Summary of the characteristics of the newly diagnosed HIV positive MSM who took part in repeated in-depth interviews.

<p>^a One US Dollar was equal to 6.80 CNY in 2010.</p><p>Summary of the characteristics of the newly diagnosed HIV positive MSM who took part in repeated in-depth interviews.</p

The characteristics of six participants who practiced unprotected anal intercourse after the diagnosis of HIV positive.

<p>The characteristics of six participants who practiced unprotected anal intercourse after the diagnosis of HIV positive.</p

Percentages and risk estimations of low self-efficacy^a by parental migration among girls.

<p>Variables adjusted included school, grade, ethnicity, perceived living standard (as a surrogate of family income) and gender and education of the guardian in the multivariate models.</p>a<p>Self-efficacy was measured by the smoking self-efficacy questionnaire (SEQ-12), participants with scores below than the 25^th percentile of all were defined as low self-efficacy.</p>b<p>Risks were estimated among all girls.</p>c<p>Risks were estimated among girls with paternal or maternal migration only.</p

Percentages and risk estimations of past 30-day smoking and low self-efficacy^a by parental migration among boys.

<p>Variables adjusted included school, grade, ethnicity, perceived living standard (as a surrogate of family income) and gender and education of the guardian in the multivariate models.</p>a<p>Self-efficacy was measured by the smoking self-efficacy questionnaire (SEQ-12), participants with scores below than the 25^th percentile of all were defined as low self-efficacy.</p>b<p>Risks were estimated among all boys.</p>c<p>Risks were estimated among boys with paternal or maternal migration only.</p

Categorization of the Examined Genetic Association Studies

<p>IQR, interquartile range; N, sample size (as median and interquartile range); StatSig, statistically significant at the 0.05 level.</p

Melanoma Imaging Using ¹⁸F‑Labeled α‑Melanocyte-Stimulating Hormone Derivatives with Positron Emission Tomography

Melanocortin 1 receptor (MC1R) is specifically expressed in the majority of melanomas, a leading cause of death related to skin cancers. Accurate staging and early detection is crucial in managing melanoma. Based on the α-melanocyte-stimulating hormone (αMSH) sequence, MC1R-targeted peptides have been studied for melanoma imaging, predominately for use with single-photon emission computed tomography, with few attempts made for positron emission tomography (PET). ¹⁸F is a commonly used PET isotope due to readily available cyclotron production, pure positron emission, and a favorable half-life (109.8 min). In this study, we aim to design and evaluate αMSH derivatives that enable radiolabeling with ¹⁸F for PET imaging of melanoma. We synthesized three imaging probes based on the structure of Nle⁴-cyclo­[Asp⁵-His-d-Phe⁷-Arg-Trp-Lys¹⁰]-NH₂ (Nle-CycMSH_hex), with a Pip linker (CCZ01064), an Acp linker (CCZ01070), or an Aoc linker (CCZ01071). ¹⁸F labeling was enabled by an ammoniomethyl-trifluoroborate (AmBF₃) moiety. <i>In vitro</i> competition binding assays showed subnanomolar inhibition constant (<i>K</i>_i) values for all three peptides. The ¹⁸F radiolabeling was performed via a one-step ¹⁸F–¹⁹F isotope exchange reaction that resulted in high radiochemical purity (>95%) and good molar activity (specific activity) ranging from 40.7 to 66.6 MBq/nmol. All three ¹⁸F-labeled peptides produced excellent tumor visualization with PET imaging in C57BL/6J mice bearing B16-F10 tumors. The tumor uptake was 7.80 ± 1.77, 5.27 ± 2.38, and 5.46 ± 2.64% injected dose per gram of tissue (%ID/g) for [¹⁸F]­CCZ01064, [¹⁸F]­CCZ01070, and [¹⁸F]­CCZ01071 at 1 h post-injection (p.i.), respectively. Minimal background activity was observed except for kidneys at 4.99 ± 0.20, 4.42 ± 0.54, and 13.55 ± 2.84%ID/g, respectively. The best candidate [¹⁸F]­CCZ01064 was further evaluated at 2 h p.i., which showed increased tumor uptake at 11.96 ± 2.31%ID/g and further reduced normal tissue uptake. Moreover, a blocking study was performed for CCZ01064 at 1 h p.i., where tumor uptake was significantly reduced to 1.97 ± 0.60%ID/g, suggesting the tumor uptake was receptor mediated. In conclusion, [¹⁸F]­CCZ01064 showed high tumor uptake, low normal tissue uptake, and fast clearance and is therefore a suitable and promising candidate for PET imaging of melanoma

Targeting the Neuropeptide Y1 Receptor for Cancer Imaging by Positron Emission Tomography Using Novel Truncated Peptides

The neuropeptide Y₁ receptor (Y1R) is overexpressed in many human cancers, particularly breast cancer. Due to stability issues, limited success has been achieved for Y1R imaging agents, including full length and truncated neuropeptide Y (NPY) analogues. The goal of this study was to evaluate the possibility of using radiolabeled truncated NPY analogues to visualize Y1R expression in a preclinical model of Y1R-positive tumor. Four truncated NPY analogues were synthesized based on the sequence of [Pro³⁰, Tyr³², Leu³⁴]­NPY­(28–36), also known as BVD15. We substituted Tyr⁵ and Arg⁶ with unnatural amino acids aiming to enhance plasma stability while maintaining good receptor binding affinity to Y1R. In addition, we substituted Leu⁴ to Lys⁴ in order to conjugate via an optional linker the DOTA chelator for ⁶⁸Ga labeling. Receptor binding affinity and plasma stability of these compounds were evaluated. Positron emission tomography/computed tomography (PET/CT) imaging and biodistribution studies were performed using immune-compromised mice bearing HEK293T::WT and HEK293T::hY1R tumors. [Lys­(Ga-DOTA)⁴, Bip⁵]­BVD15 (CCZ01035), [Lys­(Ahx-Ga-DOTA)⁴, Bip⁵]­BVD15 (CCZ01053), and [Lys­(Pip-Ga-DOTA)⁴, Bip⁵]­BVD15 (CCZ01055) demonstrated good binding affinity to Y1R (<i>K</i>_i = 23.4–32.3 nM), while [Lys­(Ga-DOTA)⁴, Har⁶]­BVD15 (P05067) showed poor binding affinity (<i>K</i>_i > 1000 nM). In addition, CCZ01055 exhibited low binding affinity (<i>K</i>_i > 1000 nM) to Y2R and Y4R, demonstrating its selectivity to Y1R. The former three peptides showed improved <i>in vitro</i> plasma stability of 7–16% remaining intact after 1 h incubation. PET/CT imaging and biodistribution studies for ⁶⁸Ga-labeled CCZ01053, CCZ01035, and CCZ01055 showed that radioactivity was mainly cleared by the renal pathway, and HEK293T::hY1R tumors were clearly visualized with minimal background activity with the latter two. Of these two tracers, [⁶⁸Ga]­CCZ01055 provided lower kidney accumulation and higher contrast, i.e., average uptake ratios of Y1R tumor to wild type tumor, blood, and muscle are 3.87 ± 0.83, 4.12 ± 1.14, and 17.6 ± 4.64, respectively. Furthermore, Y1R tumor uptake with [⁶⁸Ga]­CCZ01055 was significantly reduced with coinjection of 100 μg of peptide YY, confirming the specificity of tumor accumulation was receptor mediated. We successfully developed the first Y1R-targeting truncated NPY analogues for PET imaging in a preclinical model, and [⁶⁸Ga]­CCZ01055 is a critical template for designing improved imaging agents to detect Y1R expressing cancers

Additional file 3: of Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial

Announcement of funding of DAA Trial by PCORI. (DOCX 486 kb

Additional file 1: of A preliminary validation of the Brief COPE instrument for assessing coping strategies among people living with HIV in China

Multilingual abstracts in the six official working languages of the United Nations. (PDF 204 kb