bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoprevention of malaria with long-acting oral and injectable drugs: an updated target product profile
Authors: El Gaaloul Myriam , Tchouatieu Andre Marie , Kayentao Kassoum , Campo Brice , Buffet Benedicte , Ramachandruni Hanu , Ndiaye Jean Louis , Wells Timothy N. C. , Audibert Celine , Achan Jane , Donini Cristina , Barsosio Hellen C. , Tinto Halidou 
Published: October 2024

AbstractMalaria is preventable, but the burden of disease remains high with over 249 million cases and 608,000 deaths reported in 2022. Historically, the most important protective interventions have been vector control and chemopreventive medicines with over 50 million children receiving seasonal malaria chemoprevention in the year 2023. Two vaccines are approved and starting to be deployed, bringing additional protection for children up to 36 months. However, the impact of these currently available tools is somewhat limited on various fronts. Vaccines exhibit partial efficacy, are relatively costly, and not accessible in all settings. The challenges encountered with chemoprevention are barriers to acceptability and feasibility, including frequency of dosing, and the lack of options in the first trimester of pregnancy and for women living with HIV. Also, the emergence of resistance against chemopreventive medicines is concerning. To address these limitations, a target product profile (TPP) is proposed as a road map to guide innovation and to boost the quest for novel chemopreventive alternatives. This TPP describes the ideal product attributes, while acknowledging potential trade-offs that may be needed. Critically, it considers the target populations most at risk; primarily infants, children, and pregnant women. Malaria control and elimination requires appropriate chemoprevention, not only in areas of high endemicity and transmission, but also in lower transmission areas where immunity is declining, as well as for travellers from areas where malaria has been eliminated. New medicines should show acceptable safety and tolerability, with high and long protective efficacy. Formulations and costs need to support operational adherence, access, and effectiveness. Next generation long-acting oral and injectable drugs are likely to constitute the backbone of malaria prevention. Therefore, the perspectives of front-line experts in malaria prevention, researchers, and those involved in drug development are captured in the TPP. This inclusive approach aims at concentrating efforts and aligning responses across the community to develop new and transformative medicines.
An unbiased, sustainable, evidence-informed Universal Food Guide: a timely template for national food guides
Authors: Dean Elizabeth , Xu Jia , Jones Alice Yee-Men , Vongsirinavarat Mantana , Lomi Constantina , Kumar Pintu , Ngeh Etienne , Storz Maximilian A. 
Published: October 2024

Abstract
Background
Although national food guides are designed, ostensibly, to translate scientific evidence with respect to food, dietary patterns, and health, their development has increasingly become a corporate/political process as well as scientific one; often with corporate/political influences overriding science. Our aim was to construct an unbiased, sustainable, evidence-informed Universal Food Guide to serve as a template for countries to develop their unique guides, thereby, provide a valid resource for health professionals, health authorities, and the public.

Methods
To address our aim, we conducted an integrative review of multiple evidence-informed sources (e.g., established databases, evidence syntheses, scholarly treatises, and policy documents) related to four areas: 1. Food guides’ utility and conflicts of interest; 2. The evidence-based healthiest diet; 3. Constituents of the Universal Food Guide template; and 4. Implications for population health; regulation/governance; environment/climate/planetary health; and ethics.

Results
The eating pattern that is healthiest for humans (i.e., most natural, and associated with maximal health across the life cycle; reduced non-communicable disease (NCD) risk; and minimal end-of-life illness) is whole food, low fat, plant-based, especially vegan, with the absence of ultra-processed food. Disparities in national food guide recommendations can be explained by factors other than science, specifically, corporate/political interests reflected in heavily government-subsidized, animal-sourced products; and trends toward dominance of daily consumption of processed/ultra-processed foods. Both trends have well-documented adverse consequences, i.e., NCDs and endangered environmental/planetary health. Commitment to an evidence-informed plant-based eating pattern, particularly vegan, will reduce risks/manifestations of NCDs; inform healthy food and nutrition policy regulation/governance; support sustainable environment/climate and planetary health; and is ethical with respect to ‘best’ evidence-based practice, and human and animal welfare.

