bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting fitness epistasis in recent admixed populations with genome-wide data
Authors: Zhu Xiaofeng , Ni Xumin , Zhou Mengshi , Wang Heming , He Karen , Broeckel Uli , Hanis Craig , Kardia Sharon , Redline Susan , Cooper Richard , Tang Hua 
Published: November 2019

Abstract
Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, has an important contribution for adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is less detectable and remains poorly understood in human populations owing to the limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to strong confounding effect in a recently admixed population. Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value<8.11×10 -7 ) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pair of epistatic regions. We observed multiple pairs of co-expressed genes between the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in GTEx. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to better understand adaptive evolution.
Urinary continence outcomes of four years of follow-up and predictors of early and late urinary incontinence in patients undergoing robot-assisted radical prostatectomy
Authors: Li Xing , Zhang Huan , Jia Zhuo , Wang Yunpeng , Song Yong , Liao Limin , Zhang Xu 
Published: November 2019

Abstract
Background Although the wide application of robot-assisted radical prostatectomy (RARP) in recent years, studies about long urinary continence were few. In this study, we aimed to examine the outcomes of continence rates (CRs) and determine the predictive factors of early and late urinary incontinence (UI) in patients with prostate cancer (PCa) undergoing RARP.Methods This retrospective study included 650 patients treated with RARP who completed perioperative data and at least one year of follow-up from January 2009 to November 2017. We analyzed the preoperative, intraoperative, and postoperative parameters of the patients. Continence was defined as no pad use. CRs from one to 48 months postoperatively were examined. Logistic regression analysis was performed to evaluate the associations between the risk factors and UI in the early and late stages.Results CRs of the patients at one, three, six, 12, 24, 36, and 48 months postoperatively were 40.62%, 60.92%, 71.38%, 78.77%, 79.96%, 79.51%, and 76.50%, respectively. There were no significant differences in CR from 12 to 48 months postoperatively ( P =0.766). Logistic regression analysis proved that pelvic lymph node dissection (PLND) was a significant predictor of UI at one month, while age was an independent predictor of UI at six and 12 months, respectively. Other variables were not statistically significant predictors.Conclusions Our results demonstrated that CR gradually improved with time within one year and stabilized one year after the surgery. PLND and age were significant determinants of continence in the early and late stages, respectively. These parameters could be used for preoperatively identifying patients at high risk for UI and counselling about postoperative expectations for urinary continence.
A multi-stakeholder approach to the co-production of the research agenda for medicines optimisation
Authors: Fellenor John , Britten Nicky , Courtenay Molly , Payne Rupert A , Valderas Jose , Denholm Rachel , Duncan Polly , McCahon Deborah , Tatnell Lynn , Fitzgerald Richard , Warmoth Krystal , Gillespie David , Turner Katrina , Watson Margaret 
Published: November 2019

Abstract
Background
Over one billion prescription items are dispensed in the United Kingdom annually. Up to 50% of medicines are not used as intended, resulting in sub-optimal health outcomes and harm. Medicines optimisation is ‘a person-centred approach to safe and effective medicines use, to ensure people obtain the best possible outcomes from their medicines’. The purpose of this study was to co-produce a prioritised research agenda for medicines optimisation using a multi-stakeholder (patient, public and health professionals) approach.
Methods
A three-stage, multiple method process was used including: generation of preliminary research questions (Stage 1) using a modified Nominal Group Technique; electronic consultation and ranking with a wider multi-stakeholder group (Stage 2); a face-to-face, one-day consensus meeting involving representatives from all stakeholder groups (Stage 3).
Results
In total, 92 research questions were identified during Stages 1 and 2 and ranked in order of priority during stage 3. Questions were categorised into four areas: ‘Patient Concerns’ [e.g. is there a shared decision (with patients) about using each medicine?], ‘Polypharmacy’ [e.g. how to design health services to cope with the challenge of multiple medicines use?], ‘Non-Medical Prescribing’ [e.g. how can the contribution of non-medical prescribers be optimised in primary care?], and ‘Deprescribing’ [e.g. what support is needed by prescribers to deprescribe?]. A significant number of the 92 questions were generated by Patient and Public Involvement representatives, which demonstrates the importance of including this stakeholder group when identifying research priorities.
Conclusions
A wide range of research questions was generated reflecting concerns which affect patients, practitioners, the health service, as well the ethical and philosophical aspects of the prescribing and deprescribing of medicines. These questions should be used to set future research agendas and funding commissions.
LipoDDx: a mobile application for identification of rare lipodystrophy syndromes
Authors: Araujo-Vilar David , Fernández-Pombo Antia , Rodríguez-Carnero Gemma , Martínez-Olmos Miguel Angel , Cantón Ana , Villar-Taibo Rocio , Hermida-Ameijeiras Alvaro , Santamaría-Nieto Alicia , Díaz-Ortega Carmen , Martínez-Rey Carmen , Antela Antonio , Losada Elena , Muy-Pérez Andrés , González-Méndez Blanca , Sánchez-Iglesias Sofía 
Published: November 2019

