bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal dynamics and influencing factors of human brucellosis in Mainland China from 2005–2021
Authors: Zhang Meng , Chen Xinrui , Bu Qingqing , Tan Bo , Yang Tong , Qing Liyuan , Wang Yunna , Deng Dan
Published: January 2024

Background

Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level.

Methods

The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors.

Results

From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence.

Conclusions

Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.
Challenge of ending TB in China: tuberculosis control in primary healthcare sectors under integrated TB control model–a systematic review and meta-analysis
Authors: Chen Xi , Zhou Jiani , Yuan Quan , Zhang Rui , Huang Chunji , Li Ying
Published: January 2024

Background

China has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China.

Methods

This review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality.

Results

Forty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients’ treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)].

Conclusion

It is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.
Using meta-learning to recommend an appropriate time-series forecasting model
Authors: Talkhi Nasrin , Akhavan Fatemi Narges , Jabbari Nooghabi Mehdi , Soltani Ehsan , Jabbari Nooghabi Azadeh
Published: January 2024

Background

There are various forecasting algorithms available for univariate time series, ranging from simple to sophisticated and computational. In practice, selecting the most appropriate algorithm can be difficult, because there are too many algorithms. Although expert knowledge is required to make an informed decision, sometimes it is not feasible due to the lack of such resources as time, money, and manpower.

Methods

In this study, we used coronavirus disease 2019 (COVID-19) data, including the absolute numbers of confirmed, death and recovered cases per day in 187 countries from February 20, 2020, to May 25, 2021. Two popular forecasting models, including Auto-Regressive Integrated Moving Average (ARIMA) and exponential smoothing state-space model with Trigonometric seasonality, Box-Cox transformation, ARMA errors, Trend, and Seasonal components (TBATS) were used to forecast the data. Moreover, the data were evaluated by the root mean squared error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and symmetric mean absolute percentage error (SMAPE) criteria to label time series. The various characteristics of each time series based on the univariate time series structure were extracted as meta-features. After that, three machine-learning classification algorithms, including support vector machine (SVM), decision tree (DT), random forest (RF), and artificial neural network (ANN) were used as meta-learners to recommend an appropriate forecasting model.

Results

The finding of the study showed that the DT model had a better performance in the classification of time series. The accuracy of DT in the training and testing phases was 87.50% and 82.50%, respectively. The sensitivity of the DT algorithm in the training phase was 86.58% and its specificity was 88.46%. Moreover, the sensitivity and specificity of the DT algorithm in the testing phase were 73.33% and 88%, respectively.

Conclusion

In general, the meta-learning approach was able to predict the appropriate forecasting model (ARIMA and TBATS) based on some time series features. Considering some characteristics of the desired COVID-19 time series, the ARIMA or TBATS forecasting model might be recommended to forecast the death, confirmed, and recovered trend cases of COVID-19 by the DT model.
Sexual violence in nightlife and positive bystander intervention in an English city
Authors: Quigg Zara , Bates Rebecca , Butler Nadia , Smith Chloe , Wilson Charley , Atkinson Amanda , Bellis Mark A
Published: January 2024

Background

Nightlife environments are high risk settings for sexual violence and bystander intervention programmes are being developed in response. However, more research is needed to understand nightlife-related sexual violence, and factors that influence bystander interventions. This study examined nightlife patron’s experiences of sexual violence and associated factors; and relationships between attitudes towards, awareness and experience of sexual violence, and confidence to intervene.

Methods

Cross-sectional on-street survey of nightlife patrons (N = 307, aged 18+) on a night out in an English city. Surveys (7.30pm-1.30am; Wednesday-Saturday) established sexual violence awareness, myth acceptance, and experience, and confidence to intervene. Participant’s socio-demographics, nightlife alcohol consumption, and frequency of nightlife usage were collected.

Results

58.0% had ever experienced sexual violence whilst on a night out. In adjusted analyses, sexual violence was higher amongst females (adjusted odds ratio [AOR] 4.0; p < 0.001), and regular nightlife patrons (AOR 2.1; p < 0.05). The majority agreed that they would feel confident asking someone who has experienced sexual violence if they are okay/would like support (92.2%). In adjusted analyses, confidence to intervene was higher amongst those who agreed that sexual violence was an issue in nightlife (AOR 3.6; p < 0.05), however it reduced as sexual violence myth acceptance increased (AOR 0.5; p < 0.05).

