bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexin 2 regulates secretion of immunoglobulin in antibody‐secreting cells
Authors: Tsuru Emi , Oryu Kohei , Sawada Ken , Nishihara Makoto , Tsuda Masayuki
Published: November 2019

Introduction

Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes.

Methods

We examined the expression of CPLXs and SNAREs in lymphocytes. To study the effect of CPLXs on the immune system in vivo, we analyzed the immune phenotype of CPLX2 KO mice. Furthermore, antibodies secretion from the peritoneal cavity, spleen, and bone marrow cells of wild‐type (WT) and CPLX2 KO mice were determined.

Results

CPLX2 was detected in B cells but not in T cells, while other CPLXs and SNAREs were expressed at a similar level in both B and T cells. To clarify the function of CPLX2 in B lymphocytes, serum concentrations of immunoglobulin G (IgG), IgA, IgM, and IgE were measured in WT and CPLX2 KO mice using enzyme‐linked immunosorbent assay. The level of IgM, which mainly consists of natural antibodies, was higher in KO mice than that in WT mice, while the levels of other antibodies were similar in both types of mice. Additionally, we found that spontaneous secretion of IgM and IgG1 was enhanced from the splenic antibody‐secreting cells (ASCs) of CPLX2 KO mice.

Conclusion

Our data suggest that CPLX2 inhibits spontaneous secretion of IgM and IgG1 from splenic ASCs. This study provides new insight into the mechanism of antibody secretion of ASCs.
High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment
Authors: Ge Weiting , Hu Hanguang , Cai Wen , Xu Jinhong , Hu Wangxiong , Weng Xingyue , Qin Xin , Huang Yanqin , Han Weidong , Hu Yeting , Yu Jiekai , Zhang Wufeng , Ye Sisi , Qi Lina , Huang Pingjie , Chen Lirong , Ding Kefeng , Wang Li Dong , Zheng Shu
Published: November 2019

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients’ prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high‐risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five‐gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan–Meier and Cox regression analyses confirmed that the five‐gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15–5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33–17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high‐risk tumors indicated that mutations of the five‐gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high‐risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer‐related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low‐risk tumors. The signature identified the high‐risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.
TCP‐based traceroute: An evaluation of different probing methods
Authors: Caiazza Chiara , Luconi Valerio , Vecchio Alessio
Published: November 2019

Traceroute is the most commonly used tool, not only for network diagnostics, but also for discovering the topology of the Internet. We evaluated the discovery capability of three variations of TCP‐based traceroute: the first uses SYN segments as probes, the other two operate on an existing connection and use DATA and ACK segments as probes. Experimental results show that using different types of probes is useful to obtain a richer view of the Internet, both in terms of IP interfaces and autonomous systems.
Characterization of a prevascularized biomimetic tissue engineered scaffold for bone regeneration
Authors: Cipriano James , Lakshmikanthan Adhithi , Buckley Christian , Mai Linh , Patel Het , Pellegrini Michael , Freeman Joseph W.
Published: November 2019

Significant bone loss due to disease or severe injury can result in the need for a bone graft, with over 500,000 procedures occurring each year in the United States. However, the current standards for grafting, autografts and allografts, can result in increased patient morbidity or a high rate of failure respectively. An ideal alternative would be a biodegradable tissue engineered graft that fulfills the function of bone while promoting the growth of new bone tissue. We developed a prevascularized tissue engineered scaffold of electrospun biodegradable polymers PLLA and PDLA reinforced with hydroxyapatite, a mineral similar to that found in bone. A composite design was utilized to mimic the structure and function of human trabecular and cortical bone. These scaffolds were characterized mechanically and in vitro to determine osteoinductive and angioinductive properties. It was observed that further reinforcement is necessary for the scaffolds to mechanically match bone, but the scaffolds are successful at inducing the differentiation of mesenchymal stem cells into mature bone cells and vascular endothelial cells. Prevascularization was seen to have a positive effect on angiogenesis and cellular metabolic activity, critical factors for the integration of a graft.
TRIM59 predicts poor prognosis and promotes pancreatic cancer progression via the PI3K/AKT/mTOR‐glycolysis signaling axis
Authors: Li Rongkun , Weng Li , Liu Bingyan , Zhu Lili , Zhang Xiaoxin , Tian Guangang , Hu Lipeng , Li Qing , Jiang Shuheng , Shang Mingyi
Published: November 2019

Aberrant expression of the tripartite motif containing 59 (TRIM59) has been reported to participate in the development and progression of various human cancers. However, its expression pattern and cellular roles in pancreatic cancer (PC) remains unclear. In our study, we found that TRIM59 expression was significantly increased in PC tissues and was positively correlated with several malignant behaviors and poor overall survival of PC patients based on bioinformatics analysis and immunohistochemistry staining. Functionally, small interfering RNA–mediated TRIM59 depletion inhibited cell proliferation and migration in vitro, while TRIM59 overexpression promoted cell proliferation and migration in vitro and drove tumor growth and liver metastasis in vivo. Mechanically, TRIM59 was found to enhance glycolysis through activating the PI3K/AKT/mTOR pathway, ultimately contributing to PC progression. Taken together, our results demonstrate that TRIM59 may be a potential predictor for PC and promotes PC progression via the PI3K/AKT/mTOR‐glycolysis signaling pathway, which establishes the rationale for targeting the TRIM59‐related pathways to treat PC.
Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR‐92b‐3p
Authors: Zhang Wei , Duan Wenfei , Mo Zhifeng , Wang Jianen , Yang Wenbin , Wu Wenrong , Li Xian , Lin Shuihua , Tan Yuanfei , Wei Wei
Published: November 2019