Abstract
Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Objective: Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®.Design and participants: 40 clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 15 people. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease.Results: LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p <0.01).Conclusions: LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies with around 80% effectiveness, which will be of help to doctors who are not experts in this field.
Health-related quality of life in children and adults with X-linked hypophoshatemia
Authors: Yanes María Isabel Luis , Díaz-Curiel Manuel , Peris Pilar , Calderón Carmen , Marín Silvia , Ramon-Krauel Marta , Hernández Julio , Broseta José Jesús , Espinosa Laura , Mendizábal Santiago , Pérez-Sukia Leyre , Martínez Víctor , Palazón Cristina , Piñero Juan Antonio , Calleja Miguel Ángel , Espín Jaime , Ariceta Gema , Nieto-Vázquez Iria , Jiménez Antonio 
Published: November 2019

Abstract
Background
X-linked hypophosphatemia (XLH) is an inherited type of severe rickets leading to deformities and can sometimes become a debilitating condition. Its impact on health-related quality of life (HRQoL) has not been extensively studied.
Results
Using standardized questionnaires in 21 children and 29 adults with confirmed XLH, we observed significant impaired HRQoL.
Children had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). The mean EQ-5D-3L/EQ-5D-3L proxy index was 0.79 ± 0.15 and the mean VAS score was 68.33 ± 16.61.
Adults had lower HRQoL, particularly with problems in walking (93%, with 3.45% unable to walk independently) and pain (86%, with 3.45% experiencing extreme pain). They also reported problems when carrying out their usual activities (80%) and washing or dressing themselves (>50%), and 65% of adult patients reported symptoms of anxiety and/or depression. The differences compared with the general Spanish population were significant, especially in the mobility and pain/discomfort dimensions of the EQ-5D-5L instrument.
Caregivers and parents showed mild reduction in HRQoL, with a mean EQ-5D-5L index value (0.82 ± 0.16) and a mean VAS score (75.48 ± 17.24) smaller than that found in the general Spanish population.
Conclusions
X-linked hypophosphatemia reduced health-related quality of life despite treatment. These results evidenced limitations of conventional treatment in preventing disease complications, which in turn impaired quality of life in pediatric and adult patients.
Disease progression modeling of Alzheimer’s disease according to education level
Authors: Kim Ko Woon , Woo Sook Young , Kim Seonwoo , Kim Yeshin , Jang Hyemin , Cho Soo Hyun , Kim Si Eun , Kim Seung Joo , Kim Hee Jin , Na Duk L. , Seo Sang Won 
Published: November 2019

Abstract
Background
To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to dementia and to investigate the effect of education level on the whole disease spectrum.
Methods
We enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB) score. Three cohorts, SCI (n=85), amnestic mild cognitive impairment (AMCI, n=240), and AD dementia (ADD, n=240), were overlapped in two consecutive cohorts (SCI and AMCI, AMCI and ADD) to construct a model of disease course, and a model with multiple single-cohorts was estimated using a mixed-effect model. To examine the effect of education level on disease progression, the disease progression model was developed with data from lower (≤12) and higher (>12) education groups.
Results
Disease progression takes 277.0 months (23.1 years) to advance from 0 to 18 points using the CDR-SB score. Based on our predictive equation, it takes 101.9 months to progress from SCI to AMCI and 71.1 months to progress from AMCI to ADD. The rate of CDR-SB progression was different according to education level. The lower-education group showed faster CDR-SB progression from SCI to AMCI compared to the higher-education group, and this trend disappeared from AMCI to ADD.
Conclusion
In the present study, we developed a disease progression model of AD spectrum from preclinical to the end stage of the disease. Our findings suggest that the contribution of education to cognitive decline varies depending on disease stage.
Secular trend analysis of antibiotic consumption in China’s hospitals 2011-2018, a retrospective analysis of sales data
Authors: Wushouer Haishaerjiang , Zhou Yue , Zhang Xi , Fu Mengyuan , Fan Daiming , Shi Luwen , Guan Xiaodong 
Published: November 2019

