bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure and chemorheological behavior of whipped cream as affected by rice bran protein addition
Authors: Ghorbani‐HasanSaraei Azade , Rafe Ali , Shahidi Seyed‐Ahmad , Atashzar Azin
Published: January 2019

The effect of rice bran protein (RBP) isolate addition on the rheological and structural properties of commercial whipped cream with 25% and 35% fat was investigated. Results showed that increasing the fat content from 25% to 35% leads to an increase in the elastic modulus. Furthermore, by increasing the amount of RBP from 1% to 3% in both creams, significant increase occurred in the complex modulus. As the fat content increased from 25% to 35%, the slope of flow behavior was increased, which revealed more thinning behavior and pseudoplasticity index of cream. The cream containing 35% fat and 3% RBP had also shown the low index (n = 0.298) which confirmed the firmer structure of the cream. The maximum consistency index (k) obtained was 9.41 for the cream with 35% fat and 3% RBP, which approved its strong foam structure. In general, according to our results it is obvious that whipped cream with the highest amount of fat and the lowest value of protein can lead to maximum stability of the whipping cream. Among the samples, the lowest stiffness was observed in cream of 35% fat, containing 3% rice bran protein. However, cream containing 35% fat and 1% RBP had convenient overrun and good stability. The microstructural results showed that the cream structure has relatively large globular aggregates in network and develops large pores, which permit to retain sufficient water/air. By increasing the fat content of cream from 25% to 35%, the voids and spaces in the cream were significantly decreased and the pores become less which improve the foam structure. Therefore, it can be concluded the cream with more fat has the more overrun and stability. In general, it is possible to improve the foam structure of cream by substituting fat by RBP.
Nutritional and sensory quality of composite extruded complementary food
Authors: Forsido Sirawdink Fikreyesus , Duguma Haile Tesfaye , Lema Tefera Belachew , Sturm Barbara , Hensel Oliver
Published: January 2019

Complementary foods in Ethiopia have nutritional and sensory limitations which can be attributed to cereal‐dominated ingredients and lack of appropriate processing techniques. This study aimed to optimize the nutritional and sensory quality of complementary food product through compositing and extrusion of various local ingredients. A constrained D‐optimal mixture experiment with 13 runs was designed. Accordingly, 55–65 g/100 g oats, 11–23 g/100 g soybean and 6–11 g/100 g linseed, and a premix of 9.9 g/100 g sugar, 0.6 g/100 g table salt, three g/100 g moringa and 1.5 g/100 g fenugreek were blended and extruded using a co‐rotating twin screw extruder with set parameters. Statistical model evaluation and optimization were done using Minitab version 16 software package. There is a statistically significant (p < 0.05) association between the blend of oats and soybean, oats and linseed, soybean and linseed, and the protein, fat, carbohydrate, fiber, ash, β‐carotene content as well as aroma, taste, and consistency. On the contrary, there is a no statistically significant (p < 0.05) association between the blends and moisture, energy, and zinc content together with appearance and overall acceptability. The optimal blending ratio was 55.0 g/100 g oats, 21.0 g/100 g soybean, and 9.0 g/100 g linseed plus 15.0 g/100 g premix. Evidence‐based selection of locally grown plant‐based ingredients, an optimal mixture of these ingredients and optimal processing, can result in a complementary food product with an improved dietary quality for children in low‐income settings.
Market quality and the connectedness of steel rebar and other industrial metal futures in China
Authors: Indriawan Ivan , Liu Qingfu , Tse Yiuman
Published: January 2019

We examine the market quality of China's steel rebar futures, along with three other important industrial metal futures. Steel rebar futures are the most active metal futures contracts in China. Our analyses show that while steel rebar and copper futures are comparable in terms of informational efficiency, they are more informationally efficient than iron ore and aluminum futures, with low bid–ask spread, volatility persistence, pricing error variance, and probability of informed trading. We find a bidirectional connection between iron ore and steel rebar futures. Furthermore, we show that these metal futures are weakly related to the Chinese stock market.
Unmet health care and health care utilization
Authors: Bataineh Hana , Devlin Rose Anne , Barham Vicky
Published: January 2019

The objective of this study is to examine the causal effect of health care utilization on unmet health care needs. An IV approach deals with the endogeneity between the use of health care services and unmet health care, using the presence of drug insurance and the number of physicians by health region as instruments. We employ three cycles of the Canadian Community Health Survey confidential master files (2003, 2005, and 2014). We find a robustly negative relationship between health care use and unmet health care needs. One more visit to a medical doctor on average decreases the probability of reporting unmet health care needs by 0.014 points. The effect is negative for the women‐only group whereas it is statistically insignificant for men; similarly, the effect is negative for urban dwellers but insignificant for rural ones. Health care use reduces the likelihood of reporting unmet health care. Policies that encourage the use of health care services, like increasing the coverage of public drug insurance and increasing after hours accessibility of physicians, can help reduce the likelihood of unmet health care.
Techniques and outcomes in microsurgical soft palate reconstruction
Authors: Fries Charles Anton , Al Deek Nidal , Wei Fu‐Chan
Published: January 2019

Introduction

The soft palate is a multilayered intrinsically mobile structure, with a critical role in maintaining the airway, swallowing, and speech. We describe our technique of microsurgical reconstruction and analyze patient reported outcomes.

