bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between sleep duration, cognition and dementia: a Mendelian randomization study
Authors: Henry Albert , Katsoulis Michail , Masi Stefano , Fatemifar Ghazaleh , Denaxas Spiros , Acosta Dionisio , Garfield Victoria , Dale Caroline E 
Published: March 2019

AbstractBackgroundShort and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.MethodsWe conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N = 395 803) and summary statistics from the International Genomics of Alzheimer’s Project (N cases/controls = 17 008/37 154) to investigate the potential impact of sleep duration on cognitive outcomes.ResultsLinear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI) = 0–2%; P = 0.008] slower reaction time and 3% more errors in visual-memory test (95% CI = 0–6%; P = 0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep = 1.10 (95% CI = 0.76–1.57); P = 0.62], decline in reaction time [OR = 1.28 (95% CI = 0.49–3.35); P = 0.61], all-cause dementia [OR = 1.19 (95% CI = 0.65–2.19); P = 0.57] or Alzheimer’s disease risk [OR = 0.89 (95% CI = 0.67–1.18); P = 0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity = 3.44e–9) and reaction time (P for non-linearity = 6.66e–16).ConclusionsLinear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition.
Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV
Authors: Morrow Mary , MaWhinney Samantha , Coyle Ryan P , Coleman Stacey S , Gardner Edward M , Zheng Jia-Hua , Ellison Lucas , Bushman Lane R , Kiser Jennifer J , Anderson Peter L , Castillo-Mancilla Jose R 
Published: March 2019

AbstractBackgroundTenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression in persons living with HIV (PLWH) taking tenofovir disoproxil fumarate (TDF). However, its value as a predictor of future viremia remained unknown.MethodsBlood for plasma viral load (VL) and TFV-DP in DBS were collected (up to 3 visits within 48 weeks) in PLWH on TDF. TFV-DP cut points were selected using logistic prediction models maximizing the area under the receiver operation characteristic curve, and estimated adjusted odds ratio (aOR) of future viremia (≥20 copies/mL) were compared to the highest TFV-DP category.ResultsAmong all 451 participants in the analysis, aOR of future viremia for participants with TFV-DP <800 and 800 to <1650 fmol/punch were 4.7 (95% CI, 2.6–8.7; P < .0001) and 2.1 (95% CI, 1.3–3.3; P = .002) versus ≥1650 fmol/punch, respectively. These remained significant for participants who were virologically suppressed at the time of the study visit (4.2; 95% CI, 1.5–12.0; P = .007 and 2.2; 95% CI, 1.2–4.0; P = .01).ConclusionsTFV-DP in DBS predicts future viremia in PLWH on TDF, even in those who are virologically suppressed. This highlights the utility of this biomarker to inform about adherence beyond VL.Clinical Trials Registration. NCT02012621.
On- and off-label utilization of dalbavancin and oritavancin for Gram-positive infections
Authors: Morrisette Taylor , Miller Matthew A , Montague Brian T , Barber Gerard R , McQueen R Brett , Krsak Martin 
Published: March 2019

AbstractBackgroundLong-acting lipoglycopeptides (laLGPs) are FDA approved only for acute bacterial skin and skin structure infections (ABSSSIs). However, these antibiotics show promise for off-label use, reductions in hospital length of stay (LOS) and healthcare cost savings.ObjectivesTo assess the effectiveness, safety, impact on LOS and estimated cost savings from laLGP treatment for Gram-positive infections.MethodsRetrospective cohort of adult patients who received at least one dose of laLGPs at the University of Colorado Health system. Descriptive statistics were utilized for analysis.ResultsOf 59 patients screened, 56 were included: mean age 47 years, 59% male and 30% injection drug users/polysubstance abusers (dalbavancin, 71%; oritavancin, 25%; both, 4%). Most common indications for laLGP: ABSSSIs (36%), osteomyelitis (27%) and endocarditis (9%). Most common isolated pathogens: MSSA and MRSA (25% and 19%, respectively), Enterococcus faecalis (11%) and CoNS (11%). Previous antibiotics were administered for a median of 13 days (IQR = 7.0–24.5 days) and laLGPs for a median of one dose (IQR = 1–2 doses). Ten (18%) patients were lost to follow-up. Clinical failure was found in 7/47 (15%) cases with adequate follow-up. Mild adverse effects occurred in six (11%) patients. Projected reduction in hospital LOS and health-system costs were 514 days (9.18 days/person average) and $963456.72 ($17204.58/person average), respectively.ConclusionsProspective trials are needed to validate the use of these antibiotics for Gram-positive infections in practice, with the hope that they will reduce hospital LOS and the need for daily antibiotic infusions to provide alternative options for patients not qualifying for outpatient parenteral antimicrobial therapy.
Learning to detect and understand drug discontinuation events from clinical narratives
Authors: Liu Feifan , Pradhan Richeek , Druhl Emily , Freund Elaine , Liu Weisong , Sauer Brian C , Cunningham Fran , Gordon Adam J , Peters Celena B , Yu Hong 
Published: March 2019

Abstract

Objective
Identifying drug discontinuation (DDC) events and understanding their reasons are important for medication management and drug safety surveillance. Structured data resources are often incomplete and lack reason information. In this article, we assessed the ability of natural language processing (NLP) systems to unlock DDC information from clinical narratives automatically.

Materials and Methods
We collected 1867 de-identified providers’ notes from the University of Massachusetts Medical School hospital electronic health record system. Then 2 human experts chart reviewed those clinical notes to annotate DDC events and their reasons. Using the annotated data, we developed and evaluated NLP systems to automatically identify drug discontinuations and reasons at the sentence level using a novel semantic enrichment-based vector representation (SEVR) method for enhanced feature representation.

Results
Our SEVR-based NLP system achieved the best performance of 0.785 (AUC-ROC) for detecting discontinuation events and 0.745 (AUC-ROC) for identifying reasons when testing this highly imbalanced data, outperforming 2 state-of-the-art non–SEVR-based models. Compared with a rule-based baseline system for discontinuation detection, our system improved the sensitivity significantly (57.75% vs 18.31%, absolute value) while retaining a high specificity of 99.25%, leading to a significant improvement in AUC-ROC by 32.83% (absolute value).

Conclusion
Experiments have shown that a high-performance NLP system can be developed to automatically identify DDCs and their reasons from providers’ notes. The SEVR model effectively improved the system performance showing better generalization and robustness on unseen test data. Our work is an important step toward identifying reasons for drug discontinuation that will inform drug safety surveillance and pharmacovigilance.
Endocrine and Metabolic Diseases Among Colorectal Cancer Survivors in a Population-Based Cohort
Authors: Hawkins Makenzie L , Blackburn Brenna E , Rowe Kerry , Snyder John , Deshmukh Vikrant G , Newman Michael , Fraser Alison , Smith Ken , Herget Kimberly , Ganz Patricia A , Samadder N Jewel , Hashibe Mia 
Published: March 2019

Abstract

Background
There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors.

Methods
A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1–5 years, 5–10 years, and &gt;10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease.

Results
Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1–5 years postdiagnosis, CRC survivors’ risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1–5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5–10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95).

Conclusions
Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1–5 years, 5–10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.
Meta-Analysis of Anxiety in Parents of Young People with Chronic Health Conditions
Authors: Pinquart Martin 
Published: March 2019

Abstract

Objective
Chronic health conditions are often associated with uncertainty and threats which may cause anxiety in the family members. The present meta-analysis analyzed whether parents of children with chronic physical diseases and/or sensory/physical disabilities show higher anxiety levels than parents of healthy/nondisabled children or test norms.

Methods
The databases PSYCINFO, MEDLINE, Google Scholar, CINAHL, and PSYNDEX were searched for relevant studies. In total, 486 studies were identified that fulfilled the inclusion criteria.

