bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials
Authors: Patson Noel , Mukaka Mavuto , Otwombe Kennedy N. , Kazembe Lawrence , Mathanga Don P. , Mwapasa Victor , Kabaghe Alinune N. , Eijkemans Marinus J. C. , Laufer Miriam K. , Chirwa Tobias 
Published: March 2020

Abstract
Background
Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy.

Methods
The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019.

Results
Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n = 18, 100%) and mean/median (n = 2, 11.1%). Results presentation included tabular (n = 16, 88.9%) and text description (n = 2, 11.1%). Univariate inferential methods were reported in most trials (n = 16, 88.9%); including Chi square/Fisher’s exact test (n = 12, 66.7%), t test (n = 2, 11.1%) and Mann–Whitney/Wilcoxon test (n = 1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n = 3, 16.7%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n = 7, 38.9%).

Conclusion
The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.
Economic valuation of health benefits from using geologic data to communicate radon risk potential
Authors: Chiavacci Scott J. , Shapiro Carl D. , Pindilli Emily J. , Casey Clyde F. , Rayens Mary Kay , Wiggins Amanda T. , Andrews William M. , Hahn Ellen J. 
Published: March 2020

Abstract
Background
Radon exposure is the second leading cause of lung cancer worldwide and represents a major health concern within and outside the United States. Mitigating exposure to radon is especially critical in places with high rates of tobacco smoking (e.g., Kentucky, USA), as radon-induced lung cancer is markedly greater among people exposed to tobacco smoke. Despite homes being a common source of radon exposure, convincing homeowners to test and mitigate for radon remains a challenge. A new communication strategy to increase radon testing among Kentucky homeowners utilizes fine-scale geologic map data to create detailed radon risk potential maps. We assessed the health benefits of this strategy via avoided lung cancer and associated premature mortality and quantified the economic value of these benefits to indicate the potential utility of using geologic map data in radon communication strategies.

Methods
We estimated the change in radon testing among all 120 counties in Kentucky following a new communication strategy reliant on geologic maps. We approximated the resultant potential change in radon mitigation rates and subsequent expected lung cancer cases and mortality avoided among smokers and non-smokers exposed to 4 pCi/L of radon in the home. We then applied the value of a statistical life to derive the economic value of the expected avoided mortality.

Results
The new communication strategy is estimated to help 75 Kentucky residents in 1 year avoid exposure to harmful radon levels via increased testing and mitigation rates. This equated to the potential avoidance of approximately one premature death due to lung cancer, with a net present value of $3.4 to $8.5 million (2016 USD).

Conclusions
Our analysis illustrates the potential economic value of health benefits associated with geologic map data used as part of a communication strategy conveying radon risk to the public. Geologic map data are freely available in varying resolutions throughout the United States, suggesting Kentucky’s radon communication strategy using geologic maps can be employed in other states to educate the public about radon. As this is only a single application, in a single state, the economic and health benefits of geologic map data in educating the public about radon are likely to exceed our estimates.
Recent changes in the Dutch foodscape: socioeconomic and urban-rural differences
Authors: Pinho Maria Gabriela M. , Mackenbach Joreintje D. , den Braver Nicole R. , Beulens Joline J. W. , Brug Johannes , Lakerveld Jeroen 
Published: March 2020

Abstract
Background
Obesogenic food environments may influence dietary behaviours and contribute to obesity. Few countries quantified changes in their foodscape. We explored how the availability of different types of food retailers has changed in the Netherlands across levels of neighbourhood socioeconomic status (SES) and urbanisation.

Methods
This longitudinal ecological study conducted in the Netherlands had as unit of analysis administrative neighbourhoods. From 2004 to 2018, the geographic location and type of each food retailer were objectively assessed by a commercial company. Food retailers were categorised as local food shops, fast food restaurants, food delivery, restaurants, supermarkets, and convenience stores. Information on neighbourhood SES and urbanisation was obtained from Central Bureau of Statistics (CBS). To test the change in the counts of food retailers we used negative binomial generalized estimating equations (GEE), with neighbourhoods as the group variable, time as the independent variable and the counts of each type of food retailer as outcome. To account for changes in population density, analyses were adjusted for the number of inhabitants per neighbourhood. We tested effect modification by adding an interaction term for neighbourhood SES and urbanisation to the models.

