bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of an oxygen planar optode to assess the effect of high velocity microsprays on oxygen penetration in a human dental biofilms in-vitro
Authors: Khosravi Yalda , Kandukuri Rala D.P. , Palmer Sara R. , Gloag Erin S. , Borisov Sergey M. , Starke E. Michelle , Ward Marilyn T. , Kumar Purnima , de Beer Dirk , Chennu Arjun , Stoodley Paul 
Published: August 2020

Abstract
Background
Dental plaque biofilms are the causative agents of caries, gingivitis and periodontitis. Both mechanical and chemical strategies are used in routine oral hygiene strategies to reduce plaque build-up. If allowed to mature biofilms can create anoxic microenvironments leading to communities which harbor pathogenic Gram-negative anaerobes. When subjected to high velocity fluid jets and sprays biofilms can be fluidized which disrupts the biofilm structure and allows the more efficient delivery of antimicrobial agents.

Methods
To investigate how such jets may disrupt anoxic niches in the biofilm, we used planar optodes to measure the dissolved oxygen (DO) concentration at the base of in-vitro biofilms grown from human saliva and dental plaque. These biofilms were subject to “shooting” treatments with a commercial high velocity microspray (HVM) device.

Results
HVM treatment resulted in removal of much of the biofilm and a concurrent rapid shift from anoxic to oxic conditions at the base of the surrounding biofilm. We also assessed the impact of HVM treatment on the microbial community by tracking 7 target species by qPCR. There was a general reduction in copy numbers of the universal 16S RNA by approximately 95%, and changes of individual species in the target region ranged from approximately 1 to 4 log reductions.

Conclusion
We concluded that high velocity microsprays removed a sufficient amount of biofilm to disrupt the anoxic region at the biofilm-surface interface.
One-week multidisciplinary post-graduate palliative care training: an outcome-based program evaluation
Authors: Paal Piret , Brandstötter Cornelia , Bükki Johannes , Elsner Frank , Ersteniuk Anna , Jentschke Elisabeth , Stähli Andreas , Slugotska Iryna 
Published: August 2020

Abstract
Background
A multi-professional, post-graduate, one-week palliative care training program was piloted in November 2019 at the University of Ivano-Frankivsk, Ukraine. A formal evaluation of this program was performed.

Methods
This is a comparative, retrospective outcome-based evaluation of an educational intervention. Participants completed evaluation forms at the end of the course (post-intervention = T1), covering demographics, comparative retrospective self-assessment (40 items, 6-point Likert scale), organizational aspects, and general feedback (free text). At T1, the responses represent actual self-assessment, pre-interventional (T0) scores were generated by retrospective self-assessment. The Retrospective Performance Gain (RPG) was calculated on group level for the comparative self-assessment, demographic and organizational variables were analyzed by descriptive statistics, and free text answers were processed by qualitative methodology (content analysis).

Results
Fifty-three of 56 attendants from all professions relevant to palliative care completed the evaluation forms (response 94,6%), with mean age 39y (22–64) and mean working experience 13,6y (1–44). Overall ratings of the program were very positive. Comparative retrospective self-assessment demonstrated a marked RPG from T0 to T1 on all items. Free text comments emphasized the need for regular nation-wide educational programs and for further education in bereavement care; inter-professional practice; communication; palliative care philosophy; professional self-care; specific nursing skills; dementia care; and advocacy, while the general contribution of the program to palliative care development in Ukraine was acknowledged.

Conclusions
Systematic evaluation of a post-graduate international training program in palliative care may provide a mutual learning experience and map country-specific barriers and facilitators that have to be addressed when setting up palliative care services.
Insulin: too much of a good thing is bad
Authors: Kolb Hubert , Kempf Kerstin , Röhling Martin , Martin Stephan 
Published: August 2020

Abstract
Background
Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions.

Main body
The physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling (“insulin resistance”), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production.

Conclusions
The detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.
Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009
Authors: Rojek Amanda M. , Martin Genevieve E. , Horby Peter W. 
Published: August 2020

Abstract
Background
New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics.

Methods
We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease.

Results
Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended.

Conclusion
Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.
Laryngopharyngeal reflux in chronic obstructive pulmonary disease - a multi-centre study
Authors: Sanchez Julia , Schumann Desiree M. , Karakioulaki Meropi , Papakonstantinou Eleni , Rassouli Frank , Frasnelli Matthias , Brutsche Martin , Tamm Michael , Stolz Daiana 
Published: August 2020

AbstractReflux of gastric content has been associated with recurrent exacerbations of chronic obstructive pulmonary disease (COPD). We aimed to assess the prevalence of laryngopharyngeal reflux (LPR) in COPD and if LPR is a contributing factor to clinically relevant outcomes in COPD. We evaluated a total of 193 COPD patients (GOLD I-IV) with a 24-h laryngo-pharyngeal pΗ-monitor. LPR was observed in 65.8% of COPD patients and it was not significantly associated with clinically relevant outcomes of COPD. Treatment with PPI significantly decreased the upright RYAN score (p = 0.047) without improving lung function. Furthermore, the presence or severity of LPR cannot be diagnosed based solely on symptoms and questionnaires.
Effect of niacin monotherapy on high density lipoprotein composition and function
Authors: Gordon Scott M. , Amar Marcelo J. , Jeiran Kianoush , Stagliano Michael , Staller Emma , Playford Martin P. , Mehta Nehal N. , Vaisar Tomas , Remaley Alan T. 
Published: August 2020

Abstract
Background
Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.

Methods
A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement.

Results
In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C − 20%, q < 0.01; and triglyceride − 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL’s ability to influence endothelial function.

Conclusion
Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.
Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat
Authors: Fawad Ayesha , Fernandez Celine , Bergmann Andreas , Struck Joachim , Nilsson Peter M. , Bennet Louise , Orho-Melander Marju , Melander Olle 
Published: August 2020

Abstract
Background
In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown.

Aim
To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals.

Setting/ methods
Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides.

Results
An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12–31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43–0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46–78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18–0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively.

Conclusion
Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.
Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KATP channels through CaMKII activation
Authors: Ma Yanzhuo , Cheng Nancy , Sun Junping , Lu Jonathan Xuhai , Abbasi Shahrzad , Wu Geru , Lee An-Sheng , Sawamura Tatsuya , Cheng Jie , Chen Chu-Huang , Xi Yutao 
Published: August 2020

Abstract
Background
Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation plays a critical role in cardiomyocyte (CM) apoptosis and arrhythmia. Functional ATP-sensitive potassium (KATP) channels are essential for cardiac protection during ischemia. In cultured CMs, L5 low-density lipoprotein (LDL) induces apoptosis and QTc prolongation. L5 is a highly electronegative and atherogenic aberrant form of LDL, and its levels are significantly higher in patients with cardiovascular-related diseases. Here, the role of L5 in cardiac injury was studied by evaluating the effects of L5 on CaMKII activity and KATP channel physiology in CMs.

Methods
Cultured neonatal rat CMs (NRCMs) were treated with a moderate concentration (ie, 7.5 μg/mL) of L5 or L1 (the least electronegative LDL subfraction). NRCMs were examined for apoptosis and viability, CaMKII activity, and the expression of phosphorylated CaMKIIδ and NOX2/gp91phox. The function of KATP and action potentials (APs) was analyzed by using the patch-clamp technique.

Results
In NRCMs, L5 but not L1 significantly induced cell apoptosis and reduced cell viability. Furthermore, L5 decreased Kir6.2 expression by more than 50%. Patch-clamp analysis showed that L5 reduced the KATP current (IKATP) density induced by pinacidil, a KATP opener. The partial recovery of the inward potassium current during pinacidil washout was susceptible to subsequent inhibition by the IKATP blocker glibenclamide. Suppression of IKATP by L5 significantly prolonged the AP duration. L5 also significantly increased the activity of CaMKII, the phosphorylation of CaMKIIδ, and the expression of NOX2/gp91phox. L5-induced apoptosis was prevented by the addition of the CaMKII inhibitor KN93 and the reactive oxygen species scavenger Mn (III)TBAP.

Conclusions
L5 but not L1 induces CM damage through the activation of the CaMKII pathway and increases arrhythmogenicity in CMs by modulating the AP duration. These results help to explain the harmful effects of L5 in cardiovascular-related disease.
Treatment plan quality during online adaptive re-planning
Authors: van Timmeren Janita E. , Chamberlain Madalyne , Krayenbuehl Jérôme , Wilke Lotte , Ehrbar Stefanie , Bogowicz Marta , Hartley Callum , Zamburlini Mariangela , Andratschke Nicolaus , Garcia Schüler Helena , Pavic Matea , Balermpas Panagiotis , Ryu Chaehee , Guckenberger Matthias , Tanadini-Lang Stephanie 
Published: August 2020

Abstract
Background
Online adaptive radiotherapy is intended to prevent plan degradation caused by inter-fractional tumor volume and shape changes, but time limitations make online re-planning challenging. The aim of this study was to compare the quality of online-adapted plans to their respective reference treatment plans.

Methods
Fifty-two patients treated on a ViewRay MRIdian Linac were included in this retrospective study. In total 238 online-adapted plans were analyzed, which were optimized with either changing of the segment weights (n = 85) or full re-optimization (n = 153). Five different treatment sites were evaluated: prostate, abdomen, liver, lung and pelvis. Dosimetric parameters of gross tumor volume (GTV), planning target volume (PTV), 2 cm ring around the PTV and organs at risk (OARs) were considered. The Wilcoxon signed-rank test was used to assess differences between online-adapted and reference treatment plans, p < 0.05 was considered significant.

Results
The average duration of the online adaptation, consisting of contour editing, plan optimization and quality assurance (QA), was 24 ± 6 min. The GTV was slightly larger (average ± SD: 1.9% ± 9.0%) in the adapted plans than in the reference plans (p < 0.001). GTV-D95% exhibited no significant changes when considering all plans, but GTV-D2% increased by 0.40% ± 1.5% on average (p < 0.001). There was a very small yet significant decrease in GTV-coverage for the abdomen plans. The ring Dmean increased on average by 1.0% ± 3.6% considering all plans (p < 0.001). There was a significant reduction of the dose to the rectum of 4.7% ± 16% on average (p < 0.001) for prostate plans.

Conclusions
Dosimetric quality of online-adapted plans was comparable to reference treatment plans and OAR dose was either comparable or decreased, depending on treatment site. However, dose spillage was slightly increased.
Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer
Authors: Wen Kuo-Chang , Sung Pi-Lin , Wu Alexander T. H. , Chou Ping-Chieh , Lin Jun-Hung , Huang Chi-Ying F. , Yeung Sai-Ching J. , Lee Mong-Hong 
Published: August 2020

Abstract
Background
Ovarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer.

Methods
We applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy.

Results
We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo.

Conclusions
This study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.
Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum β-lactamase-producing Escherichia coli: a mathematical modelling study
Authors: Kardaś-Słoma Lidia , Yazdanpanah Yazdan , Perozziello Anne , Zahar Jean-Ralph , Lescure François-Xavier , Cousien Anthony , Lucet Jean-Christophe 
Published: August 2020

Abstract
Background
The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.

Methods
We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.

Results
The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0–5.6) or 6.6% (6.3–6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9–62.0) to 68.8% (68.3–69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33–62%. Antibiotic restriction by 50% reduced the transmission by 2–6%.

Conclusions
The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.