bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of uncharted RNA sequences to tumor identity in lung adenocarcinoma
Authors: Wang Yunfeng , Xue Haoliang , Aglave Marine , Lainé Antoine , Gallopin Mélina , Gautheret Daniel 
Published: February 2022

AbstractThe identity of cancer cells is defined by the interplay between genetic, epigenetic transcriptional and post-transcriptional variation. A lot of this variation is present in RNA-seq data and can be captured at once using reference-free, k-mer analysis. An important issue with k-mer analysis, however, is the difficulty of distinguishing signal from noise. Here, we use two independent lung adenocarcinoma datasets to identify all reproducible events at the k-mer level, in a tumor versus normal setting. We find reproducible events in many different locations (introns, intergenic, repeats) and forms (spliced, polyadenylated, chimeric etc.). We systematically analyze events that are ignored in conventional transcriptomics and assess their value as biomarkers and for tumor classification, survival prediction, neoantigen prediction and correlation with the immune microenvironment. We find that unannotated lincRNAs, novel splice variants, endogenous HERV, Line1 and Alu repeats and bacterial RNAs each contribute to different, important aspects of tumor identity. We argue that differential RNA-seq analysis of tumor/normal sample collections would benefit from this type k-mer analysis to cast a wider net on important cancer-related events. The code is available at https://github.com/Transipedia/dekupl-lung-cancer-inter-cohort.
PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
Authors: Tinsley Samantha L , Allen-Petersen Brittany L 
Published: February 2022

Abstract
The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth.
The relationship between ageing and changes in the human blood and brain methylomes
Authors: Bryant Patrick , Elofsson Arne 
Published: February 2022

Abstract
Changes in DNA methylation have been found to be strongly correlated with age, enabling the creation of ‘epigenetic clocks’. Previously, studies on the relationship between ageing and DNA methylation have assumed a linear relationship. Here, we show that several markers show a non-linear behaviour. In particular, we observe a tendency for saturation with age, especially in the cerebellum. Further, we show that the relationships between significant methylation changes and ageing are different in different tissues. We suggest a straightforward method of assessing all methylation-age relationships and cluster them according to their relative fold change. Our fold change selection outperforms the most common epigenetic clocks in predicting age for the cerebellum, but not for Blood or the Frontal Cortex. Further, we find that the saturation of methylation observed at older ages for the cerebellum explains why epigenetic clocks consistently underestimate the age there. The findings imply that assuming linear correlations might cause biologically important markers to be missed.
PANDA2: protein function prediction using graph neural networks
Authors: Zhao Chenguang , Liu Tong , Wang Zheng 
Published: February 2022

AbstractHigh-throughput sequencing technologies have generated massive protein sequences, but the annotations of protein sequences highly rely on the low-throughput and expensive biological experiments. Therefore, accurate and fast computational alternatives are needed to infer functional knowledge from protein sequences. The gene ontology (GO) directed acyclic graph (DAG) contains the hierarchical relationships between GO terms but is hard to be integrated into machine learning algorithms for functional predictions. We developed a deep learning system named PANDA2 to predict protein functions, which used the cutting-edge graph neural network to model the topology of the GO DAG and integrated the features generated by transformer protein language models. Compared with the top 10 methods in CAFA3, PANDA2 ranked first in cellular component ontology (CCO), tied first in biological process ontology (BPO) but had a higher coverage rate, and second in molecular function ontology (MFO). Compared with other recently-developed cutting-edge predictors DeepGOPlus, GOLabeler, and DeepText2GO, and benchmarked on another independent dataset, PANDA2 ranked first in CCO, first in BPO, and second in MFO. PANDA2 can be freely accessed from http://dna.cs.miami.edu/PANDA2/.
Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues
Authors: Hsieh Yuan-Pang , Naler Lynette B , Ma Sai , Lu Chang 
Published: February 2022