Conclusion
The Universal Food Guide that serves as a template for national food guides is both urgent and timely given the well-documented health-harming influences that corporate stakeholders/politicians and advisory committees with conflicts of interest, exert on national food guides. Such influence contributes to the largely-preventable NCDs and environmental issues. Policy makers, health professionals, and the public need unbiased, scientific evidence as informed by the Universal Food Guide, to inform their recommendations and choices.
Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM®: a prospective observational study
Authors: Sunnersjö Lotta , Ymén Isak , Schött Ulf , Hillarp Andreas , Undén Johan , Kander Thomas 
Published: October 2024

Abstract
Background
Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®.

Methods
Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.

Results
In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.

Conclusions
The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.

Trial registration
The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.
Diurnal patterns of accelerometer-measured physical activity and sleep and risk of all-cause mortality: a follow-up of the National Health and Nutrition Examination Surveys (NHANES)
Authors: Zhang Yue , Kivimäki Mika , Carrillo-Larco Rodrigo M. , Cheng Yangyang , Zhou Yaguan , Wang Hui , Yuan Changzheng , Xu Xiaolin 
Published: October 2024

Abstract
Background
Physical activity and sleep are established modifiable lifestyle factors, but the optimal time of the day of these behaviours for health is unknown. This study examined the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality.

Methods
This prospective cohort study included 6,673 participants who have attended the accelerometer assessment in the 2011–2014 National Health and Nutrition Examination Surveys (NHANES). Diurnal patterns of accelerometer-measured physical activity and sleep were identified using K-means clustering analysis. All-cause mortality was ascertained from the accelerometer measurement to December 31, 2019 (median follow-up 6.8 years). Survey-weighted Cox proportional hazard models were performed to estimate the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality.

Results
Diurnal patterns identified were: early-morning (32.4%), midday (42.5%), and late-afternoon (25.1%) for physical activity; and irregular sleep (37.4%), morning lark (33.6%), and night owl (29.0%) for sleep. After adjusting for volume of physical activity, sleep duration and other potential covariates, the early-morning physical activity pattern (hazard ratio 1.36, 95% confidence interval 1.13–1.64) and irregular sleep pattern (1.42, 1.01–1.99) were independently associated with higher risk of all-cause mortality, compared with midday physical activity and morning lark sleep patterns, respectively. In addition, participants with the combined pattern of early-morning physical activity and irregular sleep had higher risk of all-cause mortality compared to those with midday physical activity combined with a morning lark sleep pattern (1.92, 1.33–2.78). Several sociodemographic differences were observed in the strength of these associations.

Conclusions
Wearable activity-rest monitoring data showed that peak physical activity in the early morning and irregular sleep diurnal patterns are associated with increased mortality risk, and the combination of these patterns further exaggerated the risk. Public health program should acknowledge that the diurnal patterns of physical activity and sleep, in addition to their duration and frequency, may play a crucial role in lifestyle-based health promotion and management strategies.
Breastfeeding frequency and incidence of type 2 diabetes among women with previous gestational diabetes compared to those without: a historical cohort study in the UK
Authors: Eades Claire , Hoddinott Pat , Cameron Dawn , Evans Josie 
Published: October 2024

Abstract
Background
There is a growing body of research to suggest that women with gestational diabetes are less likely to initiate and continue breastfeeding than those who have not had however findings are mixed. There is limited research in the UK assessing the frequency of breastfeeding in women with gestational diabetes, none reporting the association of breastfeeding with incidence of type 2 diabetes and existing research has not adequately adjusted for potential confounders. This study aims to assess frequency of breastfeeding among women with gestational diabetes compared to those without, and to explore how breastfeeding influences risk of future type 2 diabetes in women with gestational diabetes while adjusting for known confounders.

