bluuebunny/crossref_metadata_2025 huggingface dataset:
Microwave‐Assisted Synthesis and Characterization of Stearic Acid Sucrose Ester: A Bio‐Based Surfactant
Authors: Kondamudi Narasimharao , McDougal Owen M.
Published: March 2019

Sugar esters of fatty acids are bio‐based surfactants that were synthesized by transesterification of table sugar (sucrose) with stearic acid methyl ester (SAME) in high yield and purity using an optimized microwave‐assisted method. The maximum surfactant product yield of 88.2% was obtained by combining reactants with potassium methoxide and irradiating the mixture with microwaves to achieve an ideal reaction temperature of 132 °C over 21 min. The synthetic procedure described herein minimized undesirable sugar pyrolysis as evidenced by retention of white color characteristic of a pure bio‐based surfactant product. The experiment implemented Box–Behnken design for response surface methodology to refine reaction parameters for optimal product yield. The following parameters were augmented: the irradiation time, the mole ratio of catalyst to sucrose, and temperature.
Changes in the perception of bitter constituents in thermally treated yeast extract
Authors: Alim Aygul , Song Huanlu , Yang Chao , Liu Ye , Zou Tingting , Zhang Yu , Zhang Songpei
Published: March 2019

BACKGROUND

Many studies have been performed over the past four decades to identify and quantify the odor‐active key volatiles in yeast extract (YE) but knowledge of the nonvolatile taste compounds is still rather fragmentary. In particular, research on bitter peptides with various structures during the thermal treatment of YE is still scarce.

RESULTS

Compounds imparting a bitter taste to thermally treated YE were investigated using sensory‐guided fractionation. This research found that when the treatment temperature reached 130 °C, bitter peptides were generated. Sensory evaluation of the purified, synthesized peptides revealed that four of these peptides showed a pronounced bitter taste with a taste dilution (TD) factor from 5 to 9. Guidance is provided for the production of bitter peptides in the flavor industry.

CONCLUSION

Based on results from previous work on umami peptides, and this study, keeping the thermal reaction temperature under 120 °C could maximize the umami flavor and control bitterness so that it remains in an acceptable range. © 2019 Society of Chemical Industry
Establishment of pressurized liquid extraction followed by HPLC–MS/MS method for the screening of adrenergic drugs, steroids, sedatives, colorants and antioxidants in swine feed
Authors: Wang Yanxin , Peng Dapeng , Zhu Yufei , Xie Shuyu , Pan Yuanhu , Chen Dongmei , Tao Yanfei , Yuan Zonghui
Published: March 2019

A facile and sensitive multi‐residue detection approach of pressurized liquid extraction following high‐performance liquid chromatography tandem mass spectrometry was established to detect the residues of adrenergic drugs, steroids, sedative, colorant and antioxidant in feed. The conditions employed for pressurized liquid extraction involved acetonitrile/ethyl acetate (1:1, v/v) as the extracting solvent, the temperature 80°C, two cycles and a static time of 10 min. The extraction was followed by a solid‐phase extraction clean‐up step. The separation of samples was done by C18 column with the mobile phase of 5 mM ammonium acetate solution and acetonitrile with 0.1% formic acid. The limits of quantification ranged from 0.03 to 1 μg/kg, limits of detection were in a range of 0.01–0.5 μg/kg, and average recoveries were 70.4–98.6%. The pressurized liquid extraction procedure was optimized and overall method was validated in terms of sensitivity, linearity, selectivity, matrix effect, accuracy, recovery and stability of the target drugs in the pressurized liquid extraction extracts solution. The screening method was proved to be fast, selective, accurate and sensitive for screening drugs.
Ultrasound‐Guided Percutaneous Microwave Ablation for Substernal Goiter: Initial Experience
Authors: Cui Rui , Yu Jie , Han Zhi‐yu , Liu Fang‐yi , Yu Xiao‐ling , Liang Ping
Published: March 2019

Objectives

To preliminarily evaluate the safety, effectiveness, and feasibility of microwave ablation (MWA) for substernal goiter (SSG) in select patients and to provide a relevant treatment reference for further studies.

Methods

From April 2017 to December 2017, 10 patients with SSG were treated by MWA. All patients were followed for at least 3 months to observe the therapeutic effects and complications. Therapeutic effects were assessed at follow‐up for the relief of patients’ symptoms, resolution of the cosmetic grade, and volume reduction rate (VRR) of SSG. Possibly related factors for the 3‐month VRR of the nodules were analyzed.

Results

The study included 9 female patients and 1 male patient with a mean age ± SD of 56.8 ± 10.1 years (range, 34–70 years). The mean volume of the nodules was 52.9 ± 27.9 mL (range, 23.7–122.6 mL). The nodule volume was significantly reduced at the 3‐month follow‐up (17.5 ± 9.5 mL; P < .05). The mean 3‐month VRR of the index nodule was 66.7% ± 7.1%. A higher ablated portion‐to‐nodule ratio 1 day after MWA predicted a higher 3‐month VRR (Spearman r = 0.646; P = .044). The mean symptom score (from 4.5 ± 1.7 to 1.5 ± 1.0; P = .005) and cosmetic grade (from 3.3 ± 0.5 to 2.2 ± 0.4; P = .004) declined significantly 3 months after the procedure. No complications or unexpected side effects were observed.

