bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation
Authors: Mohamed Mohamed-Eslam F. , Trueman Sheryl , Othman Ahmed A. , Han Jian-Hwa , Ju Tzuchi R. , Marroum Patrick 
Published: October 2019

Abstract
Upadacitinib is a selective Janus Kinase 1 inhibitor which is being developed for the treatment of several inflammatory diseases including rheumatoid arthritis. Upadacitinib was evaluated in Phase 3 studies as an oral extended-release (ER) formulation administered once daily. The purpose of this study was to develop a level A in vitro–in vivo correlation (IVIVC) for upadacitinib ER formulation. The pharmacokinetics of four upadacitinib extended-release formulations with different in vitro release characteristics and an immediate-release capsule formulation of upadacitinib were evaluated in 20 healthy subjects in a single-dose, randomized, crossover study. In vivo pharmacokinetic data and in vitro dissolution data (USP Dissolution Apparatus 1; pH 6.8; 100 rpm) were used to establish a level A IVIVC. Three formulations were used to establish the IVIVC, and the fourth formulation was used for external validation. A non-linear IVIVC best described the relationship between upadacitinib in vitro dissolution and in vivo absorption profiles. The absolute percent prediction errors (%PE) for upadacitinib Cmax and AUC were less than 10% for all three formulations used to establish the IVIVC, as well as for the %PE for the external validation formulation and the overall mean internal validation. Model was cross-validated using the leave-one-out approach; all evaluated cross-validation runs met the regulatory acceptance criteria. A level A IVIVC was successfully developed and validated for upadacitinib ER formulation, which meets the FDA and EMA regulatory validation criteria and can be used as surrogate for in vivo bioequivalence.
U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study
Authors: Hu Lihua , Hu Guiping , Xu Benjamin Ping , Zhu Lingjuan , Zhou Wei , Wang Tao , Bao Huihui , Cheng Xiaoshu 
Published: October 2019

Abstract

Background
In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality.

Methods
This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality.

Results
During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females.

Conclusion
Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.
IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction
Authors: Joustra Sjoerd D , Roelfsema Ferdinand , van Trotsenburg A S Paul , Schneider Harald J , Kosilek Robert P , Kroon Herman M , Logan John G , Butterfield Natalie C , Zhou Xiang , Toufaily Chirine , Bak Beata , Turgeon Marc-Olivier , Brûlé Emilie , Steyn Frederik J , Gurnell Mark , Koulouri Olympia , Le Tissier Paul , Fontanaud Pierre , Duncan Bassett J H , Williams Graham R , Oostdijk Wilma , Wit Jan M , Pereira Alberto M , Biermasz Nienke R , Bernard Daniel J , Schoenmakers Nadia 
Published: October 2019

AbstractContextThe X-linked immunoglobulin superfamily, member 1 (IGSF1), gene is highly expressed in the hypothalamus and in pituitary cells of the POU1F1 lineage. Human loss-of-function mutations in IGSF1 cause central hypothyroidism, hypoprolactinemia, and macroorchidism. Additionally, most affected adults exhibit higher than average IGF-1 levels and anecdotal reports describe acromegaloid features in older subjects. However, somatotrope function has not yet been formally evaluated in this condition.ObjectiveWe aimed to evaluate the role of IGSF1 in human and murine somatotrope function.Patients, Design, and SettingWe evaluated 21 adult males harboring hemizygous IGSF1 loss-of-function mutations for features of GH excess, in an academic clinical setting.Main Outcome MeasuresWe compared biochemical and tissue markers of GH excess in patients and controls, including 24-hour GH profile studies in 7 patients. Parallel studies were undertaken in male Igsf1-deficient mice and wild-type littermates.ResultsIGSF1-deficient adult male patients demonstrated acromegaloid facial features with increased head circumference as well as increased finger soft-tissue thickness. Median serum IGF-1 concentrations were elevated, and 24-hour GH profile studies confirmed 2- to 3-fold increased median basal, pulsatile, and total GH secretion. Male Igsf1-deficient mice also demonstrated features of GH excess with increased lean mass, organ size, and skeletal dimensions and elevated mean circulating IGF-1 and pituitary GH levels.ConclusionsWe demonstrate somatotrope neurosecretory hyperfunction in IGSF1-deficient humans and mice. These observations define a hitherto uncharacterized role for IGSF1 in somatotropes and indicate that patients with IGSF1 mutations should be evaluated for long-term consequences of increased GH exposure.
EUROPEAN SURVEY OF FITNESS TRENDS FOR 2020
Authors: Batrakoulis Alexios 
Published: October 2019

