bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relation Between Cortisol and Anthropometric Measurements Throughout Lifespan: A Systematic Review and Meta-Analysis
Authors: van der Valk Eline S , Abawi Ozair , Mohseni Mostafa , Abdelmoumen Amir , Wester Vincent L , van der Voorn Bibian , Iyer Anand M , van den Akker Erica L T , Hoeks Sanne E , de Rijke Yolanda B , Stalder Tobias , van Rossum Elisabeth F C 
Published: May 2021

Abstract
Introduction: Recently, cross-sectional studies report associations between long-term glucocorticoid levels in scalp hair (HairGC) and obesity. However, there is a wide variation in studied outcomes and associations, possibly caused by differences in population characteristics, e.g. age, sex, dispersion of adiposity, and used laboratory methods. The aim of this systematic review and meta-analysis was to investigate the relation between HairGC and anthropometrics and to explore possible moderators of this association. Methods: We searched the Medline, Embase, Cochrane, Web of Science, Scopus, Cinahl, PsycInfo, and Google Scholar databases for articles that relate HairGC to measures of adiposity (date 11-16-2020). Primary outcomes were correlations between hair cortisol (HairF) and cortisone (HairE), and anthropometrics: BMI, waist circumference (WC) and waist-hip-ratio (WHR). Authors were contacted to provide missing outcome information. Pooled correlation coefficients were calculated using random effects models. Assessment of heterogeneity was performed using the I2 statistic. Exploratory moderator analyses were performed with subgroup analyses and meta-regression. This systematic review was performed in accordance to the PRISMA guidelines. Results: Our systematic search identified 150 cohorts, comprising a total of 37,107 unique individuals, of which 15,033 sampled from population-based cohorts. For BMI, the pooled correlation for HairF was 0.121 (95% CI 0.083–0.158, n=26,941; I2 94.2%, p&lt;0.001) and for HairE 0.108 (95% CI 0.047–0.167, n=7,250; I2 52%, p&lt;0.01). For WC, the pooled correlation for HairF was 0.111 (95% CI 0.058–0.164, n=10,290; I2 63%, p&lt;0.01) and for HairE 0.200 (95% CI 0.137–0.264, n=2,198; I2 0%, p=0.42). For WHR, the pooled correlation for HairF was 0.102 (95% CI 0.040–0.163, n=6,865; I2 27%, p=0.14) and for HairE 0.261 (95% CI 0.195–0.330, n=1,314; I2 0%, p=0.40). A higher percentage of male participants was related to stronger correlations with WC (p&lt;0.001), but not with BMI and WHR. Mean age, mean BMI, and mean HairGC levels of the cohorts did not significantly moderate the pooled correlations, neither did the used laboratory techniques (immunoassays vs mass spectrometry-based assays).
Conclusion: This unique, large meta-analysis demonstrates that long-term endogenous glucocorticoids as assessed by HairGC show small but consistent correlations to measures of obesity, despite a large heterogeneity between the included cohorts. The strongest associations were found between HairE and WC and between HairE and WHR. This suggests that glucocorticoid levels in the high-normal range, especially cortisone, may contribute to or reflect the state of specifically central adiposity, even within the general population.
Effects of Glucagon-Like-Peptide-1 Analogue Treatment in Genetic Obesity
Authors: Welling Mila Sofie , de Groot Cornelis J , Kleinendorst Lotte , van der Voorn Bibian , Burgerhart Jan Steven , van der Valk Eline S , van Haelst Mieke M , van den Akker Erica L T , van Rossum Elisabeth F C 
Published: May 2021

