bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using theory and user‐centered design in digital health: The development of the mychoice communication tool to prepare patients and improve informed decision making regarding clinical trial participation
Authors: Fleisher Linda , Bass Sarah Bauerle , Shwarz Michelle , Washington Armenta , Nicholson Andrea , Alhajji Mohammed , Geynisman Daniel M. , Maurer Laurie , Greener Judith , Kenny Cassidy 
Published: October 2019

AbstractObjectiveDesigning salient digital health interventions requires theoretically‐based formative research and user‐center design with stakeholder input throughout impacting content and technology design. mychoice is a theory‐based, stakeholder‐guided digital health tool to improve clinical trial informed decision making, particularly among African American patients.Methodsmychoice was developed by (1) mixed‐methods formative research, including in‐depth interviews (n=16) and surveys (N=41) with African American cancer patients who had and had not participated in a clinical trial; (2) e‐tool design process including perceptual mapping analysis to prioritize messages, multi‐disciplinary team and stakeholder input; and (3) iterative production and user testing.ResultsInterview findings showed that clinical trial participants expressed more positive attributes about and an openness to consider clinical trials, even though they expressed common concerns such as “fear of being a guinea pig”. Survey results indicated that clinical trial participants expressed they had been given information to make the decision (P = .001), while those who had not more frequently reported (P > .001) that no one had talked to them about trials. Perceptual mapping indicated that values such as “helping find a cure” or “value to society” had little resonance to those who had not participated, providing message strategy for prototype development. User testing of the tool resulted in modifications; the most significant was the adaptation to a multi‐cultural version.ConclusionsWith the promise of digital health interventions, theory‐guided, user‐centered and best practice development is critical and mychoice serves as an example of the application of these principles.
Using smart‐messaging to enhance mindfulness‐based cognitive therapy for cancer patients: A mixed methods proof of concept evaluation
Authors: Wells Chloe , Malins Sam , Clarke Simon , Skorodzien Iwona , Biswas Sanchia , Sweeney Tim , Moghaddam Nima , Levene Jo 
Published: October 2019

AbstractObjectiveDepression and anxiety lead to reduced treatment adherence, poorer quality of life, and increased care costs amongst cancer patients. Mindfulness‐based cognitive therapy (MBCT) is an effective treatment, but dropout reduces potential benefits. Smart‐message reminders can prevent dropout and improve effectiveness. However, smart‐messaging is untested for MBCT in cancer. This study evaluates smart‐messaging to reduce dropout and improve effectiveness in MBCT for cancer patients with depression or anxiety.MethodsFifty‐one cancer patients attending MBCT in a psycho‐oncology service were offered a smart‐messaging intervention, which reminded them of prescribed between‐session activities. Thirty patients accepted smart‐messaging and 21 did not. Assessments of depression and anxiety were taken at baseline, session‐by‐session, and one‐month follow‐up. Logistic regression and multilevel modelling compared the groups on treatment completion and clinical effectiveness. Fifteen post‐treatment patient interviews explored smart‐messaging use.ResultsThe odds of programme completion were eight times greater for patients using smart‐messaging compared with non‐users, controlling for age, gender, baseline depression, and baseline anxiety (OR = 7.79, 95% CI 1.75 to 34.58, p = .007). Smart‐messaging users also reported greater improvement in depression over the programme (B = ‐2.33, SEB = .78, p = .004) when controlling for baseline severity, change over time, age, and number of sessions attended. There was no difference between groups in anxiety improvement (B = ‐1.46, SEB = .86, p = .097). In interviews, smart‐messaging was described as a motivating reminder and source of personal connection.ConclusionsSmart‐messaging may be an easily integrated telehealth intervention to improve MBCT for cancer patients.
Impact of fear of cancer recurrence on survival among lymphoma patients
Authors: Kim Seok Jin , Kang Danbee , Kim Im Ryung , Yoon Sang Eun , Kim Won Seog , Butow Phyllis N. , Guallar Eliseo , Cho Juhee 
Published: October 2019

