bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restored Ketosis Drives Anticancer Immunity in Colorectal Cancer
Authors: Montrose David C. , Galluzzi Lorenzo 
Published: April 2022

AbstractDietary interventions including alterations in the amount or type of specific macronutrients have been shown to mediate antineoplastic effects in preclinical tumor models, but the underlying mechanisms are only partially understood. In this issue of Cancer Research, Wei and colleagues demonstrate that restoring ketogenesis in the colorectal cancer microenvironment decreases the KLF5-dependent synthesis of CXCL12 by cancer-associated fibroblasts, ultimately enhancing tumor infiltration by immune effector cells and increasing the therapeutic efficacy of an immune checkpoint inhibitor specific for PD-1. These findings provide a novel, therapeutically actionable link between suppressed ketogenesis and immunoevasion in the colorectal cancer microenvironment.See related article by Wei et al., p. 1575
Multi-omics Profiling Shows BAP1 Loss Is Associated with Upregulated Cell Adhesion Molecules in Uveal Melanoma
Authors: Baqai Usman , Purwin Timothy J. , Bechtel Nelisa , Chua Vivian , Han Anna , Hartsough Edward J. , Kuznetsoff Jeffim N. , Harbour J. William , Aplin Andrew E. 
Published: April 2022

AbstractBRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is mutated in cancer, including uveal melanoma. Loss-of-function BAP1 mutations are associated with uveal melanoma metastasis and poor prognosis, but the mechanisms underlying these effects remain unclear. Upregulation of cell–cell adhesion proteins is involved with collective migration and metastatic seeding of cancer cells. Here, we show that BAP1 loss in uveal melanoma patient samples is associated with upregulated gene expression of multiple cell adhesion molecules (CAM), including E-cadherin (CDH1), cell adhesion molecule 1 (CADM1), and syndecan-2 (SDC2). Similar findings were observed in uveal melanoma cell lines and single-cell RNA-sequencing data from uveal melanoma patient samples. BAP1 reexpression in uveal melanoma cells reduced E-cadherin and CADM1 levels. Functionally, knockdown of E-cadherin decreased spheroid cluster formation and knockdown of CADM1 decreased growth of BAP1-mutant uveal melanoma cells. Together, our findings demonstrate that BAP1 regulates the expression of CAMs which may regulate metastatic traits.Implications:BAP1 mutations and increased metastasis may be due to upregulation of CAMs.
Using narratives to reduce HIV stigma in rural Ecuador: A health education intervention
Authors: Casapulla Sharon , Gómez-Urrego Guillermo , Madrid Claudia , Iles Chelsea , Keener Chris , Viola Jennifer , Sanchez Alexandra , Orquera Cristina , Kingori Caroline 
Published: April 2022

Objective: To determine the efficacy of using a narrative-based intervention to reduce HIV stigma among members of the general public in a rural community in Ecuador. Design: This cross-sectional intervention study involved a convenience sample of 133 participants from Cariamanga, Ecuador. We used a post-test only comparison group design. Setting: The number of adults living with HIV in Ecuador is increasing. Stigma and discrimination are among the greatest barriers to HIV prevention, access to treatment, care and support. Stigma is also associated with negative health outcomes. The study took place in the rural community of Cariamanga, Loja, Ecuador. Method: The intervention included (1) a fact-based presentation, (2) video stories from two individuals living with HIV and (3) a structured group discussion. Data were collected using an HIV Stigma Scale and an HIV Knowledge Assessment. Data were analysed using independent t-test and multivariate analysis of variance (MANOVA). Results: Participants who received the intervention had higher HIV knowledge scores ( p < .001; d = 2.06) and lower stigma scores (0.59) subsequent to the intervention than the comparison group (1.02, p < .001; d = 1.05). Conclusion: This narrative-based educational intervention was effective in reducing HIV-related stigma. Public health practitioners should consider including narratives as a component of future health education interventions aimed at reducing HIV-related stigma.
Comparison of cytoreductive partial versus radical nephrectomy in metastatic renal cell carcinoma: To be on the horns of a dilemma
Authors: Shemshaki Hamidreza , Al-Mamari Said Abdallah , Al-Hooti Qais , Geelani Ishfaq Ahmed , Al Salmi Issa , Narayana Kurukkal Santosh , Kumar Santhosh , Al Julandani Amani , Sadeghzadeh Samira 
Published: April 2022

