bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional differences in Purkinje cell morphology in the cerebellar vermis of male mice
Authors: Nedelescu Hermina , Abdelhack Mohamed , Pritchard Arwel T.
Published: January 2018

Regional differences in dendritic architecture can influence connectivity and dendritic signal integration, with possible consequences for neuronal computation. In the cerebellum, analyses of Purkinje cells (PCs), which are functionally critical as they provide the sole output of the cerebellar cortex, have suggested that the cerebellar cortex is not uniform in structure as traditionally assumed. However, the limitations of traditional staining methods and microscopy capabilities have presented difficulties in investigating possible local variations in PC morphology. To address this question, we used male mice expressing green fluorescent protein selectively in PCs. Using Neurolucida 360 with confocal image stacks, we reconstructed dendritic arbors of PCs residing in lobule V (anterior) and lobule IX (posterior) of the vermis. We then analyzed morphologies of individual arbors and the structure of the assembled “jungle,” comparing these features across anatomical locations and age groups. Strikingly, we found that in lobule IX, half of the reconstructed PCs had two primary dendrites emanating from their soma, whereas fewer than a quarter showed this characteristic in lobule V. Furthermore, PCs in lobule V showed more efficient spatial occupancy compared to lobule IX, as well as greater packing density and increased arbor overlap in the adult. When analyzing complete ensembles of PC arbors, we also observed “hot spots” of increased dendritic density in lobule V, whereas lobule IX showed a more homogeneous spread of dendrites. These differences suggest that input patterns and/or physiology of PCs could likewise differ along the vermis, with possible implications for cerebellar function.
Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease
Authors: Pike Nancy A. , Roy Bhaswati , Gupta Ritika , Singh Sadhana , Woo Mary A. , Halnon Nancy J. , Lewis Alan B. , Kumar Rajesh
Published: January 2018

Background

Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2‐relaxometry procedures, which measure free water content and show tissue injury.

Methods

Proton‐density and T2‐weighted images, using a 3.0‐Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire‐9 [PHQ‐9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole‐brain T2‐relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001).

Results

SVHD subjects showed significantly increased BAI and PHQ‐9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2‐relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para‐hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2‐relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD.

Conclusions

Adolescents with SVHD showed significant brain injury with variable male–female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition.
The onset of fretting at the head‐stem connection in hip arthroplasty is affected by head material and trunnion design under simulated corrosion conditions
Authors: Rowan Fiachra E. , Wach Amanda , Wright Timothy M. , Padgett Douglas E.
Published: January 2018

Mechanically assisted crevice corrosion (MACC) is a mechanism for trunnion damage in total hip arthroplasties (THAs). Retrieval studies have shown reduced MACC‐related damage for ceramic heads compared with cobalt–chromium (CoCr) heads. We propose that ceramic heads demonstrate fretting at higher cyclic compressive loads than CoCr heads on titanium alloy trunnions in a simulated corrosion model. A closed electrochemical chamber was used to measure fretting current onset loads for two modern titanium alloy trunnions (Zimmer 12/14 and Stryker V‐40) in which trunnion failure has been reported. Ceramic and CoCr alloy 36 + 0 mm heads were impacted on each trunnion and cyclically loaded at 3 Hz with increasing magnitude from 100 to 3,400 N for 540 cycles. Onset load was the cyclic compressive load at which the slope of the average fretting current increased significantly. A CoCr head with V40 trunnion demonstrated the lowest onset load (1,400 N), while the V40 trunnion with a ceramic head showed the highest onset load (2,200 N). Significant differences occurred in average fretting current between head materials for V40 trunnions (p < 0.001) at loads over 2,000 N. CoCr‐12/14 and ceramic‐12/14 couples demonstrated similar onset loads (2,000 N). All head–trunnion combinations showed cyclical fretting response to loading at 100 N. Head material composition was observed to increase fretting at the taper junction but the effect was taper geometry dependent. Using ceramic heads may reduce the phenomena of trunnion fretting and corrosion but the effect of both trunnion geometry and metallurgy warrants further investigation. Statement of clinical significance: Trunnion corrosion may occur with titanium alloy stems regardless of the head material used. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1630–1636, 2018.
Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis
Authors: Maerz Tristan , Sherman Eric , Newton Michael , Yilmaz Ali , Kumar Praveen , Graham Stewart F. , Baker Kevin C.
Published: January 2018

