bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of physical activity in detailed intensity ranges with body composition and physical function. a cross-sectional study among sedentary older adults
Authors: Savikangas Tiina , Tirkkonen Anna , Alen Markku , Rantanen Taina , Fielding Roger A. , Rantalainen Timo , Sipilä Sarianna 
Published: January 2020

Abstract
Background
Physical activity is crucial to maintain older adults’ health and functioning, but the health benefits of particular activity intensities remain unclear. The aim of this cross-sectional study was to peruse the distribution of physical activity, and to investigate the associations of particular physical activity intensities with body composition and physical function among older adults.

Methods
The sample comprised of 293 community-dwelling sedentary or at most moderately active older adults (42% men, mean age 74 ± 4 years). Physical activity was measured with a hip-worn tri-axial accelerometer over seven consecutive days, and investigated in detailed intensity range and in categories of sedentary, light and moderate-to-vigorous activity. Fat percent and appendicular lean mass were measured with DXA. Physical function was assessed by six-minutes walking test (6-min walk), maximal walking speed over 10 m (10-m walk) and Short Physical Performance Battery (SPPB). Associations were estimated with partial correlation adjusted for sex and age.

Results
Participants spent on average 602 min per day sedentary, 210 min in light activity and 32 min in moderate-to-vigorous activity. Light and moderate-to-vigorous activity were negatively associated with fat percent (r = − 0.360 and r = − 0.384, respectively, p < 0.001 for both), and positively with SPPB, 10-m walk and 6-min walk results (r = 0.145–0.279, p < 0.01, for light and r = 0.220–0.465, p < 0.001, for moderate-to-vigorous activity). In detailed investigation of the intensity range, associations of physical activity with fat percent, 6-min walk and 10-m walk were statistically significant from very light intensity activity onward, whereas significant associations between physical activity and SPPB were observed mostly at higher end of the intensity range. Sedentary time was positively associated with fat percent (r = 0.251, p < 0.001) and negatively with 6-min walk (r = − 0.170, p < 0.01).

Conclusion
Perusing the physical activity intensity range revealed that, among community-dwelling sedentary or at most moderately active older adults, physical activity of any intensity was positively associated with lower fat percent and higher walking speed over long and short distances. These findings provide additional evidence of the importance of encouraging older adults to engage in physical activity of any intensity. More intervention studies are required to confirm the health benefits of light-intensity activity.
The omics revolution: beyond genomics. A meeting report
Authors: Nice E. C. 
Published: January 2020

AbstractThe “omics revolution: beyond genomics” satellite meeting, run under the auspices of the Australian Peptide Association, The Human Proteome Organisation (HUPO) and the HUPO Australia/New Zealand Chromosome 7 initiative, was held at the Oaks Resort, Port Douglas, Queensland, Australia, on 8th September 2019, immediately prior to the 13th Australian Peptide Conference. The meeting, which had over 100 participants representing Australasia, Europe and America, focused on recent advances in omics-related technologies, including mass spectrometry, biosensors and CryoEM, which will assist in the clinical translation of proteomics towards precision/personalized medicine. An overview of the conference and a summary of the oral presentations are presented.
1-1-8 one-step sevoflurane wash-in scheme for low-flow anesthesia: simple, rapid, and predictable induction
Authors: Tribuddharat Sirirat , Sathitkarnmanee Thepakorn , Vattanasiriporn Naruemon , Thananun Maneerat , Nonlhaopol Duangthida , Somdee Wilawan 
Published: January 2020

Abstract
Background
Sevoflurane is suitable for low-flow anesthesia (LFA). LFA needs a wash-in phase. The reported sevoflurane wash-in schemes lack simplicity, target coverage, and applicability. We proposed a one-step 1-1-8 wash-in scheme for sevoflurane LFA to be used with both N2O and Air. The objective of our study was to identify time for achieving each level of alveolar concentration of sevoflurane (FAS) from 1 to 3.5% in both contexts.

Methods
We recruited 199 adults requiring general anesthesia with endotracheal intubation and controlled ventilation—102 in group N2O and 97 in group Air. After induction and intubation, a wash-in was started using a fresh gas flow of O2:N2O or O2:Air at 1:1 L·min− 1 plus sevoflurane 8%. The ventilation was controlled to maintain end-tidal CO2 of 30–35 mmHg.

Results
The rising patterns of FAS and inspired concentration of sevoflurane (FIS) are similar, running parallel between the groups. The FAS/FIS ratio increased from 0.46 to 0.72 within 260 s in group N2O and from 0.42 to 0.69 within 286 s in group Air. The respective time to achieve an FAS of 1, 1.5, 2, 2.5, 3, and 3.5% was 1, 1.5, 2, 3, 3.5, and 4.5 min in group N2O and 1, 1.5, 2, 3, 4, and 5 min in group Air. The heart rate and blood pressure of both groups significantly increased initially then gradually decreased as FAS increased.

Conclusions
The 1-1-8 wash-in scheme for sevoflurane LFA has many advantages, including simplicity, coverage, swiftness, safety, economy, and that it can be used with both N2O and Air. A respective FAS of 1, 1.5, 2, 2.5, 3, and 3.5% when used with N2O and Air can be expected at 1, 1.5, 2, 3, 3.5, and 4.5 min and 1, 1.5, 2, 3, 4, and 5 min.

Trial registration
This study was retrospectively registered with ClinicalTrials.gov (NCT03510013) on June 8, 2018.
General practitioners’ views on use of patient reported outcome measures in primary care: a cross-sectional survey and qualitative study
Authors: Turner Grace M. , Litchfield Ian , Finnikin Sam , Aiyegbusi Olalekan Lee , Calvert Melanie 
Published: January 2020

Abstract
Background
Patient reported outcome measures (PROMs) are increasingly used to assess impact of disease and treatment on quality of life and symptoms; however, their use in primary care is fragmented.
We aimed to understand how PROMs are currently being used in primary care, the barriers and facilitators of this use and if appropriate how it might be optimised.

Methods
Cross-sectional survey and semi-structured interviews among general practitioners (GPs) in England. GPs’ opinions were explored using an electronic, self-completed questionnaire disseminated to 100 GPs via an online doctors’ community and semi-structured qualitative interviews with 25 GPs.

Results
Most GPs surveyed (77/100; 77%) reported using one or more PROM, primarily to aid clinical management (n = 66) or as screening/diagnostic tools (n = 62).
Qualitative interviews highlighted challenges in identifying and selecting PROMs; however, some GPs valued PROMs for shared decision making and to direct patient discussions. The interviews identified key barriers to PROM use including: time constraints; insufficient knowledge; lack of integration into clinical systems; and PROMs being mandated without consultation or explanation. Evidence of the benefit of PROMs is required to promote uptake and use of PROMs in primary care.

Conclusion
Implementation of PROMs in primary care requires integration with clinical systems, a bottom-up approach to PROM selection and system design involving meaningful consultation with patients and primary care clinicians and training/support for use.
Unmet needs of patients with cancer in their last year of life as described by caregivers in a developing world setting: a qualitative study
Authors: Cox-Seignoret Karen , Maharaj Rohan G. 
Published: January 2020

AbstractBackgroundPalliative care is in its infancy in most of the developing world. We set out to explore the lived experiences of families and caregivers of recently deceased cancer patients in Trinidad and Tobago and to determine the unmet needs of the patients and what recommendations could be derived to improve the current services.MethodsA phenomenological approach with purposeful sampling was used. Participants were referred by key health professionals. Face-to-face interviews were conducted. Interviews were transcribed verbatim, with analysis and data collection occurring concurrently. Thematic content analysis was used to determine common domains, themes and sub-themes.ResultsInterviews were completed with 15 caregivers. All were spouses or children of the deceased. Ages of the deceased ranged from 43 to 93, the average being 65.5 years. The deceased experienced a variety of cancers including lung, colorectal and oesophageal.Unmet needs were identified under 4 domains of institutions, community, the family unit and the wider society. Institutional unmet needs were delayed diagnosis and treatment and poor inter-institution coordination. Medical and nursing care failed in the areas of health care providers’ attitudes, pain management and communication. The family unit lacked physical and psychosocial support for the caregiver and financial aid for the family unit. Societal needs were for public education to address myths and cultural beliefs around cancer.ConclusionThere is need for systemic interventions to improve the care of those dying from cancer in Trinidad and Tobago. Stakeholders need to commit to palliative care as a public health priority, implementing education, planning services and mobilizing community resources.
Prevention and management of CVD in LMICs: why do ethnicity, culture, and context matter?
Authors: Anand Shuchi , Bradshaw Christina , Prabhakaran Dorairaj 
Published: January 2020