Abstract
BRCA1 germline mutation carriers are predisposed to breast cancers. Epigenomic regulations have been known to strongly interact with genetic variations and potentially mediate biochemical cascades involved in tumorigenesis. Due to the cell-type specificity of epigenomic features, profiling of individual cell types is critical for understanding the molecular events in various cellular compartments within complex breast tissue. Here, we produced cell-type-specific profiles of genome-wide histone modifications including H3K27ac and H3K4me3 in basal, luminal progenitor, mature luminal and stromal cells extracted from a small pilot cohort of pre-cancer BRCA1 mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+), using a low-input ChIP-seq technology that we developed. We discovered that basal and stromal cells present the most extensive epigenomic differences between mutation carriers (BRCA1mut/+) and non-carriers (BRCA1+/+), while luminal progenitor and mature luminal cells are relatively unchanged with the mutation. Furthermore, the epigenomic changes in basal cells due to BRCA1 mutation appear to facilitate their transformation into luminal progenitor cells. Taken together, epigenomic regulation plays an important role in the case of BRCA1 mutation for shaping the molecular landscape that facilitates tumorigenesis.
Impact of environmental pollution on the obesogenic environment
Authors: Martínez-Esquivel Adriana , Trujillo-Silva Daniela Joyce , Cilia-López V Gabriela 
Published: February 2022

Abstract
Obesity figures in the world continue to increase, representing a multifactorial and multidimensional problem. Efforts to contribute to reduction in obesity have led to the study of this condition from different approaches, including the obesogenic environment (OE), which is harmful to health due to the multiple factors that compose the OE. Some of the most important factors are stress, lifestyle, and urban design, framed in a food system that provides caloric foods and contributes to intake of hypercaloric diets. The OE exacerbates the obesogenic process and chronic low-grade inflammation. However, these factors are not the only ones responsible for obesity. Environmental pollutants also contribute, because they interfere with metabolic processes that regulate lipid accumulation and increase body adiposity. In this review, we analyze the relationship between pollution and obesogenic processes. We postulate the inclusion of environmental pollution within the factors and definition of the OE.
Serum Interleukin 6 Level and Nutrition Status as Potential Predictors of Clinical Leprosy Development Among Household Contacts in Endemic Areas
Authors: Oktaria Salma , Anfasa Fatih , Menaldi Sri Linuwih , Bramono Kusmarinah , Nijsten Tamar E C , Thio Hok Bing 
Published: February 2022

Abstract

Background
Leprosy is a chronic infectious disease that can lead to severe lifelong disabilities. Close contacts of patients with leprosy have a higher risk of acquiring the disease. Nevertheless, there is a lack of reliable markers to predict Mycobacterium leprae infection. We aimed to identify new potential markers for developing clinical leprosy among contacts.

Methods
Serum levels of interleukin (IL) 6, IL-8, IL-10, hemoglobin, ferritin, and transferrin saturation were measured in 67 patients with multibacillary leprosy (MB), 65 household contacts (HHCs) of MB patients, and 127 endemic controls (ECs). By means of multivariate logistic regression and receiver operating characteristic (ROC) analyses, we analyzed baseline variables and laboratory parameters that showed significant differences between MB in the HHC and EC groups and obtained the respective areas under the curve (AUC). Optimal cutoff values of the associated cytokines were also determined.

Results
Elevated IL-6 level was observed in MB patients compared to HHCs and ECs (P = .022 and .0041, respectively). Anemia and iron deficiency were also higher in the MB group compared to HHCs or ECs (P &lt; .001). Likewise, we observed an increased risk of having MB leprosy in underweight HHCs (odds ratio [OR], 2.599 [95% confidence interval {CI}, .991–6.820]) and underweight ECs (OR, 2.176 [95% CI, 1.010–4.692]). Further ROC analysis showed that high serum IL-6 level, underweight, anemia, and iron deficiency can discriminate leprosy from their HHCs (AUC, 0.843 [95% CI, .771–.914]; P = .000; optimal cutoff value of IL-6 = 9.14 pg/mL).

