bluuebunny/crossref_metadata_2025_split huggingface dataset:
Root coverage of a maxillary lateral incisor with gingival recession, gingival stillman’s cleft, bony exostosis, and denture stomatitis: a case report with 3-year follow-up
Authors: Xie Chengjie , Liu Yeungyeung , Yu Huimin , Mei Jie 
Published: February 2022

Abstract
Background
Coronally advanced flap combined with connective tissue graft is considered as the golden standard of root coverage. Although Miller class I recession is considered to get complete root coverage, there are some uncommon conditions in different cases. This case reported a maxillary lateral incisor with a gingival recession, a stillman’s cleft, a bony exostosis and a denture stomatitis.

Case presentation
A 27-year-old female with a gingival recession, a stillman’s cleft and a bony exostosis was treated by coronally advanced flap combined with connective tissue graft technique, and the complete coverage was achieved. Later a denture stomatitis occurred when an acrylic removable partial denture was used, however the gingival margin was not affected. The denture stomatitis disappeared when a new denture with casting palatal plane was produced. In this case of 3-year follow-up, the gingival contour remained stable and the outcome was satisfactory.

Conclusion
Coronally advanced flap combined with connective tissue graft technique is a classic manner to treat gingival recession especially for a long term stability, even when there is a gingival stillman’s cleft, a bony exostosis and a denture stomatitis.
Developing a framework to describe stigma related to cervical cancer and HPV in western Kenya
Authors: Ginjupalli Ramya , Mundaden Rachel , Choi Yujung , Herfel Emily , Oketch Sandra Yvonne , Watt Melissa H. , Makhulo Breandan , Bukusi Elizabeth Anne , Huchko Megan 
Published: February 2022

Abstract
Background
Despite a high prevalence of human papillomavirus (HPV) and cervical cancer in low and middle-income countries, stigma remains an issue. Addressing HPV and cervical cancer stigma could significantly improve health outcomes for these conditions. The objective of this study was to identify the manifestations of stigma and their potential impacts on health-seeking behavior.

Methods
Twenty-six in-depth interviews were conducted with women living with HIV, HIV-negative women, community health volunteers, and health care providers in Kisumu, Kenya in 2019. The interviews were designed to draw out existing attitudes or experiences related to stigma within the community. We conducted a thematic analysis of the interviews to identify internalized, anticipated, and discriminatory attitudes.

Results
Within internalized attitudes, a prominent observed theme was a fear of death associated with a positive HPV test. This stemmed from a lack of understanding of differences between HPV and cervical cancer and posed a significant barrier for women deciding to seek screening or to continue with treatment. Discriminatory attitudes of community members, including assumptions of promiscuity, infidelity, or HIV status, were perceived to prevent women from accessing screening and treatment opportunities. The interviews also exhibited a limited awareness of HPV in this region, which may have contributed to a lack of enacted stigma towards people living with HPV or cervical cancer.

Conclusion
Stigma has the potential to lead to decreased screening and treatment uptake through its drivers. This includes a decreased perception of personal risk due to a lack of knowledge, which results in increased HPV-risk behaviors. Future research must focus on creating and integrating stigma-reducing interventions, primarily to encourage women to seek out primary and secondary preventative measures.
An ethical analysis of clinical triage protocols and decision-making frameworks: what do the principles of justice, freedom, and a disability rights approach demand of us?
Authors: Zhu Jane , Brenna Connor T. A. , McCoy Liam G. , Atkins Chloë G. K. , Das Sunit 
Published: February 2022

Abstract
Background
The expectation of pandemic-induced severe resource shortages has prompted authorities to draft and update frameworks to guide clinical decision-making and patient triage. While these documents differ in scope, they share a utilitarian focus on the maximization of benefit. This utilitarian view necessarily marginalizes certain groups, in particular individuals with increased medical needs.

