bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations
Authors: Kugel Curtis H. , Douglass Stephen M. , Webster Marie R. , Kaur Amanpreet , Liu Qin , Yin Xiangfan , Weiss Sarah A. , Darvishian Farbod , Al-Rohil Rami N. , Ndoye Abibatou , Behera Reeti , Alicea Gretchen M. , Ecker Brett L. , Fane Mitchell , Allegrezza Michael J. , Svoronos Nikolaos , Kumar Vinit , Wang Daniel Y. , Somasundaram Rajasekharan , Hu-Lieskovan Siwen , Ozgun Alpaslan , Herlyn Meenhard , Conejo-Garcia Jose R. , Gabrilovich Dmitry , Stone Erica L. , Nowicki Theodore S. , Sosman Jeffrey , Rai Rajat , Carlino Matteo S. , Long Georgina V. , Marais Richard , Ribas Antoni , Eroglu Zeynep , Davies Michael A. , Schilling Bastian , Schadendorf Dirk , Xu Wei , Amaravadi Ravi K. , Menzies Alexander M. , McQuade Jennifer L. , Johnson Douglas B. , Osman Iman , Weeraratna Ashani T. 
Published: June 2018

Abstract
Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1.
Experimental Design: We analyzed the relationship between age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumoral immune microenvironment in young versus aged mice and confirmed our findings in human melanoma biopsies.
Results: Patients over the age of 60 responded more efficiently to anti-PD-1, and likelihood of response to anti-PD-1 increased with age, even when we controlled for prior MAPKi therapy. Placing genetically identical tumors in aged mice (52 weeks) significantly increased their response to anti-PD1 as compared with the same tumors in young mice (8 weeks). These data suggest that this increased response in aged patients occurs even in the absence of a more complex mutational landscape. Next, we found that young mice had a significantly higher population of regulatory T cells (Tregs), skewing the CD8+:Treg ratio. FOXP3 staining of human melanoma biopsies revealed similar increases in Tregs in young patients. Depletion of Tregs using anti-CD25 increased the response to anti-PD1 in young mice.
Conclusions: While there are obvious limitations to our study, including our inability to conduct a meta-analysis due to a lack of available data, and our inability to control for mutational burden, there is a remarkable consistency in these data from over 500 patients across 8 different institutes worldwide. These results stress the importance of considering age as a factor for immunotherapy response. Clin Cancer Res; 24(21); 5347–56. ©2018 AACR.
See related commentary by Pawelec, p. 5193
Nuclear PTEN Localization Contributes to DNA Damage Response in Endometrial Adenocarcinoma and Could Have a Diagnostic Benefit for Therapeutic Management of the Disease
Authors: Mukherjee Ananda , Patterson Amanda L. , George Jitu W. , Carpenter Tyler J. , Madaj Zachary B. , Hostetter Galen , Risinger John I. , Teixeira Jose M. 
Published: June 2018

Abstract
Endometrial adenocarcinoma (EndoCA) is the most common gynecologic cancer type in the United States, and its incidence is increasing. The majority of patients are disease-free after surgical resection of stage I tumors, which is often followed by radiotherapy, but most patients with advanced disease recur and have a poor prognosis, largely because the tumors become refractory to cytotoxic chemotherapies. PTEN, a commonly mutated tumor suppressor in EndoCAs, is well known for its ability to inhibit the AKT/mTOR signaling pathway. Nuclear functions for PTEN have been proposed as well, but whether those affect EndoCA development, progression, or outcomes is not well understood. Using immunohistochemistry, nuclear PTEN expression was observed in approximately half of EndoCA patient tumors, independent of grade and cytoplasmic PTEN expression. Higher levels of the DNA damage response (DDR) marker, γH2AX, were observed by immunohistochemistry and immunofluorescence in human EndoCA tumor sections that were PTEN-negative, in murine EndoCA tissues that were genetically modified to be PTEN-null, and in Ishikawa EndoCA cells, which do not express endogenous PTEN. Overexpression of exogenous PTEN-WT or PTEN-NLS, a modified PTEN with an added nuclear localization signal, significantly improved both DDR and G2–M transition in Ishikawa cells treated with a DNA-damaging agent. Whereas PARP inhibition with Olaparib was not as effective in Ishikawa cells expressing native or PTEN-NLS, inhibition with Talazoparib was not affected by PTEN overexpression. These results suggest that nuclear PTEN subcellular localization in human EndoCA could be diagnostic when considering DDR therapeutic intervention. Mol Cancer Ther; 17(9); 1995–2003. ©2018 AACR.
Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Miedema Michael D. , Dardari Zeina A. , Kianoush Sina , Virani Salim S. , Yeboah Joseph , Knickelbine Thomas , Sandfort Veit , Rodriguez Carlos J. , Nasir Khurram , Blaha Michael J. 
Published: June 2018