Conclusions
Our results suggest that serum IL-6 and nutrition status could serve as potential prognostic markers for the development of clinical leprosy in infected individuals.
Similar Mortality Among United States Veterans With Invasive and Noninvasive Pneumonia due to Group B Streptococcus
Authors: Banks Richard E , Wilson Brigid M , Bej Taissa , Briggs Janet M , Song Sunah , Goto Michihiko , Jump Robin L P , Perez Federico 
Published: February 2022

Abstract

Background
The nosology of noninvasive pneumonia due to group B Streptococcus (GBS) is not well defined. This study compared clinical characteristics and outcomes of patients with invasive pneumonia and noninvasive pneumonia caused by GBS.

Methods
We conducted a retrospective cohort study among Veterans Affairs (VA) healthcare users between 2008 and 2017. Using data from electronic health records, we identified patients who had blood or respiratory cultures that grew GBS and had invasive pneumonia or noninvasive pneumonia. We analyzed patient and infection characteristics associated with all-cause mortality, including among the subset of patients with cultures that were monomicrobial for GBS.

Results
Among 1791 patients with GBS pneumonia, 646 (36%) cases were invasive and 1145 (64%) were noninvasive. Among those, 535 and 424 cases of invasive and noninvasive pneumonia, respectively, had cultures that were monomicrobial for GBS. All-cause 30-day mortality among those with monomicrobial GBS pneumonia was 15% for both those with invasive and noninvasive disease, respectively. Increasing age, severity of illness, healthcare exposure in the previous 90 days, and polymicrobial infection with Staphylococcus aureus were independently associated with all-cause mortality at 30 days.

Conclusions
In this large cohort, even when considering cases for which GBS was the only pathogen recovered, &gt;40% of GBS pneumonia cases were noninvasive. All-cause mortality was comparable for invasive and noninvasive pneumonia. These findings suggest that the burden of GBS pneumonia may be greater than previously recognized by surveillance of invasive GBS disease and may inform treatment and prevention efforts.
Long-term Prognosis Following Vascular Graft Infection: A 10-Year Cohort Study
Authors: Sixt Thibault , Aho Serge , Chavanet Pascal , Moretto Florian , Denes Eric , Mahy Sophie , Blot Mathieu , Catherine François-Xavier , Steinmetz Eric , Piroth Lionel 
Published: February 2022

Abstract

Background
Vascular graft infection (VGI) remains a severe disease with high mortality and relapse rates. We performed a retrospective single-center cohort study to highlight factors associated with long-term all-cause mortality in patients with vascular graft infection.

Methods
All patients hospitalized in our facility over 10 years for VGI were included. VGI was defined by the presence of a vascular graft or an aortic stent graft (stent or fabric), associated with 2 criteria among clinical, biological, imaging, or microbiological elements in favor of VGI. The primary outcome was all-cause mortality. Empirical antibiotic therapy was considered as appropriate when all involved pathogens were susceptible in vitro to the antibiotics used. The surgical strategy was defined as nonoptimal when the graft was not removed in a late-onset surgery (&gt;3 months) or no surgery was performed.

Results
One hundred forty-six patients were included. Empirical antibiotic therapy was administered in 98 (67%) patients and considered appropriate in 55 (56%) patients. Surgery was performed in 136 patients (96%) and considered as optimal in 106 (73%) patients. In multivariable analysis, appropriate empirical antibiotic therapy was associated with a lower probability of mortality (hazard ratio, 0.47 [95% confidence interval, .30–.79]; P = .002). Long-term survival did not differ according to whether the surgical strategy was considered optimal or not (log-rank = 0.66).

Conclusions
Appropriate empirical antibiotic therapy is a cornerstone of the management of VGI. Whenever possible, antibiotics must be associated with optimal surgical management. However, surgery could potentially be avoided in comorbid patients who are treated with appropriate antibiotics.
N064A (Alliance): Phase II Study of Panitumumab, Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma
Authors: Halfdanarson Thorvardur R , Foster Nathan R , Kim George P , Haddock Michael G , Dakhil Shaker R , Behrens Robert J , Alberts Steven R 
Published: February 2022

Abstract

Background
This North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.