Conclusion

Sexual violence is a pertinent issue in nightlife. Programmes aiming to address nightlife-related sexual violence must address the wider social norms that promote sexual violence, and ensure patrons understand the extent and significance of the issue, to increase confidence to positively intervene.
Association of sun-seeking behaviors with indoor tanning behavior in US white females during high school/college in Nurses’ Health Study II
Authors: Seo Bojung , Yang Sheng , Cho Eunyoung , Qureshi Abrar A , Han Jiali
Published: January 2024

Background

Frequent exposure to ultraviolet light has more detrimental and longer-term effects on the skin in early life than in adulthood. Teenagers with strong sun-seeking behaviors may be more likely to use an indoor tanning bed than those who seek less sun. We aimed to examine associations between sun-seeking behaviors and indoor tanning behavior during high school/college in US females.

Methods

In this cross-sectional study, we used data from The Nurses’ Health Study II, a large prospective cohort of US female nurses. We included a total of 81,746 white females who provided responses on the average annual frequency of indoor tanning during high school/college. Our study exposures were number of times/week spent outdoors in a swimsuit and percentage of time wearing sunscreen at the pool/beach as a teenager, weekly hours spent outdoors in direct sunlight during the daytime during high school/college, and number of severe sunburns that blistered between ages 15–20 years. The main outcome was annual frequency of indoor tanning bed usage during high school/college.

Results

In multivariable-adjusted logistic regression, we demonstrated positive associations between sun-seeking behaviors and indoor tanning use. Specifically, teenagers who spent 7 times/week outdoors in a swimsuit (adjusted odds ratio [aOR], 95% confidence interval [CI] for daily vs. <1/week: 2.68, 1.76–4.09) were more likely to use indoor tanning beds ≥ 12 times/year. Teenagers with ≥ 10 sunburns (aOR, 95% CI for ≥ 10 vs. never: 2.18, 1.53–3.10) were more likely to use indoor tanning beds ≥ 12 times/year. Also, teenagers/undergraduates who spent ≥ 5 h/week outdoors in direct sunlight (aOR, 95% CI for ≥ 5 h/week vs. <1 h/week: 2.18, 1.39–3.44) were more likely to use indoor tanning ≥ 12 times/year. However, there was not a significant association between average usage of sunscreen at the pool/beach and average usage of indoor tanning beds. Multivariable-adjusted linear regression models also showed similar results.

Conclusions

Teenagers who spent more time outdoors in a swimsuit/direct sunlight or got more sunburns tended to use indoor tanning more frequently. These findings provide evidence that teenagers with stronger sun-seeking behaviors may have more exposure to artificial ultraviolet radiation as well.
Different wavelengths of laser: are they significant for treatment of denture stomatitis?: an in-vitro study
Authors: El-Din Mai Salah , El-Sharkawy Ahlam , Abdelrahman Hams , Hanno Kenda I.
Published: January 2024

Background

Denture stomatitis (DS) is an inflammatory disorder that affects the mucosal surface underneath the dentures and frequently causes oral mucosal irritation, discomfort, and altered taste perception, which prevents people from consuming enough nutrients. One of the main causes of DS is an overgrowth of the fungus Candida albicans (C. albicans). A possible alternative treatment for Candida infections is thought to be laser therapy. The aim of this study was to evaluate how different wavelengths of laser would affect growth and pathogenic properties of Candida albicans.

Methods

A concentration of 106 viable cells/ml of Candida albicans were used in the preparation process. Four groups were created from the specimens. Culturing of the control group was completed with no intervention. The other 3 groups received laser radiation for 60 seconds at a power of 1W. The 2nd and 3rd groups were irradiated with diode laser at a wavelength of 940 nm and 980 nm respectively. The 4th group was irradiated with Nd-YAG laser at a wavelength of 1064 nm. Turbidimetric growth was defined as variations in the optical density of fungal growth. These measures were made at three different times: baseline, 48 hours, and 72 hours.

Results

In both groups of diode laser, the growth of Candida albicans showed no remarkable differences at baseline, after 48 and 72 hours using a power of 1 W and duration of 60 seconds. The Nd-YAG group showed significant increase in optical density after 48 hrs then significant decrease after 72 hrs. The optical density values in the control group showed no notable difference between the control and diode study groups at different time periods. However, the Nd:YAG group showed a statistically significant difference compared to the control and the 2 diode laser groups.

