bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist
Authors: Parker Victoria E R , Robertson Darren , Wang Tao , Hornigold David C , Petrone Marcella , Cooper Aidan T , Posch Maximilian G , Heise Tim , Plum-Moerschel Leona , Schlichthaar Heike , Klaus Beate , Ambery Philip D , Meier Juris J , Hirshberg Boaz 
Published: October 2019

AbstractContextCotadutide is a dual receptor agonist with balanced glucagon-like peptide-1 and glucagon activity.ObjectiveTo evaluate different doses of cotadutide and investigate underlying mechanisms for its glucose-lowering effects.Design/settingRandomized, double-blind, phase 2a study conducted in 2 cohorts at 5 clinical trial sites.PatientsParticipants were 65 adult overweight/obese patients with type 2 diabetes mellitus; 63 completed the study; 2 were withdrawn due to AEs.InterventionOnce-daily subcutaneous cotadutide or placebo for 49 days. Doses (50–300 µg) were uptitrated weekly (cohort 1) or biweekly (cohort 2).Main outcome measuresCo-primary end points (cohort 1) were percentage changes from baseline to end of treatment in glucose (area under the curve from 0 to 4 hours [AUC0–4h]) post–mixed-meal tolerance test (MMTT) and weight. Exploratory measures included postprandial insulin and gastric emptying time (GET; cohort 2).ResultsPatients received cotadutide (cohort 1, n = 26; cohort 2, n = 20) or placebo (cohort 1, n = 13; cohort 2, n = 6). Significant reductions were observed with cotadutide vs placebo in glucose AUC0–4h post MMTT (least squares mean [90% CI], −21.52% [−25.68, −17.37] vs 6.32% [0.45, 12.20]; P &lt; 0.001) and body weight (−3.41% [−4.37, −2.44] vs −0.08% [−1.45, 1.28]; P = 0.002). A significant increase in insulin AUC0–4h post MMTT was observed with cotadutide (19.3 mU.h/L [5.9, 32.6]; P = 0.008) and GET was prolonged on day 43 with cotadutide vs placebo (t½: 117.2 minutes vs −42.9 minutes; P = 0.0392).ConclusionThese results suggest that the glucose-lowering effects of cotadutide are mediated by enhanced insulin secretion and delayed gastric emptying.Trial RegistrationClinicalTrials.gov, NCT03244800.
Activation of Notch Signaling by Oocytes and Jag1 in Mouse Ovarian Granulosa Cells
Authors: Hubbard Nisan , Prasasya Rexxi D , Mayo Kelly E 
Published: October 2019

Abstract
The Notch pathway plays diverse and complex roles in cell signaling during development. In the mammalian ovary, Notch is important for the initial formation and growth of follicles, and for regulating the proliferation and differentiation of follicular granulosa cells during the periovulatory period. This study seeks to determine the contribution of female germ cells toward the initial activation and subsequent maintenance of Notch signaling within somatic granulosa cells of the ovary. To address this issue, transgenic Notch reporter (TNR) mice were crossed with Sohlh1-mCherry (S1CF) transgenic mice to visualize Notch-active cells (EGFP) and germ cells (mCherry) simultaneously in the neonatal ovary. To test the involvement of oocytes in activation of Notch signaling in ovarian somatic cells, we ablated germ cells using busulfan, a chemotherapeutic alkylating agent, or investigated KitWv/Wv (viable dominant white-spotting) mice that lack most germ cells. The data reveal that Notch pathway activation in granulosa cells is significantly suppressed when germ cells are reduced. We further demonstrate that disruption of the gene for the Notch ligand Jag1 in oocytes similarly impacts Notch activation and that recombinant JAG1 enhances Notch target gene expression in granulosa cells. These data are consistent with the hypothesis that germ cells provide a ligand, such as Jag1, that is necessary for activation of Notch signaling in the developing ovary.
Accuracy of fruit-fly eclosion rhythms evolves by strengthening circadian gating rather than developmental fine-tuning
Authors: Varma Vishwanath , Krishna Shambhavi , Srivastava Manishi , Sharma Vijay Kumar , Sheeba Vasu 
Published: October 2019

