaging platforms such as fluorescent and IR spectroscopy.
Is sugar extracted from plants less healthy than sugar consumed within plant tissues? The sugar anomaly
Authors: Qi Xin , Tester Richard
Published: November 2020

There are dilemmas in the minds of consumers with respect to sugar consumption – they would like to consume sugars for sweetness, but in a healthy (and perhaps guilt free!) way. In a sense, consumers believe that if sugar does not appear as an ingredient on the product label, but is intrinsic in the food (and will appear as a nutrient), it is ‘good’. As an ingredient, however, it is viewed as a ‘bad chemical’ associated with tooth decay and obesity. The reality is that unless processing induced modifications have occurred, the sugar molecule within a plant tissue is the same molecule structure as present in purified sugar. The same calorific value. However, there is an argument that humans eat too refined food and that if sugars were eaten in their natural context (e.g. within a fruit), their presence and concentration would be in harmony (where different nutrients complement and balance the sugar concentration) with the human body. This reflects the process of eating, satiety, presence of other nutrients (including water) and the associated impact of the indigestible components of plant foods on the transit/nutrient bioavailability control and thus benefits through the gut. The authors explore these issues in this article and seek to provide a scientific basis to different sides of the argument – sugar is good or bad depending on how (in which format and how much/how concentrated) it is consumed. More importantly perhaps, how should sugar consumption – an important nutrient – be managed to optimize the benefits but reduce the disadvantages? © 2020 Society of Chemical Industry
Penicillic acid in fruits: method development, validation by liquid chromatography–tandem mass spectrometry and survey in southern China
Authors: Guan Wenbi , You Yingxin , Li Jialing , Hong Jiaying , Wu Haiying , Rao Yanna
Published: November 2020

BACKGROUND

Penicillic acid (PA) is produced by Aspergillus spp. and Penicillium spp., which are common postharvest and storage fungi of fruits. PA can be of concern for human health because of its toxicity and high fruit consumption by the population. However, no data on PA occurrence in various fruits have yet been reported. A quick, easy, cheap, effective, rugged and safe (QuEChERS) approach for PA determination in various fruits was developed and applied to explore PA incidence in fruits.

RESULTS

The modified QuEChERS procedure with extraction by ethyl acetate and purification by multi‐walled carbon nanotubes (MWCNTs), primary secondary amine (PSA) and octadecyl silane (C18) was established to determine PA in various fruits by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). The average recoveries were 72.9–102.2% and relative standard deviations (RSDs) were 1.3–7.9%. A total of 161 fruits samples, including kiwi, apple, peach, grape and mandarin/orange, were collected in southern China. The incidence of PA in fruits was 14.9% and the levels of PA contamination were 0.200–0.596 μg kg−1. Our results suggested that orange/mandarin, grape and kiwi were favorable matrices for Aspergillus spp. and Penicillium spp. to produce PA, rather than peach and apple.

CONCLUSION

To the best of our knowledge, this is the first report about PA contamination in various fruits in China. Our study emphasizes the necessity of the current established method, which could be used for continuous monitoring of PA and reducing the health risk to Chinese consumers. © 2020 Society of Chemical Industry
Effects of tri‐frequency ultrasound‐ethanol pretreatment combined with infrared convection drying on the quality properties and drying characteristics of scallion stalk
Authors: Zhou Cunshan , Wang Zezhi , Wang Xule , Yagoub Abu EA , Ma Haile , Sun Yanhui , Yu Xiaojie
Published: November 2020

BACKGROUND

Having short drying time and attractive product quality are important in fruit and vegetable dehydration processing. In this work, tri‐frequency (20, 40 and 60 kHz) ultrasound‐ethanol pretreatment, ultrasound‐water pretreatment and ethanol pretreatment were employed before infrared convection drying (ICD) of scallion stalks, which was aimed at improving the drying process and quality of the end products. The mass transfer, drying characteristics (moisture ratio and drying rate and quality properties of scallion (rehydration, color, flavor, optical microscope image, moisture distribution and microbiological quality) were analyzed.

