bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediation role of low birth weight on the factors associated with newborn mortality and the moderation role of institutional delivery in the association of low birth weight with newborn mortality in a resource-poor setting
Authors: Kananura Rornald Muhumuza 
Published: May 2021

ObjectivesTo assess low birth weight’s (LBW) mediation role on the factors associated with newborn mortality (NM), including stillbirth and the role of institutional delivery in the association between LBW and NM.Design and participantsI used the 2011–2015 event histories health demographic data collected by Iganga-Mayuge Health Demographic and Surveillance Site (HDSS). The dataset consisted of 10 758 registered women whose birth occurred at least 22 weeks of the gestation period and records of newborns’ living status 28 days after delivery.SettingThe Iganga-Mayuge HDSS is in Eastern Uganda, which routinely collects health and demographic data from a registered population of at least 100 000 people.Outcome measureThe study’s key outcomes or endogenous factors were perinatal mortality (PM), late NM and LBW (mediating factor).ResultsThe factors that were directly associated with PM were LBW (OR=2.55, 95% CI 1.15 to 5.67)), maternal age of 30+ years (OR=1.68, 95% CI 1.21 to 2.33), rural residence (OR=1.38, 95% CI 1.02 to 1.85), mothers with previous experience of NM (OR=3.95, 95% CI 2.86 to 5.46) and mothers with no education level (OR=1.63, 95% CI 1.21 to 2.18). Multiple births and mother’s prior experience of NM were positively associated with NM at a later age. Institutional delivery had a modest inverse role in the association of LBW with PM. LBW mediated the association of PM with residence status, mothers’ previous NM experience, multiple births, adolescent mothers and mothers’ marital status. Of the total effect attributable to each of these factors, LBW mediated +47%, +15%, +100%, +54% and −45% of rural resident mothers, mothers with previous experience of newborn or pregnancy loss, multiple births, adolescent mothers and mothers with partners, respectively.ConclusionLBW mediated multiple factors in the NM pathways, and the effect of institutional delivery in reducing mortality among LBW newborns was insignificant. The findings demonstrate the need for a holistic life course approach that gears the health systems to tackle NM.
Promoting convergence and closing gaps: a blueprint for the revision of the European Union Tobacco Tax Directive
Authors: López-Nicolás Ángel , Branston J Robert 
Published: May 2021

Background and aimsDespite the European Union (EU) Tobacco Tax Directive (TTD), a lack of convergence in EU tobacco prices promotes high levels of cross-border shopping and down-trading from factory-made (FM) to roll-your-own tobacco (RYO) cigarettes. This study presents a blueprint for reform, whereby minimum taxes are related to the overall price level in the EU and where taxation of RYO is related to that of FM.MethodsLongitudinal data on prices and taxes on FM and RYO in 25 member states over 2011–2019 are used to estimate econometric models for their weighted average prices as a function of taxes. Two scenarios are simulated with the models’ estimates: a baseline scenario for the actual tax stance pertaining to 2020 and a reform scenario implementing the blueprint.ResultsThe baseline results show that, while the prices of both products have experienced a slight increase since 2016 in real terms, the dispersion in the prices of FM across countries has increased and the difference in the prices of RYO within countries has widened. The results for the reform scenario show dispersion would diminish both EU-wide and in hotspots for cross-border sales of FM. The reform would also lead to a substantial reduction in the price gap between FM and RYO.ConclusionTo promote price convergence and close the price gap between FM and RYO, the revised TTD should ensure minimum FM taxes track a measure of their average EU price, and RYO taxes are related to FM taxes.
Functional Assessment of 3D Printed Prosthesis in Children with Congenital Hand Differences-A Prospective Observational Study
Authors: Bhat Anil K. , M Vamsikrishna , Acharya Ashwath M. 
Published: May 2021