Results
We found moderate elevations of anxiety symptoms in parents of young people with chronic conditions (g = .54 standard deviation units). About 16% of the parents fulfilled the criteria for an anxiety disorder. Parents of young people with neuromuscular disorders, HIV-infection/AIDS, and cancer during active treatment showed large elevations of anxiety symptoms. Elevations of anxiety symptoms were smaller in the cases of longer lasting chronic conditions, longer time since the end of active treatment, in families of older children, in samples with lower percentages of mothers, and in studies from economically developed countries compared to less developed countries.

Conclusion
Measures for preventing and reducing anxiety symptoms in parents of young people with neuromuscular disorders, HIV-infection/AIDS, and those undergoing cancer treatments are particularly needed.
Alteration of flavonoid pigmentation patterns during domestication of food crops
Authors: Paauw Misha , Koes Ronald , Quattrocchio Francesca M 
Published: March 2019

AbstractFlavonoids are plant pigments that provide health benefits for human and animal consumers. Understanding why domesticated crops have altered pigmentation patterns and unraveling the molecular/genetic mechanisms that underlie this will facilitate the breeding of new (healthier) varieties. We present an overview of changes in flavonoid pigmentation patterns that have occurred during crop domestication and, where possible, link them to the molecular changes that brought about the new phenotypes. We consider species that lost flavonoid pigmentation in the edible part of the plant at some point during domestication (like cereals). We also consider the converse situation, for example eggplant (aubergine), which instead gained strong anthocyanin accumulation in the skin of the fruit during domestication, and some varieties of citrus and apple that acquired anthocyanins in the fruit flesh. Interestingly, the genes responsible for such changes are sometimes closely linked to, or have pleiotropic effects on, important domestication genes, suggesting accidental and perhaps inevitable changes of anthocyanin patterning during domestication. In other cases, flavonoid pigmentation patterns in domesticated crops are the result of cultural preferences, with examples being found in varieties of citrus, barley, wheat, and maize. Finally, and more recently, in some species, anthocyanins seem to have been the direct target of selection in a second wave of domestication that followed the introduction of industrial food processing.
Aethionema arabicum: a novel model plant to study the light control of seed germination
Authors: Mérai Zsuzsanna , Graeber Kai , Wilhelmsson Per , Ullrich Kristian K , Arshad Waheed , Grosche Christopher , Tarkowská Danuše , Turečková Veronika , Strnad Miroslav , Rensing Stefan A , Leubner-Metzger Gerhard , Mittelsten Scheid Ortrun 
Published: March 2019

AbstractThe timing of seed germination is crucial for seed plants and is coordinated by internal and external cues, reflecting adaptations to different habitats. Physiological and molecular studies with lettuce and Arabidopsis thaliana have documented a strict requirement for light to initiate germination and identified many receptors, signaling cascades, and hormonal control elements. In contrast, seed germination in several other plants is inhibited by light, but the molecular basis of this alternative response is unknown. We describe Aethionema arabicum (Brassicaceae) as a suitable model plant to investigate the mechanism of germination inhibition by light, as this species has accessions with natural variation between light-sensitive and light-neutral responses. Inhibition of germination occurs in red, blue, or far-red light and increases with light intensity and duration. Gibberellins and abscisic acid are involved in the control of germination, as in Arabidopsis, but transcriptome comparisons of light- and dark-exposed A. arabicum seeds revealed that, upon light exposure, the expression of genes for key regulators undergo converse changes, resulting in antipodal hormone regulation. These findings illustrate that similar modular components of a pathway in light-inhibited, light-neutral, and light-requiring germination among the Brassicaceae have been assembled in the course of evolution to produce divergent pathways, likely as adaptive traits.
Key changes in gene expression identified for different stages of C4 evolution in Alloteropsis semialata
Authors: Dunning Luke T , Moreno-Villena Jose J , Lundgren Marjorie R , Dionora Jacqueline , Salazar Paolo , Adams Claire , Nyirenda Florence , Olofsson Jill K , Mapaura Anthony , Grundy Isla M , Kayombo Canisius J , Dunning Lucy A , Kentatchime Fabrice , Ariyarathne Menaka , Yakandawala Deepthi , Besnard Guillaume , Quick W Paul , Bräutigam Andrea , Osborne Colin P , Christin Pascal-Antoine 
Published: March 2019

AbstractC4 photosynthesis is a complex trait that boosts productivity in tropical conditions. Compared with C3 species, the C4 state seems to require numerous novelties, but species comparisons can be confounded by long divergence times. Here, we exploit the photosynthetic diversity that exists within a single species, the grass Alloteropsis semialata, to detect changes in gene expression associated with different photosynthetic phenotypes. Phylogenetically informed comparative transcriptomics show that intermediates with a weak C4 cycle are separated from the C3 phenotype by increases in the expression of 58 genes (0.22% of genes expressed in the leaves), including those encoding just three core C4 enzymes: aspartate aminotransferase, phosphoenolpyruvate carboxykinase, and phosphoenolpyruvate carboxylase. The subsequent transition to full C4 physiology was accompanied by increases in another 15 genes (0.06%), including only the core C4 enzyme pyruvate orthophosphate dikinase. These changes probably created a rudimentary C4 physiology, and isolated populations subsequently improved this emerging C4 physiology, resulting in a patchwork of expression for some C4 accessory genes. Our work shows how C4 assembly in A. semialata happened in incremental steps, each requiring few alterations over the previous step. These create short bridges across adaptive landscapes that probably facilitated the recurrent origins of C4 photosynthesis through a gradual process of evolution.
Widespread Pressure Pain Hyperalgesia Is Not Related to Pain in Patients with Parkinson’s Disease
Authors: Ferreira-Sánchez María R , Moreno-Verdú Marcos , Cano-de-la-Cuerda Roberto , Fernández-de-las-Peñas César , Güeita-Rodríguez Javier , Ortega-Santiago Ricardo 
Published: March 2019

Abstract

Objective
Pain is one of the most frequent nonmotor impairments in Parkinson’s disease (PD) and is hypothesized to be associated with altered nociceptive pain processing. Our aims were to investigate differences in widespread pressure pain sensitivity between PD patients with and without pain and healthy controls and to assess the relationship of health-related quality of life and sleep quality with pressure pain sensitivity.

Methods
Nineteen PD patients with pain (12 men, age = 68 ± 9 years), 19 PD patients without pain (11 men, age = 69 ± 8 years), and 19 matched controls participated. Pressure pain thresholds (PPTs) were assessed bilaterally over the cervical spine, the second metacarpal, and the tibialis anterior by an assessor blinded to the subject’s condition. Patients were assessed in a dopamine-medicated (ON) state. Pain intensity (numerical pain rating scale, 0–10), health-related quality of life (39-item Parkinson’s Disease Questionnaire), and sleep quality (Pittsburgh Sleep Quality Index) were also assessed.

Results
No significant differences existed between PD patients, with or without pain, and healthy controls on PPTs over the cervical spine, the second metacarpal, or the tibialis anterior muscle (all P &gt; 0.3). PPTs were lower in females than in males in all groups (P &lt; 0.01). In PD patients with pain, worse quality of sleep was associated with higher widespread pressure pain sensitivity (–0.607 &lt; r &lt; –0.535, P &lt; 0.05). No other significant association was observed.

Conclusions
This study revealed no differences in widespread pressure hyperalgesia between PD patients with or without pain (ON state) and controls. Although dopamine may modulate pain responses, other mechanisms seems to also be implicated in altered nociceptive pain processing in patients with PD.
Early use of alcohol associated with sociodemographic, nutritional and lifestyle factors: survival analysis with Brazilian students
Authors: Pinto T J P , Mendonça E P , Bloch K V , Cunha G M , Coutinho E S F 
Published: March 2019

Abstract

Background
To evaluate the early age of onset (AOO) of alcohol consumption and its association with sociodemographic, nutritional and lifestyle characteristics.

Methods
A national cross-sectional multi-centered study assessed 12–17-year old adolescents from 1247 public and private schools in 124 Brazilian municipalities with more than 100 000 habitants. Our variable of interest was the AOO of alcohol consumption. Covariates comprised sociodemographic status, lifestyle habits and nutritional parameters. We used adapted survival models to investigate the association between covariates and the AOO of alcohol consumption.

Results
From a sample of 67 672 adolescents, 50% were females. The mean AOO of alcohol consumption was 12.9 years. Male adolescents had a lower mean age of alcohol experimentation when compared to females in Northeast and South regions. The difference between private and public school for AOO was observed only for the Northeast Region (12.6 versus 13.1, respectively). Adolescents who reported smoking or mental health problems or from the Southern Region presented earlier alcohol use. Physical activity and overweight were positively associated with earlier use of alcohol.

Conclusions
There is no homogeneity in the AOO of alcohol consumption among adolescents, which should be considered when formulating public policies and government campaigns directed toward reducing alcohol consumption.
Is NPP proportional to GPP? Waring’s hypothesis 20 years on
Authors: Collalti A , Prentice I C 
Published: March 2019

AbstractGross primary production (GPP) is partitioned to autotrophic respiration (Ra) and net primary production (NPP), the latter being used to build plant tissues and synthesize non-structural and secondary compounds. Waring et al. (1998; Net primary production of forests: a constant fraction of gross primary production? Tree Physiol 18:129–134) suggested that a NPP:GPP ratio of 0.47 ± 0.04 (SD) is universal across biomes, tree species and stand ages. Representing NPP in models as a fixed fraction of GPP, they argued, would be both simpler and more accurate than trying to simulate Ra mechanistically. This paper reviews progress in understanding the NPP:GPP ratio in forests during the 20 years since the Waring et al. paper. Research has confirmed the existence of pervasive acclimation mechanisms that tend to stabilize the NPP:GPP ratio and indicates that Ra should not be modelled independently of GPP. Nonetheless, studies indicate that the value of this ratio is influenced by environmental factors, stand age and management. The average NPP:GPP ratio in over 200 studies, representing different biomes, species and forest stand ages, was found to be 0.46, consistent with the central value that Waring et al. proposed but with a much larger standard deviation (±0.12) and a total range (0.22–0.79) that is too large to be disregarded.
Associations Between Sleep Disturbance and Chronic Pain Intensity and Function
Authors: Burgess Helen J. , Burns John W. , Buvanendran Asokumar , Gupta Rajnish , Chont Melissa , Kennedy Mary , Bruehl Stephen 
Published: March 2019

Objectives:
Sleep disturbance and chronic pain are related. The present study evaluated both direct and indirect (mediated) pathways through which sleep disturbance might be related to chronic pain intensity and function.

Methods:
In total, 87 individuals (64% female) with chronic low back pain but not using opioids daily completed questionnaires assessing their sleep disturbance, chronic pain intensity, function, depression, anxiety, positive affect, and catastrophizing.

Results:
Greater sleep disturbance was associated with greater pain intensity, worse function, greater emotional distress, lower positive affect, and higher levels of catastrophizing. Cross-sectional mediation analyses revealed that the positive associations between sleep disturbance and chronic pain intensity were conveyed statistically not only by significant indirect effects of elevated emotional distress, lower positive affect, and greater catastrophizing associated with sleep disturbance, but also by significant direct effects of sleep disturbance on chronic pain intensity. Similarly, we found that the associations between sleep disturbance and impaired function were conveyed statistically not only by significant indirect effects of elevated chronic pain intensity associated with sleep disturbance, but also by significant direct effects of sleep disturbance on function.

Discussion:
Sleep disturbance was related significantly with chronic pain intensity and function by both direct and indirect pathways. These results are consistent with an emerging literature highlighting the potential significance of sleep disturbance in chronic pain patients, and provide further support for addressing sleep disturbance in the assessment and management of chronic pain.