Results
In Dutch neighbourhoods between 2004 and 2018, a 120 and 35% increase was found in the count of food delivery outlets and restaurants, respectively, and a 24% decrease in count of local food shops. Stratified analyses showed an increase in the availability of supermarkets and convenience stores in the more urbanised and lower SES neighbourhoods, while a decrease was observed in the less urbanised and higher SES neighbourhoods.

Conclusions
We observed considerable changes in the Dutch foodscape. Over a 14 years period, the foodscape changed towards a higher availability of food retailers offering convenience and ready-to-eat foods. These findings can help policy makers aiming to promote a healthier food environment and obesity prevention.
The self-organization model reveals systematic characteristics of aging
Authors: Wang Yin , Huang Tao , Li Yixue , Sha Xianzheng 
Published: March 2020

AbstractBackgroundAging is a fundamental biological process, where key bio-markers interact with each other and synergistically regulate the aging process. Thus aging dysfunction will induce many disorders. Finding aging markers and re-constructing networks based on multi-omics data (i.e. methylation, transcriptional and so on) are informative to study the aging process. However, optimizing the model to predict aging have not been performed systemically, although it is critical to identify potential molecular mechanism of aging related diseases.MethodsThis paper aims to model the aging self-organization system using a series of supervised learning methods, and study complex molecular mechanisms of aging at system level: i.e. optimizing the aging network; summarizing interactions between aging markers; accumulating patterns of aging markers within module; finding order-parameters in the aging self-organization system.ResultsIn this work, the normal aging process is modeled based on multi-omics profiles across different tissues. In addition, the computational pipeline aims to model aging self-organizing systems and study the relationship between aging and related diseases (i.e. cancers), thus provide useful indicators of aging related diseases and could help to improve prediction abilities of diagnostics.ConclusionsThe aging process could be studied thoroughly by modelling the self-organization system, where key functions and the crosstalk between aging and cancers were identified.
A qualitative exploration of the experiences of community health animation on malaria control in rural Malawi
Authors: Malenga Tumaini , Griffiths Frances E. , van den Berg Marrit , van den Berg Henk , van Vugt Michèle , Phiri Kamija Samuel , Manda-Taylor Lucinda , Umar Eric 
Published: March 2020

Abstract
Background
While great strides have been achieved in fighting malaria through the Roll Back Malaria (RBM) strategy, the recent world malaria report shows an increase in malaria-related deaths compared to previous years. Malaria control tools are efficacious and effective in preventing the disease; however, the human behaviour aspect of the intervention strategies is weak due to heavy reliance on positive human health behaviour. The challenge lies in adoption of control interventions by the target population which, to an extent, may include access to prevention and treatment tools. We present a qualitative assessment of the use of the Health Animator (HA) model for Information, Education and Communication (IEC) to improve adoption and use of malaria control by promoting positive health behaviours.

Results
We conducted 3 Focus Group Discussions (FGDs) and 23 individual in-depth interviews (IDIs) with HAs. Each FGD consisted of 8 participants. Data was analysed using QSR International NVivo 10 software. There are four main themes emerging regarding HA experiences. The perceptions include; collaborative work experience, personal motivation and growth, community participation with health animation and challenges with implementation. Results suggest that HAs were pleased with the training as they gained new information regarding malaria, which affected their use of malaria control interventions within their families. Knowledge was well assimilated from the trainings and influenced personal growth in becoming a community leader. Support from the leadership within the village and the health system was important in legitimising the main messages. The community responded positively to the workshops valued the information imparted. The voluntary nature of the work in a poverty-stricken community affected sustainability.