Apply It!
From this article, the reader should understand the following concepts:
• Identify the top 20 trends for Europe based on input from survey respondents.
• Use the most popular trends in the European health and fitness industry to support the fight against the inactivity epidemic.
• Explore demographic relationships among fitness trend survey respondents in Europe.
REGIONAL COMPARISONS: THE WORLDWIDE SURVEY OF FITNESS TRENDS
Authors: Kercher Vanessa , Feito Yuri , Yates Brandon 
Published: October 2019

Apply It!
From this article, the reader should understand the following concepts:
• Identify and compare top 20 fitness trends for North America, China, Europe, and South America.
• Recognize similarities and differences in fitness trends between North America, China, Europe, and South America.
•Identify regional trends in the commercial, corporate, clinical, community health, and fitness industry for North America, China, Europe, and South America.
Can Static Stretching Reduce Stiffness of the Triceps Surae in Older Men?
Authors: HIRATA KOSUKE , YAMADERA RYOSUKE , AKAGI RYOTA 
Published: October 2019

ABSTRACTPurposeThe purpose of this study was to investigate reductions of muscle stiffness induced by static stretching in older and younger men.MethodsTwenty older (62–83 yr) and 20 younger (21–24 yr) men were recruited. Ankle dorsiflexion static stretching was consisted of 90 s × 5 repetitions. Before and after the stretching, the dorsiflexion range of motion (RoM), passive plantar flexion torque, and shear modulus (an index of stiffness) of the medial (MG) and lateral gastrocnemius and the soleus were measured.ResultsRoM, passive torque, and shear modulus of the triceps surae measured at the maximal dorsiflexion angle before stretching were significantly lower for the older group than the younger group. This suggests a weak stretching intensity for older compared with younger people. The stretching significantly improved RoM for both groups. For the older group, a significant reduction in passive torque was only observed at a 15° dorsiflexion angle, and the shear modulus was significantly decreased only for the distal region of MG. For the younger group, passive torque was significantly reduced for the entire RoM, and a significant decrease in shear modulus was found for the central and distal regions of MG and lateral gastrocnemius. A significant correlation between the muscle shear modulus measured at the maximal dorsiflexion angle before stretching and a stretching-induced decrease in muscle shear modulus was observed for older and younger participants. This indicates that the higher stretching intensity can reduce more muscle stiffness.ConclusionStatic stretching can reduce muscle stiffness regardless of age, although the stretching effect on muscle stiffness was limited for older people. This might be due to a lower stretching intensity for older than younger people.
Prediction of Polyp Pathology Using Convolutional Neural Networks Achieves “Resect and Discard” Thresholds
Authors: Zachariah Robin , Samarasena Jason , Luba Daniel , Duh Erica , Dao Tyler , Requa James , Ninh Andrew , Karnes William 
Published: October 2019

OBJECTIVES:
Reliable in situ diagnosis of diminutive (≤5 mm) colorectal polyps could allow for “resect and discard” and “diagnose and leave” strategies, resulting in $1 billion cost savings per year in the United States alone. Current methodologies have failed to consistently meet the Preservation and Incorporation of Valuable endoscopic Innovations (PIVIs) initiative thresholds. Convolutional neural networks (CNNs) have the potential to predict polyp pathology and achieve PIVI thresholds in real time.

METHODS:
We developed a CNN-based optical pathology (OP) model using Tensorflow and pretrained on ImageNet, capable of operating at 77 frames per second. A total of 6,223 images of unique colorectal polyps of known pathology, location, size, and light source (white light or narrow band imaging [NBI]) underwent 5-fold cross-training (80%) and validation (20%). Separate fresh validation was performed on 634 polyp images. Surveillance intervals were calculated, comparing OP with true pathology.

RESULTS:
In the original validation set, the negative predictive value for adenomas was 97% among diminutive rectum/rectosigmoid polyps. Results were independent of use of NBI or white light. Surveillance interval concordance comparing OP and true pathology was 93%. In the fresh validation set, the negative predictive value was 97% among diminutive polyps in the rectum and rectosigmoid and surveillance concordance was 94%.

