bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study
Authors: Reimondo Giuseppe , Castellano Elena , Grosso Maurizio , Priotto Roberto , Puglisi Soraya , Pia Anna , Pellegrino Micaela , Borretta Giorgio , Terzolo Massimo 
Published: January 2020

Abstract

Context
The frequency of adrenal incidentalomas and their association with comorbid conditions have been assessed mostly in retrospective studies that may be prone to ascertainment bias.

Objective
The objective of this work is to evaluate the frequency of adrenal incidentalomas and their associated comorbid conditions.

Design
A prospective cohort study was conducted.

Setting
This study took place at a radiology department at a public hospital.

Participants
Unselected outpatients who underwent an abdominal computed tomography (CT) from January 2017 to June 2018. Patients with known or suspected adrenal disease or malignancy were excluded.

Exposure
All abdominal CT scans were evaluated by an experienced radiologist. Hormonal workup including a 1-mg dexamethasone suppression test was performed in patients bearing adrenal incidentalomas.

Main Outcome and Measure
Frequency of adrenal incidentalomas in abdominal CT of unselected patients; frequency of comorbid conditions, and hormonal workup in patients bearing adrenal incidentalomas.

Results
We recruited 601 patients, and in 7.3% of them an adrenal tumor was found serendipitously. The patients bearing an adrenal incidentaloma had higher body mass index (P = .009) and waist circumference (P = .004) and were more frequently diabetic (P = .0038). At multivariable regression analysis, diabetes was significantly associated with the presence of adrenal incidentalomas (P = .003). Autonomous cortisol secretion was observed in 50% of patients who did not suppress cortisol less than 50 nmol/L after 1 mg dexamethasone.

Conclusions
The frequency of adrenal incidentalomas is higher than previously reported. Moreover, adrenal incidentalomas are tied to increased risk of type 2 diabetes. This finding is free from ascertainment bias because patients with adrenal incidentalomas were drawn from a prospective cohort with the same risk of diabetes as the background population.
Poor Sleep Is Related to Metabolic Syndrome Severity in Adolescents With PCOS and Obesity
Authors: Simon Stacey , Rahat Haseeb , Carreau Anne-Marie , Garcia-Reyes Yesenia , Halbower Ann , Pyle Laura , Nadeau Kristen J , Cree-Green Melanie 
Published: January 2020

Abstract

Context
Polycystic ovary syndrome (PCOS) is a common endocrine disorder and is associated with metabolic syndrome (MS). Development of MS in PCOS is likely multifactorial and may relate to poor sleep.

Objective
The objective of this research is to investigate differences in objective markers of sleep in adolescents with obesity and PCOS with and without MS. We also aimed to examine the relationships between markers of sleep with MS markers.

Design
A cross-sectional study was conducted.

Participants
Participants included adolescents with PCOS and obesity with MS (N = 30) or without MS (N = 36).

Outcome Measures
Hormone and metabolic measurements, abdominal magnetic resonance imaging for hepatic fat fraction, actigraphy to estimate sleep, and overnight polysomnography (PSG).

Results
Adolescents with obesity and PCOS who also had MS had significantly worse sleep-disordered breathing including higher apnea-hypopnea index (AHI, P = .02) and arousal index (P = .01) compared to those without MS. Actigraphy showed no differences in habitual patterns of sleep behaviors including duration, timing, or efficiency between groups. However, a greater number of poor sleep health behaviors was associated with greater number of MS components (P = .04). Higher AHI correlated with higher triglycerides (TG) (r = 0.49, P = .02), and poorer sleep efficiency correlated with higher percentage of liver fat (r = –0.40, P = .01), waist circumference (r = –0.46, P &lt; .01) and higher TG (r = –0.34, P = .04).