Main body
Here, we posit that engagement with the disability critique demands that we broaden our understandings of justice and fairness in clinical decision-making and patient triage. We propose the capabilities theory, which recognizes that justice requires a range of positive capabilities/freedoms conducive to the achievement of meaningful life goals, as a means to do so. Informed by a disability rights critique of the clinical response to the pandemic, we offer direction for the construction of future clinical triage protocols which will avoid ableist biases by incorporating a broader apprehension of what it means to be human.

Conclusion
The clinical pandemic response, codified across triage protocols, should embrace a form of justice which incorporates a vision of pluralistic human capabilities and a valuing of positive freedoms.
Productivity analysis of regional-level hospital care in the Czech republic and Slovak Republic
Authors: Vaňková Ivana , Vrabková Iveta 
Published: February 2022

AbstractBackgroundProviding hospital care is an essential objective of national health policies. The countries that share common history, when they emerged from the same health system and similar conditions in the early 1990s, after the division of Czechoslovakia, became the objects of evaluation of the development of technical efficiency of hospital care. The subsequent development of their health care system also was very similar, but no longer entirely identical. The article aims to identify the trends and disparities in the productivity of the capacities of hospital care on the regional level (NUTS III.) in the Czech Republic and the Slovak Republic in 2009–2018 before the COVID-19 pandemic using the multi-criteria decision methods.MethodsThe window analysis as a dynamic DEA method based on moving averages and also the Malmquist Index, that allows the evaluation of changes in relative efficiency and of changes in the production possibilities frontier have become the key methods for evaluating the over time efficiency evolution. To model technical efficiency, an output-oriented method assuming constant returns to scale was chosen. Aggregated input and output parameters for each region were the object of study.ResultsThe results showed that differences in the efficiency trends in terms of the examined parameters among the individual regions are slightly greater in the Czech Republic than in the Slovak Republic. The least efficient regions are those where capital cities are located. Furthermore, the analysis showed that in 2018 all of the Slovak Republic regions improved its productivity compared to 2009 and that technological conditions had a significant impact on this improvement. The results of the Czech Republic regions show productivity improvement in 57% of the regions that, on the contrary, was due to changes in technical efficiency.ConclusionsIt should be recommended to the state- and regional-level governments to refrain from unilaterally preferring the orientation of public policies on the efficiency of the provision of hospital care, and rather focus on increasing the quality and availability of hospital care, especially in smaller, rural, and border regions, in the interest of population safety during pandemics and other emergencies.
Comprehensive analysis of N6-methyladenosine regulators with the tumor immune landscape and correlation between the insulin-like growth factor 2 mRNA-binding protein 3 and programmed death ligand 1 in bladder cancer
Authors: Cui Jianfeng , Zhu Yaofeng , Liu Xiaochen , Wang Wenfu , Jiang Xuewen , Xia Yangyang , Zhou Guanwen , Chen Shouzhen , Shi Benkang 
Published: February 2022

Abstract
Background
N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications of RNA. However, there is limited information about the potential roles of m6A regulators in tumor immunity. Therefore, in this study, we aimed to testify the functions of m6A regulators in bladder cancer as well as their association with the tumor immune landscape.

Methods
We reported the variation and expression levels of m6A regulators in the TCGA database and GTEx database of bladder cancer. Clusters, risk score patterns, and nomograms were constructed to evaluate the function and prognostic value of m6A regulators. Furthermore, we constructed nomogram to evaluate the prognosis of the individual patients. The correlation between insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and programmed cell death ligand 1 (PD-L1) was evaluated both in vitro and in vivo.

Results
We found that the tumor grade and DNA damage pathways were strongly correlated with distinct clusters. Furthermore, two risk score groups with six m6A regulators were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analysis, which could be regarded as independent prognostic markers in patients with bladder cancer. The risk score pattern was linked to the tumor immune landscape, indicating a correlation between immune checkpoints and m6A regulators. Moreover, an m6A regulator, IGF2BP3, was found to be highly expressed in the tumor samples, regulating both the total and membrane-bound PD-L1 expression levels.