Abstract
Introduction: Obesity is highly prevalent, comes with serious health burden and is difficult to treat. In a minority, there is a genetic cause for the obesity. In these patients, therapy-resistant obesity is often observed despite intensive lifestyle treatment. Moreover, it is still unclear whether bariatric surgery is less successful in genetic obesity. Liraglutide is a Glucagon-Like-Peptide-1 (GLP-1) receptor agonist or GLP-1 analogue, showing positive effects on metabolic parameters, satiety and weight loss in lifestyle-induced obesity. We present our experiences of GLP-1 analogue treatment in patients with genetic obesity disorders. Methods: Adults with overweight or severe obesity and a molecularly proven genetic cause were treated with liraglutide 3,0 mg daily, in addition to ongoing intensive supportive lifestyle treatment. Anthropometrics, metabolic parameters, resting energy expenditure (REE), side effects, and subjectively reported satiety and quality of life were assessed. Results: Two patients with a heterozygous pathogenic melanocortin 4 recepter variant and two patients with 16p11.2 deletion syndrome, ranging in age between 21 and 32 years and in BMI between 28.1 and 55.7 kg/m2 at baseline, were treated. At end of follow-up, ranging between 33 weeks and 12 years, a mean change in BMI and waist circumference was observed of -5.7 ± 3.8 kg/m2 and -15.2 ± 21.1 cm, respectively. All patients reported better quality of life, three of them also reported improved satiety. Moreover, improvement of metabolic parameters was seen. No clear effect on REE was observed. Two patients experienced mild side effects, e.g. nausea and stomach pain, for a brief period.
Conclusion: We here show beneficial effects of GLP-1 analogues on weight, metabolic parameters, and quality of life in four patients with genetic obesity. Satiety improved in three of the four patients. All patient achieved at least the clinically relevant 5–10% weight loss. Our findings suggest that GLP-1 analogue treatment might be an effective treatment option, in addition to a healthy lifestyle, for patients with genetic obesity.
Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Obese Type Two Diabetes Patients in an Endocrine Clinic
Authors: Shaghouli Amna Ali , Aranky Rola M 
Published: May 2021

Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases that is expected to become the main cause for liver transplantation by 2030.1 Its prevalence is increasing globally and regionally, and it is set to become the leading cause of chronic liver disease in many parts of the world. However, the epidemiology and demographic characteristics of NAFLD vary worldwide.2About 20% to 30% of the patients progress to develop nonalcoholic steatohepatitis (NASH), a subtype of NAFLD, with features of hepatocyte injury such as hepatocyte ballooning. NASH can develop to fibrosis, cirrhosis, and even hepatocellular carcinoma.3 NAFLD is correlated with obesity and insulin resistance in most cases in the Western world.2In Kuwait, obesity prevalence is estimated to be 39% for adult males and 52% for adult females.4 There is no pharmacotherapy approved for NAFLD treatment, and the main treatment is lifestyle modifications focusing on body fat loss.5
Methods: In 18 months duration, a total number of 306 patients who attended an endocrine clinic in Kuwait for general health checkups with an average BMI of 33.6 (Kg/m2) were requested to do an abdominal ultrasound for fatty liver screening. And out of 306 patients, 218 patients (71% of the patients) were diagnosed with NAFLD, the rest 29% of the patients either didn’t come back for a follow up or were not diagnosed with NAFLD.
Results: 218 patients have NAFLD, 153 of them are females and 65 are males with an average age and weight of 56.4 years and 87.9kg respectively. 78% of the patients were diabetic with an average HbA1c of 7.6%. The abdominal ultrasound showed the following result:83 patients had NAFLD grade 184 patients had NAFLD grade 2 21 patients had NAFLD grade 3While 30 patients had no grading, the results showed that they have a fatty liver with no grades mentioned. Also, reports showed that 27 patients had liver cirrhosis.
The 218 patients were requested to do blood test and average results of the following parameter were as shown at baseline:
Ferritin 98.3 ng/mLHemoglobin 13.5 g/dLPlatelets 274.5 x1000/cmmAST 23.8 U/LALT 27.9 U/LDirect Bilirubin 3.5 umol/LTotal Bilirubin 8.9 umol/LThe average calculated NAFLD, BARD and Fib-4 scores were -1.1, 3 and 1.1 respectively. All patients were unaware of NAFLD.
Conclusion: 78% of the study population had NAFLD and were unaware of that. More researches on NAFLD awareness and occurrence in the region are required.
The Effectiveness of Adding Pharmacotherapy to Dietary Counseling for Veterans in a Veterans Health Administration Move! Weight Management Program
Authors: Alvarez Diego Alcaraz , Salter Mary F , Gupta Namita , Thangavelu Thiyagarajan , Desouza Cyrus V 
Published: May 2021

Abstract
Background: Over 78% of veterans are overweight or obese. MOVE! is the VA’s national evidence-based self-management program. This program focuses on health and wellness through healthy eating, physical activity, and behavior change (1). We evaluated the effects of adding pharmacotherapy to dietitian coaching in a real-world MOVE! Program in the VA Nebraska-Western Iowa Health Care System.
Methods: A systematic retrospective and prospective chart review were completed of 66 patients who completed a minimum of 6 months of medication at our Weight Loss Medicine clinic from June 2017 to February 2020. Body composition was measured using SECA Bio Electrical Impedance Analyzer. Descriptive statistics were used to analyze weight changes, fat mass (FM), and fat-free mass (FFM) changes at 6 and 12 months after starting weight loss medications.
Results: The percentage of patients with a 5% decrease in weight from baseline after at least 6 months with pharmacotherapy was 47% and a 10% decrease was 36% after 12 months. In 6 months, a decrease of a minimum of 5% was seen with GLP-1 (semaglutide or liraglutide) 55 % (29/53), orlistat 11% (1/9), and bupropion-topiramate 25 % (1/4). An average of 3.4% FM decrease and a 3.47% FFM increase was seen from baseline to 6 months and 4.8% FM decrease and 4.7% FFM increase was seen from baseline to 12 months.
Conclusion: A clinically significant decrease in weight was seen at 6 and 12 months after starting weight loss medication in addition to monthly MOVE! Dietitian visits. A significant decrease was seen in FM and an increase in FFM. Veteran’s receiving a GLP-1 had a greater amount of weight loss compared with Orlistat and bupropion-topiramate. Weight loss medication is recommended as an adjunct to dietitian counseling for optimizing weight loss.
References
1 Kinsinger LS, Jones KR, Kahwati L et al. Design and dissemination of the MOVE! Weight-Management Program for Veterans. Prev Chronic Dis 2009; 6: A98
The Association of the Polychlorinated Biphenyl Class of Endocrine Disruptors With Polycystic Ovary Syndrome and Thyroid Dysfunction
Authors: Brennan Edwina , Cunningham Thomas Keith , Sathyapalan Thozhukat , Atkin Stephen Lawrence 
Published: May 2021

Abstract
Introduction:. Polychlorinated biphenyls (PCBs) are a class of endocrine disruptors with a long half-life in the body that are associated with irregular menses, growth and development delay, increased cancer risk, thyroid disorders and an increased risk of diabetes. Higher levels of PCBs have been related to polycystic ovary syndrome (PCOS). PCB toxicity depends on their structure, with coplanar PCBs being most toxic (akin to dioxins); therefore, PCB subtypes were determined to see if they differed in women with PCOS compared to normal controls. Methods:. PCB levels were compared in Caucasian women with (n=29) and without (n=30) PCOS and related to metabolic features. PCBs were fractionated then analysed by high-resolution gas chromatography-unit resolution mass spectrometry. Results:. The control and PCOS groups were age and BMI matched (p=ns); insulin resistance was not different (HOMA 1.7±1.0 v 2±1.6, p=ns) but free androgen index was increased in PCOS (p&lt;0.004). PCB-118, 138, 153 and 180 were found in all subjects, whilst fewer subjects showed PCB-28(15/59), PCB-52(4/59) or PCB-101(26/59). There was no difference for PCB-188,138,153 and 180 between controls and PCOS, but all correlated with increasing age (p&lt;0.01) and decreasing estimated glomerular filtration rate (p&lt;0.05); no correlations with BMI, HOMA, testosterone, TSH or T3 were found; however, PCB-118 (the only coplanar PCB detected) associated with an increased T4/T3 ratio (p&lt;0.01). Conclusion. Despite PCBs being banned over a decade ago, PCBs were detected, but did not differ between age and BMI matched women with and without PCOS. Thyroid dysfunction may be only associated with toxic coplanar PCBs, such as PCB-118 that was associated with a higher T4/T3 ratio.
In Utero Exposure to 17α-Hydroxyprogesterone Caproate May Contribute to Increasing Incidence Rates of Early-Onset Cancer
Authors: Murphy Caitlin C , Cirillo Piera M , Krigbaum Nickilou Y , Cohn Barbara 
Published: May 2021