Background: Children with congenital differences who require prosthesis, have special needs due to their growth and psychosocial factors. Cosmetic or body-powered prosthesis provides basic functional needs but poses a financial burden on the family. Prostheses with advanced functions need to be deferred until adulthood. 3D printed prosthesis is a novel alternative being cost-effective for children. Since limited literature is available on the functionality of 3D printed prosthesis and none in the South Asian population, this study was done to assess its utility in congenital hand amputations. Methods: Fourteen children with congenital hand amputations were selected for a prospective observational study. Unilateral below Elbow test (UBET), Box and Block test and ABILHAND questionnaire were used for assessment with and without prosthesis after six months. Results: Eleven patients completed the follow-up. Box and Block test improved from a mean score of 24 to 35 with the prosthesis implying an improvement in manual gross dexterity (p −0.049). UBET (p −0.002) and ABILHAND questionnaire (p < 0.001) showed a decrease in score with the use of a prosthesis which suggested a lack of lateral and tripod pinch in the current design of a prosthesis. Patients with below elbow prosthesis performed better. Conclusions: 3D printed prostheses are an excellent option for use as a transitional prosthesis as they are inexpensive, serves to improve needs with respect to grasping activities at both wrist and elbow level amputation and customizable according to patients’ need and limb deficiency and replaceable as the child grows with age. Current designs are useful with respect to grasping activities.
First-Line Afatinib plus Cetuximab for EGFR-Mutant Non–Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study
Authors: Cortot Alexis B. , Madroszyk Anne , Giroux-Leprieur Etienne , Molinier Olivier , Quoix Elisabeth , Bérard Henri , Otto Josiane , Rault Isabelle , Moro-Sibilot Denis , Raimbourg Judith , Amour Elodie , Morin Franck , Hureaux José , Moreau Lionel , Debieuvre Didier , Morel Hugues , Renault Aldo , Pichon Eric , Huret Benjamin , Charpentier Sandrine , Denis Marc G. , Cadranel Jacques 
Published: May 2021

Abstract

Purpose:
Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC.

Patients and Methods:
In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed.

Results:
Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received.

Conclusions:
These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Authors: Raad Nour , Bittihn Philip , Cacheux Marine , Jeong Dongtak , Ilkan Zeki , Ceholski Delaine , Kohlbrenner Erik , Zhang Lu , Cai Chen-Leng , Kranias Evangelia G. , Hajjar Roger J. , Stillitano Francesca , Akar Fadi G. 
Published: May 2021

Background:

Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN
R14del
) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear.

Methods:

To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN
WT
(wildtype [WT], n=12) or the heterozygous human PLN
R14del
mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing.

Results:
Adverse electrophysiological remodeling was evident in the absence of significant structural or hemodynamic changes. R14del hearts exhibited increased arrhythmia susceptibility compared with wildtype. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to β-adrenergic stimulation. A steep repolarization gradient at the left ventricular/right ventricular interface provided the substrate for interventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. Once sustained, these circuits evolved into high-frequency rotors, which in their majority were pinned to the right ventricle. These rotors exhibited unique spatiotemporal dynamics that promoted their increased stability in R14del compared with wildtype hearts.

Conclusions:

Our findings highlight the crucial role of primary electric remodeling caused by the hPLN
R14del
mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of PLN
R14del
induced cardiomyopathy.
Investigation of precipitation characteristics under the action of acoustic waves in the source region of the Yellow River
Authors: Shi Yang , Wei Jiahua , Ren Yan , Qiao Zhen , Li Qiong , Zhu Xiaomei , Kang Beiming , Pan Peichong , Cao Jiongwei , Wang Guangqian 
Published: May 2021

AbstractAcoustic agglomerations have increasingly attracted widespread attention as a cost-effective and environmentally friendly approach for fog removal and weather modification. In this study, research on precipitation interference and the agglomeration performance of droplet aerosols under large-scale acoustic waves was presented. In total, 49 field experiments in the source region of the Yellow River (SRYR) in the summer of 2019 were performed to reveal the influences of acoustic waves on precipitation, such as the radar reflectivity factor (Z), rain rate (R), and raindrop size distribution (DSD). A monitoring system that consisted of rain gauges and raindrop spectrometers was employed to monitor near-ground rainfall within a 5 km radius of the field site. The ground-based observations showed that acoustic waves could significantly affect the rainfall distribution and microstructure of precipitation particles. The average values of rainfall increased by 18.98%, 10.61%, and 8.74% within 2 km, 3 km and 5 km of the operation center with acoustic application. The changing trend of microphysical parameters of precipitation was roughly in line with variation of acoustic waves for stratiform cloud. Moreover, there was a good quadratic relationship between the spectral parameters λ and μ. Raindrop kinetic energy (eK) and the radar reflectivity factor (Z) both exhibited a power function relationship with the rain rate (R).
The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal
Authors: Engevik Melinda A. , Danhof Heather A. , Hall Anne , Engevik Kristen A. , Horvath Thomas D. , Haidacher Sigmund J. , Hoch Kathleen M. , Endres Bradley T. , Bajaj Meghna , Garey Kevin W. , Britton Robert A. , Spinler Jennifer K. , Haag Anthony M. , Versalovic James 
Published: May 2021

Abstract
Background
Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium.

