bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults
Authors: Pitter Gisella , Zare Jeddi Maryam , Barbieri Giulia , Gion Massimo , Fabricio Aline S. C. , Daprà Francesca , Russo Francesca , Fletcher Tony , Canova Cristina 
Published: September 2020

Abstract
Background
Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence.

Methods
The study comprised 16,224 individuals aged 20–39 years. Pregnant women (n = 327), or individuals with missing information on the selected covariates (n = 111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP ≥ 140 mmHg)/diastolic blood pressure (DBP ≥ 90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders.

Results
Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61–2.47), 1.60 mmHg (95%CI 0.92–2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR = 1.06 (1.01–1.11), PFOS OR = 1.13 (1.03–1.23), PFHxS OR = 1.08 (1.02–1.15), PFNA OR = 1.20 (1.02–1.40).

Conclusions
Our findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.
Methamphetamine use and HIV risk behavior among men who inject drugs: causal inference using coarsened exact matching
Authors: Noroozi Mehdi , Higgs Peter , Noroozi Alireza , Armoon Bahram , Mousavi Bentolhoda , Alikhani Rosa , Bazrafshan Mohammad Rafi , Astaneh Ali Nazeri , Bayani Azadeh , Moghaddam Ladan Fattah 
Published: September 2020

AbstractBackgroundUnderstanding the association between methamphetamine (MA) use and HIV risk behavior among people who inject drugs (PWID) will assist policy-makers and program managers to sharpen the focus of HIV prevention interventions. This study examines the relationship between MA use and HIV risk behavior among men who inject drugs (MWID) in Tehran, Iran, using coarsened exact matching (CEM).MethodsData for these analyses were derived from a cross-sectional study conducted between June and July 2016. We assessed three outcomes of interest—all treated as binary variables, including distributive and receptive needle and syringe (NS) sharing and condomless sex during the month before interview. Our primary exposure of interest was whether study participants reported any MA use in the month prior to the interview. Firstly, we report the descriptive statistics for the pooled samples and matched sub-samples using CEM. The pooled and matched estimates of the associations and their 95% CI were estimated using a logistic regression model.ResultsOverall, 500 MWID aged between 18 and 63 years (mean = 28.44, SD = 7.22) were recruited. Imbalances in the measured demographic characteristics and risk behaviors between MA users and non-users were attenuated using matching. In the matched samples, the regression models showed participants who reported MA use were 1.82 times more likely to report condomless sex (OR = 1.82 95% CI 1.51, 4.10;P= 0.031), and 1.35 times more likely to report distributive NS sharing in the past 30 days, as compared to MA non-users (OR = 1.35 95% CI 1.15–1.81). Finally, there was a statistically significant relationship between MA use and receptive NS sharing in the past month. People who use MA in the last month had higher odds of receptive NS sharing when compared to MA non-users (OR = 4.2 95% CI 2.7, 7.5;P= 0.013).ConclusionsOur results show a significant relationship between MA use and HIV risk behavior among MWID in Tehran, Iran. MA use was related with increased NS sharing, which is associated with higher risk for HIV exposure and transmission.
Non-destructive phenotyping for early seedling vigor in direct-seeded rice
Authors: Anandan Annamalai , Mahender Anumalla , Sah Rameswar Prasad , Bose Lotan Kumar , Subudhi Hatanath , Meher Jitendra , Reddy Janga Nagi , Ali Jauhar 
Published: September 2020

Abstract
Background
Early seedling vigor is an essential trait of direct-seeded rice. It helps the seedlings to compete with weeds for water and nutrient availability, and contributes to better seedling establishment during the initial phase of crop growth. Seedling vigor is a complex trait, and phenotyping by a destructive method limits the improvement of this trait through traditional breeding. Hence, a non-invasive, rapid, and precise image-based phenotyping technique is developed to increase the possibility to improve early seedling vigor through breeding in rice and other field crops.

Results
To establish and assess the methodology using free-source software, early seedling vigor was estimated from images captured with a digital SLR camera in a non-destructive way. Here, the legitimacy and strength of the method have been proved through screening seven diverse rice cultivars varying for early seedling vigor. In the regression analysis, whole-plant area (WPA) estimated by destructive-flatbed scanner (WPAs) and non-destructive imaging (WPAi) approaches was strongly related (R2 > 83%) and suggested that WPAi can be adapted in place of destructive methods to estimate seedling vigor. In addition, this study has identified a set of new geometric traits (convex hull and top view area) for screening breeding lines for early seedling vigor in rice, which decreased the time by 80% and halved the cost of labor in data observation.