Ample evidence have demonstrated that long noncoding RNAs small nucleolus RNA host gene 14 (SNHG14) serves as a master regulator in various cancers. However, the exact mechanism of SNHG14 in colorectal cancer (CRC) remains unknown. In the present study, we concentrate on the potential function of SNHG14 in the pathogenesis of CRC. From the quantitative reverse transcription‐polymerase chain reaction results, SNHG14 was found to be downregulated in CRC tissues compared with the normal mucous samples, and its low expression was significantly correlated with poor clinical outcomes. Overexpression of SNHG14 inhibited cell growth, induced cell apoptosis, suppressed migration and invasion by inhibiting epithelial‐mesenchymal transition process. Furthermore, mechanistic studies revealed that miR‐92b‐3p could rescue the CRC progress induced by SNHG14. Consequently, SNHG14 exhibited low expression in CRC tissues and involved in CRC progression and metastasis by competing for miR‐92b‐3p, and SNHG14 could be used as a valuable biomarker and therapeutic target for CRC.
Impact of modulation of telomerase and cancer stem‐cell marker OCT4 axis in cervical cancer pathogenesis with underlying HPV16 infection
Authors: Tiwari Diptika , Ray Das Chandana , Sultana Rizwana , Kakoti Shantipriya , Aasif Khan Mohammad , Dongre Anita , Husain Syed Akhtar , Bose Purabi Deka , Bose Sujoy
Published: November 2019

Lacunae exist in the molecular event(s) specificity associated with cervical cancer (CaCx) pathogenesis. The present study aimed to evaluate the significance of telomerase‐cervical cancer stem cells (CSCs) modulation in CaCx pathogenesis with underlying HPV16 infection. The study included HPV16 positive cases only (N = 65) of the total enrolled cases from Northeast India. The analysis of viral load and the differential messenger RNA expression of E6, E7, hTERT, hTR, and cancer stem‐cell markers was studied by real‐time polymerase chain reaction. Further the protein and colocalization study for E6, hTERT, and oct4 was performed by immunofluorescence. The real‐time polymerase chain reaction based analysis showed an upregulation of HPV16 viral oncoprotein E6 and E7, and telomerase component hTERT and hTR expression and their correlation in CaCx susceptibility and severity. The hTERT expression correlated with viral load; while the E6 and telomerase protein expression colocalized in the nucleus. The CSCs marker octamer‐binding transcription factor 4 (OCT4) was significantly upregulated in CaCx cases, was associated with CaCx susceptibility and severity, and colocalized with E6 expression in the nucleus as revealed from the immunofluorescence studies. To conclude, the telomerase‐OCT4 axis modulation holds key in HPV16 CaCx pathogenesis mediated by HPV16 E6 viral oncoprotein expression, and underlines its potential for therapeutic targeting.
Retracted: AIB1 induces epithelial‐mesenchymal transition in gastric cancer via the PI3K/AKT signaling
Authors: Diao Lei , Li Yang , Mei Qiao , Han Wei , Hu Jing
Published: November 2019

Amplified in breast cancer 1 (AIB1) is overexpression in various cancers and promotes tumor cell proliferation, survival, and invasiveness. However, the role of AIB1 in the regulation of gastric cancer (GC) cell epithelial‐mesenchymal transition (EMT) is still largely unclear. In the present study, immunohistochemistry showed that AIB1 was upregulated in our cohort of patients with GC and correlated with poor survival. Knockdown of AIB1 reduced the invasive ability of GC cells, downregulated the expression of epithelial cell marker E‐cadherin, and upregulated mesenchymal cell marker vimentin. AIB1 overexpression elicited the opposite effect. PI‐103, the inhibitor of the PI3K/AKT signaling, partially reversed AIB1 overexpression mediated a decrease in E‐cadherin and an increase in vimentin. The present data demonstrated that AIB1 augmented the EMT via activation of PI3K/AKT signaling. In conclusion, our results suggested a novel role of AIB1 in GC invasion and EMT and raised the possibility of using this molecule as an indicator for GC treatment.
Mediator subunit MED1 modulates intranuclear dynamics of the thyroid hormone receptor
Authors: Femia Matthew R. , Evans Rochelle M. , Zhang Jibo , Sun Xiaopeng , Lebegue Caroline J. , Roggero Vincent R. , Allison Lizabeth A.
Published: November 2019