Conclusions

Different laser parameters have a different effect on growth and pathogenic properties of Candida albicans. Diode laser therapy with wavelengths 940 and 980 nm used in continuous mode with power of 1 W for duration of 60 seconds can result in proliferation of Candida albicans instead of destroying them. Nd:YAG laser, used in pulsed mode, with power of 1 W for a duration of 60 seconds can be used to destroy Candida albicans and therefore, can be used as an effective treatment for denture stomatitis.
Pharmacist and student evaluation of a preceptor training program in a regional Australian University: a multi-method study
Authors: Knott Gillian J , Mylrea Martina F , Glass Beverley D
Published: January 2024

Background

Increased emphasis on workplace-based learning within pharmacy curricula has led to a focus on the quality of preceptors and the provision of preceptor training, with a diverse range of training programs for preceptors being developed across the globe. To ensure that preceptors are trained appropriately and deemed to be competent in their role, it is essential that all training programs are suitably evaluated. This research aimed to evaluate an online preceptor training program at a regional Australian University.

Methods

Kirkpatrick’s four level model for assessment of training was used to evaluate this program. A multi method approach included a preceptor post training survey and interviews and a student survey evaluating the preceptor. Preceptor survey data were analysed using descriptive statistics and content analysis, while inductive thematic analysis was used to analyse the interviews. Student evaluations of trained and untrained preceptors were compared to determine whether training had impacted on student-rated preceptor effectiveness.

Results

Twenty-eight preceptor post-training surveys were received, ten preceptor post-training interviews were conducted, and 35 student surveys were completed. The program was rated positively overall, with notable mention by preceptors of the interactive networking session. Following their first post-training student placement, preceptors found that their overall confidence levels had improved, particularly in relation to student management, evaluating students and providing feedback. Student evaluations of preceptors revealed improved ratings of trained versus untrained preceptors, especially as effective communicators.

Conclusions

This study demonstrated that training had a positive impact on preceptor attitudes, behaviour and confidence levels. From the perspective of the student, training was also found to improve preceptor performance. These results highlight the beneficial effects of training for preceptors, to optimize the student placement experience and their preparation for future practice.
Targeting cholesterol impairs cell invasion of all breast cancer types
Authors: Maja Mauriane , Verfaillie Marie , Van Der Smissen Patrick , Henriet Patrick , Pierreux Christophe E. , Sounni Nor Eddine , Tyteca Donatienne
Published: January 2024

Background

Breast cancer clinical outcome relies on its intrinsic molecular subtype and mortality is almost exclusively due to metastasis, whose mechanism remains unclear. We recently revealed the specific contribution of plasma membrane cholesterol to the invasion of malignant MCF10CAIa but not premalignant MCF10AT and normal MCF10A cell lines in 2D, through invadopodia formation and extracellular matrix (ECM) degradation. In the present study, we address the impact of breast cancer subtypes, mutations and aggressiveness on cholesterol implication in breast cancer cell invasion and 3D spheroid invasion and growth.

Methods

We used nine breast cancer cell lines grouped in four subtypes matching breast tumor classification. Four of these cell lines were also used to generate 3D spheroids. These cell lines were compared for cell invasion in 2D and 3D, spheroid growth in 3D, gelatin degradation, cortactin expression, activation and subcellular distribution as well as cell surface cholesterol distribution and lipid droplets. The effect of plasma membrane cholesterol depletion on all these parameters was determined in parallel and systematically compared with the impact of global matrix metalloproteinase (MMP) inhibition.

Results

The six invasive cell lines in 2D were sensitive to partial cholesterol depletion, independently of their subtype, aggressiveness or mutation. Nevertheless, the effect was stronger in the three cell lines able to degrade gelatin. 3D spheroid invasion was also reduced after cholesterol depletion in all breast cancer subtypes tested. Notably, targeting cholesterol was more powerful than MMP inhibition in reducing invasion in both 2D and 3D culture models. Moreover, cholesterol depletion in the six invasive cell lines impaired cortactin distribution in the perinuclear region where invadopodia localized. Breast cancer cell line aggressiveness relied on cholesterol-enriched domains at the ECM-free side and intracellular lipid droplets. Furthermore, the three gelatin-degrading cell lines were characterized by increased cholesterol-enriched submicrometric domains at their ECM-contact side.