AbstractObjectiveThis study aimed to evaluate fear of cancer recurrence (FCR) among lymphoma patients who completed treatment and its impact on survival and quality of life (QOL).MethodsIn this prospective cohort study, 467 lymphoma patients were included who completed treatment with curative intent between February 2012 and March 2017. FCR was measured using a question from the Korean version of the QOL in Cancer Survivors Questionnaire. QOL and general health and functioning were measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐C30. Participants were actively followed up for all‐cause and disease‐specific mortality.ResultsIn total, 16.3% of the patients had severe FCR. The adjusted hazard ratio (HR) for all‐cause mortality comparing participants with and without severe FCR was 2.52 (95% CI = 1.15‐5.54), and the association was stronger in indolent non‐Hodgkin lymphoma (NHL) (HR = 6.77; 95% CI = 1.04‐43.92). Participants with severe FCR were also at higher risk of lymphoma‐specific mortality (HR = 2.62; 95% CI = 1.13‐6.05) than patients without severe FCR. Patients with severe FCR had significantly worse general health status (64.3 vs 71.0, P = .03) and physical (82.4 vs 76.7, P < .01), emotional (68.5 vs 84.8, P < .001), and social functioning (67.8 vs 84.2, P < .001) than patients without severe FCR.ConclusionsA substantial number of participants with lymphoma experience FCR after treatment completion, even in the case of indolent lymphomas. Given the negative impact of severe FCR on survival and general health and functional status, active monitoring and appropriate management of FCR should be considered in clinical settings.
NAGbinder: An approach for identifying N‐acetylglucosamine interacting residues of a protein from its primary sequence
Authors: Patiyal Sumeet , Agrawal Piyush , Kumar Vinod , Dhall Anjali , Kumar Rajesh , Mishra Gaurav , Raghava Gajendra P.S. 
Published: October 2019

AbstractN‐acetylglucosamine (NAG) belongs to the eight essential saccharides that are required to maintain the optimal health and precise functioning of systems ranging from bacteria to human. In the present study, we have developed a method, NAGbinder, which predicts the NAG‐interacting residues in a protein from its primary sequence information. We extracted 231 NAG‐interacting nonredundant protein chains from Protein Data Bank, where no two sequences share more than 40% sequence identity. All prediction models were trained, validated, and evaluated on these 231 protein chains. At first, prediction models were developed on balanced data consisting of 1,335 NAG‐interacting and noninteracting residues, using various window size. The model developed by implementing Random Forest using binary profiles as the main principle for identifying NAG‐interacting residue with window size 9, performed best among other models. It achieved highest Matthews Correlation Coefficient (MCC) of 0.31 and 0.25, and Area Under Receiver Operating Curve (AUROC) of 0.73 and 0.70 on training and validation data set, respectively. We also developed prediction models on realistic data set (1,335 NAG‐interacting and 47,198 noninteracting residues) using the same principle, where the model achieved MCC of 0.26 and 0.27, and AUROC of 0.70 and 0.71, on training and validation data set, respectively. The success of our method can be appraised by the fact that, if a sequence of 1,000 amino acids is analyzed with our approach, 10 residues will be predicted as NAG‐interacting, out of which five are correct. Best models were incorporated in the standalone version and in the webserver available at https://webs.iiitd.edu.in/raghava/nagbinder/
Building better enzymes: Molecular basis of improved non‐natural nucleobase incorporation by an evolved DNA polymerase
Authors: Ouaray Zahra , Singh Isha , Georgiadis Millie M. , Richards Nigel G. J. 
Published: October 2019

AbstractObtaining semisynthetic microorganisms that exploit the information density of “hachimoji” DNA requires access to engineered DNA polymerases. A KlenTaq variant has been reported that incorporates the “hachimoji” P:Z nucleobase pair with a similar efficiency to that seen for Watson–Crick nucleobase incorporation by the wild type (WT) KlenTaq DNA polymerase. The variant polymerase differs from WT KlenTaq by only four amino acid substitutions, none of which are located within the active site. We now report molecular dynamics (MD) simulations on a series of binary complexes aimed at elucidating the contributions of the four amino acid substitutions to altered catalytic activity. These simulations suggest that WT KlenTaq is insufficiently flexible to be able to bind AEGIS DNA correctly, leading to the loss of key protein/DNA interactions needed to position the binary complex for efficient incorporation of the “hachimoji” Z nucleobase. In addition, we test literature hypotheses about the functional roles of each amino acid substitution and provide a molecular description of how individual residue changes contribute to the improved activity of the KlenTaq variant. We demonstrate that MD simulations have a clear role to play in systematically screening DNA polymerase variants capable of incorporating different types of nonnatural nucleobases thereby limiting the number that need to be characterized by experiment. It is now possible to build DNA molecules containing nonnatural nucleobase pairs in addition to A:T and G:C. Exploiting this development in synthetic biology requires engineered DNA polymerases that can replicate nonnatural nucleobase pairs. Computational studies on a DNA polymerase variant reveal how amino acid substitutions outside of the active site yield an enzyme that replicates nonnatural nucleobase pairs with high efficiency. This work will facilitate efforts to obtain bacteria possessing an expanded genetic alphabet.
Performance of the SAEM and FOCEI Algorithms in the Open‐Source, Nonlinear Mixed Effect Modeling Tool nlmixr
Authors: Schoemaker Rik , Fidler Matthew , Laveille Christian , Wilkins Justin J. , Hooijmaijers Richard , Post Teun M. , Trame Mirjam N. , Xiong Yuan , Wang Wenping 
Published: October 2019

