bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Activatable Cancer-Targeted Hydrogen Peroxide Probe for Photoacoustic and Fluorescence Imaging
Authors: Weber Judith , Bollepalli Laura , Belenguer Ana M. , Antonio Marco Di , De Mitri Nicola , Joseph James , Balasubramanian Shankar , Hunter Christopher A. , Bohndiek Sarah E. 
Published: August 2019

AbstractReactive oxygen species play an important role in cancer, however, their promiscuous reactivity, low abundance, and short-lived nature limit our ability to study them in real time in living subjects with conventional noninvasive imaging methods. Photoacoustic imaging is an emerging modality for in vivo visualization of molecular processes with deep tissue penetration and high spatiotemporal resolution. Here, we describe the design and synthesis of a targeted, activatable probe for photoacoustic imaging, which is responsive to one of the major and abundant reactive oxygen species, hydrogen peroxide (H2O2). This bifunctional probe, which is also detectable with fluorescence imaging, is composed of a heptamethine carbocyanine dye scaffold for signal generation, a 2-deoxyglucose cancer localization moiety, and a boronic ester functionality that specifically detects and reacts to H2O2. The optical properties of the probe were characterized using absorption, fluorescence, and photoacoustic measurements; upon addition of pathophysiologic H2O2 concentrations, a clear increase in fluorescence and red-shift of the absorption and photoacoustic spectra were observed. Studies performed in vitro showed no significant toxicity and specific uptake of the probe into the cytosol in breast cancer cell lines. Importantly, intravenous injection of the probe led to targeted uptake and accumulation in solid tumors, which enabled noninvasive photoacoustic and fluorescence imaging of H2O2. In conclusion, the reported probe shows promise for the in vivo visualization of hydrogen peroxide.Significance:This study presents the first activatable and cancer-targeted hydrogen peroxide probe for photoacoustic molecular imaging, paving the way for visualization of hydrogen peroxide at high spatiotemporal resolution in living subjects.
Menopausal Hormone Therapy and Risk of Melanoma: A Nationwide Register-Based Study in Finland
Authors: Botteri Edoardo , Støer Nathalie C. , Weiderpass Elisabete , Pukkala Eero , Ylikorkala Olavi , Lyytinen Heli 
Published: August 2019

Abstract

Background:
The association between use of menopausal hormone therapy and risk of cutaneous melanoma is highly debated. We investigated the issue in a Finnish nationwide cohort of women ages 50 years or older.

Methods:
All women who had purchased hormone therapy between 1994 and 2007 were identified from the national Medical Reimbursement Registry and linked to the Finnish Cancer Registry. We calculated standardized incidence ratios (SIR) to compare incidence of cutaneous melanoma among hormone therapy users with that of the general population.

Results:
During a mean follow-up of 15.6 years, 1,695 incident cutaneous melanoma cases were identified among 293,570 women who had used hormone therapy for at least 6 months. The SIRs for women who used unopposed estrogen therapy and combined estrogen–progestin therapy (EPT) for 6 to 59 months were 1.20 [95% confidence interval (CI), 1.06–1.35] and 1.00 (95% CI, 0.87–1.14; Pheterogeneity = 0.04). The SIRs for women who used estrogen therapy and EPT for at least 60 months were 1.37 (95% CI, 1.22–1.52) and 1.23 (95% CI, 1.13–1.34; Pheterogeneity = 0.15). We did not find significant differences between oral and transdermal administrations, nor between doses of estrogens.

Conclusions:
Use of hormone therapy, especially estrogen therapy, was associated with an increased risk of cutaneous melanoma. EPT use of less than 5 years was not associated with an increased risk of cutaneous melanoma.

Impact:
Our results add to the growing body of epidemiologic evidence that the use of unopposed estrogens in menopause increases the risk of cutaneous melanoma, while the addition of progestins might counteract the detrimental effect.
A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors
Authors: Doi Toshihiko , Muro Kei , Ishii Hiroshi , Kato Terufumi , Tsushima Takahiro , Takenoyama Mitsuhiro , Oizumi Satoshi , Gemmoto Kazuto , Suna Hideaki , Enokitani Kouki , Kawakami Tetsuyoshi , Nishikawa Hiroyoshi , Yamamoto Noboru 
Published: August 2019

Abstract

Purpose:
Regulatory T cells (Tregs) expressing CC chemokine receptor 4 (CCR4) can suppress antitumor immune responses and are associated with poor prognoses in several cancers. We assessed the safety and efficacy of combined mogamulizumab (anti-CCR4 antibody) and nivolumab [anti-programmed death-1 (PD-1) antibody] in immunotherapy-naïve patients with advanced/metastatic solid tumors.

