bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Medical Comorbidities on Survival Disparities in a Multiethnic Group of Patients with De Novo Metastatic Breast Cancer
Authors: Wallner Lauren P. , Chen Lie H. , Hogan Tiffany A. , Brasfield Farah M. , Haque Reina 
Published: July 2022

Abstract

Background:
The influence of common medical comorbidities on mortality and racial/ethnic disparities in mortality among women with metastatic breast cancer remains largely unknown.

Methods:
In this longitudinal study, women with newly diagnosed stage IV breast cancer were identified in a large, diverse, integrated healthcare delivery system from January 2009 to December 2017 (n = 995) and followed through December 31, 2018, for all-cause (overall) and breast cancer–specific mortality via electronic health records. We computed overall and breast cancer–specific mortality rates by race/ethnicity and Elixhauser comorbidity index (ECI). Multivariable-adjusted hazard ratios (HR) assessing the influence of race/ethnicity and comorbidity status on overall and breast cancer–specific mortality were estimated using proportional hazards regression adjusted for age, breast cancer subtype, geocoded income, and palliative cancer treatments.

Results:
Nearly 17% of this cohort had diabetes and 45% had hypertension. Overall, 644 deaths occurred in the cohort (median follow-up time of 1.8 years), of which 88% were breast cancer related. The risk of overall mortality was increased in Asian/Pacific Islander (PI; adjusted HR = 1.45; 95% CI, 1.10–1.92) and African American/Black women (adjusted HR = 1.34; 95% CI, 1.02–1.76) when compared with white women. Women with more comorbidities (ECI ≥ 5) had more than 3-fold higher overall mortality rate than those without any comorbidities [602/1,000 person-year (PY) vs. 175/1,000 PY]. Similar associations were found for breast cancer–specific mortality.

Conclusions:
Medical comorbidities are associated with an increased risk of overall mortality among women with de novo metastatic disease and may influence racial/ethnic disparities in mortality.

Impact:
Optimizing the management of medical comorbidities in metastatic breast cancer patients may also help reduce disparities in breast cancer–related mortality.
HPV DNA as a Biomarker in Oropharyngeal Cancer: A Step in the Right Direction
Authors: Colevas A. Dimitrios 
Published: July 2022

SummaryLack of prospectively planned follow-up and minimal characterization of the patient population studied complicate interpretation of circulating human papillomavirus (HPV) DNA as a prognostic biomarker for patients with HPV-associated oropharyngeal carcinoma treated with curative intent.See related article by Berger et al., p. 4292
Using CD69 PET Imaging to Monitor Immunotherapy-Induced Immune Activation
Authors: Edwards Kimberly J. , Chang Bryan , Babazada Hasan , Lohith Katheryn , Park Daniel H. , Farwell Michael D. , Sellmyer Mark A. 
Published: July 2022

AbstractImmune checkpoint inhibitors (ICI) have been effective in treating a subset of refractory solid tumors, but only a small percentage of treated patients benefit from these therapies. Thus, there is a clinical need for reliable tools that allow for the early assessment of response to ICIs, as well as a preclinical need for imaging tools that aid in the future development and understanding of immunotherapies. Here we demonstrate that CD69, a canonical early-activation marker expressed on a variety of activated immune cells, including cytotoxic T cells and natural killer (NK) cells, is a promising biomarker for the early assessment of response to immunotherapies. We have developed a PET probe by radiolabeling a highly specific CD69 mAb, H1.2F3, with Zirconium-89 (89Zr), [89Zr]-deferoxamine (DFO)-H1.2F3. [89Zr]-DFO-H1.2F3 detected changes in CD69 expression on primary mouse T cells in vitro and detected activated immune cells in a syngeneic tumor immunotherapy model. In vitro uptake studies with [89Zr]-DFO-H1.2F3 showed a 15-fold increase in CD69 expression for activated primary mouse T cells, relative to untreated resting T cells. In vivo PET imaging showed that tumors of ICI-responsive mice had greater uptake than the tumors of nonresponsive and untreated mice. Ex vivo biodistribution, autoradiography, and IHC analyses supported the PET imaging findings. These data suggest that the CD69 PET imaging approach detects CD69 expression with sufficient sensitivity to quantify immune cell activation in a syngeneic mouse immunotherapy model and could allow for the prediction of therapeutic immune responses to novel immunotherapies.
Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study
Authors: Farland Leslie V. , Degnan William J. , Bell Melanie L. , Kasner Scott E. , Liberman Ava L. , Shah Divya K. , Rexrode Kathryn M. , Missmer Stacey A. 
Published: July 2022

Background:
Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up.

Methods:

Participants in the NHSII cohort study (Nurses’ Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50,
≥
50 years), infertility history, body mass index (<25,
≥
25 kg/m
2
), and menopausal status.

Results:
We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10–1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%–71%]) and hormone therapy (16% mediated [95% CI, 5%–40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status.

Conclusions:
We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.
Pathways to an International Agreement to Leave Fossil Fuels in the Ground
Authors: van Asselt Harro , Newell Peter 
Published: July 2022

Abstract
To achieve the Paris Agreement’s temperature goal, fossil fuel production needs to undergo a managed decline. While some frontrunner countries have already begun to adopt policies and measures restricting fossil fuel supply, an outstanding question is how international cooperation in support of a managed decline of fossil fuel production could take shape. This article explores two possible pathways—one following a club model and the other more akin to a multilateral environmental agreement. Specifically, the article discusses the participants in an international agreement; the forum through which cooperation will take place; the modalities, principles, and procedures underpinning the agreement; and the incentives to induce cooperation. The article concludes that the most likely scenario at this juncture is the emergence of club arrangements covering particular fossil fuel sources and groups of actors that, over time, give rise to growing calls for a more coordinated and multilateral response.
Comparative genomics reveals the molecular mechanism of salt adaptation for zoysiagrasses
Authors: Wang Wei , Shao An , Xu Xiao , Fan Shugao , Fu Jinmin 
Published: July 2022

Abstract
Background
Zoysiagrass (Zoysia spp.) is a warm-season turfgrass. It is widely used as turfgrasses throughout the world, offers good turf qualities, including salt tolerance, resistance to drought and heat. However, the underlying genetic mechanism of zoysiagrass responsive to salt stress remains largely unexplored.

Results
In present study, we performed a whole-genome comparative analysis for ten plant genomes. Evolutionary analysis revealed that Chloridoideae diverged from Panicoideae approximately 33.7 million years ago (Mya), and the phylogenetic relationship among three zoysiagrasses species suggested that Zoysia matrella may represent an interspecific hybrid between Zoysia japonica and Zoysia pacifica. Genomic synteny indicated that Zoysia underwent a genus-specific whole-genome duplication (WGD) event approximately 20.8 Mya. The expression bais of homologous genes between the two subgenomes suggested that the B subgenome of Z. japonica contributes to salt tolerance. In additon, comparative genomic analyses revealed that the salt adaptation of Zoysia is likely attributable to the expanded cytochrome P450 and ABA biosynthetic gene families. Furthermore, we further found that many duplicated genes from the extra WGD event exhibited distinct functional divergence in response to salt stress using transcriptomic analysis, suggesting that this WGD event contributed to strong resistance to salt stress.

Conclusions
Here, our results revealed that expanded cytochrome P450 and ABA biosynthetic gene families, and many of those duplicated genes from recent zoysia-specific WGD event contributed to salt adaptation of zoysiagrass, which provided insight into the genetic underpinning of salt adaptation and valuable information for further studies on salt stress-related traits in Zoysia.
Prognostic value of platelet count-related ratios on admission in patients with pyogenic liver abscess
Authors: Li Shixiao , Yu Sufei , Qin Jiajia , Peng Minfei , Qian Jiao , Zhou Peng 
Published: July 2022

Abstract
Objective
The purpose of the current study was to evaluate the association between C-reactive protein-to-platelet ratio (CPR), neutrophil-to-lymphocyte*platelet ratio (NLPR) and fibrinogen-to-platelet ratio (FPR) and the prognoses of pyogenic liver abscess (PLA) patients.

Methods
A cohort of 372 patients with confirmed PLA were enrolled in this retrospective study between 2015 and 2021. Laboratory data were collected on admission within 24 h. The demographic characteristics and clinical features were recorded. Risk factors for outcomes of PLA patients were determined via multivariate logistic regression analyses, and optimal cut-off values were estimated by using the receiver operating characteristic (ROC) curve analysis.

Results
Out of 372 patients, 57.8% were men, 80 (21.5%) developed sepsis, and 33 (8.9%) developed septic shock. The levels of CPR, NLPR and FPR were significantly increased in the development of sepsis, and prolonged hospital stays in PLA patients. The multivariate logistic regression analysis indicated that the CPR (OR: 2.262, 95% CI: 1.586–3.226, p < 0.001), NLPR (OR: 1.118, 95% CI: 1.070–1.167, p < 0.001) and FPR (OR: 1.197, 95% CI: 1.079–1.329, p = 0.001) were independent risks of PLA patients with sepsis, and NLPR (OR: 1.019, 95% CI: 1.004–1.046, p = 0.019) was shown to be an independent predictor of prolonged hospital stays. The ROC curve results showed that the three biomarkers had different predictive values, and CPR proved to work best, with a ROC value of 0.851 (95% CI: 0.807–0.896, p < 0.001) for sepsis.