ABSTRACT
Fruit flies (Drosophila melanogaster) eclose from their pupae mainly around dawn. The timing of eclosion is thought to confer adaptive benefits to the organisms and thus shows remarkable accuracy. However, it is not clear what factors are involved in the evolution of such accuracy in natural populations. In this study, we examined the relative contributions of gating of eclosion by the circadian clock versus clock-independent developmental rates and light-induced responses in the eclosion phenotype exhibited by fly populations that have evolved greater accuracy in eclosion rhythms compared to controls. We compared variation in timing of transitions between early developmental stages (pupariation and pigmentation), overall development time under constant light conditions – where circadian clocks are dysfunctional – and eclosion profiles when developmental rate was manipulated using different larval densities in selected and control stocks. Our results showed that stocks that have evolved greater accuracy of eclosion rhythms due to artificial selection do not show reduced individual variation in pupariation and pigmentation time compared to controls, though they do exhibit lower variation in eclosion time. Selected stocks also did not show lower variation in eclosion time under constant light conditions in contrast to the greater accuracy seen under light-dark cycles. Moreover, manipulations of developmental rate by varying larval density and inducing eclosion by changing onset of light phase did not alter the eclosion profile of selected stocks as much as it did controls, since selected stocks largely restricted eclosion to the daytime. These results suggest that fly populations selected for greater accuracy have evolved accurate eclosion rhythms primarily by strengthening circadian gating of eclosion rather than due to fine-tuning of clock-independent developmental processes.
This article has an associated First Person interview with the first author of the paper.
Interactive Clustered Heat Map Builder: An easy web-based tool for creating sophisticated clustered heat maps
Authors: Ryan Michael C. , Stucky Mark , Wakefield Chris , Melott James M. , Akbani Rehan , Weinstein John N. , Broom Bradley M. 
Published: October 2019

Clustered heat maps are the most frequently used graphics for visualization and interpretation of genome-scale molecular profiling data in biology. Construction of a heat map generally requires the assistance of a biostatistician or bioinformatics analyst capable of working in R or a similar programming language to transform the study data, perform hierarchical clustering, and generate the heat map. Our web-based Interactive Heat Map Builder can be used by investigators with no bioinformatics experience to generate high-caliber, publication quality maps. Preparation of the data and construction of a heat map is rarely a simple linear process. Our tool allows a user to move back and forth iteratively through the various stages of map generation to try different options and approaches. Finally, the heat map the builder creates is available in several forms, including an interactive Next-Generation Clustered Heat Map that can be explored dynamically to investigate the results more fully.
The use of indirect resin composite restorations in the management of localized anterior tooth wear: a clinical update part 2
Authors: Hansrani Virat Kumar , Laverty Dominic , Brunton Paul 
Published: October 2019

This article will focus on the active management of localized anterior tooth wear using indirect resin composite restorations. Emphasis will be placed on minimally invasive methods of tooth preparation in order to preserve biological tooth tissue in an already compromised tooth structure. Active management commits the patient to considerable long-term maintenance and it is important, as with any treatment, that the advantages and disadvantages are fully explained to the patient. CPD/Clinical Relevance: Numerous epidemiological studies have reported tooth wear to be increasing in incidence amongst the general population. This article aims to provide a methodical conservative approach in the management of the worn dentition.
Weighted Inequalities for Integral Operators with Almost Homogeneous Kernels
Authors: Urciuolo Marta 
Published: October 2019

Abstract
Let 𝑚 ∈ 𝑛 and 𝑎1, . . . , 𝑎𝑚 be real numbers such that for each 𝑖, 𝑎𝑖 ≠ 0 and 𝑎𝑖 ≠ 𝑎𝑗 if 𝑖 ≠ 𝑗. In this paper we study integral operators of the form
𝑇𝑓 (𝑥) = ∫ 𝑘1 (𝑥 – 𝑎1𝑦) . . . 𝑘𝑚 (𝑥 – 𝑎𝑚𝑦) 𝑓 (𝑦) 𝑑𝑦,
with .
If φ
𝑖,𝑗 satisfy certain uniform regularity conditions out of the origin, we obtain the boundedness of 𝑇 : 𝐿𝑝(𝑤) → 𝐿𝑝(𝑤) for all power weights 𝑤 in adequate Muckenhoupt classes.
On the Fourier Expansions of Eisenstein Series of Some Types
Authors: Kachakhidze Nikoloz 
Published: October 2019