Conclusions

Our preliminary results support the effectiveness and safety of MWA for local control of SSG. This technology can be applied in select patients with SSG who are ineligible for surgery.
WHAT EVERY LEADER NEEDS TO KNOW ABOUT THE POWER OF SPONSORSHIP
Authors: Hewlett Sylvia Ann
Published: March 2019

Hewlett, founder of the Center for Talent Innovation (CTI), a think tank, writes about a “professional relationship in which an executive or manager identifies and chooses an outstanding junior talent, develops that person's career, and reaps significant rewards for these efforts.” She lists and explains “seven steps to effective sponsorship,” which in her words are: identify potential protégés, include a variety of perspectives, inspire to tap into passion and purpose, instruct to fill skill gaps, inspect your prospects, instigate a deal, and invest in three ways. Examples are drawn from such disparate sources as Los Angeles Lakers basketball superstar LeBron James and executives John Rogers and Mellody Hobson of Ariel Investments.
Scalable Trehalose‐Functionalized Hydrogel Synthesis for High‐Temperature Protection of Enzymes
Authors: Panescu Priera H. , Ko Jeong Hoon , Maynard Heather D.
Published: March 2019

Herein, a scalable, two‐step synthesis of a trehalose hydrogel for the thermostabilization of enzymes is reported. A reaction between vinylbenzyl chloride and trehalose in base, followed by a redox‐initiated radical polymerization of the resulting mixture, produces the gel in 88% yield. The reaction scale can be increased 100‐fold while maintaining a 76% yield. Additionally, various solvents are investigated for purification, and more sustainable manufacturing solvents are selected. When the three major enzymes utilized in animal feed, phytase, β‐glucanase, and xylanase, are heated to 90 °C in the hydrogel, greater than 98% activity is retained. Lastly, quantitative release of enzyme from the gel within 4 h is demonstrated. The scalable synthesis of the trehalose hydrogel, combined with its ability to stabilize and release a variety of animal feed enzymes, makes this technology promising for use with enzymes important in animal food production.
Syndiospecific Coordination Polymerization of Si‐H‐Containing Styrenes Catalyzed by Scandium Complex and Synthesis of Styrene‐Based Triblock Copolymers
Authors: Yu Hui , Yang Ke , Niu Hui , Yu Jialin , Dong Jinghan , Wang Jing , Li Yang
Published: March 2019

The controlled syndiospecific polymerization of three Si‐H‐containing styrenes, that is, 4‐(methylhydrosilyl)styrene (FSt‐1), 4‐(dimethylhydrosilyl)styrene (FSt‐2) and 4‐(diisopropylhydrosilyl)styrene (FSt‐3), is realized in the presence of (C5Me4SiMe3)Sc (CH2C6H5)2(THF)/[Ph3C][B(C6F5)4]. Then a series of FSt‐b‐styrene‐b‐FSt triblock copolymers (FSt‐St‐FSt) are synthesized facilely via a sequential monomer feeding process (FSt‐2, styrene, and FSt‐2, respectively) during the polymerization. The syndiotactic polystyrene (sPS) block in the middle endows the copolymer with high melting point above 250 °C, whereas the Si‐H groups on monomer FSt‐2 introduce functional pendants to the end‐blocks (with Si–H content of 31–63 mol%). Finally by a mild and high‐effective hydrosilylation reaction, novel polar‐group functionalized sPS is obtained.
Hemi Masticatory Spasm: Series of 7 Cases and Review of Literature
Authors: Radhakrishnan Divya M. , Goyal Vinay , Shukla Garima , Singh Mamta Bhushan , Ramam M.
Published: March 2019

Background

Hemi masticatory spasm (HMS) is a rare movement disorder affecting muscles of mastication attributed to dysfunction of motor branch of trigeminal nerve and is characterized by painful spasm of masticatory muscles. Microvascular compression leading to focal demyelination of motor branch of trigeminal nerve is the most speculated on mechanism of HMS. Treatment options range from medical to surgical approaches, but botulinm toxin (BTX) has now become the preferred treatment.

Cases

We report a retrospective review of 7 cases of HMS, supported by electrophysiological and clinical findings. All the cases had excellent response to BTX therapy.

Discussion and Conclusion

In this article, we highlight the delay in diagnosis of HMS attributed to rarity, long course of illness, association with hemiatrophy, “Lichen Sclerosus et Atrophicus,” and scleroderma/morphea. Considering the favorable outcome to BTXs, surgical treatment can be avoided or delayed in majority except secondary cases.
Use of a sequential chimeric perforator flap for one‐stage reconstruction of complex soft tissue defects of the extremities
Authors: Qing Liming , Wu Panfeng , Yu Fang , Zhou Zhengbing , Tang Juyu
Published: March 2019

Background

One‐stage reconstruction of complex soft tissue defects of the extremities is a challenging problem. Repair of complex soft tissue defects requires adequate skin tissues to cover the large surface wound and special tissues for obliterating the dead space. The chimeric flap is one of the most popular approaches for reconstruction of complex soft tissue defects. However, the problems of donor‐site morbidity and inability to repair very large defects at one‐stage remain. The purpose of this study was to present our clinical experience using sequential chimeric perforator flaps for reconstruction of complex extremity defects with primary closure of the donor site.