Abstract
Background: 17α-hydroxyprogesterone caproate (17-OHPC) is a synthetic progestogen introduced in the 1950s to treat habitual and threatened abortion in pregnant women. Although 17-OHPC is still available (tradename Makena), little is known about its effects on health of adult offspring, and questions concerning safety and effectiveness remain. For example, progestogens have been implicated in cancer, and trends in the use of 17-OHPC in early pregnancy during the 1950s and 60s parallel increasing incidence rates of certain cancers in young adults, such as early-onset colorectal cancer, born during that time. Methods: We examined the effect of 17-OHPC exposure in utero on risk of cancer in adult offspring in the Child Health and Development Studies, a cohort of women receiving prenatal care between June 1959 and September 1966, with deliveries through June 1967 (n=18,751 live births excluding neonatal deaths among 14,507 mothers). Diagnosed conditions and prescribed medications were abstracted from mothers’ medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received 17-OHPC (tradenames Delalutin and Proluton) in early pregnancy, defined as day 1 - 140 of gestation. Incident cancers diagnosed in offspring through 2018 were ascertained by linkage with the California Cancer Registry. Results: Among 18,751 live births, 954 cancers were diagnosed at ages 18 - 58 years. The most frequent cancers were breast (20.9%), cervical (10.9%), colorectal (7.1%), and prostate (5.9%) cancer and melanoma (9.2%). Although few mothers (n=181, 1.0%) received 17-OHPC in early pregnancy, in utero exposure was more common in offspring diagnosed with cancer (n=18, 1.9%) compared to those without cancer (n=163, 0.9%). Conditions indicating 17-OHPC included threatened abortion (54.0%), amnionitis (9.4%), and incompetent cervix (3.0%). 17-OHPC increased risk of any cancer in offspring (OR 2.08, 95% CI 1.27, 3.40), with particularly striking associations for colorectal (OR 4.78, 95% CI 1.49, 15.41) and prostate (OR 3.83, 95% CI 0.93, 15.83) cancer. There was no association between conditions indicating 17-OHPC and risk of any cancer in offspring (threatened abortion: n=1,891 mothers, OR 1.07, 95% CI 0.87, 1.32), or with use of other progestogens within 6 months prior to pregnancy (medroxyprogesterone acetate: n=50 mothers, OR 0.38, 95% CI 0.05, 2.76). Conclusions: Findings support susceptibility of multiple organ systems to endocrine disruption during early development and risk of cancer decades later - and may partly explain increasing rates of early-onset colorectal cancer. Even before mechanisms of carcinogenesis are elucidated, caution using 17-OHPC and other endocrine-active pharmaceuticals in early pregnancy is warranted, especially in the absence of a clear short-term benefit, and given the possible effect on risk of cancer in adult offspring.
Favorable Prognostics of Post-Exercise Irisine Released as Prophylaxis of Serious Covid-19 in Obese Elderly
Authors: de Oliveira Arthu Línniker Lopes , Jales Césia Santos , de Queiroz Silva Igor Thiago Borges 
Published: May 2021

Abstract
Studies sought epidemiological profiles to establish risk groups for Covid-19’s evolution and discovered that the age group above 65 years old is one of the most severely affected, due to the presence of other comorbidities. In the USA approximately 55 million individuals are above that age range and more than 23 million are elderly obese individuals, alongside the high mortality rate in this population and lack of proven effective medicine against Covid-19, therapeutic alternatives against this disease are sought. With the occurrence of inflammatory pulmonary conditions increased by SARS-Cov-2 infection, irisin was indicated as having a potential preventive action. This peptide is secreted endogenously by striated skeletal muscles with fibronectin type III domain-containing protein 5 (FNDC5) proteolysis, when preceded by continued exercise of low to moderate intensity for more than 20 uninterrupted minutes. Regarding the weight variant, previous studies showed low levels of FNDC5 in people with excess fatty acids (in humans, adipose tissue divides into white, favoring the deposit of lipids, triglycerides and fat, more easily inflamed, and brown that stimulates thermogenesis). Among other functions, FNDC5 also stimulates the coactivator 1-alpha of PPAR gamma (PGC-1α) which corroborates with the uncoupling between the Uncoupling Protein 1 (UCP1) and the mitochondria. When UCP1 is disincorporated from this organelle, it becomes active and inhibits ATP synthesis, releasing heat, as well as favoring fatty acid oxidation and provides the mechanism of browning of white fat. After this conversion, irisin reduces ¼ of lipid accumulation present in the adipocyte by lipolysis, significantly increasing the levels of serum triglycerides and glycerols, as well as considerably reducing oxidative stress and DNA damage. Other genes expressed by irisin also assist in the fat browning process, such as TMEM26, ELOVL3, CIDEa and COX7a. Regarding the age variant, the SARS-CoV-2 Spike protein benefits from the high concentration of angiotensin-converting enzyme 2 (ACE2) receptors, present in elderly pulmonary alveoli, which bind to the airway and enable contagion. However, ACE2 is negatively regulated by Tribbles homolog 3 (TRIB3) protein from its connection to the nucleocapsid protein of the virus, generating some protection for the individual when TRIB3 is at satisfactory levels. In elderly men, this protein is below normal levels, making this population more vulnerable to SARS-CoV-2 infection. Moreover, it was verified that irisin’s weekly synthesis promoted by regular physical exercises triples TRIB3 levels in pulmonary alveoli. In short, this hormone was able to negatively modulate two important risk factors related to the inflammatory profile of this elderly population (weight and age), and thus irisin should be considered a potential molecule in the prevention against Covid-19.
Histone Lysine Demethylase 1A Is a Master Regulator of Genes Necessary for Trophoblast Cell Proliferation
Authors: Bouma Gerrit J , Ali Asghar , Hord Taylor K , Parsons Agata M , Anthony Russell Vernon , Bruemmer Jason E , Winger Quinton A 
Published: May 2021