The free and open‐source package nlmixr implements pharmacometric nonlinear mixed effects model parameter estimation in R. It provides a uniform language to define pharmacometric models using ordinary differential equations. Performances of the stochastic approximation expectation‐maximization (SAEM) and first order‐conditional estimation with interaction (FOCEI) algorithms in nlmixr were compared with those found in the industry standards, Monolix and NONMEM, using the following two scenarios: a simple model fit to 500 sparsely sampled data sets and a range of more complex compartmental models with linear and nonlinear clearance fit to data sets with rich sampling. Estimation results obtained from nlmixr for FOCEI and SAEM matched the corresponding output from NONMEM/FOCEI and Monolix/SAEM closely both in terms of parameter estimates and associated standard errors. These results indicate that nlmixr may provide a viable alternative to existing tools for pharmacometric parameter estimation.
Sufficient dimension folding in regression via distance covariance for matrix‐valued predictors
Authors: Sheng Wenhui , Yuan Qingcong 
Published: October 2019

AbstractIn modern data, when predictors are matrix/array‐valued, building a reasonable model is much more difficult due to the complicate structure. However, dimension folding that reduces the predictor dimensions while keeps its structure is critical in helping to build a useful model. In this paper, we develop a new sufficient dimension folding method using distance covariance for regression in such a case. The method works efficiently without strict assumptions on the predictors. It is model‐free and nonparametric, but neither smoothing techniques nor selection of tuning parameters is needed. Moreover, it works for both univariate and multivariate response cases. In addition, we propose a new method of local search to estimate the structural dimensions. Simulations and real data analysis support the efficiency and effectiveness of the proposed method.
PINK1 overexpression protects against cerebral ischemia through Parkin regulation
Authors: Wen Youliang , Gu Yueming , Tang Xiaodong , Hu Ziwei 
Published: October 2019

AbstractMitochondrial dynamics and function are important for cell survival regulation under stress. In this study, we report that cerebral ischemia/reperfusion (I/R) injury significantly reduced mitochondrial function through reduced PTEN‐induced kinase 1 (PINK1) expression, ATP (Adenosine triphosphate) levels, and increased oxidative stress compared to sham rats. PINK1 overexpression mice significantly improved mitochondrial function by increased mitochondrial complex I, II, and III activities and ATP levels with concomitant decline in reactive oxygen species levels. PINK1 overexpression mice after I/R injury significantly reduced apoptosis through downregulation of cytochrome c, p53 expressions compared to cerebral I/R injury rats. Furthermore, we showed from parkin siRNA studies that PINK1 regulated phosphorylation parkin is critical to the protection against cerebral I/R injury. Altogether, we show that PINK1 mediated parkin regulation is key to the protection against cerebral I/R injury through regulation of mitochondrial function and apoptosis.
Low-energy effective field theory below the electroweak scale: matching at one loop
Authors: Dekens Wouter , Stoffer Peter 
Published: October 2019

Abstract
We compute the one-loop matching between the Standard Model Effective Field Theory and the low-energy effective field theory below the electroweak scale, where the heavy gauge bosons, the Higgs particle, and the top quark are integrated out. The complete set of matching equations is derived including effects up to dimension six in the power counting of both theories. We present the results for general flavor structures and include both the C P -even and C P -odd sectors. The matching equations express the masses, gauge couplings, as well as the coefficients of dipole, three-gluon, and four-fermion operators in the low-energy theory in terms of the parameters of the Standard Model Effective Field Theory. Using momentum insertion, we also obtain the matching for the C P -violating theta angles. Our results provide an ingredient for a model-independent analysis of constraints on physics beyond the Standard Model. They can be used for fixed- order calculations at one-loop accuracy and represent a first step towards a systematic next-to-leading-log analysis.
Histone deacetylase inhibitor CG200745 ameliorates high-fat diet-induced hypertension via inhibition of angiotensin II production
Authors: Yoon Ga-Eun , Jung Jin Ki , Lee Yun-Han , Jang Byeong-Churl , In Kim Jee 
Published: October 2019