Methods
Historical cohort study using routinely collected health care data from Fife and Tayside Health Boards, Scotland, UK including all women diagnosed with gestational diabetes between 1993 and 2015 and a matched comparator cohort (n = 4,968). Women with gestational diabetes were followed up until a diagnosis of type 2 diabetes, the end of the study, or date of death. Multinomial logistic regression was used to estimate odds ratios for breastfeeding for the whole sample and the association between breastfeeding and development of type 2 diabetes in women with gestational diabetes was assessed by Cox regression.

Results
Women with a diagnosis of gestational diabetes, who were younger, overweight/obese or living in the most deprived areas were significantly less likely to exclusively breastfeed for a duration of longer than eight weeks. Risk of developing type 2 diabetes among women with gestational diabetes was significantly higher for those who exclusively breastfed less than 8 weeks, lived in the most deprived areas or had a family history of diabetes.

Conclusions
This study confirms the important role of a short duration of exclusive breastfeeding in protecting women with gestational diabetes against type 2 diabetes but highlights the challenges to breastfeeding in this group. Interventions are needed to support breastfeeding among women with gestational diabetes that are acceptable to younger, overweight/obese women living in deprived areas.
Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia
Authors: Vallejo-Cremades Mayte , Merino Javier , Carmona Rita , Córdoba Laura , Salvador Beatriz , Martínez Leopoldo , Tovar Juan Antonio , Llamas Miguel Ángel , Muñoz-Chápuli Ramón , Fresno Manuel 
Published: October 2024

Abstract
Background
Congenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage.

Methods
We have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages.

Results
We found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206+ and Arg1+) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARβ, in the affected lungs and the diaphragm and in macrophages in vitro.

Conclusions
Our research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.
Quality of life and unmet needs in patients with fabry disease: a qualitative study
Authors: Morales Montserrat , Cruz Jordi , Brignani Eduardo , Acuña Laura , Lázaro Esther , Soria Cristina 
Published: October 2024

Abstract
Background
Patients with Fabry disease (FD) consider their quality of life to be significantly affected. The majority of studies evaluate the quality of life using quantitative measures and standardised scales that offer relevant information about experience with the disease in multiple aspects. The main objective of the research was to examine in depth the quality of life and unmet needs of patients diagnosed with FD in relation to their disease and treatment. A qualitative and transversal study was carried out in two stages: (a) nine semi-structured qualitative interviews with patients and one representative of the patient association, conducted individually by phone; (b) a focus group was set up with three patients diagnosed with FD and one relative. A deductive, thematic analysis approach was used for data coding and analysis.

Results
The analysis of the interviews revealed various relevant themes: experience with the disease, impact on daily activities, experience of the family and work environment, experience related to treatment and healthcare professionals, and unmet support needs. Diagnosis has a significant impact on both those suffering from the disease and on the family environment. The symptoms and evolution of the disease are highly variable among the patients interviewed and depend on the years diagnosed as well as the time taken to receive the diagnosis. The families of the interviewees have to go through an adjustment process in light of the significant psychological impact brought about by the disease. Patients show various unmet needs. The need mentioned most is to have more information, support, and understanding from people around them and society, improving empathy and raising awareness about the difficulties faced by people with FD while giving the disease visibility. A lack of social understanding is highlighted as one of the main challenges, as this does not only affect the emotional management of the disease but also has repercussions on working life and social relationships.