ACL rupture is a major risk factor for post‐traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. Thirty‐six female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post‐injury time points: 72 h, 4 weeks, 10 weeks (n = 6). Serum was collected and analyzed by1H nuclear magnetic resonance (NMR) spectroscopy and combined direct injection and liquid chromatography (LC)‐mass spectrometry (MS)/MS (DI‐MS). Univariate and multivariate statistics were used to analyze metabolomic data, and predictive biomarker models were analyzed by receiver operating characteristic (ROC) analysis. Topological pathway analysis was used to identify perturbed pathways. Two hundred twenty‐two metabolites were identified by1H NMR and DI‐MS. Differences in the serum metabolome between ACLR and Control were dominated by medium‐ and long‐chain acylcarnitine species. Further, decreases in several tryptophan metabolites were either found to be significantly different in univariate analysis or to play important contributory roles to multivariate model separation. In addition to acylcarnitines and tryptophan metabolites, glycine, carnosine, and D‐mannose were found to differentiate ACLR from Control. Glycine, 9‐hexadecenoylcarnitine, trans‐2‐Dodecenoylcarnitine, linoelaidyl carnitine, hydroxypropionylcarnitine, and D‐Mannose were identified as biomarkers with high area under ROC curve values and high predictive accuracies. Our analysis provides new information regarding the potential contribution of inflammatory processes and immune dysregulation to the onset and progression of PTOA following ACL injury. As these processes have most commonly been associated with inflammatory arthropathies, larger‐scale studies elucidating their involvement in PTOA development and progression are necessary. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1969–1979, 2018.
Feasibility of Assessing Prognostic Nutrition Index in Patients With Rectal Cancer Who Receive Preoperative Chemoradiotherapy
Authors: Okugawa Yoshinaga , Toiyama Yuji , Oki Satoshi , Ide Shozo , Yamamoto Akira , Ichikawa Takashi , Kitajima Takahito , Fujikawa Hiroyuki , Yasuda Hiromi , Saigusa Susumu , Hiro Junichiro , Yoshiyama Shigeyuki , Kobayashi Minako , Araki Toshimitsu , Kusunoki Masato
Published: January 2018

Background

Malnutrition can adversely affect treatment responses and oncological outcomes in cancer patients. However, among patients with rectal cancer who undergo chemoradiotherapy (CRT), the significance of peri‐treatment nutrition assessment as a predictor of treatment response and outcome remains unclear.

Objective

The aim of this study was to determine whether the Prognostic Nutrition Index (PNI) based on peri‐treatment serum can be used as a predictor of treatment response and outcome in patients with rectal cancer who undergo CRT.

Design, Setting, and Patients

We analyzed 114 patients with rectal cancer who received preoperative CRT followed by total mesorectal excision at our institution.

Results

Post‐CRT PNI was significantly lower than pre‐CRT PNI in rectal cancer patients. Although post‐CRT PNI did not significantly correlate with either overall survival or disease‐free survival, low pre‐CRT PNI was significantly associated with shorter overall survival and disease‐free survival in this population and was also an independent risk factor for ineffectiveness of long‐course preoperative CRT. Finally, low pre‐CRT PNIs were a stronger indicator of poor prognosis and early recurrence in patients with pathological lymph node metastasis (who generally need to receive postoperative chemotherapy), than in those with no pathological lymph node metastasis.

Conclusion

Pretreatment PNI could be useful in evaluating and managing patients with rectal cancer who undergo CRT followed by curative resection.
Influence of the drying method on the bioactive compounds and pharmacological activities of rhubarb
Authors: Sun Jiachen , Wu Yueting , Dong Shengjie , Li Xia , Gao Wenyuan
Published: January 2018

BACKGROUND

Raw rhubarb samples that have been subjected to different drying procedures will have different therapeutic effects, possibly due to processing‐induced variations in the chemical composition. In the present work, the fresh materials were processed by smoking, sun‐drying, shade‐drying and oven‐drying at low, moderate and high temperatures. To facilitate the selection of a suitable drying method for rhubarb, the quality of rhubarb processed under various drying conditions was evaluated based on the simultaneous determination of multiple bioactive constituents in combination with bioactivity assays.

RESULTS

The total concentrations of 12 compounds in smoked rhubarb were higher than the concentrations of the same components in raw rhubarb and rhubarb products processed using other drying techniques. Smoked rhubarb was found to substantially inhibit Na+/K+‐ATPase and thrombin. In addition, higher content of anthraquinones led to higher Na+/K+‐ATPase inhibitory activities, and higher gallic acid content increased the antithrombin capacity.

CONCLUSION

The results confirmed that post‐harvest fresh plant materials, especially roots, were still physiologically active organs that could undergo series of anti‐dehydration mechanisms, including the production of related secondary metabolites during the early stages of dehydration. Therefore, the proper design of drying processes could enhance the quality of rhubarb as well as other similar medicinal plants. © 2018 Society of Chemical Industry
The effect of cooking temperature on the aggregation and digestion rate of myofibrillar proteins in Jinhua ham
Authors: Zhou Chang‐Yu , Pan Dao‐Dong , Sun Yang‐Ying , Li Chun‐Bao , Xu Xing‐Lian , Cao Jin‐Xuan , Zhou Guang‐Hong
Published: January 2018

BACKGROUND

In order to evaluate the effect of cooking temperature on the nutrition quality of dry‐cured hams, 60 biceps femoris samples from 16 Jinhua hams were divided into four groups (control, 70, 100 and 120 °C) and cooked for 30 min. Carbonyl content, sulfhydryl groups, surface hydrophobicity, microstructure, protein aggregation and digestibility of myofibrillar proteins were investigated.

RESULTS

Cooking promoted carbonylation and decreased sulfhydryl groups in a temperature‐dependent way. Scanning electron microscopy and Nile Red revealed that protein aggregation became a main phenomenon at 120 °C; it coincided with surface hydrophobicity. The increased carbonyl content and decreased sulfhydryl groups contributed to the formation of aggregates. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis profiles showed the initial difference in proteolysis rate among four groups. The in vitro digestibility of pepsin and of trypsin and α‐chymotrypsin increased from the control to 100 °C and decreased from 100 to 120 °C.

