bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observations on the Natural History of Camurati-Engelmann Disease
Authors: Hughes Peter , Hassan Ibrahim , Que Lorna , Mead Patricia , Lee Jessica Heejong , Love Donald R , Prosser Debra O , Cundy Tim 
Published: January 2019

ABSTRACT

Camurati-Engelmann disease (OMIM 31300) is a rare cranio-tubular bone dysplasia characterized by osteosclerosis of the long bones and skull caused by dominantly-inherited mutations in the transforming growth factor beta 1 (TGFB1) gene. A wide variation in phenotype has been recognized, even within families carrying the same mutation. In addition, aspects of the natural history of the disorder, in particular whether it is always progressive or can remit spontaneously, remain uncertain. In a large kindred carrying a TGFB1 gene mutation (c.653G &gt; A; p.R218H) we have attempted to clarify the extent of phenotypic variability and the natural history of the disease through detailed individual histories of symptoms, and skeletal imaging by both radiography and scintigraphy. Only one subject had the classical childhood onset with bone pain in the legs and gait disturbance. Eight subjects reported the onset of leg pain in their teenage years that, by their early 20s, had either resolved or persisted at a low level. Two of these eight later developed cranial nerve palsies. There was a wide variation in the radiographic appearance in adults, but disease extent and activity in long bones, as assessed by scintigraphy, was inversely correlated with age (p &lt; 0.025). In younger subjects the radiographic and scintigraphic appearances were concordant, but in older subjects the scintigram could be quiescent despite florid radiographic changes. Sequential scintigrams in two subjects showed reduced activity in the later scan. One subject had suffered meningoencephalitis in early childhood that resulted in paresis of one arm. The affected arm showed markedly less disease involvement, implicating mechanical or growth factors in its etiology. Our data suggest that the natural history of Camurati-Engelmann disease can be benign, and that disease activity commonly attenuates in adulthood. Severe cases of childhood onset and/or with cranial nerve involvement, may occur only in a minority of mutation carriers. © 2019 American Society for Bone and Mineral Research.
Thoracic Kyphosis on Chest CT Scans Is Associated With Incident Vertebral Fractures in Smokers
Authors: van Dort Mayke J , Driessen Johanna HM , Romme Elisabeth APM , Geusens Piet , Willems Paul C , Smeenk Frank WJM , Wouters Emiel FM , van den Bergh Joop PW 
Published: January 2019

ABSTRACT

Greater kyphosis angles lead to increased loading on vertebral bodies in computational models. However, results about the relationship between severity of kyphosis and incident vertebral fracture (VF) risk have been conflicting. Therefore, the aim of this study was to evaluate associations between 1) prevalent VFs and severity of kyphosis, and 2) severity of kyphosis and incident VF risk in smokers with or without chronic obstructive pulmonary disease (COPD). Former and current smokers with or without COPD were included. CT scans were made at baseline, 1-year, and 3-year follow-up. VFs were evaluated on superposed sagittal CT reconstructions. Kyphosis was measured as the angle between the lines above T4 and below T9 or T12. We included 1239 subjects (mean age 61.3 ± 8.0 years, 61.1% male, 80.6% with COPD), of whom 253 (20.4%) had a prevalent VF and 294 (23.7%) an incident VF within 3 years. Presence, number, and severity of prevalent VFs were associated with a greater kyphosis angle. The mean increase in kyphosis angle within 3 years was small but significantly greater in subjects with incident VFs compared with those without (2.2 ± 4.1 versus 1.2 ± 3.9 degrees, respectively, for T4 to T12 angle, p &lt; 0.001). After adjustment for bone attenuation (BA) and prevalent VFs, baseline kyphosis angle was associated with incident VFs within 1 and 3 years (angle T4 to T12 per +1 SD, hazard ratio [HR] = 1.34 [1.12–1.61] and HR 1.29 [1.15–1.45], respectively). Our data showed that a greater kyphosis angle at baseline was independently associated with increased risk of incident VFs within 1 and 3 years, supporting the theory that greater kyphosis angle contributes to higher biomechanical loads in the spine. © 2019 American Society for Bone and Mineral Research.
Parathyroid-Targeted Overexpression of Regulator of G-Protein Signaling 5 (RGS5) Causes Hyperparathyroidism in Transgenic Mice
Authors: Balenga Nariman , Koh James , Azimzadeh Pedram , Hogue Joyce , Gabr Mostafa , Stains Joseph P , Olson John A 
Published: January 2019