Methods
The treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.

Results
Fifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.

Conclusion
The combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier NCT00601627).
Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms
Authors: Rhee John Y , Torun Nurhan , Neilan Tomas G , Guidon Amanda C 
Published: February 2022

Abstract
Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.
A Narrative Review of the Literature on the Recruitment of Younger Police Officers in Age and in Service: What Are the Implications for the Police in England and Wales?
Authors: Williams Emma , Sondhi Arun 
Published: February 2022

Abstract
The Police Uplift Programme in England and Wales aims to recruit more than 20,000 new police officers into the service. There is little known about the potential consequences associated with a large-scale recruitment drive and the effect of introducing a younger cohort of officers into the ranks of the police. This article is based on a narrative review of 2,110 English-language titles including grey literature exploring the implications for the police who are younger in age and service workforce profile. Titles were identified through electronic and handsearching methods. Fifty-nine titles were assessed for inclusion, of which 48 were subject to a full-text review. The majority of papers were from North America. Three themes were identified from the review: (1) issues related to cultural considerations including younger officers’ preference for transparent and linear relationships and highlighting an emphasis on public service; (2) well-being and work–life balance considerations; and (3) harnessing the skill base through effective recruitment and retention practices. The findings suggest that police forces can create a narrative for new recruits as adult learners committed to public service combined with enhanced leadership styles that prioritize teamwork, transparency, and personal development.
The Polls—Trends
Authors: Banai Ayelet , Votta Fabio , Seitz Rosa 
Published: February 2022

Abstract
This article presents trends in public opinion toward immigration in the European Union (EU), between 2002 and 2018. Immigration is a salient and contentious issue in contemporary politics across Europe and is used by Eurosceptic parties in both government and opposition to mobilize support. Public opinion data—drawn from the European Social Survey and the Eurobarometer—reveals the following noteworthy trends over the past two decades. First, positive public attitudes toward immigration have increased across member states, with a temporary setback in 2015–16. Second, immigration is a divisive issue throughout the EU. While public opinion in some regions generally favors immigration, opinion is divided everywhere. Third, despite regional variations between northern, western, and southern Europe, EU-wide trends suggest the emergence of a collective public opinion, crossing national borders. Fourth, despite vocal political opposition to immigration, solid majorities of the public view immigration favorably over time and across regions. To the numerous studies of European public opinion on immigration, this article contributes a useful overview of the long-term trends, with regional and EU-wide presentation and data visualization.
The Assessment Gap: Racial Inequalities in Property Taxation
Authors: Avenancio-León Carlos F , Howard Troup 
Published: February 2022

AbstractWe document a nationwide “assessment gap” that leads local governments to place a disproportionate fiscal burden on racial and ethnic minorities. We show that holding taxing jurisdictions and property tax rates fixed, Black and Hispanic residents face a 10%–13% higher tax burden for the same bundle of public services. We decompose this disparity into between- and within-neighborhood components and find that just over half of it arises between neighborhoods. We then present evidence on mechanisms. Property assessments are less sensitive to neighborhood attributes than market prices are. This generates spatial variation in tax burden within jurisdiction and leads to overtaxation of communities with a high share of minority residents. We also find appeals behavior and appeals outcomes differ by race within neighborhood. Inequality does not arise from (i) racial differences in transaction prices or (ii) differences in features of the housing stock.
Colchicine use and the risk of CKD progression: a multicentre nested case-control study
Authors: Kim Hyung Woo , Joo Young Su , Yun Hae-Ryong , Kim Jae Young , Jhee Jong Hyun , Roh Yun Ho , Park Jung Tak , Chang Tae Ik , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok 
Published: February 2022

Abstract

Objectives
Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout.

Methods
We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3–G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex.

Results
Overall, 3085 patients with CKD progression were matched to 11 715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3.

Conclusion
Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout.