bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative medicine in cancer survivors
Authors: Viscuse Paul V. , Price Katharine , Millstine Denise , Bhagra Anjali , Bauer Brent , Ruddy Kathryn J. 
Published: April 2017

Purpose of review
Due to medical advances and an aging population, the number of cancer survivors continues to rise. Survivors often experience late and long-term sequelae of cancer and its treatment (e.g., fatigue, pain, fear of recurrence, and stress). As a result, some patients have utilized or expressed interest in integrative medicine (IM) modalities for prevention of recurrence, optimizing health, enhancing quality of life, and managing symptoms. The purpose of this review is to focus on research published during the past year that informs our understanding of the utility of IM for cancer survivors.

Recent findings
Physical activity, diet, dietary supplements, mind–body modalities, acupuncture, and massage therapy all may play a role in the management of the physical (e.g., fatigue and pain) and emotional (e.g., anxiety and fear) issues faced by cancer survivors.

Summary
IM therapies are appealing to and utilized by many cancer survivors and may reduce symptom burden. Clinicians who provide cancer survivorship care may improve patient care by understanding the evidence for and against their use.
Xinxuekang Regulates Reverse Cholesterol Transport by Improving High-density Lipoprotein Synthesis, Maturation, and Catabolism
Authors: Dong Guang-xin , Li Wen-wen , Wang Ruo-zhu , Zou Wen-jun , Zhong Zhen-dong , Li Bo-gang 
Published: April 2017

Abstract:
Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has been clinically shown to attenuate atherosclerosis; however, the underlying antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol homeostasis, reverse cholesterol transport (RCT) is a potential target for these beneficial effects. This study investigated the effects of XXK on RCT and related proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an increase in the expression level of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which in turn stimulated cholesterol efflux and reduced aortic atherosclerotic lesion area. XXK also increased high-density lipoprotein (HDL) synthesis by modulating the peroxisome proliferator–activated receptor γ/liver X receptor α/ATP-binding cassette transporter A1 pathway and promoted HDL maturity by increasing serum lecithin–cholesterol acyltransferase. In addition, XXK improved the selective uptake of HDL-cholesteryl ester by increasing the expression of scavenger receptor class B type I. This is the first study to show that XXK confers a regulation of RCT, at least in part, by improving HDL synthesis, maturation, and catabolism.
Cardiac Outcomes After Perinatal Sertraline Exposure in Mice
Authors: Haskell Sarah E. , Lo Cecilia , Kent Mitchell E. , Eggleston Timothy M. , Volk Kenneth A. , Reinking Benjamin E. , Roghair Robert D. 
Published: April 2017

Abstract:Selective serotonin reuptake inhibitors are prescribed to 6%–10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg·kg−1·d−1IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1–14 to encompass the developmental window analogous to human gestation. Sertraline-exposed mice had increased cardiac hydroxyproline content, decreased 5-HT2Breceptor mRNA levels, and increased 5-HT2Areceptor and serotonin transporter mRNA levels on postnatal day 21 (P< 0.05). These changes were associated with diminished exercise capacity at 6 weeks (P< 0.05) and decreased adult shortening fraction and stroke volume at 5 months. Isolated cardiomyocytes from neonatal sertraline-exposed mice had significantly decreased proliferation, cross-sectional area, and phosphorylation of Akt (P< 0.05 vs. neonatal control mice). Perinatal sertraline exposure alters neonatal cardiac development and produces long-standing changes in adult cardiac function and exercise capacity. Further studies are needed to assess whether similar findings are present in the growing population that has been exposed to selective serotonin reuptake inhibitors during development.
Aging and Sexual Differences of the Human Skull
Authors: Toledo Avelar Luiz Eduardo , Cardoso Márcio Alberto , Santos Bordoni Leonardo , de Miranda Avelar Lorena , de Miranda Avelar João Victor 
Published: April 2017

Background:
The aging process of the face comprises all layers: skin, subcutaneous fat, muscles, and skeleton, and the signs of aging depend mainly on which layer is mostly affected.

Objective:
To evaluate the aging facial skeleton, as well as establish the sexual differences, areas with a strong predisposition to resorption, and aesthetic repercussion for better treatment approach.

Methods:
Skulls from the Forensic Anthropology Department of the Institute of Forensic Medicine of Belo Horizonte, Brazil, were classified according to gender and age group (i.e., <20 years, 20–50 years, >50 years). Structural changes were classified according to gender and age group.

Results:
Of the 241 skulls included, 192 were male skulls and 49 female. Sexual dimorphism and age-related peculiarities are described herein.

Conclusions:
The knowledge of the anatomy of the aging face, taking into consideration all the layers (skin, fat pads, muscles, and bones), as a whole, for the treatment of folds and shadows is vital for a better and more natural final aesthetic outcome.
Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress
Authors: Lovallo William R. , Enoch Mary-Anne , Sorocco Kristen H. , Vincent Andrea S. , Acheson Ashley , Cohoon Andrew J. , Hodgkinson Colin A. , Goldman David 
Published: April 2017

ABSTRACT

Objective
Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA).