Abstract
Bases of the spaces of Eisenstein series 𝐸𝑘(Γ0(4𝑁), χ) (𝑘 ∈ ℕ, 𝑘 ≥ 3, 𝑁 is an odd natural and square-free) and , ℕ is an odd natural and square-free) are constructed for any Dirichlet character mod 4𝑁 and Fourier expansions of these series are obtained.
Kenneth Waltz talks through Mark Rothko: Visual metaphors in the discipline of International Relations Theory
Authors: Güner Serdar Ş. 
Published: October 2019

Abstract
Semiotics constitutes an untapped and interdisciplinary source of enrichment for the discipline of International Relations (IR) theory. We propose two visual metaphors to that effect to interpret the figure depicting the central claim of structural realism (SR) offered by late Kenneth Waltz who is one of the most disputed, read, and inspiring IR theorists. The figure is the tenor of both metaphors. The vehicles are two paintings by Mark Rothko, namely, “Green and Tangerine on Red” and the “Number 14.” The metaphors generate innumerable meanings for the tenor and eliminate the criticism that SR is a static and an ahistorical theory. Thus, they benefit the Discipline characterised by academic cleavages on the meaning of theory, science, and production of knowledge.
Trends of Suicidal Behaviors Among High School Students in the United States: 1991–2017
Authors: Lindsey Michael A. , Sheftall Arielle H. , Xiao Yunyu , Joe Sean 
Published: October 2019

OBJECTIVES:
To determine if racial and ethnic subgroups of adolescents are at high risk for engagement in suicidal behaviors.

METHODS:
Using the nationally representative school-based Youth Risk Behavior Survey from the years 1991 to 2017, we conducted logistic regression analyses to examine trends by different racial and ethnic groups, with each suicide indicator serving as a dichotomous outcome. Participants included 198 540 high school students.

RESULTS:
Across all sex and race and ethnic groups, there were significant linear decreases in self-reported suicidal ideation and suicide plans from 1991 to 2017. Female adolescents (odds ratio [OR], 0.98; P &lt; .001) had significant decreases in attempts over time. Black adolescents had positive linear trends for suicide attempts among both boys (OR, 1.04; P &lt; .001) and girls (OR, 1.02; P = .003). Black adolescent boys (OR, 1.04; P = .048) had a significant linear increase in injury by attempt.

CONCLUSIONS:
The results suggest that, over time, black youth have experienced an increase in suicide attempts, which is troubling because attempts are the most prominent risk factor associated with suicide death. For black boys, a significant increase in injury by attempt occurred, which suggests that black boys may be engaging in increasingly lethal means when attempting suicide. Examining trends of suicidal thoughts and behaviors over time by sex and race and ethnicity allow us to determine where to focus prevention and intervention efforts. Future research should examine the underlying reasons for these changes observed in US high school students.
Innovative Intestification of Testing of Strength Endurance in Physical Education of Students With Chronic Diseases
Authors: Koryahin V. M. , Blavt O. S. , Ponomaryov S. V. 
Published: October 2019

The study objective is to substantiate and implement modern information-communication technologies (ICT) means for improving the testing of strength endurance of hands and upper body of students with chronic diseases in physical education.
Materials and methods. To solve the research tasks used the methods of comparing and contrasting are used and analysis, synthesis, abstraction, formalization and technical modelling.
Results. The result of a scientific search aimed at integrating ICT into test control of strength endurance of students with chronic diseases is a device of capacitive sensor testing. The designed capacitive touch tester is based on a combination of modern nanotechnology and microprocessor systems, including smart phone’s, tablets, etc. It is a constructive solution for electronic measuring systems of spatial position of objects based on capacitive sensor devices.
Conclusions. The effectiveness of using the designed device in testing students’ of strength endurance of hands and upper body is achieved through the ease of use and compactness of the device, student-friendly testing procedure and the efficiency and reliability of control.
The Relationship between Mutation in HOXB1 Gene and Acute Myeloid Leukemia
Authors: Vahidi Mehrjardi Mohammad Yahya , Aghaei Zarch Seyed Mohsen , Dehghani Mohammadreza 
Published: October 2019