Abstract
Background
Low- and middle-income countries now experience the highest prevalence and mortality rates of cardiovascular disease.

Main text
While improving the availability and delivery of proven, effective therapies will no doubt mitigate this burden, we posit that studies evaluating cardiovascular disease risk factors, management strategies and service delivery, in diverse settings and diverse populations, are equally critical to improving outcomes in low- and middle-income countries. Focusing on examples drawn from four cardiovascular diseases — coronary artery disease, stroke, diabetes and kidney disease — we argue that ethnicity, culture and context matter in determining the risk factors for disease as well as the comparative effectiveness of medications and other interventions, particularly diet and lifestyle interventions.

Conclusion
We believe that a host of cohort studies and randomized control trials currently being conducted or planned in low- and middle-income countries, focusing on previously understudied race/ethnic groups, have the potential to increase knowledge about the cause(s) and management of cardiovascular diseases across the world.
16S rDNA microbiome composition pattern analysis as a diagnostic biomarker for biliary tract cancer
Authors: Lee Huisong , Lee Hyeon Kook , Min Seog Ki , Lee Won Hee 
Published: January 2020

Abstract
Background
The aim of this study is to investigate the composition of microbiota in biliary tract cancer patients and healthy adults by metagenome analysis and evaluate its potential values as biomarkers for biliary tract cancer.

Methods
Patients who were diagnosed with biliary tract cancer or benign inflammation were enrolled in this study. The control group consisted of healthy adults who presented with no history of significant medical issues. We isolated bacteria-derived extracellular vesicles in the plasma. The microbiome composition was investigated with 16S rDNA metagenome analysis. We evaluated each microbiome to ensure suitability for the biliary tract cancer prediction model.

Results
A total of 155 patients were included in this study: 24 patients with diagnosed biliary tract cancers, 43 diagnosed with cholecystitis or cholangitis, and 88 healthy adults. The microbiome composition pattern of the biliary tract cancer differed from the microbiome composition pattern seen in healthy adult group in beta diversity analysis. The percent composition of microbiota was found to be different from the phylum to genus level. Differences in the composition of the Bifidobacteriaceae and Pseudomonaceae families and Corynebacteriaceae Corynebacterium, Oxalobacteraceae Ralstonia and Comamonadaceae Comamonas species may be used to develop predictive models for biliary tract cancer.

Conclusion
Biliary tract cancer patients have altered microbiome composition, which represents a promising biomarker to differentiate malignant biliary tract disease from normal control group.
Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis
Authors: Neuwirt Hannes , Bouchal Jan , Kharaishvili Gvantsa , Ploner Christian , Jöhrer Karin , Pitterl Florian , Weber Anja , Klocker Helmut , Eder Iris E. 
Published: January 2020

Abstract
Background
Androgen receptor targeted therapies have emerged as an effective tool to manage advanced prostate cancer (PCa). Nevertheless, frequent occurrence of therapy resistance represents a major challenge in the clinical management of patients, also because the molecular mechanisms behind therapy resistance are not yet fully understood. In the present study, we therefore aimed to identify novel targets to intervene with therapy resistance using gene expression analysis of PCa co-culture spheroids where PCa cells are grown in the presence of cancer-associated fibroblasts (CAFs) and which have been previously shown to be a reliable model for antiandrogen resistance.