Methods

From August 2013 to March 2017, 12 patients with complex soft tissue defects underwent extremity reconstruction using sequential chimeric perforator flaps, which were composed of a chimeric anterolateral thigh perforator (ALTP) flap and an additional free perforator flap. The skin paddles were placed side‐by‐side to cover the large surface soft tissue defects, and the muscle component was used to obliterate the dead space. Of these patients, one was injured by a crushing accident, while the other 11 patients were injured in traffic accidents.

Results

The size of the skin paddles ranged from 26 cm × 8 cm–10 cm × 6 cm to 30 cm × 8.5 cm–29 cm × 9 cm. The muscle paddle size ranged from 2 cm × 3 cm × 4 cm to 22 cm × 4 cm × 2 cm. All‐components of the sequential chimeric flaps survived in all‐patients. Vascular compromise was observed in one case. One case suffered minor wound‐edge necrosis and was treated conservatively. Primary closure of donor‐site was successfully achieved in all‐patients, and all‐donor‐site wounds healed uneventfully. The mean follow‐up time was 15.25 months. Most of the cases showed a satisfactory contour, and only two patients presented with mildly bulky appearance that treated with a debulking procedure.

Conclusions

The sequential chimeric perforator flap is an alternative procedure for reconstruct complex soft tissue defects of the extremities. This approach allows for flexible design, a larger cutaneous area, and low donor site morbidity.
Periodic nonautonomous differential equations with noninstantaneous impulsive effects
Authors: Yang Peng , Wang JinRong , Fečkan Michal
Published: March 2019

In this paper, we study a new class of periodic nonautonomous differential equations with periodic noninstantaneous impulsive effects. A concept of noninstantaneous impulsive Cauchy matrix is introduced, and some basic properties are considered. We give the representation of solutions to the homogeneous problem and nonhomogeneous problem by using noninstantaneous impulsive Cauchy matrix, and the variation of constants method, adjoint systems, and periodicity of solutions is verified under standard periodicity conditions. Further, we show the existence and uniqueness of solutions of semilinear problem and establish existence result for periodic solutions via Brouwer fixed point theorem and uniqueness and global asymptotic stability via Banach fixed point theorem.
Glucomannans Alleviated the Progression of Diabetic Kidney Disease by Improving Kidney Metabolic Disturbance
Authors: Chen Haihong , Nie Qixing , Hu Jielun , Huang Xiaojun , Zhang Ke , Nie Shaoping
Published: March 2019

Scope

This study is aimed to investigate the kidney protective effects of glucomannans from Dendrobium officinale stem, konjac, and Aloe vera leaves on type 2 diabetic rats and explore its potential mechanisms.

Methods and results

Pathological and metabolomics analysis methods are adopted in this study. Compared with the model group, lower levels of fasting blood glucose, serum insulin, and glycated serum protein are observed in glucomannan‐treated groups. Concentrations of serum low‐density lipoprotein cholesterol, total cholesterol, triacylglycerols, and nonesterified fatty acid are significantly decreased by glucomannan treatment. Furthermore, glucomannan treatment significantly decreased the levels of uric acid, creatinine, urea in serum, and glycosuria, ketone body, and protein in the urine. Histopathological analysis showed that glucomannan treatment normalized the architecture of glomerulus. Metabolomic analysis indicated glucomannan treatment could improve urea cycle, metabolism of lipid, glucose, and amino acids on diabetes. In particular, the konjac glucomannan treatment is more effective in lipid and glucose regulation. Glucomannan from D. officinale is more effective in balancing the urea cycle and amino acid metabolism.

Conclusions

The disturbance of lipid, glucose, and amino acid metabolism is closely associated with the advancement of diabetic kidney disease, and glucomannan treatment could be efficient in the management of diabetic kidney disease.
An 8‐channel receive array for improved 31P MRSI of the whole brain at 3T
Authors: van Uden Mark J. , Peeters Tom H. , Rijpma Anne , Rodgers Christopher T. , Heerschap Arend , Scheenen Tom W. J.
Published: March 2019

Purpose

To demonstrate a 1H/31P whole human brain volume coil configuration for 3 Tesla with separate 31P transmit and receive components that maintains 1H MRS performance and delivers optimal 31P MRSI with 1H decoupling.

Methods

We developed an 8‐channel 31P receive array coil covering the head to be used as an insert for a commercial double‐tuned 1H/31P birdcage transmit‐receive coil. This retains the possibility of using low‐power rectangular pulses for 1H‐decoupled 3D 31P MRSI (nominal resolution 17.6 cm3; acquisition duration 13 min) but increases the SNR with the receive sensitivity of 31P surface coils. The performance of the combined coil setup was evaluated by measuring 1H and 31P SNR with and without the 31P receive array and by assessing the effect of the receive array on the transmit efficiencies of the birdcage coil.

