bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with a malaria outbreak at Tongogara refugee camp in Chipinge District, Zimbabwe, 2021: a case–control study
Authors: Takarinda Kudzai Patience , Nyadundu Simon , Govha Emmanuel , Gombe Notion Tafara , Chadambuka Addmore , Juru Tsitsi , Tshimanga Mufuta 
Published: March 2022

Abstract
Background
Malaria is a leading cause of morbidity and mortality among forcibly displaced populations, including refugees, approximately two-thirds of whom reside in malaria endemic regions. Data from the rapid disease notification system (RDNS) reports for Manicaland Province in Zimbabwe showed that despite implementation of malaria control initiatives, there was an increase in number of malaria cases above action thresholds at Tongogara refugee camp in Chipinge district during weeks 12–14 of 2021. An investigation that described the outbreak by person, place and time was conducted. Malaria emergency preparedness, response, and appropriateness of case management were assessed. The factors associated with contracting malaria were determined to enable the formulation of appropriate interventions, establish control, and prevent future malaria outbreaks among this vulnerable population.

Methods
A 1:1 unmatched case–control study involving 80 cases and 80 controls was conducted using interviewer-administered questionnaires at household level. Data was entered into Epi Data version 3.1 and quantitative analysis was done using Epi Info™ version 7.2.2.6 to generate medians, proportions, odds ratios and their 95% confidence intervals.

Results
Malaria cases were distributed throughout the 10 residential sections within Tongogara refugee camp, the majority being from section 7, 28 (35%). Despite constituting 11% of the total population, Mozambican nationals accounted for 36 (45%) cases. Males constituted 47 (59%) among cases which was comparable to controls 43 (54%), p = 0.524. The median age for cases was 15 years [Interquartile range (IQR), 9–26] comparable to controls, which was 17 years (IQR, 10–30) (p = 0.755). Several natural and man-made potential vector breeding sites were observed around the camp. Risk factors associated with contracting malaria were engaging in outdoor activities at night [AOR = 2.74 (95% CI 1.04–7.22), wearing clothes that do not cover the whole body during outdoor activities [AOR 4.26 (95% CI, 1.43–12.68)], while residing in a refugee housing unit reduced the risk of contracting malaria [AOR = 0.18 (CI, 0.06–0.55)].

Conclusions
The malaria outbreak at Tongogara refugee camp reemphasizes the role of behavioural factors in malaria transmission. Intensified health education to address human behaviours that expose residents to malaria, habitat modification, and larviciding to eliminate mosquito breeding sites were recommended.
The ecdysone receptor regulates several key physiological factors in Anopheles funestus
Authors: Maharaj Surina , Ekoka Elodie , Erlank Erica , Nardini Luisa , Reader Janette , Birkholtz Lyn-Marie , Koekemoer Lizette L. 
Published: March 2022

Abstract
Background
Malaria is a devastating disease, transmitted by female Anopheles mosquitoes infected with Plasmodium parasites. Current insecticide-based strategies exist to control the spread of malaria by targeting vectors. However, the increase in insecticide resistance in vector populations hinder the efficacy of these methods. It is, therefore, essential to develop novel vector control methods that efficiently target transmission reducing factors such as vector density and competence. A possible vector control candidate gene, the ecdysone receptor, regulates longevity, reproduction, immunity and other physiological processes in several insects, including malaria vectors. Anopheles funestus is a prominent vector in sub-Saharan Africa, however, the function of the ecdysone receptor in this mosquito has not previously been studied. This study aimed to determine if the ecdysone receptor depletion impacts An. funestus longevity, reproduction and susceptibility to Plasmodium falciparum infection.

Methods
RNA interference was used to reduce ecdysone receptor expression levels in An. funestus females and investigate how the above-mentioned phenotypes are influenced. Additionally, the expression levels of the ecdysone receptor, and reproduction genes lipophorin and vitellogenin receptor as well as the immune gene, leucine rich immune molecule 9 were determined in ecdysone receptor-depleted mosquitoes using quantitative polymerase chain reaction.

Results
Ecdysone receptor-depleted mosquitoes had a shorter lifespan, impaired oogenesis, were less fertile, and had reduced P. falciparum infection intensity.

Conclusions
Overall, this study provides the first experimental evidence that supports ecdysone receptor as a potential target in the development of vector control measures targeting An. funestus.
Comparing the use of conventional and three-dimensional printing (3DP) in mandibular reconstruction
Authors: Truscott Ailis , Zamani Reza , Akrami Mohammad 
Published: March 2022

Abstract
Background
There are a number of clinical disorders that require mandibular reconstruction (MR). Novel three-dimensional (3D) printing technology enables reconstructions to be more accurate and beneficial to the patient. However, there is currently no evidence identifying which techniques are better suited for MR, based on the type of clinical disorder the patient has. In this study, we aim to compare 3D techniques with conventional techniques to identify how best to reconstruct the mandible based on the clinical cause that necessitates the reconstructive procedure: cancerous or benign tumours, clinical disorders, infection or disease and trauma or injury.

