bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol outlets and alcohol consumption in changing environments: prevalence and changes over time
Authors: Auchincloss Amy H. , Niamatullah Saima , Adams Maura , Melly Steven J. , Li Jingjing , Lazo Mariana 
Published: February 2022

Abstract
Background
To examine whether changes in density of neighborhood alcohol outlets affected changes in alcohol consumption 1-year after regulatory changes increased alcohol availability.

Methods
Person-level data came from a population-based cohort (aged 21–64) residing in/around the Philadelphia, Pennsylvania metropolitan area (2016–2018, N = 772). Fifty-eight percent lived in a state that began implementing new regulations (Pennsylvania) and the remainder lived in states without major regulatory changes (Delaware and New Jersey). Alcohol consumption was assessed as days per week (pw), drinks pw, high consumption (≥8 drinks pw), and binge drinking. Availability of off-premise alcohol outlets was assessed using 1-mile density and distance. Regression models adjusted for age, gender, race/ethnicity, income, education, health status, state and population density.

Results
Cross-sectional analyses found that higher outlet density was associated with more alcohol consumption (days, drinks, high consumption; all p < 0.03) and residing farther from an outlet was associated with less alcohol consumption (days and drinks; all p < 0.04). In longitudinal analyses, relative to no change in outlets, exposure to more outlets was associated with 64% higher odds of drinking on more days pw (p < 0.049) and 55% higher odds of consuming more drinks pw (p < 0.081). However, the longitudinal association between changes in outlets and changes in consumption did not differ for residents in Pennsylvania vs. nearby states. In cross-sectional and longitudinal analyses, outlets were not related to binge drinking.

Conclusion
Off-premise outlets were associated with alcohol consumption consistently in cross-sectional analysis and in some longitudinal analyses. Results can inform future studies that wish to evaluate longer-term changes in increased alcohol availability and effects on consumption.
Cost, cost-consequence and cost-effectiveness evaluation of a practice change intervention to increase routine provision of antenatal care addressing maternal alcohol consumption
Authors: Szewczyk Zoe , Reeves Penny , Kingsland Melanie , Doherty Emma , Elliott Elizabeth , Wolfenden Luke , Tsang Tracey W. , Dunlop Adrian , Searles Andrew , Wiggers John 
Published: February 2022

Abstract
Background
Implementation of antenatal clinical guideline recommendations for addressing maternal alcohol consumption is sub-optimal. There is a complete absence of evidence of the cost and cost-effectiveness of delivering practice change interventions addressing maternal alcohol consumption amongst women accessing maternity services. The study sought to determine the cost, cost-consequence and cost-effectiveness of developing and delivering a multi-strategy practice change intervention in three sectors of a health district in New South Wales, Australia.

Methods
The trial-based economic analyses compared the costs and outcomes of the intervention to usual care over the 35-month period of the stepped-wedge trial. A health service provider perspective was selected to focus on the cost of delivering the practice change intervention, rather than the cost of delivering antenatal care itself. All costs are reported in Australian dollars ($AUD, 2019). Univariate and probabilistic sensitivity analyses assessed the effect of variation in intervention effect and costs.

Results
The total cost of delivering the practice change intervention across all three sectors was $367,646, of which $40,871 (11%) were development costs and $326,774 (89%) were delivery costs. Labour costs comprised 70% of the total intervention delivery cost. A single practice change strategy, ‘educational meetings and educational materials’ contributed 65% of the delivery cost. Based on the trial’s primary efficacy outcome, the incremental cost effectiveness ratio was calculated to be $32,570 (95% CI: $32,566–$36,340) per percent increase in receipt of guideline recommended care. Based on the number of women attending the maternity services during the trial period, the average incremental cost per woman who received all guideline elements was $591 (Range: $329 - $940) . The average cost of the intervention per eligible clinician was $993 (Range: $640-$1928).

Conclusion
The intervention was more effective than usual care, at an increased cost. Healthcare funders’ willingness to pay for this incremental effect is unknown. However, the strategic investment in systems change is expected to improve the efficiency of the practice change intervention over time. Given the positive trial findings, further research and monitoring is required to assess the sustainability of intervention effectiveness and whether economies of scale, or reduced costs of intervention delivery can be achieved without impact on outcomes.

Trial registration
The trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).
Transfer of knowledge to diagnose infant abuse and its incidence – a time-series analysis from Sweden
Authors: Högberg Ulf 
Published: February 2022

Abstract
Aim
To analyse the transfer of knowledge on how to detect physical abuse, especially shaken baby syndrome/abusive head trauma (SBS/AHT), and its association to trends in infant abuse diagnoses (maltreatment and assault).