DISCUSSION:
This study demonstrates the feasibility of in situ diagnosis of colorectal polyps using CNN. Our model exceeds PIVI thresholds for both “resect and discard” and “diagnose and leave” strategies independent of NBI use. Point-of-care adenoma detection rate and surveillance recommendations are potential added benefits.
Detección de Candidatos a Microcalcificaciones Mamarias Agrupadas en Mamografías
Authors: Sandino Garzon Alvaro Andres , Herrera García Rodrigo Javier 
Published: October 2019

Contexto: Las microcalcificaciones mamarias son lesiones no palpables que están presentes aproximadamente en el 55% de los casos de cáncer de mama; son un hallazgo muy frecuente en mamografías y pueden ser un indicador de esta enfermedad en sus primeras fases.
Método: Se implementó un método para el realce de microcalcificaciones mamarias basado en análisis multirresolución a través de la transformada wavelet. Posteriormente se realiza una segmentación aproximada de candidatos utilizando los parámetros estadísticos de la distribución de coeficientes y se seleccionaron aquellos que cumplían con ciertos parámetros de longitud y distribución. Por último, se emplea un modelo de clasificación binaria utilizando máquinas de soporte vectorial para clasificar imágenes con microcalcificaciones mamarias agrupadas.
Resultados: Se realizó la tarea de clasificación binaria entre imágenes con tejido mamario sano y con microcalcificaciones utilizando una máquina de soporte vectorial (Support-vector machine, SVM, por sus siglas en inglés) utilizando kernel lineal. Las métricas de evaluación para el algorítmo fueron: área bajo la curva (AUC) de 93.6 %, precisión de 89.4 %, sensibilidad de 88.4% y especificidad de 90.5 %.
Conclusiones: En el presente trabajo se utilizó el tamaño y la distribución como criterios para la segmentación y caracterización de microcalcificaciones mamarias agrupadas, que en la evaluación clínica son medidas cuantitativas para la detección de cáncer de seno en sus primeras etapas. Dado que el tejido mamario presenta un bajo contraste se propuso un método de realce que logra desenmascarar algunas microcalcificaciones que son poco evidentes. Con el enfoque propuesto se logró clasificar correctamente la mayoría de imágenes de tejido mamario con microcalcificaciones agrupadas ya sea en distribuciones
segmentarias, lineales o ramificadas.
Elevation of serum adiponectin in mildly decreased glomerular filtration rate
Authors: Mahima Apinya , Kongkhum Sudawadee , Bordeerat Narisa Kengtong , Fongsupa Somsak , Rerksngarm Thaval , Siripurkpong Pilaiwan 
Published: October 2019

Abstract

Background
Adiponectin secreted by adipocytes plays a key role in insulin sensitivity, anti-inflammation, and antiatherosclerosis. It is involved in several conditions including obesity, type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease (CKD). Glomerular filtration rate is monitored to indicate the kidney function and CKD progression.

Objective
To assess the serum adiponectin levels in individuals with normal and mildly decreased glomerular filtration rate, analyze the association of serum adiponectin with various physical and biological parameters, and test whether serum adiponectin is the risk factor of mildly decreased glomerular filtration rate.

Methods
This cross-sectional study was conducted in 172 individuals with 35–60 years of age. Serum samples were collected and divided into two groups, based on estimated glomerular filtration rate (eGFR): 90 with normal eGFR (G1, eGFR ≥90 mL/min/1.73 m2) and 82 with mildly decreased eGFR (G2, eGFR = 60–89 mL/min/1.73 m2). Anthropometric data were recorded. Serum adiponectin was measured by enzyme-linked immunosorbent assay.

Results
Serum adiponectin levels were significantly increased in individuals with mildly decreased eGFR (G2), compared to G1 (8.23 ± 3.26 µg/mL and 6.57 ± 3.24 µg/mL, respectively; P = 0.001). Serum adiponectin was positively associated with age and high-density lipoprotein cholesterol but negatively associated with weight, body mass index, triglyceride, and waist and hip circumferences. Univariate analysis showed that serum adiponectin was significantly correlated with mildly decreased eGFR; however, when adjusting for confounding factors, there were no correlations. Furthermore, multivariate regression analysis showed that individuals at the age of 46–55 years (4.0; 95% CI: 1.9–8.3) and > 55 years (11.4; 95% CI: 3.7–35.5) were significantly correlated with mildly decreased eGFR.

