bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Peptide Probe Enables Photoacoustic-Guided Imaging and Drug Delivery to Lung Tumors in K-rasLA2 Mutant Mice
Authors: Jung Hyunkyung , Park Sungjo , Gunassekaran Gowri Rangaswamy , Jeon Mansik , Cho Young-Eun , Baek Moon-Chang , Park Jae Yong , Shim Gayong , Oh Yu-Kyoung , Kim In-San , Kim Chulhong , Lee Byungheon 
Published: June 2019

Abstract

The lack of molecular targets and targeting probes remains a major drawback for targeted imaging and drug delivery in lung cancer. In this study, we exploited in vivo phage display to identify a novel targeting probe that homes to the tumor in a K-rasLA2 mutant mouse lung cancer model. Compared with other candidate peptides selected from 5 rounds of phage display, the CRQTKN peptide homed to tumor nodules in the lung of mutant mice at higher levels. Photoacoustic tomography of mutant mice detected lung tumors via tumor homing of the near-infrared fluorescence dye-labeled CRQTKN peptide. Ex vivo photoacoustic images of isolated organs further demonstrated tumor homing of the CRQTKN peptide, whereas minimal accumulation was observed in control organs, such as the liver. Compared with untargeted liposomes and doxorubicin, doxorubicin-loaded liposomes whose surface was modified with the CRQTKN peptide more efficiently delivered doxorubicin and reduced the number or size of tumor lesions in K-rasLA2 mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinity-based identification was used to detect TNF receptor superfamily member 19L (TNFRSF19L), which was upregulated in lung tumors of mutant mice, as the receptor for the CRQTKN peptide. In conclusion, these results suggest that the CRQTKN peptide is a promising targeting probe for photoacoustic-guided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L.

Significance:
These findings present a new tumor-targeting probe for photoacoustic-guided detection and drug delivery.
Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer
Authors: Lieu Christopher H. , Golemis Erica A. , Serebriiskii Ilya G. , Newberg Justin , Hemmerich Amanda , Connelly Caitlin , Messersmith Wells A. , Eng Cathy , Eckhardt S. Gail , Frampton Garrett , Cooke Matthew , Meyer Joshua E. 
Published: June 2019

Abstract

Purpose:
The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer.

Experimental Design:
DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established.

Results:
Overall genomic alteration rates in the younger (&lt;40) and older (≥50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53 (FDR &lt; 0.01) and CTNNB1 (FDR = 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR &lt; 0.01), KRAS (FDR &lt; 0.01), BRAF (FDR &lt; 0.01), and FAM123B (FDR &lt; 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR &lt; 0.01), BRAF (FDR &lt; 0.01), and KRAS (FDR &lt; 0.01).

Conclusions:
Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.
Analysis of the Genomic Landscape in ALK+ NSCLC Patients Identifies Novel Aberrations Associated with Clinical Outcomes
Authors: Couëtoux du Tertre Mathilde , Marques Maud , Tremblay Lise , Bouchard Nicole , Diaconescu Razvan , Blais Normand , Couture Christian , Pelsser Vincent , Wang Hangjun , Higenell Valerie , Izzi Luisa , Gambaro Karen , Hoffert Cyrla , Srivastava Archana , Spatz Alan , Rousseau Caroline , McNamara Suzan , Cohen Victor , Batist Gerald , Agulnik Jason 
Published: June 2019

Abstract
Rearrangements in the anaplastic lymphoma kinase (ALK) gene are found in approximately 5% of non–small cell lung carcinoma (NSCLC). Here, we present a comprehensive genomic landscape of 11 patients with ALK+ NSCLC and investigate its relationship with response to crizotinib. Using whole-exome sequencing and RNAseq data, we identified four rare ALK fusion partners (HIP1, GCC2, ERC1, and SLC16A7) and one novel partner (CEP55). At the mutation level, TP53 was the most frequently mutated gene and was only observed in patients with the shortest progression-free survival (PFS). Of note, only 4% of the genes carrying mutations are present in more than 1 patient. Analysis of somatic copy number aberrations (SCNA) demonstrated that a gain in EML4 was associated with longer PFS, and a loss of ALK or gain in EGFR was associated with shorter PFS. This study is the first to report a comprehensive view of the ALK+ NSCLC copy number landscape and to identify SCNA regions associated with clinical outcome. Our data show the presence of TP53 mutation as a strong prognostic indication of poor clinical response in ALK+ NSCLC. Furthermore, new and rare ALK fusion partners were observed in this cohort, expanding our knowledge in ALK+ NSCLC.
Regulation of health workforce in India
Authors: Lal Dharmesh K. 
Published: June 2019