Abstract
Background: This study was aimed to explore the secular trends of antibiotic consumption over an 8-year period. Methods: We retrospectively analysed aggregated monthly surveillance data on antibiotic sales to 586 hospitals from 28 provinces in China from January 2011 to December 2018. Information including generic name, sales amount, dosage form, strength, the route of administration, and geographical data were collected. Population weighted Antibiotic consumption was expressed in DDD per 1,000 inhabitants per day (DID). WHO’s ‘Access, Watch, Reserve’ categorization was also adopted to analyse antibiotic consumption. Results: Between 2011 and 2018, total antibiotic consumption in China’s hospitals increased by 38.2% (from 4.8 DID in 2010 to 6.7 DID in 2018). Antibiotic consumption was stable or had moderately decreased in 13 provinces, while the other 15 provinces had substantially increased. Cephalosporins were the most consumed antibiotics, accounted for 26.9% of the total antibiotic consumption. In 2018, antibiotics in the Access category comprised 20.0% of total consumption, where antibiotics in the Watch category consumed the most with 72.2%. Population-weighted antibiotic consumption was larger in secondary hospitals than tertiary hospitals (7.3 DID VS 6.6 DID). The antibiotics consumption of oral form was almost two times the consumption of parenteral forms in secondary hospitals, whereas the proportion of tertiary hospitals was about the same. Conclusions: Although efforts were made towards restricting antibiotics in the past decade by Chinese government, antibiotic consumption demonstrated an upward trend during the study period. More efforts are needed to explore the quality of antibiotic usage in terms of rationality.
Effects of Perioperative Transcutaneous Electrical Acupoint Stimulation on Monocytic HLA-DR Expression in Patients undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass: Study Protocol for a Double-blind Randomized Controlled Trial
Authors: Chen Wen-ting , Wei Jin-feng , Wang Lan , Zhang Deng-wen , Tang Wei , Wang Jian , Yong Yue , Wang Jing , Zhou Ya-lan , Yuan Lan , Fu Guo-qiang , Wang Sheng , Song Jian-gang 
Published: November 2019

Abstract
Background: Cardiac surgery involving cardiopulmonary bypass (CPB) is known to be associated with a transient postoperative immunosuppression. When severe and persistent, this immune dysfunction predisposes patients to infectious complications, which contributes to a prolonged stay in the intensive care unit (ICU), even mortality. The effective prevention and treatment methods are still lacking. Recent studies revealed that acupuncture related techniques, such as electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), are able to produce effective cardioprotection and immunomodulation in adult and pediatric patients undergoing cardiac surgery with CPB, which leads to enhanced recovery. However, whether perioperative application of TEAS, a non-invasive technique, is able to improve immunosuppression of the patients with post cardiosurgical conditions is unknown. Thus, as a preliminary study, the main objective is to evaluate the effects of TEAS on the postoperative expression of monocytic human leukocyte antigen (-D related) (mHLA-DR), a standardized “global” biomarker of injury or sepsis-associated immunosuppression, in patients receiving on-pump Coronary Artery Bypass Grafting (CABG). Methods: This clinical study was a single-center clinical trial. The 88 patients scheduled to receive CABG under CPB will be randomized into 2 groups: the group of TEAS, and the group of transcutaneous acupoint pseudo - electric stimulation (Sham TEAS). Monocytic HLA-DR expression serves as a primary endpoint, and other laboratory parameters (e.g. IL-6, IL-10) and clinical outcomes (e.g. postoperative infectious complications, ICU stay time, and mortality) as the secondary endpoints. In addition, immune indicators, such as high mobility group protein 1 (HMGB1) and regulatory T cell (Treg) will also be measured. Discussion: The current study is a preliminary mono-centric clinical trial with a non-clinical primary endpoint, expression of mHLA-DR, aiming at determining whether perioperative application of TEAS has a potential to reverse CABG-associated immunosuppression. Although the immediate clinical impact of this study is limited, its results would inform further large sample clinical trial with using relevant patient-centered clinical outcomes as primary endpoints.
Cooking up Diverse Diets: Advancing Biodiversity in Food and Agriculture through Collaborations with Chefs
Authors: Moreau Tara , Speight David 
Published: November 2019

ABSTRACTBiodiversity in and across food and agriculture systems provides tremendous value to present and future generations. However, across the world we are losing genes, species, and ecosystems faster than we can account for them. With one million plant and animal species at risk of extinction, our society is challenged to address the drivers of ecosystem degradation and species loss. Increasingly, the negative impacts of agriculture and food systems on biodiversity are being raised as well as the global risks to health associated with unhealthy diets. Recent efforts in North America to raise awareness of crop diversity and coordinate plant conservation efforts culminated in a symposium with botanic gardens, agricultural researchers, wild land managers, conservation organizations, academics, and government bodies. The gathering focused primarily on production‐side solutions such as crop diversity, crop wild relative conservation, and agricultural education. Although not present at the symposium, chefs were commonly highlighted and discussed as key collaborators in plant conservation through their important role in connecting consumers to agriculture production and new food plants. This paper shares examples of chefs and culinary programs working to impact agriculture, diets, and plant diversity. To critically assess which chef and culinary programs are having the greatest impact future researched is needed, but as we race to save plant species from extinction, it is clear that chefs connect to consumers in unique ways and are important potential allies in cooking up new sustainable consumption and production patterns that support biodiversity in food systems.
A Macroscopic Analytical Model for Pressure Wave Propagation in the Water of a Variably Saturated Porous Medium
Authors: Kalisman Doron , Sorek Shaul , Yakirevich Alexander , Kamai Tamir 
Published: November 2019

Core Ideas
Pressure waves in pore water can affect transport phenomena.
A macroscopic analytical model follows pressure waves traveling in the pore water.
Pressure attenuation is predicted through soil hydraulic and mechanical properties.
Soil water pressure measurements indicate that soil texture impacts the attenuation.
A macroscopic one‐dimensional analytical model has been developed for the attenuation of low‐frequency pressure waves in the water of a variably saturated porous medium. The developed model associates pressure amplitude attenuation with pore scales. Pressure propagation in a single pore size is described by a linear wave equation, and the composition of characteristic pore sizes are combined for representing the porous medium. The capillary bundle approach allows for a geometrical abstraction of the pore sizes and the definition of the water‐filled capillaries under different water content states. This approach allows the pore water pressure attenuation to be addressed directly with readily available soil properties and parameters. Theoretical findings backed by experimental observations in three soils under saturated conditions indicate that the pressure wave attenuates more rapidly in the water of fine‐textured soils than coarser ones. Furthermore, the results indicate that the effect of larger pores on pressure attenuation is significant at high water contents, but the pore‐size distribution and the smaller pores dominantly control the pressure attenuation as the water content decreases. The developed model is consistent with previous studies and with the theory of Biot for waves in composite media.
Seismic detectability of carbonates in the deep Earth: A nuclear inelastic scattering study
Authors: Chariton Stella , McCammon Catherine , Vasiukov Denis M. , Stekiel Michal , Kantor Anastasia , Cerantola Valerio , Kupenko Ilya , Fedotenko Timofey , Koemets Egor , Hanfland Michael , Chumakov Alexandr I. , Dubrovinsky Leonid 
Published: November 2019

AbstractCarbonates play an important role in the transport and storage of carbon in the Earth’s mantle. However, the abundance of carbon and carbonates in subduction zones is still an unknown quantity. To determine the most abundant accessory phases and how they influence the dynamical processes that operate within the Earth, investigations on the vibrational, elastic, and thermodynamic properties of these phases are crucial for interpreting seismological observations. Recently, the nuclear inelastic scattering (NIS) method has proved to be a useful tool to access information on the lattice dynamics, as well as to determine Debye sound velocities of Fe-bearing materials. Here we derive the acoustic velocities from two carbonate compositions in the FeCO3-MgCO3 binary system up to ~70 GPa using the NIS method. We conclude that more Mg-rich samples, in this case (Fe0.26Mg0.74)CO3, have ~19% higher sound velocities than the pure end-member Fe composition. In addition, we observed a significant velocity increase after the Fe2+ spin transition was complete. After laser heating of FeCO3 at lower mantle conditions, we observed a dramatic velocity drop, which is probably associated with thermal decomposition to another phase. Parallel to our NIS experiments, we conducted a single-crystal X-ray diffraction (SCXRD) study to derive the equation of states of FeCO3 and (Fe0.26Mg0.74)CO3. The combined information from NIS (i.e., Debye velocities) and SCXRD (i.e., densities and bulk moduli) experiments enabled us to derive the primary and shear wave velocities of our samples. Our results are consistent with results obtained by other methods in previous studies, including Brillouin spectroscopy, inelastic X-ray scattering, and DFT calculations, supporting NIS as a reliable alternative method for studying the elastic properties of Fe-bearing systems at high pressures and temperatures. Finally, we discuss the seismic detectability of carbonates. We determine that nearly 22 wt% CO2 must be present in the subduction slab to detect a 1% shear wave velocity decrease compared to non-carbonated lithologies at the transition zone to lower mantle boundary depths.