RESULTS

All pretreatments have decreased the drying time by 33.34–83.34% compared to the control, while ultrasound‐ethanol pretreatment provided the highest time reduction (83.34%). The reason is that the volatility of ethanol have replaced air in the tissue, which produced a better osmotic dehydration effect and the cavitation effect of ultrasound changed the cell function of the material, so that the food tissue was rapidly compressed and expanded, resulting in damage to the cell structure. Ultrasonic‐ethanol pretreatment has greatly reduced the water loss and dry matter of fresh scallion, improved the rehydration effect of dried scallion, better retained the color and flavor of scallion and effectively reduced the microbiological quality of the scallion.

CONCLUSION

The tri‐frequency ultrasound‐ethanol pretreatment has effectively improved the drying process and quality characteristics of the dried scallion. Therefore, this research has a great contribution to the drying technology, as evident in the remarkable reduction in drying time and the improvement in the quality of the end product. © 2020 Society of Chemical Industry
Spatial mapping of collagen content and structure in human intervertebral disk degeneration
Authors: Zeldin Lawrence , Mosley Grace E. , Laudier Damien , Gallate Zachary S. , Gansau Jennifer , Hoy Robert C. , Poeran Jashvant , Iatridis James C.
Published: November 2020

Collagen plays a key structural role in both the annulus fibrosus (AF) and nucleus pulposus (NP) of intervertebral disks (IVDs). Changes in collagen content with degeneration suggest a shift from collagen type II to type I within the NP, and the activation of pro‐inflammatory factors is indicative of fibrosis throughout. While IVD degeneration is considered a fibrotic process, an increase in collagen content with degeneration, reflective of fibrosis, has not been demonstrated. Additionally, changes in collagen content and structure in human IVDs with degeneration have not been characterized with high spatial resolution. The collagen content of 23 human lumbar L2/3 or L3/4 IVDs was quantified using second harmonic generation imaging (SHG) and multiple image processing algorithms, and these parameters were correlated with the Rutges histological degeneration grade. In the NP, SHG intensity increased with degeneration grade, suggesting fibrotic collagen deposition. In the AF, the entropy of SHG intensity was reduced with degeneration indicating increased collagen uniformity and suggesting less‐organized lamellar structure. Collagen orientation entropy decreased throughout most IVD regions with increasing degeneration grade, further supporting a loss in collagen structural complexity. Overall, SHG imaging enabled visualization and quantification of IVD collagen content and organization with degeneration. There was an observed shift from an initially complex structure to more uniform structure with loss of microstructural elements and increased NP collagen polarity, suggesting fibrotic remodeling.
The role oftour‐operatorsas intermediaries of tourists' preferences for corporate social responsibility
Authors: Araña Jorge E. , León Carmelo J.
Published: November 2020

This paper investigates the potential gap in Tour Operators (TOs) assessments of tourists' preferences for Corporate Social Responsibility (CSR) in tourism. It utilizes discrete choice experiments to assess both tourists and TOs preferences. Results show that TOs understand tourists' average preferences for CSR policies but fail to predict the heterogeneity of preferences. Three market segments were found, with different preferences, socio‐economic backgrounds, spending levels, and source regions. The results can help explain the lag of tourism companies in undertaking some of the CSR policies that might be of interest to tourists, and might assist the development of more sustainable tourism.
In search of fresher air: The influence of relative air quality on vacationers' perceptions of destinations' restorative qualities
Authors: Yang Yang , Chen Ganghua
Published: November 2020

This study aimed to unveil the effects of relative air quality on vacationers' perceived destination restorative qualities. Using survey‐based data and second‐hand air quality data, our regression results showed a higher level of relative air pollution was associated with vacationers' lower evaluations of a destination's “physically away” quality. These effects were moderated by the number of visits to the destination and travel distance. We found that vacationers' evaluations of the “physically away” quality were also damaged by higher relative levels of PM2.5, PM10, and NO2. This study contributes to the literature on relationships between air quality and tourist destination experience.
Reduced Recovery Times with Total Intravenous Anesthesia in Patients with Obstructive Sleep Apnea
Authors: Stewart Matthew , Estephan Leonard , Thaler Adam , Zhan Tingting , Connors Kevin , Malkani Kabir , Hunt Patrick , Boon Maurits , Huntley Colin
Published: November 2020

Objectives/Hypothesis

There is currently no standard of care in terms of anesthesia modality for patients receiving upper airway surgery with comorbid obstructive sleep apnea (OSA). Although both total intravenous anesthesia (TIVA) and volatile gas anesthesia are commonly utilized in ambulatory otolaryngology surgery, it is currently unclear if there are any advantages with one modality over the other. We hypothesize that patients receiving upper airway surgery with comorbid OSA will have quicker recovery times with TIVA.

