bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the Box–Behnken design for the production of soluble curcumin: Skimmed milk powder inclusion complex for improving the treatment of colorectal cancer
Authors: Jamal Moideen Muthu Mohamed , Alqahtani Ali , Venkatesan Krishnaraju , Ahmad Fazil , Krisharaju Kalpana , Gayasuddin Mohammed , Shaik Rasheed Ahemad , Ibraheem Khalid Mohamad Morsy , Salama Mohamed EL‐dosoky Mohamed , Abed Sally Yussef
Published: October 2020

The main objective of this study was to develop a soluble product of the practically insoluble curcumin (CMN) to treat colorectal cancer more effectively than with pure CMN. To improve the solubility of CMN, various hydrophilic carriers of skimmed milk powder (SMP), polyvinylpyrrolidone (PVP), and mannitol (MNT) were utilized to prepare solid dispersion (SD) binary complexes. The prepared complexes were characterized in terms of their aqueous solubility and in vitro drug release and analyzed by Fourier transform infrared spectrophotometry, powder X‐ray diffractometry, scanning electron microscopy, dynamic light scattering, and the novel dyeing test. Based on this characterization, the best SD complex was optimized using the Box–Behnken design (RSM‐BBD). These results showed that the solubility of CMN was greatly improved in combination with SMP. The SD of CMN with SMP produced significantly improved solubility (0.646 ± 0.024 mg/ml) and dissolution (54.94 ± 3.21% at 5 min). Further, solid‐state characterization revealed that the complex exhibited intermolecular inclusion of the drug and carrier. Also, the complex did not undergo any chemical modification owing to its amorphous form, and the novel dye test showed better coloring impact, indicating the solubility of CMN. The in vitro cytotoxicity of the complex showed that 50% inhibition (IC50) of SW480 and Caco‐2 cells was achieved at a considerably lower concentration than that of pure CMN. Flow cytometry analysis confirmed that the cell cycle arrest was at G2/M phase (43.26% and 65.14%), and DNA fragmentation analysis investigation confirmed that the complex induced more DNA damage during apoptosis.
Extraction of polysaccharides from Codonopsis pilosula by fermentation with response surface methodology
Authors: Yuan Shuai , Xu Chang‐Yuan , Xia Jie , Feng Yan‐Ni , Zhang Xi‐Feng , Yan You‐Yu
Published: October 2020

Codonopsis pilosula is a kind of traditional Chinese medicine used to treat weak spleens, stomach problems, anemia, and fatigue. Polysaccharide is one of main components of Codonopsis pilosula. In this study, response surface methodology (RSM) was used to optimize the extraction parameters of Codonopsis pilosula polysaccharides (CPP) by fermentation. The exaction temperature (°C), yeast liquid volume (2 mg/ml, ml), and time (h) were employed effects. Results indicated that the best extraction conditions were the following: extraction temperature 24.75°C, yeast liquid volume 2.96 ml (5.92 mg), and a fermentation time of 21.03 hr. After purification with DE52 and Sephadex G‐100, the molecular structure was determined by ultraviolet–visible (UV) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) (1H and 13C). The monosaccharide composition of CPP1 was determined to be mannose (1.76%), glucose (97.38%), and arabinose (0.76%). CPP1 exhibited high antioxidant activities in scavenging ABTS radicals, ferreous ions, and superoxide ion radicals. Thus, CPP1 could be used as an antioxidant or functional food.
Case of epithelioid hemangioendothelioma occurring in the postradiation setting for breast cancer
Authors: Hahn Elan , Dickson Brendan C. , Gupta Abha A. , Nofech‐Mozes Sharon
Published: October 2020

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor, which is typically characterized by recurrent fusion genes. EHEs most commonly occur in the lung, liver, bone, and internal organs. EHE has rarely been reported to occur in the post‐radiotherapeutic setting, the breast site or in association with breast cancer. The differential diagnosis for radiation‐associated vascular lesions of the breast is classically limited to atypical vascular lesion and angiosarcoma and does not include EHE. We present the case of a woman with a history of breast cancer and post‐surgical radiotherapy who went on to develop an EHE of the chest wall skin within 3 years of the completion of radiotherapy. Microscopically, the lesion was infiltrative and composed of anastomosing nests of epithelioid‐to‐spindled cells with eosinophilic and vacuolated cytoplasm. By immunohistochemistry, the cells were positive for ERG, D2‐40, and CD31. The diagnosis was confirmed by identification of a characteristic WWTR1‐CAMTA1 fusion gene using RNA sequencing. This case expands our understanding of radiation‐associated tumors.
2015 American Thyroid Association guidelines and thyroid‐stimulating hormone suppression after thyroid lobectomy
Authors: Reed Robert , Strumpf Andrew , Martz Teresa G. , Kavanagh Kaitlin J. , Fedder Katherine L. , Jameson Mark J. , Shonka David C.
Published: October 2020

Background

2015 American Thyroid Association (ATA) guidelines recommended more conservative treatment in low‐risk well‐differentiated thyroid cancer (WDTC), stating that lobectomy alone may be sufficient. The guidelines further recommend mild thyroid‐stimulating hormone (TSH) level suppression (0.5‐2 mU/L) for this population. Our goal is to evaluate the natural history of patients undergoing lobectomy to determine the percentage that would require postoperative levothyroxine supplementation under these guidelines.

Methods

Retrospective chart review of 168 patients that underwent lobectomy between 2010 and 2019 was performed. Preoperative and postoperative TSH values and the rate of patients prescribed levothyroxine were analyzed.

Results

Thirty‐five percent of patients were prescribed levothyroxine postoperatively. At 6 weeks postoperatively, 66% had TSH value of >2; this increased to 76% by 6 to 12 months.

Conclusion

To adhere to ATA guidelines for WDTC managed with lobectomy alone, the majority of patients (76%) would require postoperative levothyroxine supplementation. Low preoperative TSH was found to be the most significant predictor for postoperative TSH < 2.
C/EBPα/miR‐7 Controls CD4+ T‐Cell Activation and Function and Orchestrates Experimental Autoimmune Hepatitis in Mice
Authors: Zhao Juanjuan , Chu Fengyun , Xu Hualin , Guo Mengmeng , Shan Shan , Zheng Wen , Tao Yijing , Zhou Ya , Hu Yan , Chen Chao , Ren Tao , Xu Lin
Published: October 2020

Background and Aims

Increasing evidence in recent years has suggested that microRNA‐7 (miR‐7) is an important gene implicated in the development of various diseases including HCC. However, the role of miR‐7 in autoimmune hepatitis (AIH) is unknown.

Approach and Results

Herein, we showed that miR‐7 deficiency led to exacerbated pathology in Concanavalin‐A‐induced murine acute autoimmune liver injury (ALI) model, accompanied by hyperactivation state of CD4+ T cells. Depletion of CD4+ T cells reduced the effect of miR‐7 deficiency on the pathology of ALI. Interestingly, miR‐7 deficiency elevated CD4+ T‐cell activation, proliferation, and cytokine production in vitro. Adoptive cell transfer experiments showed that miR‐7
def
CD4+ T cells could exacerbate the pathology of ALI. Further analysis showed that miR‐7 expression was up‐regulated in activated CD4+ T cells. Importantly, the transcription of pre‐miR‐7b, a major resource of mature miR‐7 in CD4+ T cells, was dominantly dependent on transcription factor CCAAT enhancer binding protein alpha (C/EBPα), which binds to the core promoter region of the miR‐7b gene. Global gene analysis showed that mitogen‐activated protein kinase 4 (MAPK4) is a target of miR‐7 in CD4+ T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4+ T cells with or without miR‐7 deficiency. Our studies document the important role of miR‐7 in the setting of AIH induced by Concanavalin‐A. Specifically, we provide evidence that the C/EBPα/miR‐7 axis negatively controls CD4+ T‐cell activation and function through MAPK4, thereby orchestrating experimental AIH in mice.

Conclusions

This study expands on the important role of miR‐7 in liver‐related diseases and reveals the value of the C/EBPα/miR‐7 axis in CD4+ T‐cell biological function for the pathogenesis of immune‐mediated liver diseases.
Transcriptomic analysis reveals novel mechanisms of SARS‐CoV‐2 infection in human lung cells
Authors: Yang Shaomin , Wu Songbin , Yu Zhijian , Huang Jiabin , Zhong Xia , Liu Xiaodong , Zhu Hua , Xiao Lizu , Deng Qiwen , Sun Wuping
Published: October 2020

Background

Severe acute respiratory syndrome coronavirus clade 2 (SARS‐CoV‐2) is a single‐stranded RNA virus responsible for the global pandemic of the coronavirus disease‐2019 (COVID‐19). To date, there are still no effective approaches for the prevention and treatment of COVID‐19.

Objective

The present study aims to explore the possible mechanisms of SARS‐CoV‐2 infection in human lung cells.

Methods

Data interpretation was conducted by recruiting bioinformatics analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis using downloaded data from the NCBI Gene Expression Omnibus database.

Results

The present study demonstrated that SARS‐CoV‐2 infection induces the upregulation of 14 interferon‐stimulated genes, indicative of immune, and interferon responses to the virus. Notably, genes for pyrimidine metabolism and steroid hormone biosynthesis are selectively enriched in human lung cells after SARS‐CoV‐2 infection, suggesting that altered pyrimidine metabolism and steroid biosynthesis are remarkable, and perhaps druggable features after SARS‐CoV‐2 infection. Besides, there is a strong positive correlation between viral ORF1ab, ORF6, and angiotensin‐converting enzyme 2 (ACE2) expression in human lung cells, implying that ACE2 facilitates SARS‐CoV‐2 infection and replication in host cells probably through the induction of ORF1ab and ORF6.
How do finance companies' advantages affect competitive strategies in short‐ and intermediate‐term loan markets? A theoretical analysis
Authors: Tseng Jauling
Published: October 2020

The emergence of finance companies has affected the competitive strategies of financial service industry and has also altered the financing patterns of various borrowers. This study's theoretical model illustrates that finance companies are able to offer larger loans and reach risky niche‐market borrowers more easily than banks can because of certain advantages of the finance company's business model, including unique funding sources, cross‐subsidization, relatively low collateralization costs, and extensive financial intermediation. The resulting loan terms are typically more attractive than those that banks can offer, including higher loan‐granting ratios. These advantages can expand borrowers' financing sources and thereby reduce their financing difficulties. This is especially the case for risky borrowers or entrepreneurs who operate small‐ and medium‐size enterprises. Such borrowers, who typically face liquidity constraints and are thus willing to pay higher interest rates, are more inclined to obtain operating funds from finance companies than from banks.
Improving predictive capacity of the Amino acid Derivative Reactivity Assay test method for skin sensitization potential with an optimal molar concentration of test chemical solution
Authors: Imamura Mika , Wanibuchi Sayaka , Yamamoto Yusuke , Kojima Hajime , Ono Atsushi , Kasahara Toshihiko , Fujita Masaharu
Published: October 2020

The Amino acid Derivative Reactivity Assay (ADRA) is a convenient and effective in chemico test method for assessing covalent binding of test chemicals with protein‐derived nucleophilic reagents as a means of predicting skin sensitization potential. Although the original molar‐concentration approach to ADRA testing was not suitable for testing multiconstituent substances of an unknown composition, a weight‐concentration approach that is suitable for such substances was developed, which also led to the realization that test chemical solutions prepared to molar concentrations higher than the original 1 mM would reduce false negative results as well as enhance predictive capacity. The present study determined an optimal molar‐concentration that achieves even higher predictive capacity than the original ADRA. Eight chemicals that were false negatives when tested with 1 mM test chemical solutions were retested with test chemical solutions between 2 and 5 mM, which showed 4 mM to be the optimal molar‐concentration for ADRA testing. When 82 chemicals used in the original development were retested with 4 mM test chemical solutions, false negative results were reduced by four. When an additional 85 chemicals used to evaluate the weight‐concentration approach to ADRA were retested, the results essentially replicated those obtained with 0.5 mg/ml test chemical solutions and gave 10 fewer false negatives than original ADRA with 1 mM solutions. A comparison of these results for 136 chemicals showed that ADRA testing with 4 mM solutions achieved a four percentage point improvement in accuracy over original ADRA and a two percentage point improvement over DPRA testing.
Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation
Authors: Abuna Rodrigo P. F. , Almeida Luciana O. , Souza Alann T. P. , Fernandes Roger R. , Sverzut Thales F. V. , Rosa Adalberto L. , Beloti Marcio M.
Published: October 2020

Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl‐histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic‐based therapies to treat bone diseases.
Clinicohistological correlation of etiological spectrum of chronic liver disease diagnosed during noncirrhotic stages in children: Can need of liver biopsy be obviated?
Authors: Samanta Tryambak , Basu Rajarshi , Purkait Radheshyam , Kar Sudipta , Das Debasis , Ganguly Sutapa
Published: October 2020

Background and Aim

Limited data exist regarding the etiological spectrum of the subset of chronic liver diseases (CLDs) diagnosed in noncirrhotic states in children. Our primary objective was to study the clinicoetiological profile of CLDs detected in noncirrhotic stages in children younger than 12 years of age. The secondary objective was to find the hepatic histological correlation of provisional diagnosis by different ranks of doctors.

Methods

This was an observational epidemiological study, cross‐sectional in design, conducted in a tertiary‐care setting over a 2‐year period.

Results

Thirty‐seven cases were enrolled, with a mean ± SD age of 8 ± 4.1 years and a male:female ratio of 1.8:1. Etiologies noted were Wilson disease (n = 8), autoimmune hepatitis (n = 4), secondary hemochromatosis (n = 4), chronic hepatitis B (n = 3), chronic hepatitis C (n = 2), non‐alcoholic steatohepatitis (n = 2), progressive familial intrahepatic cholestasis (n = 2), extrahepatic biliary atresia (n = 2), Alagille syndrome (n = 1), galactosemia (n = 1), Gaucher disease (n = 1), Niemann‐Pick disease (n = 1), and Budd–Chiari syndrome (n = 1), with an inconclusive diagnosis in five children. Relevant investigations were ordered more frequently by the specialist consultant (SC) and super specialist (SS) combined in comparison with the senior resident (SR) and junior resident (JR) together. (P = 0.0013). Irrelevance of the tests ordered was significantly higher in the junior tier (JR and SR; SR > JR) in contrast to the senior tier of doctors (SC and SS) (P < 0.01). The clinicohistological correlation of an etiological diagnosis significantly differed between the junior and senior ranks of physicians. We noted that an ideal clinical acumen could help to avoid liver biopsy for etiological diagnosis in 78.3% (29/37) of the study population.

Conclusion

Interpretation of clinical presentation by the senior set of doctors is preferable, which could obviate the need for liver biopsy regarding diagnosis in a proportion of pediatric CLD patients.
Impact of gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging on the prognosis of hepatocellular carcinoma after surgery
Authors: Shimada Shingo , Kamiyama Toshiya , Kakisaka Tatsuhiko , Orimo Tatsuya , Nagatsu Akihisa , Asahi Yoh , Sakamoto Yuzuru , Abo Daisuke , Kamachi Hirofumi , Taketomi Akinobu
Published: October 2020

Background and Aim

Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (EOB‐MRI) has been recognized as a useful imaging technique to distinguish the biological behavior of hepatocellular carcinoma (HCC).

