bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACE inhibitory peptides in standard and fermented deer velvet: an in silico and in vitro investigation
Authors: Haines Stephen R. , McCann Mark J. , Grosvenor Anita J. , Thomas Ancy , Noble Alasdair , Clerens Stefan 
Published: December 2019

Abstract
Background
The use of deer velvet antler (DVA) as a potent traditional medicine ingredient goes back for over 2000 years in Asia. Increasingly, though, DVA is being included as a high protein functional food ingredient in convenient, ready to consume products in Korea and China. As such, it is a potential source of endogenous bioactive peptides and of ‘cryptides’, i.e. bioactive peptides enzymatically released by endogenous proteases, by processing and/or by gastrointestinal digestion. Fermentation is an example of a processing step known to release bioactive peptides from food proteins. In this study, we aimed to identify in silico bioactive peptides and cryptides in DVA, before and after fermentation, and subsequently to validate the major predicted bioactivity by in vitro analysis.

Methods
Peptides that were either free or located within proteins were identified in the DVA samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by database searching. Bioactive peptides and cryptides were identified in silico by sequence matching against a database of known bioactive peptides. Angiotensin-converting enzyme (ACE) inhibitory activity was measured by a colorimetric method.

Results
Three free bioactive peptides (LVVYPW, LVVYPWTQ and VVYPWTQ) were solely found in fermented DVA, the latter two of which are known ACE inhibitors. However matches to multiple ACE inhibitor cryptides were obtained within protein and peptide sequences of both unfermented and fermented DVA. In vitro analysis showed that the ACE inhibitory activity of DVA was more pronounced in the fermented sample, but both unfermented and fermented DVA had similar activity following release of cryptides by simulated gastrointestinal digestion.

Conclusions
DVA contains multiple ACE inhibitory peptide sequences that may be released by fermentation or following oral consumption, and which may provide a health benefit through positive effects on the cardiovascular system. The study illustrates the power of in silico combined with in vitro methods for analysis of the effects of processing on bioactive peptides in complex functional ingredients like DVA.
Experience of oncology residents with death: a qualitative study in Mexico
Authors: Álvarez-del-Río Asunción , Ortega-García Edwin , Oñate-Ocaña Luis , Vargas-Huicochea Ingrid 
Published: December 2019

Abstract
Background
Physicians play a fundamental role in the care of patients at the end of life that includes knowing how to accompany patients, alleviate their suffering and inform them about their situation. However, in reality, doctors are part of this society that is reticent to face death and lack the proper education to manage it in their clinical practice. The objective of this study was to explore the residents’ concepts of death and related aspects, their reactions and actions in situations pertaining to death in their practice, and their perceptions about existing and necessary training conditions.

Methods
A qualitative approach was used to examine these points in depth based on interviews conducted with seven oncology residents.

Results
Participants do not have a clear concept of death and, although it is seen as a common phenomenon, they consider it an enemy to beat. The situations to which respondents react more frequently with frustration and sadness after the death of patients were when they felt emotionally involved, if they identify with the patient, in cases of pediatric patients and with patients who refuse treatment. To deal with death, participants raise barriers and attempt to become insensitive. Although residents in this study recognize the importance of training to learn how to better deal with death, it seems they are not fully invested in reaching more of it.

Conclusions
Participants face death in a daily basis without the necessary training, which appears to impact them more than they are willing to accept. They do not achieve their goals managing situations regarding death as well as they assume they do. Despite recognizing the need of more training and support for better coping with death, they prefer to continue to learn from their experience.

Trial registration
Not applicable.
Improving rare disease classification using imperfect knowledge graph
Authors: Li Xuedong , Wang Yue , Wang Dongwu , Yuan Walter , Peng Dezhong , Mei Qiaozhu 
Published: December 2019

Abstract
Background
Accurately recognizing rare diseases based on symptom description is an important task in patient triage, early risk stratification, and target therapies. However, due to the very nature of rare diseases, the lack of historical data poses a great challenge to machine learning-based approaches. On the other hand, medical knowledge in automatically constructed knowledge graphs (KGs) has the potential to compensate the lack of labeled training examples. This work aims to develop a rare disease classification algorithm that makes effective use of a knowledge graph, even when the graph is imperfect.

