bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ceramides improve cardiovascular risk prediction beyond low-density lipoprotein cholesterol
Authors: Leiherer Andreas , Muendlein Axel , Saely Christoph H , Laaksonen Reijo , Fraunberger Peter , Drexel Heinz 
Published: January 2024

Abstract

Aims
Low-density lipoprotein cholesterol (LDL-C) is the best documented cardiovascular risk predictor and at the same time serves as a target for lipid-lowering therapy. However, the power of LDL-C to predict risk is biased by advanced age, comorbidities, and medical treatment, all known to impact cholesterol levels. Consequently, such biased patient cohorts often feature a U-shaped or inverse association between LDL-C and cardiovascular or overall mortality. It is not clear whether these constraints for risk prediction may likewise apply to other lipid risk markers in particular to ceramides and phosphatidylcholines.

Methods and results
In this observational cohort study, we recorded cardiovascular mortality in 1195 patients over a period of up to 16 years, comprising a total of 12 262 patient-years. The median age of patients at baseline was 67 years. All participants were either consecutively referred to elective coronary angiography or diagnosed with peripheral artery disease, indicating a high cardiovascular risk. At baseline, 51% of the patients were under statin therapy. We found a U-shaped association between LDL-C and cardiovascular mortality with a trough level of around 150 mg/dL of LDL-C. Cox regression analyses revealed that LDL-C and other cholesterol species failed to predict cardiovascular risk. In contrast, no U-shaped but linear association was found for ceramide- and phosphatidylcholine-containing markers and these markers were able to significantly predict the cardiovascular risk even after multivariate adjustment.

Conclusion
We thus suggest that ceramides- and phosphatidylcholine-based predictors rather than LDL-C may be used for a more accurate cardiovascular risk prediction in high-risk patients.
The risks to refugee law of humanitarian responses to flight from Ukraine
Authors: Dauvergne Catherine 
Published: January 2024

Abstract
This article argues that the humanitarian outpouring of support that has greeted those fleeing the war in Ukraine exposes fragility in international refugee law. Over and over again, humanitarianism has proven insufficient to address the protection needs of refugees. The politics of humanitarianism present many advantages to states and are potentially highly motivating to publics, but they are an insufficient substitute for legally-grounded human rights protections. The current humanitarian moment is raising a number of questions about refugee law, and is fostering considerable confusion about the role of law in responding to those fleeing Ukraine. Despite refugee law's imperfections and biases, in a world that is increasingly hostile to migrants, international refugee law is the strongest tool available. In the face of the humanitarian surge of the moment, it is important to defend the core protection commitments of refugee law, even as we work to improve the law's shortcomings. While it is tempting to shy away from anything that could be perceived as a critique of the compassion and generosity we are witnessing, as scholars and advocates we should use this moment to draw important lessons about how to strengthen refugee law.
The challenge for the ‘rest’: insertion, agency spaces and recognition in world politics
Authors: Chagas-Bastos Fabrício H 
Published: January 2024

Abstract
One of the long-standing questions for scholars and policy-makers—in particular in western capitals—is how to treat the rise of new powers in world politics. Although past research has paved the way for studying power transitions, we still lack conceptual tools to understand the behaviour of peripheral states which move between different power positions. How can we explain, from the point of view of those in the margins, how such power transitions happen? To put it differently, how does a rise to power happen for states in the peripheries and semi-peripheries? I argue in this article that not all states have agentic capacities to act (e.g., to rise to a less peripheral position or to seek better status). There has been a silent and tacit consensus around the fact that peripheral states must first be recognized and accepted by systemic/hierarchy gatekeepers as actors who can fully exercise their agency in global hierarchies. I present the concept of international insertion, which contributes to a more nuanced understanding of how rising powers behave in world politics, and helps to explain why there are no discernible heightened tensions from a strategic–military perspective when peripherical countries move (or try to move) towards mid-system (or improved status) positions within regional and global hierarchies.
The false promise of nuclear risk reduction
Authors: Pelopidas Benoît , Egeland Kjølv 
Published: January 2024

