bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthy Ageing and Biomarkers Cohort Study (HABCS): a cohort profile
Authors: Lv Yuebin , Mao Chen , Yin Zhaoxue , Li Furong , Wu Xianbo , Shi Xiaoming 
Published: October 2019

PurposeThe Chinese Longitudinal Healthy Longevity Survey Biomarkers Cohort (Healthy Ageing and Biomarkers Cohort Study (HABCS)) was established to investigate the determinants of healthy aging and mortality among the oldest old in China. Besides collecting health status, behavioural and sociodemographic circumstances, the present study also gathers comprehensive data for the elderly by simultaneously collecting, detecting, analysing blood and urine, respectively.ParticipantsHABCS is a community-based longitudinal multiwave study of older men and women aged 65 or above. Baseline survey and the follow-up surveys with replacement for deceased elderly were conducted in eight longevity areas in China, which cover the northern, middle and southern parts of China. Between 2008 and 2017, 6333 participants were included in HABCS, comprising 1385 centenarians, 1350 nonagenarians, 1294 octogenarians, 1577 younger elderly (aged 65–79).Findings to dateWe have found that higher baseline levels of (1) total cholesterol, (2) low-density lipoprotein cholesterol (LDL-C) and (3) superoxide dismutase activity were associated with greater cognitive decline. While (4) higher LDL-C level was associated with lower risk of all-cause mortality. There was a reverse association between (5) plasma vitamin D and cognitive impairment in cross-sectional and prospective study.Future plansWe are currently exploring the relationships between various biomarkers and different outcomes such as cognitive function and mortality. This longitudinal cohort study will be continued in the future.
Recovery priorities in degenerative cervical myelopathy: a cross-sectional survey of an international, online community of patients
Authors: Davies Benjamin , Mowforth Oliver , Sadler Iwan , Aarabi Bizhan , Kwon Brian , Kurpad Shekar , Harrop James S , Wilson Jefferson R , Grossman Robert , Fehlings Michael G , Kotter Mark 
Published: October 2019

ObjectivesTo establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM).DesignA cross-sectional, observational study.SettingPatients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity.Participants481 individuals suffering from DCM completed the online survey fully.Main outcome measuresFunctional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significancep<0.05.ResultsOf 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (p<0.005) who prioritised walking, even among patients with lower pain scores.ConclusionsThis is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs.
Low-value clinical practices in adult traumatic brain injury: an umbrella review protocol
Authors: Tardif Pier-Alexandre , Moore Lynne , Lauzier François , Farhat Imen , Archambault Patrick , Lamontagne Francois , Chassé Michael , Stelfox Henry Thomas , Gabbe Belinda J , Lecky Fiona , Kortbeek John , Lessard-Bonaventure Paule , Truchon Catherine , Turgeon Alexis F 
Published: October 2019

IntroductionTraumatic brain injury (TBI) leads to 50 000 deaths, 85 000 disabilities and costs $60 billion each year in the USA. Despite numerous interventions and treatment options, the outcomes of TBI have improved little over the last three decades. In a previous scoping review and expert consultation survey, we identified 13 potentially low-value clinical practices in acute TBI. The objective of this umbrella review is to synthesise the evidence on potentially low-value clinical practices in the care of acute TBI.Methods and analysisUsing umbrella review methodology, we will search Cochrane Central Register of Controlled Trials, Embase, Epistemonikos, International Prospective Register of Systematic Reviews (PROSPERO) and PubMed to identify systematic reviews evaluating the effect of potential intrahospital low-value practices using tailored population, intervention, comparator, outcome and study design questions based on the results of a previous scoping review. We will present data on the methodological quality of these reviews (Assessing the Methodological Quality of Systematic Reviews-2), reported effect sizes and strength of evidence (Grading of Recommendations, Assessment, Development and Evaluation).Ethics and disseminationEthics approval is not required as original data will not be collected. Knowledge users from five healthcare quality organisations and clinical associations are involved in the design and conduct of the study. Results will be disseminated in a peer-reviewed journal, at international scientific meetings and to clinical, healthcare quality and patient–partner associations. This work will support the development of metrics to measure the use of low-value practices, inform policy makers on potential targets for deimplementation and in the long term reduce the use of low-value clinical practices in acute TBI care.PROSPERO registration numberCRD42019132428.
Survey of the pattern of antibiotic dispensing in private pharmacies in Nepal
Authors: Nepal Anant , Hendrie Delia , Robinson Suzanne , Selvey Linda A 
Published: October 2019