Background: Cytoreductive radical nephrectomy (cRN) with immunotherapy is the treatment of choice in patients with metastatic renal cell carcinoma (mRCC). Limited data are available on the role of cytoreductive partial nephrectomy (cPN) in mRCC. This study is a systematic review and meta-analysis of the evidence regarding survival rates comparing cPN versus cRN. Methods: PubMed/Medline, Scopus, Google Scholar, EMBASE, and the Cochrane Library were reviewed in December 2021 according to PRISMA. Four articles including 2669 patients were selected to enroll in the study. The identified reports were reviewed and their methodological quality was subjected to total quality assessment. The outcomes were cancer specific survival (CSS) and overall survival rate (OS). Results: Totally 2669 patients, 542 in cPN and 2127 in cRN groups enrolled in final analysis. Of the preoperative data, there were significant differences in preoperative size of tumor between cRN and cPN patients ( p < 0.001), however Fuhrman grades were comparable between groups (low grade: p =  0.51, high grade: p =  0.76). There were comparable results in 1-year ( p =  0.07), 2-year ( p =  0.08), and 3-year ( p =  0.71) CSS rates between cPN versus cRN. There was no significant difference between cPN versus cRN in OS rate ( p =  0.61). Conclusion: There are comparable results between cPN and cRN in CSS and OS rate. However, due to a lack of data, future study will need to do more extensive studies using prospectively recorded patient features to evaluate the cPN and cRN in the metastatic setting.
Lack of Association of rs12702634 in RPA3-UMAD1 With Interstitial Lung Diseases in Japanese Rheumatoid Arthritis Patients
Authors: Higuchi Takashi , Oka Shomi , Furukawa Hiroshi , Shimada Kota , Tohma Shigeto 
Published: April 2022

Background: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. Methods: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. Results: No association was detected for rs12702634 with ILD in RA ( P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association ( P = .0996, OR 1.52, 95% CI 0.92–2.49). Conclusions: The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.
The European NUTS-level election dataset: A tool to map European electoral geography
Authors: Schraff Dominik , Vergioglou Ioannis , Demirci Buket Buse 
Published: April 2022

Datasets on subnational election results in Europe frequently do not match with regional statistics available for cross-national research, mainly because territorial statistical units change over time and do not map onto the national electoral districts. This hinders consistent comparative research across time. This research note introduces EU-NED, a new dataset on subnational election data that covers national and European parliamentary elections for European countries over the past 30 years. EU-NED’s major contribution is that it provides election results on disaggregated levels of the statistical territorial units used by Eurostat with an unprecedented consistency and temporospatial scope. Moreover, EU-NED is integrated with the Party Facts platform, allowing for a seamless integration of party-level data. Using EU-NED, we present first descriptive evidence on the European electoral geography and suggest avenues of how EU-NED can facilitate future comparative political science research in Europe.
Telomere length and stroke recurrence after ischemic stroke and TIA
Authors: Zhang Xing , Cheng Si , Li Zixiao , Gu Hongqiu , Jiang Yingyu , Li Hao , Meng Xia , Wang Yongjun 
Published: April 2022