Study Design

Retrospective chart review from January 2019 to December 2019.

Methods

All patients aged 18 and older receiving upper airway surgery (upper airway stimulation, nasal surgery, modified uvulopalatopharyngoplasty) were included. Patients were excluded when there was incomplete or missing data in the electronic medical record.

Results

Eighty‐six patients received gas anesthesia and 62 patients received TIVA. Phase I recovery times were significantly reduced by surgery and by severity of OSA: nasal surgery, upper airway stimulation, and modified uvulopalatopharyngoplasty had a reduction of 35.5 minutes (P < .001), 42.5 minutes (P < .001), and 36 minutes (P = .022), respectively. In terms of severity, mild, moderate, and severe OSA had reductions of 23.5 minutes (P = .004), 52 minutes (P = .004), and 47 minutes (P < .001), respectively. The severity of OSA generally correlated with increased time spent in Phase I: as severity increased, Phase I time increased by 16.8 minutes for the gas cohort (P < .001), whereas in the TIVA cohort, it increased only 4.3 minutes (P = .489).

Conclusion

Patients having upper airway surgery with comorbid OSA that received TIVA (propofol and remifentanil) spent significantly less time in Phase I and the recovery room overall compared to those receiving volatile gas anesthesia in the form of sevoflurane, and this correlated with the severity of OSA.

Level of Evidence

3. Laryngoscope, 131:925–931, 2021
Regional Peak Mucosal Cooling Predicts Radiofrequency Treatment Outcomes of Nasal Valve Obstruction
Authors: Wu Zhenxing , Krebs Jillian P. , Spector Barak M. , Otto Bradley A. , Zhao Kai , Farag Alexander A.
Published: November 2020

Objectives/Hypothesis

Low energy radiofrequency may offer effective treatment for narrow or obstructed nasal valve, yet its precise mechanism is not fully understood.

Study Design

Prospective, nonrandomized, case series.

Methods

Twenty prospective patients with internal nasal valve obstruction underwent office‐based Vivaer treatment (Aerin Medical, Inc) under local anesthesia. Computational fluid dynamics (CFD) models were constructed based on the pre‐ and 90 days post‐procedure computed tomography (CT) scans to identify salient changes in nasal airflow parameters.

Results

Patients' Nasal Obstruction Symptom Evaluation score (NOSE: pre‐treatment 78.89 ± 11.57; post‐treatment 31.39 ± 18.30, P = 5e‐7) and Visual Analog Scale of nasal obstruction (VAS: pre‐treatment 6.01 ± 1.83; post‐treatment 3.44 ± 2.11, P = 1e‐4) improved significantly at 90 days after the minimally invasive approach. Nasal airway volume in the treatment area increased ~7% 90 days post‐treatment (pre‐treatment 5.97 ± 1.20, post‐treatment 6.38 ± 1.50 cm3, P = .018), yet there were no statistically significant changes in the measured peak nasal inspiratory flowrate (PNIF, pre‐treatment: 60.16 ± 34.49; post‐treatment: 72.38 ± 43.66 ml/s; P = .13) and CFD computed nasal resistance (pre‐treatment: 0.096 ± 0.065; post‐treatment: 0.075 ± 0.026 Pa/(ml/s); P = .063). As validation, PNIF correlated significantly with nasal resistance (r = 0.47, P = .004). Among all the variables, only the peak mucosal cooling posterior to the nasal vestibule significantly correlated with the NOSE at baseline (r = −0.531, P = .023) and with post‐treatment improvement (r = 0.659, P = .003).