Conclusions
Among girls with PCOS and obesity, sleep-disordered breathing was more prevalent in those with MS, and poor sleep behaviors were associated with metabolic dysfunction and more MS symptoms. Sleep health should be included in the assessment of adolescents with PCOS and obesity.
Nephrocalcinosis, Renal Dysfunction, and Calculi in Patients With Primary Hypoparathyroidism on Long-Term Conventional Therapy
Authors: Saha Soma , Kandasamy Devasenathipathy , Sharma Raju , Bal Chandrasekhar , Sreenivas Vishnubhatla , Goswami Ravinder 
Published: January 2020

AbstractContextThere are concerns about the long-term safety of conventional therapy on renal health in patients with hypoparathyroidism. Careful audit of these would help comparisons with upcoming parathyroid hormone therapy.ObjectiveWe investigated nephrocalcinosis, renal dysfunction, and calculi, their predictors and progression over long-term follow-up in patients with primary hypoparathyroidism (PH).Design and SettingAn observational study at a tertiary care center was conducted.Participants and MethodsA total of 165 PH patients receiving conventional therapy were evaluated by radiographs, ultrasonography, and computed tomography. Their glomerular filtration rate (GFR) was measured by Tc-99m-diethylenetriamine penta-acetic acid clearance. Clinical characteristics, serum total calcium, phosphorus, creatinine, hypercalciuria, and fractional excretion of phosphorus (FEPh) at presentation and during follow-up were analyzed as possible predictors of renal complications. Controls were 165 apparently healthy individuals.ResultsNephrocalcinosis was present in 6.7% of PH patients but not in controls. Patients younger than 15 years at presentation and with higher serum calcium-phosphorus product were at higher risk. Nephrocalcinosis showed no significant association with cataract and intracranial calcification. Prevalence of renal calculi was comparable between hypoparathyroid patients and controls (5% vs 3.6%, P = .58). Fourteen percent of patients had a GFR less than 60 mL/min/1.73 m2. Increased FEPh during follow-up was the significant predictor of low GFR. Nephrocalcinosis developed in 9% of patients over 10 years of conventional therapy.ConclusionA total of 6.7% of PH patients had nephrocalcinosis, and 14% showed renal dysfunction. Prevalence of renal calculi was similar in patients and controls. Nine percent of patients developed nephrocalcinosis over 10 years of conventional therapy.
Postmenopausal Dense Breasts Maintain Premenopausal Levels of GH and Insulin-like Growth Factor Binding Proteins in Vivo
Authors: Dabrosin Nina , Dabrosin Charlotta 
Published: January 2020

Abstract

Context
Dense breast tissue is associated with 4 to 6 times higher risk of breast cancer by poorly understood mechanisms. No preventive therapy for this high-risk group is available. After menopause, breast density decreases due to involution of the mammary gland. In dense breast tissue, this process is haltered by undetermined biological actions. Growth hormone (GH) and insulin-like binding proteins (IGFBPs) play major roles in normal mammary gland development, but their roles in maintaining breast density are unknown.

Objective
To reveal in vivo levels of GH, IGFBPs, and other pro-tumorigenic proteins in the extracellular microenvironment in breast cancer, in normal breast tissue with various breast density in postmenopausal women, and premenopausal breasts. We also sought to determine possible correlations between these determinants.

Setting and Design
Microdialysis was used to collect extracellular in vivo proteins intratumorally from breast cancers before surgery and from normal human breast tissue from premenopausal women and postmenopausal women with mammographic dense or nondense breasts.

Results
Estrogen receptor positive breast cancers exhibited increased extracellular GH (P &lt; .01). Dense breasts of postmenopausal women exhibited similar levels of GH as premenopausal breasts and significantly higher levels than in nondense breasts (P &lt; .001). Similar results were found for IGFBP-1, -2, -3, and -7 (P &lt; .01) and for IGFBP-6 (P &lt;.05). Strong positive correlations were revealed between GH and IGFBPs and pro-tumorigenic matrix metalloproteinases, urokinase-type plasminogen activator, Interleukin 6, Interleukin 8, and vascular endothelial growth factor in normal breast tissue.

Conclusions
GH pathways may be targetable for cancer prevention therapeutics in postmenopausal women with dense breast tissue.
Genetic Risk, a Healthy Lifestyle, and Type 2 Diabetes: the Dongfeng-Tongji Cohort Study
Authors: Han Xu , Wei Yue , Hu Hua , Wang Jing , Li Zhaoyang , Wang Fei , Long Tengfei , Yuan Jing , Yao Ping , Wei Sheng , Wang Youjie , Zhang Xiaomin , Guo Huan , Yang Handong , Wu Tangchun , He Meian 
Published: January 2020

Abstract

Objective
The objective of this study is to examine whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profiles.

