bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol modified DP7 and pantothenic acid induce dendritic cell homing to enhance the efficacy of dendritic cell vaccines
Authors: Zhang Rui , Tang Lin , Li Qing , Tian Yaomei , Zhao Binyan , Zhou Bailing , Yang Li 
Published: December 2021

AbstractDendritic cell (DC)-based cancer vaccines have so far achieved good therapeutic effects in animal experiments and early clinical trials for certain malignant tumors. However, the overall objective response rate in clinical trials rarely exceeds 15%. The poor efficiency of DC migration to lymph nodes (LNs) (< 5%) is one of the main factors limiting the effectiveness of DC vaccines. Therefore, increasing the efficiency of DC migration is expected to further enhance the efficacy of DC vaccines. Here, we used DP7-C (cholesterol modified VQWRIRVAVIRK), which can promote DC migration, as a medium. Through multiomics sequencing and biological experiments, we found that it is the metabolite pantothenic acid (PA) that improves the migration and effectiveness of DC vaccines. We clarified that both DP7-C and PA regulate DC migration by regulating the chemokine receptor CXCR2 and inhibiting miR-142a-3p to affect the NF-κB signaling pathway. This study will lay the foundation for the subsequent use of DP7-C as a universal substance to promote DC migration, further enhance the antitumor effect of DC vaccines, and solve the bottleneck problem of the low migration efficiency and unsatisfactory clinical response rate of DC vaccines.
New Horizons. A New Paradigm for Treating to Target with Second-Generation Obesity Medications
Authors: Garvey W Timothy 
Published: December 2021

Abstract
In treating obesity as a chronic disease, the essential goal of weight loss therapy is not the quantity of weight loss as an end unto itself but rather the prevention and treatment of complications to enhance health and mitigate morbidity and mortality. This perspective on obesity care is consistent with the complications-centric American Association of Clinical Endocrinology (AACE) obesity guidelines and the diagnostic term of adiposity-based chronic disease (ABCD). Many complications require 10% to 20% weight loss to achieve therapeutic goals; however, existing obesity medications fail to produce ≥10% weight loss in the majority of patients. In June, 2021, semaglutide 2.4 mg/week was approved for chronic weight management. Phase 3 clinical trials demonstrated that this medication produced &gt; 10% placebo-subtracted weight loss, more than half of patents lost ≥15%, and over one third lost ≥20% of baseline weight. This essentially doubles effectiveness over existing obesity medications, provides sufficient weight loss to ameliorate a broad range of complications, and qualifies as the first member of a second-generation class of obesity medications. The advent of second-generation medications fully enables a treat-to-target approach for management of ABCD as a chronic disease. Specifically, with this degree of efficacy, second-generation medications permit active management of body weight as a biomarker to targets associated with effective treatment and prevention of specific complications. ABCD can now be managed similar to other chronic diseases such as type 2 diabetes, hypertension, and atherosclerosis, which are treated to biomarker targets that can be modified based on the clinical status of individual patients [ie, hemoglobin A1c (HbA1c), blood pressure, and low-density lipoprotein cholesterol (LDL-c)] to prevent the respective complications of these diseases.
Low Progesterone and Low Estradiol Levels Associate With Abdominal Aortic Aneurysms in Men
Authors: Ohlsson Claes , Langenskiöld Marcus , Smidfelt Kristian , Poutanen Matti , Ryberg Henrik , Norlén Anna-Karin , Nordanstig Joakim , Bergström Göran , Tivesten Åsa 
Published: December 2021

Abstract

Context
Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.

Objective
We aimed to describe the associations between serum sex steroids and early, screening-detected AAA in men.

Methods
We validated a high-sensitivity liquid chromatography–tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥ 30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.

Outcomes included
associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.

Results
Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI, 1.18-2.22]) and estradiol (1.40 [95% CI, 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI, 2.25-7.31]).