Conclusions
There is need to empower communities with strategies within their reach. Functioning traditional social support structures are a crucial element in sustainability. Voluntarism is also key for sustainability, especially for rural and remote communities with limited sources of income.
Mobile-bearing insert used with total knee arthroplasty does not rotate on the tibial tray during a squatting activity: a cross-sectional study
Authors: Hoshi Kenji , Watanabe Goro , Kurose Yasuo , Tanaka Ryuji , Fujii Jiro , Gamada Kazuyoshi 
Published: March 2020

Abstract
Background
Total knee arthroplasty (TKA) is commonly performed around the world. Implant designs include fixed-bearing and mobile-bearing. Mobile-bearing design was developed as a rotating platform that allows axial rotation of the insert around the longitudinal axis. This phenomenon may limit full exploitation of the characteristics of the mobile-bearing insert, which may cause wearing and reduce longevity. However, there is limited knowledge on rotational behavior of the polyethylene mobile-bearing insert under weight-bearing conditions. We aimed at determining the rotational motion of each component at full extension and flexed positions during a squatting activity after TKA.

Methods
This study was a cross-sectional study (level 4) involving patients with severe knee osteoarthritis scheduled to receive TKA. We examined 13 knees of 11 patients after mobile-bearing TKA (NexGen LPS-Flex, Zimmer Inc.) at 10 weeks and 1 year postoperatively. Four identical metallic beads were embedded into the insert. Wide-base squatting was chosen for analyses. Three-dimensional in vivo poses of the prostheses were created using a 3D-to-2D registration technique. During flexion, rotation of the femoral component relative to the insert (FEM/INS) and tibial component (FEM/TIB) as well as insert rotation relative to the tibial component (INS/TIB) were computed. Repeated measure 2-way ANOVA and post hoc test was used.

Results
In the fully extended position, FEM/INS was significantly smaller than INS/TIB both at 10 weeks (− 0.3° vs. 6.3°, p = .013) and 1 year (− 0.8° vs. 4.9°, p = .011), respectively. During the squatting activity, rotation motions of FEM/TIB, FEM/INS, INS/TIB were 5.7°, 5.9°, and 1.8° at 10 weeks and 6.3°, 5.5°, and 1.6° at 1 year, respectively. Rotation motion of FEM/INS was significantly greater than that of INS/TIB at both 10 weeks (p < .001) and 1 year (p < .001).

Conclusions
The mobile-bearing insert enhances the compatibility of FEM/INS in extension; the amount of INS/TIB rotation is significantly smaller than that of FEM/INS during a squatting activity. This information will inform surgeons to take caution to perform TKA with a fixed insert in which 6.3° of rotational offset would be added to the rotational alignment at FEM/INS at full extension.

Trial registration
UMIN-CTR, UMIN000024196. Retrospectively registered on 9 September 2016.
Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells—first phase I/II human clinical study
Authors: Hertegård Stellan , Nagubothu Srinivasa Rau , Malmström Emma , LeBlanc Katarina 
Published: March 2020

Abstract
Background
Vocal fold (VF) scarring, caused by surgery or inflammation, often results in severe voice problems or aphonia. Effective lasting treatment is lacking. Previous in vitro and in vivo animal studies reported positive effects on VF scar resolution with mesenchymal stromal cell (MSC) implantation. The principal aim of this study was to examine safety aspects and secondly treatment efficacy vocal fold function in patients with VF scarring and severe voice problems.

Methods
In this open-label phase I/II study, 16 patients were treated with surgical scar resection followed by injection of autologous MSCs (0.5–2 × 106 MSCs/patient). Patients were monitored 1 year for serious adverse events (SAE) or minor complications. Therapeutic efficacy on treated VFs was evaluated by measurement of VF vibrations using high-speed laryngoscopy (HSL) and phonation pressure threshold (PTP) for elasticity and VF function. Patients self-reported voice change using the Voice Handicap Index (VHI).

Results
No SAE or minor side effects were reported. Video ratings of VF vibrations and digitized analysis of HSL and PTP were significantly improved for 62–75% of the patients (depending on parameter). Two patients showed deteriorated VF vibrations, but improved PTP. VHI was significantly improved in 8 patients, with the remaining experiencing no significant change.

