bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the feasibility of introducing triple artemisinin-based combination therapy in the malaria treatment policy in Vietnam
Authors: Cao Van Anh Thi , Nguyen Thieu Quang , Le Quyen Duong , Boon Wouter P. C. , Moors Ellen H. M. , Dondorp Arjen M. , de Haan Freek , Amaratunga Chanaki 
Published: October 2023

Abstract
Background
This study investigates the processes regarding changing malaria treatment policies in Vietnam. Moreover, it explores the feasibility of introducing triple artemisinin-based combination therapy (TACT) in Vietnam to support the national malaria control and elimination plan.

Methods
Data were collected via 12 in-depth interviews with key stakeholders, combined with a review of policy documents.

Results
TACT is considered as a useful backup strategy in case future treatment failures with current artemisinin-based combination therapy (ACT) would occur. Moreover, TACT is also considered as a promising strategy to prevent the re-establishment of malaria. However, regulatory procedures and implementation timelines for TACT were expected to be lengthy. Therefore, strategies to engage national decision-makers, regulators, and suppliers should be initiated soon, stipulating the benefits of TACT deployment. In Vietnam, a procedure to apply for an import permit without registration that has previously been applied to the introduction of artesunate-pyronaridine was proposed to accelerate the introduction of TACT. Global-level support through the World Health Organization recommendations and prequalification were considered critical for supporting the introduction of TACT in Vietnam.

Conclusions
Appropriate approach strategies and early stakeholder engagement will be needed to accelerate the introduction of TACT in Vietnam.
Global mosquito observations dashboard (GMOD): creating a user-friendly web interface fueled by citizen science to monitor invasive and vector mosquitoes
Authors: Uelmen Johnny A. , Clark Andrew , Palmer John , Kohler Jared , Van Dyke Landon C. , Low Russanne , Mapes Connor D. , Carney Ryan M. 
Published: October 2023

Abstract
Background
Mosquitoes and the diseases they transmit pose a significant public health threat worldwide, causing more fatalities than any other animal. To effectively combat this issue, there is a need for increased public awareness and mosquito control. However, traditional surveillance programs are time-consuming, expensive, and lack scalability. Fortunately, the widespread availability of mobile devices with high-resolution cameras presents a unique opportunity for mosquito surveillance. In response to this, the Global Mosquito Observations Dashboard (GMOD) was developed as a free, public platform to improve the detection and monitoring of invasive and vector mosquitoes through citizen science participation worldwide.

Methods
GMOD is an interactive web interface that collects and displays mosquito observation and habitat data supplied by four datastreams with data generated by citizen scientists worldwide. By providing information on the locations and times of observations, the platform enables the visualization of mosquito population trends and ranges. It also serves as an educational resource, encouraging collaboration and data sharing. The data acquired and displayed on GMOD is freely available in multiple formats and can be accessed from any device with an internet connection.

Results
Since its launch less than a year ago, GMOD has already proven its value. It has successfully integrated and processed large volumes of real-time data (~ 300,000 observations), offering valuable and actionable insights into mosquito species prevalence, abundance, and potential distributions, as well as engaging citizens in community-based surveillance programs.

Conclusions
GMOD is a cloud-based platform that provides open access to mosquito vector data obtained from citizen science programs. Its user-friendly interface and data filters make it valuable for researchers, mosquito control personnel, and other stakeholders. With its expanding data resources and the potential for machine learning integration, GMOD is poised to support public health initiatives aimed at reducing the spread of mosquito-borne diseases in a cost-effective manner, particularly in regions where traditional surveillance methods are limited. GMOD is continually evolving, with ongoing development of powerful artificial intelligence algorithms to identify mosquito species and other features from submitted data. The future of citizen science holds great promise, and GMOD stands as an exciting initiative in this field.
Superior TRAIL gene expression and cancer cell apoptosis mediated by highly branched-linear poly(β-amino ester)s
Authors: Zhao Yitong , Bo Tao , Wang Chenfei , Yao Dingjin , Pan Chaolan , Xu Weiyi , Zhou Hao , Li Ming , Zhang Si 
Published: October 2023

AbstractExtensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy. H-LPAEs exhibit a more uniform distribution of linear segments and branching units, leading to excellent DNA condensation and favorable physicochemical properties of H-LPAE/DNA polyplexes. In SW1353 and BMSC cells, the optimized H-LPAEs, H-LPAEB4−S5−TMPTA, achieves superior gene transfection efficiency of 58.0% and 33.4%, which were 2.5-fold and 2.0-fold higher than that of the leading commercial gene transfection reagent, Lipofectamine 3000. Excitingly, H-LPAEB4−S5−TMPTA mediated 56.7% and 28.1% cell apoptosis in HepG2 cells and HeLa cells highlighting its potential application in cancer gene therapy. In addition, locally administered H-LPAEB4−S5−TMPTA delivered TRAIL DNA to HepG2 xenograft tumors and inhibited tumor growth in vivo. This study not only proposes a novel strategy for synthesizing poly(β-amino ester)s with a unique branched-linear topology but also identifies a promising candidate for highly efficient TRAIL gene transfection.
Evaluating the risk of endometriosis based on patients’ self-assessment questionnaires
Authors: Zieliński Krystian , Drabczyk Dajana , Kunicki Michał , Drzyzga Damian , Kloska Anna , Rumiński Jacek 
Published: October 2023

Abstract
Background
Endometriosis is a condition that significantly affects the quality of life of about 10 % of reproductive-aged women. It is characterized by the presence of tissue similar to the uterine lining (endometrium) outside the uterus, which can lead lead scarring, adhesions, pain, and fertility issues. While numerous factors associated with endometriosis are documented, a wide range of symptoms may still be undiscovered.

Methods
In this study, we employed machine learning algorithms to predict endometriosis based on the patient symptoms extracted from 13,933 questionnaires. We compared the results of feature selection obtained from various algorithms (i.e., Boruta algorithm, Recursive Feature Selection) with experts’ decisions. As a benchmark model architecture, we utilized a LightGBM algorithm, along with Multivariate Imputation by Chained Equations (MICE) and k-nearest neighbors (KNN), for missing data imputation. Our primary objective was to assess the model’s performance and feature importance compared to existing studies.

Results
We identified the top 20 predictors of endometriosis, uncovering previously overlooked features such as Cesarean section, ovarian cysts, and hernia. Notably, the model’s performance metrics were maximized when utilizing a combination of multiple feature selection methods. Specifically, the final model achieved an area under the receiver operator characteristic curve (AUC) of 0.85 on the training dataset and an AUC of 0.82 on the testing dataset.

Conclusions
The application of machine learning in diagnosing endometriosis has the potential to significantly impact clinical practice, streamlining the diagnostic process and enhancing efficiency. Our questionnaire-based prediction approach empowers individuals with endometriosis to proactively identify potential symptoms, facilitating informed discussions with healthcare professionals about diagnosis and treatment options.
Should additional value elements be included in cost-effectiveness analysis in pharmacoeconomic evaluation: a novel commentary
Authors: Sun Lihua , Li Shiqi , Peng Xiaochen 
Published: October 2023

AbstractIn recent years, international academics recognized that quality-adjusted life-years (QALYs) may not always fully capture the benefits produced by an intervention, and considered incorporating additional elements of value into cost-effectiveness analysis (CEA). Examples of these elements are adherence-improving factors, insurance value, value of hope, and real option value, which form the “value flower”. In order to explore whether it is scientific and reasonable to incorporate additional elements into CEA, this paper focuses on what pharmacoeconomic evaluation should do and what it can do. By elaborating the connotation of value, the connotation of decision, and tracing the origin of pharmacoeconomic evaluation, we believe that it is unscientific and unreasonable to incorporate additional elements of value into CEA, which has exceeded the essential connotation and capability of pharmacoeconomic evaluation. The analysis results belong to the theoretical level, empirical test is needed to verify the correctness and scientificity of this conclusion in the future.
Assessing public health preparedness and response in the European Union- a review of regional simulation exercises and after action reviews
Authors: Utheim Mari Nythun , Gawad Mohamed , Nygård Karin , Macdonald Emily , Falk Monica 
Published: October 2023

Abstract
Background
Improving response capacities in the EU requires a good overview of capacities at both country and Union level. The International Health Regulations (2005) Monitoring and Evaluation framework assesses capacities in countries. It includes semi-quantitative tools such as State Parties Annual Report (SPAR) and Joint External Evaluation (JEE). After Action Reviews (AAR) and Simulation Exercises (SimEx) were included to identify weaknesses in the functionality of capacities which are not addressed bySPAR and JEE. This study presents an analysis of the use of qualitative tools at regional level, in Europe. It aims to identify their added value by comparing them to standardised monitoring tools and lessons learned from COVID-19, and considers ways to improve their use in assessing capacities in the EU.