Abstract
Obesity is growing rapidly worldwide due to consumption of westernized diet and lack of exercise. Obesity is one of the major risk factors of hypertension. The novel histone deacetylase (HDAC) inhibitor CG200745 was originally developed to treat various cancers. Previous studies showed that CG200745 attenuated hypertension through inhibition of cardiac hypertrophy and fibrosis in deoxycorticosterone acetate-induced hypertensive rat. The purpose of this study is to investigate the role and underlying mechanism of CG200745 in high-fat diet (HFD)-induced hypertension. Nine-week old C57BL/6 mice were fed a normal diet (ND) or HFD for 17 weeks. Each group of mice was treated with vehicle or CG200745 by intraperitoneal injection for 9 days. HFD group showed higher body weight, blood pressure (BP), HDAC activities, angiotensinogen and renin expressions in kidney, angiotensin-converting enzyme (ACE) expression in the lung, serum angiotensin II (Ang II) concentration, and myosin light chain20 (MLC20) phosphorylation in mesenteric artery compared with ND group. CG200745 lowered BP, HDAC activity, renin and angiotensinogen in the kidney, ACE in the lung, serum Ang II level, and phosphorylation of MLC20 in HFD group. In conclusion, CG200745 ameliorated HFD-induced hypertension through inhibition of HDAC/Ang II/vascular contraction axis. Our results offer CG200745 as a novel therapeutic option for HFD-induced hypertension.
Early-life blockade of NMDA receptors induces epigenetic abnormalities in the adult medial prefrontal cortex: possible involvement in memory impairment in trace fear conditioning
Authors: Latusz Joachim , Maćkowiak Marzena 
Published: October 2019

Abstract
Rationale
Several findings indicate that early-life dysfunction of N-methyl-d-aspartate (NMDA) receptors might cause schizophrenia-like abnormalities in adulthood that might be induced by impairments in epigenetic regulation.

Objectives
In the present study, we investigated whether postnatal blockade of NMDA receptors (within the first 3 weeks of life) by the competitive antagonist CGP 37849 (CGP) might affect some epigenetic markers in the adult medial prefrontal cortex (mPFC).

Methods
Histone H3 phosphorylation at serine 10 (H3S10ph), histone H3 acetylation at lysine 9 or 14 (H3K9ac or H3K14ac, respectively), or expression of histone deacetylase (HDAC) 2, HDAC5, myocyte enhancer factor (MEF) 2D and activity-regulated cytoskeleton-associated protein (Arc) were analysed. Moreover, we also evaluated whether the deacetylase inhibitor sodium butyrate (SB; 1.2 mg/kg, ip) could prevent behavioural and neurochemical changes in the mPFC induced by CGP during memory retrieval in the trace fear conditioning paradigm.

Results
The results showed that CGP administration increased the number of H3S10ph nuclei but did not affect H3K9ac and H3K14ac or HDAC2 protein levels. However, CGP administration altered the HDAC5 mRNA and protein levels and increased the mRNA and protein levels of MEF2D. CGP also increased Arc mRNA, which was correlated with an increase in the amount of Arc DNA bound to MEF2D. SB given 2 h after training prevented impairment of the freezing response and disruption of epigenetic markers (H3S10ph, HDAC5, MEF2D) and Arc expression during memory retrieval induced by CGP administration.

Conclusions
The early-life blockade of NMDA receptors impairs some epigenetic regulatory processes in the mPFC that are involved in fear memory formation.
Phyllosphere of Submerged Plants in Bathing Lakes as a Reservoir of Fungi—Potential Human Pathogens
Authors: Biedunkiewicz Anna , Sucharzewska Ewa , Kulesza Kamila , Nowacka Karolina , Kubiak Dariusz 
Published: October 2019