Conclusion

Minimal remodeling of the nasal valve (7% in this study) may have a profound effect on perceived nasal obstruction, despite little effect on nasal resistance, or PNIF. The results corroborated our previous findings that subjective relief of nasal obstruction correlates with regional mucosal cooling rather than nasal resistance or peak flow rate, a potential target for future effective, personalized therapeutic approaches.

Level of Evidence

4 Laryngoscope, 131:E1760–E1769, 2021
Sialendoscopy and Sjogren's Disease: A Systematic Review
Authors: Coca Kimberly K. , Gillespie M. Boyd , Beckmann Nicholas A. , Zhu Rongshun , Nelson Tamara M. , Witt Robert L.
Published: November 2020

Objectives/Hypothesis

This study is a systematic review of the literature which seeks to estimate the expected treatment outcomes of a patient with Sjogren's syndrome (SS) undergoing therapeutic sialendoscopy.

Study Design

Systematic Review.

Methods

PubMed, Scopus, and Cochrane library databases were used to search for studies published as of August 2020 regarding the treatment outcomes of SS with sialendoscopy. The key search terms included “Sjogren's syndrome” and “sialendoscopy.” Only studies in the English language involving more than one human patient were included. PRISMA guidelines were followed in study inclusion and data extraction. The primary outcome assessed was improvement in patient symptoms.

Results

Six studies met criteria and were analyzed in this review, including 125 patients undergoing sialendoscopy of parotid and/or submandibular glands as well as 25 controls. Of these patients, 90% were female with an age range of 18 to 79 years. There was significant diversity in outcome reporting tools. The outcomes of symptom improvement were pooled qualitatively based on improvement noted in each study. Outcomes were defined as partial improvement if the measured outcomes improved and complete improvement if measured outcomes resolved entirely. Despite the limited number of studies on this topic, this meta‐analysis suggests that a similar study of therapeutic sialendoscopy could expect to provide at least temporary improvement of symptoms 90% to 99% of the time.

Conclusions

This review provides support for the application of sialendoscopy in the treatment of SS salivary disease. Larger studies with consistent outcome reporting tools and control groups are needed to validate these results and provide a consistent therapy protocol. Laryngoscope, 131:1474–1481, 2021
Mitochondrial and Clearance Impairment in p.D620N VPS35 Patient‐Derived Neurons
Authors: Hanss Zoé , Larsen Simone B. , Antony Paul , Mencke Pauline , Massart François , Jarazo Javier , Schwamborn Jens C. , Barbuti Peter A. , Mellick George D. , Krüger Rejko
Published: November 2020

Background

VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria‐derived vesicles. The p.D620N mutation of VPS35 causes an autosomal‐dominant form of Parkinson's disease (PD), clinically representing typical PD.

Objective

Most of the studies on p.D620N VPS35 were performed on human tumor cell lines, rodent models overexpressing mutant VPS35, or in patient‐derived fibroblasts. Here, based on identified target proteins, we investigated the implication of mutant VPS35 in autophagy, lysosomal degradation, and mitochondrial function in induced pluripotent stem cell‐derived neurons from a patient harboring the p.D620N mutation.

Methods

We reprogrammed fibroblasts from a PD patient carrying the p.D620N mutation in the VPS35 gene and from two healthy donors in induced pluripotent stem cells. These were subsequently differentiated into neuronal precursor cells to finally generate midbrain dopaminergic neurons.

Results

We observed a decreased autophagic flux and lysosomal mass associated with an accumulation of α‐synuclein in patient‐derived neurons compared to controls. Moreover, patient‐derived neurons presented a mitochondrial dysfunction with decreased membrane potential, impaired mitochondrial respiration, and increased production of reactive oxygen species associated with a defect in mitochondrial quality control via mitophagy.