CONCLUSION

The increased digestibility could be attributed to the oxidation of proteins and exposing recognition sites of digestive enzymes, while the decreased digestibility was due to the formation of aggregates. Cooking was a main factor that affected the digestibility of Jinhua ham, and cooking at 100 °C could be an ideal way to gain the highest digestibility of Jinhua ham. © 2018 Society of Chemical Industry
Preferential adsorption of flavonoids from peanut shell by amino‐modified Fe3O4 nanoparticles (MNP‐NH2)
Authors: Cao Xuexiao , Wang Meng , Sun Lili , Ren Xiaoliang , Pei Gaosheng
Published: January 2018

BACKGROUND

The highly selective capture of individual components of complex systems such as Chinese medicine extracts is a great challenge. With the rapid development of nanoscience, magnetic materials have attracted increased attention as suitable candidates for use in drug transport vehicles.

RESULTS

In this work, amino‐modified Fe3O4 nanoparticles (MNP‐NH2) have been synthesized and successfully used to selectively isolate luteolin, a type of flavonoid, from peanut shell, coupled with high‐performance liquid chromatography. MNP‐NH2 were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometer analysis, which showed that the amino functional groups were successfully bound to the surface of the magnetic particles. Adsorption of six different flavonoids by MNP‐NH2 showed that the mechanism of adsorption was related to the number of ortho‐phenolic hydroxyl groups. The optimized adsorption conditions were extraction for 40 min at 30 °C by single‐factor experiments and the final elution conditions were determined to be 5 mL of 20% glacial acetic acid (methanol:water = 60:40) and ultrasonication for 40 min by L9 (34) orthogonal test.

CONCLUSION

Based on these findings, we first created a method for separating luteolin from peanut shell extract by MNP‐NH2. This newly developed magnetic method of extracting chemical compounds from herbal foodstuffs and medicines provides new ideas for the utilization of a cash crop. © 2018 Society of Chemical Industry
Unraveling the metabolic response of Brassica oleracea exposed to Xanthomonas campestris pv. campestris
Authors: Tortosa María , Cartea María E , Rodríguez Víctor M , Velasco Pablo
Published: January 2018

BACKGROUND

Brassica crops together with cereals represent the basis of world supplies. Due to their importance, the production losses caused by Xanthomonas campestris pv. campestris (Xcc) infection represent a high economic impact. Understanding molecular and biochemical mechanisms of plants is essential to develop resistant crops with durable protection against diseases. In this regard, metabolomics has emerged as a valuable technology to provide an overview of the biological status of a plant exposed to a disease. This study investigated the dynamic changes in the metabolic profile of Brassica oleracea plants during an Xcc infection from leaves collected at five different days post infection using a mass spectrometry approach.

RESULTS

Results showed that Xcc infection causes dynamic changes in the metabolome of B. oleracea. Moreover, induction/repression pattern of the metabolites implicated in the response follows a complex dynamics during infection progression, indicating a complex temporal response. Specific metabolic pathways such as alkaloids, coumarins or sphingolipids are postulated as promising key role candidates in the infection response.

CONCLUSION

This work tries to decipher the changes produced on Brassica crops metabolome under Xcc infection and represents a step forward in the understanding of B. oleracea–Xcc interaction. © 2018 Society of Chemical Industry
The health‐nutrition dimension: a methodological approach to assess the nutritional sustainability of typical agro‐food products and the Mediterranean diet
Authors: Azzini Elena , Maiani Giuseppe , Turrini Aida , Intorre Federica , Lo Feudo Gabriella , Capone Roberto , Bottalico Francesco , El Bilali Hamid , Polito Angela
Published: January 2018

BACKGROUND

The aim of this paper is to provide a methodological approach to evaluate the nutritional sustainability of typical agro‐food products, representing Mediterranean eating habits and included in the Mediterranean food pyramid.

RESULTS

For each group of foods, suitable and easily measurable indicators were identified. Two macro‐indicators were used to assess the nutritional sustainability of each product. The first macro‐indicator, called ‘business distinctiveness’, takes into account the application of different regulations and standards regarding quality, safety and traceability as well as the origin of raw materials. The second macro‐indicator, called ‘nutritional quality’, assesses product nutritional quality taking into account the contents of key compounds including micronutrients and bioactive phytochemicals. For each indicator a 0–10 scoring system was set up, with scores from 0 (unsustainable) to 10 (very sustainable), with 5 as a sustainability benchmark value. The benchmark value is the value from which a product can be considered sustainable. A simple formula was developed to produce a sustainability index.

CONCLUSION

The proposed sustainability index could be considered a useful tool to describe both the qualitative and quantitative value of micronutrients and bioactive phytochemical present in foodstuffs. This methodological approach can also be applied beyond the Mediterranean, to food products in other world regions. © 2018 Society of Chemical Industry
Vacuum impregnation of firming agents in red raspberries
Authors: Quintanilla Armando , Mencía Alejandra , Powers Joseph , Rasco Barbara , Tang Juming , Sablani Shyam S
Published: January 2018

BACKGROUND

Red raspberries are a delicate and highly perishable fruit with a fragile pulp tissue. In this study we used vacuum impregnation (VI) methods to incorporate pectin and calcium chloride into whole red raspberries to improve their firmness. Specifically, we impregnated low methoxyl pectin (LMP) at 10 g of pectin kg−1 of solution and calcium chloride (CaCl2·2H2O) at 30 g calcium kg−1 of pectin, and on the other side pectin methylesterase (PME) at 10 g of enzyme kg−1 of solution, and (CaCl2·2H2O) at 10 g of calcium kg−1 of solution, into whole red raspberries. We tested three vacuum levels 33.9, 50.8, and 67.8 kPa, three vacuum impregnation times 2, 7, and 15 min, and two temperatures, 20 and 40 °C, during VI treatment. Maximum force (FM) and gradient (GC3) were evaluated to assess raspberry firmness.

RESULTS

A vacuum level of 50.8 kPa, processing time of 7 min, and a LMP and calcium infusion at 20 °C resulted in the firmest fruit compared to the other treatments. At these VI treatment conditions, FM and GC3 values of red raspberries obtained were 28 N, and 8.4 N mm−1, respectively.

CONCLUSION

The optimal VI conditions identified in this study can be used to improve firmness and structural integrity of red raspberries by infusion of LMP and calcium. Findings on vacuum‐impregnated red raspberries may be used to develop dehydrofrozen berries for incorporation into bakery and dairy products. © 2018 Society of Chemical Industry
Evaluation of extended antibiotic prophylaxis in patients undergoing indicated non‐cosmetic panniculectomy at the time of gynecologic surgery
Authors: Patibandla Jay R. , Kufel Christina N. , Hopkins Michael P.
Published: January 2018

Background

Panniculectomy at time of gynecologic surgery is used to improve visualization and prevent major complications in morbidly obese patients. We examine the role of extended antibiotic prophylaxis in prevention of surgical site infections (SSI), specifically based on patient risk factors (hypertension, diabetes, smoking).

Methods

A prospective cohort study of all women who underwent panniculectomy at the time of gynecologic surgery from September 2014 to March 2016 at a university‐affiliated hospital. The EAP cohort received standard antibiotics (cefazolin, 2 g) and continued oral antibiotic (doxycycline) for 10 days afterwards. Patients in this cohort were compared to historical controls from the same institution from 1990 to 2014. Specific attention was paid to the reduction of SSIs in patients with hypertension, diabetes, and a history of smoking.

Results

The mean age was 56.0 ± 12.6 years, and mean body mass index 44.5 ± 9.3 kg/m2 (range 31‐63.4 kg/m2). The EAP cohort experienced fewer surgical‐site infections overall, however these results were not significantly decreased from the historical controls, (13/56 [23.2%] vs 94/300 [31.3%]; P = 0.469).

Conclusion

Though initially promising, extended antibiotic prophylaxis did not reduce surgical site infections in the obese women after indicated non‐cosmetic panniculectomy at the time of gynecologic surgery.
Determination of synephrine in feeds by a novel quick, easy, cheap, effective, rugged, and safe solid‐phase extraction method combined with UHPLC–MS/MS
Authors: Song Yue , Chai Tingting , Lou Shengting , Zhao Yuechen , Zhang Xining , Yang Shuming , Qian Yongzhong , Qiu Jing
Published: January 2018

To detect and quantify synephrine in feed, an effective analytical method based on quick, easy, cheap, effective, rugged, and safe solid‐phase extraction coupled to ultra high performance liquid chromatography with tandem mass spectrometry was developed with isotopic internal standards. Pretreatment was performed using quick, easy, cheap, effective, rugged, and safe solid‐phase extraction with primary secondary amine and C18 sorbent as sorbents in combination with Oasis MCX column clean‐up to extract and purify feed samples. Tandem mass spectrometry detection in positive ion mode was conducted in positive multiple reaction monitoring mode in addition to the quantitative internal standard method. Two transitions of synephrine at m/z 168.1/150.0 and 168.1/135.0 were selected, and m/z 168.1/135.0 was determined as the quantification ion pair. D9‐Terbutaline was selected as an internal standard, for which m/z 235.1/153.0 was selected as the quantification ion pair. Good linearity was shown for synephrine in the range of 0.5–50 μg/L, and the correlation coefficient exceeded 0.999. The recoveries in three different feed samples at three spiked levels were 81.42–112.08%, and the relative standard deviations were not greater than 14.66%. The method proposed in this study was reliable and highly effective, and its sensitivity, accuracy, and precision are suitable for determining synephrine residues in feed samples.
An assessment of value dimensions in hiking tourism: Pathways toward quality of life
Authors: Lee Seonjeong Ally , Manthiou Aikaterini , Chiang Lanlung , Tang Liang Rebecca
Published: January 2018

Enhancing quality of life is one of the primary motives for people to participate in tourism activities. Particularly, hiking tourism has become increasingly popular in recent years due to its benefits on tourists' physical and mental health. Focusing on the context of hiking tourism, this study examined the role of tourists' perceived value on their quality of life through the engagement and connections with nature. Data were collected from hikers in the Astraka Refuge between two mountains, Astraka and Lapatos, in Greece. The results indicated that tourists' perceived value influences their engagement in hiking tourism and connections with nature, which further lead to their quality of life. This study enriches the literature of quality of life by the investigation of the term in the hiking tourism context. The results also provide suggestions for destination marketers to promote hiking tourism.
Circadian genes and risk of prostate cancer in the prostate cancer prevention trial
Authors: Chu Lisa W. , Till Cathee , Yang Baiyu , Tangen Catherine M. , Goodman Phyllis J. , Yu Kai , Zhu Yong , Han Summer , Hoque Ashraful M. , Ambrosone Christine , Thompson Ian , Leach Robin , Hsing Ann W.
Published: January 2018

Circadian genes have been considered as a possible biological mechanism for the observed relationship between circadian rhythm disruptions and increased risk of hormone‐related cancers. In the current study, we investigated the relationship between circadian gene variants and prostate cancer risk and whether reducing bioavailable testosterone modifies the circadian genes‐prostate cancer relationship. We conducted a nested case‐control study among Caucasian men in the Prostate Cancer Prevention Trial (PCPT), a randomized placebo‐controlled clinical trial to assess if finasteride (an androgen bioactivation inhibitor) could prevent prostate cancer. We evaluated the associations between 240 circadian gene variations and prostate cancer risk among 1092 biopsy‐confirmed prostate cancer cases and 1089 biopsy‐negative controls in the study (642 cases and 667 controls from the placebo group; 450 cases and 422 controls from the finasteride group), stratified by treatment group. Among men in the finasteride group, there were suggestive associations between NPAS2 variants and total prostate cancer risk, with one SNP remaining statistically significant after Bonferroni correction (rs746924, odds ratio [OR] = 1.5, P = 9.6 × 10−5). However, we found little evidence of increased prostate cancer risk (overall or by low/high grade) associated with circadian gene variations in men of the placebo group, suggesting potential modification of genetic effects by treatment. We did not find strong evidence that circadian gene variants influenced prostate cancer risk in men who were not on finasteride treatment. There were suggestive associations between NPAS2 variants and prostate cancer risk among men using finasteride, which warrants further investigations.
Genetic and small molecule inhibition of arylamine N‐acetyltransferase 1 reduces anchorage‐independent growth in human breast cancer cell line MDA‐MB‐231
Authors: Stepp Marcus W. , Doll Mark A. , Carlisle Samantha M. , States J. Christopher , Hein David W.
Published: January 2018

Arylamine N‐acetyltransferase 1 (NAT1) expression is reported to affect proliferation, invasiveness, and growth of cancer cells. MDA‐MB‐231 breast cancer cells were engineered such that NAT1 expression was elevated or suppressed, or treated with a small molecule inhibitor of NAT1. The MDA‐MB‐231 human breast cancer cell lines were engineered with a scrambled shRNA, a NAT1 specific shRNA or a NAT1 overexpression cassette stably integrated into a single flippase recognition target (FRT) site facilitating incorporation of these different genetic elements into the same genomic location. NAT1‐specific shRNA reduced NAT1 activity in vitro by 39%, increased endogenous acetyl coenzyme A levels by 35%, and reduced anchorage‐independent growth (sevenfold) without significant effects on cell morphology, growth rates, anchorage‐dependent colony formation, or invasiveness compared to the scrambled shRNA cell line. Despite 12‐fold overexpression of NAT1 activity in the NAT1 overexpression cassette transfected MDA‐MB‐231 cell line, doubling time, anchorage‐dependent cell growth, anchorage‐independent cell growth, and relative invasiveness were not changed significantly when compared to the scrambled shRNA cell line. A small molecule (5E)‐[5‐(4‐hydroxy‐3,5‐diiodobenzylidene)‐2‐thioxo‐1,3‐thiazolidin‐4‐one (5‐HDST) was 25‐fold more selective towards the inhibition of recombinant human NAT1 than N‐acetyltransferase 2. Incubation of MDA‐MB‐231 cell line with 5‐HDST resulted in 60% reduction in NAT1 activity and significant decreases in cell growth, anchorage‐dependent growth, and anchorage‐independent growth. In summary, inhibition of NAT1 activity by either shRNA or 5‐HDST reduced anchorage‐independent growth in the MDA‐MB‐231 human breast cancer cell line. These findings suggest that human NAT1 could serve as a target for the prevention and/or treatment of breast cancer.
An instrumental variable approach to distinguishing perceptions from preferences for beer brands
Authors: Malone Trey , Lusk Jayson L.
Published: January 2018

Recent developments in behavioral economics have prompted interest in identifying how product perceptions and beliefs influence decision making. Using a branded discrete choice experiment for beer, this article uses the control function approach and plausible instruments to correct for the endogeneity problem in a way that is applicable in a wide range of circumstances. Even after correction, we find that perceptions substantially affect consumer choices. In the context of brand equity for beer brands, we find that the perceived taste and brand familiarity are key determinants of choice.
Local and systemic coagulation marker response to musculocutaneous flap ischemia–reperfusion injury and remote ischemic conditioning: An experimental study in a porcine model
Authors: Krag Andreas Engel , Hvas Christine Lodberg , Kiil Birgitte Jul , Eschen Gete Toft , Damsgaard Tine Engberg , Hvas Anne‐Mette
Published: January 2018

Background

Remote ischemic conditioning (RIC) administered by non‐lethal periods of extremity ischemia and reperfusion attenuates ischemia–reperfusion injury. We aimed to investigate the local and systemic coagulation marker response to flap ischemia–reperfusion injury, and the effects of RIC on coagulation markers following flap ischemia–reperfusion injury.

Methods

A musculocutaneous latissimus dorsi flap was subjected to 4 h of ischemia followed by 7 h of reperfusion in 16 female Danish Landrace pigs (39 kg). Systemic venous blood samples were collected 1 h before flap reperfusion. Flap and systemic venous blood samples were collected at reperfusion and hourly during reperfusion. We measured thrombin generation, fibrinogen, von Willebrand factor, antithrombin, thrombin‐antithrombin complex, activated partial thromboplastin time (aPTT), and prothrombin time (PT). RIC was performed 1 h before flap reperfusion in the intervention group by three 10‐min periods of hind limb ischemia and reperfusion (n = 8). RIC was not performed in the control group (n = 8).

Results

Local and systemic coagulation marker changes were comparable following flap ischemia–reperfusion injury. Flap ischemia–reperfusion injury reduced thrombin generation lag time from 2.0 ± 0.3 to 1.6 ± 0.3 min (P < .001), time‐to‐peak thrombin from 3.5 ± 0.3 to 3.0 ± 0.5 min (P = .001), peak thrombin from 79.6 ± 8.1 to 74.5 ± 7.1 nM (P = .033), endogenous thrombin potential from 211 ± 24 to 197 ± 19 nM × min (P = .01), antithrombin from 0.91 ± 0.07 to 0.79 ± 0.06 103 IU/l (P = .002), and aPTT from 37 ± 21 to 21 ± 9 s (P = .017). RIC increased peak thrombin (P < .001), endogenous thrombin potential (P < .001), and aPTT (P = .019).

Conclusions

The local coagulation marker response to musculocutaneous flap ischemia–reperfusion could be measured systemically by moderate hypercoagulation. RIC did not substantially influence coagulation markers following musculocutaneous flap ischemia–reperfusion injury.
A collagen‐coated PGA conduit for interpositional‐jump graft with end‐to‐side neurorrhaphy for treating facial nerve paralysis in rat
Authors: Niimi Yosuke , Matsumine Hajime , Takeuchi Yuichi , Hironobu Osaki , Tsunoda Satoshi , Miyata Mariko , Yamato Masayuki , Sakurai Hiroyuki
Published: January 2018

Purpose

This study investigated the potential of collagen‐coated polyglycolic acid (PGA) tube with interpositional jump graft (IPJG) in rat.

Materials and Methods

A total of 16 Lewis rats were used in this study. Facial nerve paralysis was created by ligating facial nerve trunk with a ligature clip. The rats were divided into 3 groups. Nerve conduit group (n = 6) were treated by IPJG with collagen‐coated PGA tubes between the facial nerve trunks and the hypoglossal nerves. Autograft group (n = 6) were treated by IPJG with the greater auricular nerves. As the control group (n = 4), non‐treated‐model rats with facial nerve paralysis were used. The number of myelinated fibers, fiber diameter, axon diameter, myelin thickness, and g‐ratio, were analyzed histologically at 13 weeks after surgery. Compound muscle action potential (CMAP) and retrograde tracing were measured.

Result

Although the number of myelinated fibers in autograft group (1957 ± 775) had significantly higher than that of nerve conduit group (90 ± 41, P < .05), the nerve conduit group showed the regeneration of myelinated nerve axons. CMAP amplitude values of the autograft (4706 ± 1154 µV) and the nerve conduit groups (4119 ± 1397 µV) were significantly higher than that of the control group (915 ± 789 µV, P < .05). Retrograde tracing confirmed the double innervation of mimetic muscles by the facial and hypoglossal nucleus in both groups.

Conclusion

This study showed histologically and physiologically the superior effectiveness of performing IPJG with a collagen‐coated PGA conduit in a rat model.
De Novo Design of Bioactive Small Molecules by Artificial Intelligence
Authors: Merk Daniel , Friedrich Lukas , Grisoni Francesca , Schneider Gisbert
Published: January 2018

Generative artificial intelligence offers a fresh view on molecular design. We present the first‐time prospective application of a deep learning model for designing new druglike compounds with desired activities. For this purpose, we trained a recurrent neural network to capture the constitution of a large set of known bioactive compounds represented as SMILES strings. By transfer learning, this general model was fine‐tuned on recognizing retinoid X and peroxisome proliferator‐activated receptor agonists. We synthesized five top‐ranking compounds designed by the generative model. Four of the compounds revealed nanomolar to low‐micromolar receptor modulatory activity in cell‐based assays. Apparently, the computational model intrinsically captured relevant chemical and biological knowledge without the need for explicit rules. The results of this study advocate generative artificial intelligence for prospective de novo molecular design, and demonstrate the potential of these methods for future medicinal chemistry.
Dynamics of an age‐structured host‐vector model for malaria transmission
Authors: Wang Xia , Chen Yuming , Liu Shengqiang
Published: January 2018

In this paper, we propose a host‐vector model for malaria transmission by incorporating infection age in the infected host population and nonlinear incidence for transmission from infectious vectors to susceptible hosts. One novelty of the model is that the recovered hosts only have temporary immunity and another is that successfully recovered infected hosts may become susceptible immediately. Firstly, the existence and local stability of equilibria is studied. Secondly, rigorous mathematical analyses on technical materials and necessary arguments, including asymptotic smoothness and uniform persistence of the system, are given. Thirdly, by applying the fluctuation lemma and the approach of Lyapunov functionals, the threshold dynamics of the model for a special case were established. Roughly speaking, the disease‐free equilibrium is globally asymptotically stable when the basic reproduction number is less than one and otherwise the endemic equilibrium is globally asymptotically stable when no reinfection occurs. It is shown that the infection age and nonlinear incidence not only impact on the basic reproduction number but also could affect the values of the endemic steady state. Numerical simulations were performed to support the theoretical results.
On a generalized variable‐coefficient Gardner equation with linear damping and dissipative terms
Authors: de la Rosa R. , Recio E. , Garrido T. M. , Bruzón M. S.
Published: January 2018

In this paper, a generalized variable‐coefficient Gardner equation which involves a linear damping term and a dissipative term is studied. This equation broadens out a large number of equations previously considered. The equivalence group is used to simplify the analysis of the equation. The gauging of arbitrary elements of the family allows us to perform an exhaustive study of the Lie symmetries admitted by the family. Finally, by means of the multiplier method, we classify all low‐order conservation laws of the equations that have been obtained by applying the gauging.
NMR‐based approach reveals seasonal metabolic changes in mate (Ilex paraguariensis A. St.‐Hil.)
Authors: Freitas Deisy dos Santos , Nunes Wilian da Silva , do Prado Apparecido Rafael , Lopes Thiago Inácio Barros , Alcantara Glaucia Braz
Published: January 2018

Ilex paraguariensis (mate) is a species native to South America and is widely consumed in countries such Argentina, Uruguay, Paraguay, and Brazil. Mate consumption is associated with several phytotherapeutic functions, in addition to its cultural and regional importance. However, the harvest period can affect the properties of the mate, due to variations in the constituent proportions, as a consequence of seasonal changes. In this work, we employed nuclear magnetic resonance and chemometrics to evaluate the chemical variations in leaf extracts of I. paraguariensis over the four seasons of the year. We found significant changes in the levels of glucose, myo‐inositol, caffeine, theobromine, and fatty acids. These changes can be related to resource allocation for the flowering period, or to responses to environmental stresses, such as temperature.
Dynamic measurement of oxygen extraction fraction using a multiecho asymmetric spin echo (MASE) pulse sequence
Authors: Yin Yayan , Zhang Yaoyu , Gao Jia‐Hong
Published: January 2018

Purpose

The oxygen extraction fraction (OEF), an important parameter for assessing brain oxygen metabolism, is a key marker of brain health. Dynamic measurement of the OEF is currently limited by the long acquisition time. In this study, a noninvasive method for rapidly and effectively assessing dynamic changes in the OEF during brain stimulation is proposed.

Methods

A novel pulse sequence using the multi‐echo asymmetric spin echo with an echo‐planar imaging acquisition scheme was developed to improve the temporal resolution of functional OEF measurements. A theoretical formulation that describes the multi‐echo asymmetric spin echo signal dephasing phenomena in the presence of deoxygenated hemoglobin was established. A functional motor experiment was performed using human subjects, in which both OEF maps using the multi‐echo asymmetric spin echo sequence and blood oxygenation level–dependent maps using a
‐weighted gradient‐echo echo‐planar imaging sequence were generated and compared.

Results

The activation maps for both OEF and blood oxygenation level–dependent maps revealed significant changes in the motor cortex. Our results, which were consistent with the previous reports, showed that the average relative changes in the OEF and blood oxygenation level–dependent signal were −22% and 2.0%, respectively.

Conclusion

Obtaining dynamic OEF measurements during functional experiments with the proposed multi‐echo asymmetric spin echo method is feasible. Magn Reson Med 80:1118–1124, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
Time‐course study of macrophage infiltration and inflammation in cast immobilization–induced atrophied muscle of mice
Authors: Kawanishi Noriaki , Funakoshi Tomoko , Machida Shuichi
Published: January 2018

Introduction: Macrophage infiltration may play an important role in mediating the development of muscle atrophy. However, temporal differences in the activation of muscle atrophy signaling pathways and the progress of macrophage infiltration during the atrophic phases of cast immobilization are currently unknown. Methods: C57BL/6J mice were euthanized after cast immobilization at 1, 3, 7, and 14 days. Results: Skeletal muscle macrophage numbers were unchanged on days 1 and 3 after immobilization, but were elevated on days 7 (2.7‐fold, P < 0.01) and 14 (4.1‐fold, P < 0.01). Ubiquitin ligase expression was increased 1 and 3 days after cast immobilization, as was the LC3‐II/LC3‐I ratio. Discussion: Atrophy signaling pathway activation, but not macrophage infiltration, was observed during the early phase after cast immobilization. Our findings indicate that macrophage infiltration may contribute very little to the early phase of muscle atrophy after cast immobilization. Muscle Nerve 57: 1006–1013, 2018
Sub‐minute kinetics of human red cell fumarase: 1H spin‐echo NMR spectroscopy and 13C rapid‐dissolution dynamic nuclear polarization
Authors: Shishmarev Dmitry , Wright Alan J. , Rodrigues Tiago B. , Pileio Giuseppe , Stevanato Gabriele , Brindle Kevin M. , Kuchel Philip W.
Published: January 2018