Methods

A retrospective analysis was performed using the University of Washington head and neck disease specific Quality of Life (UWQOL) questionnaire and the Hirose Standard speech analysis tool. Swallowing function and diet were recorded.

Results

Twenty cases were reviewed; nine were available for post hoc analysis. Anterolateral thigh flaps were used in 19 cases, in combination with vastus lateralis muscle in 5 cases.

Speech intelligibility was graded “excellent” in 8 of 9 cases and moderate in 1 of 9. All tolerated an oral diet. Mean UWQOL score was 424.4/600 (SD ± 141.9) for physical and 461.7/600 (SD ± 141.9) for emotional‐social domains.

Conclusion

Reconstruction of the soft palate using velopharyngeal narrowing with free anterolateral thigh flap delivers good functional outcomes.
The BRUCE‐ATR Signaling Axis Is Required for Accurate DNA Replication and Suppression of Liver Cancer Development
Authors: Ge Chunmin , Vilfranc Chrystelle L. , Che Lixiao , Pandita Raj K. , Hambarde Shashank , Andreassen Paul R. , Niu Liang , Olowokure Olugbenga , Shah Shimul , Waltz Susan E. , Zou Lee , Wang Jiang , Pandita Tej K. , Du Chunying
Published: January 2019

Replication fork stability during DNA replication is vital for maintenance of genomic stability and suppression of cancer development in mammals. ATR (ataxia‐telangiectasia mutated [ATM] and RAD3‐related) is a master regulatory kinase that activates the replication stress response to overcome replication barriers. Although many downstream effectors of ATR have been established, the upstream regulators of ATR and the effect of such regulation on liver cancer remain unclear. The ubiquitin conjugase BRUCE (BIR Repeat containing Ubiquitin‐Conjugating Enzyme) is a guardian of chromosome integrity and activator of ATM signaling, which promotes DNA double‐strand break repair through homologous recombination. Here we demonstrate the functions for BRUCE in ATR activation in vitro and liver tumor suppression in vivo. BRUCE is recruited to induced DNA damage sites. Depletion of BRUCE inhibited multiple ATR‐dependent signaling events during replication stress, including activation of ATR itself, phosphorylation of its downstream targets CHK1 and RPA, and the mono‐ubiquitination of FANCD2. Consequently, BRUCE deficiency resulted in stalled DNA replication forks and increased firing of new replication origins. The in vivo impact of BRUCE loss on liver tumorigenesis was determined using the hepatocellular carcinoma model induced by genotoxin diethylnitrosamine. Liver‐specific knockout of murine Bruce impaired ATR activation and exacerbated inflammation, fibrosis and hepatocellular carcinoma, which exhibited a trabecular architecture, closely resembling human hepatocellular carcinoma (HCC). In humans, the clinical relevance of BRUCE down‐regulation in liver disease was found in hepatitis, cirrhosis, and HCC specimens, and deleterious somatic mutations of the Bruce gene was found in human hepatocellular carcinoma in the Cancer Genome Atlas database. Conclusion: These findings establish a BRUCE‐ATR signaling axis in accurate DNA replication and suppression of liver cancer in mice and humans and provides a clinically relevant HCC mouse model.
Natural convection boundary layer flow of nanofluids around different stations of the sphere and into the plume above the sphere
Authors: Ashraf Muhammad , Khan Anwar , Gorla Rama Subba Reddy
Published: January 2019

The main intent of the present study is to investigate the natural convection boundary layer flow of nanofluids around different stations of the sphere and eruption of the fluid from the boundary layer in to the plume above the sphere. It is pertinent to point out that in this study heated sphere is treated as point source. The system of transport boundary layer equations is based on the effects of Brownian motion and thermophoresis. The system of dimensioned boundary layer equations is transformed into nondimensional form. Later, the nondimensional form of the mathematical model is solved numerically by using implicit finite difference method. The solution of the problem depends on a controlling parameters Prandtl number Pr, Lewis number , thermophoresis parameter , and Brownian motion parameter . Particularly, it is observed that for Lewis number , Prandtl number Pr, Brownian motion parameter , and thermophoresis parameter the velocity profile is maximum at station and minimum at station . On the other hand temperature distribution is uniform at each station around the sphere and slightly reduced for . It is also observed that nanoparticles concentration is maximum at station and minimum at station We also established the result that with the increase of skin friction is reduced while the heat and mass flux are increased in the plume region‐III.
Haptic exploration of depicted and real objects by 9‐month‐old infants
Authors: Shuwairi Sarah Margaret
Published: January 2019

Previous research yielded conflicting reports as to whether infants grasped at both depicted and real objects, which led to questions about the nature of their conceptual understanding of objects represented in pictures. This study set out to further clarify whether infants actually grasp at pictured objects compared to real objects and other flat patterned surfaces. Categorical types of actions, number of successive actions, total frequency counts, transitions between hands, and hand height were evaluated. Infants responded with more persistent actions and overall contact toward the pictured object relative to both the real object and flat pattern. They also lifted and peeked underneath the picture as if searching for the depicted object. Infants did not respond equivocally toward all the display types, nor did they grasp at the pictured object or flat patterned surface. Grasping was only observed toward the actual object. They appear to more actively engage in selective, highly coordinated actions toward depicted objects to learn how they may differ from real objects and other flat surfaces. Methodological variations in coding schemes may underlie the divergent interpretation of infants' actions.