The thyroid hormone receptors (TRs) mediate thyroid hormone (T3)‐dependent gene expression. The nuclear import and export signals that direct TR shuttling are well characterized, but little is known about factors modulating nuclear retention. We used fluorescence‐based nucleocytoplasmic scoring and fluorescence recovery after photobleaching in transfected cells to investigate whether Mediator subunits MED1 and MED13 play a role in nuclear retention of TR. When MED1 was overexpressed, there was a striking shift towards a greater nuclear localization of TRβ1 and the oncoprotein v‐ErbA, subtypes with cytosolic populations at steady‐state, and TRβ1 intranuclear mobility was reduced. For TRα1, there was no observable change in its predominantly nuclear distribution pattern or mobility. Consistent with a role for MED1 in nuclear retention, the cytosolic TRα1 and TRβ1 population were significantly greater in MED1−/− cells, compared with MED1+/+ cells. Exposure to T3 and epidermal growth factor, which induces MED1 phosphorylation, also altered TR intranuclear dynamics. Overexpression of miR‐208a, which downregulates MED13, led to a more cytosolic distribution of nuclear‐localized TRα1; however, overexpression of MED13 had no effect on TRβ1 localization. The known binding site of MED1 overlaps with a transactivation domain and nuclear export signal in helix 12 of TR's ligand‐binding domain (LBD). Coimmunoprecipitation assays demonstrated that TR's LBD interacts directly with exportins 5 and 7, suggesting that binding of exportins and MED1 to TR may be mutually exclusive. Collectively, our data provide evidence that MED1 promotes nuclear retention of TR, and highlight the dual functionality of helix 12 in TR transactivation and nuclear export.
Next‐generation sequencing reveals unique combination of mutations in cis of CSF3R in atypical chronic myeloid leukemia
Authors: Yun Jae Won , Yoon Jung , Jung Chul Won , Lee Ki‐O , Kim Jong Won , Kim Sun‐Hee , Kim Hee‐Jin
Published: November 2019

Background

Atypical chronic myeloid leukemia (aCML) is a hematologic disorder characterized by leukocytosis with increased dysplastic neutrophils and their precursors. In CSF3R gene, the activation mutation including T618I is frequently reported in aCML but is rarely accompanied by truncation mutations. Herein, we report a unique aCML patient with two CSF3R mutations (T618I and Y779*) in the same DNA strand.

Methods

High‐coverage next‐generation sequencing for 40 genes related with myeloid leukemia was performed. Sanger sequencing was performed to confirm CSF3R mutations. To confirm whether two CSF3R mutations are in cis or not, TA cloning was used. Clinical information and bone marrow pathology were reviewed by two hematopathologists.

Results

In the patient diagnosed with aCML in bone marrow study, two CSF3R mutations, (T618I and Y779*) a SETBP1 mutation (G870S) and an U2AF1 mutation (Q157P), were identified by high‐coverage next‐generation sequencing. The two CSF3R mutations were confirmed to be located in the same DNA strand by TA cloning, indicating that the two mutations are harbored in one malignant clone. The SETBP1 mutation is known to be related with poor prognosis in aCML. Likewise, the patient was refractory to hydroxyurea and showed disease progression. Additionally, we discussed the potential therapeutic targets by reviewing the molecular profile of the patient.

Conclusion

We believe that the accurate diagnosis and maximum therapeutic chance could be achieved by profiling the mutations and their characteristics.
The role of relationship proximity to witnessed community violence and youth outcomes
Authors: Elsaesser Caitlin , Kennedy Traci M. , Tredinnick Lorin
Published: November 2019

Aims

This study examines whether the relational proximity to the victim or perpetrator of witnessed community violence is associated with youth symptoms.

Methods

Data come from the Longitudinal Studies of Child Abuse and Neglect, a national high‐risk sample. The sample included 12‐year‐old youth (N = 720) who had witnessed violence in their lifetimes. Ordinary least squares (OLS) regressions tested whether relationship proximity differentiated youth functioning (social competency, withdrawal, anxiety/depression, delinquency, and aggression), and whether gender moderated these effects.

Results

Witnessing violence toward a parent was associated with greater withdrawal, delinquency, and aggression symptoms. Witnessing violence perpetrated by a stranger was associated with lower social competency, higher anxiety/depression, and higher delinquency. Two perpetrator associations differed by gender.

Conclusion

Findings suggest important differences in outcomes based on relational proximity to victims and perpetrators. The particularly widespread associations between witnessing violence against a parent and youth functioning underscore the importance of targeting interventions toward youth with parent victims.
Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders
Authors: Shomali Navid , Gharibi Tohid , Vahedi Ghasem , Mohammed Rebar N. , Mohammadi Hamed , Salimifard Sevda , Marofi Faroogh
Published: November 2019

Nonhematopoietic stem cells as a delivery platform of therapeutic useful genes have attracted widespread attention in recent years, owing to gained a long lifespan, easy separation, high proliferation, and high transfection capacity. Mesenchymal stem/stromal cells (MSCs) are the choice of the cells for gene and cell therapy due to high self‐renewal capacity, high migration rate to the site of the tumor, and with immune suppressive and anti‐inflammatory properties. Hence, it has a high potential of safety genetic modification of MSCs for antitumor gene expression and has paved the way for the clinical application of these cells to target the therapy of cancers and other diseases. The aim of gene therapy is targeted treatment of cancers and diseases through recovery, change, or enhancement cell performance to the sustained secretion of useful therapeutic proteins and induction expression of the functional gene in intended tissue. Recent developments in the vectors designing leading to the increase and durability of expression and improvement of the safety of the vectors that overcome a lot of problems, such as durability of expression and the host immune response. Nowadays, gene therapy approach is used by MSCs as a delivery vehicle in the preclinical and the clinical trials for the secretion of erythropoietin, recombinant antibodies, coagulation factors, cytokines, as well as angiogenic inhibitors in many blood disorders like anemia, hemophilia, and malignancies. In this study, we critically discuss the status of gene therapy by MSCs as a delivery vehicle for the treatment of blood disorders. Finally, the results of clinical trial studies are assessed, highlighting promising advantages of this emerging technology in the clinical setting.
Astrocyte elevated gene 1 (AEG‐1) promotes anoikis resistance and metastasis by inducing autophagy in hepatocellular carcinoma
Authors: Zhu Hai‐Dan , Liu Lian , Deng Huan , Li Zheng‐Bo , Sheng Jia‐Qi , He Xing‐Xing , Tian De‐An , Li Pei‐Yuan
Published: November 2019