Methods

We analyzed 217 hepatectomy recipients with HCCs measuring 10 cm or less. We divided the patients into a decreased intensity (DI) group (n = 189, 87%) and an increased or neutral intensity (INI) group (n = 28, 13%) according to the ratio of tumor intensity to liver intensity during the hepatobiliary phase (HBP). According to the ratio of the maximum tumor diameter (including peritumoral hypointensity) between HBP images and precontrast T1‐weighted images (RHBPP), we divided the patients as follows: The group whose RHBPP was ≥1.036 was the high RHBPP group (n = 60, 28%), and the group whose RHBPP was <1.036 was the low RHBPP group (n = 157, 72%). We investigated the prognoses and clinicopathological characteristics of these patients.

Results

DI versus INI was not a prognostic factor for either survival or recurrence; however, a high RHBPP was an independent predictor of unfavorable survival and recurrence in patients. In addition, the INI group showed significantly lower α‐fetoprotein (AFP) levels and higher rates of well‐differentiated HCC and ICGR15 ≥15% than the DI group. The high RHBPP group showed significantly higher rates of vascular invasion and poorly differentiated HCC than the low RHBPP group.

Conclusions

A high RHBPP by EOB‐MRI is a preoperative predictor of vascular invasion and an unfavorable prognostic factor for survival and recurrence. These patients might be considered for highly curative operations such as anatomical liver resection.
Summer precipitation characteristics on the southern Tibetan plateau
Authors: Zeng Chen , Zhang Fan , Wang Li , Chen Deliang
Published: October 2020

Precipitation is an important source of streamflow and a critical parameter in hydrological studies. However, spatiotemporal variation of precipitation in the Tibetan Plateau (TP) has been poorly characterized due to the limited distribution of meteorological stations mostly in the lowlands. In this study, we set‐up rain gauges to study summer precipitation on mountain slopes in three catchments of the southern TP from 2013 to 2016. We studied the precipitation gradients (PGs) averaged during the Indian monsoon season (PGms), as well as daily PGs (PGd) and unit PGs (PGu) under various precipitation intensity grades (PIGs) and subdiurnal precipitation distributions. We also analysed the correlations between the PGs and precipitation amounts under various PIGs. Results showed that the mean PGms, PGd and PGu in the study catchments were 0.0071–0.0082% for monsoon season, 0.11–0.13 mm·100 m−1 d−1 and 2.2–3.1%·100 m−1 for the total (nonintensity‐graded) precipitation, but varied widely under different PIGs. PGms, PGd and PGu were all strongly correlated to precipitation amounts, which were relatively consistent between years but varied between different catchments. In addition, the correlations showed a steep positive slope under fine precipitation but became flat or even negative with increasing PIG. Generally, two distinct precipitation peaks were noted in each of the three catchments: a dispersed peak in the morning, and a stronger but sharper peak at around 18:00 LST; overall, this subdiurnal pattern was temporally stable. The mean precipitation durations of the three catchments were approximately 1.0–1.4 hr (nonintensity‐graded) and increased from <0.5 hr, to <1 hr, 2–5 hr and 6–11 hr for trace, light, moderate and heavy precipitation intensities, respectively. Among the various PG units, both PGd and PGu better represented precipitation at different altitudes than that of PGms. Summer precipitation in the study catchments was influenced more by valley‐scale convection than by large‐scale monsoon circulation.
Clinicopathological and prognostic analyses of 86 resected pulmonary lymphoepithelioma‐like carcinomas
Authors: Chen Jiafei , Gu Chang , Chen Xiaojian , Dai Chenyang , Zhao Shengnan , Xie Huikang , Fei Ke , Chen Chang
Published: October 2020

Background

Pulmonary lymphoepithelioma‐like carcinoma (LELC) is a rare subtype of primary lung cancer. The present study aims at investigating clinicopathological features and prognostic characteristics of the resected pulmonary LELC.

Methods

Patients with resected pulmonary LELC were identified in our hospital from December 2008 to December 2018. Data of these patients were retrospectively reviewed, clinicopathological features and prognostic characteristics were analyzed subsequently.

Results

In total, 86 patients were enrolled in the study, including 39 (45.3%) males and 47 (54.7%) females. Most of the serum tumor markers were normal. Immunohistochemical staining result showed frequent differentiation traits of epithelial tissue such. Positive PD‐L1 (15 of 19, 78.9%) and PD‐1 (13 of 17, 76.5%) were also common, but cancer‐related genetic mutation was scarce (1 of 47, 2.1%). Survival analyses demonstrated that the N stage (p = .011) and extent of resection (p = .023) were identified as independent predictive factors for overall survival.

Conclusions

Pulmonary LELC is a distinctive subtype of lung cancer with several exclusive traits, such as the trend to happen among nonsmoking young people, epithelial origin of tumor differentiation, frequent expression of the immune checkpoint, and scarce presence of driver mutation. In addition, pulmonary LELC was apt to get a favorable outcome, especially in cases diagnosed and treated in the early stage.
Perioperative therapy in metastatic colorectal cancer: Pattern of use and survival outcomes
Authors: Alese Olatunji B. , Zakka Katerina , Huo Xingyue , Jiang Renjian , Shaib Walid L. , Akce Mehmet , Behera Madhusmita , Sullivan Patrick , Wu Christina , El‐Rayes Bassel F.
Published: October 2020

Background

Multimodality therapy of metastatic colorectal cancer (mCRC) is currently considered the standard of care. The aim of this study was to evaluate the impact of perioperative therapy on surgical resection in mCRC.

Methods

The National Cancer Database was analyzed for affected patients between 2004 and 2013. Univariate and multivariate analyses were done to identify factors associated with patient outcomes. Kaplan–Meier analysis and Cox proportional hazards models were used for the association between patient characteristics and survival.

Results

About 61,940 patients with mCRC were identified. Mean age = 63.4 years (SD ± 14). About 69% had a colon primary and 32% had only one metastatic site. Only 49% of those who underwent surgery for both primary and metastatic sites received postoperative chemotherapy (p < .001). Negative prognostic factors included no chemotherapy received (hazard ratio [HR], 2.32; 2.27–2.37; p < .001), more than three metastatic sites (HR, 2.28; 2.09–2.48; p < .001), year of diagnosis between 2004 and 2008 (HR, 1.71; 1.15–1.20; p < .001) and colon tumor location with right worse than left‐sided (HR, 1.21; 1.19–1.24; p < .001). Five‐year overall survival for resection of the primary and metastatic site (28.2%) was higher than for no surgical treatment (4.7%).

Conclusion

Perioperative therapy was associated with improved survival, following resection of metastatic sites or primary tumor.
Development of a Bioinspired, Self‐Adhering, and Drug‐Eluting Laryngotracheal Patch
Authors: Miar Solaleh , Dion Gregory R. , Montelongo Sergio , Ong Joo L. , Bizios Rena , Guda Teja
Published: October 2020

Objectives/Hypothesis

Novel laryngotracheal wound coverage devices are limited by complex anatomy, smooth surfaces, and dynamic pressure changes and airflow during breathing. We hypothesize that a bioinspired mucoadhesive patch mimicking how geckos climb smooth surfaces will permit sutureless wound coverage and also allow drug delivery.

Study Design

ex‐vivo.

Methods

Polycaprolactone (PCL) fibers were electrospun onto a substrate and polyethylene glycol (PEG) – acrylate flocks in varying densities were deposited to create a composite patch. Sample topography was assessed with laser profilometry, material stiffness with biaxial mechanical testing, and mucoadhesive testing determined cohesive material failure on porcine tracheal tissue. Degradation rate was measured over 21 days in vitro along with dexamethasone drug release profiles. Material handleability was evaluated via suture retention and in cadaveric larynges.

Results

Increased flocking density was inversely related to cohesive failure in mucoadhesive testing, with a flocking density of PCL‐PEG‐2XFLK increasing failure strength to 6880 ± 1810 Pa compared to 3028 ± 791 in PCL‐PEG‐4XFLK density and 1182 ± 262 in PCL‐PEG‐6XFLK density. The PCL‐PEG‐2XFLK specimens had a higher failure strength than PCL alone (1404 ± 545 Pa) or PCL‐PEG (2732 ± 840). Flocking progressively reduced composite stiffness from 1347 ± 15 to 763 ± 21 N/m. Degradation increased from 12% at 7 days to 16% after 10 days and 20% after 21 days. Cumulative dexamethasone release at 0.4 mg/cm2 concentration was maintained over 21 days. Optimized PCL‐PEG‐2XFLK density flocked patches were easy to maneuver endoscopically in laryngeal evaluation.

Conclusions

This novel, sutureless, patch is a mucoadhesive platform suitable to laryngeal and tracheal anatomy with drug delivery capability.

Level of Evidence

NA Laryngoscope, 131:1958–1966, 2021
Does cannabis alleviate tinnitus? A review of the current literature
Authors: Narwani Vishal , Bourdillon Alexandra , Nalamada Keerthana , Manes R. Peter , Hildrew Douglas M.
Published: October 2020

Objective(s)

Endocannabinoid pathways have been proposed to affect the underlying pathophysiology of tinnitus. The aim of this study is to evaluate the scope and findings of existing literature on the relationship between cannabis and cannabinoid pathways and tinnitus.

Methods

We conducted a review of animal, clinical and survey studies investigating the relationship between the use of cannabis‐derived agents and tinnitus. Using pertinent keywords and MeSH terms on PubMed, relevant studies were identified, yielding four animal studies, two large cross‐sectional survey studies, one clinical cross‐over study, and one case report.

Results

Animal studies revealed that cannabinoid receptor expression in the cochlear nucleus varied with tinnitus symptomatology and the use of cannabinoid agents either increased or had no effect on tinnitus‐related behavior. Survey studies yielded conflicting results between cannabis use and tinnitus in the general population. Clinical data is largely lacking, although a small cohort study showed a dose‐dependent relationship between tetrahydrocannabinol consumption and frequency of tinnitus episodes in patients receiving treatment for cancer.

Conclusion

While animal studies have revealed that cannabinoid receptors likely have a role in modulating auditory signaling, there is no compelling data either from animal or human studies for the use of cannabinoids to alleviate tinnitus. Further research is necessary to elucidate their precise role to guide development of therapeutic interventions.

Level of Evidence

NA.
Laryngeal complications of COVID‐19
Authors: Naunheim Matthew R. , Zhou Allen S. , Puka Elefteria , Franco Ramon A. , Carroll Thomas L. , Teng Stephanie E. , Mallur Pavan S. , Song Phillip C.
Published: October 2020

Objective

To describe and visually depict laryngeal complications in patients recovering from coronavirus disease 2019 (COVID‐19) infection along with associated patient characteristics.

Study design

Prospective patient series.

Setting

Tertiary laryngology care centers.

Subjects and methods

Twenty consecutive patients aged 18 years or older presenting with laryngological complaints following recent COVID‐19 infection were included. Patient demographics, comorbid medical conditions, COVID‐19 diagnosis dates, symptoms, intubation, and tracheostomy status, along with subsequent laryngological symptoms related to voice, airway, and swallowing were collected. Findings on laryngoscopy and stroboscopy were included, if performed.

Results

Of the 20 patients enrolled, 65% had been intubated for an average duration of 21.8 days and 69.2% requiring prone‐position mechanical ventilation. Voice‐related complaints were the most common presenting symptom, followed by those related to swallowing and breathing. All patients who underwent flexible laryngoscopy demonstrated laryngeal abnormalities, most frequently in the glottis (93.8%), and those who underwent stroboscopy had abnormalities in mucosal wave (87.5%), periodicity (75%), closure (50%), and symmetry (50%). Unilateral vocal fold immobility was the most common diagnosis (40%), along with posterior glottic (15%) and subglottic (10%) stenoses. 45% of patients underwent further procedural intervention in the operating room or office. Many findings were suggestive of intubation‐related injury.

Conclusion

Prolonged intubation with prone‐positioning commonly employed in COVID‐19 respiratory failure can lead to significant laryngeal complications with associated difficulties in voice, airway, and swallowing. The high percentage of glottic injuries underscores the importance of stroboscopic examination. Otolaryngologists must be prepared to manage these complications in patients recovering from COVID‐19.

Level of evidence

IV.
Biodegradable conducting polymeric materials for biomedical applications: a review
Authors: Jadoun Sapana , Riaz Ufana , Budhiraja Vaibhav
Published: October 2020

The biodegradable conducting polymers have attracted considerable attention for the last two decades, as a unique class of new biomaterials for emerging both the properties of conducting polymers, that is electrical conductivity, and biocompatible polymers, that is biodegradability. These new biomaterials emerged as the best option for immense potential in biomedical applications. Here, we review the recent developments towards biodegradable conducting polymers and their applications in biomedical fields. Firstly, we introduce the biomaterials and their biocompatibility, followed by a short discussion on conducting polymers and their new hybrid biodegradable conducting polymers along with their applications in biomedical fields such as tissue engineering, drug delivery, biosensors and antibacterial activity. At last, we sum up this review with current challenges and future perspectives.
openPR — A computational tool for CT conversion assessment with proton radiography
Authors: Deffet Sylvain , Cohilis Marie , Souris Kevin , Salvo Koen , Depuydt Tom , Sterpin Edmond , Macq Benoit
Published: October 2020

Purpose

One of the main sources of uncertainty in proton therapy is the conversion of the Hounsfield Units of the planning CT to (relative) proton stopping powers. Proton radiography provides range error maps but these can be affected by other sources of errors as well as the CT conversion (e.g., residual misalignment). To better understand and quantify range uncertainty, it is desirable to measure the individual contributions and particularly those associated to the CT conversion.

Methods

A workflow is proposed to carry out an assessment of the CT conversion solely on the basis of proton radiographs of real tissues measured with a multilayer ionization chamber (MLIC). The workflow consists of a series of four stages: (a) CT and proton radiography acquisitions, (b) CT and proton radiography registration in postprocessing, (c) sample‐specific validation of the semi‐empirical model both used in the registration and to estimate the water equivalent path length (WEPL), and (d) WEPL error estimation. The workflow was applied to a pig head as part of the validation of the CT calibration of the proton therapy center PARTICLE at UZ Leuven, Belgium.

Results

The CT conversion‐related uncertainty computed based on the well‐established safety margin rule of 1.2 mm + 2.4% were overestimated by 71% on the pig head. However, the range uncertainty was very much underestimated where cavities were encountered by the protons. Excluding areas with cavities, the overestimation of the uncertainty was 500%. A correlation was found between these localized errors and HUs between −1000 and −950, suggesting that the underestimation was not a consequence of an inaccurate conversion but was probably rather due to the resolution of the CT leading to material mixing at interfaces. To reduce these errors, the CT calibration curve was adapted by increasing the HU interval corresponding to the air up to −950.

Conclusion

The application of the workflow as part of the validation of the CT conversion to RSPs showed an overall overestimation of the expected uncertainty. Moreover, the largest WEPL errors were found to be related to the presence of cavities which nevertheless are associated with low WEPL values. This suggests that the use of this workflow on patients or in a generalized study on different types of animal tissues could shed sufficient light on how the contributions to the CT conversion‐related uncertainty add up to potentially reduce up to several millimeters the uncertainty estimations taken into account in treatment planning. All the algorithms required to perform the workflow were implemented in the computational tool named openPR which is part of openREGGUI, an open‐source image processing platform for adaptive proton therapy.
The Use of Visceral Proteins as Nutrition Markers: An ASPEN Position Paper
Authors: Evans David C. , Corkins Mark R. , Malone Ainsley , Miller Sarah , Mogensen Kris M. , Guenter Peggi , Jensen Gordon L. ,   the ASPEN Malnutrition Committee
Published: October 2020

Serum albumin and prealbumin, well‐known visceral proteins, have traditionally been considered useful biochemical laboratory values in a nutrition assessment. However, recent literature disputes this contention. The aim of this document is to clarify that these proteins characterize inflammation rather than describe nutrition status or protein‐energy malnutrition. Both critical illness and chronic illness are characterized by inflammation and, as such, hepatic reprioritization of protein synthesis occurs, resulting in lower serum concentrations of albumin and prealbumin. In addition, the redistribution of serum proteins occurs because of an increase in capillary permeability. There is an association between inflammation and malnutrition, however, not between malnutrition and visceral‐protein levels. These proteins correlate well with patients’ risk for adverse outcomes rather than with protein‐energy malnutrition. Therefore, serum albumin and prealbumin should not serve as proxy measures of total body protein or total muscle mass and should not be used as nutrition markers. This paper has been approved by the American Society for Parenteral and Enteral Nutrition Board of Directors.
Prenatal assessment of congenital diaphragmatic hernia at north american fetal therapy network centers: A continued plea for standardization
Authors: Perrone Erin E. , Abbasi Nimrah , Cortes Magdalena Sanz , Umar Uzma , Ryan Greg , Johnson Anthony , Ladino‐Torres Maria , Ruano Rodrigo ,   North American Fetal Therapy Network (NAFTNet)
Published: October 2020

Introduction

Prenatal work‐up for congenital diaphragmatic hernia (CDH) is important for risk stratification, standardization, counseling, and optimal therapeutic choice. To determine current practice patterns regarding prenatal CDH work‐up, including prenatal ultrasound and magnetic resonance imaging (MRI) use, and to identify areas for standardization of such evaluation between fetal centers.

Methods

A survey regarding prenatal CDH work‐up was sent to each member center of the North American Fetal Therapy Network (NAFTNet) (n = 36).

Results

All responded. Sonographic measurement of lung‐to‐head ratio (LHR) was determined by all, 89% (32/36) of which routinely calculate observed‐to‐expected LHR. The method for measuring LHR varied: 58% (21/36) used a “trace” method, 25% (9/36) used “longest axis,” and 17% (6/36) used an “antero‐posterior” method. Fetal MRI was routinely used in 78% (28/36) of centers, but there was significant variability in fetal lung volume measurement. Whereas all generated a total fetal lung volume, the planes, methodology and references values varied significantly. All evaluated liver position, 71% (20/28) evaluated stomach position and 54% (15/28) quantified the degree of liver herniation. More consistency in workup was seen between centers offering fetal intervention.

Conclusion

Prenatal CDH work‐up and management differs considerably among North American fetal diagnostic centers, highlighting a need for its standardization.
Allosteric modulation of adenosine A1 and cannabinoid 1 receptor signaling by G‐peptides
Authors: Touma Anja M. , Malik Rabia U. , Gupte Tejas , Sivaramakrishnan Sivaraj
Published: October 2020

While allosteric modulation of GPCR signaling has gained prominence to address the need for receptor specificity, efforts have mainly focused on allosteric sites adjacent to the orthosteric ligand‐binding pocket and lipophilic molecules that target transmembrane helices. In this study, we examined the allosteric influence of native peptides derived from the C‐terminus of the Gα subunit (G‐peptides) on signaling from two Gi‐coupled receptors, adenosine A1 receptor (A1R) and cannabinoid receptor 1 (CB1). We expressed A1R and CB1 fusions with G‐peptides derived from Gαs, Gαi, and Gαq in HEK 293 cells using systematic protein affinity strength modulation (SPASM) and monitored the impact on downstream signaling in the cell compared to a construct lacking G‐peptides. We used agonists N6‐Cyclopentyladenosine (CPA) and 5’‐N‐Ethylcarboxamidoadenosine (NECA) for A1R and 2‐Arachidonoylglycerol (2‐AG) and WIN 55,212‐2 mesylate (WN) for CB1. G‐peptides derived from Gαi and Gαq enhance agonist‐dependent cAMP inhibition, demonstrating their effect as positive allosteric modulators of Gi‐coupled signaling. In contrast, both G‐peptides suppress agonist‐dependent IP1 levels suggesting that they differentially function as negative allosteric modulators of Gq‐coupled signaling. Taken together with our previous studies on Gs‐coupled receptors, this study provides an extended model for the allosteric effects of G‐peptides on GPCR signaling, and highlights their potential as probe molecules to enhance receptor specificity.
Hall Effect Characterization of α‐Irradiated p‐Type 4H‐SiC
Authors: Frye Clint D. , Murphy John W. , Shao Qinghui , Voss Lars F. , Harrison Sara E. , Edgar James H. , Nikolić Rebecca J.
Published: October 2020