Background

The potential impact of the 2016 United States Preventive Services Task Force (
USPSTF
) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (
ASCVD)
warrants further analysis.

Methods and Results

We studied participants from MESA (Multi‐Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000–2002) and over follow‐up between
USPSTF
and the 2013 American College of Cardiology/American Heart Association (
ACC
/
AHA
) guidelines. Coronary artery calcium (
CAC
) was measured at baseline. Absolute
ASCVD
event rates were calculated according to eligibility categories for each guideline. Among 4962
MESA
participants (aged 59.3±8.8 years, 47.2% female), compared with
ACC
/
AHA
guidelines, baseline statin eligibility by
USPSTF
was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010–2012]). Compared with
ACC
/
AHA
, participants eligible by
USPSTF
were less likely to have zero
CAC
at baseline (36.6% versus 41.2%) and had higher rates of hard
ASCVD
events per 1000 person‐years (11.6 [95% confidence interval, 10.2–13.3] versus 10.0 [8.9–11.3]). The hard
ASCVD
event rate in those eligible by
ACC
/
AHA
but not
USPSTF
was 6.5 (4.9–8.5) events per 1000 person‐years, with the rate varying significantly according to baseline
CAC
(4.2 [2.7–6.7] events in those with
CAC
=0, 12.8 [8.3–19.9] events in those with
CAC
>100).

Conclusions

In
MESA
, compared with
ACC
/
AHA
, the
USPSTF
statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had
ASCVD
rates that varied significantly according to baseline
CAC
, suggesting
CAC
could aid clinical decision making for statins in these individuals.
Morpho-molecular characterization of Peroneutypa (Diatrypaceae, Xylariales) with two novel species from Thailand
Authors: SHANG QIU-JU , HYDE KEVIN D. , JEEWON RAJESH , KHAN SEHROON , PROMPUTTHA ITTHAYAKORN , PHOOKAMSAK RUNGTIWA 
Published: June 2018

Three species of Peroneutypa were collected from dead wood in Thailand. Two new taxa P. diminutiasca and P. rubiformis are herein described, illustrated and compared with related taxa, based on the evidence from morphology and phylogenetic analyses. Details for the holomorphs of P. rubiformis and the third species P. scoparia are provided. Phylogenetic analyses of a combined ITS and TUB2 DNA sequence dataset support their placement in the genus Peroneutypa (Diatrypaceae, Xylariales). An updated key to Peroneutypa species is also provided.
Dynamical Insights into Extreme Short-Term Precipitation Associated with Supercells and Mesovortices
Authors: Nielsen Erik R. , Schumacher Russ S. 
Published: June 2018

Abstract
In some prominent extreme precipitation and flash flood events, radar and rain gauge observations have suggested that the heaviest short-term rainfall accumulations (up to 177 mm h−1) were associated with supercells or mesovortices embedded within larger convective systems. In this research, we aim to identify the influence that rotation has on the storm-scale processes associated with heavy precipitation. Numerical model simulations conducted herein were inspired by a rainfall event that occurred in central Texas in October 2015 where the most extreme rainfall accumulations were collocated with meso-β-scale vortices. Five total simulations were performed to test the sensitivity of precipitation processes to rotation. A control simulation, based on a wind profile from the aforementioned event, was compared with two experiments with successively weaker low-level shear. With greater environmental low-level shear, more precipitation fell, in both a point-maximum and an area-averaged sense. Intense, rotationally induced low-level vertical accelerations associated with the dynamic nonlinear perturbation vertical pressure gradient force were found to enhance the low- to midlevel updraft strength and total vertical mass flux and allowed access to otherwise inhibited sources of moisture and CAPE in the higher-shear simulations. The dynamical accelerations, which increased with the intensity of the low-level shear, dominated over buoyant accelerations in the low levels and were responsible for inducing more intense low-level updrafts that were sustained despite a stable boundary layer.
Impact of the South China Sea Summer Monsoon on the Indian Ocean Dipole
Authors: Zhang Yazhou , Li Jianping , Xue Jiaqing , Feng Juan , Wang Qiuyun , Xu Yidan , Wang Yuehong , Zheng Fei 
Published: June 2018

AbstractThis paper investigates the impact of the South China Sea summer monsoon (SCSSM) on the Indian Ocean dipole (IOD). The results show that the SCSSM has a significant positive relationship with the IOD over the boreal summer [June–August (JJA)] and fall [September–November (SON)]. When the SCSSM is strong, the enhanced southwesterly winds that bring more water vapor to the western North Pacific (WNP) lead to surplus precipitation in the WNP, inducing anomalous ascending there. Consequently, the anomalous descending branch of the SCSSM Hadley circulation (SCSSMHC) develops over the Maritime Continent (MC), favoring deficit precipitation in situ. The precipitation dipole over the WNP and MC as well as the enhanced SCSSMHC leads to intensification of the southeasterly anomalies off Sumatra and Java, which then contributes to the negative sea surface temperature (SST) anomalies through the positive wind–evaporation–SST and wind–thermocline–SST (Bjerknes) feedbacks. Consequently, a positive IOD develops because of the increased zonal gradient of the tropical Indian Ocean SST anomalies and vice versa. The SCSSM has a peak correlation with the IOD when the former leads the latter by three months. This implies that a positive IOD can persist from JJA to SON and reach its mature phase within the frame of the positive Bjerknes feedback in SON. In addition, the local and remote SST anomalies in the tropical Indian and Pacific Oceans have a slight influence on the relationship between the SCSSM and precipitation dipole over the WNP and MC.
A Coupled System for Investigating the Physics of Wave–Ice Interactions
Authors: Orzech Mark D. , Shi Fengyan , Veeramony Jayaram , Bateman Samuel , Calantoni Joseph , Kirby James T. 
Published: June 2018

AbstractA coupled model system has been developed to investigate the physics of wave attenuation and ice edge retreat in the marginal ice zone (MIZ) at small scales [O(m)]. A phase-dependent finite-volume/finite-difference fluid dynamics model is used to simulate waves and currents, and a discrete element software package is employed to represent ice floes as bonded collections of individually tracked smaller particles. We first review the development of the coupled system, with an emphasis on the coupling software and the representation of wave–ice shear stress. Then we describe a series of simulations that were conducted to evaluate and qualitatively validate the performance of the coupled models. The system produced reasonable results for cases of a vertically oscillating ice block and a free-floating ice floe in monochromatic waves. In larger-scale simulations involving multiple ice floes and pancake ice, estimated transmission and reflection coefficients were similar to those obtained from alternate models and/or data, although numerical dissipation may have reduced estimates of transmitted wave energy in longer wave flumes. Challenges and limitations involving relative length scales in the coupled wave and ice domains are explained and discussed.
Relationship between body weight perception and weight-related behaviours
Authors: Sirirassamee Tawima , Phoolsawat Sasiwan , Limkhunthammo Supakorn 
Published: June 2018

Objectives This study aimed to examine the prevalence of weight misperception and to explore the association of weight perception with physical activity and dietary intake. Methods A population-based, nationally representative cross-sectional survey was conducted of 920 Thai adolescents aged 13 to 24 years. Respondents were selected using stratified multistage sampling. Respondents who agreed to participate were asked to complete the Youth Risk Behavior Questionnaire. Results Females were more likely than males to misperceive themselves as overweight (21.8% vs. 11.7%), whereas males were more likely than females to misperceive themselves as underweight (12.3% vs. 3.4%). Males were more likely than females to report a high intake of vegetables (45.7% vs. 38.0%), milk (39.1% vs. 38.0%), 100% fruit juice (20.9% vs. 17.7%) and soda or pop (38.5% vs. 20.6%). Males were also more likely than females to report vigorous physical activity of more than 60 minutes per day (38.1% vs. 21.3%) and vigorous exercise to strengthen or tone muscles (37.3% vs. 13.2%). Conclusions Gender differences in dietary intake and physical activity were identified. However, there were no significant differences in dietary intake and physical activity between adolescents who correctly perceived themselves as overweight and those who misperceived themselves as overweight.
Phonological activation of first language (Spanish) and second language (English) when learning third language (Slovak) novel words
Authors: Mulík Stanislav , Carrasco-Ortiz Haydee , Amengual Mark 
Published: June 2018

Objectives/Research Questions: This study investigates whether bilinguals activate lexical knowledge from both their dominant first language (L1; Spanish) and their less-dominant second language (L2; English) during novel third language (L3; Slovak) word learning. Moreover, it examines the extent to which L2 activation in L3 lexical learning depends on the level of L2 proficiency. Methodology: Stimuli included 120 auditory Slovak words with substantial phonological overlap with either English or Spanish (homophones) or with neither language (control words), and their written Spanish translations. Two groups of participants (with high and low-proficiency in L2 English) completed paired-associate learning, correct/incorrect translation recognition and backward translation tasks on Slovak–Spanish translation equivalents to examine the facilitation effect of homophones with either Spanish or English. Data and Analysis: Response times, accuracy scores and correct translation counts were collected from 35 Spanish–English bilinguals and analyzed by means of repeated measures analyses of variance. Findings/Conclusions: The phonological similarity of novel L3 words with participants’ L2 words showed similar facilitation effects as phonological similarity with L1 words. This implies an involuntary activation of bilinguals’ less-dominant L2, even when not overtly present in the L3 lexical learning task. Moreover, the low-proficiency group experienced a higher facilitation for L1 than for L2 homophones, but overall lower facilitation in L3 lexical learning than the high-proficiency group. These findings suggest that bilinguals can activate lexical knowledge from both of their languages during novel L3 word learning, but the activation of the less-dominant L2 depends on participants’ L2 proficiency. Originality: We investigated how Spanish–English bilinguals incorporate vocabulary from an understudied language (i.e. Slovak) into their lexical system to test the language non-selective hypothesis in a multilingual lexical context. Significance: Our research contributes to the study of the degree of language dominance and its implications for L3 lexical learning and parallel activation of multilinguals’ languages.
Evaluation of the lamina cribrosa in patients with diabetes mellitus using enhanced depth imaging spectral-domain optical coherence tomography
Authors: Akkaya Serkan , Küçük Bekir , Doğan Hatice Karaköse , Can Ertuğrul 
Published: June 2018

Purpose: To compare the lamina cribrosa thickness and anterior lamina cribrosa depth between patients with and without diabetes mellitus and to investigate the effect of metabolic control and duration of diabetes mellitus on lamina cribrosa thickness and anterior lamina cribrosa depth using enhanced depth imaging spectral-domain optical coherence tomography. Methods: A total of 70 patients were enrolled in this cross-sectional study and were divided into the diabetes and control groups. Intraocular pressure, circumpapillary retinal nerve fibre layer thickness, anterior lamina cribrosa depth and lamina cribrosa thickness were compared between the groups. Results: In the control group, the mean intraocular pressure was 14.6 ± 3.1 (mean ± standard deviation) mmHg, mean circumpapillary retinal nerve fibre layer thickness was 105.41 ± 5.86 μm, mean anterior lamina cribrosa depth was 420.3 ± 90.2 μm and mean lamina cribrosa thickness was 248.5 ± 5.4 μm. In the diabetes group, the mean intraocular pressure was 13.9 ± 2.2 mmHg, mean circumpapillary retinal nerve fibre layer thickness was 101.37 ± 10.97 μm, mean anterior lamina cribrosa depth was 351.4 ± 58.6 μm and mean lamina cribrosa thickness was 271.6 ± 33.9 μm. Lamina cribrosa thickness was significantly higher ( p < 0.001) and anterior lamina cribrosa depth was significantly lower ( p = 0.003) in the diabetes group. There was no statistical difference between the groups with regard to age, spherical equivalent, axial length, circumpapillary retinal nerve fibre layer thickness and intraocular pressure ( p  = 0.69, 0.26, 0.47, 0.06 and 0.46, respectively). Lamina cribrosa thickness and anterior lamina cribrosa depth were not significantly correlated with duration of diabetes mellitus (lamina cribrosa thickness: r = −0.078, p = 0.643; anterior lamina cribrosa depth: r = −0.062, p = 0.710) or HbA1c levels (lamina cribrosa thickness: r = −0.078, p = 0.596; anterior lamina cribrosa depth: r = −0.228, p = 0.169). Conclusion: The results of this study showed that the optical coherence tomography measurement of lamina cribrosa revealed thicker and more anteriorly positioned lamina cribrosa for patients with diabetes mellitus compared with those for healthy controls.
Safety and tolerability of intrathecal liposomal amphotericin B (AmBisome) for cryptococcal meningitis: a retrospective study in HIV-infected patients
Authors: Alvarez-Uria Gerardo , Midde Manoranjan , Battula Jayaram , Pujari Himachandra N.B. 
Published: June 2018