Conclusions
The method demonstrated here is affordable and easy to establish as a phenotypic platform. It is suitable for most glasshouses/net houses for characterizing genotypes to understand the plasticity of shoots under a given environment at the seedling stage. The methodology explained in this experiment has been proven to be practical and suggested as a technique for researchers involved in direct-seeded rice. Consequently, it will help in the simultaneous screening of genotypes in large numbers, the identification of donors, and in gaining information on the genetic basis of the trait to design a breeding program for direct-seeded rice.
A modified method for enzymatic isolation of and subsequent wax extraction from Arabidopsis thaliana leaf cuticle
Authors: Vráblová Martina , Vrábl Daniel , Sokolová Barbora , Marková Dominika , Hronková Marie 
Published: September 2020

Abstract
Background
The plant cuticle represents one of the major adaptations of vascular plants to terrestrial life. Cuticular permeability and chemical composition differ among species. Arabidopsis thaliana is a widely used model for biochemical and molecular genetic studies in plants. However, attempts to isolate the intact cuticle from fresh leaves of Arabidopsis have failed so far. The goal of this study was to optimise an enzymatic method for cuticle isolation of species with a thin cuticle and to test it on several A. thaliana wild types and mutants.

Results
We developed a method for isolation of thin cuticles that allows reducing the isolation time, the separation of abaxial and adaxial cuticles, and avoids formation of wrinkles. Optical microscopy was used for studying cuticle intactness and scanning electron microscopy for visualisation of external and internal cuticle structures after isolation. Wax extracts were analysed by GC–MS. Isolation of intact cuticle was successful for all tested plants. The wax compositions (very-long-chained fatty acids, alcohols and alkanes) of intact leaves and isolated cuticles of wild type Col-0 were compared.

Conclusions
We conclude that the optimised enzymatic method is suitable for the isolation of A. thaliana adaxial and abaxial cuticles. The isolated cuticles are suitable for microscopic observation. Analysis of wax composition revealed some discrepancies between isolated cuticles and intact leaves with a higher yield of wax in isolated cuticles.
Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway
Authors: Yang Yang , Wang Qi , Song Dongjian , Zen Ruirui , Zhang Lei , Wang Yingjun , Yang Heying , Zhang Da , Jia Jia , Zhang Jiao , Wang Jiaxiang 
Published: September 2020

Abstract
Background
Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death.

Methods
The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice.

Results
The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice.

Conclusions
Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.
CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK
Authors: Xue Jimeng , Xu Liling , Zhu Huaqun , Bai Mingxin , Li Xin , Zhao Zhen , Zhong Hua , Cheng Gong , Li Xue , Hu Fanlei , Su Yin 
Published: September 2020

Abstract
Background
Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis.

Methods
Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade.

Results
The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner.

Conclusions
These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.
In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2
Authors: Orozco-Aguilar Josué , Alfaro-Alarcón Alejandro , Acuña-Amador Luis , Chaves-Olarte Esteban , Rodríguez César , Quesada-Gómez Carlos 
Published: September 2020

Abstract
Background
Based on MLST analyses the global population of C. difficile is distributed in eight clades, of which Clade 2 includes the “hypervirulent” NAP1/RT027/ST01 strain along with various unexplored sequence types (STs).

Methods
To clarify whether this clinically relevant phenotype is a widespread feature of C. difficile Clade 2, we used the murine ileal loop model to compare the in vivo pro-inflammatory (TNF-α, IL-1β, IL-6) and oxidative stress activities (MPO) of five Clade 2 clinical C. difficile isolates from sequence types (STs) 01, 41, 67, and 252. Besides, we infected Golden Syrian hamsters with spores from these strains to determine their lethality, and obtain a histological evaluation of tissue damage, WBC counts, and serum injury biomarkers (LDH, ALT, AST, albumin, BUN, creatinine, Na+, and Cl−). Genomic distances were calculated using Mash and FastANI to explore whether the responses were dictated by phylogeny.

Results
The ST01 isolate tested ranked first in all assays, as it induced the highest overall levels of pro-inflammatory cytokines, MPO activity, epithelial damage, biochemical markers, and mortality measured in both animal models. Statistically indistinguishable or rather similar outputs were obtained for a ST67 isolate in tests such as tissue damage, neutrophils count, and lethal activity. The results recorded for the two ST41 isolates tested were of intermediate magnitude and the ST252 isolate displayed the lowest pathogenic potential in all animal experiments. This ordering matched the genomic distance of the ST01 isolate to the non-ST01 isolates.

Conclusions
Despite their close phylogenic relatedness, our results demonstrate differences in pathogenicity and virulence levels in Clade 2 C. difficile strains, confirm the high severity of infections caused by the NAP1/RT027/ST01 strain, and highlight the importance of C. difficile typing.
Linking chemical and disease entities to ontologies by integrating PageRank with extracted relations from literature
Authors: Ruas Pedro , Lamurias Andre , Couto Francisco M. 
Published: September 2020

Abstract
Background
Named Entity Linking systems are a powerful aid to the manual curation of digital libraries, which is getting increasingly costly and inefficient due to the information overload. Models based on the Personalized PageRank (PPR) algorithm are one of the state-of-the-art approaches, but these have low performance when the disambiguation graphs are sparse.