Background: HOX genes are an exceedingly preserved family of homeodomain-involving transcription factors. They are related to a number of malignancies, comprising acute myeloid leukemia (AML). This study aimed to evaluate the effect of HOXB1 7bp deletion mutation on HOXB1gene expression in 36 individuals.
Materials and Methods: The present cross-sectional study was done on a large Iranian family. In this experimental study, 5 homozygous 7bp deletion individuals along with their unaffected siblings and their parents were investigated. The candidate gene, HOXB1 was screened and analyzed in blood samples of these participants. After RNA extraction, cDNA was synthesized according to manufacturer’s protocol. HOXB1 expression level was analyzed by 2ΔΔCT method. All laboratory procedures used in this experimental study were carried out in genetic laboratory of Shahid Sadoughi University of Medical Sciences.
Results: Sequence analysis of HOXB1 gene by ABI Prism 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) revealed a family with 5 homozygous (22±17 years) and 22 healthy heterozygous carriers (42±19 years) for 7bp deletion in HOXB1 gene along with 9 healthy wild type (55±41 years). Gene expression analysis by RT-qPCR demonstrated that expression level of HOXB1 gene in wild type and heterozygous carriers specimens had similar levels (p=0.05).
Conclusion: Although HOXB1 mutations has been reported in AML, but association between HOXB1 mutation and AML was not found in our study. Additionally, HOXB1 expression levels showed no significant difference between wild type and heterozygous carriers. So, HOXB1 gene expression cannot provide a powerful tool to differentiate wild type from heterozygous carries.
Staged Treatment of Chronic Locked Fracture-Dislocation of the Calcaneus
Authors: Liu Jane , Slotkin Steven , Zeni Ferras 
Published: October 2019

Case:
A 49-year-old woman presented 5 months after a missed locked fracture-dislocation of the calcaneus. This was treated with a Taylor spatial frame for deformity correction before definitive open reduction internal fixation with subtalar fusion. She is now 4 and a half years postoperative with an active lifestyle and no pain.

Conclusions:
Staged treatment using a Taylor spatial frame is a useful tool to address chronic locked chronic fracture-dislocations of the calcaneus.
Pseudoaneurysm of the Popliteal Artery Leading to Foot Drop After Arthroscopic Anterior Cruciate Ligament Reconstruction: A Rare Complication
Authors: Joshi Amit , Singh Nagmani , Pradhan Ishor , Basukala Bibek 
Published: October 2019

Case:
A 32-year-old man underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) using hamstring autograft. He complained of persistent posterior knee pain in the postoperative period and at 4 weeks postsurgery developed foot drop and intense posterior knee pain. On clinicoradiological evaluation, a popliteal pseudoaneurysm (PSA) was diagnosed. The patient underwent surgical exploration, excision of the PSA, and primary repair of the popliteal artery. The foot drop recovered at 3 months post–second surgery follow-up.

Conclusions:
Persistent posterior knee pain and popliteal fossa swelling in a patient after ACLR should raise a suspicion of popliteal PSA. Identifying these lesions early can prevent further complications such as common peroneal nerve palsy.
Analysis of the incidence of newborn's healthcare associated infections and intrauterine infections in several maternity hospitals in Moscow
Authors: Ivanova M. V. 
Published: October 2019

Purpose of the study. To estimate the incidence of newborn's healthcare associated infections (HAI) and intrauterine infections in the Russian Federation, Moscow and three maternity hospitals in Moscow. Materials and methods. The retrospective epidemiological analysis of neonates HAIs and intrauterine infections during 2008–2017 was performed in the Russian Federation and Moscow and during 2009–2017 in three maternity hospitals (MH) in Moscow. In this study the maternity hospitals would be known as MH № X01, № X02 and № X03. Also, in this study, the calculation and analysis of the proportion of cases of newborn's HAIs and intrauterine infections with laboratory confirmation were performed in Moscow's maternity hospitals. The data was selected from Form № 2 for the Russian Federation and Moscow. Also, the data of the maternity hospitals was drawn from the base of the Hygiene and Epidemiology Center in Moscow. The morbidity rate of HAIs and intrauterine infections of newborns was counted on 1,000 newborns. Microsoft Office Excel 2010 software packages were used for this purpose. The calculation of the increase / decrease rate was made by the method of least squares. Results. The incidence of intrauterine infections and HAIs of newborns in the Russian Federation, Moscow, and maternity hospitals is characterized by the next mutual trends – a significant dominance cases of intrauterine infections' over the cases of HAI, extremely irregular registration and distribution of the nosologies' proportion. Concerning to the dynamics of morbidity during 2009–2017 in maternity hospitals in Moscow, the HAIs newborn's incidence has tendency of decline, and intrauterine infections has considerable increase of the incidence. This consistent pattern is observed in all described maternity hospitals. The structure of the incidence in maternity hospitals is similar to each other. The leading diagnoses among intrauterine infections are intrauterine infection without a lesion and intrauterine pneumonia. The interest of other infections is about 1%. The proportion of cases with laboratory confirmation of the newborn's HAIs and intrauterine infections is extremely small. Besides that, there were identified some indirect signs of poor-quality registration of nosocomial infections. Conclusion. Significant difference in the number of cases of newborn's HAIs and intrauterine infections and their multidirectional incidence trends, once again point to the concealment of a part of nosocomial infections, under such diagnoses, as intrauterine infection without a lesion and intrauterine pneumonia. Laboratory confirmation of cases of HAIs and intrauterine infections in the maternity hospitals is carried out only by a small proportion of patients. Thereby, the incidence rates of HAIs of newborns and intrauterine infections in maternity hospitals in Moscow raise doubts about their reliability.
A Discretization-Independent Distributed Well Model
Authors: Jayasinghe Savithru , Darmofal David L. , Dow Eric , Galbraith Marshall C. , Allmaras Steven R. 
Published: October 2019

Summary
In this paper, we present a new well model for reservoir simulation. The proposed well model relates the volumetric flow rate and the bottomhole pressure (BHP) of the well to the reservoir pressure through a spatially distributed source term that is independent of the numerical method and the discrete mesh used to solve the flow problem. This is in contrast to the widely used Peaceman–type well models, which are inherently tied to a particular numerical discretization by the definition of an equivalent well radius.
The proposed distributed well model does not require the calculation of an equivalent well radius. Hence, it can be readily applied to finite–difference, finite–volume (FV), or finite–element discretizations on arbitrarily unstructured meshes, which also makes it an attractive option for mesh–adaptation schemes. The new well model is demonstrated on a steady-state single-phase flow problem and an unsteady two-phase flow problem, using a conventional FV method and a high–order discontinuous Galerkin (DG) method. The distributed well model produces error–convergence behaviors that are very similar to the Peaceman well model on uniform structured meshes, but its applicability to high–order discretizations and mesh–adaptation schemes allows for higher convergence rates and more cost-efficient solutions, especially on adapted unstructured meshes.
Low risk patients with acute atrial fibrillation and elevated high-sensitivity troponin do not have increased incidence of pathological stress test: a prospective cohort study
Authors: Thelin Johan , Gerward Sofia , Melander Olle 
Published: October 2019

Abstract
Background
Many patients with atrial fibrillation (AF) or atrial flutter (AFL) and rapid ventricular response (RVR) have elevated high-sensitivity troponin T (hsTnT) values. Elevated hsTnT is an independent risk marker for cardiovascular events and mortality. The aim was to examine if AF/AFL patients with RVR and elevated hsTnT have an increased incidence of pathological cardiac stress tests, indicating need of further evaluation for coronary artery disease (CAD).
Methods
We prospectively included 90 AF/AFL patients without known heart failure and CAD presenting with AF/AFL and RVR. Half of the patients had elevated hsTnT (cases) and half had levels below the 99th percentile (controls). All patients were discharged in sinus rhythm. After approximately one week in sinus rhythm a new hsTnT was analysed and the patients performed a bicycle exercise stress test within the 30 day follow-up. The primary endpoint was a pathological stress test confirmed by a pathological SPECT myocardial perfusion imaging or a coronary angiography.
Results
None of the controls reached the primary endpoint. Two patients (4%) out of the 45 cases reached the primary endpoint (p= 0.49 vs controls), but only one was found to have significant CAD at subsequent coronary angiography.
Conclusions
Patients with paroxysmal AF/AFL, without history of CAD and heart failure, who present with a RVR and minor hsTnT elevations do not have an increased incidence of pathological stress test compared to patients with hsTnT values below the 99th percentile.