Highlights

Do infants actually grasp at real objects, pictured objects and flat patterned surfaces alike?

They engaged in reliably greater manual exploration of depicted objects, and grasping was only observed toward actual objects.

Selective actions toward depicted objects reveals emergent underlying conceptual understanding of pictures relative to 3D objects and other flat surfaces.
The genomic imprint of cancer therapies helps timing the formation of metastases
Authors: Németh Eszter , Krzystanek Marcin , Reiniger Lilla , Ribli Dezső , Pipek Orsolya , Sztupinszki Zsófia , Glasz Tibor , Csabai István , Moldvay Judit , Szallasi Zoltan , Szüts Dávid
Published: January 2019

A retrospective determination of the time of metastasis formation is essential for a better understanding of the evolution of oligometastatic cancer. This study was based on the hypothesis that genomic alterations induced by cancer therapies could be used to determine the temporal order of the treatment and the formation of metastases. We analysed the whole genome sequence of a primary tumour sample and three metastatic sites derived from autopsy samples from a young never‐smoker lung adenocarcinoma patient with an activating EGFR mutation. Mutation detection methods were refined to accurately detect and distinguish clonal and subclonal mutations. In comparison to a panel of samples from untreated smoker or never‐smoker patients, we showed that the mutagenic effect of cisplatin treatment could be specifically detected from the base substitution mutations. Metastases that arose before or after chemotherapeutic treatment could be distinguished based on the allele frequency of cisplatin‐induced dinucleotide mutations. In addition, genomic rearrangements and late amplification of the EGFR gene likely induced by afatinib treatment following the acquisition of a T790M gefitinib resistance mutation provided further evidence to tie the time of metastasis formation to treatment history. The established analysis pipeline for the detection of treatment‐derived mutations allows the drawing of tumour evolutionary paths based on genomic data, showing that metastases may be seeded well before they become detectable by clinical imaging.
Fiber intake and the risk of head and neck cancer in the prostate, lung, colorectal and ovarian (PLCO) cohort
Authors: Kawakita Daisuke , Lee Yuan‐Chin Amy , Gren Lisa H. , Buys Saundra S. , La Vecchia Carlo , Hashibe Mia
Published: January 2019

Although the protective role of dietary fiber on cancer risk has been reported in several epidemiological studies, the association of fiber intake on head and neck cancer (HNC) risk is still unclear. We investigated the association between fiber intake and the risk of HNC using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Among 101,700 participants with complete dietary information, 186 participants developed HNC during follow‐up (January 1998 to May 2011). Dietary data were collected using a self‐administered food‐frequency questionnaire (1998–2005). We estimated hazard ratios (HRs) and the corresponding 95% confidence intervals (CI), using the Cox proportional hazards model. Higher intake of total fiber, insoluble fiber and soluble fiber was associated with decreased HNC risks, with a significant trend. The HRs of highest vs. the lowest tertile of intake were 0.43 (95%CI: 0.25–0.76) for total fiber, 0.38 (95%CI: 0.22–0.65) for insoluble fiber, and 0.44 (95%CI: 0.25–0.79) for soluble fiber. These inverse association were consistent in oral cavity and pharyngeal cases, but the impact of fiber intake was weaker in laryngeal cases. We did not observe any significant interaction of potential confounders, including smoking and drinking, with total fiber intake on HNC risk. These findings support evidence of a protective role of dietary fiber on HNC risk.
One‐carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
Authors: Vrieling Alina , Bueno‐De‐Mesquita H. Bas , Ros Martine M. , Kampman Ellen , Aben Katja K. , Büchner Frederike L. , Jansen Eugène H. , Roswall Nina , Tjønneland Anne , Boutron‐Ruault Marie‐Christine , Cadeau Claire , Chang‐Claude Jenny , Kaaks Rudolf , Weikert Steffen , Boeing Heiner , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Sieri Sabina , Palli Domenico , Panico Salvatore , Peeters Petra H. , Weiderpass Elisabete , Skeie Guri , Jakszyn Paula , Chirlaque María‐Dolores , Ardanaz Eva , Sánchez María‐José , Ehrnström Roy , Malm Johan , Ljungberg Börje , Khaw Kay‐Tee , Wareham Nick J. , Brennan Paul , Johansson Mattias , Riboli Elio , Kiemeney Lambertus A.
Published: January 2019

Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case–control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre‐diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non‐aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98–1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02–1.75; p‐heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62–10.81, p‐interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81–1.95; p‐heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.
TRIM28 haploinsufficiency predisposes to Wilms tumor
Authors: Diets Illja J. , Hoyer Juliane , Ekici Arif B. , Popp Bernt , Hoogerbrugge Nicoline , van Reijmersdal Simon V. , Bhaskaran Rajith , Hadjihannas Michel , Vasileiou Georgia , Thiel Christian T. , Seven Didem , Uebe Steffen , Ilencikova Denisa , Waanders Esmé , Mavinkurve‐Groothuis Annelies M.C. , Roeleveld Nel , de Krijger Ronald R. , Wegert Jenny , Graf Norbert , Vokuhl Christian , Agaimy Abbas , Gessler Manfred , Reis André , Kuiper Roland P. , Jongmans Marjolijn C.J. , Metzler Markus
Published: January 2019

Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss‐of‐function effect of the mutations identified. The tumors showed an epithelial‐type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss‐of‐heterozygosity (LOH) of the TRIM28‐locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial‐type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH.
Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models
Authors: Depetter Yves , Geurs Silke , De Vreese Rob , Goethals Sophie , Vandoorn Elien , Laevens Alien , Steenbrugge Jonas , Meyer Evelyne , de Tullio Pascal , Bracke Marc , D'hooghe Matthias , De Wever Olivier
Published: January 2019

Our study investigates the biochemical and functional impact of selective histone deacetylase 6 (HDAC6) inhibitors, a promising class of novel therapeutics, in several cancer models. Selective HDAC6 inhibitors (Tubathian A, Tubastatin A, Tubacin and Ricolinostat) and a non‐selective HDAC inhibitor (Vorinostat) were evaluated on cancer cell lines derived from multiple tumour types in both an in vitro and in vivo setting as potential cancer therapeutics. Selective HDAC6 inhibitors resulted in α‐tubulin acetylation with no impact on histone acetylation but failed to show any anti‐cancer properties. Only the use of high concentrations of selective HDAC6 inhibitors resulted in co‐inhibition of other HDAC enzymes and consequently in reduced growth, migratory and/or invasive activity of cancer cells in vitro as well as in vivo. The specificity of HDAC6 inhibition was confirmed using a CRISPR/Cas9 knockout cell line. Our results suggest that selective HDAC6 inhibitors may fall short as potential single agent anti‐cancer drugs and prove that many previous data regarding this promising class of compounds need to be interpreted with great care due to their use in high concentrations resulting in low selectivity and potential off‐target effects.
MET activation confers resistance to cetuximab, and prevents HER2 and HER3 upregulation in head and neck cancer
Authors: Novoplansky Ofra , Fury Matthew , Prasad Manu , Yegodayev Ksenia , Zorea Jonathan , Cohen Limor , Pelossof Raphael , Cohen Liz , Katabi Nora , Cecchi Fabiola , Joshua Ben‐Zion , Popovtzer Aron , Baselga Jose , Scaltriti Maurizio , Elkabets Moshe
Published: January 2019

An understanding of the mechanisms underlying acquired resistance to cetuximab is urgently needed to improve cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Here, we present a clinical observation that MET pathway activation constitutes the mechanism of acquired resistance to cetuximab in a patient with HNSCC. Specifically, RNA sequencing and mass spectrometry analysis of cetuximab‐sensitive (CetuxSen) and cetuximab‐resistant (CetuxRes) tumors indicated MET amplification and overexpression in the CetuxRes tumor compared to the CetuxSen lesion. Stimulation of MET in HNSCC cell lines was sufficient to reactivate the MAPK pathway and to confer resistance to cetuximab in vitro and in vivo. In addition to the direct role of MET in reactivation of the MAPK pathway, MET stimulation abrogates the well‐known cetuximab‐induced compensatory feedback loop of HER2/HER3 expression. Mechanistically, we showed that the overexpression of HER2 and HER3 following cetuximab treatment is mediated by the ETS homologous transcription factor (EHF), and is suppressed by MET/MAPK pathway activation. Collectively, our findings indicate that evaluation of MET and HER2/HER3 in response to cetuximab in HNSCC patients can provide the rationale of successive line of treatment.
The neonicotinoids acetamiprid and imidacloprid impair neurogenesis and alter the microglial profile in the hippocampal dentate gyrus of mouse neonates
Authors: Nakayama Akira , Yoshida Manami , Kagawa Nao , Nagao Tetsuji
Published: January 2019

Acetamiprid (ACE) and imidacloprid (IMI) are widely used neonicotinoid pesticides. They bind selectively to insect nicotinic acetylcholine receptors (nAChRs) and are considered non‐hazardous to mammals. Few studies have assessed the activation of vertebrate nAChRs and the neurodevelopmental toxicity following in utero or neonatal exposure to neonicotinoids; therefore, we evaluated the effects of ACE or IMI exposure on neurogenesis and microglial profiles in the developing hippocampal dentate gyrus (DG) of mouse neonates. Mice were exposed to ACE, IMI (both 5 mg/kg/day) or nicotine (0.5 mg/kg/day) from postnatal day (P)12 to P26 by oral gavage. On P27, brains were removed, and neurogenesis and microglial activation in the hippocampal DG were examined via immunohistochemistry. A reduction in neurogenesis in the hippocampal DG of neonates following ACE, IMI and nicotine treatment was found. Additionally, neonicotinoid‐exposed newborns showed an increase in the number of amoeboid‐type and activated M1‐type microglia. These results suggest that exposure to ACE and IMI impairs neurogenesis and alters microglial profiles in the developing hippocampal DG following oral dosing in an early postnatal period. A better understanding of the potential effects of these pesticides on human infant health is an important goal of our research.
Calcium Deficiency Rickets in African Adolescents: Cortical Bone Histomorphometry
Authors: Schnitzler Christine M , Pettifor John M
Published: January 2019

Rickets due to dietary calcium deficiency has been well described in black African children, but less is known about this condition in black adolescents. We investigated 26 black adolescents (19 males aged 11 to 19 years and 7 females aged 12 to 15 years) with rachitic leg deformities and 20 controls by routine iliac crest undecalcified cortical bone histomorphometry for disturbances of bone turnover and for mineralization defects, including severity of osteocytic osteolysis (Ot.Olysis) and periosteocytic osteolysis (Peri.Ot.Olysis) of the lacunar‐canalicular space. Serum levels of calcium (sCa), 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D (1,25(OH)2D), and total alkaline phosphatase (ALP) were measured. Histomorphometry showed varying degrees of severity of secondary hyperparathyroidism (20 HPT) characterized by hyperosteoidosis, increased erosion, and porosis. Because osteoid was neither being mineralized nor eroded (osteoclasts cannot erode osteoid), it increasingly blocked bone surface needed for osteoclastic resorption. Where osteoid covered >50% of bone surface, osteoid thickness, severity of Ot.Olysis, and extent of Peri.Ot.Olysis increased, sCa and 25OHD declined, and 1,25(OH)2D and ALP increased. At 80% osteoid cover, bone remodeling had all but ceased, secondary HPT had changed to osteomalacia, and serum biochemical results had deteriorated further. Disease severity was greater in males than in females, likely because males grow faster and for longer than females. In conclusion, this cross‐sectional clinical case study presents cortical bone histomorphometric data of secondary HPT and its transition to osteomalacia in black adolescents with rickets attributable to dietary calcium deficiency. The bone disease was most severe in older adolescent males. Importantly, bone pathology of calcium deficiency rickets in adolescents was not confined to bone surfaces but also manifested at osteocyte level as Ot.Olysis and Peri.Ot.Olysis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption
Authors: Schepper Jonathan D , Collins Fraser L. , Rios-Arce Naiomy Deliz , Raehtz Sandi , Schaefer Laura , Gardinier Joseph D , Britton Robert A. , Parameswaran Narayanan , McCabe Laura R
Published: January 2019

Antibiotic treatment, commonly prescribed for bacterial infections, depletes and subsequently causes long-term alterations in intestinal microbiota composition. Knowing the importance of the microbiome in the regulation of bone density, we investigated the effect of postantibiotic treatment on gut and bone health. Intestinal microbiome repopulation at 4-weeks postantibiotic treatment resulted in an increase in the Firmicutes:Bacteroidetes ratio, increased intestinal permeability, and notably reduced femoral trabecular bone volume (approximately 30%, p < 0.01). Treatment with a mucus supplement (a high-molecular-weight polymer, MDY-1001 [MDY]) prevented the postantibiotic-induced barrier break as well as bone loss, indicating a mechanistic link between increased intestinal permeability and bone loss. A link between the microbiome composition and bone density was demonstrated by supplementing the mice with probiotic bacteria. Specifically, Lactobacillus reuteri, but not Lactobacillus rhamnosus GG or nonpathogenic Escherichia coli, reduced the postantibiotic elevation of the Firmicutes:Bacteroidetes ratio and prevented femoral and vertebral trabecular bone loss. Consistent with causing bone loss, postantibiotic-induced dysbiosis decreased osteoblast and increased osteoclast activities, changes that were prevented by both L. reuteri and MDY. These data underscore the importance of microbial dysbiosis in the regulation of intestinal permeability and bone health, as well as identify L. reuteri and MDY as novel therapies for preventing these adverse effects. © 2018 American Society for Bone and Mineral Research.
Sirt1 Promotes Osteogenic Differentiation and Increases Alveolar Bone Mass via Bmi1 Activation in Mice
Authors: Wang Hua , Hu Zixuan , Wu Jun , Mei Yukun , Zhang Qian , Zhang Hengwei , Miao Dengshun , Sun Wen
Published: January 2019