Most electrical characterization of radiation damage to semiconductors is conducted on full devices or on low‐doped material. However, evaluating the radiation hardness is challenging in less mature semiconductor systems where low‐doped material is unavailable and full devices are difficult to realize. Herein, temperature‐dependent Hall effect measurements are used to demonstrate α particle‐induced radiation effects in p‐type 4H‐SiC with a room temperature hole concentration of . The 4H‐SiC is irradiated by α particles from a 210Po source over a fluence of –. Modeling the hole concentration as a function of temperature shows that α radiation causes hole compensation through the introduction of hole traps. The radiation also induces a reduction in hole mobility due to an increase in defect‐related scattering centers. At low temperatures and increasingly higher fluences, the conduction mechanism changes from band conduction to another mechanism.
Blending collagen, methylcellulose, and whey protein in films as a greener alternative for food packaging: Physicochemical and biodegradable properties
Authors: da Silva Filipini Gabriel , Romani Viviane Patrícia , Guimarães Martins Vilásia
Published: October 2020

Alternative materials to replace the synthetic plastics are being developed using agro‐based sources, but despite their promising results, these materials still need to have their performance improved to be used in packaging. Blending different molecules can combine the properties of each polymer resulting in the overall performance improvement of the material. In the present study, collagen, whey protein, and methylcellulose were investigated in the development of individual films and blends. They were produced by the casting technique and evaluated for their packaging‐related characteristics (including mechanical, barrier, and color properties), microstructure, thermal properties, and biodegradability in soil. Methylcellulose films presented excellent technological properties, such as total solubility in water, high tensile strength (15.78 MPa), transparency (30.4%), and good barrier to water vapor (0.43 g·mm/h·m2·kPa). In the blends with collagen and whey protein, it was responsible by the increase in tensile strength, barrier, and thermal properties. Collagen films presented the highest elongation at break (101.4%), while whey protein films showed lower solubility in water (28.3%). All the samples tested were completely biodegraded in 10 days in soil. Potential applications for the materials developed include soluble sachets for powdered foods due to the high solubility of some samples, as well as oil containers and capsules for instant coffee machines.
A general theory for the characterization of submeso‐scale motions and turbulence in the atmospheric surface layer
Authors: Urbancic Gabin H. , Suomi Irene , Vihma Timo
Published: October 2020

Oscillations in wind speed and temperature are commonly observed in the atmospheric surface layer due to the ubiquitous presence of submeso‐scale motions (SSMs). These motions are of particular importance during stable and low‐wind conditions as their amplitudes are large compared with the background turbulence. We characterize both SSMs and turbulence by utilizing a universal feature of the Eulerian autocorrelation function (EAF) called the negative lobe. The negative lobe is the first negative minimum in the EAF and occurs when an oscillation is present in the signal. A novel analytic formulation of the EAF allows for the representation of both turbulence and SSMs over all atmospheric conditions. This is accomplished by taking into account the separation of scales between turbulence and SSMs. In addition to SSMs during stable conditions and for weak winds, large‐amplitude oscillations are also observed during moderate to high winds. These oscillations are caused by large‐scale turbulent structures known as longitudinal streaks and are correctly represented by the new theory. Due to the general applicability of the new theory, it is possible to develop a new and improved understanding of SSMs and turbulence.
Real‐time versus thermal desorption selected ion flow tube mass spectrometry for quantification of breath volatiles
Authors: Slingers Gitte , Vanden Eede Martin , Lindekens Jill , Spruyt Maarten , Goelen Eddy , Raes Marc , Koppen Gudrun
Published: October 2020

Rationale

Selected ion flow tube mass spectrometry (SIFT‐MS) is versatile, rapidly provides result output and determines a wide range of volatiles, making it suitable for biomedical applications. When direct sampling into the SIFT‐MS instrument is impractical, combining thermal desorption (TD) and SIFT‐MS might offer a solution as it allows sample storage on sorbent tubes for later analysis. This work compares off‐line TD SIFT‐MS and real‐time SIFT‐MS for the quantification of selected breath volatiles.

Methods

Ten healthy non‐smoking individuals provided 60 breath samples per method. For off‐line analysis, breath was collected onto sorbent tubes via a breath sampler provided with filtered inspiratory air. After TD, samples were re‐collected in Tedlar bags which were then connected to the SIFT‐MS instrument. For real‐time analysis, breath was sampled directly into the instrument. In both cases the analytical method included a total of 155 product ions, and 14 selected volatiles were quantified. The agreement between the methods was assessed using Pearson correlation coefficients and Bland–Altman plots.

Results

Overall, correlations between real‐time and off‐line analysis were moderate to very strong (r = 0.43–0.92) depending on the volatile of interest, except for 2,3‐butanedione and styrene. The difference between real‐time and off‐line measured breath concentrations (average bias) ranged between −14.57 and 20.48 ppbv. For acetone and isoprene, it was 251.53 and 31.9 ppbv, respectively.

Conclusions

Real‐time SIFT‐MS and off‐line TD SIFT‐MS for quantification of selected breath volatiles did not show optimal agreement. Analyzing a multitude of analytes in breath via direct exhalation into a SIFT‐MS instrument for real‐time analysis is challenging. On the other hand, off‐line analysis using a breath collection device also has its issues such as possible sample losses due to selective absorption depending on the sorbent used or during desorption and transfer to the instrument. Despite these drawbacks, both methods were moderately well correlated.