Results
B. dentium displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the B. dentium genome. B. dentium was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose, B. dentium could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that B. dentium can consume dietary substances. In contrast to other bifidobacteria, B. dentium was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in B. dentium by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment.

Conclusions
Taken together, we conclude that B. dentium is well adapted for commensalism in the gastrointestinal tract.
Transcriptome and metabolite profiling analyses provide insight into volatile compounds of the apple cultivar ‘Ruixue’ and its parents during fruit development
Authors: Liu Xiaojie , Hao Nini , Feng Ruifang , Meng Zhipeng , Li Yanan , Zhao Zhengyang 
Published: May 2021

Abstract
Background
Aroma is one the most crucial inherent quality attributes of fruit. ‘Ruixue’ apples were selected from a cross between ‘Pink Lady’ and ‘Fuji’, a later ripening yellow new cultivar. However, there is little known about the content and composition of aroma compounds in ‘Ruixue’ apples or the genetic characters of ‘Ruixue’ and its parents. In addition, the metabolic pathways for biosynthesis of aroma volatiles and aroma-related genes remain poorly understood.

Results
Volatile aroma compounds were putatively identified using gas chromatography-mass spectrometry (GC–MS). Our results show that the profile of volatile compounds changes with ripening. Aldehydes were the dominant volatile compounds in early fruit development, with alcohols and esters increasing dramatically during maturation. On the basis of a heatmap dendrogram, these aroma compounds clustered into seven groups. In ripe fruit, esters and terpenoids were the main aroma volatiles in ripening fruit of ‘Pink Lady’ and ‘Fuji’ apples, and they included butyl 2-methylbutanoate; propanoic acid, hexyl ester; propanoic acid, hexyl ester; hexanoic acid, hexyl ester; acetic acid, hexyl ester and (Z, E)-α-farnesene. Interestingly, aldehydes and terpenoids were the dominant volatile aroma compounds in ripening fruit of ‘Ruixue’, and they mainly included hexanal; 2-hexenal; octanal; (E)-2-octenal; nonanal and (Z, E)-α-farnesene. By comparing the transcriptome profiles of ‘Ruixue’ and its parents fruits during development, we identified a large number of aroma-related genes related to the fatty acid, isoleucine and sesquiterpenoid metabolism pathways and transcription factors that may volatile regulate biosynthesis.

Conclusions
Our initial study facilitates a better understanding of the volatile compounds that affect fruit flavour as well as the mechanisms underlying differences in flavour between ‘Ruixue’ and its parents.
The suitability of panoramic radiographs for clinical decision making regarding root angulation compared to cone-beam computed tomography
Authors: Alqareer Athbi , Nada Rania , Ghayyath Aref , Baghdady Mariam , Allareddy Veerasathpurush 
Published: May 2021

Abstract
Background
The study compared clinical decisions regarding root angulation correction and root proximity based on the interpretation of Panoramic (PAN) versus Cone-Beam Computed Tomography (CBCT) images.

Methods
A total of 864 teeth from 36 existing, radiographic patient records at a university dental clinic with concurrent PAN and CBCT images were assessed using PANs, then using CBCTs in a blinded manner by two orthodontists. Teeth were rated regarding the need for root repositioning, the direction of repositioning and existence of root proximity. Frequencies, rating time and intra- and inter-examiner Cohen’s Kappa were calculated.

Results
There was 73.7–84.5% agreement between PAN-based and CBCT-based orthodontists’ decisions regarding the need to reposition roots. Root proximity was more frequently reported on PANs than CBCTs by one examiner (p = 0.001 and p = 0.168). Both PANs and CBCTs had moderate to substantial intra-examiner, within-radiograph-type reliability with Kappa values of 0.686–0.79 for PANs, and 0.661 for CBCTs (p < 0.001). Inter-examiner and inter-radiograph-type Kappa values ranged from 0.414 to 0.51 (p < 0.001). Using CBCT decisions as a reference, 78.9% of PAN decisions were coincident, 9.3% would have been repositioned on CBCT but not on PAN, 11.3% would not have been repositioned on CBCT but were on PAN, and 0.3% would have been repositioned in the opposite direction on CBCT versus PAN. Additionally, CBCT images required more time per tooth to assess than PANs (p < 0.001).

