bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the prevalence of cancer risk factors at the small area level in Australia
Authors: Hogg James , Cameron Jessica , Cramb Susanna , Baade Peter , Mengersen Kerrie 
Published: December 2023

Abstract
Background
Cancer is a significant health issue globally and it is well known that cancer risk varies geographically. However in many countries there are no small area-level data on cancer risk factors with high resolution and complete reach, which hinders the development of targeted prevention strategies.

Methods
Using Australia as a case study, the 2017–2018 National Health Survey was used to generate prevalence estimates for 2221 small areas across Australia for eight cancer risk factor measures covering smoking, alcohol, physical activity, diet and weight. Utilising a recently developed Bayesian two-stage small area estimation methodology, the model incorporated survey-only covariates, spatial smoothing and hierarchical modelling techniques, along with a vast array of small area-level auxiliary data, including census, remoteness, and socioeconomic data. The models borrowed strength from previously published cancer risk estimates provided by the Social Health Atlases of Australia. Estimates were internally and externally validated.

Results
We illustrated that in 2017–2018 health behaviours across Australia exhibited more spatial disparities than previously realised by improving the reach and resolution of formerly published cancer risk factors. The derived estimates revealed higher prevalence of unhealthy behaviours in more remote areas, and areas of lower socioeconomic status; a trend that aligned well with previous work.

Conclusions
Our study addresses the gaps in small area level cancer risk factor estimates in Australia. The new estimates provide improved spatial resolution and reach and will enable more targeted cancer prevention strategies at the small area level. Furthermore, by including the results in the next release of the Australian Cancer Atlas, which currently provides small area level estimates of cancer incidence and relative survival, this work will help to provide a more comprehensive picture of cancer in Australia by supporting policy makers, researchers, and the general public in understanding the spatial distribution of cancer risk factors. The methodology applied in this work is generalisable to other small area estimation applications and has been shown to perform well when the survey data are sparse.
Revolutionizing the female reproductive system research using microfluidic chip platform
Authors: Yan Jinfeng , Wu Tong , Zhang Jinjin , Gao Yueyue , Wu Jia-Min , Wang Shixuan 
Published: December 2023

AbstractComprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes’ manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere.
Graphical Abstract
Identifying the natural products in the treatment of atherosclerosis by increasing HDL-C level based on bioinformatics analysis, molecular docking, and in vitro experiment
Authors: Chen Yilin , Zhang Fengwei , Sun Jijia , Zhang Lei 
Published: December 2023

Abstract
Background
Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the efficacy and safety of natural products in treating atherosclerosis (AS). However, the study of raising HDL-C levels through natural products to treat AS still needs to be explored.

Methods
The gene sets associated with AS were collected and identified by differential gene analysis and database query. By constructing a protein–protein interaction (PPI) network, the core submodules in the network are screened out. At the same time, by calculating node importance (Nim) in the PPI network of AS disease and combining it with Kyoto Encyclopedia of genes and genomes (KEGG) pathways enrichment analysis, the key target proteins of AS were obtained. Molecular docking is used to screen out small natural drug molecules with potential therapeutic effects. By constructing an in vitro foam cell model, the effects of small molecules on lipid metabolism and key target expression of foam cells were investigated.

Results
By differential gene analysis, 451 differential genes were obtained, and a total of 313 disease genes were obtained from 6 kind of databases, then 758 AS-related genes were obtained. The enrichment analysis of the KEGG pathway showed that the enhancement of HDL-C level against AS was related to Lipid and atherosclerosis, Cholesterol metabolism, Fluid shear stress and atherosclerosis, PPAR signaling pathway, and other pathways. Then we intersected 31 genes in the core module of the PPI network, the top 30 genes in Nims, and 32 genes in the cholesterol metabolism pathway, and finally found 3 genes. After the above analysis and literature collection, we focused on the following three related gene targets: APOA1, LIPC, and CETP. Molecular docking showed that Genistein has a good binding affinity for APOA1, CETP, and LIPC. In vitro, experiments showed that Genistein can up-regulated APOA1, LIPC, and CETP levels.

Conclusions
Based on our research, Genistein may have the effects of regulating HDL-C and anti-atherosclerosis. Its mechanism of action may be related to the regulation of LIPC, CETP, and APOA1 to improve lipid metabolism.
Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation
Authors: Zhu Hong , Xiao Feng , Xiao Yao , Guo Yun , Shan Xuesong , Zhang Zhe , Zhang Lieliang , Guo Hua 
Published: December 2023

Abstract
Background
Inflammasomes in astrocytes have been shown to play a crucial role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Cannabinoid Receptor 2(CB2R), a G protein-coupled receptor (GPCR), is considered a promising therapeutic target in inflammation-related disorders. This study aims to explore the role of CB2R in regulating NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated neuroinflammation in astrocytes.