Abstract
In a context of intensifying great power competition and deep divergences of view between nuclear and non-nuclear powers on the urgency of nuclear abolition, ‘nuclear risk reduction’ has gained renewed attention as a pragmatic framework for managing and progressively reducing nuclear dangers. The idea is simple: with more fundamental policy changes either undesirable or out of reach, advocates of nuclear non-proliferation and disarmament should focus their efforts on the international community's shared interest in reducing the risk of nuclear use and escalation, identifying and implementing limited measures to sequester nuclear risk scenarios. Drawing on historical scholarship, archival documents and theories of ‘normal’ and ‘epistemic’ accidents, we argue that the risk reduction agenda offers a false promise for those seeking durable, shared solutions to the nuclear predicament. The risk reduction framework demands access to an unattainable level of knowledge, encourages overconfidence in managerial control and fails to provide meaningful policy guidance. Examining in detail the scholarship of Thomas Schelling, we maintain that the risk reduction agenda remains heavily circumscribed by the requirements of credible nuclear deterrence.
Prevalent vs Incident Screen: Why Does It Matter?
Authors: Hayward Jessica H , Lee Amie Y , Sickles Edward A , Ray Kimberly M 
Published: January 2024

Abstract
There are important differences in the performance and outcomes of breast cancer screening in the prevalent compared to the incident screening rounds. The prevalent screen is the first screening examination using a particular imaging technique and identifies pre-existing, undiagnosed cancers in the population. The incident screen is any subsequent screening examination using that technique. It is expected to identify fewer cancers than the prevalent screen because it captures only those cancers that have become detectable since the prior screening examination. The higher cancer detection rate at prevalent relative to incident screening should be taken into account when analyzing the medical audit and effectiveness of new screening technologies.
Antimicrobial Stewardship Teams in Veterans Affairs and Nonfederal Hospitals in the United States: A National Survey of Antimicrobial Stewardship Practices
Authors: Hawes Armani M , Greene M Todd , Ratz David , Fowler Karen E , Kendall Ronald E , Patel Payal K 
Published: January 2024

Abstract
In a cross-sectional survey of US acute care hospitals, antimicrobial stewardship programs were present in most Veterans Affairs and nonfederal hospitals but varied in team composition, scope, and impact. Diagnostic stewardship was common across hospitals. Veterans Affairs hospitals had increased reach in outpatient settings. Telestewardship remains an opportunity in all hospital systems.
Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil
Authors: Araújo-Pereira Mariana , Arriaga María B , Carvalho Anna Cristina C , Spener-Gomes Renata , Schmaltz Carolina A S , Nogueira Betânia M F , Figueiredo Marina C , Turner Megan M , Cordeiro-Santos Marcelo , Rolla Valeria C , Sterling Timothy R , Andrade Bruno B , Kritski Afrânio L ,   for the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil Consortium, Rocha Michael S , Nascimento Vanessa , Santos Saulo R N , Costa Alysson G , Garcia Leandro Sousa , de Sousa Carvalho Brenda K , de Loiola Bruna P , Gomes-Silva Adriano , Ignácio Francine P , Lourenço Maria C , Silva Elisangela C , Mello Mayla , Souza Alexandra B , Benjamin Aline , Moreira Adriana S R , de Oliveira Jamile G , Cavalcante Solange , Durovni Betina , Lapa-e-Silva José R 
Published: January 2024

Abstract

Background
The high burden of drug-resistant tuberculosis (TB) is a problem to achieve the goals of the End TB Strategy by 2035. Whether isoniazid monoresistance (Hr) affects anti-TB treatment (ATT) outcomes remains unknown in high-burden countries.

Methods
We evaluated determinants of ATT outcome among pulmonary TB cases reported to the National Notifiable Disease Information System (SINAN) between June 2015 and June 2019, according to drug sensitivity testing (DST) results. Binomial logistic regression models were employed to evaluate whether Hr was associated with an unfavorable ATT outcome: death or failure, compared to cure or treatment completion.

Results
Among 60 804 TB cases reported in SINAN, 21 197 (34.9%) were included in the study. In this database, the frequency of unfavorable outcomes was significantly higher in those with Hr in contrast to isoniazid-sensitive persons with pulmonary TB (9.1% vs 3.05%; P &lt; .001). Using a binomial logistic regression model, Hr was independently associated with unfavorable outcomes (odds ratio, 3.34 [95% confidence interval, 2.06–5.40]; P &lt; .001).