Conclusion

Together, our data suggest cell surface cholesterol combined with lipid droplet labeling as a breast cancer cell aggressiveness marker. They also open the way to test other cholesterol-targeting drugs in more complex models to further evaluate whether cholesterol could represent a strategy in breast cancer therapy.
Involvement of the tumour necrosis factor receptor system in glioblastoma cell death induced by palbociclib-heptamethine cyanine dye conjugate
Authors: Cooper Elizabeth , Oyagawa Caitlin R. M. , Johnson Rebecca , Choi Peter J. , Foliaki Jena Macapagal , Correia Jason , Schweder Patrick , Heppner Peter , Mee Edward , Turner Clinton , Faull Richard , Denny William A. , Dragunow Mike , Jose Jiney , Park Thomas I-H.
Published: January 2024

Glioblastoma is the most common and aggressive primary brain tumour in adults. The development of anti-brain cancer agents are challenged by the blood-brain barrier and the resistance conferred by the local tumour microenvironment. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence compounds that have recently emerged as promising agents for drug delivery. We conjugated palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, to an HMCD, MHI-148, and conducted drug activity analysis on primary patient-derived glioblastoma cell lines. In addition to the expected cytostatic activity, our in vitro studies revealed that palbociclib-MHI-148 conjugate resulted in an almost 100-fold increase in cytotoxicity compared to palbociclib alone. This shift of palbociclib from cytostatic to cytotoxic when conjugated to MHI-148 was due to increased DNA damage, as indicated by an increase in γH2AX foci, followed by an increased expression of key extrinsic apoptosis genes, including TP53, TNFR1, TRAIL, FADD and caspase 8. In addition, we observed a time-dependent increase in the cell surface expression of TNFR1, consistent with an observed increase in the secretion TNFα, followed by TNFR1 endocytosis at 48 h. The treatment of patient GBM cells with the palbociclib-MHI-148 conjugate prevented TNFα-induced NFκB translocation, suggesting conjugate-induced TNFR1 signalling favoured the TNFR1-mediated apoptotic response rather than the pro-inflammatory response pathway. Notably, pharmacological inhibition of endocytosis of TNFR1, and siRNA-knockdown of TNFR1 reversed the palbociclib-MHI-148-induced cell death. These results show a novel susceptibility of glioblastoma cells to TNFR1-dependent apoptosis, dependent on inhibition of canonical NFκB signalling using our previously reported palbociclib-HMCD conjugate.
ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1
Authors: Li Yu-kun , Gao An-bo , Zeng Tian , Liu Dan , Zhang Qun-feng , Ran Xiao-min , Tang Zhen-zi , Li Yan , Liu Jue , Zhang Ting , Shi Gang-qing , Zhou Wen-chao , Zou Wen-da , Peng Juan , Zhang Juan , Li Hui , Zou Juan
Published: January 2024

Background

Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated.

Methods

The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking.

Results

Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis.

Conclusion

Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
CD4 T-cell aging exacerbates neuroinflammation in a late-onset mouse model of amyotrophic lateral sclerosis
Authors: Zaccai Shir , Nemirovsky Anna , Lerner Livnat , Alfahel Leenor , Eremenko Ekaterina , Israelson Adrian , Monsonego Alon
Published: January 2024