Conclusion

We describe for the first time the impact of the p.D620N VPS35 mutation on autophago‐lysosome pathway and mitochondrial function in stem cell‐derived neurons from an affected p.D620N carrier and define neuronal phenotypes for future pharmacological interventions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Quercetin‐3‐O‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ1‐42‐Induced AD‐Like Mice and SH‐SY5Y Cells
Authors: Xu Mengdai , Huang Hao , Mo Xiaoxing , Zhu Yalun , Chen Xi , Li Xiaoqin , Peng Xiaobo , Xu Zihui , Chen Liangkai , Rong Shuang , Yang Wei , Liu Shuang , Liu Liegang
Published: November 2020

Scope

Alzheimer's disease (AD) is characterized by amyloid‐β (Aβ) related imbalance, Tau‐hyperphosphorylation, and neuroinflammation, in which Aβ and neuroinflammation can induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD. As of yet, there are no effective treatments clinically. Thus, it is focused on the potential benefit of quercetin‐3‐O‐glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome.

Methods and results

AD mice model built through intracerebroventricular injection of Aβ1‐42and AD cell model developed through the SH‐SY5Y cell line and Aβ1‐42are used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high‐throughput pyrosequencing of 16S rRNA are assessed. Data show that Q3G attenuates neuroinflammation and brain IR in Aβ1‐42‐injected mice and relieves apoptosis in Aβ1‐42‐treated SH‐SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorates Aβ accumulation and Tau phosphorylation, restores CREB and BDNF levels in the hippocampus , and reverses Aβ1‐42‐induced cognitive impairment. Besides, Q3G restores Aβ1‐42‐induced reduction of short‐chain fatty acids (SCFAs) and gut microbiota dysbiosis.

Conclusion

Q3G can alleviate brain IR through directly acting on the brain or modulating the gut‐brain axis, ultimately to relieve Aβ1‐42‐induced cognitive dysfunction.
Patterning of graphene for highly sensitive strain sensing on various curved surfaces
Authors: Xu Wei , Huang Yuehua , Zhao Xuanliang , Jiang Xin , Yang Tingting , Zhu Hongwei
Published: November 2020

In recent years, graphene based flexible strain sensors have attracted great attention. Although various designed micro/nanostructure morphologies have been introduced to optimize the performance parameters such as sensitivity and working range, there are relatively limited studies on the effective patterning of graphene on various substrates on curved surfaces to manufacture functional devices. In this work, we report a general route to realize the patterning of graphene into predesigned structure on a variety of complex curved substrates. The methodology involves a combination of polydopamine surface modification of the substrate and the spraying process of graphene. The polydopamine modification method preserves the intrinsic electrical properties and stability of graphene, and the modification process by self‐polymerization of dopamine is available on many types of materials of complex shape. This general approach of interface modification to achieve free patterning has capability of large‐scale fabrication. By this interface‐enhancement patterning method, sensing structure of cut‐through channel crack has been obtained, resulting in flexible strain sensors with adjusted high sensitivity (gauge factor of 100–2000 at 1% strain), little hysteresis and conformality of complex surfaces. In addition, the strain sensor array has also been fabricated to detect the deformation spatial distribution of complex curved structural components, thereby expanding their potential applications in wearable electronics.
Inventory renewal for a perishable product: Economies of scale and age‐dependent demand
Authors: Chen Li‐Ming , Sapra Amar
Published: November 2020

We consider a finite‐horizon, periodic‐review system for a perishable product at a retailer that faces stochastic, age‐dependent demand and loses excess demand, if any. For this system, we build three models that capture two sources of unfilled demand, insufficient inventory and inappropriate age, and penalize them at different rates. The models are characterized by increasing replenishment flexibility, and the goal of each model is to identify when to place an order and the quantity whenever an order is placed. In the first model, reorder intervals are equal. In the second model, reorder intervals can vary across orders. In the third model, reorder intervals continue to remain flexible but the retailer can also partially salvage her inventory whenever she has excess inventory. Using the models, we explore the effect of lost‐sales penalties on the structure of the optimal value function. We find that the inventory‐related cost in a period may lack convexity if the ratio of penalties for stockout and high age is below a threshold, which percolates to the value function as well. We also identify properties of the optimal replenishment policy for the three models. Finally, we conduct numerical experiments to identify the marginal value added by the flexibility in reorder intervals and the option to partially salvage inventory as a function of model parameters.
Acute Kidney Injury Incidence in Hospitalized Patients and Implications for Nutrition Support
Authors: Meyer Daniel , Mohan Anju , Subev Emiliya , Sarav Menaka , Sturgill Daniel
Published: November 2020

Hospitalized adult patients suffer from high rates of acute kidney injury (AKI), which puts them at risk for multiple nutrition problems. The etiology and management strategy of AKI has major implications for the management of the hospitalized patient. The purpose of this review is to understand the incidence and management of AKI in hospitalized adult patients and review the challenges to providing adequate nutrition support.
Cross‐borehole geoelectrical time‐lapse monitoring of in situ chemical oxidation and permeability estimation through induced polarization
Authors: Bording Thue , Kühl Anders Kristian , Fiandaca Gianluca , Christensen Jørgen Fjeldsø , Christiansen Anders Vest , Auken Esben
Published: November 2020

Worldwide, soil contamination due to industrial activities is a major issue. One method for remediation of contaminated sites is in situ chemical oxidation, where an oxidizing agent is injected into the contaminated soil. Normally, monitoring wells are established in the remediation area for tracking the oxidizing agent. However, wells only provide point information of the injectant spread. This issue can be addressed using cross‐borehole resistivity and induced polarization tomography, by mapping the electrical properties in the entire remediation volume and by deriving, through petrophysical relations, the hydraulic properties of the medium. Here we present a proof‐of‐concept study, performed over one year as part of a larger remediation project, where resistivity and time‐domain induced polarization data were acquired among 10 boreholes, before and after two rounds of injection of oxidizing agents. The time‐lapse resistivity models, obtained through a focusing inversion scheme that favours compact time‐lapse changes, clearly show the oxidizing agent spread as highly conductive anomalies and confirmed by water conductivity measurements in boreholes. The time‐lapse inversions also show spatial variability in the injectant spread, with some areas not reached. The induced polarization data quality decreased significantly just after the injection rounds, because of the decrease in resistivity and induced polarization signal level, so that induced polarization time‐lapse inversions were not feasible. However, the induced polarization data were used for background characterization and to estimate permeability. In particular, there is a good match between the imaged low‐permeability zones and the areas in which the injectant did not spread, identified by the time‐lapse resistivity inversions. Furthermore, geological samples confirm the presence of fine‐grained sediments in the estimated low‐permeability zones. While time‐lapse resistivity tomography may be used for documenting the injectant spread, induced polarization permeability estimates prior to injection can be used to better tailor the remediation in terms of dimension and location of injection filters.
A numerical dispersion‐suppressed method for shallow seismic migration
Authors: Liu Yanli , Li Zhenchun , Wang Jiao , Sun Miaomiao , Liu Qiang
Published: November 2020

Reverse time migration can accurately image underground earth structures. However, for shallow seismic exploration, the seismic wave velocity is often lower than the velocity in the middle‐deep layers, which causes numerical dispersion for finite‐difference schemes and leads to poor seismic imaging quality. Suppressing numerical dispersion by grid encryption or increasing the finite‐difference order seriously reduces computational efficiency, which is not the optimal solution. To improve the imaging quality without sacrificing computational efficiency, a regularization factor is added to the acoustic wave equation to correct the phase velocity of high wave‐number components. An appropriate regularization factor can eliminate numerical dispersion that results from large grid interval schemes and can reduce the size of computational grids and improve computational efficiency. For simulations in the frequency domain, reducing the grid size also means reducing computer memory requirements. Numerical experiments indicate that the regularization factor should match the degree of numerical dispersion. Larger regularization factors can suppress serious numerical dispersion. However, excessively large regularization factors may destroy the effective wave field. Different numerical models verify the effectiveness of the improved acoustic equation for suppressing numerical dispersion and maintaining amplitudes and provide a novel means to improve the shallow seismic image quality.
Porous exponential domination number of some graphs
Authors: Çiftçi Canan , Aytaç Aysun
Published: November 2020