Conclusions
PAN-based clinical decisions regarding root angulation had comparable statistical reliability and substantial agreement with CBCT-based clinical decisions.
Cost-effectiveness analysis of ranibizumab for retinal vein occlusion patients in China from the societal perspective
Authors: Ni Weiyi , Liu Jia , Jiang Yawen , Wu Jing 
Published: May 2021

Abstract
Background
Clinical trials in China have demonstrated that ranibizumab can improve the clinical outcomes of branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). However, no economic evaluation of ranibizumab has been conducted among Chinese patient population.

Methods
To provide insights into the economic profile of ranibizumab among Chinese RVO population, a Markov state-transition model was used to predict the outcomes of ranibizumab comparing to laser photocoagulation and observational-only care from the societal perspective. This model simulated changes in patient visuality, quality-adjusted of life years (QALY), medical costs, and direct non-medical costs of individuals with visual impairment due to BRVO or CRVO in lifetime. The base-case analysis used an annual discount rate of 5% for costs and benefits following the China Guidelines for Pharmacoeconomic Evaluations. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model.

Results
The base-case incremental cost-effectiveness ratio (ICER) comparing ranibizumab to laser photocoagulation was ¥65,008/QALY among BRVO patients and was ¥65,815/QALY among CRVO patients, respectively. Comparing to the 2019 gross domestic product (GDP) per capita of ¥71,000, both two ICERs were far below the cost-effective threshold at three times of GDP per capita (¥213,000). The deterministic and probabilistic sensitivity analyses demonstrated the base-case results were robust in most of the simulation scenarios.

Conclusion
The current Markov model demonstrated that ranibizumab may be cost-effective compared with laser photocoagulation to treat BRVO and cost-effective compared to observation-only care to treat CRVO in China from the societal perspective.
Prediabetes and risk of heart failure: the link grows stronger
Authors: Wu Jian-di , Liang Dong-liang , Xie Yue 
Published: May 2021

AbstractIn a recently published paper in Cardiovascular Diabetology, Sinha et al. (Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project. Cardiovasc Diabetol. 2021;20(1):66) reported that prediabetes (defined as a fasting plasma glucose concentration of 100–125 mg/dL) was associated with a higher lifetime risk of heart failure in middle-aged White adults and Black women, with the association attenuating in older Black women. This study provides important evidence that the risk of heart failure is increased in people with a fasting plasma glucose concentration as low as 100 mg/dL, supporting the definition of prediabetes according to the American Diabetes Association guideline. The study also strongly supports the notion that prediabetes should be regarded not only as a high-risk state for the development of diabetes but also as a risk factor for cardiovascular morbidity.
Exoskeleton-assisted walking improves pulmonary function and walking parameters among individuals with spinal cord injury: a randomized controlled pilot study
Authors: Xiang Xiao-Na , Zong Hui-Yan , Ou Yi , Yu Xi , Cheng Hong , Du Chun-Ping , He Hong-Chen 
Published: May 2021

AbstractBackgroundExoskeleton-assisted walking (EAW) is expected to improve the gait of spinal cord injury (SCI) individuals. However, few studies reported the changes of pulmonary function (PF) parameters after EAW trainings. Hence, we aimed to explore the effect of EAW on PF parameters, 6-min walk test (6MWT) and lower extremity motor score (LEMS) in individuals with SCI and to compare those with conventional trainings.MethodsIn this prospective, single-center, single-blinded randomized controlled pilot study, 18 SCI participants were randomized into the EAW group (n = 9) and conventional group (n = 9) and received 16 sessions of 50–60 min training (4 days/week, 4 weeks). Pulmonary function parameters consisting of the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow (FEF), peak expiratory flow, and maximal voluntary ventilation, 6MWT with assisted devices and LEMS were reported pre- and post-training.ResultsValues of FVC (p = 0.041), predicted FVC% (p = 0.012) and FEV1(p = 0.013) were significantly greater in EAW group (FVC: 3.8 ± 1.1 L; FVC%pred = 94.1 ± 24.5%; FEV1: 3.5 ± 1.0 L) compared with conventional group (FVC: 2.8 ± 0.8 L; FVC%pred = 65.4 ± 17.6%; FEV1: 2.4 ± 0.6 L) after training. Participants in EAW group completed 6MWT with median 17.3 m while wearing the exoskeleton. There was no difference in LEMS and no adverse event.ConclusionsThe current results suggest that EAW has potential benefits to facilitate PF parameters among individuals with lower thoracic neurological level of SCI compared with conventional trainings. Additionally, robotic exoskeleton helped walking.Trial registration: Registered on 22 May 2020 at Chinese Clinical Trial Registry (ChiCTR2000033166).http://www.chictr.org.cn/edit.aspx?pid=53920&htm=4.