Conclusions
The results of this study revealed that the m6A clusters and patterns play crucial roles in the regulation of tumor immunity, which may be used to develop comprehensive treatment strategies for the management of bladder cancer.
Best interests and low thresholds: legal and ethical issues relating to needle and syringe services for under 18s in Sweden
Authors: Barrett Damon , Petersson Frida , Turner Russell 
Published: February 2022

AbstractAccess for legal minors to needle and syringe programmes raises a number of practical, legal and ethical challenges that traverse clinical practice, child protection and child rights. This article addresses the current legal age restriction on access to needle and syringe programmes (NSPs) in Sweden. Based on legislation and legislative preparatory works, it traces the rationale for retaining an age restriction in the context of a policy priority to improve access for people who inject drugs. Building on threshold theory and child rights literature, the article unpacks the apparent tension between protecting the low threshold nature of service provision, child protection duties of healthcare staff, and the best interests of the child. It explores whether this tension could be alleviated through replacing a legal age restriction for all with best interests assessments for each individual, and discusses the potential ethical and practical challenges involved in such a change.
Scavenger receptor CD36 governs recruitment of myeloid cells to the blood–CSF barrier after stroke in neonatal mice
Authors: Rayasam Aditya , Mottahedin Amin , Faustino Joel , Mallard Carina , Vexler Zinaida S. 
Published: February 2022

Abstract
Background
Ischemic stroke induces the activation and recruitment of peripheral leukocytes to the injured brain. These cells can infiltrate the brain through multiple routes, either by penetrating blood–brain barrier or via blood–CSF barriers at the meninges or the choroid plexus (CP). We previously showed that myeloid cell trafficking via the CP occurs early after neonatal arterial stroke and modulates injury. CD36 is a receptor that mediates function of endothelial cells and cells of the monocyte lineage under various neurodegenerative conditions and can influence brain injury after neonatal stroke. Here we asked whether CD36 impacts injury by altering leukocyte trafficking through the CP in neonatal mice subjected to transient middle cerebral artery occlusion (tMCAO).

Methods
In neonatal mice with intact or globally disrupted CD36 signalling (CD36 KO), we characterized the phenotypes of myeloid cells by flow cytometry and the underlying gene expression signatures in the CPs contralateral and ipsilateral to tMCAO by RNA sequencing analyses, focussing on early post-reperfusion time window.

Results
Flow cytometry in the isolated CPs revealed that CD36 mediates stepwise recruitment of myeloid cells to the CP ipsilateral to tMCAO early after reperfusion, with a predominant increase first in inflammatory monocyte subsets and neutrophils followed by patrolling monocytes. RNA sequencing analyses demonstrated marked changes in gene expression in the CP ipsilateral compared to the CP contralateral to tMCAO in wild type mice. Changes were further modified by lack of CD36, including distinction in several clusters of genes involved in inflammatory, metabolic and extracellular matrix signalling in the CP ipsilateral to tMCAO.

Conclusion
Altogether, our data suggest cooperation between blood–CSF–brain interface via the CP through CD36-mediated signalling following neonatal stroke with a key role for inflammatory monocytes and neutrophils.
Copper-catalyzed dicarbonyl stress in NAFLD mice: protective effects of Oleuropein treatment on liver damage
Authors: Santini Silvano Junior , Tarantino Giovanni , Iezzi Antonella , Alisi Anna , Balsano Clara 
Published: February 2022

AbstractBackgroundNonalcoholic fatty liver disease (NAFLD) or more appropriately, metabolic associated fatty liver disease (MAFLD), is the hepatic manifestation of metabolic syndrome. An imbalance of copper homeostasis has been described in the progression of NAFLD/MAFLD toward NASH/MASH. We were interested in understanding whether the chelating activity of Oleuropein (Ole) was able to improve the copper accumulation and the related pro-oxidant and glycative damage in the liver of mice fed HFD.MethodsTwelve C57BL/6J mice fed normal diet (ND) or high-fat diet (HFD) for 16 weeks and then thirty two female and male mice fed ND or HFD for 8 weeks adding Ole for the following 8 weeks were studied.ResultsAltered expression of copper-trafficking genes and proteins (CTR1, CTR2, ATP7B, COX17, CCS, and ATOX1) induced imbalance of copper homeostasis combined with an increase in dicarbonyl stress in the liver of HFD fed mice. Interestingly enough, glyoxalase system was improved by Ole administration and the Ole related protective effects differ in the two sexes of mice.ConclusionsOur study highlights the role of the dicarbonyl stress in the pathogenesis of NAFLD and suggests Ole as a natural copper chelator to prevent the liver damage induced by methyglyoxal pathway derangement.
Lipid metabolism contribute to the pathogenesis of IgA Vasculitis
Authors: Liu Ying , Wen Min , He Qingnan , Dang Xiqiang , Feng Shipin , Liu Taohua , Ding Xuewei , Li Xiaoyan , He Xiaojie 
Published: February 2022

Abstract
Background and objectives
The underlying mechanism of IgA vasculitis (IgAV) and IgA vasculitis with nephritis (IgAVN) remains unclear. Therefore, there are no accurate diagnostic methods. Lipid metabolism is related to many immune related diseases, so this study set out to explore the relationship of lipids and IgAV and IgAVN.

Methods
Fifty-eighth patients with IgAV and 28 healthy controls were recruited, which were divided into six separate pools to investigate the alterations of serum lipids according to the clinical characteristics: healthy controls group (HCs) and IgAV group (IgAVs), IgAVN group (IgAV-N) and IgAV without nephritis group (IgAV-C), initial IgAV group (IgAV0) and IgAV in treatment with glucocorticoids group (IgAV1).

Results
31 identified lipid ions significantly changed in IgAVs with p < 0.05, variable importance of the projection (VIP) > 1 and fold change (FC) > 1.5. All these 31 lipid ions belong to 6 classes: triacylglycerols (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine, ceramide, and lysophosphatidylcholine. TG (16:0/18:1/22:6) +NH4 over 888875609.05, PC (32:1) +H over 905307459.90 and PE (21:4)-H less than 32236196.59 increased the risk of IgAV significantly (OR>1). PC (38:6) +H was significantly decreased (p < 0.05, VIP>1 and FC>1.5) in IgAVN. PC (38:6) less than 4469726623 conferred greater risks of IgAV (OR=45.833, 95%CI: 6.689~341.070).

Conclusion
We suggest that lipid metabolism may affect the pathogenesis of IgAV via cardiovascular disease, insulin resistance, cell apoptosis, and inflammation. The increase of TG(16:0/18:1/22:6) + NH4, and PC(32:1) + H as well as PE (21:4)-H allow a good prediction of IgAV. PE-to-PC conversion may participate in the damage of kidney in IgAV. PC (38:6) + H may be a potential biomarker for IgAVN.
Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway
Authors: Andreuzzi Eva , Fejza Albina , Polano Maurizio , Poletto Evelina , Camicia Lucrezia , Carobolante Greta , Tarticchio Giulia , Todaro Federico , Di Carlo Emma , Scarpa Melania , Scarpa Marco , Paulitti Alice , Capuano Alessandra , Canzonieri Vincenzo , Maiero Stefania , Fornasarig Mara , Cannizzaro Renato , Doliana Roberto , Colombatti Alfonso , Spessotto Paola , Mongiat Maurizio 
Published: February 2022

Abstract
Background
Colorectal cancer is one of the most frequent and deadly tumors. Among the key regulators of CRC growth and progression, the microenvironment has emerged as a crucial player and as a possible route for the development of new therapeutic opportunities. More specifically, the extracellular matrix acts directly on cancer cells and indirectly affecting the behavior of stromal and inflammatory cells, as well as the bioavailability of growth factors. Among the ECM molecules, EMILIN-2 is frequently down-regulated by methylation in CRC and the purpose of this study was to verify the impact of EMILIN-2 loss in CRC development and its possible value as a prognostic biomarker.

Methods
The AOM/DSS CRC protocol was applied to Emilin-2 null and wild type mice. Tumor development was monitored by endoscopy, the molecular analyses performed by IHC, IF and WB and the immune subpopulations characterized by flow cytometry. Ex vivo cultures of monocyte/macrophages from the murine models were used to verify the molecular pathways. Publicly available datasets were exploited to determine the CRC patients’ expression profile; Spearman’s correlation analyses and Cox regression were applied to evaluate the association with the inflammatory response; the clinical outcome was predicted by Kaplan-Meier survival curves. Pearson correlation analyses were also applied to a cohort of patients enrolled in our Institute.

Results
In preclinical settings, loss of EMILIN-2 associated with an increased number of tumor lesions upon AOM/DSS treatment. In addition, in the early stages of the disease, the Emilin-2 knockout mice displayed a myeloid-derived suppressor cells-rich infiltrate. Instead, in the late stages, lack of EMILIN-2 associated with a decreased number of M1 macrophages, resulting in a higher percentage of the tumor-promoting M2 macrophages. Mechanistically, EMILIN-2 triggered the activation of the Toll-like Receptor 4/MyD88/NF-κB pathway, instrumental for the polarization of macrophages towards the M1 phenotype. Accordingly, dataset and immunofluorescence analyses indicated that low EMILIN-2 expression levels correlated with an increased M2/M1 ratio and with poor CRC patients’ prognosis.

Conclusions
These novel results indicate that EMILIN-2 is a key regulator of the tumor-associated inflammatory environment and may represent a promising prognostic biomarker for CRC patients.
Somatic mutational profiles and germline polygenic risk scores in human cancer
Authors: Liu Yuxi , Gusev Alexander , Heng Yujing J. , Alexandrov Ludmil B. , Kraft Peter 
Published: February 2022

Abstract
Background
The mutational profile of cancer reflects the activity of the mutagenic processes which have been operative throughout the lineage of the cancer cell. These processes leave characteristic profiles of somatic mutations called mutational signatures. Mutational signatures, including single-base substitution (SBS) signatures, may reflect the effects of exogenous or endogenous exposures.

Methods
We used polygenic risk scores (PRS) to summarize common germline variation associated with cancer risk and other cancer-related traits and examined the association between somatic mutational profiles and germline PRS in 12 cancer types from The Cancer Genome Atlas. Somatic mutational profiles were constructed from whole-exome sequencing data of primary tumors. PRS were calculated for the 12 selected cancer types and 9 non-cancer traits, including cancer risk determinants, hormonal factors, and immune-mediated inflammatory diseases, using germline genetic data and published summary statistics from genome-wide association studies.

Results
We found 17 statistically significant associations between somatic mutational profiles and germline PRS after Bonferroni correction (p < 3.15 × 10−5), including positive associations between germline inflammatory bowel disease PRS and number of somatic mutations attributed to signature SBS1 in prostate cancer and APOBEC-related signatures in breast cancer. Positive associations were also found between age at menarche PRS and mutation counts of SBS1 in overall and estrogen receptor-positive breast cancer. Consistent with prior studies that found an inverse association between the pubertal development PRS and risk of prostate cancer, likely reflecting hormone-related mechanisms, we found an inverse association between age at menarche PRS and mutation counts of SBS1 in prostate cancer. Inverse associations were also found between several cancer PRS and tumor mutation counts.

Conclusions
Our analysis suggests that there are robust associations between tumor somatic mutational profiles and germline PRS. These may reflect the mechanisms through hormone regulation and immune responses that contribute to cancer etiology and drive cancer progression.