Patients and Methods:
This study (NCT02476123) comprised dose-escalation (3+3 design) and expansion parts. Patients received nivolumab (3.0 mg/kg) every 2 weeks, with mogamulizumab (0.3 or 1.0 mg/kg in dose escalation, 1.0 mg/kg in expansion) once weekly for 4 weeks, then every 2 weeks, until progression or unacceptable toxicity. Primary objective was safety; secondary objectives were antitumor effects, pharmacokinetics, and immunogenicity. Exploratory biomarker analyses were conducted.

Results:
Ninety-six patients were enrolled (July 2015−November 2016): six patients in the dose-escalation part and 90 in the expansion part. No dose-limiting toxicities were observed in the dose-escalation part. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 29% of patients in the expansion part (no grade 5 TRAEs). The most frequent TRAEs were rash (39%), rash maculopapular (20%), diarrhea (13%), stomatitis (12%), and pruritus (11%). There were four (27%) confirmed tumor responses among 15 patients with hepatocellular carcinoma, and one confirmed and two unconfirmed responses among 15 patients with pancreatic adenocarcinoma. During treatment, populations of effector Tregs (CD4+CD45RA−FoxP3high) decreased and CD8+ T cells in tumor-infiltrating lymphocytes increased.

Conclusions:
Combining an anti–PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer immunotherapy.
Diversity of butterflies of the Shettihalli Wildlife Sanctuary, Shivamogga District, Karnataka, India
Authors: Harisha M.N. , Prakash Harish , Hosetti B.B. , Kumara Vijaya 
Published: August 2019

A study was conducted on the diversity of butterflies by using the pollard walk method in the tropical dry deciduous habitats of Shettihalli Wildlife Sanctuary, Shivamogga District, Karnataka, from February 2010 to January 2011. A total of 151 species of butterflies belonging to 99 genera and five families was recorded. The family Nymphalidae was the most dominant with the highest number of species (52 species; 35%), followed by Lycaenidae (33 species; 22%), Hesperiidae (25 species; 17%), Pieridae (24 species; 16%), and Papilionidae (15 species: 10%). The study also revealed 24 species of butterflies which are protected under various schedules of Indian Wildlife Protection Act, 1972, and 13 species as being endemic to the Western Ghats, peninsular India and Sri Lanka.
Rediscovery of Nilgiri Mallow Abutilon neelgerrense var. fischeri T.K. Paul & M.P. Nayar (Malvaceae) after a century from southern India
Authors: Nimbalkar Varsha Vilasrao , Ravichandran Arun Prasanth , Sardesai Milind Madhav 
Published: August 2019

Abutilon neelgerrense var. fischeri T.K. Paul & M.P. Nayar, a rare endemic taxon, has been rediscovered after a century from Theni District in Tamil Nadu. The present study provides detailed morphological description, key to the varieties with additional characters and images.
First videos of endemic Zanzibar Servaline Genet Genetta servalina archeri, African Palm Civet Nandinia binotata (Mammalia: Carnivora: Viverridae) and other small carnivores on Unguja Island, Tanzania
Authors: Goldman Helle V. , Walsh Martin T. 
Published: August 2019

The faunal diversity of the densely populated island of Unguja, Zanzibar archipelago, Tanzania, includes several endemic mammals. Camera-trapping in Jozani-Chwaka Bay National Park and Kiwengwa–Pongwe Forest Reserve in September 2017 captured the first video footage of the Zanzibar Servaline Genet Genetta servalina archeri, an endemic subspecies first formally described in 1998. Other native small carnivores were also recorded on video for the first time during this survey, including the African Palm Civet Nandinia binotata, which was first documented in print as present in Unguja in 2004. Also camera-trapped in 2017 were the Zanzibar Slender Mongoose Herpestes sanguineus rufescens and the Zanzibar Bushy-tailed Mongoose Bdeogale crassicauda tenuis. Follow-up camera-trapping in Jozani-Chwaka Bay National Park in August 2018 captured additional video of the Zanzibar Servaline Genet and the African Palm Civet. No images were obtained of the African Civet Civettictis civetta, or of the two introduced species—the Banded Mongoose Mungos mungo and the Small Indian Civet Viverricula indica—in either year. As the remaining natural habitat in Zanzibar shrinks in size and becomes fragmented, it is increasingly urgent to document the archipelago’s carnivores and other fauna, so that sound conservation measures can be implemented.
Examining the Prevalence of Adverse Childhood Experiences and Associated Cardiovascular Disease Risk Factors Among Low-Income Uninsured Adults
Authors: Allen Heidi , Wright Bill J. , Vartanian Keri , Dulacki Kristen , Li Hsin-Fang 
Published: August 2019