Conclusions
The results indicate that local injection of autologous MSC into scarred VFs with severe voice problems may offer a safe and feasible therapeutic option. VF vibration and elasticity were improved in approximately two thirds of treated patients.
This clinical study is registered in clinicaltrials.gov (ID: NCT01981330). Retrospective registration of first patient (20130511). https//: register.clinicaltrials.gov/.
Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model
Authors: Yang Yanhua , Pan Qi , Zou Kaijie , Wang Haixing , Zhang Xiaoting , Yang Zhengmeng , Lee Wayne Yuk Wai , Wei Bo , Gu Weidong , Yang Yunzhi Peter , Lin Sien , Li Gang 
Published: March 2020

Abstract
Background
Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO.

Methods
Unilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1β. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology.

Results
The number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates.

Conclusion
This study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation.
Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats
Authors: Ishiuchi Naoki , Nakashima Ayumu , Doi Shigehiro , Yoshida Ken , Maeda Satoshi , Kanai Ryo , Yamada Yumi , Ike Takeshi , Doi Toshiki , Kato Yukio , Masaki Takao 
Published: March 2020

AbstractBackgroundMesenchymal stem cells (MSCs) have been reported to promote the regeneration of injured tissue via their paracrine abilities, which are enhanced by hypoxic preconditioning. In this study, we examined the therapeutic efficacy of hypoxia-preconditioned MSCs on renal fibrosis and inflammation in rats with ischemia-reperfusion injury (IRI).MethodsMSCs derived from rats and humans were incubated in 1% O2conditions (1%O2MSCs) for 24 h. After IRI, 1%O2MSCs or MSCs cultured under normoxic conditions (21%O2MSCs) were injected through the abdominal aorta. At 7 or 21 days post-injection, the rats were sacrificed and their kidneys were analyzed. In in vitro experiments, we examined whether 1%O2MSCs enhanced the ability to produce anti-fibrotic humoral factors using transforming growth factor (TGF)-β1-stimulated HK-2 cells incubated with conditioned medium from MSCs.ResultsAdministration of rat 1%O2MSCs (1%O2rMSCs) attenuated renal fibrosis and inflammation more significantly than rat 21%O2MSCs. Notably, human 1%O2MSCs (1%O2hMSCs) also attenuated renal fibrosis to the same extent as 1%O2rMSCs. Flow cytometry showed that 1%O2hMSCs did not change human leukocyte antigen expression. Further in vitro experiments revealed that conditioned medium from 1%O2MSCs further suppressed TGF-β1-induced fibrotic changes in HK-2 cells compared with 21%O2MSCs. Hypoxic preconditioning enhanced vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) secretion. Interestingly, VEGF knockdown in 1%O2MSCs attenuated HGF secretion and the inhibition of TGF-β1-induced fibrotic changes in HK-2 cells. In addition, VEGF knockdown in 1%O2hMSCs reduced the anti-fibrotic effect in IRI rats.ConclusionsOur results indicate that hypoxia-preconditioned MSCs are useful as an allogeneic transplantation cell therapy to prevent renal fibrosis and inflammation.
Functional diversity and abundance of nitrogen cycle-related genes in paddy soil
Authors: Khanal Anamika , Lee Ji-Hoon 
Published: March 2020

AbstractThe nitrogen cycle and the associated microbes play an important role in natural ecosystems, including terrestrial habitats; they also have a major effect on climate change. The aim of this study was to explore microbial communities in rice paddy soil by detecting and quantifying some key functional genes involved in the nitrogen cycle using molecular techniques such as conventional polymerase chain reaction (PCR), clone library construction, sequencing, phylogenetic analysis, and real-time PCR. The genes analyzed were as follows: nitrogenase reductase gene (nifH), hydrazine synthase gene (hzsA), nitrous oxide reductase gene (nosZ), copper-containing (nirK) and cytochrome cd1-containing (nirS) nitrite reductase genes, nitrite oxidoreductase gene (nxrB), and ammonium monooxygenase gene (amoA). The sequence assessment using the clone library targeting these genes revealed high diversity and dominance of bacterial communities. Furthermore, real-time PCR using SYBR green dye and some primers specific for each gene revealed the high abundance of nxrB (4.1 × 109 ± 0.4 × 109 copies g−1 soil) and low abundance of hzsA (4.0 × 105 ± 1.1 × 105 copies g−1 soil). The findings of our study will be useful to explore microbial communities in terrestrial habitats, such as agricultural paddy fields.