Conclusions
Serum adiponectin was significantly elevated in individuals with mildly decreased eGFR and may be a modulation factor, but was not an independent risk factor for mildly kidney damage. Further study is needed to clarify its potential benefits as monitoring biomarker for CKD progression.
Clinical outcomes of acute respiratory distress syndrome in a university hospital
Authors: Sanguanwong Natthawan , Kongpolprom Napplika 
Published: October 2019

Abstract

Background
Mortality rates of acute respiratory distress syndrome (ARDS) are different, depending on severity, etiology, and management.

Objective
To determine 7-day and 28-day mortalities, hospital length of stay (LOS), duration of mechanical ventilation (MV) of ARDS patients, and factors associated with poor outcomes.

Methods
A retrospective study was conducted to review the database of ARDS patients admitted in medical intensive care units (ICUs) at a university hospital between 2010 and 2014. The cases were identified by using International Classification of Diseases, 10th Revision (ICD-10) code-J80 ARDS.

Results
Of 266 patients, 11.7%, 44.4%, and 44% fulfilled mild, moderate, and severe ARDS criteria, respectively. The main cause of ARDS was pneumonia. The 7-day and 28-day mortalities, median LOS, and median MV duration were 31.1%, 69.3%, 18, and 11 days, respectively. Pressure control was the most favorite mode, used with average tidal volume (TV) of 8.63 (2.16) mL/kg ideal body weight (IBW). Recruitment maneuver was most frequently used as adjunctive intervention, whereas prone position was applied to 3.75% of the patients. One-third of the patients received neuromuscular blockades. The median 7-day fluid balance was +6,600 mL. The mean PaO2/FiO2 ratio during the first 3 days, cumulative fluid balance on day 3, and average daily calories during the first week were independent predictors for adjusted 7-day mortality, whereas Acute Physiology and Chronic Health Evaluation (APACHE II) score, fluid balance on day 1, cumulative fluid balance, and average daily calories during the first week were independent predictors for adjusted 28-day mortality.

Conclusions
The 28-day mortality of ARDS was high. In addition, TV and fluid balance were greater than protective limits. These findings indicated the potential improvement of ARDS outcomes in our hospital.
Proportion of vulvar premalignant and malignant lesions in overall vulvar specimens in Thailand
Authors: Trongpisutsak Ananya , Tantbirojn Patou , Lertkhachonsuk Ruangsak 
Published: October 2019

Abstract

Background
Vulvar lesion is one of the common gynecologic problems.

Objective
To assess the proportion of vulvar premalignant and malignant lesions in overall vulvar specimens and to evaluate the clinicopathologic features of each vulvar lesion in King Chulalongkorn Memorial Hospital (KCMH).

Methods
Pathological microscopic slides and medical records of the patients who underwent vulvar-related operations between January 1, 2002 and December 31, 2015 were reviewed. Patients’ clinical characteristics and pathologic features were evaluated and analyzed.

Results
A total number of 700 patients were included. The proportion of malignant and premalignant lesions in overall vulvar specimens were 16.3% and 8.4%, respectively. Squamous cell carcinoma was the most common malignant vulvar lesion (48.2%), whereas vulvar intraepithelial neoplasia 1 (VIN1) (33.9%) was the most common lesion in the premalignant group. On multivariate analysis, four clinical factors were significantly associated with malignancy risk: increased parity (odds ratio [OR] 1.19, P = 0.010), large tumor size (OR 2.00, P < 0.001), lesion at clitoris (OR 16.67, P = 0.002), and erythematous lesion (OR 2.41, P = 0.026).