Conclusions
Hr detected prior to ATT was predictive of unfavorable outcomes at the national level in Brazil. Our data reinforce the need for high-TB-burden countries to prioritize DST to detect Hr. Effective treatment regimens for Hr-TB are needed to improve outcomes.
Psychosocial interventions to improve sexual functioning in women with cancer: a systematic review of randomized controlled trials
Authors: Carney Lauren M , Schnur Julie B , Morgan Orly , Hyun Christine , Magin Zachary E , Martin Lily , Montgomery Guy H 
Published: January 2024

Abstract

Introduction
Many women with cancer struggle with sexual side effects during and after treatment. Although preliminary evidence indicates that psychosocial interventions may be efficacious in improving sexual functioning for women with cancer, no systematic review has summarized the state of the science in this area.

Objectives
The primary goal of this review was to narratively synthesize the results of randomized controlled trials (RCTs) testing the efficacy of psychosocial interventions to address sexual dysfunction in women with cancer. A secondary goal was to describe the diversity of the included samples (ie, racial/ethnic and sexual minority).

Methods
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted examining RCTs of psychosocial interventions to improve sexual functioning for women with cancer. Articles were identified using MEDLINE, Embase, PsycINFO, and Cochrane CENTRAL. Two reviewers independently assessed each article for inclusion, with a third to resolve discrepancies.

Results
Seventeen studies were included in the review, 12 of which provided sufficient information to calculate effect sizes. Ten of the 12 studies primarily aimed to improve sexual functioning, all of which demonstrated positive effects on at least 1 outcome of sexual functioning. In the 2 RCTs of psychosocial interventions in which sexual function was a secondary aim, effects were negligible (ds = −0.04 and −0.15). Commonalities among the studies with large effect sizes were that they included education, mindfulness/acceptance, and communication/relationship skills as intervention components. Of note, there was an overall lack of sample diversity across studies, and most studies failed to report the race/ethnicity or sexual orientation of the participants.

Conclusion
Results support interventions targeting sexual functioning outcomes for women with cancer and suggest that multimodal interventions including education, mindfulness/acceptance, and communication/relationship skills may be most effective. Future research should also focus on examining the efficacy and potential adaptations of extant sexual functioning interventions for underrepresented groups.
The impact of prophylactic mastectomy on sexual well-being: a systematic review
Authors: Scotto Ludovica , Pizzoli Silvia Francesca Maria , Marzorati Chiara , Mazzocco Ketti , Pravettoni Grabriella 
Published: January 2024

Abstract

Introduction
Considering the increasing women’s awareness of health promotion and disease prevention programs, mutation carriers are inevitably asked to face important decisions concerning the possibility of undergoing prophylactic mastectomy. Risk-reducing mastectomy (RRM) has become increasingly more common, although it has a significant impact on women’s quality of life and sexual well-being.

Objectives
The systematic review aims to evaluate the impact of RRM on the sexuality of women with breast cancer.

Methods
According to Cochrane Collaboration guidelines and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, the study quantified the effects of frontline work on the mental health of healthcare workers. This review followed the PRISMA guidelines. Three databases were systematically searched from inception to December 2022. The expression (“sexuality” OR “sexual” OR “sex”) AND (“prophylactic mastectomy” OR “risk-reducing mastectomy”) was searched in PubMed, Ovid Medline, and Embase. Twenty-two articles published in English until 2022 were selected.

Results
Two studies investigated sexual experience after risk-reducing surgeries as a single outcome, while other studies analyzed the relationship between sexuality and psychosocial outcomes, risk perception, and satisfaction. In all of the included studies, significant findings in sexual dysfunction were found. The most reported problems were related to sexual satisfaction and attractiveness, body image, and loss of femininity. Last, women reported changes in the relationship with their partners.