Results

Compared to the birdcage coil alone, the 31P insert in combination with the birdcage achieved an average 31P SNR gain of 1.4 ± 0.4 in a center partition of the brain. The insert did not cause losses in 1H MRS performance and transmit efficiency, whereas for 31P approximately 20% more power was needed to achieve the same γB1.

Conclusion

The new coil configuration allows 1H MRSI and optimal 1H‐decoupled 3D 31P MRSI, with increased SNR of the human brain without patient repositioning, for clinical and research purposes at 3 Tesla.
Outcomes of right colon continent urinary pouch using standardized reporting methods
Authors: Myers Jeremy B. , Martin Christopher , Cheng Philip J. , Zhang Chong , Presson Angela P.
Published: March 2019

Aims

Studies of right colon pouch urinary diversion estimate risk of perioperative complications, 1%‐50%, and reoperation, 1%‐69%. This wide range is due to variable outcome measurements and reporting methods; it is also unclear which factors increase the risk of complications and reoperation. We sought to characterize the impact of patient‐specific factors on risk of complications, readmission, and reoperation after right colon pouch urinary diversion.

Methods

Patients undergoing right colon pouch urinary diversion from January 2010 to April 2017 were analyzed. Outcomes included: high‐grade complications within 90 days (Clavien‐Dindo grade ≥3), readmission within 90 days, and reoperation at any time during follow‐up. Patient‐specific factors were analyzed to establish any associations with these outcomes.

Results

During the study period, 53 patients underwent the procedure and the average follow‐up was 30 (standard deviation [SD] 21.5) months; 90‐day high‐grade complications were 22% and readmission was 45%. The cumulative rate of any reoperation was 53% and major reoperation was 32%. Diabetes was associated with an increased risk of both postoperative complications and reoperation. Larger body mass index and prior abdominal surgery were associated with increased risk of readmission.

Conclusions

Overall the rate of postoperative complications, readmissions, and reoperation was high, but in agreement with other contemporary series. This study helps to further characterize surgical outcomes after right colon pouch urinary diversion, however, similar to other studies in the literature, the rarity of the procedure limits the power to establish a link between preoperative patient factors and outcomes.
End‐of‐Trial Health Outcomes in Look AHEAD Participants who Elected to have Bariatric Surgery
Authors: Wadden Thomas A. , Chao Ariana M. , Bahnson Judy L. , Bantle John P. , Clark Jeanne M. , Gaussoin Sarah A. , Jakicic John M. , Johnson Karen C. , Miller Gary D. , Unick Jessica L. , Yanovski Susan Z. ,   the Look AHEAD Research Group
Published: March 2019

Objective

This study examined end‐of‐trial health outcomes in participants in the Action for Health in Diabetes (Look AHEAD) trial who had bariatric surgery during the approximately 10‐year randomized intervention.

Methods

Data were obtained from the Look AHEAD public access database of 4,901 individuals with type 2 diabetes and overweight/obesity who were assigned to intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group. Changes in outcomes in participants who had bariatric surgery were compared with those in participants with BMI ≥ 30 kg/m2 who remained in the ILI and DSE groups.

Results

A total of 99 DSE and 97 ILI participants had bariatric surgery. At randomization, these 196 participants were significantly younger and more likely to be female and to have higher BMI than the remaining ILI (N = 1,972) and DSE (N = 2,009) participants. At trial’s end, surgically treated participants lost 19.3% of baseline weight, compared with 5.8% and 3.3% for the ILI and DSE groups, respectively, and were more likely to achieve partial or full remission of their diabetes.

Conclusions

The large, sustained improvements in weight and diabetes observed in this self‐selected sample of surgically treated participants are consistent with results of multiple randomized trials.
An efficient and convenient strategy toward fire safety and water resistance of polypropylene composites through design and synthesis of a novel mono‐component intumescent flame retardant
Authors: Liu Haichao , Li Sheng , Zhang Zhiyong , Li Bin , Xu Miaojun
Published: March 2019

A novel mono‐component flame‐retardant additive poly (dimethylol melamine piperazine pyrophosphate) defined as PDMPP was synthesized from formaldehyde, melamine, and piperazine pyrophosphate. Its chemical structure was well characterized by Fourier transform infrared spectroscopy, 13C and 31P solid‐state nuclear magnetic resonance, and elemental analysis tests. PDMPP was incorporated into polypropylene (PP) matrix, and the fire‐retardant performance, thermal properties, and water resistance of PP composites were investigated in detail. PP/23 wt% PDMPP composites before and after water resistance tests both achieved UL‐94V‐0 grade during vertical burning tests, and the limiting oxygen index was slightly declined from 26.7% to 26.3%. Small amount of PDMPP was extracted by hot water, and the weight loss percentage was 0.67% during water resistance tests. The piperazine and triazine rings in PDMPP contributed to a much better char‐forming capability, and then a greatly expanded and coherent char residue was generated during combustion and exhibited excellent isolation effect. The heat release rate, carbon monoxide production, and smoke production rate of the flame‐retarded PP composites before and after water resistance tests were effectively suppressed to a low level. Consequently, the introduction of PDMPP apparently improved the fire safety of PP composites as well as excellent water‐resistant performance.
Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy‐induced nausea and vomiting in pediatric cancer patients
Authors: Mora Jaume , Valero Miguel , DiCristina Cara , Jin Mandy , Chain Anne , Bickham Kara
Published: March 2019

Background

Current antiemetic regimens are less effective in children than in adults. Fosaprepitant was recently approved for prevention of chemotherapy‐induced nausea and vomiting (CINV) in children aged six months and older.

Procedure

The pharmacokinetic (PK)/pharmacodynamic (PD) profile, safety, and tolerability of a single intravenous dose of fosaprepitant administered concomitantly with ondansetron with/without dexamethasone were evaluated in pediatric patients with cancer receiving emetogenic chemotherapy. PK/PD from three doses of fosaprepitant (3.0, 1.2, and 0.4 mg/kg, up to 150, 60, and 20 mg, respectively) were compared with placebo in 2‐ to 17‐year‐old subjects; an open‐label amendment evaluated a fourth dose (5.0 mg/kg, up to 150 mg) in those under 12 years old. Historical adult PK data were used for comparison. Efficacy was measured as an exploratory endpoint.

Results

PK data were evaluable for 167/234 subjects who completed cycle one. Aprepitant exposures were dose proportional; adolescents (12 to 17 years) receiving fosaprepitant 150 mg had exposures similar to adults at the same dose. Higher weight‐normalized doses (5 mg/kg) were necessary for children aged < 12 years to achieve comparable adult exposures. The adverse event profile was typical of cancer patients receiving emetogenic chemotherapy. Drug‐related adverse events were reported in 16 (6.8%) subjects, with hiccups being most common (n = 5; 2.1%).

Conclusions

Intravenous fosaprepitant was well tolerated by pediatric subjects with cancer, and dose‐proportional exposures were observed. Subjects < 12 years old required higher doses to achieve comparable adult exposures.
End‐tidal carbon dioxide monitoring revealed severe complications during cardiothoracic surgery
Authors: Qiu Yongsheng , Xu Lei , Jia Yingping
Published: March 2019

Introduction

With the continuous progress being made in medicine and surgery, increasingly more advanced technology and monitoring equipment are being used in anesthesia, end‐tidal carbon dioxide (PETCO2) monitoring revealed serious complications of cardiothoracic surgery.

Case presentation

A 3‐year‐old boy with a body weight of 15 kg presented with a >1‐month history of a heart murmur. At the moment of arterial catheter ligation, the PETCO2 decreased from 37 to 15 mmHg, while the blood pressure, heart rate, and airway resistance did not change significantly. After re‐separation of the ligation catheter, the surgeons carefully exposed the ductus and left pulmonary artery again and ligated the ductus arteriosus.

Conclusion

This case suggests that PETCO2 monitoring reflects the circulatory status and pulmonary blood flow.
Central precocious puberty as a prelude of gonad dysplasia
Authors: Li Lele , Gong Chunxiu
Published: March 2019

There is increasing evidence that patients with gonad dysplasia, as characterized by absent or incomplete puberty, can also exhibit central precocious puberty (CPP). Herein, we review the reported cases that manifest with both gonad dysplasia and CPP. Further, we examine the hypothesis that these patients exhibit a normal hypothalamic‐pituitary‐gonadal axis, hypogonadism, and the presence of residual gonadal function, and that the onset of disease is related to early initiation of the hypothalamic‐pituitary‐gonadal axis. Thus, we suggest that CPP is a prelude of some partial hypogonadism.
Personality and Sleep: Neuroticism and Conscientiousness Predict Behaviourally Recorded Sleep Years Later
Authors: Križan Zlatan , Hisler Garrett
Published: March 2019

Sleep is one key feature of people's lives that defines their daily routine and reflects overall health and well–being. To test the relevance of personality for core aspects of sleep, we examined if personality traits across the five broad personality domains predicted behaviourally recorded, week–long sleep characteristics up to five years later (alongside subjective sleep quality). Data from 382 participants (63% female, aged 34–82 years) were drawn from the longitudinal study on Midlife in the United States Study—Biomarker project. In terms of mean tendencies, both neuroticism and conscientiousness signalled more sleep continuity (fewer interruptions) alongside better subjective quality. In terms of intra–individual sleep variability, neuroticism predicted more variability in sleep duration, continuity, and subjective sleep quality, while conscientiousness predicted less variability in sleep duration and sleep continuity. Extraversion, agreeableness, and openness traits did not generally foreshadow behaviourally recoded sleep, only higher ratings of subjective quality. These links were robust to the impact of demographic factors and were not moderated by the duration of time between personality and sleep assessments. The findings distinguish which personality traits foreshadow core aspects of sleep and also implicate multiple traits as predictors of variability, not just mean tendencies, in behaviourally recorded sleep. © 2019 European Association of Personality Psychology
Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1
Authors: Mehnert Martin , Li Wenxue , Wu Chongde , Salovska Barbora , Liu Yansheng
Published: March 2019

CRISPR‐Cas gene editing holds substantial promise in many biomedical disciplines and basic research. Due to the important functional implications of non‐histone chromosomal protein HMG‐14 (HMGN1) in regulating chromatin structure and tumor immunity, gene knockout of HMGN1 is performed by CRISPR in cancer cells and the following proteomic regulation events are studied. In particular, DIA mass spectrometry (DIA‐MS) is utilized, and more than 6200 proteins (protein‐ FDR 1%) and more than 82 000 peptide precursors are reproducibly measured in the single MS shots of 2 h. HMGN1 protein deletion is confidently verified by DIA‐MS in all of the clone‐ and dish‐ replicates following CRISPR. Statistical analysis reveals 147 proteins change their expressions significantly after HMGN1 knockout. Functional annotation and enrichment analysis indicate the deletion of HMGN1 induces histone inactivation, various stress pathways, remodeling of extracellular proteomes, cell proliferation, as well as immune regulation processes such as complement and coagulation cascade and interferon alpha/ gamma response in cancer cells. These results shed new lights on the cellular functions of HMGN1. It is suggested that DIA‐MS can be reliably used as a rapid, robust, and cost‐effective proteomic‐screening tool to assess the outcome of the CRISPR experiments.
Consequences of interleukin 1β‐triggered chronic inflammation in the mouse prostate gland: Altered architecture associated with prolonged CD4+ infiltration mimics human proliferative inflammatory atrophy
Authors: Ashok Arya , Keener Rebecca , Rubenstein Michael , Stookey Stephanie , Bajpai Sagar , Hicks Jessica , Alme Angela K. , Drake Charles G. , Zheng Qizhi , Trabzonlu Levent , Yegnasubramanian Srinivasan , De Marzo Angelo M. , Bieberich Charles J.
Published: March 2019

Background

Elevated expression of the proinflammatory cytokine interleukin 1β (IL‐1β) has been observed in expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome, and genetic polymorphisms associated with the IL1B gene are linked to increased risk for aggressive prostate cancer.

Methods

To study the role of IL‐1β expression in prostate inflammation, we examined IL1B expression in human prostatic proliferative inflammatory atrophy (PIA) lesions and developed a tetracycline‐regulated human IL1B transgene in the mouse prostate.

Results

Here, we demonstrate that IL1B expression is a common finding in human PIA lesions, which harbored focal IL1B expression in epithelial and stromal compartments. Human IL1B expression in the mouse prostate elicited acute and chronic inflammation. Penetrance and expressivity were variable and tunable by altering transgene dosage and the presence of an exogenous inducible marker antigen (green fluorescent protein). Inflammation was characterized by infiltration of CD4+ T cells, demonstrating an adaptive immune response. Chronic inflammation persisted after doxycycline (Dox) withdrawal. Reactive epithelia increased expression of downstream cytokines, and altered glandular architecture was observed upon sustained induction of IL1B. Immunohistochemical analyses revealed a higher proliferative index and decreased Nkx3.1 expression in inflamed mouse prostates.

Conclusions

These data implicate IL‐1β in human prostate pathology and this model provides a versatile platform to interrogate molecular mechanisms of inflammation‐associated prostate pathologies associated with episodic or sustained IL‐1β expression.
The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center
Authors: Nie Ling , Pan Xiuyi , Zhang Mengni , Yin Xiaoxue , Gong Jing , Chen Xueqin , Xu Miao , Zhou Qiao , Chen Ni
Published: March 2019

Background

Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial.

Method

In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core‐needle biopsy in the West China Hospital.

Result

Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P = 0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%,
P = 0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC‐P) (10.0% vs 18.6%,
P = 0.012). Follow‐up analysis found that patients who progressed to castration‐resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)‐sensitive cases (14.1% vs 23.5%,
P = 0.042), but Kaplan‐Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG‐positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases,
ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG‐positive cells were identified neither by IHC nor FISH.

Conclusion

This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC‐P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT.
Long‐lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically‐induced prostatic inflammation
Authors: Ni Jianshu , Mizoguchi Shinsuke , Bernardi Kyrie , Suzuki Takahisa , Kurobe Masahiro , Takaoka Eiichiro , Wang Zhou , DeFranco Donald B. , Tyagi Pradeep , Gu Baojun , Yoshimura Naoki
Published: March 2019

Background

Benign prostatic hyperplasia (BPH) is one of the major causes of lower urinary tract symptoms (LUTS), including storage LUTS such as urinary frequency and urgency. Recently, a growing number of clinical studies indicate that prostatic inflammation could be an important pathophysiological mechanism inducing storage LUTS in patients with BPH. Here we aimed to investigate whether nonbacterial prostatic inflammation in a rat model induced by intraprostatic formalin injection can lead to long‐lasting bladder overactivity and changes in bladder afferent neuron excitability.

Methods

Male Sprague‐Dawley rats were divided into four groups (n = 12 each): normal control group, 1‐week prostatic inflammation group, 4‐week inflammation group, and 8‐week inflammation group. Prostatic inflammation was induced by formalin (10%; 50 µL per lobe) injection into bilateral ventral lobes of the prostate. Voiding behavior was evaluated in metabolic cages for each group. Ventral lobes of the prostate and the bladder were then removed for hematoxylin and eosin (HE) staining to evaluate inflammation levels. Continuous cystometrograms (CMG) were recorded to measure intercontraction intervals (ICI) and voided volume per micturition. Whole‐cell patch clamp recordings were performed on dissociated bladder afferent neurons labeled by fluorogold injected into the bladder wall, to examine the electrophysiological properties.

Results

Results of metabolic cage measurements showed that formalin‐treated rats exhibited significantly (P < 0.05) increases in micturition episodes/12 hours and decrease in voided volume per micturition at every time point post injection. Continuous CMG illustrated the significant (
P < 0.05) higher number of nonvoiding contractions per void and shorter ICI in formalin‐treated rats compared with control rats. HE staining showed significant prostatic inflammation, which declined gradually, in prostate tissues of formalin‐induced rats. In patch clamp recordings, capsaicin‐sensitive bladder afferent neurons from rats with prostatic inflammation had significantly (
P < 0.05) lower thresholds for spike activation and a “multiple” firing pattern compared with control rats at every time point post injection.

Conclusions

Formalin‐induced prostatic inflammation can lead to long‐lasting bladder overactivity in association with bladder afferent neuron hyperexcitability. This long‐lasting model could be a useful tool for the study of inflammation‐related aspects of male LUTS pathophysiology.
The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta‐analysis
Authors: Oh Mok , Alkhushaym Nasser , Fallatah Saad , Althagafi Abdulhamid , Aljadeed Rana , Alsowaida Yazed , Jeter Joanne , Martin Jennifer R. , Babiker Hani M. , McBride Ali , Abraham Ivo
Published: March 2019

Background

A prior meta‐analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent
BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta‐analysis of overall
BRCA mutation carriers and in subgroups to (1) estimate PCa risk in
BRCA mutation carriers, (2) evaluate the frequency of
BRCA mutation carriers in patients with PCa, and (3) compare cancer‐specific survival (CSS) and overall survival (OS) among
BRCA mutation carriers and noncarriers.

Methods

We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type (
BRCA1 or
BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age‐sex‐adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random‐effects models, in two‐sided statistical tests.

Results

A total of 8 cohort, 7 case‐control, 4 case‐series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier (
BRCA1 and/or
BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58‐2.29), with
BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03‐3.47) than
BRCA1 (OR = 1.35, 95% CI = 1.03‐1.76). The frequency of
BRCA1 and
BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64‐2.30) and CSS (HR = 2.63, 95% CI = 2.00‐3.45) were significantly worse among
BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11‐1.99) and CSS (HR = 1.07, 95% CI = 0.38‐2.96) were statistically not significant when comparing
BRCA1 carriers and noncarriers.

Conclusions

There is a 1.90‐fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64‐fold greater risk of PCa in
BRCA2 carriers compared to a moderate 1.35‐fold greater risk in
BRCA1 carriers. The frequency of
BRCA2 mutations was higher than
BRCA1 mutations among patients with PCa.
BRCA2 but not
BRCA1 mutations were associated with higher PCa mortality. The
BRCA mutation may be a clinical factor to stratify high‐risk patients and guide clinical strategies for more effective treatments for patients with PCa.
Dietary palmitate cooperates with Src kinase to promote prostate tumor progression
Authors: Kim Sungjin , Yang Xiangkun , Yin Amelia , Zha Junyi , Beharry Zanna , Bai Aiping , Bielawska Alicja , Bartlett Michael G. , Yin Hang , Cai Houjian
Published: March 2019

Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer. In this study, we demonstrate that high‐fat diets (HFDs) promoted pathological transformation mediated by the synergy of Src and androgen receptor in vivo. Additionally, a diet high in saturated fat significantly enhanced proliferation of Src‐mediated xenograft tumors in comparison with a diet high in unsaturated fat. The saturated fatty acid palmitate, a major constituent in a HFD, significantly upregulated the biosynthesis of palmitoyl‐CoA in cancer cells in vitro and in xenograft tumors in vivo. The exogenous palmitate enhanced Src‐dependent mitochondrial β‐oxidation. Additionally, it elevated the amount of C16‐ceramide and total saturated ceramides, increased the level of Src kinase localized in the cell membrane, and Src‐mediated downstream signaling, such as the activation of mitogen‐activated protein kinase and focal adhesion kinase. Our results uncover how the metabolism of dietary palmitate cooperates with elevated Src kinase in the acceleration of prostate tumor progression.
Optical, Electrical, and Thermoelectric Properties of Hydrothermally Synthesized Bi2Te3 Nanoflakes
Authors: Mohamed Mohamed Abdullah Abdullah , Ali Hazem Mahmoud , Ibrahim Eslam Mohamed Mohamed , Wakkad Moustafa Mohamed
Published: March 2019

Thermoelectric power generators are promising for clean energy production through converting the waste heat to electricity in environmentally friendly ways without any noise or pollutants. This work reports a facile method to synthesize Bi2Te3 nanoflakes with an investigation of their structural, optical, and thermoelectric properties. Various techniques such as X‐ray diffraction, field emission scanning electron microscope, transmission electron microscope, and energy dispersive spectroscopy are used to characterize the synthesized compound. The results confirmed that the nanoflakes crystallize in a rhombohedral structure with an average diameter and thickness ≈31.2 and 27 nm, respectively. A narrow optical band gap of 0.43 eV is determined for the prepared nanoflakes confirming the potential of employing the nanoflakes in optoelectronic applications. The results of the thermoelectric measurements imply that the synthesized nanoflakes have high power factor values at high temperatures compared to those previously reported for the same compound by other research groups. The power factor values make the synthesized nanoflakes promising candidate for thermoelectric applications.
Does bottle color protect red wine from photo‐oxidation?
Authors: Guerrini Lorenzo , Pantani Ottorino‐Luca , Politi Styliani , Angeloni Giulia , Masella Piernicola , Calamai Luca , Parenti Alessandro
Published: March 2019

Even if bottled red wines have an extended shelf life, they undergo several chemical changes, and producers are well aware of the importance of the packaging. However, there is a lack of research into the effect of light on their composition. Therefore, the storage conditions of a Sangiovese wines with respect to artificial light exposure (present/absent) and bottle color (transparent, brown, and green) were investigated. Thirty‐five chemical characteristics (physicochemical, UV‐VIS indexes, and volatile compounds) were recorded after 6 months of storage. Light exposure caused significant differences in total SO2 and a shift from red to yellow/orange color. For wines kept in transparent bottles, total red pigments, total phenol index, monomeric anthocyanins, copigmentation, chemical age, and some volatile compounds showed significant differences, depending on whether it was exposed to light or not. On the contrary, light exposure was found not significant for the wine stored in green and brown bottles, Finally, an overall increase in variability was found for light‐exposed wine in transparent bottles which could be considered, in itself, a measure of lack of quality.
A linguistic risk prioritization approach for failure mode and effects analysis: A case study of medical product development
Authors: Wang Liang , Hu Yu‐Ping , Liu Hu‐Chen , Shi Hua
Published: March 2019

Failure mode and effects analysis (FMEA) is a widely used risk management technique for identifying the potential failures from a system, design, or process and determining the most serious ones for risk reduction. Nonetheless, the traditional FMEA method has been criticized for having many deficiencies. Further, in the real world, FMEA team members are usually bounded rationality, and thus, their psychological behaviors should be considered. In response, this study presents a novel risk priority model for FMEA by using interval two‐tuple linguistic variables and an integrated multicriteria decision‐making (MCDM) method. The interval two‐tuple linguistic variables are used to capture FMEA team members' diverse assessments on the risk of failure modes and the weights of risk factors. An integrated MCDM method based on regret theory and TODIM (an acronym in Portuguese for interactive MCDM) is developed to prioritize failure modes taking experts' psychological behaviors into account. Finally, an illustrative example regarding medical product development is included to verify the feasibility and effectiveness of the proposed FMEA. By comparing with other existing methods, the proposed linguistic FMEA approach is shown to be more advantageous in ranking failure modes under the uncertain and complex environment.
Characterization of the all‐E. coli transcription‐translation system myTXTL by mass spectrometry
Authors: Garenne David , Beisel Chase L. , Noireaux Vincent
Published: March 2019

Rationale

Cell‐free transcription‐translation (TXTL) is becoming a popular technology to prototype and engineer biological systems outside living organisms. TXTL relies commonly on a cytoplasmic extract that provides the molecular components necessary to recapitulate gene expression in vitro, where most of the available systems are derived from E. coli. The proteinic and enzymatic composition of lysates, however, is typically unknown. In this work, we analyzed by mass spectrometry the molecular constituents of the all‐E. coli TXTL platform myTXTL prepared from the E. coli strain BL21 Rosetta2.

Methods

Standard TXTL reactions were assembled and executed for 10–12 hours at 29°C. In addition to a no‐DNA control, four DNA programs were executed in separate reactions to synthesize the reporter protein deGFP as well as the phages MS2, phix174 and T7. The reactions were treated according to standard procedures (trypsin treatment, cleaning) before performing liquid chromatography/mass spectrometry (LC/MS). Data analysis was performed using Sequest and protein identification using Scaffold.

Results

A total of 500–800 proteins were identified by LC/MS in the blank reactions. We organized the most abundant protein sets into several categories pertaining, in particular, to transcription, translation and ATP regeneration. The synthesis of deGFP was easily measured. The major structural proteins that compose the three phages MS2, phix174 and T7 were also identified.

Conclusions

Mass spectrometry is a practical tool to characterize biochemical solutions as complex as a cell‐free TXTL reaction and to determine the presence of synthesized proteins. The data presented demonstrate that the composition of TXTL based on lysates can be used to validate some underlying molecular mechanisms implicated in cell‐free protein synthesis. The composition of the lysate shows significant differences with respect to similar studies on other E. coli strains.