Methods
PubMed, Scopus, Embase and Medline were searched to identify relevant papers that outline the clinical differences between 3D and conventional techniques in MR. Data were evaluated to provide a clear outline of suitable techniques for surgery.

Results
20 of 2749 papers met inclusion criteria. These papers were grouped based on the clinical causes that required MR into four categories: malignant or benign tumour resection; mandibular trauma/injury and other clinical disorders.

Conclusions
The majority of researchers favoured 3D techniques in MR. However, due to a lack of standardised reporting in these studies it was not possible to determine which specific techniques were better for which clinical presentations.
H2O2-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs
Authors: Chen Youlu , Chen Zuoguan , Duan Jianwei , Gui Liang , Li Huiyang , Liang Xiaoyu , Tian Xinxin , Liu Kaijing , Li Yongjun , Yang Jing 
Published: March 2022

AbstractPeripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs.
Graphical Abstract
Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing
Authors: Xia Wenzheng , Li Minxiong , Jiang Xingyu , Huang Xin , Gu Shuchen , Ye Jiaqi , Zhu Liaoxiang , Hou Meng , Zan Tao 
Published: March 2022

AbstractAged skin wounds heal poorly, resulting in medical, economic, and social burdens posed by nonhealing wounds. Age-related defects in repair are associated with reduced myofibroblasts and dysfunctional extracellular matrix (ECM) deposition. Bidirectional cell-cell communication involving exosome-borne cargo such as micro RNAs (miRs) has emerged as a critical mechanism for wound healing and aged tissue regeneration. Here we report that at the wound edge, aged fibroblasts display reduced migration and differentiation into myofibroblasts, with impaired ECM deposition, when compared with young tissue. Proper activation of fibroblasts to myofibroblasts may alleviate age-related defects in wound healing. Herein, an exosome-guided cell technique was performed to induce effective wound healing. Supplementing wounds with exosomes isolated from young mouse wound-edge fibroblasts (exosomesYoung) significantly improved the abundance of myofibroblasts and wound healing in aged mice and caused fibroblasts to migrate and transition to myofibroblasts in vitro. To determine the underlying mechanism, we found that exosomal transfer of miR-125b to fibroblasts inhibited sirtuin 7 (Sirt7), thus accelerating myofibroblast differentiation and wound healing in aged mice. Notably, after epidermal inhibition of miR-125b or overexpression of Sirt7 in fibroblasts, migration and myofibroblast transition were perturbed. Our findings thus reveal that miR-125b is transferred through exosomes from young fibroblasts to old fibroblasts contributes to promoting fibroblast migration and transition to counteract aging, suggesting a potential avenue for anti-aging interventions in wound healing.
Graphical Abstract
Using qualitative research to develop an elaboration of the TIDieR checklist for interventions to enhance vaccination communication: short report
Authors: Glenton Claire , Carlsen Benedicte , Winje Brita Askeland , Eilers Renske , Wennekes Manuela Dominique , Hoffmann Tammy C. , Lewin Simon ,   The VITAL Consortium
Published: March 2022

Abstract
Background
The COVID-19 pandemic has led to an increased interest in communication with the public regarding vaccination. Our recent Cochrane qualitative evidence synthesis points to several factors that could influence the implementation and success of healthcare worker communication with older adults about vaccination. However, it is often difficult to assess whether factors identified as potentially important in qualitative studies have been considered in randomized trials because of poor trial reporting. We therefore decided to use our qualitative evidence synthesis findings to encourage better reporting of vaccination communication interventions in trials by developing an elaboration of the TIDieR (Template for Intervention Description and Replication) checklist for intervention reporting.

Methods
We examined the findings from our Cochrane qualitative evidence synthesis on healthcare workers’ perceptions of and experiences with communicating about vaccination with adults over the age of 50 years. We identified factors that could influence the implementation and uptake, and thereby the effectiveness, of vaccination communication interventions. We then drafted a list of the information elements we would need from trial reports to assess whether these factors had been considered in the development of the interventions evaluated in these trials. Finally, we compared our list of information elements to the TIDieR checklist items. We were able to align all of our information elements with the TIDieR items. However, for several of the TIDieR items, we developed a more detailed description to ensure that relevant information would be captured sufficiently in trial reports.

Results
We developed elaborations for the following TIDieR items: “Why” (item 2), “What—materials” (item 3), “Who provided” (item 5), “How” (item 6), “Where” (item 7) and “Tailoring” (item 9).

Conclusions
Both qualitative research and trials of intervention effectiveness are critical to furthering our understanding of what works, where, for whom and through which mechanisms. However, a key ingredient for developing this understanding is adequate reporting of intervention design, content and implementation in randomized trials. We hope that this elaboration of the TIDier checklist will improve reporting of interventions in trials focused on vaccine communication with older adults, and thereby enhance the usability of this research for developing future communication strategies.
METTL14-mediated N6-methyladenosine modification of ITGB4 mRNA inhibits metastasis of clear cell renal cell carcinoma
Authors: Liu Zhuonan , Sun Tianshui , Piao Chiyuan , Zhang Zhe , Kong Chuize 
Published: March 2022

Abstract
Background
Integrin β4 (ITGB4) participates in tumorigenesis and progression of several malignancies, but its role and related mechanisms in clear cell renal cell carcinoma (ccRCC) remain unclear.

Methods
Quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry were used to detect mRNA and protein levels of relevant genes. Biological functions of ITGB4 and methyltransferase-like 14 (METTL14) were determined by in vitro and in vivo experiments. The levels of N6-methyladenosine (m6A) in ccRCC tissues and adjacent normal tissues were calculated via total RNA m6A quantification assay. The m6A modification of ITGB4 was demonstrated via m6A RNA immunoprecipitation (MeRIP), RIP and luciferase reporter assays.

Results
ITGB4 was significantly overexpressed in ccRCC tissues and high level of ITGB4 predicted poor prognosis as well as metastasis. Functionally, ITGB4 stimulated ccRCC cell migration and invasion in vitro and metastasis in vivo with epithelial–mesenchymal transition (EMT) strengthened. Mechanically, the total levels of m6A were reduced in ccRCC tissues. METTL14, a favorable factor for ccRCC patients’ prognosis, facilitated m6A modification on ITGB4 3′UTR and subsequently accelerated ITGB4 mRNA degradation, leading to its declined expression. Furthermore, the METTL14-mediated inhibition of ITGB4 expression was dependent on the YTH domain family protein 2 (YTHDF2), which acted as an m6A reader to bind to ITGB4 mRNA and to promote its decay. In addition, we demonstrated that knockdown of METTL14 promoted ccRCC cell migration, invasiveness and metastasis as well as stimulating the EMT process and the PI3K/AKT signal by overexpressing ITGB4.

Conclusion
Our study reveals that METTL14 inhibits ITGB4 expression via m6A modification to attenuate metastasis and EMT of ccRCC cells, suggesting the METTL14/ITGB4 axis as a potential prognostic biomarker and therapeutic target for ccRCC.
Combination of artesunate and WNT974 induces KRAS protein degradation by upregulating E3 ligase ANACP2 and β-TrCP in the ubiquitin–proteasome pathway
Authors: Gong Rui-Hong , Chen Minting , Huang Chunhua , Wong Hoi Leong Xavier , Kwan Hiu Yee , Bian Zhaoxiang 
Published: March 2022

Abstract
Background
KRAS mutation is one of the dominant gene mutations in colorectal cancer (CRC). Up to present, targeting KRAS for CRC treatment remains a clinical challenge. WNT974 (LGK974) is a porcupine inhibitor that interferes Wnt signaling pathway. Artesunate (ART) is a water-soluble semi-synthetic derivative of artemisinin.

Methods
The synergistic effect of ART and WNT974 combination in reducing CRC cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RT-PCR was utilized for the mRNA levels of KRAS, CUL7, ANAPC2, UBE2M, RNF123, SYVN1, or β-TrCP. Western blot assay was utilized for the protein levels of NRAS, HRAS, KRAS, ANAPC2, β-TrCP, GSK-3β, p-Akt (Ser473), t-Akt, p-PI3K (Tyr458), t-PI3K, p-mTOR (Ser2448), t-mTOR. Xenograft mouse model assay was performed for the anti-CRC effect of combination of ART and WNT974 in vivo. IHC assay was utilized for the levels of KRAS, β-TrCP, GSK-3β or ANAPC2 in tumor tissues.

Results
Our study shows that the combination of WNT974 and ART exhibits synergistic effect in reducing CRC growth. The combination treatment significantly reduces KRAS protein level and activity in CRC cells. Interestingly, the combination treatment increases E3 ligases ANAPC2 expression. Our data show that overexpression of ANAPC2 significantly reduces KRAS protein levels, which is reversed by MG132. Knockdown of ANAPC2 in CRC abolishes the combination treatment-reduce KRAS expression. Besides, the treatment also increases the expressions of GSK-3β and E3 ligase β-TrCP that is known to degrade GSK-3β-phosphorylated KRAS protein. Knockdown of β-TrCP- and inhibition of GSK-3β abolish the combination treatment-induce KRAS ubiquitination and reduction in expression. Last but not least, combination treatment suppresses PI3K/Akt/m-TOR signaling pathway.