Background:
Adverse childhood experiences (ACEs) are linked to poor adult health outcomes, including cardiovascular disease. However, little is known about its prevalence, specifically in low-income populations. The objective of this study was to estimate the extent of ACEs in a low-income, nonclinical, uninsured adult population and assess the relationship between ACEs and cardiovascular disease risk factors.

Methods and Results:
This study leverages the OHIE’s (Oregon Health Insurance Experiment) study population, uninsured adults who were randomly selected to apply for Medicaid, and data collected through in-person health screenings. We objectively measured obesity, cholesterol, blood pressure, and blood sugar. Smoking, physical activity, and history of chronic disease were self-reported. Independent variables were the 10-item ACEs questions covering neglect, abuse, and household dysfunction. The sample consisted of 12 229 low-income, nonelderly uninsured adults who participated in the OHIE health screenings from 2009 to 2010. A total of 5929 (48%) returned a follow-up survey reporting ACEs in 2012. ACEs were more prevalent in low-income adults compared with previous estimates in a general clinical population, with notably high rates of emotional abuse, emotional neglect, and household dysfunction. ACEs were statistically associated with higher rates of obesity, smoking, and physical inactivity, but not high cholesterol or diabetes mellitus. We detected a strong relationship between ACEs and a self-reported history of a hypertension diagnosis but no statistically significant differences in being hypertensive.

Conclusions:
This study design allowed us to assess the prevalence of ACEs among uninsured low-income adults and the association between ACEs and clinical indicators of cardiovascular disease risk that are difficult to ordinarily observe. Low-income adults have high rates of ACEs than previous prevalence estimates and ACEs were associated with higher rates of multiple cardiovascular disease risk factors. As states continue to expand Medicaid to the previously uninsured, providers may want to consider incorporating trauma-based approaches to care delivery.
HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction Implications for Statin Treatment in HIV Patients
Authors: Chelvanambi Sarvesh , Gupta Samir K. , Chen Xingjuan , Ellis Bradley W. , Maier Bernhard F. , Colbert Tyler M. , Kuriakose Jithin , Zorlutuna Pinar , Jolicoeur Paul , Obukhov Alexander G. , Clauss Matthias 
Published: August 2019

Rationale:
Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role in cardiovascular diseases. A possible cofactor may be persistence of the early HIV response gene Nef, which we have demonstrated recently to persist in the lungs of HIV+ patients on antiretroviral therapy. Previously, we have reported that HIV strains with Nef, but not Nef-deleted HIV strains, cause endothelial proinflammatory activation and apoptosis.

Objective:
To characterize mechanisms through which HIV-Nef leads to the development of cardiovascular diseases using ex vivo tissue culture approaches as well as interventional experiments in transgenic murine models.

Methods and Results:
Extracellular vesicles derived from both peripheral blood mononuclear cells and plasma from HIV+ patient blood samples induced human coronary artery endothelial cells dysfunction. Plasma-derived extracellular vesicles from antiretroviral therapy+ patients who were HIV-Nef+ induced significantly greater endothelial apoptosis compared with HIV-Nef-plasma extracellular vesicles. Both HIV-Nef expressing T cells and HIV-Nef-induced extracellular vesicles increased transfer of cytosol and Nef protein to endothelial monolayers in a Rac1-dependent manner, consequently leading to endothelial adhesion protein upregulation and apoptosis. HIV-Nef induced Rac1 activation also led to dsDNA breaks in endothelial colony forming cells, thereby resulting in endothelial colony forming cell premature senescence and endothelial nitric oxide synthase downregulation. These Rac1-dependent activities were characterized by NOX2-mediated reactive oxygen species production. Statin treatment equally inhibited Rac1 inhibition in preventing or reversing all HIV-Nef-induction abnormalities assessed. This was likely because of the ability of statins to block Rac1 prenylation as geranylgeranyl transferase inhibitors were effective in inhibiting HIV-Nef-induced reactive oxygen species formation. Finally, transgenic expression of HIV-Nef in endothelial cells in a murine model impaired endothelium-mediated aortic ring dilation, which was then reversed by 3-week treatment with 5 mg/kg atorvastatin.