Background and Objective: Shortening telomere length (TL), as an indicator of aging, has been associated with increased risk of cardiovascular disease and incident stroke. However, there are limited data relating to the association between TL and recurrent stroke. Methods: Patients from the Third China National Stroke Registry who had whole genome sequencing (WGS) were selected. TL was estimated using TelSeq based on binary sequence alignment/map files derived from WGS data. Cox proportional hazards regression models were performed to assess the association of TL with recurrent stroke. Results: A total of 8041 patients with ischemic stroke (IS) or transient ischemic attack (TIA) were included. Mean TL was 2.14 ± 0.82 kb. Patients in the lowest tertile of TL had higher incidence of stroke recurrence compared to those in the middle and highest tertile (6.4% vs 5.9% vs 5.2%), but the difference was not longer significant after adjusting for age, sex, cardiovascular risk factors and stroke severity. Similarly, when analyzing TL as a continuous variable, the HR per 1000 bp increase in TL was significant 0.88 (0.79–0.98), but after adjusting for co-variates, was no longer significant (0.91; 95% confidence interval (CI), 0.81–1.02). In patients aged > 65 years, but not in younger patients, after adjusting for co-variates, TL was significantly associated with stroke recurrence. Compared to the lowest tertile, HRs (95% CI) after adjustment for all co-variates for the middle and highest tertiles were 0.78 (0.55–1.10) and 0.67 (0.46–0.98), respectively, with p for trend of 0.03. In analyses using TL as a continuous variable, adjusted HR (95% CI) per 1000 bp increase in TL was 0.80 (0.66–0.96). However, there was no significant interaction between TL and age on risk of stroke recurrence ( p for interaction = 0.09). Conclusions: In Chinese IS or TIA patients, no independent association was found between TL and risk of stroke recurrence after adjusting for co-variates. We found a possible association in older patients but this needs replicating.
Association Between Virtual Care Use and Same-Day Primary Care Access in VA Primary Care-Mental Health Integration
Authors: Haderlein Taona P. , Dobalian Aram , Raja Pushpa V. , Der-Martirosian Claudia 
Published: April 2022

Introduction: Same-day referrals from primary care to mental health increase subsequent mental health treatment engagement. VA Primary Care-Mental Health Integration (PC-MHI) clinics offer integrated mental health services embedded in primary care clinics, providing a key entry point to mental health care. Although telehealth use expanded rapidly after the onset of COVID-19, the impact of telehealth on same-day primary care access among new PC-MHI mental health patients is unknown. To address this knowledge gap, we examined associations between telehealth use and same-day primary care access in VA PC-MHI. Methods: We examined electronic health record data to identify same-day primary care appointments among PC-MHI patients who initiated care during 3/1/2018 to 10/29/2021. We used logistic regression analyses to evaluate the effect of telehealth on same-day primary care access. Time, demographic characteristics, mental health diagnoses (PTSD and depression), and substance use disorder diagnosis were evaluated as covariates. Results: New PC-MHI patients who were seen via telehealth were less likely to receive same-day primary care access than patients seen in person (OR: 0.54; 95% CI: 0.41-0.71; P < .001). Conclusions: Despite the potential advantages of using telehealth to increase access, VA patients with an initial PC-MHI visit via telehealth were less likely than patients seen in person to be referred from primary care. Telehealth may adversely affect primary care referrals to mental health services, an outcome that could ultimately reduce specialty mental health care continuity. There is an urgent need to identify strategies to facilitate PC-MHI care coordination in the telehealth context.
Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients
Authors: Li Wei , Li Tiandong , Sun Chenguang , Du Yimeng , Chen Linna , Du Chunyan , Shi Jianxiang , Wang Weijie 
Published: April 2022