ObjectivesPrivate pharmacies are widely established in most low/middle-income countries (LMICs) including Nepal, and are often considered as a patient’s first point of contact for seeking healthcare. The aim of this study was to investigate the pattern of antibiotic dispensing in private pharmacies through exit interviews with patients to review their medication information.Design and settingCross-sectional study. Data collection was carried out in 60 days at 33 randomly selected private pharmacies in the Rupandehi district of Nepal.ParticipantsPatients attending private pharmacies (n=1537).Main outcome measureThe pattern of antibiotic prescribing and dispensing was investigated using WHO’s core prescribing indicator, ‘the percentage of patients prescribed an antibiotic’. Frequency distributions were presented based on patients’ characteristics, sources of antibiotic, registration status of pharmacies and education of the pharmacist or drug retailer, and disease or condition. χ2tests and regression analysis were applied to explore factors associated with the pattern of antibiotic dispensing.ResultsOf patients attending private pharmacies, the proportion receiving at least one antibiotic (38.4%) was above the WHO recommended value (20.0%–26.8%). The most commonly dispensed antibiotics were cefixime (16.9%) and the third-generation cephalosporins (38.0%) class. High dispensing rates of antibiotics for selected conditions (eg, respiratory infections, diarrhoeal cases) appeared contrary to international recommendations. The percentage of antibiotic dispensed was highest for patients who obtained their medicines from unlicensed pharmacies (59.1%). Young people were more likely to receive antibiotics than other age groups.ConclusionsThe antibiotic dispensing pattern from private pharmacies in Nepal was high compared with WHO guidelines, suggesting initiatives to reduce inappropriate use of antibiotics should be implemented. The findings of this study may be generalisable to other LMICs in order to assist in developing policies and guidelines to promote more appropriate dispensing and prescribing practices of antibiotics and limit the spread of antibiotic resistance.
Protocol for a quasiexperimental study testing the effectiveness of strengthening growth monitoring and promotion in community clinics for improving the nutritional status of under-two children in rural Bangladesh
Authors: Hossain Muttaquina , Ferdous Tarana -E- , Islam Ziaul , Billah Sk Masum , Bulbul Md M Islam , Rahman Md Mezanur , Ahmed Tahmeed 
Published: October 2019

IntroductionThe Government of Bangladesh is implementing growth monitoring and promotion (GMP) through community clinics (CC) to improve the nutritional status of children. However, little primary evidence is available on the effectiveness of GMP when delivered through CCs. We aim to examine the effectiveness of GMP activities strengthened in CCs to improve the nutritional status of children under 2 years of age.Methods and analysisThis is a quasiexperimental, two-arm, mixed methods study. In the intervention arm, a non-governmental organisation is providing support to strengthen GMP implementation in the 30 CCs. The comparison arm has no intervention to strengthen GMP implementation in the 30 CCs. Study participants will be under-two children and their caregivers, and CC service providers (community healthcare provider, CHCP). We will collect quantitative information on children and mothers’ anthropometry, sociodemographic condition, food security, children’s feeding practices, morbidity and vaccination history at baseline, and follow them up every third month thereafter for 12 months. We will collect qualitative information on (1) knowledge, skill and practice of CHCPs to implement GMP; (2) mothers/caregivers’ perception, knowledge and experience of GMP from CCs; (3) experience and suggestions of programme managers about operational challenges and for improving quality of GMP service delivery; and (4) views of the concerned policy planners to strengthen GMP at the CC level. Qualitative information will be collected through key informant and in-depth interviews at baseline and endline. The primary outcome will be the change observed in length-for-age Z-score of children. A difference-in-difference and linear mixed effects analysis of quantitative data will be done. Thematic analysis will be conducted for qualitative information. Triangulation of data derived from different methods will be carried out.Ethics and disseminationThis study received ethical approval from the Institutional Review Board of International Centre for Diarrhoeal Disease Research, Bangladesh, and results will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberNCT03824756
Non-invasive intraventricular pressure differences estimated with cardiac MRI in subjects without heart failure and with heart failure with reduced and preserved ejection fraction
Authors: Londono-Hoyos Francisco , Segers Patrick , Hashmath Zeba , Oldland Garrett , Koppula Maheshwara Reddy , Javaid Khuzaima , Miller Rachana , Bhuva Rushikkumar , Vasim Izzah , Tariq Ali , Witschey Walter , Akers Scott , Chirinos Julio Alonso 
Published: October 2019