Conclusions
It seems necessary to define possible strategies that help to improve the quality of life of patients and their experience with the disease. Some recommendations obtained from the study include: facilitate access to mental health professionals for patients and their families; improve training for specialists and coordination among them; and carry out actions to raise awareness of the disease that are aimed at the general public, the patients themselves, and the people around them.
Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation
Authors: Daga Kanupriya R. , Larey Andrew M. , Morfin Maria G. , Chen Kailin , Bitarafan Sara , Carpenter Jana M. , Hynds Hannah M. , Hines Kelly M. , Wood Levi B. , Marklein Ross A. 
Published: October 2024

Abstract
Background
Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of the brain, to exert their immunomodulatory effects. In response to inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative of their function e.g. morphology and secretion. However, these changes in response to MSC-EVs are not well understood. Additionally, no disease-relevant screening tools to assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed a quantitative, high throughput morphological profiling approach to assess the response of microglia to neuroinflammation- relevant signals and whether this morphological response can be used to indicate the bioactivity of MSC-EVs.

Results
Using an immortalized human microglia cell-line, we observed increased size (perimeter, major axis length) and complexity (form factor) upon stimulation with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Upon treatment with MSC-EVs, the overall morphological score (determined using principal component analysis) shifted towards the unstimulated morphology, indicating that MSC-EVs are bioactive and modulate microglia. The morphological effects of MSC-EVs in TNF-α /IFN-γ stimulated cells were concomitant with reduced secretion of 14 chemokines/cytokines (e.g. CXCL6, CXCL9) and increased secretion of 12 chemokines/cytokines (e.g. CXCL8, CXCL10). Proteomic analysis of cell lysates revealed significant increases in 192 proteins (e.g. HIBADH, MEAK7, LAMC1) and decreases in 257 proteins (e.g. PTEN, TOM1, MFF) with MSC-EV treatment. Of note, many of these proteins are involved in regulation of cell morphology and migration. Gene Set Variation Analysis revealed upregulation of pathways associated with immune response, such as regulation of cytokine production, immune cell infiltration (e.g. T cells, NK cells) and morphological changes (e.g. Semaphorin, RHO/Rac signaling). Additionally, changes in microglia mitochondrial morphology were measured suggesting that MSC-EV modulate mitochondrial metabolism.

Conclusion
This study comprehensively demonstrates the effects of MSC-EVs on human microglial morphology, cytokine secretion, cellular proteome, and mitochondrial content. Our high-throughput, rapid, low-cost morphometric approach enables screening of MSC-EV batches and manufacturing conditions to enhance EV function and mitigate EV functional heterogeneity in a disease relevant manner. This approach is highly generalizable and can be further adapted and refined based on selection of the disease-relevant signal, target cell, and therapeutic product.
Imaging of upper breakpoints of buried active faults through microtremor survey technology
Authors: Qiao-Ling Li , Hui Zhang , Xiao-Dong Lei , Chen Li 
Published: October 2024

AbstractDetecting buried active faults presents the challenge of precisely locating the upper breakpoint, the shallowest point in the Quaternary system where faults occur. Microtremor survey technology, unaffected by urban electromagnetic interference, offers an eco-friendly and efficient method for investigating buried faults and stratigraphic structures in urban areas. This research uses microtremor survey technology to identify the upper breakpoint of the buried Nankou-Sunhe Fault in Changping, Beijing. For data collection, 17 microtremor survey points were deployed across the northern section of the Nankou-Sunhe fault, employing a three-point nested circular array with a point spacing of approximately 200 m to form a profile spanning approximately 320 m. For data analysis, the spatial autocorrelation method was utilized. Each measurement point was divided into 9 sets of radii, ranging from a minimum of approximately 4 m to a maximum of 28 m. The correlation coefficients for each set were calculated, and the dispersion curve for each measurement point was generated by fitting the average coefficients with the Bessel function of the first kind of order zero. The apparent S-wave velocity was determined directly from the dispersion curve using empirical formulas and interpolated to generate the contour cross-section map. Integrating the section and inverted S-wave velocity data can significantly enhance interpretation accuracy, and based on these data, the spatial development characteristics and upper breakpoint locations of the Nankou-Sunhe fault zone were analyzed, and the strata shallower than 100 m were deduced. The results align well with known geological data, such as luminescence dating and 14C dating from boreholes at nearby locations.
Graphical Abstract