AbstractBackgroundPancreatic cancer (PC) is a malignancy with a poor prognosis and high mortality. Surgical resection is the only “curative” treatment. However, only a minority of patients with PC can obtain surgery. Improving the overall survival (OS) rate of patients with PC is still a major challenge. Molecular biomarkers are a significant approach for diagnostic and predictive use in PCs. Several prediction models have been developed for patients newly diagnosed with PC that is operable or patients with advanced and metastatic PC; however, these models require further validation. Therefore, precise biomarkers are urgently required to increase the efficiency of predicting a disease-free survival (DFS), OS, and sensitivity to immunotherapy in PC patients and to improve the prognosis of PC.MethodsIn the present study, we first evaluated the highly and selectively expressed targets in PC, using the GeoMxTM Digital Spatial Profiler (DSP) and then, we analyzed the roles of these targets in PCs using TCGA database.ResultsLAMB3, FN1, KRT17, KRT19, and ANXA1 were defined as the top five upregulated targets in PC compared with paracancer. The TCGA database results confirmed the expression pattern of LAMB3, FN1, KRT17, KRT19, and ANXA1 in PCs. Significantly, LAMB3, FN1, KRT19, and ANXA1 but not KRT17 can be considered as biomarkers for survival analysis, univariate and multivariate Cox proportional hazards model, and risk model analysis. Furthermore, in combination, LAMB3, FN1, KRT19, and ANXA1 predict the DFS and, in combination, LAMB3, KRT19, and ANXA1 predict the OS. Immunotherapy is significant for PCs that are inoperable. The immune checkpoint blockade (ICB) analysis indicated that higher expressions of FN1 or ANXA1 are correlated with lower ICB response. In contrast, there are no significant differences in the ICB response between high and low expression of LAMB3 and KRT19.ConclusionsIn conclusion, LAMB3, FN1, KRT19, and ANXA1 are good predictors of PC prognosis. Furthermore, FN1 and ANXA1 can be predictors of immunotherapy in PCs.
Imageless navigation for primary total hip arthroplasty: a meta-analysis study
Authors: Migliorini Filippo , Cuozzo Francesco , Oliva Francesco , Eschweiler Joerg , Hildebrand Frank , Maffulli Nicola 
Published: April 2022

Abstract
Background
There has been a growing interest in imageless navigation for primary total hip arthroplasty (THA). Its superiority over standard THA is debated. This meta-analysis compared surgical duration, implant positioning, Harris Hip Score and rate of dislocation of imageless navigation versus conventional THA.

Methods
The present study was conducted according to the PRISMA 2020 guidelines. All the clinical trials comparing imageless navigation versus conventional for primary THA were accessed. In January 2022, the following databases were accessed: PubMed, Web of Science, Google Scholar and Embase. No time constraints were used for the search. The outcomes of interest were to compare cup inclination and anteversion, leg length discrepancy, surgical duration, Harris Hip Score and rate of dislocation of imageless navigation versus conventional THA.

Results
Twenty-one studies (2706 procedures) were retrieved. Fifty-two percent of patients were women. There was between-group comparability at baseline in terms of age, body mass index (BMI), visual analogue scale, Harris Hip Score and leg length discrepancy (P > 0.1). Compared with conventional THA, the navigated group demonstrated slightly lower leg length discrepancy (P = 0.02) but longer duration of the surgical procedure (P < 0.0001). Cup anteversion (P = 0.6) and inclination (P = 0.5), Harris Hip Score (P = 0.1) and rate of dislocation (P = 0.98) were similar between the two interventions.

Conclusion
Imageless navigation may represent a viable option for THA.
DualGCN: a dual graph convolutional network model to predict cancer drug response
Authors: Ma Tianxing , Liu Qiao , Li Haochen , Zhou Mu , Jiang Rui , Zhang Xuegong 
Published: April 2022

Abstract
Background
Drug resistance is a critical obstacle in cancer therapy. Discovering cancer drug response is important to improve anti-cancer drug treatment and guide anti-cancer drug design. Abundant genomic and drug response resources of cancer cell lines provide unprecedented opportunities for such study. However, cancer cell lines cannot fully reflect heterogeneous tumor microenvironments. Transferring knowledge studied from in vitro cell lines to single-cell and clinical data will be a promising direction to better understand drug resistance. Most current studies include single nucleotide variants (SNV) as features and focus on improving predictive ability of cancer drug response on cell lines. However, obtaining accurate SNVs from clinical tumor samples and single-cell data is not reliable. This makes it difficult to generalize such SNV-based models to clinical tumor data or single-cell level studies in the future.

Results
We present a new method, DualGCN, a unified Dual Graph Convolutional Network model to predict cancer drug response. DualGCN encodes both chemical structures of drugs and omics data of biological samples using graph convolutional networks. Then the two embeddings are fed into a multilayer perceptron to predict drug response. DualGCN incorporates prior knowledge on cancer-related genes and protein–protein interactions, and outperforms most state-of-the-art methods while avoiding using large-scale SNV data.

Conclusions
The proposed method outperforms most state-of-the-art methods in predicting cancer drug response without the use of large-scale SNV data. These favorable results indicate its potential to be extended to clinical and single-cell tumor samples and advancements in precision medicine.
Mass recalibration for desorption electrospray ionization mass spectrometry imaging using endogenous reference ions
Authors: Inglese Paolo , Huang Helen Xuexia , Wu Vincen , Lewis Matthew R. , Takats Zoltan 
Published: April 2022

Abstract
Background
Mass spectrometry imaging (MSI) data often consist of tens of thousands of mass spectra collected from a sample surface. During the time necessary to perform a single acquisition, it is likely that uncontrollable factors alter the validity of the initial mass calibration of the instrument, resulting in mass errors of magnitude significantly larger than their theoretical values. This phenomenon has a two-fold detrimental effect: (a) it reduces the ability to interpret the results based on the observed signals, (b) it can affect the quality of the observed signal spatial distributions.

Results
We present a post-acquisition computational method capable of reducing the observed mass drift by up to 60 ppm in biological samples, exploiting the presence of typical molecules with a known mass-to-charge ratio. The procedure, tested on time-of-flight and Orbitrap mass spectrometry analyzers interfaced to a desorption electrospray ionization (DESI) source, improves the molecular annotation quality and the spatial distributions of the detected ions.

Conclusion
The presented method represents a robust and accurate tool for performing post-acquisition mass recalibration of DESI-MSI datasets and can help to increase the reliability of the molecular assignment and the data quality.
Cellulose-mediated floc formation by the activated sludge bacterium Shinella zoogloeoides ATCC 19623
Authors: Gao Na , Dai Jingcheng , Liu Yaqi , Li Shuyang , Wang Jing , Lu Wenxuan , Qiu Dongru 
Published: April 2022

Abstract
Background
Bacterial floc formation plays a central role in the activated sludge (AS) process. The formation of AS flocs has long been known to require exopolysaccharide biosynthesis. We had demonstrated that both expolysaccharides and PEP-CTERM (a short C-terminal domain includes a near-invariant motif Pro-Glu-Pro (PEP)) proteins were required for floc-forming in Zoogloea resiniphila MMB, a dominant AS bacterium. However, the PEP-CTERM proteins are not encoded in the genome of AS bacterium Shinella zoogloeoides ATCC 19623 (formerly known as Zoogloea ramigera I-16-M) and other sequenced AS bacteria strains. The mechanism underlying floc formation of Shinella and related AS bacteria remained largely unclear.

Results
In this study, we have sequenced and annotated the complete genome of S. zoogloeoides ATCC 19623 (aka I-16-M), previously isolated in USA and treated as the neotype for the AS floc-forming bacterium Zoogloea ramigera I-16-M, and another AS strain XJ20 isolated in China. Mariner transposon mutagenesis had been conducted to isolate floc-forming-deficient mutants in the strain ATCC 19623 as previously performed by using Tn5 transposon three decades ago. The transposon insertional sites of multiple mutants were mapped to the gene cluster for bacterial cellulose synthesis (bcs) and secretion, and the role played by these genes in floc-formation had been further confirmed by genetic complementation. Interestingly, the restriction map of this bcs locus-flanking region was highly similar to that of the previously identified DNA fragment required for floc-formation in 1980s. Cellulase treatment abolished the floc-forming phenotype of S. zoogloeoides ATCC 19623 but not that of Z. resiniphila MMB strain. The FTIR spectral analyses revealed that the samples extracted from S. zoogloeoides ATCC 19623 were cellulose polymer.

Conclusion
Our results indicated that we have largely reproduced and completed the unfinished pioneering work on AS floc-formation mechanism, demonstrating that the floc-formation and flocculating capability of Shinella were mediated by extracellular cellulose polymers.