Conclusion
RRM has a major impact on body image that affects sexual functioning and quality of life. These implications must be considered during treatment selection.
Progress and perspective of organoid technology in breast cancer research
Authors: Huang Changsheng , Jin Hongyan 
Published: January 2024

Abstract
Breast cancer, a malignant tumor with a high incidence in women, lacks in vitro research models that can represent the biological functions of breast tumors in vivo. As a new biological tool, the organoid model has unique advantages over traditional methods, such as cell culture and patient-derived xenografts. Combining organoids with other emerging technologies, such as gene engineering and microfluidic chip technology, provides an effective method to compensate for the deficiencies in organoid models of breast cancer in vivo. The emergence of breast cancer organoids has provided new tools and research directions in precision medicine, personality therapy, and drug research. In this review, we summarized the merits and demerits of organoids compared to traditional biological models, explored the latest developments in the combination of new technologies and organoid models, and discussed the construction methods and application prospects of different breast organoid models.
A Propensity Score–Matched Analysis of the Impact of Carcinoma In Situ on the Clinical Outcomes in Patients with Upper Tract Urothelial Carcinomas—A Nationwide Multi-Institutional Cohort Study
Authors: Wong Shin Mei , Ke Hung-Lung , Li Wei-Ming , Chang Chao-Hsiang , Huang Chi-Ping , Wu Shu-Yu , Tsai Yao-Zhou , Huang Steven K. , Tsing Wen-Hsin , Chen I-Hsuan Alan , Lin Jen-Tai , Tsai Chung-You , Cheng Pai-Yu , Jiang Yuan-Hong , Lee Yu-Khun , Chiang Bing-Juin , Chen Yung-Tai , Chuech Leonard S. , Hsueh Thomas Y. , Lin Wei Yu , Wu Chia-Chang , Tseng Jen-Shu , Chen Pi-Che , Huang Chao-Yuan , Hong Jian-Hua 
Published: January 2024

Purpose:
This study aimed to explore the clinical prognostic features of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) with carcinoma in situ (CIS) compared with those without it.

Material and Methods:
We retrospectively reviewed the data of 3285 patients with UTUC. Propensity scores were calculated using a logistic regression model to regress disease status on various baseline covariates, including cell type, tumor size, histology, lymphovascular invasion, surgical margin, and pathological stage. Using these scores, we adopted a one-to-two pair matching approach to form matched pairs between the two groups, ensuring patients within each pair had similar propensity score values. Prognostic factors were identified using univariate and multivariate Cox regression models. The Kaplan-Meier method was used to estimate the rates of prognostic outcomes, and survival curves were compared using the stratified log-rank test.

Results:
Matched cohorts of 810 patients without and 405 with CIS from each group were compared. There was no discernible difference in the 5-year overall survival. The Kaplan-Meier curves for cancer-specific survival were significantly different in the adjusted group only (P = .043). Multivariate Cox regression analyses indicated that disease-free and bladder recurrence-free survival rates were similar between the two groups. The CIS status was not significantly correlated with the disease-free or bladder recurrence-free survival (P = .066 and .179, respectively).

Conclusions:
Patients with UTUC with CIS did not exhibit significantly worse oncologic outcomes than those without it.
A rare case report of Huntington’s disease with severe psychiatric symptoms as initial manifestations
Authors: Lv Chenling , Zhang Zhenzhong , Zhang Yan , Zhong Lin , Yu Ziqiang , Guo Dengjun 
Published: January 2024

Introduction
Huntington’s disease (HD) stands as an inherited and progressive neurodegenerative ailment distinguished by chorea-esque movement patterns, which manifest as archetypal symptoms. The presence of pronounced psychiatric onset symptoms in patients can considerably amplify the intricacies of accurate diagnosis.

Case presentation
A 43-year-old gentleman was admitted with a five-year chronicle of delusions, hallucinations, and irritability. He had previously received a diagnosis of schizophrenia and had been subjected to a regimen of antipsychotic medications for a span exceeding four years. However, subsequent to the application of cerebral MRI and genetic testing, his condition was conclusively redetermined as HD.