Conclusions
Our data clearly show that the combination treatment significantly enhances KRAS protein degradation via the ubiquitination ubiquitin–proteasome pathway, which is also demonstrated in xenograft mouse model. The study provides strong scientific evidence for the development of the combination of WNT974 and ART as KRAS-targeting therapeutics for CRC treatment.
Weight outcomes of NU-HOME: a randomized controlled trial to prevent obesity among rural children
Authors: Fulkerson Jayne A. , Horning Melissa , Barr-Anderson Daheia J. , Sidebottom Abbey , Linde Jennifer A. , Lindberg Rebecca , Friend Sarah , Beaudette Jennifer , Flattum Colleen , Freese Rebecca L. 
Published: March 2022

Abstract
Background
Rural children are at greater obesity risk than their urban peers. The NU-HOME study is an innovative collaborative effort to prevent childhood obesity in rural communities. Weight outcomes of the NU-HOME study, a family-meal focused randomized controlled trial (RCT) are described. We hypothesized that compared to control group children, intervention group children would have significantly lower weight-related post-intervention (PI) outcomes.

Methods
Participants were 114 dyads (7–10 year-old rural children and a parent). In 2017–2018 and 2018–2019, research staff measured height, weight and body fat at baseline (BL) and PI. Families were randomized to intervention (n = 58) or control (n = 56) groups without blinding. Designed with Social Cognitive Theory and community engagement, the NU-HOME program included seven monthly sessions delivered in community settings and four goal-setting calls. The program engaged entire families to improve healthy eating, physical activity, family meals and the home food environment. Multiple linear and logistic regression models tested PI outcomes of child BMIz-score, percent body fat, percent over 50th percentile BMI, and overweight/obesity status by treatment group, adjusted for BL values and demographics (n = 102).

Results
No statistically significant intervention effects were seen for child BMIz or overweight/obesity status. However, a promising reduction in boys’ percent body fat (− 2.1, 95% CI [− 4.84, 0.63]) was associated with the intervention.

Conclusions
Although our findings were in the hypothesized direction, making significant impacts on weight-related outcomes remains challenging in community trials. Comprehensive family-focused programming may require intensive multi-pronged interventions to mitigate complex factors associated with excess weight gain.

Clinical trial registration
This study is registered with NIH ClinicalTrials.gov: NCT02973815.
Television viewing time and all-cause mortality: interactions with BMI, physical activity, smoking, and dietary factors
Authors: Swain Christopher T. V. , Bassett Julie K. , Hodge Allison M. , Dunstan David W. , Owen Neville , Yang Yi , Jayasekara Harindra , Hébert James R. , Shivappa Nitin , MacInnis Robert J. , Milne Roger L. , English Dallas R. , Lynch Brigid M. 
Published: March 2022

Abstract
Background
Higher levels of time spent sitting (sedentary behavior) contribute to adverse health outcomes, including earlier death. This effect may be modified by other lifestyle factors. We examined the association of television viewing (TV), a common leisure-time sedentary behavior, with all-cause mortality, and whether this is modified by body mass index (BMI), physical activity, smoking, alcohol intake, soft drink consumption, or diet-associated inflammation.

Methods
Using data from participants in the Melbourne Collaborative Cohort Study, flexible parametric survival models assessed the time-dependent association of self-reported TV time (three categories: < 2 h/day, 2–3 h/day, > 3 h/day) with all-cause mortality. Interaction terms were fitted to test whether there was effect modification of TV time by the other risk factors.

Results
From 19,570 participants, 4,417 deaths were reported over a median follow up of 14.5 years. More TV time was associated with earlier mortality; however, this relationship diminished with increasing age. The hazard ratio (HR) and 95% confidence interval (95% CI) for > 3 h/day compared with < 2 h/day of TV time was 1.34 (1.16, 1.55) at 70 years, 1.14 (1.04, 1.23) at 80 years, and 0.95 (0.84, 1.06) at 90 years. The TV time/mortality relationship was more evident in participants who were physically inactive (compared with active; p for interaction < 0.01) or had a higher dietary inflammatory index score (compared with a lower score; p for interaction = 0.03). No interactions were detected between TV time and BMI, smoking, alcohol intake, nor soft-drink consumption (all p for interaction > 0.16).

Conclusions
The relationship between TV time and all-cause mortality may change with age. It may also be more pronounced in those who are otherwise inactive or who have a pro-inflammatory diet.