Astrocyte elevated gene 1 (AEG‐1) is overexpressed in hepatocellular carcinoma (HCC) and is strongly associated with tumor metastasis. Anoikis resistance and autophagy may play an important role in the survival of circulating tumor cells. However, the relationship among AEG‐1, anoikis resistance, autophagy, and metastasis in HCC is still not clear. The results of this study indicate that AEG‐1 expression is increased in HCC cell lines grown in suspension culture. AEG‐1 could enhance anoikis resistance to promote the survival of detached HCC cells. Moreover, the anoikis resistance appears to be partly dependent on autophagy. Regulating AEG‐1 expression changed the autophagy levels to modulate anoikis resistance, likely acting via the protein kinase RNA‐like ER kinase (PERK)‐eIF2α‐ATF4‐CHOP signaling axis. Finally, inhibiting autophagy by RNA interference prevented the AEG‐1‐promoted metastasis of HCC xenografts to the liver and lungs of nude mice. Taken together, AEG‐1 is a key contributor to anoikis resistance and metastasis by inducing autophagy in vitro and in vivo, and it may be a potential target for therapeutic intervention in HCC.
Diagnostic and prognostic significance of serum miRNA‐146‐a expression in Egyptian children with sepsis in a pediatric intensive care unit
Authors: Karam Rehab A. , Zidan Haidy E. , Karam Nehad A. , Abdel Rahman Doaa M. , El‐Seifi Omnia S.
Published: November 2019

Background

Previous studies have suggested a strong genetic effect on sepsis pathogenesis. The present study aimed to investigate the role of miRNA‐146‐a expression in pediatric sepsis.

Methods

The study included 55 pediatric sepsis patients and 60 control children of the same age and sex. Serum miRNA‐146‐a expression was measured using a quantitative real‐time polymerase chain reaction. C‐reactive protein, interleukin‐6, tumor necrosis factor‐α and procalcitonin levels were measured by an enzyme‐linked immunosorbent assay. The outcome of the pediatric sepsis group was determined at 28 days of follow up.

Results

The results obtained revealed that serum miRNA‐146‐a levels were significantly decreased in sepsis group compared to the control group. Serum level of miRNA‐146a correlated with sepsis severity, with the pediatric septic shock group having the lowest level, followed by the severe sepsis and sepsis groups. The miRNA‐146‐a level could indicate sepsis (area under curve = 0.803). Serum miRNA‐146‐a expression was negatively associated with C‐reactive protein, pro‐calcitonin, interleukin‐6 and tumor necrosis factor‐α. Patients with miRNA‐146‐a at a level lower than 0.4 had an increased mortality rate.

Conclusions

miRNA‐146‐a is of significant diagnostic and prognostic value in pediatric sepsis and could be used for planning therapeutic strategies.
MiR‐6838‐5p suppresses cell metastasis and the EMT process in triple‐negative breast cancer by targeting WNT3A to inhibit the Wnt pathway
Authors: Liu Guozhu , Wang Ping , Zhang Hao
Published: November 2019

Background

Triple‐negative breast cancer (TNBC) has become a common tumor that harms women's physical and mental health, as characterized by a relatively rapid recurrence and a high incidence of brain metastasis. Research increasingly suggests that microRNAs play key roles in the progress of TNBC. However, the function of miR‐6838‐5p in TNBC has not yet been reported, and requires additional exploration.

Methods

In the present study, we uncovered miR‐6838‐5p expression in TNBC cells via a quantitative reverse transcriptase‐polymerase chain reaction. Functionally, the impacts of up‐regulated or down‐regulated miR‐6838‐5p on TNBC invasiveness, Wnt pathway activation and epithelial–mesenchymal transition (EMT) were investigated via transwell and western blot assays. Mechanical analyses were utilized to unmask the miR‐6838‐5p mechanism in TNBC, including luciferase reporter, western blot and RIP assays. Rescue assays manifested the miR‐6838‐5p/WNT3A network in TNBC invasiveness through the Wnt pathway.

Results

Under‐expressed miR‐6838‐5p was found in TNBC cells. Up‐regulation of miR‐6838‐5p suppressed TNBC cell invasion, migration and blockade of the Wnt pathway. However, down‐regulation of miR‐6838‐5p led to opposite results. Furthermore, we found, via luciferase reporter, western blot and RIP assays, that miR‐6838‐5p could bind with WNT3A and negatively regulate WNT3A expression. Through rescue experiments, we demonstrated that the overexpression of WNT3A partially rescued the miR‐6838‐5p overexpression‐mediated inhibitory effect, and knockdown of WNT3A partially rescued the miR‐6838‐5p suppression‐mediated promotive effect on the progression of TNBC.