Fumarate is an important probe of metabolism in hyperpolarized magnetic resonance imaging and spectroscopy. It is used to detect the release of fumarase in cancer tissues, which is associated with necrosis and drug treatment. Nevertheless, there are limited reports describing the detailed kinetic studies of this enzyme in various cells and tissues. Thus, we aimed to evaluate the sub‐minute kinetics of human red blood cell fumarase using nuclear magnetic resonance (NMR) spectroscopy, and to provide a quantitative description of the enzyme that is relevant to the use of fumarate as a probe of cell rupture. The fumarase reaction was studied using time courses of 1H spin‐echo and 13C‐NMR spectra. 1H‐NMR experiments showed that the fumarase reaction in hemolysates is sufficiently rapid to make its kinetics amenable to study in a period of approximately 3 min, a timescale characteristic of hyperpolarized 13C‐NMR spectroscopy. The rapid‐dissolution dynamic nuclear polarization (RD‐DNP) technique was used to hyperpolarize [1,4‐13C]fumarate, which was injected into concentrated hemolysates. The kinetic data were analyzed using recently developed FmRα analysis and modeling of the enzymatic reaction using Michaelis–Menten equations. In RD‐DNP experiments, the decline in the 13C‐NMR signal from fumarate, and the concurrent rise and fall of that from malate, were captured with high spectral resolution and signal‐to‐noise ratio, which allowed the robust quantification of fumarase kinetics. The kinetic parameters obtained indicate the potential contribution of hemolysis to the overall rate of the fumarase reaction when 13C‐NMR RD‐DNP is used to detect necrosis in animal models of implanted tumors. The analytical procedures developed will be applicable to studies of other rapid enzymatic reactions using conventional and hyperpolarized substrate NMR spectroscopy.
Multiband diffusion‐weighted MRI of the eye and orbit free of geometric distortions using a RARE‐EPI hybrid
Authors: Paul Katharina , Huelnhagen Till , Oberacker Eva , Wenz Daniel , Kuehne André , Waiczies Helmar , Schmitter Sebastian , Stachs Oliver , Niendorf Thoralf
Published: January 2018

Diffusion‐weighted imaging (DWI) provides information on tissue microstructure. Single‐shot echo planar imaging (EPI) is the most common technique for DWI applications in the brain, but is prone to geometric distortions and signal voids. Rapid acquisition with relaxation enhancement [RARE, also known as fast spin echo (FSE)] imaging presents a valuable alternative to DWI with high anatomical accuracy. This work proposes a multi‐shot diffusion‐weighted RARE‐EPI hybrid pulse sequence, combining the anatomical integrity of RARE with the imaging speed and radiofrequency (RF) power deposition advantage of EPI. The anatomical integrity of RARE‐EPI was demonstrated and quantified by center of gravity analysis for both morphological images and diffusion‐weighted acquisitions in phantom and in vivo experiments at 3.0 T and 7.0 T. The results indicate that half of the RARE echoes in the echo train can be replaced by EPI echoes whilst maintaining anatomical accuracy. The reduced RF power deposition of RARE‐EPI enabled multiband RF pulses facilitating simultaneous multi‐slice imaging. This study shows that diffusion‐weighted RARE‐EPI has the capability to acquire high fidelity, distortion‐free images of the eye and the orbit. It is shown that RARE‐EPI maintains the immunity to B0 inhomogeneities reported for RARE imaging. This benefit can be exploited for the assessment of ocular masses and pathological changes of the eye and the orbit.
Expanded neurochemical profile in the early stage of Huntington disease using proton magnetic resonance spectroscopy
Authors: Adanyeguh Isaac M. , Monin Marie‐Lorraine , Rinaldi Daisy , Freeman Léorah , Durr Alexandra , Lehéricy Stéphane , Henry Pierre‐Gilles , Mochel Fanny
Published: January 2018

The striatum is a well‐known region affected in Huntington disease (HD). However, other regions, including the visual cortex, are implicated. We have identified previously an abnormal energy response in the visual cortex of patients at an early stage of HD using 31P magnetic resonance spectroscopy (31P MRS). We therefore sought to further characterize these metabolic alterations with 1H MRS using a well‐validated semi‐localized by adiabatic selective refocusing (semi‐LASER) sequence that allows the measurement of an expanded number of neurometabolites. Ten early affected patients [Unified Huntington Disease Rating Scale (UHDRS), total motor score = 13.6 ± 10.8] and 10 healthy volunteers of similar age and body mass index (BMI) were recruited for the study. We performed 1H MRS in the striatum – the region that is primarily affected in HD – and the visual cortex. The protocol allowed a reliable quantification of 10 metabolites in the visual cortex and eight in the striatum, compared with three to five metabolites in previous 1H MRS studies performed in HD. We identified higher total creatine (p < 0.05) in the visual cortex and lower glutamate (p < 0.001) and total creatine (p < 0.05) in the striatum of patients with HD compared with controls. Less abundant neurometabolites [glutamine, γ‐aminobutyric acid (GABA), glutathione, aspartate] showed similar concentrations in both groups. The protocol allowed the measurement of several additional metabolites compared with standard vendor protocols. Our study points to early changes in metabolites involved in energy metabolism in the visual cortex and striatum of patients with HD. Decreased striatal glutamate could reflect early neuronal dysfunction or impaired glutamatergic neurotransmission.
New assignment‐based neighborhoods for traveling salesman and routing problems
Authors: Glover Fred , Rego Cesar
Published: January 2018

We introduce a new class of assignment‐based neighborhoods for symmetric and asymmetric traveling salesman problems that exhibits a combinatorial leverage property, by which a tour can be generated in polynomial time that dominates an exponential number of other tours. The ejection chain perspective motivating the new neighborhoods differs from that underlying the most general assignment‐based neighborhoods proposed in the past, giving rise to new tour constructions that encompass and go beyond previous proposals. The resulting neighborhoods provide greater flexibility for generating new tours while simultaneously accounting for sparse traveling salesman graphs that were previously omitted from consideration. Finally, our approaches are applicable for improving the solution of some versions of the vehicle routing problem.