Conclusion
Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independent of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.
Oral Contraceptive and Menopausal Hormone Therapy Use and Risk of Pituitary Adenoma: Cohort and Case-Control Analyses
Authors: Cote David J , Kilgallon John L , Nawabi Noah L A , Dawood Hassan Y , Smith Timothy R , Kaiser Ursula B , Laws Edward R , Manson JoAnn E , Stampfer Meir J 
Published: December 2021

AbstractContextNo prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women.ObjectiveOur aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets.MethodsWe evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses’ Health Study and Nurses’ Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use.ResultsIn the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never.ConclusionCompared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis.
Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1
Authors: Mozar Fitya , Sharma Vikas , Gorityala Shashank , Albert Jeffrey M , Xu Yan , Montano Monica M 
Published: December 2021

Abstract
We have previously reported that hexamethylene bis-acetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound estrogen receptor α (ERα) and the androgen receptor (AR) by disrupting the interaction between these receptors and positive transcriptional elongation factor b (P-TEFb) and attenuating RNA polymerase II (RNAPII) phosphorylation at serine 2. Functional consequences of the inhibition of transcriptional activity of ERα and AR by HEXIM1 include the inhibition of ERα- and AR-dependent gene expression, respectively, and the resulting attenuation of breast cancer (BCa) and prostate cancer (PCa) cell proliferation and growth. In our present study, we determined that HEXIM1 inhibited AKR1C3 expression in BCa and PCa cells. AKR1C3, also known as 17β-hydroxysteroid dehydrogenase (17β-HSD) type 5, is a key enzyme involved in the synthesis of 17β-estradiol (E2) and 5-dihydrotestosterone (DHT). Downregulation of AKR1C3 by HEXIM1 influenced E2 and DHT production, estrogen- and androgen-dependent gene expression, and cell proliferation. Our studies indicate that HEXIM1 has the unique ability to inhibit both the transcriptional activity of the ER and AR and the synthesis of the endogenous ligands of these receptors.
Glucocorticoid Production in Lymphoid Organs: Acute Effects of Lipopolysaccharide in Neonatal and Adult Mice
Authors: Salehzadeh Melody , Hamden Jordan E , Li Michael X , Bajaj Hitasha , Wu Ruolan S , Soma Kiran K 
Published: December 2021

AbstractGlucocorticoids (GCs) are critical modulators of the immune system. The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating GC levels and is stimulated by endotoxins. Lymphoid organs also produce GCs; however, it is not known how lymphoid GC levels are regulated in response to endotoxins. We assessed whether an acute challenge of lipopolysaccharide (LPS) increases lymphoid levels of progesterone and GCs, and expression of steroidogenic enzymes and key HPA axis components (eg, corticotropin-releasing hormone [CRH], adrenocorticotropic hormone [ACTH]). We administered LPS (50 µg/kg intraperitoneally) or vehicle control to male and female C57BL/6J neonatal (postnatal day [PND] 5) and adult (PND90) mice and collected blood, bone marrow, thymus, and spleen 4 hours later. We measured progesterone, 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone via liquid chromatography–tandem mass spectrometry. We measured gene expression of key steroidogenic enzymes (Cyp11b1, Hsd11b1, and Hsd11b2) and HPA axis components (Crh, Crhr1, Pomc, and Mc2r) via quantitative polymerase chain reaction. At PND5, LPS induced greater increases in steroid levels in lymphoid organs than in blood. In contrast, at PND90, LPS induced greater increases in steroid levels in blood than in lymphoid organs. Steroidogenic enzyme transcripts were present in all lymphoid organs, and LPS altered steroidogenic enzyme expression predominantly in the spleen. Lastly, we detected transcripts of key HPA axis components in all lymphoid organs, and there was an effect of LPS in the spleen. Taken together, these data suggest that LPS regulates GC production by lymphoid organs, similar to its effects on the adrenal glands, and the effects of LPS might be mediated by local expression of CRH and ACTH.
Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice
Authors: Stamatiades George A , Toufaily Chirine , Kim Han Kyeol , Zhou Xiang , Thompson Iain R , Carroll Rona S , Chen Min , Weinstein Lee S , Offermanns Stefan , Boehm Ulrich , Bernard Daniel J , Kaiser Ursula B 
Published: December 2021

Abstract
Gonadotropin-releasing hormone (GnRH) regulates gonadal function via its stimulatory effects on gonadotropin production by pituitary gonadotrope cells. GnRH is released from the hypothalamus in pulses and GnRH pulse frequency differentially regulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion. The GnRH receptor (GnRHR) is a G protein–coupled receptor that canonically activates Gα q/11-dependent signaling on ligand binding. However, the receptor can also couple to Gα s and in vitro data suggest that toggling between different G proteins may contribute to GnRH pulse frequency decoding. For example, as we show here, knockdown of Gα s impairs GnRH-stimulated FSH synthesis at low- but not high-pulse frequency in a model gonadotrope-derived cell line. We next used a Cre-lox conditional knockout approach to interrogate the relative roles of Gα q/11 and Gα s proteins in gonadotrope function in mice. Gonadotrope-specific Gα q/11 knockouts exhibit hypogonadotropic hypogonadism and infertility, akin to the phenotypes seen in GnRH- or GnRHR-deficient mice. In contrast, under standard conditions, gonadotrope-specific Gα s knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in Gα s knockout females and postgonadectomy increases in FSH and LH are reduced both in males and females. These data suggest that GnRH may signal principally via Gα q/11 to stimulate gonadotropin production, but that Gα s plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced.
New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature
Authors: Federici Silvia , Goggi Giovanni , Quinton Richard , Giovanelli Luca , Persani Luca , Cangiano Biagio , Bonomi Marco 
Published: December 2021

Abstract
Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at “the child with delayed puberty of uncertain etiology” risk being misapplied to older adolescents likely to have permanent hypogonadism.
The Effect of Curative Treatment on Hyperglycemia in Patients With Cushing Syndrome
Authors: Herndon Justine , Kaur Ravinder Jeet , Romportl Mark , Smith Emily , Koenigs Amy , Partlow Brenda , Arteaga Leonardo , Bancos Irina 
Published: December 2021

Abstract

Context
Hyperglycemia is a common complication of Cushing syndrome (CS).

Objective
We aimed to determine the impact of curative procedure on hyperglycemia and its management in patients with CS.

Methods
This retrospective longitudinal cohort study took place 2000 to 2019 in a referral center among adults with endogenous CS and hyperglycemia. Main outcome measures included glycated hemoglobin A1c (HbA1c), intensity of hyperglycemia therapy, and improvement of hyperglycemia.

Results
In 174 patients with CS (pituitary in 106, ectopic in 25, adrenal in 43), baseline median HbA1c was 6.9% (range, 4.9-13.1), with 41 (24%) patients not on any therapy for hyperglycemia, 93 (52%) on oral medications, and 64 (37%) on insulin (median daily units of 58; range, 10-360). Following CS remission, at the end of follow-up (median 10.5 months), 37 (21%) patients demonstrated resolution of hyperglycemia, 82 (47%) demonstrated improvement, and 55 (32%) had no change or worsening in hyperglycemia. At the end of follow-up, HbA1c decreased by 0.84% (P &lt; .001) and daily insulin dose decreased by a mean of 30 units (P &lt; .001). Biochemical hypercortisolism severity score (severe vs moderate/mild: odds ratio [OR] of 2.4 [95% CI, 1.1-4.9]), and CS subtype (nonadrenal vs adrenal: OR of 2.9 [95% CI, 1.3-6.4]), but not type of hyperglycemia (diabetes vs prediabetes: OR of 2.1 [0.9-4.9]) were associated with hyperglycemia improvement at the end of follow-up.

Conclusion
Two-thirds of patients with CS and hyperglycemia demonstrate resolution or improvement of hyperglycemia after a curative procedure. Close monitoring during CS recovery is needed to ensure appropriate therapy modification.
Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity, and Insulin Sensitivity in Normoglycemic Black and White Adults
Authors: Umekwe Nkiru , Owei Ibiye , Stentz Frankie , Dagogo-Jack Sam 
Published: December 2021

Abstract
Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia, and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included oral glucose tolerance test, insulin sensitivity (Si-clamp), insulin secretion (homeostasis model assessment index of b-cell function [HOMA-B]), and body fat (dual-energy X-ray absorptiometry). Fasting plasma FGF-21 and sclerostin levels were measured with enzyme-linked immunosorbent assays. The participants’ mean (+SD) age was 50.4 ± 5.97 years; body mass index (BMI) 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dL, and 2-hour postload glucose 116 ± 5.45 mg/dL. FGF-21 levels were similar in Black people vs White people (0.36 ± 0.15 ng/mL vs 0.39 ± 0.25 ng/mL), men vs women (0.45 ± 0.14 vs 0.44 ± 0.07 ng/mL), correlated positively with BMI (r = 0.23, P = .05) and waist circumference (r = 0.27, P = .04), and inversely with FPG (r = –0.26, P = .05). Sclerostin levels also were similar in Black people (33.5 ± 17.1 pmol/L) vs White people (34.2 ± 6.41 pmol/L), men vs women (35.3 ± 9.01 pmol/L vs 32.3 ± 15.8 pmol/L), and correlated inversely with FPG (r = –0.11 to –0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was –0.31 (P = .09) compared with 0.04 (P = .89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.
The Multiply Produced Film: Collaboration, Ethnography, and Feminist Epistemology
Authors: Hong Emily 
Published: December 2021

This article introduces the “multiply produced film” as a methodology and analytic that highlights the asymmetrical dynamics inherent to collaboration. I draw on (auto)ethnographic material from the making of Get By (2014), a film on worker-community solidarity, to explore collaboration across race, class, and gender in subject matter and method. I situate the multiply produced film within a genealogy that grafts ontological insights from the anthropology of exchange onto the epistemological contributions of feminist, decolonial, and visual anthropologists committed to collaboration. I argue that as a method, collaborative filmmaking has the potential to challenge narrow Western conceptions of autonomy and authorship through shared authority and fluid roles that engender a cascading multivocality that shapes the resulting filmic form. As an analytic, the multiply produced film reveals how collaboration entails a fundamental tension between the gift-like exchanges of solidarity and the outwardly commoditized form (e.g., films, books) produced by such exchanges, raising questions about asymmetries of power, prestige, and accountability.
Machine Learning Models Based on Random Forest Feature Selection and Bayesian Optimization for Predicting Daily Global Solar Radiation
Authors: Chaibi Mohamed , Benghoulam El Mahjoub , Tarik Lhoussaine , Berrada Mohamed , El Hmaidi Abdellah 
Published: December 2021

Prediction of daily global solar radiation with simple and highly accurate models would be beneficial for solar energy conversion systems. In this paper, we proposed a hybrid machine learning methodology integrating two feature selection methods and a Bayesian optimization algorithm to predict H in the city of Fez, Morocco. First, we identified the most significant predictors using two Random Forest methods of feature importance: Mean Decrease in Impurity (MDI) and Mean Decrease in Accuracy (MDA). Then, based on the feature selection results, ten models were developed and compared: (1) five standalone machine learning (ML) models including Classification and Regression Trees (CART), Random Forests (RF), Bagged Trees Regression (BTR), Support Vector Regression (SVR), and Multi-Layer Perceptron (MLP); and (2) the same models tuned by the Bayesian optimization (BO) algorithm: CART-BO, RF-BO, BTR-BO, SVR-BO, and MLP-BO. Both MDI and MDA techniques revealed that extraterrestrial solar radiation and sunshine duration fraction were the most influential features. The BO approach improved the predictive accuracy of MLP, CART, SVR, and BTR models and prevented the CART model from overfitting. The best improvements were obtained using the MLP model, where RMSE and MAE were reduced by 17.6% and 17.2%, respectively. Among the studied models, the SVR-BO algorithm provided the best trade-off between prediction accuracy (RMSE=0.4473kWh/m²/day, MAE=0.3381kWh/m²/day, and R²=0.9465), stability (with a 0.0033kWh/m²/day increase in RMSE), and computational cost.
Фазомодульоване параметричне антистоксове вимушене комбінаційне розсіяння черенковського типу в областях самофокусування збуджуючого випромінювання
Authors: Іванісік А.І. , Ісаєнко О.Ю. , Коротков П.А. , Понежа Г.В. 
Published: December 2021

Розглянуто вплив швидкості руху фокальної точки самофокусування та фазової самомодуляції на частотно-кутові спектри випромінюванняпараметричної антистоксової компоненти вимушеного комбінаційного розсіяння. Враховано фазову самомодуляцію як збуджуючого, так ірозсіяного антистоксового випромінювання. Пояснено утворення протяжних антистоксових частотно-кутових смуг. У випадку збігання швидкості фокальної точки самофокусування з фазовою швидкістю нелінійної поляризації на антистоксовій комбінаційній частоті та фазовою швидкістю розсіяного осьового випромінювання утворюються найінтенсивніші частотно-кутові смуги, які описуються співвідношеннями, характерними для черенковського випромінювання. Зокрема, за збудження наносекундними лазерними імпульсами в толуолі такі смуги сягають довжини ≈–200 cм–1 відносно комбінаційної антистоксової частоти.