Methods
We included 17 SimEx and 2 AAR organised by the European Commission between 2005 and 2018. We categorised a total of 357 recommendations according to the IHR (2005) core capacities and to the target audience of the recommendation. We analysed the data using language analysis software. Recommendations to countries were compared to SPAR and JEE indicators. Recommendations to EU agencies were compared to the current mandates of the EU agencies, and to lessons learnt during COVID-19.

Results
Of all extracted recommendations from the exercises, 59% (211/357) targeted EU agencies, 18% (64/357) targeted countries, and 16% (57/357) targeted both. Recommendations mainly addressed areas of IHR coordination (C2), heath emergency management (C7) and risk communication (C10), and not low scoring areas. Recommendations complement SPAR indicators by identifying gaps in functionality. Eight out of ten early lessons learnt during the COVID-19 pandemic had been raised earlier as recommendations from exercises. Exercise reports did not include or result in action plans for implementation, but COVID-19 has accelerated implementation of some recommendations.

Conclusion
SimEx/AAR provide valuable insight into public health preparedness at EU level, as they assess functionality of preparedness and response mechanisms, point out gaps, and provide training and awareness on for participants, who often have key roles in public health emergencies. Better follow-up and implementation of recommendations is key to improve the regional preparedness for international public health incidents such as pandemics.
Exploratory mixed methods analysis of self-authored content from participants in a digital alcohol intervention trial
Authors: Collier Elizabeth S. , Blomqvist Jenny , Crawford Joel , McCambridge Jim , Bendtsen Marcus 
Published: October 2023

Abstract
Background
Digital interventions readily permit data capture of participant engagement with them. If future interventions are intended to be more interactive, tailored, or a useful resource offered to users, it may be valuable to examine such data. One module available in a digital alcohol intervention recently tested in a randomised control trial offered participants the opportunity to self-author prompts that were sent to them by a text message at a time of their choosing. This study thus aimed to evaluate these self-authored prompts to increase knowledge on how individuals negotiate behaviour change and assess whether intervention content can be improved in the future.

Methods
The self-authored prompts were evaluated qualitatively using a combination of content and thematic analysis. The identified themes and subcategories are exemplified using anonymized quotes, and the frequency that each identified theme was coded for among the prompts was calculated. Associations between baseline characteristics and the odds of authoring a prompt at all, as well as a prompt within each theme, were investigated using logistic regression.

Results
Five themes were identified (Encouragement Style, Level of Awareness, Reminders of reasons to reduce/quit, Strategies to reduce/quit, and Timescale), all with several subcategories. The prompts module was more likely to be used by women and older individuals, as well as those for whom reducing alcohol consumption was perceived as important, or who felt they had the know-how to do so. Participants who had immediate access to the support tool (intervention group) were more than twice as likely to author a prompt (OR = 2.36; probability of association > 99%) compared to those with 4-month delayed access (control group).

Conclusions
Individuals who engaged with the prompts module showed evidence of using the information provided in the support tool in an active way, with several showing goal setting and making plans to change their drinking behaviour. Individuals also used this opportunity to remind themselves of personal and specific reasons they wanted to change their drinking, as well as to encourage themselves to do so.
Biomechanics of sacroiliac joint fixation using lag screws: a cadaveric study
Authors: Chatain Grégoire P. , Oldham Alton , Uribe Juan , Duhon Bradley , Gardner Michael J. , Witt Jens-Peter , Yerby Scott , Kelly Brian P. 
Published: October 2023

Abstract
Background
Iliosacral screw placement is ubiquitous and now part of the surgeon’s pelvic trauma armamentarium. More recent evidence supports sacroiliac arthrodesis for treating sacroiliac joint (SIJ) dysfunction in select patients. Regardless of the surgical indication, there are currently no studies examining lag screw compression biomechanics across the SIJ. The objective of this biomechanical investigation was to quantify iliosacral implant compressive loads and to examine the insertion torque and compressive load profile over time.

Methods
Eight human cadaveric pelvic specimens underwent SIJ fixation at S1 and S2 using 11.5 and 10.0 mm iFuse-TORQ Lag implants, respectively, and standard 7.3 mm trauma lag screws. Load decay analysis was performed, and insertion and removal torques were measured.

Results
For both implants at S1 and S2 levels, the load relaxed 50% in approximately 67 min. Compressive load decay was approximately 70% on average occurring approximately 15 h post-insertion. Average insertion torque for the 11.5 mm TORQ implant at S1 was significantly greater than the trauma lag screw. Similarly, at S2, insertion torque of the 10.0 mm TORQ implant was greater than the trauma lag screw. At S1, removal torque for the 11.5 mm TORQ implant was higher than the trauma lag screw; there was no significant difference in the removal torque at S2.

Conclusions
In this study, we found that a novel posterior pelvic implant with a larger diameter, roughened surface, and dual pitch threads achieved improved insertion and removal torques compared to a standard screw. Load relaxation characteristics were similar between all implants.
Autism spectrum disorder prevalence in Italy: a nationwide study promoted by the Ministry of Health
Authors: Scattoni Maria Luisa , Fatta Laura Maria , Micai Martina , Sali Maria Enrica , Bellomo Marina , Salvitti Tommaso , Fulceri Francesca , Castellano Angela , Molteni Massimo , Gambino Giovanna , Posada Manuel , Romano Giovanna , Puopolo Maria 
Published: October 2023

Abstract
Background
This nationwide study aimed to estimate Autism Spectrum Disorder (ASD) prevalence in 7–9-year-old Italian children. Promoted by Italy's Ministry of Health and coordinated by the National Observatory for Autism at the National Institute of Health, it covered schools in northern (Lecco and Monza-Brianza), central (Rome and its province), and southern (Palermo and its province) regions from February 24, 2016, to February 23, 2018, using a multi-stage approach defined by the European Union's ASD network.

Methods
Phase one identified ASD-diagnosed children in mainstream schools through local Ministry of Education (MoE) disability registries. Phase two had a subset of schools screen 7–9-year-olds using the Social Communication Questionnaire-Life version (SCQ-L). Those with SCQ-L scores of 15 + underwent clinical consultation for ASD symptoms, cognitive abilities, and life skills. To counter potential false negatives, 20% scoring 11–14 were randomly assessed via Autism Diagnostic Interview-Revised (ADI-R).

Results
MoE data revealed 9.8 per 1000 certified ASD children in the north, 12.2 in the central, and 10.3 in the south. In phase two, 35,823 SCQ-L questionnaires were distributed across 198 schools (northern: 11,190 in 49 schools, central: 13,628 in 87 schools, southern: 11,005 in 62 schools). Of SCQ-L respondents, 2.4% (n = 390) scored above the 15 cutoff. Among these, 100 had ASD diagnoses, and 50 had other diagnoses. Among 115 families assessed, 16.5% (n = 19) received ASD diagnoses.

Conclusions
The estimated prevalence of ASD in Italy was 13.4 (11.3–16.0) per 1,000 children aged 7–9 years, with a male-to-female ratio of 4.4:1. It will guide national policies in enhancing services tailored to the specific needs of autistic children.
Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis
Authors: Qu Shanqiang , Qi Songtao , Zhang Huayang , Li Zhiyong , Wang Kaicheng , Zhu Taichen , Ye Rongxu , Zhang Wanghao , Huang Guanglong , Yi Guo-zhong 
Published: October 2023

Abstract
Background
Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism.

Methods
A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models.

Results
ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy.

Conclusion
Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.
TMEM147 aggravates the progression of HCC by modulating cholesterol homeostasis, suppressing ferroptosis, and promoting the M2 polarization of tumor-associated macrophages
Authors: Huang Jingjing , Pan Huayang , Sun Jing , Wu Jiaming , Xuan Qiyue , Wang Jinge , Ke Shanjia , Lu Shounan , Li Zihao , Feng Zhigang , Hua Yongliang , Yu Qingan , Yin Bing , Qian Baolin , Zhou Menghua , Xu Yanan , Bai Miaoyu , Zhang Yingmei , Wu Yaohua , Ma Yong , Jiang Hongchi , Dai Wenjie 
Published: October 2023

Abstract
Background
The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms.

Methods
TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of TMEM147 on the progression of HCC. Proteins interacting with TMEM147 were identified via RNA-seq, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to determine and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Extensive experimental techniques were used to study ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using immunofluorescence assay and flow cytometric analysis.

Results
TMEM147 mRNA and protein levels were increased in HCC cells, and the increased TMEM147 expression was associated with a poor survival. TMEM147 promoted tumor cell proliferation and metastases in vitro and in vivo. The protein was found to interact with the key enzyme 7-dehydrocholesterol reductase (DHCR7), which affected cellular cholesterol homeostasis and increased the extracellular levels of 27HC in HCC cells. TMEM147 also promoted the expression of DHCR7 by enhancing the activity of signal transducer and activator of transcription 2. 27HC expression upregulated glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC expression increased the lipid metabolism in macrophages and activated peroxisome proliferator-activated receptor-γ signaling, thereby activating M2 macrophage polarization and promoting HCC cell invasion and migration.

Conclusions
Our results indicate that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. These findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC.

Graphical Abstract