ABSTRACT The relationship between impaired calcium sensing, dysregulated parathyroid hormone (PTH) secretion, and parathyroid cell proliferation in parathyroid neoplasia is not understood. We previously reported that a GTPase activating protein, regulator of G-protein signaling 5 (RGS5) is overexpressed in a subset of parathyroid tumors associated with primary hyperparathyroidism (PHPT) and that RGS5 can inhibit signaling from the calcium-sensing receptor (CASR). In vivo, we found that RGS5-null mice have abnormally low PTH levels. To gain a better understanding of the potential role of RGS5 overexpression in parathyroid neoplasia and PHPT and to investigate whether inhibition of CASR signaling can lead to parathyroid neoplasia, we created and characterized a transgenic mouse strain overexpressing RGS5 specifically in the parathyroid gland. These mice develop hyperparathyroidism, bone changes reflective of elevated PTH, and parathyroid neoplasia. Further, expression of exogenous RGS5 in normal human parathyroid cells results in impaired signaling from CASR and negative feedback on PTH secretion. These results provide evidence that RGS5 can modulate signaling from CASR and support a role for RGS5 in the pathogenesis of PHPT through inhibition of CASR signaling. © 2019 American Society for Bone and Mineral Research.
Mesenchymal Cell-Derived Juxtacrine Wnt1 Signaling Regulates Osteoblast Activity and Osteoclast Differentiation
Authors: Wang Fan , Tarkkonen Kati , Nieminen-Pihala Vappu , Nagano Kenichi , Majidi Rana Al , Puolakkainen Tero , Rummukainen Petri , Lehto Jemina , Roivainen Anne , Zhang Fu-Ping , Mäkitie Outi , Baron Roland , Kiviranta Riku 
Published: January 2019

ABSTRACT

Human genetic evidence demonstrates that WNT1 mutations cause osteogenesis imperfecta (OI) and early-onset osteoporosis, implicating WNT1 as a major regulator of bone metabolism. However, its main cellular source and mechanisms of action in bone remain elusive. We generated global and limb bud mesenchymal cell–targeted deletion of Wnt1 in mice. Heterozygous deletion of Wnt1 resulted in mild trabecular osteopenia due to decreased osteoblast function. Targeted deletion of Wnt1 in mesenchymal progenitors led to spontaneous fractures due to impaired osteoblast function and increased bone resorption, mimicking the severe OI phenotype in humans with homozygous WNT1 mutations. Importantly, we showed for the first time that Wnt1 signals strictly in a juxtacrine manner to induce osteoblast differentiation and to suppress osteoclastogenesis, in part via canonical Wnt signaling. In conclusion, mesenchymal cell-derived Wnt1, acting in short range, is an essential regulator of bone homeostasis and an intriguing target for therapeutic interventions for bone diseases. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Long-Term Treatment With TNF-Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis
Authors: Beek Kimberley Johanna , Rusman Tamara , van der Weijden Maria Alida Cornelia , Lems Willem Frederik , van Denderen Johannes Christiaan , Konsta Maria , Visman Ingrid , Nurmohamed Michael Twahier , van der Horst-Bruinsma Irene Eva 
Published: January 2019

ABSTRACT

The aim of this cohort study was to evaluate the long-term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X-rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score text-decoration:underline1/text-decoration:underline20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p = 0.03) with low hip BMD and 25.3% (p &lt; 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score ≥2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters—the ankylosing spondylitis disease activity scale, the C-reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index—decreased significantly (p &lt; 0.001). The mean radiological progression (n = 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p &lt; 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration. © 2019 American Society for Bone and Mineral Research.
Hyperuricemia and gout are associated with cancer incidence and mortality: A meta‐analysis based on cohort studies
Authors: Xie Yuxiu , Xu Peng , Liu Kang , Lin Shuai , Wang Meng , Tian Tian , Dai Cong , Deng Yujiao , Li Na , Hao Qian , Zhou Linghui , Dai Zhijun , Guo Hui 
Published: January 2019

AbstractThe association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta‐analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose–response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04–1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03–1.11; females, RR = 1.06; 95% CI, 0.96–1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05–1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09–1.45; males, RR = 1.02; 95% CI, 0.80–1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01–1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99–1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12–1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.
Long noncoding RNA FEZF1‐AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR‐142/HIF‐1α and miR‐133a/EGFR upon hypoxia/normoxia
Authors: Ou Zheng‐Lin , Zhang Min , Ji Lian‐Dong , Luo Zhen , Han Tong , Lu Ye‐Bin , Li Yi‐Xiong 
Published: January 2019

AbstractNowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment‐resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR‐142/HIF‐1α and miR‐133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1‐AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR‐142 and miR‐133a; thus, we hypothesized that FEZF1‐AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1‐AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR‐142/HIF‐1α axis under hypoxic condition; however, FEZF1‐AS1 failed to affect the protein levels of HIF‐1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1‐AS1 could target miR‐133a to inhibit its expression; under the normoxic condition, FEZF1‐AS1 exerted its effect on PC cell lines through miR‐133a/EGFR axis. Taken together, FEZF1‐AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.
Fabrication of novel combinatorial drug encapsulated micelles for enhanced tumor targeting in intestinal cancer in mouse model
Authors: Yu Haixiang , Zhang Chunpeng , Zhang Kai , Zhou Yangyang , Li Chunsheng 
Published: January 2019

AbstractHindrance to successful therapy of colon cancer is generally characterized with reduced potency of a single drug at the active site of cancer, poor drug release, and most importantly, potential toxic side effects of the drug resulting in cytotoxicity. Therefore, we investigated combinatorial drug micelles which are a potent combination of twin anticancer drugs (indomethacin and piroxicam, IND+PIR mc) for successful therapeutics of colon cancer. The novel combinatorial micelles showed improved drug encapsulation efficiency, an in vitro burst release of the dual drugs, increased cytocompatibility and increased efficacy in tumor reduction (weight and volume) than in single drug micelles (IND mc or PIR mc). The improved IND+PIR MC were to have small size 150.36 ± 15.13 nm (to avoid being taken up by liver, lungs or kidney or to sediment) with poly dispersity index (PDI) value at 0.24 ± 0.01. The PDI values suggest homogenous distribution. Encapsulation efficiency of IND+PIR mc was calculated at 86%. IND+PR mc had improved biocompatibility as demonstrated by CRL‐1459™ (normal colon) cell line than IND mc or PIR mc individually. The in vivo studies in mice model clearly depict that subcutaneous tumor weight reduced by almost 75% and volume reduced drastically by 55% on administration of IND+PIR mc than IND mc or PIR mc. Furthermore, fewer side effects were found with IND+PIR mc. To conclude, IND+PIR mc may be a potential anticancer strategy to be explored more in the future.
GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects
Authors: Wang Qinghua , Ren Liwei , Wan Yun , Prud'homme Gerald J. 
Published: January 2019

AbstractDiabetes occurs when pancreatic β‐cell death exceeds β‐cell growth, which leads to loss of β‐cell mass. An effective therapy must have two actions: promotion of β‐cell replication and suppression of β‐cell death. Previous studies have established an important role for γ‐aminobutyric acid (GABA) in islet‐cell hormone homeostasis, as well as the maintenance of the β‐cell mass. GABA exerts paracrine actions on α cells in suppressing glucagon secretion, and it has autocrine actions on β cells that increase insulin secretion. Multiple studies have shown that GABA increases the mitotic rate of β cells. In mice, following β‐cell depletion with streptozotocin, GABA therapy can restore the β‐cell mass. Enhanced β‐cell replication appears to depend on growth and survival pathways involving Akt activation. Some studies have also suggested that it induces transdifferentiation of α cells into β cells, but this has been disputed and requires further investigation. In addition to proliferative effects, GABA protects β cells against injury and markedly reduces their apoptosis under a variety of conditions. The antiapoptotic effects depend at least in part on the enhancement of sirtuin‐1 and Klotho activity, which both inhibit activation of the NF‐κB inflammatory pathway. Importantly, in xenotransplanted human islets, GABA therapy stimulates β‐cell replication and insulin secretion. Thus, the intraislet GABAergic system is a target for the amelioration of diabetes therapy, including β‐cell survival and regeneration. GABA (or GABAergic drugs) can be combined with other antidiabetic drugs for greater effect.
Hypolipidemic effects of Rosmarinus officinalis L
Authors: Farkhondeh Tahereh , Samarghandian Saeed , Pourbagher‐Shahri Ali Mohammad 
Published: January 2019

AbstractDyslipidemia is one of the major risk factors for cardiovascular diseases (CVDs). Current strategies are not effective in the management of dyslipidemia. Thus, there is a necessity to find new preventative and therapeutic approaches. In recent years, herbal medicine has drawn great attention regarding the prevention and management of dyslipidemia. Rosmarinus officinalis, commonly known as rosemary, is an evergreen shrub containing several polyphenols. The plant grows in the Mediterranean and South American regions. Rosemary and its main components have antioxidant, anti‐inflammatory, and lipid‐lowering properties. The present review has focused on in vivo and in vitro studies on the hypolipidemic effects of rosemary and its main constituents as well as their functional mechanisms. Studies have described lipid‐scavenging activities of rosemary through its ﬂavonoid contents. Modulating inflammation and oxidative stress have been described as possible mechanisms by which rosemary ameliorates dyslipidemia. However, the exact mechanisms are not fully understood yet. Conducting experimental and clinical trial studies are recommended to conﬁrm the safety and efficacy of rosemary in the prevention and management of dyslipidemia and other cardio‐metabolic diseases.
Advanced strategies for combating bacterial biofilms
Authors: Sharahi Javad Yasbolaghi , Azimi Taher , Shariati Aref , Safari Hossein , Tehrani Melika Khanzadeh , Hashemi Ali 
Published: January 2019

AbstractBiofilms are communities of microorganisms that are formed on and attached to living or nonliving surfaces and are surrounded by an extracellular polymeric material. Biofilm formation enjoys several advantages over the pathogens in the colonization process of medical devices and patients' organs. Unlike planktonic cells, biofilms have high intrinsic resistance to antibiotics and sanitizers, and overcoming them is a significant problematic challenge in the medical and food industries. There are no approved treatments to specifically target biofilms. Thus, it is required to study and present innovative and effective methods to combat a bacterial biofilm. In this review, several strategies have been discussed for combating bacterial biofilms to improve healthcare, food safety, and industrial process.
Identification of Sox10‐positive cells at the dorsal fin base of juvenile flounder that are correlated with blind‐side skin ectopic pigmentation
Authors: Togawa Mai , Endo Yuna , Suzuki Nobuo , Yokoi Hayato , Suzuki Tohru 
Published: January 2019

AbstractFlounder develop left‐right asymmetric body color, with a dark ocular side and white blind side. However, ectopic pigmentation often occurs on the blind side when juveniles are reared in tanks. To examine the developmental mechanism underlying ectopic pigmentation, we first examined the pigmentation process on the blind side and the localization of chromatoblasts during spontaneous and regeneration‐stimulated ectopic pigmentation. Wild‐caught juveniles that had completed metamorphosis in a natural environment were reared in tanks, where they exhibited ectopic pigmentation on the blind side that was initiated at the base of the dorsal and anal fins, with chromatoblasts appearing at the edges of scales and melanophores spreading on the scale papilla beneath the epidermis. During tissue regeneration at the base of the dorsal fin in juvenile before ectopic pigmentation, melanophores and chromatoblasts newly appeared on regenerated blind‐side skin, resulting in rapid pigmentation at the wounded site. During regeneration‐stimulated pigmentation, gch2‐positive chromatoblasts were detected only under the regenerated epidermis. Next, we found that Sox10‐positive cells were localized in connective tissue at the base of the dorsal fin and that when connective tissue was labeled with DiO, DiO‐labeled melanophores appeared in regenerated skin of the blind side after wounding. Therefore, we conclude that in flounder juveniles, Sox10‐positive progenitors of pigment cell lineage reside at the base of the dorsal fin and start migrating to the blind‐side skin in response to specific stimuli, resulting in ectopic pigmentation. Ectopic pigmentation in flounder could be a good model for examining the flexibility of pigment cell differentiation.
Talking across generations: Family communication aboutBRCA1andBRCA2genetic cancer risk
Authors: Young Alison Luk , Butow Phyllis N. , Rhodes Paul , Tucker Katherine M. , Williams Rachel , Healey Emma , Wakefield Claire E. 
Published: January 2019

AbstractWhile family communication about aBRCA1orBRCA2(BRCA1/2) pathogenic variant can be a catalyst for the uptake of risk‐reducing measures in young adults, disseminating information within families and across generations is complex. This study aimed to explore how young adults and their families communicate about aBRCA1/2pathogenic variant, from a family systems perspective. In‐depth family interviews and questionnaires (N = 67 individuals; 21 families) were completed at four metropolitan and regional genetic clinics in Australia. Data involved thematic analysis and interpretation based on family systems theory, including the use of standardized measures. Six key themes were identified and explored: (1) Responsibility to protect, (2) “It's a woman's problem,” (3) Family culture influences communication, (4) Adversarial growth and connection, (5) Key events can be relational turning points, and (6) Health professionals can help. Family identities were solidified through the incorporation of a pathogenic variant in family scripts, while members of the family who held differing views to their families expressed less agreeableness and openness to disseminate information. The collective family's experience and perspective toward a pathogenic variant can influence a young adult's decision‐making about genetic testing, risk‐management, and family planning. The utilization of family therapy skills in routine practice would be helpful in facilitating communication and the inclusion of standardized measures is beneficial to identify individuals needing ongoing psychological support. Understanding relationship difficulties that arise from family members holding divergent views can offer insight into future research inquiry and areas of further training and clinical support.