Conclusions

In summary, the results of the present study indicate that miR‐6838‐5p suppresses cell proliferation, metastasis and the EMT process in TNBC by targeting WNT3A to inhibit the Wnt pathway, which may provide a new insight into the therapeutic strategies of TNBC.
Immunological recovery failure in cART-treated HIV-positive patients is associated with reduced thymic output and RTE CD4+ T cell death by pyroptosis
Authors: Carvalho-Silva Wlisses Henrique Veloso , Andrade-Santos José Leandro , Souto Fabrício Oliveira , Coelho Antonio Victor Campos , Crovella Sergio , Guimarães Rafael Lima
Published: November 2019

Despite more than three decades of studies and advances in combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV), the mechanisms that precisely determine immune reconstitution failure have not been completely elucidated yet. Thus, this study aimed to investigate the thymic function, immune activation, and cell death by pyroptosis and apoptosis in virologically suppressed HIV-positive patients receiving cART. Immunophenotyping analyses were performed in 57 cART-treated HIV-infected patients with undetectable plasma viral load, who were classified as immunological nonresponders (INR = 29) and immunologic responders (IR = 28). Sociodemographic and clinical data were also assessed from medical records. Twelve healthy volunteers were also included in this study. The INR showed lower pretreatment CD4+ T cell count that remained low even after 1 yr of treatment, lower CD4/CD8 ratio, lower percentage of recent thymic emigrant (RTE) CD4+ T cell (CD45RA+CD31+) and naïve CD4+ T cell (CD45RA+CD62L+), higher levels of effector memory CD4+ T cells (CD45RA-CD62L-), and higher pyroptosis levels of RTE CD4+ T cells (CD31+FLICA-Caspase1+) when compared with IR. Our findings indicate that reduced thymic function and RTE CD4+ T cell death by pyroptosis are the major mechanisms of immunological recovery failure in HIV-infected patients receiving cART.
Optimization of a minimal sample preparation protocol for imaging mass spectrometry of unsectioned juvenile invertebrates
Authors: Zink Katherine E. , Tarnowski Denise A. , Mandel Mark J. , Sanchez Laura M.
Published: November 2019

Tissue sections have long been the subject matter for the application of imaging mass spectrometry, but recently the technique has been adapted for many other purposes including bacterial colonies and 3D cell culture. Here, we present a simple preparation method for unsectioned invertebrate tissue without the need for fixing, embedding, or slicing. The protocol was used to successfully prepare a Hawaiian bobtail squid hatchling for analysis, and the resulting data detected ions that correspond to compounds present in the host only during its symbiotic colonization by Vibrio fischeri.
Two‐dimensional FIR filters model order reduction and frequency transformation: Maximum error invariance
Authors: Bouhamla Lakhdar , Adamou‐Mitiche Amel Baha Houda , Mitiche Lahcène
Published: November 2019

This paper presents a numerical study of the maximum error in model order reduction (MOR) for finite impulse response (FIR) 2‐D digital filter under frequency transformation, which is based on the Roesser state‐space formulation. This study discuss the maximum error obtained from the 2‐D balanced truncation method after and before using the frequency transformation. Several numerical examples are realized to show the invariant of the maximum error in all frequency transformation cases (single variable, two‐variable, and hybrid variable transformations).
Effect of nitrogen deficiency on the physiology and biochemical composition of microalga Scenedesmus rotundus‐MG910488
Authors: Dixit Rishibha , Singh Surendra , Singh Ajeet
Published: November 2019

The present investigation ascertains the impact of gradient concentrations of sodium nitrate on the physiology and biochemical composition of isolated microalga Scenedesmus rotundus‐MG910488. The concentrations of nitrate were selected as 0, 3.5, 7.0, 10.5, 14.0, and 17.6 mM/L in BG11 medium. The lower concentrations of nitrogen were found to be significantly decreasing the cell count and photosynthetic activity in the microalga as well as changing cell morphology. The amount of biomass, its productivity and lipid yield were significantly affected. The highest biomass of 689.15 ± 14.27 mg/L was achieved in the concentration of 17.6 mM/L with the biomass productivity of 38.28 ± 0.78 mg/L. The highest lipid accumulation of 41.46 ± 1.94% dry‐cell weight was obtained at a concentration of 3.5 mM/L, whereas the lowest lipid accumulation of 29.22 ± 1.65% at the concentration of 17.6 mM/L sodium nitrate. The fatty acid composition determines the quality of the fuel, so the characterization of fatty acid methyl esters (FAMEs) was performed by GC, and the assessment of methyl esters of fatty acid confirmed the existence of palmitic acid, oleic acid, and linoleic acid, which are essential components suitable for biodiesel production. FTIR confirms the presence of FAME components by estimating the bending and stretching of functional groups.
Endoscopic Sealing With a Polyglycolic Acid Sheet for Restoration of Vocal Fold Mucosa in Dogs
Authors: Mihashi Ryota , Chitose Shun‐ichi , Sato Fumihiko , Tanaka Hisaichiro , Sato Kiminori , Ono Takeharu , Fukahori Mioko , Sueyoshi Shintaro , Kurita Takashi , Sato Kiminobu , Umeno Hirohito
Published: November 2019

Objectives/Hypothesis

Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet.

Study Design

Animal experiment.

Methods

Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA‐bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high‐speed camera, and histological analysis was performed.

Results

The re‐epithelialization process was delayed in the PGA and PGA‐bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA‐bFGF groups compared with the control group. The PGA‐bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA‐bFGF and control groups.

Conclusions

The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects.

Level of Evidence

NA

Laryngoscope, 130:E436–E443, 2020
Pediatric Midface Fractures: Outcomes and Complications of 218 Patients
Authors: Kao Richard , Campiti Vincent J. , Rabbani Cyrus C. , Ting Jon Y. , Sim Michael W. , Shipchandler Taha Z.
Published: November 2019

Objective

To analyze management, outcomes, and complications of pediatric midface fractures.

Methods

Retrospective cohort study at an urban, single‐institution, multispecialty surgical teams, at two level 1 pediatric trauma centers. Query included subjects aged 0–17 diagnosed with midface fractures between 2012 and 2016.

Results

A total of 218 pediatric patients presented with 410 total midface fractures. The most common etiologies included motor vehicle collisions (MVC) (n = 56, 25.7%), sport‐related (n = 35, 16.1%), and assault/battery (n = 32, 14.7%). Fracture site distribution included: 125 maxillary (34 with exclusively the nasal/frontal process), 109 nasal, 47 ethmoid, 40 sphenoid, 33 zygoma, 29 frontal sinus, 21 lacrimal, and 6 palatal. Among these, there were 105 orbital, 17 naso‐orbito‐ethmoid, and 12 Le Fort fractures. One‐quarter of patients received at least one midface‐related operation during the initial encounter. Operative intervention rates for specific midface fracture subsites were not significantly different (X2 = 6.827, P = .234). One hundred thirty‐five patients (63.4%) attended follow‐up, thus known complication rate was 14.6% (n = 31). Complication rates between midface fracture subsites were not significantly different (X2 = 5.629, P = .229). Complications included facial deformity (n = 18), nasal airway obstruction (n = 8), diplopia (n = 4), hardware‐related pain (n = 3), and paresthesias (n = 3).

Conclusions

The most common sites of pediatric midface fractures involved the maxilla, and nasal bones. Three quarters of pediatric midface fractures were treated conservatively, with low rates of complications. Facial deformity was the most common complication; as such, proper management and follow‐up are important to ensure normal growth and development of the pediatric facial skeleton.

Level of Evidence

4
Acute Hypercapnia/Ischemia Alters the Esterification of Arachidonic Acid and Docosahexaenoic Acid Epoxide Metabolites in Rat Brain Neutral Lipids
Authors: Otoki Yurika , Metherel Adam H. , Pedersen Theresa , Yang Jun , Hammock Bruce D. , Bazinet Richard P. , Newman John W. , Taha Ameer Y.
Published: November 2019

In the brain, approximately 90% of oxylipins are esterified to lipids. However, the significance of this esterification process is not known. In the present study, we (1) validated an aminopropyl solid phase extraction (SPE) method for separating esterified lipids using 100 and 500 mg columns and (2) applied the method to quantify the distribution of esterified oxylipins within phospholipids (PL) and neutral lipids (NL) (i.e. triacylglycerol and cholesteryl ester) in rats subjected to head‐focused microwave fixation (controls) or CO2‐induced hypercapnia/ischemia. We hypothesized that oxylipin esterification into these lipid pools will be altered following CO2‐induced hypercapnia/ischemia. Lipids were extracted from control (n = 8) and CO2‐asphyxiated (n = 8) rat brains and separated on aminopropyl cartridges to yield PL and NL. The separated lipid fractions were hydrolyzed, purified with hydrophobic–lipophilic–balanced SPE columns, and analyzed with ultra‐high‐pressure liquid chromatography coupled to tandem mass spectrometry. Method validation showed that the 500 mg (vs 100 mg) aminopropyl columns yielded acceptable separation and recovery of esterified fatty acid epoxides but not other oxylipins. Two epoxides of arachidonic acid (ARA) were significantly increased, and three epoxides of docosahexaenoic acid (DHA) were significantly decreased in brain NL of CO2‐asphyxiated rats compared to controls subjected to head‐focused microwave fixation. PL‐bound fatty acid epoxides were highly variable and did not differ significantly between the groups. This study demonstrates that hypercapnia/ischemia alters the concentration of ARA and DHA epoxides within NL, reflecting an active turnover process regulating brain fatty acid epoxide concentrations.
Berberine Inhibits Adipogenesis in Porcine Adipocytes via AMP‐Activated Protein Kinase‐Dependent and ‐Independent Mechanisms
Authors: Yang Yongqing , Liu Fenglan , Lu Rongsheng , Jia Junli
Published: November 2019

Excessive adipogenesis in adipocytes results in obesity. Berberine, a natural isoquinoline alkaloid, has antiobesity properties. However, the underlying molecular mechanisms have remained unclear up to now. In this study, porcine adipocytes were cultured and treated with berberine. Cellular lipid content was measured by Oil Red O staining extraction. The role of an adenosine monophosphate‐activated protein kinase (AMPK) signaling pathway was evaluated by the phosphorylation detection of AMPKα protein and knockdown of AMPK alpha1 (Ampka1) gene. Gene expressions were analyzed by Western blot and real‐time reverse transcription‐polymerase chain reaction (RT‐PCR). The results showed that berberine reduced lipid accumulation in porcine adipocytes in a dose‐ and time‐dependent manner and increased phosphorylation of AMPKα. Furthermore, berberine significantly downregulated the mRNA expression of related genes to adipogenesis including peroxisome proliferator activated receptor gamma 2 (Pparg2), CCAAT/enhancer‐binding protein alpha (Cebpa), Cebp beta (Cebpb), sterol regulatory element binding transcription factor 1 (Srebf1), acetyl‐CoA carboxylase‐1 (Acc‐1), fatty acid synthase (Fas), fatty acid binding protein 4 (Fabp4), and stearoyl‐CoA desaturase 1 (Scd1). Knockdown of Ampka1 markedly reversed the inhibitory effect of berberine on lipid accumulation and mRNA expression of the above genes except Cebpb in porcine adipocytes. Meanwhile, the protein expression of these adipogenic genes in response to berberine and Ampka1 knockdown paralleled the alterations of their mRNA level. These results suggest that berberine inhibits adipogenesis in porcine adipocytes via AMPK‐dependent and ‐independent multiple mechanisms, which would provide an important idea for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.
Who's got my back? Comparing consumers' reactions to peer‐provided and firm‐provided customer support
Authors: Jiang Lan , O'Hern Matthew , Hanson Sara
Published: November 2019