Health workforce regulations are central to achieving health objectives, ensuring high and safe standards of healthcare. The health workforce regulation needs to ensure quality of education, infrastructure and continual maintenance of professionals' standards across all health professions. These measures also assure the public, other stakeholders, and practitioners that all the concerns about standards of the workforce will be addressed in transparent and consistent manner. Broadly the regulations consist of policy making, admission guidelines to the different health professional courses, defining and regulating education standards through controlling the qualifications and expertise of the faculty, teaching institutes required infrastructure, maintenance of a register, continuous upgradation and regular assessment of professional skills as well as monitoring the quackery-practice by unqualified people, investigating and dealing with problems in relation to the conduct, health or performance of registered practitioners. Healthcare in India is provided by a variety of groups with varying skill levels, across a range of systems of medicine both in the public and private sector and there are regulatory bodies for doctors, dentists, nurses and pharmacists. This paper presents Indias' Health Workforce Regulatory Model, identifying its main institutions and regulatory mechanisms.
Additions to the flora of Arunachal Pradesh State, India
Authors: Tiwari Umeshkumar Lalchand 
Published: June 2019

The paper highlights the occurrence of five angiosperm species in Arunachal Pradesh in India, namely Synedrella nodiflora (L.) Gaertn., Lindenbergia grandiflora (Buch.-Ham. ex D. Don) Benth., Balanophora polyandra Griff., Maoutia puya (Hook.) Wedd., and Isachne pulchella Roth., which are additions to the flora of the state.
A report on additions to the flora of Andaman & Nicobar Islands, India
Authors: Tagore Johny Kumar , Jansirani Ponnaiah , Soosairaj Sebastian 
Published: June 2019

The present paper deals with the collection of Monochoria hastata (L.) Solms (Pontederiaceae) and Alpinia malaccensis (Burm.f.) Roscoe (Zingiberaceae) from South and Little Andaman Islands, constituting new records for the flora of Andaman & Nicobar Islands, India.

Alpinia malaccensis, Dhanikari Botanical Gardens, Little Andaman Islands, Monochoria hastata, new distribution records, Pontederiaceae, South Andaman Islands, Zingiberaceae.
Diel activity pattern of meso-carnivores in the suburban tropical dry evergreen forest of the Coromandel Coast, India
Authors: Selvan Kangaraj Muthamizh , Krishnakumar Bawa Mothilal , Ramasamy Pasiyappazham , Thinesh Thangadurai 
Published: June 2019

Sympatric and similar body-sized species exhibit interspecific competition for resources. The present study investigated diel activity of five meso-carnivore species (Canis aureus, Felis chaus, Paradoxurus hermaphroditus, Viverricula indica, and Herpestes edwardsii) in a human-dominated region of Auroville and around Pondicherry University using camera-trap survey data. Diel activity pattern and overlap were estimated using the kernel density method. The Jungle Cat Felis chaus and the Golden Jackal Canis aureus exhibited cathemeral diel activity with a high overlap between them (Δ̂1 = 0.78). The Indian Grey Mongoose Herpestes edwardsii displayed a diurnal activity pattern and had low overlap with the Small Indian Civet Viverricula indica (Δ̂1 = 0.34). Moderate overlap was found between the Small Indian Civet and the Palm Civet Paradoxurus hermaphroditus (Δ̂1 = 0.32). Therefore, diel activity patterns of mesocarnivores indicate inter- and intra-specific trade-off competition avoidance resulting in successful foraging. The present camera-trap survey has provided insights into diel activity patterns and more attention is required to be paid to the study of feeding and breeding ecology of these species in human-dominated landscapes.
Cardiovascular Health Among Non‐Hispanic Asian Americans: NHANES, 2011–2016
Authors: Fang Jing , Zhang Zefeng , Ayala Carma , Thompson‐Paul Angela M. , Loustalot Fleetwood 
Published: June 2019

Background
Asian Americans are the fastest growing population in the United States, but little is known about their cardiovascular health (CVH). The objective of this study was to assess CVH among non‐Hispanic Asian Americans (NHAAs) and to compare these estimates to those of non‐Hispanic white (NHW) participants.

Methods and Results

Merging NHANES (National Health and Nutrition Examination Survey) data from 2011 to 2016, we examined 7 metrics (smoking, weight, physical activity, diet, blood cholesterol, blood glucose, and blood pressure) to assess CVH among 5278 NHW and 1486 NHAA participants aged ≥20 years. We assessed (1) the percentage meeting 6 to 7 metrics (ideal CVH), (2) the percentage meeting only 0 to 2 metrics (poor CVH), and (3) the overall mean CVH score. We compared these estimates between NHAAs and NHWs and among foreign‐born NHAAs by birthplace and number of years living in the United States. The adjusted prevalence of ideal CVH was 8.7% among NHAAs and 5.9% among NHWs (
P
<0.001). NHAAs were significantly more likely to have ideal CVH (adjusted prevalence ratio: 1.42; 95% CI, 1.29–1.55) compared with NHWs. Among NHAAs, there was no significant difference in ideal CVH between US‐ and foreign‐born participants, nor by number of years living in the United States. With lower body mass index thresholds (<23, normal weight) for NHAAs, there were no statistically significant differences in the adjusted prevalence of ideal CVH (6.5% versus 5.9%,
P
=0.216) between NHAAs and NHWs.

Conclusions
NHAAs had a higher prevalence of overall ideal CVH compared with NHWs. However, when using a lower body mass index threshold for NHAAs, there was no difference in ideal CVH between the groups.
Effects of the Angiotensin‐Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta‐Analysis
Authors: Wang Yiwen , Zhou Ran , Lu Chi , Chen Qing , Xu Tongda , Li Dongye 
Published: June 2019

Background
The angiotensin‐receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin‐converting enzyme inhibitor enalapril in terms of reducing cardiovascular mortality in the PARADIGM‐HF (Prospective Comparison of ARNI with angiotensin‐converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study. However, the impact of ARNI on cardiac reverse remodeling (CRR) has not been established.

Methods and Results

We conducted a meta‐analysis to compare the effects of ARNI versus angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers on CRR indices. We searched databases for studies published between 2010 and 2019 that reported CRR indices following ARNI administration. Effect size was expressed as mean difference (MD) with 95% CIs. Twenty studies enrolling 10 175 patients were included. ARNI improved functional capacity in patients with heart failure (HF) and a reduced ejection fraction (EF), including increasing New York Heart Association functional class (MD −0.79, 95% CI −0.86, −0.71) and 6‐minute walking distance (MD 27.62 m, 95% CI 15.76, 39.48). ARNI outperformed angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in terms of CRR indices, with striking changes in left ventricular EF, diameter, and volume. However, there were no significant improvements in indices except left ventricular mass index (MD −3.25 g/m
2
, 95% CI −3.78, −2.72) and left atrial volume (MD −7.20 mL, 95% CI −14.11, −0.29) in HF patients with preserved EF treated with ARNI. Improvements in CRR indices were observed at 3 months and became more significant with longer follow‐up to 12 months. The regression equation for the relationship between left ventricular EF and end‐diastolic dimension was y=0.041+0.071x+0.045x
2
+0.006x
3
.

Conclusions
ARNI distinctly improved left ventricular size and hypertrophy compared with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in HF with reduced EF patients, even after short‐term follow‐up. Patients appeared to benefit more in terms of CRR treated with ARNI as early as possible and for at least 3 months. Further large sample trials are required to determine the effects of ARNI on CRR in HF with preserved EF patients.
Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients
Authors: Luby Marie , Hsia Amie W. , Nadareishvili Zurab , Cullison Kaylie , Pednekar Noorie , Adil Malik Muhammad , Latour Lawrence L. 
Published: June 2019

Background and Purpose—
The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization.

Methods—
Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0–2 using the latest available modified Rankin Scale score.

Results—

Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%;
P
=0.001), any hemorrhagic transformation (60% versus 36%;
P
=0.04) and poor clinical outcome (67% versus 36%;
P
=0.008). Only age (odds ratio, 1.1; 95% CI, 1.01–1.12;
P
=0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93–26.92;
P
=0.003).

Conclusions—
In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00009243.
Prevalence of treatment-resistant psychoses in the community: A naturalistic study
Authors: Beck Katherine , McCutcheon Robert , Stephenson Lucy , Schilderman Marcela , Patel Natasha , Ramsay Rosalind , Howes Oliver D 
Published: June 2019

Background: Treatment-resistant schizophrenia (TRS) is a major cause of disability. Clozapine is currently the only antipsychotic medication licensed for its treatment. However, the rate of treatment resistance among outpatients with schizophrenia or other psychoses, and the rate of use of clozapine among them, is not known. Aims: The aims of this study are (a) to determine the point prevalence of treatment-resistant psychosis in a community sample, and (b) to determine the number of patients with TRS who have never had a clozapine trial. Method: Clinico-demographic data were extracted from the case notes for 202 patients from two community mental-health teams. Results: We found that 56% (99/176) had a diagnosis of TRS, and 52% (51/99) of these patients had never been treated with clozapine. Patients of non-white ethnicity were less likely to have had a clozapine trial ( p=0.009). The point prevalence of treatment resistance within the bipolar affective disorder sample was 19% (5/26). Conclusion: These findings suggest that TRS is common in the community mental-health team, and a large proportion of these patients have not received clozapine. These findings indicate that identifying and treating treatment resistance should be a focus of community services for schizophrenia.
Acute impact of an endurance race on cardiac function and biomarkers of myocardial injury in triathletes with and without myocardial fibrosis
Authors: Tahir Enver , Scherz Benedikt , Starekova Jitka , Muellerleile Kai , Fischer Roland , Schoennagel Björn , Warncke Malte , Stehning Christian , Cavus Ersin , Bohnen Sebastian , Radunski Ulf K , Blankenberg Stefan , Simon Perikles , Pressler Axel , Adam Gerhard , Patten Monica , Lund Gunnar K 
Published: June 2019

Aims The aim of this study was to investigate the occurrence of myocardial injury and cardiac dysfunction after an endurance race by biomarkers and cardiac magnetic resonance in triathletes with and without myocardial fibrosis. Methods and results Thirty asymptomatic male triathletes (45 ± 10 years) with over 10 training hours per week and 55 ± 8 ml/kg per minute maximal oxygen uptake during exercise testing were studied before (baseline) and 2.4 ± 1.1 hours post-race. Baseline cardiac magnetic resonance included cine, T1/T2, late gadolinium enhancement (LGE) and extracellular volume imaging. Post-race non-contrast cardiac magnetic resonance included cine and T1/T2 mapping. Non-ischaemic myocardial fibrosis was present in 10 triathletes (LGE+) whereas 20 had no fibrosis (LGE–). At baseline, LGE + triathletes had higher peak exercise systolic blood pressure with 222 ± 21 mmHg compared to LGE– triathletes (192 ± 30 mmHg, P < 0.01). Post-race troponin T and creatine kinase MB were similarly increased in both groups, but there was no change in T2 and T1 from baseline to post-race with 54 ± 3 ms versus 53 ± 3 ms ( P = 0.797) and 989 ± 21 ms versus 989 ± 28 ms ( P = 0.926), respectively. However, post-race left atrial ejection fraction was significantly lower in LGE + triathletes compared to LGE– triathletes (53 ± 6% vs. 59 ± 6%, P < 0.05). Furthermore, baseline atrial peak filling rates were lower in LGE –  triathletes (121 ± 30 ml/s/m2) compared to LGE + triathletes (161 ± 34 ml/s/m2, P < 0.01). Post-race atrial peak filling rates increased in LGE– triathletes to 163 ± 46 ml/s/m2, P < 0.001), but not in LGE + triathletes (169 ± 50ml/s/m2, P = 0.747). Conclusion Despite post-race troponin T release, we did not find detectable myocardial oedema by cardiac magnetic resonance. However, the unfavourable blood pressure response during exercise testing seemed to be associated with post-race cardiac dysfunction, which could explain the occurrence of myocardial fibrosis in triathletes.
Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia
Authors: Keating Amy K. , Gossai Nathan , Phillips Christine L. , Maloney Kelly , Campbell Kristen , Doan Andrew , Bhojwani Deepa , Burke Michael J. , Verneris Michael R. 
Published: June 2019

Key Points
Children treated with blinatumomab for B-ALL with MRD had few side effects and proceeded to hematopoietic cell transplant without delay. Blinatumomab given prior to transplant reduces MRD and results in favorable leukemia-free survival, toxicity, and overall survival.
Predictors of mammographic density among women with a strong family history of breast cancer
Authors: Moran Olivia , Eisen Andrea , Demsky Rochelle , Blackmore Kristina , Knight Julia A. , Panchal Seema , Ginsburg Ophira , Zbuk Kevin , Yaffe Martin , Metcalfe Kelly A. , Narod Steven A. , Kotsopoulos Joanne 
Published: June 2019

Abstract

Background
Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation.

Methods
We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates.

Results
Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant.

Conclusions
In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.