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons in the brain and spinal cord. Accumulating evidence suggests that ALS is not solely a neuronal cell- or brain tissue-autonomous disease and that neuroinflammation plays a key role in disease progression. Furthermore, whereas both CD4 and CD8 T cells were observed in spinal cords of ALS patients and in mouse models of the disease, their role in the neuroinflammatory process, especially considering their functional changes with age, is not fully explored. In this study, we revealed the structure of the CD4 T-cell compartment during disease progression of early-onset SOD1G93A and late-onset SOD1G37R mouse models of ALS. We show age-related changes in the CD4 T-cell subset organization between these mutant SOD1 mouse models towards increased frequency of effector T cells in spleens of SOD1G37R mice and robust infiltration of CD4 T cells expressing activation markers and the checkpoint molecule PD1 into the spinal cord. The frequency of infiltrating CD4 T cells correlated with the frequency of infiltrating CD8 T cells which displayed a more exhausted phenotype. Moreover, RNA-Seq and immunohistochemistry analyses of spinal cords from SOD1G37R mice with early clinical symptoms demonstrated immunological trajectories reminiscent of a neurotoxic inflammatory response which involved proinflammatory T cells and antigen presentation related pathways. Overall, our findings suggest that age-related changes of the CD4 T cell landscape is indicative of a chronic inflammatory response, which aggravates the disease process and can be therapeutically targeted.
Effects and mechanisms of Zhizi Chuanxiong herb pair against atherosclerosis: an integration of network pharmacology, molecular docking, and experimental validation
Authors: Zhang Yan , Qi Yifei , Jia Zijun , Li Yiming , Wu Liqi , Zhou Qingbing , Xu Fengqin
Published: January 2024

Background

The Zhizi Chuanxiong herb pair (ZCHP) can delay pathological progression of atherosclerosis (AS); however, its pharmacological mechanism remains unclear because of its complex components. The purpose of current study is to systematically investigate the anti-AS mechanism of ZCHP.

Methods

The databases of TCMSP, STITCH, SwissTargetPrediction, BATMAN-TCM, and ETCM were searched to predict the potential targets of ZCHP components. Disease targets associated with AS was retrieved from the GEO database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were executed using DAVID 6.8. Molecular docking method was employed to evaluate the core target binding to blood components, and animal experiments were performed to test action mechanism.

Results

A ZCHP-components-targets-AS network was constructed by using Cytoscape, included 11 main components and 52 candidate targets. Crucial genes were shown in the protein–protein interaction network, including TNF, IL-1β, IGF1, MMP9, COL1A1, CCR5, HMOX1, PTGS1, SELE, and SYK. KEGG enrichment illustrated that the NF-κB, Fc epsilon RI, and TNF signaling pathways were important for AS treatment. These results were validated by molecular docking. In ApoE−/− mice, ZCHP significantly reduced intima-media thickness, pulse wave velocity, plaque area, and serum lipid levels while increasing the difference between the end-diastolic and end-systolic diameters. Furthermore, ZCHP significantly decreased the mRNA and protein levels of TNF-α and IL-1β, suppressed NF-κB activation, and inhibited the M1 macrophage polarization marker CD86 in ApoE−/− mice.

Conclusion

This study combining network pharmacology, molecular biology, and animal experiments showed that ZCHP can alleviate AS by suppressing the TNF/NF-κB axis and M1 macrophage polarization.

Graphical Abstract
The financial burden of diabetes‐related foot disease in Australia: a systematic review
Authors: Frescos Nicoletta , Stopher Lucy , Jansen Shirley , Kaminski Michelle R.
Published: January 2024

Background

Diabetes‐related foot disease (DFD) is a common, costly, and severe complication of diabetes mellitus. DFD is associated with high rates of morbidity and mortality and poses a significant burden on patients, healthcare systems and society. While the detrimental impact of DFD is widely recognised, the precise financial implications of its management in Australia remain unclear due to inconsistent and inconclusive contemporary data. Therefore, the aim of this review was to identify, summarise and synthesise existing evidence to estimate the costs associated with DFD management in Australia.

Methods

Searches were conducted in MEDLINE, Embase, AMED, CINAHL, Joanna Briggs Institute EBP, and the Cochrane Library from November 2011 to July 2023. Australian studies investigating costs associated with DFD management were eligible for inclusion. Two independent reviewers performed the study selection, data extraction and quality assessment steps. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklist was used to assess study quality. A descriptive analysis was performed due to limited existing evidence and large heterogeneity between study populations to conduct meta‐analyses.

Results

Three economic evaluations were included in the review. One study was rated as ‘poor’, one as ‘very good’ and one as ‘excellent’ when assessed against the CHEERS checklist. The estimated cost of DFD management varied between studies and comparisons were not possible due to the different methodological approaches and data sources. The studies were unable to provide an overall cost of DFD with respect to all aspects of care as they did not capture the multi‐faceted level of care throughout the entire patient journey between sectors and over time.

Conclusion

There is limited contemporary evidence for the costs associated with DFD management within Australia, particularly related to direct costs and resource utilisation. Further research into the economic impact of DFD management is needed to inform optimisation of national service delivery and improve health outcomes for individuals with DFD in Australia. Integrating real‐world data on impact of clinical interventions with parallel economic evaluation could be a valuable approach for future research, which would offer a more comprehensive understanding of the clinical and economic outcomes beyond solely model‐based evaluations.

Trial registration

PROSPERO Registration No. CRD42022290910.
Improved prediction of bacterial CRISPRi guide efficiency from depletion screens through mixed-effect machine learning and data integration
Authors: Yu Yanying , Gawlitt Sandra , de Andrade e Sousa Lisa Barros , Merdivan Erinc , Piraud Marie , Beisel Chase L. , Barquist Lars
Published: January 2024

CRISPR interference (CRISPRi) is the leading technique to silence gene expression in bacteria; however, design rules remain poorly defined. We develop a best-in-class prediction algorithm for guide silencing efficiency by systematically investigating factors influencing guide depletion in genome-wide essentiality screens, with the surprising discovery that gene-specific features substantially impact prediction. We develop a mixed-effect random forest regression model that provides better estimates of guide efficiency. We further apply methods from explainable AI to extract interpretable design rules from the model. This study provides a blueprint for predictive models for CRISPR technologies where only indirect measurements of guide activity are available.
Simultaneous determination of 14 analgesics in postoperative analgesic solution by HPLC–DAD and LC–MS/MS
Authors: Yao Manman , Fang Baoxia , Yang Jinguo , Wang Sicen , Chen Fuchao
Published: January 2024

A green, efficient, sensitive and accurate detection method by HPLC–DAD and LC–MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The 14 mixtures were chromatographed via HPLC–DAD method which employed 0.05 mol/L potassium dihydrogen phosphate solution-acetonitrile as the mobile phase, the analytes were gradient elution on a SinoChrom ODS-BP C18 column with a total separation time of 35 min, and 14 mixtures showed a good linear relationship in the linear range. The Limit of Quantitation (LOQ) ranged from 0.10 to 20.0 µg/mL, the inter-day and intra-day precision of each analyte is within 1.1–2.0% and 0.4–1.3%, and the average absolute recovery of all compounds was above 98%. The LC–MS/MS method was used to successfully separate the 14 mixtures within 10 min which employed 0.1% formic acid-acetonitrile as the mobile phase, the analytes were gradient elution on a ACQUITY UPLC-BEH C18 column with a total separation time of 13 min, and 14 mixtures showed a good linear relationship in the linear range. The LOQ ranged from 0.005 to 0.2 ng/mL, the inter-day and intra-day precision of each analyte is within 1.2–4.1% and 0.6–3.3%, and the average absolute recovery of all compounds was above 93%. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines.
Autistic and non-autistic individuals show the same amygdala activity during emotional face processing
Authors: Langenbach Benedikt P. , Grotegerd Dominik , Mulders Peter C. R. , Tendolkar Indira , van Oort Jasper , Duyser Fleur , van Eijndhoven Philip , Vrijsen Janna N. , Dannlowski Udo , Kampmann Zarah , Koelkebeck Katja
Published: January 2024

Background

Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people’s feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples.

Methods

In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns.

Results

We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment.

Limitations

Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations.

Conclusions

Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.
Assessment of the alpha 7 nicotinic acetylcholine receptor as an imaging marker of cardiac repair-associated processes using NS14490
Authors: Reid Victoria J. M. , McLoughlin Wesley K. X. , Pandya Kalyani , Stott Holly , Iškauskienė Monika , Šačkus Algirdas , Marti Judit A. , Kurian Dominic , Wishart Thomas M. , Lucatelli Christophe , Peters Dan , Gray Gillian A. , Baker Andrew H. , Newby David E. , Hadoke Patrick W. F. , Tavares Adriana A. S. , MacAskill Mark G.
Published: January 2024

Background

Cardiac repair and remodeling following myocardial infarction (MI) is a multifactorial process involving pro-reparative inflammation, angiogenesis and fibrosis. Noninvasive imaging using a radiotracer targeting these processes could be used to elucidate cardiac wound healing mechanisms. The alpha7 nicotinic acetylcholine receptor (ɑ7nAChR) stimulates pro-reparative macrophage activity and angiogenesis, making it a potential imaging biomarker in this context. We investigated this by assessing in vitro cellular expression of ɑ7nAChR, and by using a tritiated version of the PET radiotracer [18F]NS14490 in tissue autoradiography studies.

Results

ɑ7nAChR expression in human monocyte-derived macrophages and vascular cells showed the highest relative expression was within macrophages, but only endothelial cells exhibited a proliferation and hypoxia-driven increase in expression. Using a mouse model of inflammatory angiogenesis following sponge implantation, specific binding of [3H]NS14490 increased from 3.6 ± 0.2 µCi/g at day 3 post-implantation to 4.9 ± 0.2 µCi/g at day 7 (n = 4, P < 0.01), followed by a reduction at days 14 and 21. This peak matched the onset of vessel formation, macrophage infiltration and sponge fibrovascular encapsulation. In a rat MI model, specific binding of [3H]NS14490 was low in sham and remote MI myocardium. Specific binding within the infarct increased from day 14 post-MI (33.8 ± 14.1 µCi/g, P ≤ 0.01 versus sham), peaking at day 28 (48.9 ± 5.1 µCi/g, P ≤ 0.0001 versus sham). Histological and proteomic profiling of ɑ7nAChR positive tissue revealed strong associations between ɑ7nAChR and extracellular matrix deposition, and rat cardiac fibroblasts expressed ɑ7nAChR protein under normoxic and hypoxic conditions.

Conclusion

ɑ7nAChR is highly expressed in human macrophages and showed proliferation and hypoxia-driven expression in human endothelial cells. While NS14490 imaging displays a pattern that coincides with vessel formation, macrophage infiltration and fibrovascular encapsulation in the sponge model, this is not the case in the MI model where the ɑ7nAChR imaging signal was strongly associated with extracellular matrix deposition which could be explained by ɑ7nAChR expression in fibroblasts. Overall, these findings support the involvement of ɑ7nAChR across several processes central to cardiac repair, with fibrosis most closely associated with ɑ7nAChR following MI.
Enoxaparin for VTE thromboprophylaxis during inpatient rehabilitation care: assessment of the standard fixed dosing regimen
Authors: Haim Amir , Avnery Orli , Rubin-Asher Deborah , Amir Hagay , Hashem Kaifa , Zvi Harel Ben , Ratmansky Motti
Published: January 2024

Background

We aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation.

Methods

This was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity.

Results

We found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients’ weight and renal function as defined by creatinine clearance (CrCl) (p<0.05).

Conclusions

Our study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function.

Trial registration

No. NCT103593291, registered August 2018.
Comprehensive study and scientific process to increase the accuracy in estimating the thermal conductivity of nanofluids containing SWCNTs and CuO nanoparticles using an artificial neural network
Authors: Esfe Mohammad Hemmat , Amoozad Fatemeh , Hatami Hossein , Toghraie Davood
Published: January 2024

This investigation aimed to evaluate the thermal conductivity ratio (TCR) of SWCNT-CuO/Water nanofluid (NF) using experimental data in the T range of 28–50 ℃ and solid volume fraction range of SVF = 0.03 to 1.15% by an artificial neural network (ANN). MLP network with Lundberg-Marquardt algorithm (LMA) was utilized to predict data (TCR) by ANN. In the best case, from the set of various structures of ANN for this nanofluid, the optimal structure was chosen, which consists of 2 hidden layers, the first layer with the optimal structure consisting of 5 neurons and the second layer containing 7 neurons. Eventually, for the optimal structure, the R2 coefficient and MSE are 0.9999029 and 6.33377E-06, respectively. Based on all ANN information, MOD is in a limited area of − 3% < MOD <  + 3%. Comparison of test, correlation yield, and ANN yield display that ANN evaluates laboratory information more exactly.
Face-to-face vs. blended learning in higher education: a quantitative analysis of biological science student outcomes
Authors: Harper Claire V. , McCormick Lucy M. , Marron Linda
Published: January 2024

The COVID-19 pandemic caused a rapid seismic shift to online delivery in otherwise face-to-face higher education settings worldwide. This quantitative research study sought to investigate the effect of different delivery styles and assessment types on student outcomes. Specifically, grades achieved by first year undergraduate Biological Science students at a UK Higher Education institution were compared from seven modules across two different academic years, namely 2018–2019 and 2020–2021. The academic year 2018–2019 was delivered in the traditional face-to-face manner whereas the 2020–2021 method of delivery was via blended learning. The results showed that four of the seven modules were negatively affected by the transition from face-to-face to blended delivery (p < 0.05, T-test). One module was unaffected (p > 0.05, T-test) and the remaining two modules were positively affected (p < 0.05, T-test). However, the percentage of students requiring reassessments increased with blended learning delivery although this was not significant (p < 0.05, T-test). In summary, the majority of individual module marks decreased with blended learning compared to face-to-face delivery, with an associated increase in required reassessments. Although there are positive benefits to incorporating an element of online learning for students, it is important to utilise this information in future module delivery planning to support the varying student cohorts of the future.
Enhancing forensic education: exploring the importance and implementation of evidence-based education system
Authors: Nilendu Debesh
Published: January 2024

This manuscript explores the importance of an evidence-based education system in forensic education and its implications for improving forensic training and practice.

Background The demand for graduates in forensic science, equipped with knowledge aligned with the latest best practices, is increasingly critical not only on a national scale but also in the global context. Incidents and trends underscore the urgency of implementing evidence-based education in forensic science, ensuring that the next generation of professionals is prepared to address complex crime scenes and challenges.

Body Collaboration between academia and practicing professionals is essential to keep forensic education relevant and responsive to the dynamic field's needs. An illustrative example of successful collaboration can be seen in the partnership between then India's "National Institute of Criminology and Forensic Science (NICFS)" and the "Central Bureau of Investigation (CBI)." This collaboration has significantly enhanced forensic education in India, with joint initiatives bridging the gap between theoretical knowledge and practical application.

In the realm of faculty development and training, effective strategies and programs have significantly enhanced faculty skills and knowledge in forensic science. For example, immersive workshops and mentorship programs provide educators with practical experience and keep them updated on the latest forensic techniques. Online courses and webinars further facilitate ongoing professional development, expanding educators' expertise.

Turning to the evidence-based education scenario in India, recent developments highlight substantial progress. Collaborations between Indian forensic institutions and international bodies have enriched curricula and enhanced training methodologies. India is well-positioned to meet the growing demands of the forensic science field with a cadre of highly skilled professionals.

Evidence-based education in forensic science acts as a bridge between academia and practice, enhancing training and the practice's quality. Collaborations, faculty development, and the adoption of global best practices ensure graduates are well-prepared to navigate the complexities of real-world forensic scenarios.

Conclusion By adopting evidence-based principles, addressing challenges, and implementing strategies, forensic education prepares professionals for successful careers in the field. Beyond its immediate impact, evidence-based education holds the potential to contribute to the broader justice system and enhance public trust. Through a well-prepared workforce equipped with critical thinking and problem-solving skills, evidence-based forensic education not only empowers practitioners but also fosters greater confidence in the reliability and integrity of forensic science within society.
Improving the accuracy of predicted first-arrival times using deep learning
Authors: Pu Yitao , Zhang Bo , Wei Chenglin , Xu Yingyu , Liu Hongfei
Published: January 2024

Recently, the task of first-arrival time picking for seismic shot gathers has been treated as an image segmentation problem, and deep-learning (DL) algorithms have been successfully used to predict first-arrival times. Currently, researchers mainly focus on leveraging cutting-edge DL algorithms to improve the performance of DL in first-arrival picking. There are few publications addressing the quality control of the results predicted by DL. We develop a three-step workflow to improve the accuracy of first-arrival time detection computed using DL algorithms. First, we obtain three predicted results (generation I) by applying the holistically nested U-net (HU-net) to seismic shot gathers, the envelope of seismic shot gathers, and the cosine of the instantaneous phase of seismic shot gathers. Subsequently, we obtain generation II picking by statistically analyzing the predicted generation I picking. Finally, we treat the first-arrival picking task as a constrained path search problem and the generation II picking function as the constraints. The developed workflow is applied to real seismic surveys to demonstrate its effectiveness.
Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives
Authors: McCabe Martin G. , Geoerger Birgit , Chesler Louis , Hargrave Darren , Parsons D. Williams , van Tilburg Cornelis M. , Schleiermacher Gudrun , Hickman John A. , George Sally L.
Published: January 2024

Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers.