\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{The association between serum levels of growth differentiation factor-15
and rheumatoid arthritis activity}



\author[1]{Kamal  Esalatmanesh}%
\author[1]{Hamidreza  Fayyazi}%
\author[1]{Roozbeh  Esalatmanesh}%
\author[2]{Alireza Khabbazi}%
\affil[1]{Autoimmune Diseases Research Center, Kashan University of Medical Sciences}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{March 14, 2025}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background: Macrophages play a crucial role in the pathogenesis of
rheumatoid arthritis (RA). Growth differentiation factor-15 (GDF-15)
acts as an autocrine regulator of macrophage activation. Objective: The
aim of this study was to assess serum level of GDF-15 as a potential
biomarker for detecting RA activity. Method: A total of 100 female RA
patients and 55 age matched healthy control females were enrolled. The
serum level of GDF-15 was measured using enzyme-linked immunosorbent
assay by an eBioscience kit. Results: Serum levels of GDF-15 in RA
patients with high, moderate, low and no disease activity were
989.0\selectlanguage{ngerman}±161.9, 505.6±220.5, 349.2±155.9 and 349.0±144.0 pg/ml,
respectively. GDF-15 with a cut-off value higher than 705 pg/ml was
indicative of high RA activity with sensitivity of 96\% and specificity
of 92\%. Conclusion: GDF-15 serum levels may be used as a biomarker to
predict high RA disease activity.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Title page}

\textbf{The association between serum levels of growth differentiation
factor-15 and rheumatoid arthritis} \textbf{activity}

Running title: GDF-15 in rheumatoid arthritis

Esalatmanesh K\textsuperscript{1}, Fayyazi H\textsuperscript{1},
Esalatmanesh R\textsuperscript{1}, Khabbazi \textsuperscript{2*}

\textsuperscript{1}Autoimmune Diseases Research Center, Kashan
University of Medical Sciences, Kashan, Iran

\textsuperscript{2}Connective Tissue Diseases Research Center, Tabriz
University of Medical Sciences, Tabriz, Iran

\textbf{Authors:}

Kamal Esalatmanesh: Autoimmune Diseases Research Center, Kashan
University of Medical Sciences, Kashan, Iran. Email:
kamal.esalat@yahoo.com

Hamidreza Fayyazi: Autoimmune Diseases Research Center, Kashan
University of Medical Sciences, Kashan, Iran. Email:
hamidreza.fayyazi@yahoo.com

Roozbeh Esalatmanesh: Autoimmune Diseases Research Center, Kashan
University of Medical Sciences, Kashan, Iran. Email: esalatr@gmail.com

Alireza Khabbazi: Connective Tissue Diseases Research Center, Tabriz
University of Medical Sciences, Tabriz, Iran. E-mail:
dr\_khabbazi@yahoo.com

*\textbf{Corresponding Author}

Alireza Khabbazi, MD.

Address: Connective Tissue Diseases Research Center, Flat 4, Emamreza
Hospital, Tabriz University of Medical Sciences, Golgasht St., P.O Box
5166614756, Tabriz, Iran.

E-mail: dr\_khabbazi@yahoo.com

Tel: +984133369331

\textbf{Acknowledgments}

We thank all the participants of this study who contributed with us.

\textbf{Hosted file}

\verb`Final GDF.docx`  available at \url{https://authorea.com/users/313867/articles/444271-the-association-between-serum-levels-of-growth-differentiation-factor-15-and-rheumatoid-arthritis-activity}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/313867/articles/444271-the-association-between-serum-levels-of-growth-differentiation-factor-15-and-rheumatoid-arthritis-activity}

\selectlanguage{english}
\FloatBarrier
\end{document}