Design
A prospective cohort study with a median follow-up of 4.6 years from the Dongfeng-Tongji cohort was performed.

Participants
A total of 19 005 individuals without diabetes at baseline participated in the study.

Main Variable Measure
A healthy lifestyle was determined based on 6 factors: nonsmoker, nondrinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference less than 85 cm for men and less than 80 cm for women, and higher level of physical activity. Associations of combined lifestyle factors and incident diabetes were estimated using Cox proportional hazard regression. A polygenic risk score of 88 single-nucleotide polymorphisms previously associated with diabetes was constructed to test for association with diabetes risk among 7344 individuals, using logistic regression.

Results
A total of 1555 incident diabetes were ascertained. Per SD increment of simple and weighted genetic risk score was associated with a 1.39- and 1.34-fold higher diabetes risk, respectively. Compared with poor lifestyle, intermediate and ideal lifestyle were reduced to a 23% and 46% risk of incident diabetes, respectively. Association of lifestyle with diabetes risk was independent of genetic risk. Even among individuals with high genetic risk, intermediate and ideal lifestyle were separately associated with a 29% and 49% lower risk of diabetes.

Conclusion
Genetic and combined lifestyle factors were independently associated with diabetes risk. A healthy lifestyle could lower diabetes risk across different genetic risk categories, emphasizing the benefit of entire populations adhering to a healthy lifestyle.
Associations of Endogenous Sex Hormones with Carotid Plaque Burden and Characteristics in Midlife Women
Authors: Cortés Yamnia I , Barinas-Mitchell Emma , Suder Egnot Natalie , Bhasin Shalender , Jasuja Ravi , Santoro Nanette , Thurston Rebecca C 
Published: January 2020

Abstract

Context
Endogenous sex hormones may be involved in the pathogenesis of cardiovascular disease (CVD) in women. Carotid plaque characteristics, such as echogenicity, an ultrasound measure that reflects plaque composition, may identify unstable plaques that are more likely to rupture, precipitating a CVD event. However, few studies have considered sex steroids in relation to carotid plaque and its characteristics.

Objective
To evaluate estrone (E1), estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and free T (FT) in relation to carotid plaque in women.

Design, Setting, and Participants
In MsHeart, a cross-sectional study of 304 women aged 40 to 60 years, participants underwent a carotid artery ultrasound assessment. The current analysis included MsHeart participants with carotid plaque (n = 141, 46%). E1, E2, and T were assayed using liquid chromatography–tandem mass spectrometry; FT was estimated using ensemble allostery models. Regression models were adjusted for sociodemographic characteristics and CVD risk factors.

Main Outcomes
Carotid plaque burden (number of plaques, total plaque area [TPA]) and characteristics (calcification, echogenicity) were determined using semi-automated software.

Results
SHBG was inversely related to TPA (odds ratio [OR] 0.39; 95% confidence interval [CI] 0.21, 0.74; multivariable) and higher FTs were associated with greater TPA (OR 2.89; 95% CI 1.31, 6.37; multivariable). Higher E1 was related to echogenicity (OR 2.31; 95% CI 1.26, 4.33; multivariable), characteristic of more stable plaque.

Conclusions
SHBG and FT are related to TPA while E1 is related to plaque echogenicity, suggesting these hormones have different roles in the development of carotid plaque. Our findings highlight the importance of sex hormones in the development of carotid plaque in midlife women.
Inhibition of FGFR Signaling Partially Rescues Osteoarthritis in Mice Overexpressing High Molecular Weight FGF2 Isoforms
Authors: Xiao Liping , Williams Donyell , Hurley Marja M 
Published: January 2020

Abstract
Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptors (FGFRs) are key regulatory factors in osteoarthritis (OA). HMWTg mice overexpress the high molecular weight FGF2 isoforms (HMWFGF2) in osteoblast lineage and phenocopy both Hyp mice (which overexpress the HMWFGF2 isoforms in osteoblasts and osteocytes) and humans with X-linked hypophosphatemia (XLH). We previously reported that, similar to Hyp mice and XLH subjects who develop OA, HMWTg mice also develop an OA phenotype associated with increased degradative enzymes and increased FGFR1 compared with VectorTg mice. Therefore, in this study, we examined whether in vivo treatment with the FGFR tyrosine kinase inhibitor NVP-BGJ398 (BGJ) would modulate development of the OA phenotype in knee joints of HMWTg mice. VectorTg and HMWTg mice (21 days of age) were treated with vehicle or BGJ for 13 weeks. Micro–computed tomography images revealed irregular shape and thinning of the subchondral bone with decreased trabecular number and thickness within the epiphyses of vehicle-treated HMWTg knees, which was partially rescued following BGJ treatment. Articular cartilage thickness was decreased in vehicle-treated HMWTg mice, and was restored to the cartilage thickness of VectorTg mice in the BGJ-treated HMWTg group. Increased OA degradative enzymes present in HMWTg vehicle-treated joints decreased after BGJ treatment. OA in HMWTg mice was associated with increased Wnt signaling that was rescued by BGJ treatment. This study demonstrates that overexpression of the HMWFGF2 isoforms in preosteoblasts results in osteoarthropathy that can be partially rescued by FGFR inhibitor via reduction in activated Wnt signaling.
CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential
Authors: Schlaepfer Isabel R , Joshi Molishree 
Published: January 2020

Abstract
Energy homeostasis during fasting or prolonged exercise depends on mitochondrial fatty acid oxidation (FAO). This pathway is crucial in many tissues with high energy demand and its disruption results in inborn FAO deficiencies. More than 15 FAO genetic defects have been currently described, and pathological variants described in circumpolar populations provide insights into its critical role in metabolism. The use of fatty acids as energy requires more than 2 dozen enzymes and transport proteins, which are involved in the activation and transport of fatty acids into the mitochondria. As the key rate-limiting enzyme of FAO, carnitine palmitoyltransferase I (CPT1) regulates FAO and facilitates adaptation to the environment, both in health and in disease, including cancer. The CPT1 family of proteins contains 3 isoforms: CPT1A, CPT1B, and CPT1C. This review focuses on CPT1A, the liver isoform that catalyzes the rate-limiting step of converting acyl-coenzyme As into acyl-carnitines, which can then cross membranes to get into the mitochondria. The regulation of CPT1A is complex and has several layers that involve genetic, epigenetic, physiological, and nutritional modulators. It is ubiquitously expressed in the body and associated with dire consequences linked with genetic mutations, metabolic disorders, and cancers. This makes CPT1A an attractive target for therapeutic interventions. This review discusses our current understanding of CPT1A expression, its role in heath and disease, and the potential for therapeutic opportunities targeting this enzyme.
Architectural Competitions: Creating Dialogues and Promoting Excellence?
Authors: Khan Hasan-Uddin 
Published: January 2020

Abstract
Architectural competitions have become a major way of commissioning buildings, especially for corporate and government structures. They belong to a practice that dates back to ancient Greece. This editorial essay ponders some of the critical issues raised by the two major types – project competitions and ideas competitions – through representative case studies of the Aga Khan Award for Architecture and the recent competition for master plan and buildings for the Kuwait Foundation for the Advancement of Science. The notions discussed are based on the author's personal experiences over four decades, and the roles played by the major players involved in the process – the client or sponsor, the competition organizers, the designers/architects, and the architectural juries. The article ends with a consideration of why architectural competitions are valuable in the lessons they offer and the discourses they raise, and their significance for architects and architecture more broadly.
Framing 'Islamic Art' for Aesthetic Interiors: Revisiting the 1878 Paris Exhibition
Authors: Carey Moya , Volait Mercedes 
Published: January 2020

Abstract
The 1878 Exposition Universelle in Paris is known for the substantial scope and content of its Islamic art displays – the most extensive offered to an international audience by that date. A renewed analysis of this influential event demonstrates that it featured a network of distinct – though often interlinked – installations that come under the label of 'Islamic art', situated across a complex site. These included national initiatives, such as L'Égypte des Khalifes, sponsored by the ruling Khedive of Egypt, and the purpose-built Pavillon de la Perse, constructed by master-builders dispatched from Qajar Tehran. Commercial undertakings included a display of Vincent Robinson's Iranian carpets in the British India section. At the Galerie orientale curated by Albert Goupil in the Palais du Trocadéro, other objects loaned from private collections were presented. Common across these various displays was persuasively staged architecture. This article argues for the centrality of architectural salvage and reconstruction in the early history of private and public displays of Islamic art. By examining the different individuals who created both L'Égypte des Khalifes and the Galerie orientale, article proposes a new assessment of an elite domestic culture, pursued by affluent bachelor aesthetes of the period, with many modern resonances.
Barbarism Begins at Home: Islamic Art on Display in Palermo's Museo Nazionale and Sicilian Ethnography at the 1891–92 Esposizione Nazionale
Authors: Katz Dana 
Published: January 2020

Abstract
In the last quarter of the nineteenth century, Palermo's Museo Nazionale (National Museum) displayed one of the earliest institutional collections of Islamic art in Western Europe. The museum's director, Antonino Salinas, exhibited objects demonstrating the island's material heritage, including its two-and-a-half centuries of rule by North African dynasties during the medieval period. The prevailing perception elsewhere in post-unification Italy – that Sicily was ungovernable and barbaric in nature – heightened the display's significance. Another exhibition that many Italians would have perceived as representing the 'other' was the Mostra Etnografica Siciliana (Sicilian Ethnographic Exhibition), which the folklorist Giuseppe Pitrè created for the 1891–92 Palermo Esposizione Nazionale (National Exposition). Highlighting Sicily's volatile image, the Italian press implicitly equated Pitrè's show with the so-called Abyssinian Village, which stood in the exposition fairgrounds and marked the establishment of Italy's first colony in Eritrea at a time of unprecedented imperial expansion. At the National Museum, Salinas remained undeterred, and despite associations of the island's conditions with Africa, he expanded its Islamic holdings. Likewise, Pitrè exhibited costumes, tools, and devotional objects that further accentuated regional differences at the National Exposition. In both displays, Salinas and Pitrè presented what they conceived as Sicily's unique cultural and historical patrimony.
The Masjid al-Haram: Balancing Tradition and Renewal at the Heart of Islam
Authors: Martens Muhsin Lutfi 
Published: January 2020

Abstract
The following article presents a brief history of some of the building campaigns undertaken at the Masjid al-Haram in Makkah al-Mukarramah (the Great Mosque in Mecca) during the past sixteen centuries, with a particular focus on Mimar Sinan's still-extant sixteenth-century Ottoman arcade within the mosque's central courtyard. It compares a selection of historic and contemporary responses to the appropriation of land, destruction, and rebuilding undertaken by successive Muslim rulers in and around the sanctuary, before attempting to ascertain recurrent themes and issues that have characterized this dialogue over the past 1600 years.
Rethinking the Architecture of Shushtar-Nou: A Forgotten Episode of Architectural Regionalism in 1970s Iran
Authors: Sedighi Mohamad 
Published: January 2020

Abstract
Oil revenues in the late 1960s enabled the Iranian government to fund several international architecture congresses. Throughout the 1970s, a group of young Iranian architects organized a series of architectural events, among them the second Iran International Congress of Architects (IICA), held in Persepolis-Shiraz in 1974. This Congress resulted in the 'Habitat Bill of Rights', a CIAM-like charter submitted by the Iranian government to the first UN-conference on 'Human Settlements' in 1976. This article reveals the 1974 IICA's instrumental role in shaping the discourse on architectural regionalism in the design for dwelling and human habitats, approaches to the relationship between tradition and modernity, and importantly how the architecture of Kamran Diba aimed to bridge the gap between local culture and internationalism, by forming a novel synthesis of these two approaches. To illustrate the latter, this article examines the design and development of Shushtar-Nou, a new community model designed by Diba in southwest Iran. Implicit within its design is Diba's view on the Congress debates and his goal in developing a malleable environment that accommodated growth and change over time, while preserving its core attributes.