Conclusion
Higher levels of CPR, NLPR and FPR were associated with a higher risk of poor outcomes. Moreover, a high CPR level performed best when predicting the clinical outcome in PLA patients.
Comprehensive analysis of the prognosis and immune infiltration landscape of RNA methylation-related subtypes in pancreatic cancer
Authors: Lu Siyuan , Hua Jie , Liu Jiang , Wei Miaoyan , Liang Chen , Meng Qingcai , Zhang Bo , Yu Xianjun , Wang Wei , Xu Jin 
Published: July 2022

Abstract
Background
RNA methylation refers to a form of methyl modification in RNA that modulates various epigenetic alterations. Mounting studies have focused on its potential mechanisms in cancer initiation and progression. However, the prognostic value and potential role of RNA methylation in the immune microenvironment of pancreatic cancer remain unclear.

Methods
Comprehensive bioinformatics analysis was performed to illuminate the expression profiles of RNA methylation modulators. In addition, the ConsensusClusterPlus algorithm was utilized to identify two remarkably different subtypes, and a feasible risk stratification method was established to accurately estimate prognosis. In addition, we validated our signature at the cytology and histology levels and conducted functional experiments to explore the biological functions of our key genes.

Results
Two subtypes with remarkable survival differences were identified by the consensus clustering algorithm. Cluster 2 tended to have higher expression levels of RNA methylation regulators and to be the high RNA methylation group. In addition, cluster 1 exhibited a significantly higher abundance of almost all immune cells and increased immune checkpoint expression compared to cluster 2. Chemotherapeutic sensitivity analysis indicated that there were significant differences in the sensitivity of four of the six drugs between different subgroups. Mutation investigation revealed a higher mutation burden and a higher number of mutations in cluster 2. An accurate and feasible risk stratification method was established based on the expression of key genes of each subtype. Patients with low risk scores exhibited longer survival times in one training (TCGA) and two validation cohorts (ICGC, GSE57495), with p values of 0.001, 0.0081, and 0.0042, respectively. In addition, our signature was further validated in a cohort from Fudan University Shanghai Cancer Center. The low-risk group exhibited higher immune cell abundance and immune checkpoint levels than the high-risk group. The characteristics of the low-risk group were consistent with those of cluster 1: higher stromal score, estimate score, and immune score and lower tumor purity. Additionally, cell function investigations suggested that knockdown of CDKN3 remarkably inhibited the proliferation and migration of pancreatic cancer cells.

Conclusions
RNA methylation has a close correlation with prognosis, immune infiltration and therapy in pancreatic cancer. Our subtypes and risk stratification method can accurately predict prognosis and the efficacy of immune therapy and chemotherapy.
A prospective cohort study on the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam
Authors: Le Hung Xuan , Truong Dung Thi Thuy , Tran Long Bao , Le Phuoc Hong , Pham Binh Uyen Duong , Wada Koji , Ikeda Shunya , Garidkhuu Ariuntuul , Van Phan Can , Le Ngoan Tran 
Published: July 2022

AbstractTobacco consumption, as a worldwide problem, is a risk factor for several types of cancer. In Vietnam, tobacco consumption in the form of waterpipe tobacco smoking is common. This prospective cohort study aimed to study the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam. A total of 25,619 eligible participants were followed up between 2008 and 2019. Waterpipe tobacco and cigarette smoking data were collected; semi-quantitative food frequency and lifestyle questionnaires were also utilized. Gastric cancer mortality was determined via medical records available at the state health facilities. A Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During 314,992.8 person-years of follow-up, 55 men and 25 women deaths due to gastric cancer were identified. With never-smokers as the reference, the risk of gastric cancer mortality was significantly increased in participants who were ever-smoking (HR = 2.43, 95% CI = 1.35–4.36). The positive risk was also observed in men but was not significantly increased in women. By types of tobacco use, exclusive waterpipe smokers showed a significantly increased risk of gastric cancer mortality (HR = 3.22, 95% CI = 1.67–6.21) but that was not significantly increased in exclusive cigarette smokers (HR = 1.90, 95% CI = 0.88–4.07). There was a significant positive association between tobacco smoking and gastric cancer death for indicators of longer smoking duration, higher frequency per day, and cumulative frequency of both waterpipe and cigarette smoking. Waterpipe tobacco smoking would significantly increase the risk of gastric cancer mortality in the Vietnamese population. Further studies are required to understand the waterpipe tobacco smoking-driven gastric cancer burden and promote necessary interventions.
A Southeast Asian expert consensus on the management of major depressive disorder with suicidal behavior in adults under 65 years of age
Authors: Chee Kok Yoon , Muhdi Nalini , Ali Nor Hayati , Amir Nurmiati , Bernardo Carmina , Chan Lai Fong , Ho Roger , Ittasakul Pichai , Kwansanit Patanon , Mariano Melissa Paulita , Mok Yee Ming , Tran Duy Tam , Trinh Thi Bich Huyen 
Published: July 2022

Abstract
Background
The high prevalence of suicidal behavior among individuals with major depressive disorder (MDD) in Southeast Asia (SEA) underscores the need for optimized management to address depressive symptoms, reduce suicide risk and prevent suicide in these individuals. Given the lack of clear guideline recommendations for assessing and managing these patients, regional consensus-based recommendations which take into account diverse local contexts across SEA may provide useful guidance for clinical practice.

Methods
A narrative literature review and pre-meeting survey were conducted prior to the consensus meeting of an SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with MDD with suicidal behavior. Utilizing the RAND/UCLA Appropriateness Method, the expert panel developed consensus-based recommendations on the assessment and treatment of adult patients with MDD with suicidal behavior under 65 years.

Results
Screening of adult patients under 65 years with MDD for suicide risk using both a validated assessment tool and clinical interview is recommended. An improved suicide risk stratification – incorporating both severity and temporality, or using a prevention-focused risk formulation – should be considered. For a patient with an MDD episode with low risk of suicide, use of antidepressant monotherapy, and psychotherapy in combination with pharmacological treatment are both recommended approaches. For a patient with an MDD episode with high risk of suicide, or imminent risk of suicide requiring rapid clinical response, or for a patient who had received adequate AD but still reported suicidal behavior, recommended treatment strategies include antidepressant augmentation, combination use of psychotherapy or electroconvulsive therapy with pharmacological treatment, and inpatient care. Suicide-specific psychosocial interventions are important for suicide prevention and should also be part of the management of patients with MDD with suicidal behavior.

Conclusions
There are still unmet needs in the assessment of suicide risk and availability of treatment options that can deliver rapid response in patients with MDD with suicidal behavior. These consensus recommendations on the management of adult patients with MDD with suicidal behavior under 65 years may serve as a useful guidance in diverse clinical practices across the SEA region. Clinical judgment based on careful consideration of individual circumstances of each patient remains key to determining the most appropriate treatment option.
Barriers and facilitators to utilisation of public sexual healthcare services for male sex workers who have sex with men (MSW-MSM) in The Netherlands: a qualitative study
Authors: Peters Charlotte Merel Marije , Dukers-Muijrers Nicole Helena Theodora Maria , Evers Ymke Joline , Hoebe Christian Jean Pierre Antoine 
Published: July 2022

Abstract
Background
Male sex workers who have sex with men (MSW-MSM) are a high-risk group for sexually transmitted infections (STI) including human immunodeficiency virus (HIV). Provision of sexual services by MSW-MSM has shifted to the internet. Consequently, MSW-MSM have become hidden to care for providers of sexual healthcare services (SHS). The aim of this study was to 1) assess characteristics of the MSW-MSM population and 2) assess MSW-MSM’s perceived barriers and facilitators to utilise SHS provided free and anonymously by the public health STI clinic in The Netherlands.

Methods
For this qualitative study, semi-structured individual in-depth interviews were conducted with 20 MSW-MSM who worked home-based in the Dutch province of Limburg. Participants were recruited from November 2018 to June 2019 by purposive sampling until saturation was reached via 1) five websites and smartphone applications commonly used by MSW-MSM, 2) STI clinic, 3) two gay saunas. A theory-informed interview guide was developed including themes such as sexuality, sex work, SHS and barriers and facilitators to SHS utilisation. The interviews’ recordings were transcribed verbatim and thematically analysed by inductive and deductive coding with Atlas.ti 8.

Results
The interviewed MSW-MSM were diverse in age (range: 18 – 66; median: 39.5) and mostly western European (85%). Identified barriers to SHS utilisation were lack of self-identification as homosexual and sex worker, perceived stigma on sex work and MSM, the lack of awareness of SHS and a low STI risk perception. Identified facilitators were trust in and positive attitude towards SHS, awareness of SHS’s anonymous, confidential and free-of-charge nature, high STI risk perception and knowledgeable about STI/HIV. MSW-MSM-identified implications for SHS-providers were promotion of SHS on online MSW-MSM and general platforms (e.g. Facebook), offering one-on-one online and informal communication with an SHS-provider (e.g. STI clinic nurse) and providing STI (testing) information.

Conclusion
The MSW-MSM population’s diversity and identified barriers, facilitators and implications should be taken into account to optimize accessibility and utilisation of SHS for MSW-MSM in Western Europe. SHS-providers could facilitate sex work disclosure by personally asking patients about sex in exchange for money or goods in a non-judgmental manner and explaining the medical relevance of disclosure.