Methods
We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism.

Results
Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure.

Conclusions
Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.
Improving Patient Safety in Handover From Intensive Care Unit to General Ward: A Systematic Review
Authors: Wibrandt Ida , Lippert Anne 
Published: April 2017

Objectives
Despite of the increasing knowledge about patient safety improvements in the handover process in hospitals, we still lack knowledge about what magnitude of patient safety gains can be expected from improvements in handover between the intensive care unit (ICU) and the general ward. The aim of this systematic review was to investigate which handover tools are devised and evaluated with the aim of improving patient safety in the handover process from ICU to ward and whether the described handover tools fulfill their purpose.

Methods
A systematic literature search of 6 databases was performed to answer the review question, developed by using the “Patient Population, Intervention, Comparison, Outcome” format. Two authors independently performed the selection process, as well as the data extraction and quality assessment. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement were followed.

Results
Eight studies were finally included in the qualitative analysis. One study investigated a written information tool, 1 study investigated improved verbal information, 1 study investigated the effect of an additional safety check, and 5 studies investigated a Liaison Nurse as handover tool. Because of heterogeneity among the included studies, the study results could not be pooled.

Conclusions
Not many well-conducted studies can shed light on this important topic. Giving patients and their families a supplementary written or verbal status report before transfer might improve patient safety. The introduction of a Liaison Nurse may be effective in improving communication between ICU and ward staff, which might reduce risks in patient safety. However, there is no evidence of improved mortality and/or readmission rates after introducing handover tools in the transfer from ICU to ward.
Cost-Benefit Analysis of a Support Program for Nursing Staff
Authors: Moran Dane , Wu Albert W. , Connors Cheryl , Chappidi Meera R. , Sreedhara Sushama K. , Selter Jessica H. , Padula William V. 
Published: April 2017

Objectives
A peer-support program called Resilience In Stressful Events (RISE) was designed to help hospital staff cope with stressful patient-related events. The aim of this study was to evaluate the impact of the RISE program by conducting an economic evaluation of its cost benefit.

Methods
A Markov model with a 1-year time horizon was developed to compare the cost benefit with and without the RISE program from a provider (hospital) perspective. Nursing staff who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital in the United States were included in the analysis. The cost of running the RISE program, nurse turnover, and nurse time off were modeled. Data on costs were obtained from literature review and hospital data. Probabilities of quitting or taking time off with or without the RISE program were estimated using survey data. Net monetary benefit (NMB) and budget impact of having the RISE program were computed to determine cost benefit to the hospital.

Results
Expected model results of the RISE program found a net monetary benefit savings of US $22,576.05 per nurse who initiated a RISE call. These savings were determined to be 99.9% consistent on the basis of a probabilistic sensitivity analysis. The budget impact analysis revealed that a hospital could save US $1.81 million each year because of the RISE program.

Conclusions
The RISE program resulted in substantial cost savings to the hospital. Hospitals should be encouraged by these findings to implement institution-wide support programs for medical staff, based on a high demand for this type of service and the potential for cost savings.
Quality of Handoffs in Community Pharmacies
Authors: Abebe Ephrem , Stone Jamie A. , Lester Corey A. , Chui Michelle A. 
Published: April 2017

Objectives
The aims of the study were to characterize handoffs in community pharmacies and to examine factors that contribute to perceived handoff quality.

Methods
A cross-sectional study of community pharmacists in a Midwest State of the United States. Self-administered questionnaires were used to collect information on participant and practice setting characteristics. Data were analyzed using descriptive statistics and multivariate logistic regression.

Results
A total of 445 completed surveys were returned (response rate, 82%). In almost half of the time, handoffs that occur in a community pharmacy setting were inaccurate or incomplete. Nearly half of the time handoffs occur in environments full of interruptions and distractions. More than 90% of the respondents indicated that they have undergone no formal training on proper ways of handing off information. Nearly 40% of respondents reported that their pharmacy dispensing technology does not have adequate functionality to support handing off information and that at least 50% of the time, poor handoffs result in additional work to the pharmacist because of the need for complete information before providing patient care. Multivariate analysis showed that being very familiar with patients, lower daily prescription volume, not having a 24-hour operation, and larger percentage of handoffs occurring in a synchronous fashion are all associated with better handoff quality.

Conclusions
Handoffs occur frequently and are problematic in community pharmacies. Current pharmacy environments offer limited support to conduct good handoffs, and as a result, pharmacists report loss of information. This could present as a significant patient safety hazard. Future interventions should target facilitating better communication during shift changes.
Biphasic Renal Sympathetic Response to Hemorrhagic Hypotension in Mice
Authors: Zhang Tao , Tanida Mamoru , Uchida Kunitoshi , Suzuki Yoshiro , Yang Wei , Kuda Yuhichi , Kurata Yasutaka , Tominaga Makoto , Shibamoto Toshishige 
Published: April 2017

ABSTRACT

Aim:
The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves.