Let G be a graph and S ⊆ V(G). If for all v ∈ V(G), then S is a porous exponential dominating set for G, where d(u, v) is the distance between vertices u and v. The smallest cardinality of a porous exponential dominating set is the porous exponential domination number of G and is denoted by . In this article, we examine porous exponential domination number of some shadow graphs and trees such as comet, double comet, double star, binomial tree, and generalized caterpillar graphs.
An efficient computational approach for local fractional Poisson equation in fractal media
Authors: Singh Jagdev , Ahmadian Ali , Rathore Sushila , Kumar Devendra , Baleanu Dumitru , Salimi Mehdi , Salahshour Soheil
Published: November 2020

In this article, we analyze local fractional Poisson equation (LFPE) by employing q‐homotopy analysis transform method (q‐HATM). The PE describes the potential field due to a given charge with the potential field known, one can then calculate gravitational or electrostatic field in fractal domain. It is an elliptic partial differential equations (PDE) that regularly appear in the modeling of the electromagnetic mechanism. In this work, PE is studied in the local fractional operator sense. To handle the LFPE some illustrative example is discussed. The required results are presented to demonstrate the simple and well‐organized nature of q‐HATM to handle PDE having fractional derivative in local fractional operator sense. The results derived by the discussed technique reveal that the suggested scheme is easy to employ and computationally very accurate. The graphical representation of solution of LFPE yields interesting and better physical consequences of Poisson equation with local fractional derivative.
A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma
Authors: Changou Chun A. , Shiah Her-Shyong , Chen Li-Tzong , Liu Servina , Luh Frank , Liu Shwu-Huey , Cheng Yung-Chi , Yen Yun
Published: November 2020

Trial Information

ClinicalTrials.gov  Identifier:  NCT00076609 Sponsor: Yiviva Inc. Principal Investigator: Yun Yen IRB Approved: Yes

Lessons Learned

A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies. This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.

Background

This study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical-grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV).

Methods

This study was an open-label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m2 capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21-day cycle. The primary endpoint was 6-month survival rate, and secondary endpoints were progression-free survival, overall survival, disease control rate, and safety.

Results

Thirty-nine subjects completed the study with a 46.2% stable disease rate. The median progression-free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6-month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha-fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome.

Conclusion

Our data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.
Tyrosine Side‐Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes
Authors: Bäck Marcus , Selegård Robert , Todarwal Yogesh , Nyström Sofie , Norman Patrick , Linares Mathieu , Hammarström Per , Lindgren Mikael , Nilsson K. Peter R.
Published: November 2020

Control over the photophysical properties and molecular organization of π‐conjugated oligothiophenes is essential to their use in organic electronics. Herein we synthesized and characterized a variety of anionic pentameric oligothiophenes with different substitution patterns of L‐ or D‐tyrosine at distinct positions along the thiophene backbone. Spectroscopic, microscopic, and theoretical studies of L‐ or D‐tyrosine substituted pentameric oligothiophene conjugates revealed the formation of optically active π‐stacked self‐assembled aggregates under acid conditions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies, were highly influenced by the positioning of the L‐ or D‐tyrosine moieties along the thiophene backbone. Overall, the obtained results clearly demonstrate how fundamental changes in the position of the enantiomeric side‐chain functionalities greatly affect the optical properties as well as the architecture of the self‐assembled supramolecular structures.
Undue Burden Beyond Texas: An Analysis of Abortion Clinic Closures, Births, and Abortions in Wisconsin
Authors: Venator Joanna , Fletcher Jason
Published: November 2020

In this paper, we estimate the impacts of abortion clinic closures on access to clinics in terms of distance and congestion, abortion rates, and birth rates. Between 2010 and 2017, Wisconsin passed three laws regulating abortion providers and two of five abortion clinics closed in Wisconsin, increasing the distance to the nearest clinic to 55 miles on average and to over 100 miles in the most affected counties. We use a difference‐in‐differences design to estimate the effect of changes in travel distance on births and abortions, using within‐county variation across time in distance to identify the effect. We find that a 100‐mile increase in distance to the nearest clinic is associated with 30.7 percent fewer abortions and 3.2 percent more births. We see no significant effect of increased congestion at remaining clinics on abortion rates. Interacting the legislative changes with distance, we find that the effects of distance on abortion are approximately 1.33 time stronger in the presence of laws requiring multiple physician visits to obtain an abortion. Our results suggest that even small numbers of clinic closures can result in significant restrictions to abortion access of similar magnitude to those seen in Texas where a greater number of clinics ceased operations.
Immobilization of carboxymethyl chitosan/laponite on polycaprolactone nanofibers as osteoinductive bone scaffolds
Authors: Arab‐Ahmadi Samira , Irani Shiva , Bakhshi Hadi , Atyabi Fatemeh , Ghalandari Behafarid
Published: November 2020