Method
We develop a text classification algorithm that represents a document as a combination of a “bag of words” and a “bag of knowledge terms,” where a “knowledge term” is a term shared between the document and the subgraph of KG relevant to the disease classification task. We use two Chinese disease diagnosis corpora to evaluate the algorithm. The first one, HaoDaiFu, contains 51,374 chief complaints categorized into 805 diseases. The second data set, ChinaRe, contains 86,663 patient descriptions categorized into 44 disease categories.

Results
On the two evaluation data sets, the proposed algorithm delivers robust performance and outperforms a wide range of baselines, including resampling, deep learning, and feature selection approaches. Both classification-based metric (macro-averaged F1 score) and ranking-based metric (mean reciprocal rank) are used in evaluation.

Conclusion
Medical knowledge in large-scale knowledge graphs can be effectively leveraged to improve rare diseases classification models, even when the knowledge graph is incomplete.
Plasma omentin levels are inversely associated with atherosclerosis in type 2 diabetes patients with increased plasma adiponectin levels: a cross-sectional study
Authors: Nishimura Masami , Morioka Tomoaki , Hayashi Mariko , Kakutani Yoshinori , Yamazaki Yuko , Kurajoh Masafumi , Mori Katsuhito , Fukumoto Shinya , Shioi Atsushi , Shoji Tetsuo , Inaba Masaaki , Emoto Masanori 
Published: December 2019

Abstract
Background
Omentin and adiponectin are among the anti-inflammatory and anti-atherogenic adipokines that have potentially beneficial effects on cardiovascular disorders. Recent studies indicate a paradoxical relationship between adiponectin and cardiovascular mortality across many clinical settings including type 2 diabetes. In this study, we characterized the clinical features of type 2 diabetes patients with increased adiponectin levels and examined the association between omentin and atherosclerosis in those patients.

Methods
The subjects were 413 patients with type 2 diabetes. Fasting plasma omentin and total adiponectin levels were measured by enzyme-linked immunosorbent assay. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasonography. The subjects were stratified according to the median value of plasma adiponectin.

Results
In high-adiponectin group, omentin levels were higher, while IMT tended to be greater than those in low-adiponectin group. The high-adiponectin group also exhibited older age, higher systolic blood pressure, lower kidney function, body mass index, and insulin resistance index compared to the low-adiponectin group. Multivariate analysis revealed that omentin levels were independently and negatively associated with IMT in high-adiponectin group, but not in low-adiponectin group, after adjusting for adiponectin levels and traditional cardiovascular risk factors. On the other hand, adiponectin levels were not significantly associated with IMT in either group.

Conclusions
Plasma omentin levels are inversely associated with IMT in type 2 diabetes patients with increased adiponectin levels and multiple cardiovascular risk factors. This study suggests a protective role of omentin against atherosclerosis in type 2 diabetes patients, which is potentially influenced by adiponectin level and cardiovascular risk status.
Mesenchymal stromal cells induce inhibitory effects on hepatocellular carcinoma through various signaling pathways
Authors: Ai Jafar , Ketabchi Neda , Verdi Javad , Gheibi Nematollah , Khadem Haghighian Hossein , Kavianpour Maria 
Published: December 2019

AbstractHepatocellular carcinoma (HCC) is the most prevalent type of malignant liver disease worldwide. Molecular changes in HCC collectively contribute to Wnt/β-catenin, as a tumor proliferative signaling pathway, toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB), as well as the c-Jun NH2-terminal kinase (JNK), predominant signaling pathways linked to the release of tumor-promoting cytokines. It should also be noted that the Hippo signaling pathway plays an important role in organ size control, particularly in promoting tumorigenesis and HCC development. Nowadays, mesenchymal stromal cells (MSCs)-based therapies have been the subject of in vitro, in vivo, and clinical studies for liver such as cirrhosis, liver failure, and HCC. At present, despite the importance of basic molecular pathways of malignancies, limited information has been obtained on this background. Therefore, it can be difficult to determine the true concept of interactions between MSCs and tumor cells. What is known, these cells could migrate toward tumor sites so apply effects via paracrine interaction on HCC cells. For example, one of the inhibitory effects of MSCs is the overexpression of dickkopf-related protein 1 (DKK-1) as an important antagonist of the Wnt signaling pathway. A growing body of research challenging the therapeutic roles of MSCs through the secretion of various trophic factors in HCC. This review illustrates the complex behavior of MSCs and precisely how their inhibitory signals interface with HCC tumor cells.
Usefulness of combined screening methods for rapid detection of falsified and/or substandard medicines in the absence of a confirmatory method
Authors: Opuni Kwabena Frimpong-Manso , Nettey Henry , Larbi Marvin Adjei , Amartey Salome Naa Amerley , Nti Gifty , Dzidonu Abraham , Owusu-Danso Patrick , Owusu Nicholas Amoah , Nyarko Alexander Kwadwo 
Published: December 2019

Abstract
Background
The influx of substandard and falsified medicines is a global public health challenge and its rapid detection is a key solution to the menace. This study used three screening methods and one confirmatory method for the quality assessment of 25 batches of artemether/lumefantrine dosage forms from the Ghanaian market to test that combined screening methods only can rapidly detect substandard and/or falsified medicines in areas where confirmatory methods may not be available.

Methods
The quality of artemether/lumefantrine tablet products obtained from pharmacies and licensed chemical seller shops within the Accra metropolis in Ghana were analysed using three screening methods (GPHF Minilab, Colorimetry and Counterfeit Drug Indicator) and one confirmatory method (high-performance liquid chromatography).

Results
The results showed that 18/25 batches of the artemether/lumefantrine samples passed using the combined screening and confirmatory methods and 5/25 batches of the artemether/lumefantrine samples failed using the combined screening and confirmatory methods. However, 1/25 batch of the artemether/lumefantrine samples failed using the combined screening methods but passed using the confirmatory method. Also, 1/25 batch of the artemether/lumefantrine samples passed using the combined screening methods but failed using the confirmatory method. This notwithstanding, the combined screening methods and the confirmatory method provided equivalent quality assessment profiles for 23/25 (92%) batches of the artemether/lumefantrine tablet products. Out of the 6 samples that failed the confirmatory test, 1/6, 2/6, and 3/6 failed on the high (> 110%), low (< 90%), and no active ingredient (0%), respectively. The sensitivity of Minilab, colorimetric, CoDI, and the combined screening methods at 95% confidence level were 0.5 ± 0.57, 0.83 ± 0.33, 0.75 ± 0.49, and 0.83 ± 0.33, respectively. Also, the specificity of Minilab, colorimetric, CoDI, and the combined screening methods at 95% confidence level were 1.00, 0.95 ± 0.10, 1.00, and 0.95 ± 0.10, respectively.

Conclusion
The combined screening methods may be used for rapid detection of falsified and/or substandard medicines without using a confirmatory method. However, additional research on the best combinations of screening devices/methods to rapidly detect the quality of medicines is recommended.
A current-mode system to self-measure temperature on implantable optoelectronics
Authors: Dehkhoda Fahimeh , Soltan Ahmed , Ponon Nikhil , O’Neill Anthony , Jackson Andrew , Degenaar Patrick 
Published: December 2019

AbstractBackgroundOne of the major concerns in implantable optoelectronics is the heat generated by emitters such as light emitting diodes (LEDs). Such devices typically produce more heat than light, whereas medical regulations state that the surface temperature change of medical implants must stay below + 2 °C. The LED’s reverse current can be employed as a temperature-sensitive parameter to measure the temperature change at the implant’s surface, and thus, monitor temperature rises. The main challenge in this approach is to bias the LED with a robust voltage since the reverse current is strongly and nonlinearly sensitive to the bias voltage.MethodsTo overcome this challenge, we have developed an area-efficient LED-based temperature sensor using the LED as its own sensor and a CMOS electronic circuit interface to ensure stable bias and current measurement. The circuit utilizes a second-generation current conveyor (CCII) configuration to achieve this and has been implemented in 0.35 μm CMOS technology.ResultsThe developed circuits have been experimentally characterized, and the temperature-sensing functionality has been tested by interfacing different mini-LEDs in saline models of tissue prior to in vivo operation. The experimental results show the functionality of the CMOS electronics and the efficiency of the CCII-based technique with an operational frequency up to 130 kHz in achieving a resolution of 0.2 °C for the surface temperature up to + 45 °C.ConclusionsWe developed a robust CMOS current-mode sensor interface which has a reliable CCII to accurately convey the LED’s reverse current. It is low power and robust against power supply ripple and transistor mismatch which makes it reliable for sensor interface. The achieved results from the circuit characterization and in vivo experiments show the feasibility of the whole sensor interface in monitoring the tissue surface temperature in optogenetics.
Harnessing tumor-associated macrophages as aids for cancer immunotherapy
Authors: Li Xiaolei , Liu Rui , Su Xiao , Pan Yongsha , Han Xiaofeng , Shao Changshun , Shi Yufang 
Published: December 2019

AbstractCancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority of patients with solid tumors, little or no progress has been seen, presumably due to lack of adequate approaches that can reprogram the local immunosuppressive tumor milieu and thus reinvigorate antitumor immunity. Tumor-associated macrophages (TAMs), which abundantly infiltrate most solid tumors, could contribute to tumor progression by stimulating proliferation, angiogenesis, metastasis, and by providing a barrier against antitumor immunity. Initial TAMs-targeting strategies have shown efficacy across therapeutic modalities and tumor types in both preclinical and clinical studies. TAMs-targeted therapeutic approaches can be roughly divided into those that deplete TAMs and those that modulate TAMs activities. We here reviewed the mechanisms by which macrophages become immunosuppressive and compromise antitumor immunity. TAMs-focused therapeutic strategies are also summarized.
Gambling as social practice: a complementary approach for reducing harm?
Authors: Gordon Ross , Reith Gerda 
Published: December 2019

AbstractBackgroundGambling is now a well-recognised public health issue and forms the focus of extensive harm reduction initiatives. Recent developments in policy, practice and technology, such relaxation of regulations, the increasing influence of global gambling corporations, and the development of devices such as mobile phone apps and fixed odds betting terminals (FOBTs) mean that the landscape is a complex, dynamic, and fast moving one. Gambling is now practiced using new technologies, in various spaces and places, and features in a range of social surroundings. Therefore, research is needed to inform appropriate gambling harm reduction strategies that can respond to this complex domain. Yet, research and policy approaches to the reduction of gambling harm are predominantly framed through psychological and economic models of individual behaviour, addiction, and ‘rational’ action. This is beginning to change, with a growing corpus of socio-cultural approaches to gambling research now emerging.MethodIn this article, we argue the case of recognising gambling as a social practice, the performance of which draws upon multiple elements such as technology and materials, spaces and places, language and discourse, and structures and agency. We call for a practice theory approach to gambling research that joins efforts to move beyond individual gamblers and their behaviour, to also acknowledge the interaction of multiple elements shaping gambling practices. To achieve this, we suggest that research methods such as visual ethnography can be helpful.ConclusionWe set out how a social practice perspective to gambling research can generate different insights and help inform more nuanced and appropriate gambling harm reduction initiatives.
Improving access to antiretrovirals in China: economic analyses of dolutegravir in HIV-1 patients
Authors: Punekar Yogesh Suresh , Guo Na , Tremblay Gabriel , Piercy James , Holbrook Tim , Young Benjamin 
Published: December 2019

AbstractBackgroundThe World Health Organisation recommended dolutegravir (DTG)-based antiretroviral therapy (ART) regimens are available but not reimbursed through the public reimbursement system in China. The objective of this analysis was to evaluate the cost-effectiveness of DTG (DTG + TDF/3TC) compared to efavirenz (EFV + TDF/3TC) in treatment-naive and ritonavir-boosted lopinavir (LPV/r + TDF/3TC) in first-line ART failure HIV-1-infected patients in China.MethodsA dynamic Markov model comprising of 5 response states and 6 CD4+ count-based health states was used. Efficacy, estimated as probability of virologic suppression (HIV RNA < 50 copies/mL) at 48 weeks, was obtained from a published network meta-analysis for ART-naive patients and from the DAWNING study for patients failing first-line ART. Baseline cohort characteristics were informed using DTG phase 3 studies and the DAWNING study data, respectively. Health state utilities were derived from DTG phase 3 studies. A 5-year cost-effectiveness analyses was conducted using the societal perspective. Outcomes were quality-adjusted-life-years (QALYs), life-years (LYs), incremental cost per QALYs (ICER).ResultsThe viral suppression rates for DTG + TDF/3TC were higher than EFV + TDF/3TC (75.3% vs 64.0%) in treatment-naive and LPV/r + TDF/3TC (74.8% vs 58.4%) in first-line ART failure patients. This resulted in higher QALYs for DTG + TDF/3TC in treatment-naive (4.232 vs 4.227) and first-line failure settings (4.224 vs 4.221). Total discounted cost for DTG + TDF/3TC patients (RMB 219.259 in treatment-naive and RMB 238,746 in first-line failures) were lower than comparators (EFV + TDF/3TC:RMB 221,605; LPV/r + TDF/3TC:RMB 244,364), thereby DTG dominated in both settings. Probabilistic sensitivity analyses indicated the probability of DTG + TDF/3TC being cost effective was 98.2% in treatment-naive setting and 100% in first-line failure setting at a willingness to pay threshold of RMB 100,000/QALY.ConclusionsWith lower costs, higher response rates and higher QALYs, DTG + TDF/3TC can be considered as a cost-effective alternative for treatment naive and first-line failure patients in China.
Prevalence, determinants and association of unawareness of diabetes, hypertension and hypercholesterolemia with poor disease control in a multi-ethnic Asian population without cardiovascular disease
Authors: Man Ryan E. K. , Gan Alvin Hong Wei , Fenwick Eva K. , Gan Alfred Tau Liang , Gupta Preeti , Sabanayagam Charumathi , Tan Nicholas , Wong Kah Hie , Wong Tien Yin , Cheng Ching-Yu , Lamoureux Ecosse L. 
Published: December 2019

AbstractBackgroundTo explore the prevalence and determinants of unawareness of diabetes, hypertension and hypercholesterolemia and its association with poor disease control in a multi-ethnic Asian population without cardiovascular disease (CVD).MethodsWe included 6904 Chinese, Malay and Indian individuals (mean age [SD] 58.2 [10.2] years; 52.6% female) with diabetes, hypertension and/or hypercholesterolemia from the cross-sectional population-based Singapore Epidemiology of Eye Diseases study (2004–2011). Diabetes was defined as random blood glucose ≥ 11.1 mmol/L or HbA1c > 6.5% or self-reported use of diabetes medication; hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or self-reported use of anti-hypertensive treatment; and hypercholesterolemia as total cholesterol ≥ 6.2 mmol/L or self-reported use of lipid-lowering medications. Unawareness was based on participants’ answers to the questions: “Did your medical practitioner ever tell you that you have diabetes/hypertension/high cholesterol?” The determinants of unawareness, and its association with poor disease control, were assessed using multivariable binary logistic regression models adjusted for known potential confounders.ResultsOf the 2380 (34.5%), 5386 (78.0%) and 3607 (52.2%) with diabetes, hypertension and hypercholesterolemia, respectively, unawareness rates were 30.7%, 43.1% and 40.9%, respectively. Having a higher BMI, particularly if obese, and Malay ethnicity were associated with greater unawareness of diabetes; Malay and Indian ethnicities and current smoking with greater unawareness of hypertension; and education ≤6 years, current smoking, and blue collar jobs or unemployment with greater unawareness of hypercholesterolemia (allP< 0.05). Lack of awareness of each condition was independently associated with poorer disease control in the case of hypertension and hypercholesterolemia, while the converse was true for diabetes (allP< 0.05).ConclusionsUnawareness of diabetes, hypertension, or hypercholesterolemia is high in Singapore, with risk factors varying across all three diseases, although Malay ethnicity is a consistent one. Unawareness was also associated with poor management for hypertension and hypercholesterolemia. Public health education and screening programs should target at-risk individuals, especially Malays, to reduce the likelihood of incident CVD.