Abstract
Histone lysine demethylase 1A is a master regulator of genes necessary for trophoblast cell proliferation.
A proper functioning placenta is critical for pregnancy, fetal growth and development and postnatal health. Trophoblast cell proliferation and differentiation is critical for placental development and function. Recently we demonstrated that the histone lysine demethylase KDM1A binds to androgen receptor (AR) in human and sheep trophoblast cells, and targets the same promoter region of vascular endothelial growth factor A (VEGFA), suggesting a role for KDM1A and AR in early placental angiogenesis. The goal of this study was to determine the function of KDM1A during early placental development. We hypothesized that KDM1A regulates genes that are necessary for trophoblast cell proliferation, and early placental development. To this end, both in vitro and in vivo approaches were used in this study. ACH-3P cells (human first trimester trophoblast cells (CT and EVT) fused with the choriocarcinoma cell line AC1-1) were used, and a KDM1A knock out (KO) cell line was generated using CRISPR-Cas 9 based genome editing. KDM1A KO in ACH-3P cells led to significant (P&lt;0.05) reduction in AR and VEGFA. Furthermore, factors important for cell proliferation and trophoblast cell development high mobility group AT-hook 1 (HMGA1), LIN28, and MYC protooncogene (cMYC) were significantly (P&lt;0.05) lower in KDM1A KO ACH-3P cells. Cell proliferation assays revealed a significant (P&lt;0.05) reduction in KDM1A KO ACH-3P cells compared to scramble controls. An in vivo experiment was conducted to demonstrate a role for KDM1A in placental development, using the sheep as a model. Day 9 hatched blastocysts were flushed and infected with a Lenti-CRISPRv2 KDM1A target construct (n=4) to knockout KDM1A specifically in the trophectoderm, or with SC (n=5). Infected embryos were transferred to recipient ewes and embryos were collected at gestational day 16. Data suggests that KDM1A KO in trophoblast cells is necessary for conceptus elongation. Current experiments are ongoing to determine the effects of KDM1A and AR knockdown using shRNA lentiviral target vectors on conceptus elongation and pregnancy. Collectively these results indicate that KDM1A plays a central role in regulating genes necessary for trophoblast cell proliferation.
This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2019-67015-29000 from the USDA National Institute of Food and Agriculture.
Inherited Human XY Sex Reversal and Gonadal Neoplasia Due to Enhanced Formation of Non-Specific Enhanceosomes by an Architectural Transcription Factor
Authors: Chen Yen-Shan , Racca Joseph D , Belgorosky Alicia , Weiss Michael Aaron 
Published: May 2021

Abstract
The development of organisms is regulated by a fine-tuned gene-regulatory network, which is driven by transcription factors (TFs). In the embryogenesis, these TFs control diverse cell fates and final body plan. This is precisely regulated by a specific DNA-binding process and enhanceosome formation. A model is provided by testis determination in mammals, which is initiated by a Y-encoded architectural transcription factor, SRY. Mutations in SRY cause gonadal dysgenesis leading to various developmental defects. Such mutations cluster in SRY’s high mobility group (HMG) box, a sequence-specific DNA-binding domain shared by a conserved family of TFs. Here, we have characterized several mutations at the same position in HMG box, which are compatible with either male or female phenotypes as observed in an XY father and XY daughter, respectively. These mutations, at a function-unknown motif in the SRY HMG box, markedly disturb the specific DNA affinity. On transient transfection of human and rodent cell lines, the SRY variants exhibit decreased specific DNA-binding activity (relative to wild type) are associated with mis-formed enhanceosomes. The variants’ gene regulatory activities were reduced by 2-fold relative to wild-type SRY at similar levels of mRNA expression. When engineered mutations that functions to increase the DNA-binding specificity were deployed to SRY variants, the transcriptional activity was in association with restored occupancy of sex-specific enhancer elements in principal downstream gene Sox9. Our findings define a novel mechanism of impaired organogenesis, disturbed specific DNA-binding activity of a master transcription factor, leading to a developmental decision poised at the edge of ambiguity.