The side effects and high cost of growth factors and drugs in bone tissue engineering have led to outstanding investigations of alternative osteoinductive supplements. Herein, the electrospun polycaprolactone (PCL) nanofibers were immobilized with carboxymethyl chitosan (CMC) and laponite nanoplatelets (LAP, 0.5‐3.5 wt%) to fabricate osteoinductive scaffolds for bone tissue engineering. The Fourier‐transform infrared)FTIR(and energy dispersive X‐ray (EDX) spectroscopy confirmed the chemical immobilization of CMC and LAP on the surface of PCL nanofibers. Water contact angle measurements exhibited significant improvement of surface hydrophilicity for immobilized scaffolds (<10°) comparing to the virgin PCL nanofibers (125°). The immobilization of CMC and LAP enhanced the attachment, proliferation, and osteodifferentiation of the seeded human bone marrow mesenchymal stem cells (hBM‐MSCs), as evidenced by increased calcium deposition, alkaline phosphatase (ALP) activity, and Osteonectin gene expression. Therefore, the fabricated scaffolds can serve as an appropriate substrate to support the proliferation and differentiation of stem cells to osteoplasts without any external osteoinductive stimulation.
Synthesis, properties and applications of self‐repairing carbohydrates as smart materials via thermally reversible DA bonds
Authors: Guo Ming , Chen Lei , Fang Tao , Wang Rui , Nuraje Nurxat , Brodelius Peter E.
Published: November 2020

Self‐healing carbohydrate polymers were synthesized by Diels‐Alder reaction. Intermediate products and the carbohydrate matrices were characterized by Fourier transform infrared spectroscopy (FT‐IR) and 1H NMR, while the thermally reversible properties were assessed by FT‐IR and differential scanning calorimetry. The mechanical properties, water absorption, and enzymatic degradation of starch/PVA/modified carbohydrate films were examined, as well as the relationship of the properties to the DA and rDA reactions. These results showed that DA bonds were introduced into the carbohydrate polymers successfully and endow the material with self‐healing thermal recyclability. The mixed films exhibited alternating strong and weak mechanical properties upon cycling through the DA and rDA reactions. Water absorption was limited and the films demonstrated good water resistance. The status of the DA bonds was found not to affect the enzymatic degradation rates of the various carbohydrate films.
Decreasing paint cost for sheet molding compound (SMC) compression molding
Authors: Cai Kaiyu , Bhuyan Mohammad S. K. , Zhang Dan , Villarreal Maria G. , Straus Elliott J. , Lee L. James , Castro Jose M.
Published: November 2020

Finishing, in most cases, is the most expensive step for manufacturing plastic parts in automotive and truck industry; being electrostatic painting is the desired approach for improved quality. For plastic parts to be painted electrostatically, a conductive primer needs to be applied first. In the case of SMC compression molded parts, in‐mold coating (IMC) is the primer material of choice, as it also serves to fill the surface porosity typical in SMC parts. To make the IMC conductive, the current approach is to add carbon black (CB), which results in a black colored primer. In this research, single wall carbon nanotube (SWCNT) was evaluated, as an alternative to CB, to develop a clearer version of conductive IMC. The effect of SWCNTs on both degree of lightness and electrical conductivity was experimentally evaluated. The results indicate that a clearer and slightly more conductive coating than standard IMC can be obtained by adding 0.15 wt% SWCNTs into the base IMC resin, which results in approximately 12.5% paint saving compared to standard IMC. The processability of the modified coating was shown to be only slightly less favorable than standard coating.