Conclusions:
These studies establish a mechanism by which HIV-Nef persistence despite antiretroviral therapy could contribute to ongoing HIV-related vascular dysfunction, which may then be ameliorated by statin treatment.
Association of Concurrent Changes in Metabolic Health and Weight on Cardiovascular Disease Risk: A Nationally Representative Cohort Study
Authors: Bae Ye Seul , Choi Seulggie , Lee Kiheon , Son Joung Sik , Lee Hyejin , Cho Mi Hee , Koo Hye‐Yeon , Cho In Young , Chang Jooyoung , Kim Kyuwoong , Kim Sung Min , Park Sang Min 
Published: August 2019

Background

The combined effect of transitions of metabolic health and weight on cardiovascular disease (
CVD
) remains unclear. We aimed to examine the association of concurrent changes of metabolic health and weight on
CVD
over time.

Methods and Results

The study population consisted of 205 394 from the Korean National Health Insurance Service. Metabolic health was determined by fasting serum glucose, total cholesterol, and blood pressure levels, while obesity was determined by body mass index. All participants were divided into either metabolically healthy nonobese (
MHNO
), metabolically healthy obese, metabolically unhealthy nonobese, or metabolically unhealthy obese for each of the first (2002–2003) and second (2004–2005) health screening periods, after which participants were followed‐up for
CVD
from 2006 to 2015. Cox proportional hazards regression was used to determine adjusted hazard ratios (
aHR
s) and 95%
CI
s. Among initial
MHNO
participants, those who became metabolically healthy obese (
aHR
, 1.25; 95%
CI
, 1.10–1.41), metabolically unhealthy nonobese (
aHR
, 1.23; 95%
CI
, 1.15–1.31), and metabolically unhealthy obese (
aHR
, 1.34; 95%
CI
, 1.12–1.61) had elevated risk for
CVD
compared with those who remained
MHNO
. Conversely, improving metabolic health and obesity were associated with reduced
CVD
risk among initially metabolically unhealthy nonobese to secondary
MHNO
(
aHR
, 0.79; 95%
CI
, 0.73–0.84), metabolically unhealthy obese to
MHNO
(
aHR
, 0.68; 95%
CI
, 0.58–0.81), and metabolically unhealthy obese to metabolically healthy obese (
aHR,
0.73; 95%
CI
, 0.66–0.80) participants.

Conclusions

Changes toward metabolically unhealthy or obese states resulted in increased
CVD
risk. Improving metabolic health along with reducing weight may lead to decreased risk of
CVD
.
POLSTRACC: Airborne Experiment for Studying the Polar Stratosphere in a Changing Climate with the High Altitude and Long Range Research Aircraft (HALO)
Authors: Oelhaf Hermann , Sinnhuber Björn-Martin , Woiwode Wolfgang , Bönisch Harald , Bozem Heiko , Engel Andreas , Fix Andreas , Friedl-Vallon Felix , Grooß Jens-Uwe , Hoor Peter , Johansson Sören , Jurkat-Witschas Tina , Kaufmann Stefan , Krämer Martina , Krause Jens , Kretschmer Erik , Lörks Dominique , Marsing Andreas , Orphal Johannes , Pfeilsticker Klaus , Pitts Michael , Poole Lamont , Preusse Peter , Rapp Markus , Riese Martin , Rolf Christian , Ungermann Jörn , Voigt Christiane , Volk C. Michael , Wirth Martin , Zahn Andreas , Ziereis Helmut 
Published: August 2019

AbstractThe Polar Stratosphere in a Changing Climate (POLSTRACC) mission employed the German High Altitude and Long Range Research Aircraft (HALO). The payload comprised an innovative combination of remote sensing and in situ instruments. The in situ instruments provided high-resolution observations of cirrus and polar stratospheric clouds (PSCs), a large number of reactive and long-lived trace gases, and temperature at the aircraft level. Information above and underneath the aircraft level was achieved by remote sensing instruments as well as dropsondes. The mission took place from 8 December 2015 to 18 March 2016, covering the extremely cold late December to early February period and the time around the major warming in the beginning of March. In 18 scientific deployments, 156 flight hours were conducted, covering latitudes from 25° to 87°N and maximum altitudes of almost 15 km, and reaching potential temperature levels of up to 410 K. Highlights of results include 1) new aspects of transport and mixing in the Arctic upper troposphere–lower stratosphere (UTLS), 2) detailed analyses of special dynamical features such as tropopause folds, 3) observations of extended PSCs reaching sometimes down to HALO flight levels at 13–14 km, 4) observations of particulate NOy and vertical redistribution of gas-phase NOy in the lowermost stratosphere (LMS), 5) significant chlorine activation and deactivation in the LMS along with halogen source gas observations, and 6) the partitioning and budgets of reactive chlorine and bromine along with a detailed study of the efficiency of ClOx/BrOx ozone loss cycle. Finally, we quantify—based on our results—the ozone loss in the 2015/16 winter and address the question of how extraordinary this Arctic winter was.
A Significant Bias of Tmax and Tmin Average Temperature and Its Trend
Authors: Liu Yulian , Ren Guoyu , Kang Hengyuan , Sun Xiubao 
Published: August 2019

AbstractThe systematic bias of the estimated average temperature using daily Tmax and Tmin records relative to the standard average temperature of four time-equidistant observations and its effect on the estimated trend of long-term temperature change have not been well understood. This paper attempts to evaluate the systematic bias across mainland China using the daily data of national observational stations. The results revealed that the positive bias of annual mean temperature was large, reaching 0.58°C nationally on average; regional average bias was lowest in the northwest arid region and highest in the Qinghai–Tibetan Plateau; the bias was low in spring and summer and high in autumn and winter, reaching its lowest point in mid- and late May and highest point in early November. Furthermore, the bias showed a significant upward trend in the past 50 years, with a rising rate of 0.021°C (10 yr)−1, accounting for about 12% of the overall warming as estimated from the data of the observational network; the largest positive trend bias was found in the northwest arid region, while the east monsoon region experienced the smallest change; the most remarkable increase of the bias occurred after early 1990s. These results indicate that the customarily applied method to calculate daily and monthly mean temperature using Tmax and Tmin significantly overestimates the climatological mean and the long-term trend of surface air temperature in mainland China.
The Observed Structure and Precipitation Characteristics of Southeast Atlantic Stratocumulus from Airborne Radar during ORACLES 2016–17
Authors: Dzambo Andrew M. , L’Ecuyer Tristan , Sy Ousmane O. , Tanelli Simone 
Published: August 2019

AbstractDuring the Observations of Aerosols above Clouds and Their Interactions (ORACLES) 2016 and 2017 field experiments, the Third Generation Advanced Precipitation and Cloud Radar (APR-3) flew aboard the NASA P-3 aircraft taking over 10 million profiles of stratocumulus clouds in the southeast Atlantic Ocean. This study documents cloud structure, precipitation frequency and intensity, and atmospheric stability for each flight during both field experiments. A larger cloud fraction was estimated for 2016, likely due to a larger estimated inversion strength (EIS) in the experiment area (between 6 and 10 K) compared to 2017 where EIS was on average 4–6 K lower. We used an optimal estimation retrieval to derive precipitation rates for all measurable clouds during both experiments. Over 30% of clouds observed during the 2016 experiment exhibited precipitation reaching the surface, but retrieved drizzle rates were below 0.01 mm h−1 in all but 40% of these profiles. This is in sharp contrast to the 2017 campaign where over 53% of precipitating profiles had rainfall rates larger than 0.01 mm h−1. The differences in cloud and rain fractions between the two years are most likely due to differences in the sampling environments; however, enough variations in cloud, virga, and rain fraction exist for similar environmental conditions such that additional analysis of cloud and aerosol interactions—specifically their effect on precipitation processes—needs further exploration. The extensive APR-3 sampling of drizzling stratocumulus under similar thermodynamic conditions provides a rich dataset for examining the influence of biomass burning aerosols on cloud fraction, morphology, and precipitation characteristics in this climatically important region.