Conclusion
The salient attribute of this case resides in the deferred diagnosis of HD attributable to the presence of acute psychiatric initial symptoms, a scenario bearing noteworthy ramifications for disease oversight and prognostication. This instance warrants attentive scrutiny and discourse within the professional community.
Quantifying the daily harvest of fermentation products from the human gut microbiota
Authors: Arnoldini Markus , Sharma Richa , Moresi Claudia , Chure Griffin , Chabbey Julien , Slack Emma , Cremer Jonas 
Published: January 2024

AbstractFermentation products released by the gut microbiota provide energy and important regulatory functions to the host. Yet, little quantitative information is available on the metabolite exchange between the microbiota and the human host, and thus the effective doses of fermentation products. Here, we introduce an integrative framework combining experimental characterization of major gut bacteria with a quantitative analysis of human digestive physiology to put numbers on this exchange and its dependence on diet and microbiota composition. From the complex carbohydrates fueling microbiota growth, we find most carbon ends up in fermentation products which are largely utilized by the host. This harvest of mixed fermentation products varies strongly with diet, from between 100-700 mmol/day within the US population to up to 1300 for the Hadza people of Tanzania. Accordingly, fermentation products cover between 2% and 12% of the daily energy demand of human hosts, substantially less than the 21±4% estimated for laboratory mice. In contrast, microbiota composition has little impact on the total daily harvest but determines the harvest of specific fermentation products. Butyrate, known for promoting epithelial health, shows the biggest variation. Our framework thus identifies and quantifies major factors driving the metabolic interactions and exchange of information between microbiota and host, crucial to mechanistically dissect the role of the microbiota in health and disease.
Revealing sphingolipids composition in extracellular vesicles and paternal β-cells after persistent hyperglycemia
Authors: Skalska Magdalena E. , Durak-Kozica Martyna , Stępień Ewa Ł. 
Published: January 2024

AbstractExtended periods of hyperglycemia (HG) can lead to metabolic disorders of sphingolipids (SPs) and their subsequent accumulation in cells. This accumulation can trigger a range of complications, including kidney and neurodegenerative diseases. In our study, we compared the levels of selected ceramides (CER), hexosylceramides (HexCER), and glycosphingolipids (GSLs) in potential HG biomarkers - extracellular vesicles (EVs). These EVs were derived in vitro from human β-cells cultured under both normoglycemic and high-glucose conditions (HG). We utilized Time of Flight – Secondary Ion Mass Spectrometry (ToF-SIMS) for SPs analysis. Our results confirmed that the lipid profiles of these three groups differ between large and small EVs, with some SP lipids being more enriched in EVs compared to cells. Interestingly, our study revealed that HG only regulates the lipid content from the glycosphingolipid group in relation to normoglycemia. Collectively, our findings underscore the potential applications of ToF-SIMS in characterizing the impact of different culture conditions on lipid levels. As far as we know, our study is the first which employs ToF-SIMS in analyzing the effects of HG on SP levels in EVs and their parental β-cells.Graphical abstractHighlightsToF-SIMS effectively compares glycosphingolipid content in cells and EVs.Analysis reveals lipid profile differences between EVs and their parent cells.Hyperglycemia alters glycosphingolipid content in cells and EVs per ToF-SIMS.
Detecting m6A RNA modification from nanopore sequencing using a semi-supervised learning framework
Authors: Teng Haotian , Stoiber Marcus , Bar-Joseph Ziv , Kingsford Carl 
Published: January 2024

AbstractDirect nanopore-based RNA sequencing can be used to detect post-transcriptional base modifications, such as m6A methylation, based on the electric current signals produced by the distinct chemical structures of modified bases. A key challenge is the scarcity of adequate training data with known methylation modifications. We present Xron, a hybrid encoder-decoder framework that delivers a direct methylation-distinguishing basecaller by training on synthetic RNA data and immunoprecipitation-based experimental data in two steps. First, we generate data with more diverse modification combinations through in silico cross-linking. Second, we use this dataset to train an end-to-end neural network basecaller followed by fine-tuning on immunoprecipitation-based experimental data with label-smoothing. The trained neural network basecaller outperforms existing methylation detection methods on both read-level and site-level prediction scores. Xron is a standalone, end-to-end m6A-distinguishing basecaller capable of detecting methylated bases directly from raw sequencing signals, enabling de novo methylome assembly.