Methods
Design: retrospective population-based and quasi-experimental. Setting: Sweden 1987–2019. Patients: Children below age 1 year, selected from the National Patient Register (n = 1150). Exposures: Literature search for transfer of knowledge by diffusion, dissemination and implementation, and whether supportive or disruptive of the SBS/AHT paradigm. Main outcome measure: Abuse diagnoses (maltreatment or assault). Analyses: Incidence rate, incidence rate ratio (IRR).

Results
The overall incidence rate of abuse was 32.23 per 100,000 during the years 1987–2019. It was rather stable 1987–2000. The SBS diagnosis was introduced in the late 1990s. A comprehensive increase of transfer of knowledge on physical abuse, specifically on SBS/AHT and dangers of shaking, took place from 2002 and onward through diffusion, dissemination and implementation. Maltreatment diagnoses, but not assault diagnosis, increased steeply during 2002–2007, peaking in 2008–2013 [IRR 1.63 (95% confidence interval 1.34–1.98)]. Transfer of disruptive knowledge on SBS/AHT during the period 2014–2019 was associated with a decline in maltreatment diagnoses [IRR 0.84 (95% confidence interval 0.71–0.99)].

Conclusion
An increase in maltreatment diagnoses was associated with transfer of supportive knowledge of the SBS/AHT paradigm, while a decline occurred toward the end of the study period, which might indicate a burgeoning de-implementation process.
Differential regulation of progranulin derived granulin peptides
Authors: Zhang Tingting , Du Huan , Santos Mariela Nunez , Wu Xiaochun , Pagan Mitchell D. , Trigiani Lianne Jillian , Nishimura Nozomi , Reinheckel Thomas , Hu Fenghua 
Published: February 2022

Abstract
Background
Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN is comprised of 7.5 granulin repeats and is processed into individual granulin peptides in the lysosome. However, very little is known about the levels and regulations of individual granulin peptides due to the lack of specific antibodies.

Results
Here we report the generation and characterization of antibodies specific to each granulin peptide. We found that the levels of granulins C, E and F are regulated differently compared to granulins A and B in various tissues. The levels of PGRN and granulin peptides vary in different brain regions and the ratio between granulins and PGRN is highest in the cortical region in the adult male mouse brain. Granulin-A is localized in the lysosome in both neurons and microglia and its levels in microglia increase under pathological conditions. Interestingly, the levels of granulin A in microglia change correspondingly with PGRN in response to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and the PGRN binding partner prosaposin leads to alterations in the ratios between individual granulin peptides. Granulins B, C and E are heavily glycosylated and the glycosylation patterns can be regulated.

Conclusion
Our results support that the levels of individual granulin peptides are differentially regulated under physiological and pathological conditions and provide novel insights into how granulin peptides function in the lysosome.
Anticancer and antibacterial potentials induced post short-term exposure to electromagnetic field and silver nanoparticles and related pathological and genetic alterations: in vitro study
Authors: Mohamed Aly Fahmy , Nasr Mohamed , Amer Mohamed E. , Abuamara Tamer M. M. , Abd-Elhay Wagih M. , Kaabo Hassan Fathy , Matar Emad Eldin R. , El Moselhy Laila E. , Gomah Tamer Albasyoni , Deban Mohammed Abd EL-Fatah , Shebl Rania Ibrahim 
Published: February 2022

Abstract
Background
Resistance to antibiotics and anticancer therapy is a serious global health threat particularly in immunosuppressed cancer patients. Current study aimed to estimate the antibacterial and anticancer potentials of short-term exposure to extremely low frequency electromagnetic field (ELF-EMF) and silver nanoparticles (AgNPs) either in sole or combined form.

Methods
Antibacterial activity was evaluated via determination of the bacterial viable count reduction percentage following exposure, whereas their ability to induce apoptosis in breast cancer (MCF-7) cell line was detected using annexin V-fluorescein isothiocyanate and cell cycle analysis. Also, oxidative stress potential and molecular profile were investigated.

Results
ELF-EMF and AgNPs significantly (p < 0.01) reduced K. pneumonia viable count of compared to that of S. aureus in a time dependent manner till reaching 100% inhibition when ELF-EMF was applied in combination to 10 µM/ml AgNPs for 2 h. Apoptosis induction was obvious following exposure to either ELF-EMF or AgNPs, however their apoptotic potential was intensified when applied in combination recording significantly (p < 0.001) induced apoptosis as indicated by elevated level of MCF-7 cells in the Pre G1 phase compared to control. S phase arrest and accumulation of cells in G2/M phase was observed following exposure to AgNPs and EMF, respectively. Up-regulation in the expression level of p53, iNOS and NF-kB genes as well as down-regulation of Bcl-2 and miRNA-125b genes were detected post treatment.