Abstract
This study analysed whether the littoral zone in the immediate vicinity of bathing sites retains potentially pathogenic yeasts on the phyllosphere surface and to what extent the species composition of microfungi in the phyllosphere and in surface waters is similar. The research was carried out in selected lakes located within the administrative boundaries of the city of Olsztyn, the largest city in the Masurian Lake District (NE Poland). The experiment was conducted in three summer seasons near bathing sites in three lakes, which are the most popular as recreational sites (Lake Kortowskie, Lake Tyrsko, and Lake Skanda). Microfungi isolated from the phyllosphere of 13 plant species of the littoral zone from dropped leaves of coast plants with no disease symptoms were used as the study material. The isolated fungi were identified in accordance with the accepted diagnostic procedures applied in mycological laboratories. A total of 36 yeast species of 16 genera were identified. Fungi found earlier at the bathing sites of the lakes were identified in 60% of the cases. Nine species were categorised as class BSL-2 fungi. This study provides a valuable complement of data concerning the natural composition of the littoral microbiota.
Effect of lipid saturation on amyloid-beta peptide partitioning and aggregation in neuronal membranes: molecular dynamics simulations
Authors: Ntarakas Nikolaos , Ermilova Inna , Lyubartsev Alexander P. 
Published: October 2019

Abstract
Aggregation of amyloid-$$\beta $$β (Aβ) peptides, cleaved from the amyloid precursor protein, is known as a precursor of the Alzheimer’s disease (AD). It is also known that Alzheimer’s disease is characterized by a substantial decrease of the amount of polyunsaturated lipids in the neuronal membranes of the frontal gray matter. To get insight into possible interconnection of these phenomena, we have carried out molecular dynamics simulations of two fragments of A$$\beta $$β peptide, A$$\beta $$β$$_{1-28}$$1-28 and A$$\beta $$β$$_{26-40}$$26-40, in four different lipid bilayers: two monocomponent ones (14:0-14:0 PC, 18:0-22:6 PC), and two bilayers containing mixtures of 18:0-18:0 PE, 22:6-22:6 PE, 16:0-16:0 PC and 18:1-18:1 PC lipids of composition mimicking neuronal membranes in a “healthy” and “AD” brain. The simulations showed that the presence of lipids with highly unsaturated 22:6cis fatty acids chains strongly affects the interaction of amyloid-$$\beta $$β peptides with lipid membranes. The polyunsaturated lipids cause stronger adsorption of A$$\beta $$β-peptides by the membrane and lead to weaker binding between peptides when the latter form aggregates. This difference in the behaviour observed in monocomponent bilayers is propagated in a similar fashion to the mixed membranes mimicking composition of neuronal membranes in “healthy” and “AD” brains, with “healthy” membrane having higher fraction of polyunsaturated lipids. Our simulations give strong indication that it can be physical–chemical background of the interconnection between amyloid fibrillization causing Alzheimer’s disease, and content of polyunsaturated lipids in the neuronal membranes.
Bile Duct Stones Predict a Requirement for Cholecystectomy in Older Patients
Authors: Matsui Yoichi , Hirooka Satoshi , Sakaguchi Tatsuma , Kotsuka Masaya , Yamaki So , Yamamoto Tomohisa , Kosaka Hisashi , Satoi Sohei , Sekimoto Mitsugu 
Published: October 2019

AbstractBackgroundThe requirement for elective cholecystectomy in older patients is unclear. To determine predictors for requiring elective cholecystectomy in older patients, a prospective cohort study was performed.MethodsAll patients with gallstone disease who presented to our department from 2006 to 2018 were included if they met the following criteria: (1) age 75 years or older, (2) presentation for elective cholecystectomy, and (3) preoperative diagnosis of cholecystolithiasis. Two therapeutic options, elective surgery and a wait‐and‐see approach, were offered at their initial visit. Enrolled patients were assigned to one arm of the study according to their choice of the therapeutic options. The primary endpoint was the incidence of gallstone‐related complications. The endpoint was compared between patients who underwent cholecystectomy (CH group) and those who chose a wait‐and‐see approach (No‐CH group).ResultsDuring the study period, there were 344 patients in the CH group and 161 in the No‐CH group. Among patients with a history of bile duct stones, the incidence of gallstone‐related complications in the No‐CH group was significantly higher (45% within 3 years, including two gallstone‐related deaths) than that in the CH group (RR 2.66, 95% confidence interval 1.50–4.77, p = 0.0009). Among patients with no history of bile duct stones, the incidence of gallstone‐related complications in the No‐CH group reached only 10% over the 12 years.ConclusionCholecystectomy is recommended for older patients with both histories of cholecystolithiasis and bile duct stones, whereas a wait‐and‐see approach is preferable for patients with no bile duct stone history. A history of bile duct stones is a good predictor for cholecystectomy in older patients.