Background: While mortality of HIV-related cryptococcal meningitis (CM) in developed countries is relatively low, in developing countries over half of patients die within 10 weeks. Current recommended therapies are often not suitable for resource-poor settings, and new shorter regimens are urgently needed. Intrathecal administration of liposomal amphotericin B (lAmB) has shown promising results in animal models. However, the safety and tolerability of intrathecal lAmB in humans are not well known. Methods: In this retrospective observational study, we report the tolerability and safety of intrathecal lAmB in patients with CM from an HIV cohort study in India. Results: In all, 18 patients were included in the analysis. Six were female and the median age was 40 years [interquartile range (IQR): 35–45]. The median CD4 count was 42 cells/µl (IQR: 19–127). Compared with a historical control group, the hazard ratio for mortality was 0.59 (95% confidence interval: 0.26–1.29). Two patients complained of transient lumbar pain in single occasion. One patient had a skin reaction to chlorhexidine, which was used as skin disinfectant. After initial improvement, one patient requested to stop lumbar punctures for the last 2 days of treatment. Conclusion: Intrathecal lAmB was safe and well tolerated in HIV-infected patients with CM.
Levels of Health Theory With the Example of a Case of Juvenile Rheumatoid Arthritis
Authors: Chabanov Dmitri , Tsintzas Dionysis , Vithoulkas George 
Published: June 2018

Objective. Contemporary medicine is in great need of a new patient health group classification that could be the basis for in-depth pathology assessments, disease development and prognosis, and the possibility of healing, as well as for possible complications of organism reactions to treatment processes. This classification is possible if founded on holistic approaches at the level of health assessment from the point of view of organism reactivity and resistance. Such a classification, assigning 12 levels and 4 health groups, exists in classical homeopathy. Methods. A new method for determining the group and level of health is shown in a case of juvenile rheumatoid arthritis of a generalized form in an 11-year-old girl, treated with classical homeopathy. The follow-up of the case is 18 years. Conclusion. The method allows the physician to assess the organism dynamics as a whole during the pathology development.
Possible reactivation of chromosomally integrated human herpesvirus 6 after treatment with histone deacetylase inhibitor
Authors: Politikos Ioannis , McMasters Malgorzata , Bryke Christine , Avigan David , Boussiotis Vassiliki A. 
Published: June 2018

Key Points
HDAC inhibitors might induce ciHHV-6 reactivation. In ciHHV-6 HSCT recipients posttransplant viral load can estimate persistent host chimerism when the donor is ciHHV-6 negative.
Tuberculosis elimination: where are we now?
Authors: Matteelli Alberto , Rendon Adrian , Tiberi Simon , Al-Abri Seif , Voniatis Constantia , Carvalho Anna Cristina C. , Centis Rosella , D'Ambrosio Lia , Visca Dina , Spanevello Antonio , Battista Migliori Giovanni 
Published: June 2018

Tuberculosis (TB) still represents a major public health issue in spite of the significant impact of the efforts made by the World Health Organization (WHO) and partners to improve its control. In 2014 WHO launched a new global strategy (End TB) with a vision of a world free of TB, and a 2035 goal of TB elimination (defined as less than one incident case per million). The aim of this article is to summarise the theoretical bases of the End TB Strategy and to analyse progresses and persistent obstacles on the way to TB elimination.The evolution of the WHO recommended strategies of TB control (Directly Observed Therapy, Short Course (DOTS), Stop TB and End TB) are described and the concept of TB elimination is discussed. Furthermore, the eight core activities recently proposed by WHO as the milestones to achieve TB elimination are discussed in detail. Finally, the recently published experiences of Cyprus and Oman on their way towards TB elimination are described, together with the regional experience of Latin America.New prevention, diagnostic and treatment tools are also necessary to increase the speed of the present TB incidence decline.