Conclusions
The antibacterial and anticancer potentials of these agents might be related to their ability to induce oxidative stress, suggesting their potentials as novel candidates for controlling infections and triggering cancer cells towards self-destruction.
Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients
Authors: Buttarelli Marianna , Ciucci Alessandra , Palluzzi Fernando , Raspaglio Giuseppina , Marchetti Claudia , Perrone Emanuele , Minucci Angelo , Giacò Luciano , Fagotti Anna , Scambia Giovanni , Gallo Daniela 
Published: February 2022

AbstractBackgroundHigh-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene 1) - or BRCA2-wild type (BRCAwt) HGSOC patients, resistance and progressive disease occur earlier and more often than in mutated BRCA. Identification of biomarkers helpful in predicting response to first-line chemotherapy is a challenge to improve BRCAwt HGSOC management.MethodsTo identify a gene signature that can predict response to first-line chemotherapy, pre-treatment tumor biopsies from a restricted cohort of BRCAwt HGSOC patients were profiled by RNA sequencing (RNA-Seq) technology. Patients were sub-grouped according to platinum-free interval (PFI), into sensitive (PFI > 12 months) and resistant (PFI < 6 months). The gene panel identified by RNA-seq analysis was then tested by high-throughput quantitative real-time PCR (HT RT-qPCR) in a validation cohort, and statistical/bioinformatic methods were used to identify eligible markers and to explore the relevant pathway/gene network enrichments of the identified gene set. Finally, a panel of primary HGSOC cell lines was exploited to uncover cell-autonomous mechanisms of resistance.ResultsRNA-seq identified a 42-gene panel discriminating sensitive and resistant BRCAwt HGSOC patients and pathway analysis pointed to the immune system as a possible driver of chemotherapy response. From the extended cohort analysis of the 42 DEGs (differentially expressed genes), a statistical approach combined with the random forest classifier model generated a ten-gene signature predictive of response to first-line chemotherapy. The ten-gene signature included: CKB (Creatine kinase B), CTNNBL1 (Catenin, beta like 1), GNG11 (G protein subunit gamma 11), IGFBP7 (Insulin-like growth factor-binding protein 7), PLCG2 (Phospholipase C, gamma 2), RNF24 (Ring finger protein 24), SLC15A3 (Solute carrier family 15 member 3), TSPAN31 (Tetraspanin 31), TTI1 (TELO2 interacting protein 1) and UQCC1 (Ubiquinol-cytochrome c reductase complex assembly factor). Cytotoxicity assays, combined with gene-expression analysis in primary HGSOC cell lines, allowed to define CTNNBL1, RNF24, and TTI1 as cell-autonomous contributors to tumor resistance.ConclusionsUsing machine-learning techniques we have identified a gene signature that could predict response to first-line chemotherapy in BRCAwt HGSOC patients, providing a useful tool towards personalized treatment modalities.
Multiple distinct domains of human XIST are required to coordinate gene silencing and subsequent heterochromatin formation
Authors: Dixon-McDougall Thomas , Brown Carolyn J. 
Published: February 2022

Abstract
Background
Mammalian dosage compensation is achieved by the inactivation of one X chromosome in XX individuals. In eutheria this process is initiated early in development by the long non-coding RNA XIST. Studies of the initiation of silencing by XIST have focussed on mouse models, so the domains of XIST required to induce silencing in humans, and their relationship with domains required to establish heterochromatin remain to be determined.

Methods
We have previously established an inducible XIST cDNA in somatic cells and shown it can induce silencing and recruit heterochromatic features. We now assess a series of deletions across the transgene for the ability to induce silencing and integrate these results with time-course and chromatin-remodelling inhibitor treatments to follow the steps of XIST-induced silencing and heterochromatinization.