Sirtuin 1 (Sirt1), a protein deacetylase, is a novel target for bone metabolism. To investigate whether overexpression of Sirt1 in mandibular mesenchymal stem cells (M-MSCs) increased alveolar bone mass in vivo, we generated Sirt1 transgenic mice (Sirt1TG), with Sirt1 gene expression driven by the Prx1 gene, which represents the mesenchymal lineage. Our results demonstrated that overexpression of Sirt1 in M-MSCs increased the alveolar bone volume in 1-month-old, 9-month-old, and 18-month-old Sirt1TG mice compared with age-matched wild-type (WT) mice, and in ovariectomized Sirt1TG mice compared with ovariectomized WT mice by stimulating M-MSC differentiation into osteoblasts. Treatment with resveratrol, a Sirt1 activator, increased Sirt1 binding with Bmi1 and reduced Bmi1 acetylation in a dose-dependent manner demonstrated in M-MSC cultures. Both treatment with resveratrol in M-MSC cultures and overexpressed Sirt1 in M-MSCs ex vivo cultures increased nuclear translocation of Bmi1. Furthermore, we demonstrated that deletion of Bmi1 blocked the increased alveolar bone volume in Sirt1TG mice. The Sirt1 activator resveratrol inhibited human MSC senescence and promoted their differentiation into osteoblasts, which were associated with upregulating the expression levels of Sirt1 and nuclear translocation of Bmi1. The present results suggested that Sirt1 promotes MSC proliferation and osteogenic differentiation, inhibits MSC senescence to increase alveolar bone volume by promoting the deacetylation and nuclear translocation of Bmi1. Thus, our study elucidated the mechanism by which Sirt1 increases alveolar bone mass, and these findings are important for the clinical application of the Sirt1 activator resveratrol for the promotion of alveolar bone formation and prevention of alveolar bone loss. © 2019 American Society for Bone and Mineral Research.
CD73; a key ectonucleotidase in the development of breast cancer: Recent advances and perspectives
Authors: Soleimani Anvar , Taghizadeh Eskandar , Shahsavari Shirin , Amini Yousef , Rashidpour Hatam , Azadian Esmaeel , Jafari Arash , Parizadeh Mohammad Reza , Mashayekhi Kazem , Soukhtanloo Mohammad , Jaafari Mahmoud Reza
Published: January 2019

Tumor cell invasion and metastasis are the definitive cause of mortality in breast cancer (BC). Hypoxia and pro‐inflammatory cytokines upregulate the CD73 gene in the tumor microenvironment. Subsequently, CD73 triggers molecular and cellular signaling pathways by both enzymatic and nonenzymatic pathways, which finally leads to breast tumor progression and development. In this paper, we summarize current advances in the understanding of CD73‐driven mechanisms that promote BC development and mortality. Furthermore, we evaluate the therapeutic potential of CD73 targeting in BC.
Iron overload threatens the growth of osteoblast cells via inhibiting the PI3K/AKT/FOXO3a/DUSP14 signaling pathway
Authors: Xia Demeng , Wu Jianghong , Xing Malcolm , Wang Yang , Zhang Hongyue , Xia Yan , Zhou Panyu , Xu Shuogui
Published: January 2019

Iron overload is a common stress in the development of cells. Growing evidence has indicated that iron overload is associated with osteoporosis. Therefore, enhancing the understanding of iron overload would benefit the development of novel approaches to the treatment of osteoporosis. The purpose of the present study was to analyze the effect of iron overload on osteoblast cells, via the MC3T3‐E1 cell line, and to explore its possible underlying molecular mechanisms. Ferric ammonium citrate (FAC) was utilized to simulate iron overload conditions in vitro. FAC‐induced iron overload strongly suppressed proliferation of osteoblast cells and induced apoptosis. Moreover, iron overload strongly suppressed the expression of dual‐specificity phosphatase 14 (DUSP14). Additionally, overexpression of DUSP14 protected osteoblast cells from the deleterious effects of iron overload, and this protective effect was mediated by FOXO3a. Additionally, matrine rescued the function of DUSP14 in osteoblast cells. Most importantly, our analysis demonstrated the essential role of the PI3K/AKT/FOXO3a/DUSP14 signaling pathway in the defense against iron overload in osteoblast cells. Overall, our results not only elucidate deleterious effects of iron overload, but also unveil its possible signaling pathway in osteoblast cells.
Flexible ZIFs: probing guest‐induced flexibility with CO2, N2 and Ar adsorption
Authors: Noguera‐Díaz Antonio , Villarroel‐Rocha Jhonny , Ting Valeska P , Bimbo Nuno , Sapag Karim , Mays Timothy J
Published: January 2019

BACKGROUND

The effect of framework topology on the guest‐induced flexibility of several crystalline zeolitic imidazolate frameworks (ZIF‐7, ZIF‐9, ZIF‐11 and ZIF‐12) was investigated via analysis of experimental nitrogen (N2), carbon dioxide (CO2) and argon (Ar) isotherms at 77 K (N2 and Ar) and 273 K (CO2) for gas pressures up to 0.13 MPa.

RESULTS

The experimental isotherms of these frameworks were analysed in order to investigate their structural flexibility using gases with kinetic diameters equal to or larger than the diameters of their static pore apertures. The results of gas sorption measurements indicate guest‐induced phase changes for ZIF‐7 and ZIF‐9 (SOD topologies). ZIF‐12 (RHO topology) also shows uptake for gases, despite its pore‐limiting diameter being smaller than the kinetic diameters of the adsorbed molecules.

CONCLUSIONS

This work highlights the ability of ZIFs with different framework topologies to change their structure and increase their pore aperture upon interaction with certain gases. These findings are key in the development of more selective ZIF‐based materials for important industrial applications including low‐energy gas separations, catalytic nanoreactors and sensor technology. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Solvent Free Synthesis of N‐Substituted Pyrroles Catalyzed by Calcium Nitrate
Authors: Wani Rucha R. , Chaudhari Hemchandra K. , Takale Balaram S.
Published: January 2019

Moderated and mild way for synthesizing N‐substituted pyrrole has been demonstrated herein. No solvents need to be used for this reaction, and instead, reactants themselves acted as a reaction medium. In fact, the reaction is carried out using catalytic amount of Ca(NO3)2.4H2O. The reaction conditions are selective and mild that helped to tolerate a wide variety of functional groups to give the desired products in good chemical yields.
Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis—A cross‐sectional study
Authors: Sláma Tomáš , Garbade Sven F. , Kölker Stefan , Hoffmann Georg F. , Ries Markus
Published: January 2019

Galactosialidosis (GS; OMIM #256540) is a rare multisystemic inborn glycoprotein storage disease caused by biallelic mutations in the cathepsin A gene resulting in combined deficiency of the lysosomal enzymes β‐galactosidase and α‐neuraminidase. The precise understanding of the natural course of the disease is limited. Development of enzyme replacement therapy is at the preclinical stage. The purpose of this research project was to quantitatively characterize the natural history of the condition. Quantitative analysis of all published cases in the literature with sufficient data (N = 142 patients) was carried out. Main outcome variables were survival, diagnostic delay, description of symptoms, biomarker‐phenotype associations, and radiological findings. STROBE criteria were respected. Median survival age of the cohort was 48 years. Median age of onset was 4.25 years with interquartile range (IQR) 1 to 16 years. Median age at diagnosis was 19 (IQR: 8.92‐29) years, with median diagnostic delay of 8 (IQR: 4‐12) years. Patients with residual β‐galactosidase activity of more than 8.6% (leukocytes) survived significantly longer than patients with lower enzyme activities.
Detecting lipopolysaccharide in the cytosol of mammalian cells: Lessons from MD-2/TLR4
Authors: Barker Jason H , Weiss Jerrold P
Published: January 2019

Proinflammatory immune responses to Gram-negative bacterial lipopolysaccharides (LPS) are crucial to innate host defenses but can also contribute to pathology. How host cells sensitively detect structural features of LPS was a mystery for years, especially given that a portion of the molecule essential for its potent proinflammatory properties—lipid A—is buried in the bacterial membrane. Studies of responses to extracellular and vacuolar LPS revealed a crucial role for accessory proteins that specifically bind LPS-rich membranes and extract LPS monomers to generate a complex of LPS, MD-2, and TLR4. These insights provided means to understand better both the remarkable host sensitivity to LPS and the means whereby specific LPS structural features are discerned. More recently, the noncanonical inflammasome, consisting of caspases-4/5 in humans and caspase-11 in mice, has been demonstrated to mediate responses to LPS that has reached the host cytosol. Precisely how LPS gains access to cytosolic caspases—and in what form—is not well characterized, and understanding this process will provide crucial insights into how the noncanonical inflammasome is regulated during infection. Herein, we briefly review what is known about LPS detection by cytosolic caspases-4/5/11, focusing on lessons derived from studies of the better-characterized TLR4 system that might direct future mechanistic questions.
Renal and adrenal masses containing fat at MRI: Proposed nomenclature by the society of abdominal radiology disease‐focused panel on renal cell carcinoma
Authors: Schieda Nicola , Davenport Matthew S. , Pedrosa Ivan , Shinagare Atul , Chandarana Hersch , Curci Nicole , Doshi Ankur , Israel Gary , Remer Erick , Wang Jane , Silverman Stuart G.
Published: January 2019

This article proposes a consensus nomenclature for fat‐containing renal and adrenal masses at MRI to reduce variability, improve understanding, and enhance communication when describing imaging findings. The MRI appearance of "macroscopic fat" occurs due to a sufficient number of aggregated adipocytes and results in one or more of: 1) intratumoral signal intensity (SI) loss using fat‐suppression techniques, or 2) chemical shift artifact of the second kind causing linear or curvilinear India‐ink (etching) artifact within or at the periphery of a mass at macroscopic fat–water interfaces. "Macroscopic fat" is most commonly observed in adrenal myelolipoma and renal angiomyolipoma (AML) and only rarely encountered in other adrenal cortical tumors and renal cell carcinomas (RCC). Nonlinear noncurvilinear signal intensity loss on opposed‐phase (OP) compared with in‐phase (IP) chemical shift MRI (CSI) may be referred to as "microscopic fat" and is due to: a) an insufficient amount of adipocytes, or b) the presence of fat within tumor cells. Determining whether the signal intensity loss observed on CSI is due to insufficient adipocytes or fat within tumor cells cannot be accomplished using CSI alone; however, it can be inferred when other imaging features strongly suggest a particular diagnosis. Fat‐poor AML are homogeneously hypointense on T2‐weighted (T2W) imaging and avidly enhancing; signal intensity loss at OP CSI is uncommon, but when present is usually focal and is caused by an insufficient number of adipocytes within adjacent voxels. Conversely, clear‐cell RCC are heterogeneously hyperintense on T2W imaging and avidly enhancing, with the signal intensity loss observed on OP CSI being typically diffuse and due to fat within tumor cells. Adrenal adenomas, adrenal cortical carcinoma, and adrenal metastases from fat‐containing primary malignancies also show signal intensity loss on OP CSI due to fat within tumor cells and not from intratumoral adipocytes.