Methods
In an in vivo animal model, specific targeting of astrocytic CB2R was achieved by injecting CB2R-specific adenovirus (or fork head box g1(foxg1) adenovirus) to knock down CB2R or administering CB2R agonists, inhibitors, etc., in the substantia nigra pars compacta (SNc) of mice. A PD mouse model was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induction. Animal behavioral tests, western blot, immunofluorescence, and other experiments were performed to assess the loss of midbrain tyrosine hydroxylase (TH) neurons, activation of astrocytes, and activation of the NLRP3 pathway. Primary astrocytes were cultured in vitro, and NLRP3 inflammasomes were activated using 1-methyl-4-phenylpyridinium (MPP+) or lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Western blot and ELISA experiments were conducted to assess the release of inflammatory factors. Transcriptomic sequencing and CUT&RUN techniques were employed to study the CB2R regulation of the foxg1 binding site on the autophagy molecule microtubule-associated protein 1 light chain 3 beta (MAP1LC3B).

Results
Astrocytic CB2R knockdown impaired the motor abilities of MPTP-induced mice, exacerbated the loss of TH neurons, and induced activation of the NLRP3/Caspase-1/interleukin 1 (IL-1β) pathway. Activation of CB2R significantly alleviated motor impairments in mice while reducing NLRP3 deposition on astrocytes. In vitro cell experiments showed that CB2R activation attenuated the activation of the NLRP3/Caspase-1/IL-1β pathway induced by LPS + ATP or MPP+. Additionally, it inhibited the binding of foxg1 to MAP1LC3B, increased astrocytic autophagy levels, and facilitated NLRP3 degradation through the autophagy–lysosome pathway.

Conclusion
Activation of CB2R on astrocytes effectively mitigates NLRP3-mediated neuroinflammation and ameliorates the disease characteristics of PD in mice. CB2R represents a potential therapeutic target for treating PD.
Adolescent’s and youth’s adherence to antiretroviral therapy for better treatment outcome and its determinants: multi-center study in public health facilities
Authors: Zurbachew Yihenew , Hiko Desta , Bacha Girma , Merga Hailu 
Published: December 2023

Abstract
Background
Low-adherence to Anti-retroviral therapy (ART) negatively affects the clinical, immunological, and virologic outcomes of patients. Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression which ultimately reduces morbidity and mortality. Thus, this study aimed to identify factors affecting adherence to antiretroviral therapy among adolescents and youth living with HIV.

Methods
Facility-based cross-sectional study was conducted from March 21 to April 30, 2020 among 316 respondents in selected five high-loaded hospitals with adolescent and youth clients using systematic random sampling technique. Patients’ adherence was assessed when they had reportedly taken 95% or higher of their prescribed antiretroviral drugs in the five days before the interview. Data were collected, entered into EPI Data and exported to SPSS for analysis. Binary logistic regression was used to see the association between dependent and independent variables.

Results
In this study, 316 respondents participated in the study, with a 99.7% response rate. The mean age of respondents were 17.94 years and majority of them (58.5%) were females. The overall ART adherence among adolescents and youths was found to be 70.6%. Being female (AOR = 0.323, 95% CI, 0.164–0.637), presence of opportunistic infection (AOR = 0.483, 95% CI, 0.249–0.936), taking additional medication beside ART (AOR = 0.436, 95% CI, 0.206–0.922) and availability of youth friendly services within the facility (AOR = 2.206, 95% CI, 1.031–4.721) were found to be predictors.

Conclusion
The adherence rate in this study was low which is below the recommended adherence level. Being female, taking additional medication beside ART and presence of opportunistic infection were determinants of adherence. As a result, significant work must be done on opportunistic infection prevention through health education and promotion for screening and risk reduction. Similarly, adolescents and youths service integration with the ART Clinic is strongly advised.
Gray mold and anthracnose disease detection on strawberry leaves using hyperspectral imaging
Authors: Zhang Baohua , Ou Yunmeng , Yu Shuwan , Liu Yuchen , Liu Ying , Qiu Wei 
Published: December 2023

Abstract
Background
Gray mold and anthracnose are the main factors affecting strawberry quality and yield. Accurate and rapid early disease identification is of great significance to achieve precise targeted spraying to avoid large-scale spread of diseases and improve strawberry yield and quality. However, the characteristics between early disease infected and healthy leaves are very similar, making the early identification of strawberry gray mold and anthracnose still a challenge.

Results
Based on hyperspectral imaging technology, this study explored the potential of combining spectral fingerprint features and vegetation indices (VIs) for early detection (24-h infected) of strawberry leaves diseases. The competitive adaptive reweighted sampling (CARS) algorithm and ReliefF algorithm were used for the extraction of spectral fingerprint features and VIs, respectively. Three machine learning models, Backpropagation Neural Network (BPNN), Support Vector Machine (SVM) and Random Forest (RF), were developed for the early identification of strawberry gray mold and anthracnose, using spectral fingerprint, VIs and their combined features as inputs respectively. The results showed that the combination of spectral fingerprint features and VIs had better recognition accuracy compared with individual features as inputs, and the accuracies of the three classifiers (BPNN, SVM and RF) were 97.78%, 94.44%, and 93.33%, respectively, which indicate that the fusion features approach proposed in this study can effectively improve the early detection performance of strawberry leaves diseases.

Conclusions
This study provided an accurate, rapid, and nondestructive recognition of strawberry gray mold and anthracnose disease in early stage.
Stereotactic radiosurgery of brain metastases: a retrospective study
Authors: Gruber Isabella , Weidner Karin , Treutwein Marius , Koelbl Oliver 
Published: December 2023

Abstract
Background
Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS.

Methods
Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6–22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis.

Results
Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17–0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4–64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40–63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4–26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699).

Conclusions
Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases.

Trial registration
This study is retrospectively registered (ethics approval number 23-3451-104).
Microbiological profile of patients treated for postoperative peritonitis: temporal trends 1999–2019
Authors: Montravers Philippe , Grall Nathalie , Kantor Elie , Augustin Pascal , Boussion Kevin , Zappella Nathalie 
Published: December 2023

Abstract
Background
Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT).

Methods
This retrospective monocentric analysis (1999–2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO.

Results
A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time.

Conclusions
We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO.

Graphical Abstract
Protective factors for resilience in adolescence: analysis of a longitudinal dataset using the residuals approach
Authors: Marquez Jose , Francis-Hew Louis , Humphrey Neil 
Published: December 2023

Abstract
Introduction
The residuals approach, in which residual scores from regression models are used as a proxy for resilient functioning, offers great potential to increase understanding of resilience processes. However, its application in child and adolescent wellbeing research is limited to date. We use this approach to examine how adversity exposure impacts later wellbeing (life satisfaction, and internalising mental health difficulties) in the early-to-middle adolescence transition; whether gender and ethnic differences in resilience exist; which internal and external factors confer protective effects for resilience; and, whether the protective effect of these factors differs by gender and level of adversity exposure.

Method
Secondary analysis of the #BeeWell longitudinal data set (N = 12,130 adolescents, aged 12/13 at T1 and 13/14 at T2, representative of Greater Manchester, England) was undertaken, using a series of linear regressions to establish adversity indices for later wellbeing, before assessing the protective effects of internal and external factors on resilience.

Results
Multiple adversity factors (e.g., home material deprivation, sexuality discrimination, bullying) were found to impact later wellbeing. Girls and white adolescents presented lower levels of resilience than their peers. Internal psychological factors (self-esteem, emotional regulation, optimism) consistently conferred the strongest protective effects, but behavioural/activity factors (physical activity, sleep) also contributed to resilience. Among external factors, friendships and peer support were the most salient. Physical activity yielded stronger protective effects among boys (compared to girls). Effects of protective factors were stronger among those at lower (compared to higher) levels of adversity exposure.

Conclusion
The residuals approach can make a considerable contribution to our understanding of the interplay between adversity exposure and access to protective factors in determining adolescent wellbeing outcomes. Moreover, its application provides clear implications for policy and practice in terms of prevention (of adversity exposure) and intervention (to facilitate resilience).
Activation of PI3K/AKT/mTOR signaling axis by UBE2S inhibits autophagy leading to cisplatin resistance in ovarian cancer
Authors: Zhang Mengjun , Wang Jialin , Guo Yan , Yue Haodi , Zhang Lindong 
Published: December 2023

Abstract
Background
Epithelial ovarian cancer (OC) is the fourth leading cause of cancer-related deaths in women, with a 5-year survival rate of 30%-50%. Platinum resistance is the chief culprit for the high recurrence and mortality rates. Several studies confirm that the metabolic regulation of ubiquitinating enzymes plays a vital role in platinum resistance in OC.

Methods
In this study, we selected ubiquitin-conjugating enzyme E2S (UBE2S) as the candidate gene for validation. The levels of UBE2S expression were investigated using TCGA, GTEx, UALCAN, and HPA databases. In addition, the correlation between UBE2S and platinum resistance in OC was analyzed using data from TCGA. Cisplatin-resistant OC cell lines were generated and UBE2S was knocked down; the transfection efficiency was verified. Subsequently, the effects of knockdown of UBE2S on the proliferation and migration of cisplatin-resistant OC cells were examined through the CCK8, Ki-67 immunofluorescence, clone formation, wound healing, and transwell assays. In addition, the UBE2S gene was also validated in vivo by xenograft models in nude mice. Finally, the relationship between the UBE2S gene and autophagy and the possible underlying regulatory mechanism was preliminarily investigated through MDC and GFP-LC3-B autophagy detection and western blotting experiments. Most importantly, experimental validation of mTOR agonist reversion (the rescuse experiments) was also performed.

Results
UBE2S was highly expressed in OC at both nucleic acid and protein levels. The results of immunohistochemistry showed that the level of UBE2S expression in platinum-resistant samples was significantly higher relative to the platinum-sensitive samples. By cell transfection experiments, knocking down of the UBE2S gene was found to inhibit the proliferation and migration of cisplatin-resistant OC cells. Moreover, the UBE2S gene could inhibit autophagy by activating the PI3K/AKT/mTOR signaling pathway to induce cisplatin resistance in OC in vivo and in vitro.

Conclusion
In conclusion, we discovered a novel oncogene, UBE2S, which was associated with platinum response in OC, and examined its key role through bioinformatics and preliminary experiments. The findings may open up a new avenue for the evaluation and treatment of OC patients at high risk of cisplatin resistance.