Findings
This work proposes a Named Entity Linking framework designated by Relation Extraction for Entity Linking (REEL) that uses automatically extracted relations to overcome this limitation. Our method builds a disambiguation graph, where the nodes are the ontology candidates for the entities and the edges are added according to the relations established in the text, which the method extracts automatically. The PPR algorithm and the information content of each ontology are then applied to choose the candidate for each entity that maximises the coherence of the disambiguation graph. We evaluated the method on three gold standards: the subset of the CRAFT corpus with ChEBI annotations (CRAFT-ChEBI), the subset of the BC5CDR corpus with disease annotations from the MEDIC vocabulary (BC5CDR-Diseases) and the subset with chemical annotations from the CTD-Chemical vocabulary (BC5CDR-Chemicals). The F1-Score achieved by REEL was 85.8%, 80.9% and 90.3% in these gold standards, respectively, outperforming baseline approaches.

Conclusions
We demonstrated that RE tools can improve Named Entity Linking by capturing semantic information expressed in text missing in Knowledge Bases and use it to improve the disambiguation graph of Named Entity Linking models. REEL can be adapted to any text mining pipeline and potentially to any domain, as long as there is an ontology or other knowledge Base available.
Neurologically asymptomatic cerebral oligometastatic prostate carcinoma metastasis identified on [Ga]Ga-THP-PSMA PET/CT
Authors: Ross M. I. , Bird N. , Mendichovszky I. A. , Rimmer Y. L. 
Published: September 2020

Abstract
Background
Brain metastases from prostate cancer are rare and usually only occur in the context of widespread systemic disease. This is the first case report of a solitary brain oligometastasis, in a neurologically intact prostate cancer patient with no other systemic disease, detected using [68Ga]Ga-THP-PSMA PET/CT and only the second one using a PSMA-based radiopharmaceutical.

Case presentation
We report the case of a prostate cancer patient presenting 5 years after robot-assisted laparoscopic prostatectomy with biochemical recurrence, no neurological symptoms, and in the absence of metastatic lesions in the body on conventional imaging. A solitary cerebral metastasis was detected using [68Ga]Ga-THP-PSMA PET/CT, surgically resected, leading to a drop in serum PSA and a good recovery.

Conclusion
In this case, [68Ga]Ga-THP-PSMA PET/CT resulted in a major change in clinical management and avoided additional morbidity associated with delayed diagnosis and treatment. This report demonstrates the importance of considering the presence of metastatic disease outside the conventional locations of prostate cancer spread, as well as the importance of ensuring comprehensive [68Ga]Ga-PSMA PET/CT coverage from vertex to upper thighs.
Mode of progression after radioembolization in patients with colorectal cancer liver metastases
Authors: van Roekel Caren , Jongen Jennifer M. J. , Smits Maarten L. J. , Elias Sjoerd G. , Koopman Miriam , Kranenburg Onno , Borel Rinkes Inne H. M. , Lam Marnix G. E. H. 
Published: September 2020

Abstract
Background
Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics.

Methods
Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases.

Results
Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57).

Conclusions
Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.
Considering the societal perspective in economic evaluations: a systematic review in the case of depression
Authors: Duevel Juliane Andrea , Hasemann Lena , Peña-Longobardo Luz María , Rodríguez-Sánchez Beatriz , Aranda-Reneo Isaac , Oliva-Moreno Juan , López-Bastida Julio , Greiner Wolfgang 
Published: September 2020

Abstract
Background
Depressive disorders are associated with a high burden of disease. However, due to the burden posed by the disease on not only the sufferers, but also on their relatives, there is an ongoing debate about which costs to include and, hence, which perspective should be applied. Therefore, the aim of this paper was to examine whether the change between healthcare payer and societal perspective leads to different conclusions of cost-utility analyses in the case of depression.

Methods
A systematic literature search was conducted to identify economic evaluations of interventions in depression, launched on Medline and the Cost-Effectiveness Registry of the Tufts University using a ten-year time horizon (2008–2018). In a two-stepped screening process, cost-utility studies were selected by means of specified inclusion and exclusion criteria. Subsequently, relevant findings was extracted and, if not fully stated, calculated by the authors of this work.

Results
Overall, 53 articles with 92 complete economic evaluations, reporting costs from healthcare payer/provider and societal perspective, were identified. More precisely, 22 estimations (24%) changed their results regarding the cost-effectiveness quadrant when the societal perspective was included. Furthermore, 5% of the ICURs resulted in cost-effectiveness regarding the chosen threshold (2% of them became dominant) when societal costs were included. However, another four estimations (4%) showed the opposite result: these interventions were no longer cost-effective after the inclusion of societal costs.

Conclusions
Summarising the disparities in results and applied methods, the results show that societal costs might alter the conclusions in cost-utility analyses. Hence, the relevance of the perspectives chosen should be taken into account when carrying out an economic evaluation. This systematic review demonstrates that the results of economic evaluations can be affected by different methods available for estimating non-healthcare costs.