This study demonstrates that when an individual encounters a product‐related problem, fellow consumers (i.e., one's peers) have a unique advantage in providing social support to the affected consumer. Specifically, we find that social support can be a dominant driver of consumer satisfaction when the risk of customer defection is at its highest (i.e., following an unsuccessful attempt to solve the consumer's problem). Using real‐world data from an online support community, a pilot study finds that if the problem that a consumer faces goes unsolved, satisfaction is greater when consumers receive peer‐provided versus firm‐provided support. Study 1 replicates this finding in a controlled experiment that realistically simulates an actual customer support incident in real‐time. Study 2 identifies social support as the mechanism that underlies this effect and investigates whether firm employees can take steps to appear more customer‐like and thereby replicate the advantage of peer‐provided support. Finally, Study 3 reveals an alternative strategy (i.e., utilizing multiple employees) that firms can use to enhance social support and provides evidence that peer‐provided support not only enhances satisfaction but also positively influences consumers' behavioral intentions.
Mussel‐Inspired Polymerization of Peptides: The Chemical Activation Route as Key to Broaden the Sequential Space of Artificial Mussel‐Glue Proteins
Authors: Kohn Jana M. , Riedel Jerome , Horsch Justus , Stephanowitz Heike , Börner Hans G.
Published: November 2019

A previously introduced tyrosinase‐activated polymerization of Tyr‐ and Cys‐bearing peptides yielding artificial mussel‐glue proteins is realized without the need of the specific enzyme by a chemical activation route. This decouples the sequence of polymerizable peptides (unimers) from the constraints of tyrosinase substrates and enables the polymerization of minimal motifs such as Dopa‐Lys‐Cys (Umini*KC) or Dopa‐Gly‐Cys (Umini*GC). In the polymerization procedure, sodium periodate is used to oxidize Dopa residues of the unimers to Dopa‐quinones to which the thiol of a Cys residue is added in a Michael‐type reaction. The resulting polyUmini*KC and polyUmini*GC exhibit a thiol–catechol connectivity as a potent adhesive functionality at each repeat unit. QCM‐D experiments show the excellent substrate adsorption properties of the products from the chemically activated polymerization. On aluminum oxide surfaces, polyUmini*KC rapidly forms a coating, even under seawater model conditions and the coating resists rinsing with hypersaline solution of 4.2 M salt mixtures. While the sodium periodate oxidation is less specific than the tyrosinase reaction and requires the implementation of Dopa instead of Tyr residues into the polymerizable unimers, the chemical route makes scale‐up more easily accessible.
Crosslinked Poly(N‐Isopropylacrylamide)‐Based Microfibers as Cell Manipulation Materials with Prompt Cell Detachment
Authors: Konishi Tomomi , Mizutani Akimoto Aya , Nishimoto Taihei , Tokura Yuki , Tenjimbayashi Mizuki , Homma Kenta , Matsukawa Ko , Kaku Taisei , Hiruta Yuki , Nagase Kenichi , Kanazawa Hideko , Shiratori Seimei
Published: November 2019

Stimuli‐responsive smart materials are a key to the realization of next‐generation medical technologies. Among them, the temperature‐responsive polymer poly(N‐isopropylacrylamide) (PNIPAAm) is attracting particular attention because it is easy to use in physiological conditions. PNIPAAm‐grafted surfaces can undergo temperature‐modulated cell adhesion and detachment without proteolytic enzymes, and can be used as cell‐separating materials through selective cell adhesion/detachment. However, cell detachment at reduced temperatures is problematic because it takes several hours. A novel thermoresponsive crosslinked microfiber system that can greatly reduce the cell detachment time is introduced in this study. The crosslinked fibers provide temperature‐dependent volume change, and enable cell detachment within 10 min of reducing the temperature, which is one‐sixth of the time required in previous studies. The prompt cell detachment is thought to arise from a completely new mechanism derived from fiber swelling. This system will make a significant contribution as a novel cell manipulating system for next‐generation medical technology.
Potentially functional variants of autophagy‐related genes are associated with the efficacy and toxicity of radiotherapy in patients with nasopharyngeal carcinoma
Authors: Yang Zhiguang , Liu Zhaoyu
Published: November 2019

Background

Nasopharyngeal carcinoma (NPC) is one of the major invasive malignant neoplasms of head and neck, while radiotherapy is the primary therapy for NPC. Genetic variants could affect the efficacy and toxicities of radiotherapy in NPC patients.