Discussion
We find that in addition to the previously reported necessity of the 5’ A repeat region for XIST-induced silencing, the 1 kb around the small F repeat region and a non-repetitive region at the 3’ end of the RNA are also required to silence genes. Silencing of genes up to 17 Mb from the XIST integration occurs within 2 days, while formation of a Cot-1 depleted domain is slower, and more dependent on the region encompassing Repeat F. The role of this region encompassing Repeat F in both the silencing of actively transcribed genes, the spread of H3K27me3 and the formation of a transcriptionally inert domain suggests a role in a pathway crucial for the spread of XIST across the chromatin to target distal regions of inactivation. Histone deacetylation requires only the A repeat region, with HDAC3 inhibition showing limited effect on silencing, but an impact on H3K27me3 recruitment, and as a result the recruitment of MacroH2A. Global HDAC inhibition impacted silencing in both a distance and dose-dependent fashion. The E repeat region was required for CIZ1 and H4K20me1 recruitment as well as H3K27me3; however, these appeared to act relatively independently. The H3K27me3 mark established by PRC2 integrated silencing and many of the heterochromatic features, while the PRC1 mark ubH2A appeared to be downstream of silencing in these human somatic cells.
N6-methyladenosine-dependent modification of circGARS acts as a new player that promotes SLE progression through the NF-κB/A20 axis
Authors: Zhao Xingwang , Dong Rui , Zhang Longlong , Guo Junkai , Shi Ying , Ge Lan , Wang Juan , Song Zhiqiang , Ni Bing , You Yi 
Published: February 2022

Abstract
Background
Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE

Methods
Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE.

Results
Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2).

Conclusions
The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.
Dual-energy CT with virtual monoenergetic images to improve the visualization of pancreatic supplying arteries: the normal anatomy and variations
Authors: Liang Hong-wei , Zhou Yang , Zhang Zhi-wei , Yan Gao-wu , Du Si-lin , Zhang Xiao-hui , Li Xin-you , Lv Fa-jin , Zheng Qiao , Li Yong-mei 
Published: February 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with poor prognosis, appropriate surgical resection and neoadjuvant therapy depend on the accurate identification of pancreatic supplying arteries. We aim to evaluate the ability of monoenergetic images (MEI [+]) of dual-energy CT (DECT) to improve the visualization of pancreatic supplying arteries compared to conventional polyenergetic images (PEI) and investigate the implications of vascular variation in pancreatic surgery and transarterial interventions.

Results
One hundred patients without pancreatic diseases underwent DECT examinations were retrospectively enrolled in this study. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at 40-keV MEI (+) were significantly higher than those of PEI (p < 0.05). All subjective MEI (+) scores were significantly higher than those of PEI (p < 0.05). The visualization rates were significantly higher for posterior superior pancreaticoduodenal artery (PSPDA), anterior and posterior inferior pancreaticoduodenal artery (AIPDA, PIPDA), anterior and posterior pancreaticoduodenal arcade (APAC, PPAC), transverse and caudal pancreatic artery (TPA, PCA) at 40-keV MEI (+) than those of PEI (p < 0.05). However, there were no significant differences for visualizing anterior superior pancreaticoduodenal artery (ASPDA), inferior pancreaticoduodenal artery (IPDA), dorsal and magnificent pancreatic artery (DPA, MPA) between 40-keV MEI (+) and PEI (p > 0.05). Four types of variations were observed in the origin of DPA and three to five types in the origin of PSPDA, AIPDA and PIPDA.

Conclusions
40-keV MEI (+) of DECT improves the visualization and objective and subjective image quality of pancreatic supplying arteries compared to PEI. Pancreatic supplying arteries have great variations, which has important implications for preoperative planning of technically challenging surgeries and transarterial interventions.
Bone marrow mesenchymal stem cells enhance angiogenesis and promote fat retention in fat grafting via polarized macrophages
Authors: Dang Juanli , Yang Jizhong , Yu Zhou , Chen Lin , Zhang Zhaoxiang , Wang Kai , Tang Jiezhang , Yi Chenggang 
Published: February 2022

Abstract
Background
Fat grafting is one of the most common soft tissue filling methods in plastic surgery. Bone marrow mesenchymal stem cell (BM-MSC) transplantation is an effective method for improving graft retention. However, the role of BM-MSCs in fat transplantation is not completely clear.

Methods
Human fat particles, together with BM-MSCs or PBS as a control, were subcutaneously transplanted into the backs of nude mice. Samples were taken on days 14, 30 and 90 post-grafting to calculate the fat graft retention rate, and tissue staining was evaluated. Furthermore, macrophages were treated with BM-MSC conditioned medium (BM-MSC-CM) to identify the beneficial component secreted by these stem cells.

Results
In this study, we found that BM-MSCs improved retention by enhancing angiogenesis in fat grafting. Further analysis revealed that BM-MSCs could significantly inhibit the expression of the proinflammatory M1 macrophage markers interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 in the early stages of fat grafting and promote the expression of the anti-inflammatory M2 macrophage markers Arg1, IL-10 and VEGF. Furthermore, our results showed that IL-10 secreted by BM-MSCs induced M2 macrophage polarization in vitro.

Conclusions
BM-MSC transplantation can improve the fat retention rate and promote angiogenesis, which may be related to M2 macrophages. These results help elucidate the role of BM-MSCs in fat grafting.