Methods:
RSNA, HR, and mean systemic arterial pressure were continuously measured in male pentobarbital-anesthetized C57BL/6N mice. Hemorrhagic hypotension of 50 mmHg was evoked and maintained for 10 min.

Results:
During hemorrhagic hypotension, RSNA initially increased and then sustainedly decreased, while HR progressively decreased. Vagotomy eliminated the second-phase sympathoinhibition and bradycardia, and carotid sinus denervation with vagotomy abolished the initial renal sympathoexcitation. The renal sympathoinihibition during hemorrhagic hypotension of 50 mmHg was eliminated in mice pretreated with a transient receptor potential vanilloid type 1 channel (TRPV1) inhibitor, capsazepine, and in TRPV1 knockout (TRPV1−/−) mice, but not in TRPV4 knockout mice. The bradycardia response to hemorrhagic hypotension was also absent in TRPV1−/− mice and mice pretreated with capsazepine.

Conclusion:
Hemorrhagic hypotension in anesthetized mice causes biphasic responses of RSNA with an initial increase, followed by a sustained decrease, and a progressive decrease in HR. The initial sympathoexcitation is mediated by carotid sinus baroreceptors, while the later sympathoinhibition and bradycardia are mediated via the TRPV1 signals of vagal afferents.
Cadmium-associated differential methylation throughout the placental genome: epigenome-wide association study of two US birth cohorts
Authors: Everson Todd M. , Punshon Tracy , Jackson Brian P. , Hao Ke , Lambertini Luca , Chen Jia , Karagas Margaret R. , Marsit Carmen J. 
Published: April 2017

AbstractBackgroundCadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.MethodsUsing placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.ResultsWe identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR):TNFAIP2,EXOC3L4,GAS7,SREBF1,ACOT7, andRORA. Higher placental expression ofTNFAIP2andACOT7, and lower expression ofRORA, were associated with lower birth weight z-scores (p-values < 0.05).ConclusionCd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2,ACOT7, andRORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.SignificanceCadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.
Inference of the Human Polyadenylation Code
Authors: Leung Michael K. K. , Delong Andrew , Frey Brendan J. 
Published: April 2017

AbstractProcessing of transcripts at the 3’-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which polyadenylation site is cleaved, alternative polyadenylation enables genes to produce transcript isoforms with different 3’-ends. To facilitate the identification and treatment of disease-causing mutations that affect polyadenylation and to understand the underlying regulatory processes, a computational model that can accurately predict polyadenylation patterns based on genomic features is desirable. Previous works have focused on identifying candidate polyadenylation sites and classifying sites which may be tissue-specific. What is lacking is a predictive model of the underlying mechanism of site selection, competition, and processing efficiency in a tissue-specific manner. We develop a deep learning model that trains on 3’-end sequencing data and predicts tissue-specific site selection among competing polyadenylation sites in the 3’ untranslated region of the human genome.Two neural network architectures are evaluated: one built on hand-engineered features, and another that directly learns from the genomic sequence. The hand-engineered features include polyadenylation signals, cis-regulatory elements, n-mer counts, nucleosome occupancy, and RNA-binding protein motifs. The direct-from-sequence model is inferred without prior knowledge on polyadenylation, based on a convolutional neural network trained with genomic sequences surrounding each polyadenylation site as input. Both models are trained using the TensorFlow library.The proposed polyadenylation code can predict site selection among competing polyadenylation sites in different tissues. Importantly, it does so without relying on evolutionary conservation. The model can distinguish pathogenic from benign variants that appear near annotated polyadenylation sites in ClinVar and inspect the genome to find candidate polyadenylation sites. We also provide an analysis on how different features affect the model’s performance.
Heterogeneous Contribution of Microdeletions in the Development of Common Generalized and Focal epilepsies
Authors: Pérez-Palma Eduardo , Helbig Ingo , Klein Karl Martin , Anttila Verneri , Horn Heiko , Reinthaler Eva Maria , Gormley Padhraig , Ganna Andrea , Byrnes Andrea , Pernhorst Katharina , Toliat Mohammad R. ,   EuroEPINOMICS-RE consortium,   Italian League against Epilepsy Consortium, Saarentaus Elmo , Howrigan Daniel P. , Hoffman Per , Miquel Juan Francisco , Ferrari Giancarlo De , Nürnberg Peter , Lerche Holger , Zimprich Fritz , Neubauer Bern A. , Becker Albert J. , Rosenow Felix , Perucca Emilio , Zara Federico , Weber Yvonne G. , Lal Dennis 
Published: April 2017

ABSTRACTBackgroundMicrodeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.MethodsWe assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.ResultsWhen hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1,RBFOX1andPCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.ConclusionsOur results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.