Methods

In the current study, we aimed to investigate 10 potentially functional SNPs of autophagy‐related genes (ATG) with the efficacy and toxicity of radiotherapy in 468 NPC patients.

Results

We found ATG10 rs10514231, rs1864183, and rs4703533 were significantly associated with worse efficacy of radiotherapy at both at the primary tumor and lymph node, while ATG16L2 rs10898880 was significantly associated with better efficacy of radiotherapy at both primary tumor and lymph node. Besides, we also found ATG10 rs10514231 and ATG16L2 rs10898880 were significantly associated with the occurrence of grade 3–4 oral mucositis (allelic model, for rs10514231: OR = 1.95, 95% CIs = 1.31–2.9, p = .001; for rs10898880: OR = 1.56, 95% CIs = 1.19–2.04, p = .001) and grade 3–4 myelosuppression (allelic model, for rs10514231: OR = 2.08, 95% CIs = 1.39–3.09, p < .001; for rs10898880: OR = 1.51, 95% CIs = 1.1–2.06, p = .010).

Conclusions

This should be the first report identifying ATG10 rs10514231, rs1864183, rs4703533, and ATG16L2 rs10898880 could contribute to the efficacy and toxicity of radiotherapy in NPC patients. Further investigation of the underlying molecular mechanisms and prospective clinical trials in NPC patients are needed to validate our results.
The approximately synchronizable state for a kind of coupled system of wave equations
Authors: Lu Xing
Published: November 2019

This paper deals with the approximately synchronizable state by groups for a kind of coupled system of wave equations with Dirichlet boundary controls. So far, the approximate boundary synchronization for a kind of coupled system of wave equations has already been deeply studied; however, the study on the approximately synchronizable state still needs to be done in details. In this paper, we will give some results on the determination of approximately synchronizable state by groups and the attainable set of them.
A robust multi‐sampling rate digital predistortion for ultra‐broadband power amplifiers
Authors: Liu Xin , Chen Wenhua , Chen Long , Feng Zhenghe
Published: November 2019

In this letter, a robust multisampling rate digital predistortion (DPD) scheme is proposed to linearize ultra‐broadband power amplifiers (PAs) under the limited DAC sampling rate. In the ultra‐broadband scenarios, it is no longer affordable to employ DACs with 3‐5 times over‐sampling rate, which will inevitably lead to spectrum aliasing for the sake of high order basis function and compromise the DPD performance. In order to improve the modeling accuracy, the input signal with low sampling rate will be up‐sampled firstly to generate nonaliasing basis functions. Then, after filtering and down‐sampling operation, the coefficients are extracted with low sampling rate. Moreover, the conventional behavioral model is modified with the linear‐spline basis functions to improve the stability and complexity. Measurements on Doherty PA and class‐AB PA with 100 MHz, 200 MHz, and 500 MHz bandwidth input signal at 2.1 GHz carrier frequency show the EVM can be improved to 0.71%, 0.94%, and 1.86% respectively.
Power management circuit based on micro‐electromechanical systems thermoelectric‐photoelectric integrated power generator
Authors: Li Chenglin , Liao Xiaoping , Qian Kai
Published: November 2019

Thermoelectric‐photoelectric integrated power generator and a power management circuit are designed in this letter for the inefficiency of power amplifier and the generation of massive heat of transceiver. Thermoelectric‐photoelectric integrated power generator is composed of thermoelectric power generator at surface layer and photoelectric power generator at bottom layer, absorbing both heat and light energy at the same time. The outputs of thermoelectric and photoelectric power generator are connected with power management circuit after parallel connection. Power management circuit is an interface circuit which is able to boost the small output voltage of integrated power generator from 300 mV to 3.1 V with no external power supply. The innovation is not only structure integration, but also output integration of two power generators. In addition, 3.1 V voltage from power management circuit is compatible with most interfaces in transceiver system. The integrated power generator and power management circuit form a complete power supply module for transceiver and wireless sensor node.
LDeform: Longitudinal deformation analysis for adaptive radiotherapy of lung cancer
Authors: Nadeem Saad , Zhang Pengpeng , Rimner Andreas , Sonke Jan‐Jakob , Deasy Joseph O. , Tannenbaum Allen
Published: November 2019

Purpose

Conventional radiotherapy for large lung tumors is given over several weeks, during which the tumor typically regresses in a highly nonuniform and variable manner. Adaptive radiotherapy would ideally follow these shape changes, but we need an accurate method to extrapolate tumor shape changes. We propose a computationally efficient algorithm to quantitate tumor surface shape changes that makes minimal assumptions, identifies fixed points, and can be used to predict future tumor geometrical response.

Methods

A novel combination of nonrigid iterative closest point (ICP) and local shape‐preserving map algorithms, LDeform, is developed to enable visualization, prediction, and categorization of both diffeomorphic and nondiffeomorphic tumor deformations during an extended course of radiotherapy.

Results

We tested and validated our technique on 31 longitudinal CT/MRI subjects, with five to nine time points each. Based on this tumor deformation analysis, regions of local growth, shrinkage, and anchoring are identified and tracked across multiple time points. This categorization in turn represents a rational biomarker of local response. Results demonstrate useful predictive power, with an averaged Dice coefficient and surface mean‐squared error of 0.85 and 2.8 mm, respectively, over all images.

Conclusions

We conclude that the LDeform algorithm can facilitate the adaptive decision‐making process during lung cancer radiotherapy.