ObjectiveNon-invasive assessment of left ventricular (LV) diastolic and systolic function is important to better understand physiological abnormalities in heart failure (HF). The spatiotemporal pattern of LV blood flow velocities during systole and diastole can be used to estimate intraventricular pressure differences (IVPDs). We aimed to demonstrate the feasibility of an MRI-based method to calculate systolic and diastolic IVPDs in subjects without heart failure (No-HF), and with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).MethodsWe studied 159 subjects without HF, 47 subjects with HFrEF and 32 subjects with HFpEF. Diastolic and systolic intraventricular flow was measured using two-dimensional in-plane phase-contrast MRI. The Euler equation was solved to compute IVPDs in diastole (mitral base to apex) and systole (apex to LV outflow tract).ResultsSubjects with HFpEF demonstrated a higher magnitude of the early diastolic reversal of IVPDs (−1.30 mm Hg) compared with the No-HF group (−0.78 mm Hg) and the HFrEF group (−0.75 mm Hg; analysis of variance p=0.01). These differences persisted after adjustment for clinical variables, Doppler-echocardiographic parameters of diastolic filling and measures of LV structure (No-HF=−0.72; HFrEF=−0.87; HFpEF=−1.52 mm Hg; p=0.006). No significant differences in systolic IVPDs were found in adjusted models. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters.ConclusionsOur findings suggest distinct patterns of systolic and diastolic IVPDs in HFpEF and HFrEF, implying differences in the nature of diastolic dysfunction between the HF subtypes.
Higher lattices, discrete two-dimensional holonomy and topological phases in (3 + 1)D with higher gauge symmetry
Authors: Bullivant Alex , Calçada Marcos , Kádár Zoltán , Martins João Faria , Martin Paul 
Published: October 2019

Higher gauge theory is a higher order version of gauge theory that makes possible the definition of 2-dimensional holonomy along surfaces embedded in a manifold where a gauge 2-connection is present. In this paper, we study Hamiltonian models for discrete higher gauge theory on a lattice decomposition of a manifold. We show that a construction for higher lattice gauge theory is well-defined, including in particular a Hamiltonian for topological phases of matter in [Formula: see text] dimensions. Our construction builds upon the Kitaev quantum double model, replacing the finite gauge connection with a finite gauge 2-group 2-connection. Our Hamiltonian higher lattice gauge theory model is defined on spatial manifolds of arbitrary dimension presented by slightly combinatorialized CW-decompositions (2-lattice decompositions), whose 1-cells and 2-cells carry discrete 1-dimensional and 2-dimensional holonomy data. We prove that the ground-state degeneracy of Hamiltonian higher lattice gauge theory is a topological invariant of manifolds, coinciding with the number of homotopy classes of maps from the manifold to the classifying space of the underlying gauge 2-group. The operators of our Hamiltonian model are closely related to discrete 2-dimensional holonomy operators for discretized 2-connections on manifolds with a 2-lattice decomposition. We therefore address the definition of discrete 2-dimensional holonomy for surfaces embedded in 2-lattices. Several results concerning the well-definedness of discrete 2-dimensional holonomy, and its construction in a combinatorial and algebraic topological setting are presented.
PA Linearization by Digital Predistortion and Peak-to-Average Power Ratio Reduction in Software Defined Radios
Authors: Jovanović Borisav , Milenković Srdan 
Published: October 2019

Digital predistortion (DPD), based on complex-valued memory polynomials (MP), is established as an efficient method for power amplifier (PA) linearization. The DPD facilitates compliance of the telecommunication infrastructure to strict standard specifications (transmit spectrum mask (TSM), error vector magnitude (EVM), bit error rate (BER), [Formula: see text]) by making PA more linear, while at the same time reduces the running cost of the wireless infrastructure (at both Base Transceiver Station (BTS) and User Equipment (UE) sides) by making PA more power efficient. Even when DPD is utilized, signals with high peak-to-average power ratio (PAPR) produce out-of-band PA spectrum emission due to intermodulation products affecting all above-mentioned critical standard specified parameters. The novelty proposed in this paper is as follows. PA is restricted to operate within “reasonably above” PA linear region using PAPR reduction technique. The residual nonlinearity is taken care of by DPD. The combination of DPD and PAPR PA linearization methods is implemented on software-defined radio board. The necessary steps for efficient PA linearization are presented, compensating both out-of-band and in-band signal distortions. We achieved EVM = 2.0%, ACPR [Formula: see text]50[Formula: see text]dBc, at 10[Formula: see text]W LTE modulated PA output, antenna point and PA output power of 39.5[Formula: see text]dBm.
IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation
Authors: Adi Dilare , Lu Xiao-Yi , Fu Zhen-Yan , Wei Jian , Baituola Gulinaer , Meng Ya-Jie , Zhou Yu-Xia , Hu Ao , Wang Jin-Kai , Lu Xiang-Feng , Wang Yan , Song Bao-Liang , Ma Yi-Tong , Luo Jie 
Published: October 2019

Objective:
A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined.

Approach and Results:

By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the
IDOL
gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride.

Conclusions:
Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.
TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates
Authors: Singh Rajesh K. , Haka Abigail S. , Asmal Arky , Barbosa-Lorenzi Valéria C. , Grosheva Inna , Chin Harvey F. , Xiong Yuquan , Hla Timothy , Maxfield Frederick R. 
Published: October 2019

Objective:
Aggregation and modification of LDLs (low-density lipoproteins) promote their retention and accumulation in the arteries. This is a critical initiating factor during atherosclerosis. Macrophage catabolism of agLDL (aggregated LDL) occurs using a specialized extracellular, hydrolytic compartment, the lysosomal synapse. Compartment formation by local actin polymerization and delivery of lysosomal contents by exocytosis promotes acidification of the compartment and degradation of agLDL. Internalization of metabolites, such as cholesterol, promotes foam cell formation, a process that drives atherogenesis. Furthermore, there is accumulating evidence for the involvement of TLR4 (Toll-like receptor 4) and its adaptor protein MyD88 (myeloid differentiation primary response 88) in atherosclerosis. Here, we investigated the role of TLR4 in catabolism of agLDL using the lysosomal synapse and foam cell formation.

Approach and Results:
Using bone marrow–derived macrophages from knockout mice, we find that TLR4 and MyD88 regulate compartment formation, lysosome exocytosis, acidification of the compartment, and foam cell formation. Using siRNA (small interfering RNA), pharmacological inhibition and knockout bone marrow–derived macrophages, we implicate SYK (spleen tyrosine kinase), PI3K (phosphoinositide 3-kinase), and Akt in agLDL catabolism using the lysosomal synapse. Using bone marrow transplantation of LDL receptor knockout mice with TLR4 knockout bone marrow, we show that deficiency of TLR4 protects macrophages from lipid accumulation during atherosclerosis. Finally, we demonstrate that macrophages in vivo form an extracellular compartment and exocytose lysosome contents similar to that observed in vitro for degradation of agLDL.

Conclusions:
We present a mechanism in which interaction of macrophages with agLDL initiates a TLR4 signaling pathway, resulting in formation of the lysosomal synapse, catabolism of agLDL, and lipid accumulation in vitro and in vivo.
Prognostic Value of Low Flow in Patients With High Transvalvular Gradient Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction
Authors: Maréchaux Sylvestre , Rusinaru Dan , Altes Alexandre , Pasquet Agnès , Vanoverschelde Jean Louis , Tribouilloy Christophe 
Published: October 2019

Background:

Grading of severe (aortic valve area ≤1 cm
2
) aortic stenosis with preserved left ventricular ejection fraction is based on a classification depending on flow (normal flow versus low flow) and pressure gradient (low gradient versus high gradient). The aim of the present study was to compare the outcome of patients with normal flow high gradient and low flow high gradient severe aortic stenosis (SAS) with no or minimal symptoms.

Methods:

This multicenter study enrolled 983 consecutive patients (mean age 75±11 years, 459 women) with asymptomatic or minimally symptomatic HG (mean pressure gradient ≥40 mm Hg) SAS with preserved left ventricular ejection fraction. Low flow was defined by Doppler echocardiography as a stroke volume index <30 mL/m
2
(n=131) or a stroke volume <55 mL (n=136). The end point was all-cause mortality.

Results:

During a median follow-up period of 48 (45–52) months, 225 patients (23%) died. The 60–month mortality was higher in low flow high gradient SAS compared with normal flow high gradient SAS (36±5% versus 22±2% and 38±5% versus 21±2% for stroke volume index and stroke volume, respectively, both
P
<0.0001). After adjustment for outcome predictors including aortic valve replacement as time-dependent covariate, low flow high gradient SAS displayed considerable mortality risk during follow up compared with normal flow high gradient SAS (adjusted HR 2.17 [1.51–3.13];
P
<0.0001 for stroke volume index <30 mL/m
2
and adjusted HR 1.86 [1.29–2.68];
P
=0.001, for stroke volume <55 mL). The prognostic impact of low flow was consistent in subgroups of patients.

Conclusions:
Asymptomatic or minimally symptomatic patients with low flow high gradient SAS and preserved left ventricular ejection fraction have a considerable increased risk of mortality during follow-up. These patients should be promptly considered for aortic valve replacement.