Level of Evidence: 5

Technical Efficacy Stage: 3

J. Magn. Reson. Imaging 2019;49:917–926.
Sensorineural hearing loss and cognitive impairments: Contributions of thalamus using multiparametric MRI
Authors: Xu Xiao‐Min , Jiao Yun , Tang Tian‐Yu , Zhang Jian , Lu Chun‐Qiang , Salvi Richard , Teng Gao‐Jun
Published: January 2019

Background

The thalamus is an integrative hub conveying sensory information between cortical areas and related to cognition. However, alterations of the thalamus following partial hearing deprivation remains unknown.

Purpose

To investigate the modifications of the thalamus and its seven subdivisions in terms of structure, function, and perfusion in subjects with sensorineural hearing loss (SNHL), as well as their associations with SNHL‐induced cognitive impairments.

Study Type

Cross‐sectional study.

Subjects

Thirty‐seven bilateral long‐term SNHL patients and 38 well‐matched controls.

Field Strength

3 T/BOLD, T1‐weighted imaging, arterial spin labeling (ASL).

Assessment

Quantitative measurements in the thalamus and subdivisions were obtained, including the relative volume, fractional amplitude of low‐frequency fluctuation (fALFF) within slow 5 (0.01–0.027 Hz), slow 4 (0.027–0.073 Hz), and combined frequency (0.01–0.073 Hz), as well as the whole‐brain functional connectivity. Twenty‐five SNHL patients and 20 controls underwent ASL scanning. Then correlation analysis was computed between all significant changes and cognition tests.

Statistical Tests

Continuous and categorical variables were compared by independent‐sample t‐test and chi‐square test, respectively. Quantitative MRI measurement comparisons were corrected for multiple comparison, and functional connectivity (FC) analysis used two‐sample t‐test with false‐discovery rate correction. Area under the curve (AUC) in receiver operating characteristic curve analysis was applied to evaluate the power of alterations in differentiating SNHL and controls.

Results

No significant difference in the relative volume and perfusion of seven thalamus subdivisions were observed, but a decrease in fALFF in SNHL. SNHL showed reduced thalamic connectivity with the cerebellum lobule VIII, ventral anterior cingulate cortex, insula, superior temporal gyrus, media temporal gyrus, medial frontal gyrus, Heschl's gyrus, and temporal pole. And some FC abnormalities exhibited positive correlations with cognitive tests and high discriminative power (0.8 < AUC < 1) in two groups.

Data Conclusion

SNHL led to decreased thalamic activity and widespread weakened connectivity with other brain areas.

Level of Evidence: 2

Technical Efficacy Stage: 3

J. Magn. Reson. Imaging 2019;50:787–797.
In Vivo analysis of spinopelvic kinematics and peak head‐cup contact in total hip arthroplasty patients with lumbar degenerative disc disease
Authors: Limmahakhun Sakkadech , Box Hayden N. , Arauz Paul , Hennessy David W. , Klemt Christian , Kwon Young‐Min
Published: January 2019

Anterior instability after total hip arthroplasty (THA) has been described in patients with thoracolumbar kyphotic deformity. Although compensatory posterior pelvic tilt with subsequent increased functional anteversion has been described as the mechanism, there is a paucity of in vivo data. The purpose of our study was to compare pelvic tilt, anteversion, inclination, and position of head‐cup contact points in patients with lumbar degenerative disc disease (DDD) and a matched patient cohort without DDD. A total of 50 THA, 18 hips with lumbar DDD and 32 hips without DDD, underwent CT imaging for 3D hip reconstruction. Component orientations and in vivo hip gait kinematics was quantified using a validated dual fluoroscopic imaging system. Hip kinematics and head‐cup contact points were compared. Patients with lumbar DDD demonstrated decreased maximum (5.9° ± 4.2° vs. 9.3° ± 5.4°, p = 0.02) and minimum (2.4° ± 4.1° vs. 6.2° ± 5.6°, p = 0.01) anterior pelvic tilt, and increased maximum cup anteversion (29.3° ± 8.7° vs. 25.1° ± 8.1°, p = 0.05). The peak head‐cup contact points were shifted closer to the anterior edge of the polyethylene (7.8 ± 1.7 mm vs. 9.6 ± 2.2 mm, p = 0.02). Patients with lumbar degenerative disc disease demonstrated increased posterior pelvic tilt, functional acetabular anteversion, inclination as well as shifting of the peak head‐cup contact pattern significantly closer to an anterior edge, suggesting sagittal spinopelvic deformity may predispose to anterior instability in THA patients during upright activities. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res