Methods
Gene expression changes of co-culture spheroids (LNCaP and DuCaP seeded together with CAFs) were identified by Illumina microarray profiling. Real-time PCR, Western blotting, immunohistochemistry and cell viability assays in 2D and 3D culture were performed to validate the expression of selected targets in vitro and in vivo. Cytokine profiling was conducted to analyze CAF-conditioned medium.

Results
Gene expression analysis of co-culture spheroids revealed that CAFs induced a significant upregulation of cholesterol and steroid biosynthesis pathways in PCa cells. Cytokine profiling revealed high amounts of pro-inflammatory, pro-migratory and pro-angiogenic factors in the CAF supernatant. In particular, two genes, 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (HMGCS2) and aldo-keto reductase family 1 member C3 (AKR1C3), were significantly upregulated in PCa cells upon co-culture with CAFs. Both enzymes were also significantly increased in human PCa compared to benign tissue with AKR1C3 expression even being associated with Gleason score and metastatic status. Inhibiting HMGCS2 and AKR1C3 resulted in significant growth retardation of co-culture spheroids as well as of various castration and enzalutamide resistant cell lines in 2D and 3D culture, underscoring their putative role in PCa. Importantly, dual targeting of cholesterol and steroid biosynthesis with simvastatin, a commonly prescribed cholesterol synthesis inhibitor, and an inhibitor against AKR1C3 had the strongest growth inhibitory effect.

Conclusions
From our results we conclude that CAFs induce an upregulation of cholesterol and steroid biosynthesis in PCa cells, driving them into AR targeted therapy resistance. Blocking both pathways with simvastatin and an AKR1C3 inhibitor may therefore be a promising approach to overcome resistances to AR targeted therapies in PCa.
Crosstalk between stressed brain cells: direct and indirect effects of ischemia and aglycemia on microglia
Authors: Rabenstein Monika , Vay Sabine Ulrike , Blaschke Stefan , Walter Helene Luise , Ladwig Anne , Fink Gereon Rudolf , Rueger Maria Adele , Schroeter Michael 
Published: January 2020

Abstract
Background
In cerebral ischemia, microglia have a dichotomous role in keeping the balance between pro- and anti-inflammatory mediators to avoid deleterious chronic inflammation and to leverage repair processes.

Methods
We examined functional and inflammatory markers in primary rat microglia in vitro after oxygen-glucose deprivation (OGD) or glucose deprivation (aglycemia). We then investigated the preconditioning effect of OGD or aglycemia upon a subsequent strong inflammatory stimulus, here lipopolysaccharides (LPS). Moreover, an “in vitro brain model” of neurons and glia, differentiated from primary rat neural stem cells, was exposed to OGD or aglycemia. Conditioned medium (CM) of this neuronal/glial co-culture was then used to condition microglia, followed by LPS as a “second hit.”

Results
OGD or aglycemia at sublethal doses did not significantly affect microglia function, including the expression of inflammatory markers. However, preconditioning with either OGD or aglycemia led to a decreased pro-inflammatory response to a subsequent stimulus with LPS. Interestingly, the anti-inflammatory markers IGF-1 and IL-10 were additionally reduced after such preconditioning, while expression of CD206 remained unaffected. Treatment with CM from the neuronal/glial co-culture alone did not affect the expression of inflammatory markers in microglia. In contrast, treatment with CM increased the expression of both pro- and anti-inflammatory markers in microglia upon a second hit with LPS. Interestingly, this effect could be attenuated in microglia treated with CM from neuronal/glia co-cultures preconditioned with OGD or aglycemia.

Conclusions
Data suggest specific and distinct microglia signatures in response to metabolic stress. While metabolic stress directly and indirectly applied to microglia did not mitigate their subsequent response to inflammation, preconditioning with metabolic stress factors such as OGD and aglycemia elicited a decreased inflammatory response to a subsequent inflammation stimulus.
Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats
Authors: Yuan Hongjie , Du Shibin , Chen Liping , Xu Xiaoqing , Wang Yufeng , Ji Fuhai 
Published: January 2020

Abstract
Background
Chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear.

Methods
We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund’s adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model.

Results
CFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4–6 dorsal root ganglions (DRGs) in rats. Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, CFA treatment promoted binding of C/EBPα to the NGF gene promoter region and C/EBPα siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats.

Conclusion
Collectively, the results indicated that CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of C/EBPα with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.
scMAGeCK links genotypes with multiple phenotypes in single-cell CRISPR screens
Authors: Yang Lin , Zhu Yuqing , Yu Hua , Cheng Xiaolong , Chen Sitong , Chu Yulan , Huang He , Zhang Jin , Li Wei 
Published: January 2020

AbstractWe present scMAGeCK, a computational framework to identify genomic elements associated with multiple expression-based phenotypes in CRISPR/Cas9 functional screening that uses single-cell RNA-seq as readout. scMAGeCK outperforms existing methods, identifies genes and enhancers with known and novel functions in cell proliferation, and enables an unbiased construction of genotype-phenotype network. Single-cell CRISPR screening on mouse embryonic stem cells identifies key genes associated with different pluripotency states. Applying scMAGeCK on multiple datasets, we identify key factors that improve the power of single-cell CRISPR screening. Collectively, scMAGeCK is a novel tool to study genotype-phenotype relationships at a single-cell level.
CUBIC: an atlas of genetic architecture promises directed maize improvement
Authors: Liu Hai-Jun , Wang Xiaqing , Xiao Yingjie , Luo Jingyun , Qiao Feng , Yang Wenyu , Zhang Ruyang , Meng Yijiang , Sun Jiamin , Yan Shijuan , Peng Yong , Niu Luyao , Jian Liumei , Song Wei , Yan Jiali , Li Chunhui , Zhao Yanxin , Liu Ya , Warburton Marilyn L. , Zhao Jiuran , Yan Jianbing 
Published: January 2020

Abstract
Background
Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders.

Results
Hundreds of QTL for 23 agronomic traits are uncovered with 14 million high-quality SNPs and a high-resolution identity-by-descent map, which account for an average of 75% of the heritability for each trait. We find epistasis contributes to phenotypic variance widely. Integrative cross-population analysis and cross-omics mapping allow effective and rapid discovery of underlying genes, validated here with a case study on leaf width.

Conclusions
Through the integration of experimental genetics and genomics, our study provides useful resources and gene mining strategies to explore complex quantitative traits.
Waardenburg-Shah syndrome (WS type IV): a rare case from Pakistan
Authors: Khan Taimoor Ashraf , Safdar C. Aqeel , Zameer Shehryar , Khushdil Arshad 
Published: January 2020

AbstractWaardenburg-Shah syndrome is a rare autosomal recessive [AR] inherited disorder characterized by the presence of Hirschsprung’s disease with a high likelihood of aganglionic megacolon, due to which the mortality is high. The management of the condition involves surgical intervention for the removal of the aganglionic segment of the colon. Here, we report a neonate that presented with a white forelock, white eyelashes, iris hypopigmentation, and sensorineural deafness associated with bilious vomiting, refusal to feed, and failure to pass meconium indicating intestinal obstruction.
Random X chromosome inactivation in patients with Klinefelter syndrome
Authors: Kinjo Kenichi , Yoshida Tomoko , Kobori Yoshitomo , Okada Hiroshi , Suzuki Erina , Ogata Tsutomu , Miyado Mami , Fukami Maki 
Published: January 2020

Abstract
Background
X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10–12 embryonic progenitor cells. To date, it remains unclear whether XCI ratios are normally preserved in Klinefelter syndrome (KS) patients with 47,XXY karyotype.

Methods
We examined XCI ratios in 18 KS patients through DNA methylation analysis for the polymorphic trinucleotide locus in the AR gene. The results of the KS patients were compared to previous data from healthy young women.

Results
XCI ratios in KS patients followed a normal distribution. Skewed XCI was observed in two patients, one of whom exhibited extremely skewed XCI. The frequencies of skewed and extremely skewed XCI in the KS cohort were comparable to those in healthy women.

Conclusion
This study confirmed the rarity of skewed XCI in KS patients. These results indicate that the presence of a supernumerary X chromosome during the cleavage and early blastocyst stages does not affect the developmental tempo of embryos. Our data deserve further validation.