Conclusions
The proportion of malignant and premalignant lesions in overall vulvar specimens was 24.7% in KCMH. Increased parity, large tumor size, clitoris-located lesion, and erythematous lesion were associated with increasing malignancy risk.
Effects of the initial moment and several delays perturbations in the variation formulas for a solution of a functional differential equation with the continuous initial condition
Authors: Dvalishvili Phridon , Nachaoui Abdeljalil , Tadumadze Tamaz 
Published: October 2019

Abstract
For the nonlinear functional differential equation with several constant delays, the variation formulas for its solution are proved, in which the effects of perturbations of delays and the initial moment are detected.
Generalized Olsen inequality and Schrödinger type elliptic equations
Authors: Guo Yuxing 
Published: October 2019

Abstract
In this paper, by means of the generalized Olsen type inequality, related to the Riesz potential and its commutators, the author establishes the interior estimates on the generalized Morrey space for Schrödinger type elliptic equations with potentials satisfying the reverse Hölder condition.
An aspect of optimal regression design for LSMC
Authors: Weiß Christian , Nikolić Zoran 
Published: October 2019

Abstract
Practitioners sometimes suggest to use a combination of Sobol sequences and orthonormal polynomials when applying an LSMC algorithm for evaluation of option prices or in the context of risk capital calculation under the Solvency II regime.
In this paper, we give a theoretical justification why good implementations of an LSMC algorithm should indeed combine these two features in order to assure numerical stability.
Moreover, an explicit bound for the number of outer scenarios necessary to guarantee a prescribed degree of numerical stability is derived.
We embed our observations into a coherent presentation of the theoretical background of LSMC in the insurance setting.
The crystal structure of (E)-N′-(1-(3-chloro-4-fluorophenyl) ethylidene)-2-hydroxybenzohydrazide, C15H12ClFN2O2
Authors: Yan Xifeng , Zhong Shibin , Zhang Hong 
Published: October 2019

Abstract
C15H12ClFN2O2, monoclinic, P21/c (no. 14), a = 13.9210(13) Å, b = 13.2329(15) Å, c = 18.7191(19) Å, β = 126.250(2)°, V = 2780.9(5) Å3, Z = 8, R
gt(F) = 0.0499, wR
ref(F
2) = 0.1420, T = 293(2) K.
Crystal structure of catena-poly[{μ2-1,5-bis(diphenylphosphanyl)pentane-κ2
P:P′}dichloridocadmium(II)], C29H30CdCl2P2
Authors: Tan Yee Seng , Tiekink Edward R.T. 
Published: October 2019

Abstract
C29H30CdCl2P2, orthorhombic, Pna21 (no. 33), a = 15.84368(4) Å, b = 8.46281(2) Å, c = 20.88054(8) Å, V = 2799.705(14) Å3, Z = 4, R
gt(F) = 0.0275, wR
ref(F
2) = 0.0719, T = 100(2) K.
Crystal structure of catena-[(bis(O,O′-diethyl dithiophosphato-S,S′)-μ2-1,2-bis(3-pyridylmethylene)hydrazine-N,N′)zinc(II)], {C20H30N4O4P2S4Zn}n
Authors: Tan Yee Seng , Tiekink Edward R.T. 
Published: October 2019

Abstract
C20H30N4O4P2S4Zn, triclinic, P1̄ (no. 2), a = 8.01840(1) Å, b = 8.4326(1) Å, c = 23.5086(2) Å, α = 80.478(1)°, β = 80.679(1)°, γ = 76.112(1)°, V = 1509.37(3) Å3, Z = 2, R
gt(F) = 0.0449, wR
ref(F
2) = 0.1182, T = 100(2) K.
Well-defined nickel(II) tetrazole-saccharinate complex as homogeneous catalyst on the reduction of aldehydes: scope and reaction mechanism
Authors: Frija Luís M. T. , Rocha Bruno G. M. , Kuznetsov Maxim L. , Cabral Lília I. L. , Cristiano M. Lurdes S. , Pombeiro Armando J. L. 
Published: October 2019

AbstractA new (tetrazole-saccharin)nickel complex is shown to be a valuable catalyst for the hydrosilative reduction of aldehydes under microwave radiation at low temperatures. With typical 1 mol% content of the catalyst (microwave power range of 5–15 W) most reactions are complete within 30 min. The Ni(II)-catalyzed reduction of aldehydes, with a useful scope, was established for the first time by using this catalyst, and is competitive with the most effective transition-metal catalysts known for such transformation. The catalyst reveals tolerance to different functional groups, is air and moisture stable, and is readily prepared in straightforward synthetic steps. Supported by experimental data and DFT calculations, a plausible reaction mechanism involving the new catalytic system is outlined.