bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Authors: Schoenfeld David A. , Zhou Royce , Zairis Sakellarios , Su William , Steinbach Nicole , Mathur Deepti , Bansal Ankita , Zachem Alexis L. , Tavarez Bertilia , Hasson Dan , Bernstein Emily , Rabadan Raul , Parsons Ramon 
Published: April 2022

Abstract

Subunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the tumor-suppressor protein PBRM1 (BAF180), as well as ARID2 (BAF200), that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in clear cell renal cell carcinoma (ccRCC). Here, we integrate RNA-seq, histone modification ChIP-seq, and ATAC-seq data to show that loss of PBRM1 results in de novo gains in H3K4me3 peaks throughout the epigenome, including activation of a retinoic acid biosynthesis and signaling gene signature. We show that one such target gene, ALDH1A1, which regulates a key step in retinoic acid biosynthesis, is consistently upregulated with PBRM1 loss in ccRCC cell lines and primary tumors, as well as non-malignant cells. We further find that ALDH1A1 increases the tumorigenic potential of ccRCC cells. Using biochemical methods, we show that ARID2 remains bound to other PBAF subunits after loss of PBRM1 and is essential for increased ALDH1A1 after loss of PBRM1, whereas other core SWI/SNF components are dispensable, including the ATPase subunit BRG1. In total, this study uses global epigenomic approaches to uncover novel mechanisms of PBRM1 tumor suppression in ccRCC.

Implications:
This study implicates the SWI/SNF subunit and tumor-suppressor PBRM1 in the regulation of promoter histone modifications and retinoic acid biosynthesis and signaling pathways in ccRCC and functionally validates one such target gene, the aldehyde dehydrogenase ALDH1A1.
Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial
Authors: Bangalore Sripal , Spertus John A. , Stevens Susanna R. , Jones Philip G. , Mancini G.B. John , Leipsic Jonathon , Reynolds Harmony R. , Budoff Matthew J. , Hague Cameron J. , Min James K. , Boden William E. , O’Brien Sean M. , Harrington Robert A. , Berger Jeffrey S. , Senior Roxy , Peteiro Jesus , Pandit Neeraj , Bershtein Leonid , de Belder Mark A. , Szwed Hanna , Doerr Rolf , Monti Lorenzo , Alfakih Khaled , Hochman Judith S. , Maron David J. ,   on behalf of the ISCHEMIA Research Group
Published: April 2022

Background:
Patients with significant (≥50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%–49%) on outcomes is unclear.

Methods:
Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%–49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score.

Results:

Among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate LMD. Among invasive strategy participants with intermediate LMD on coronary computed tomography angiography, 49 (7.0%) had significant (≥50% stenosis) left main stenosis on invasive angiography. Patients with intermediate LMD had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate LMD. An invasive strategy increased procedural MI and decreased nonprocedural MI with no significant difference for other outcomes including the primary end point. There was no meaningful heterogeneity of treatment effect based on intermediate LMD status except for nonprocedural MI for which there was a greater absolute reduction with invasive management in the intermediate LMD group (−6.4% versus −2.0%;
P
interaction
=0.049). The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate LMD status.

Conclusions:
In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01471522.
Nomogram for Postoperative Headache in Adult Patients Undergoing Elective Cardiac Surgery
Authors: Wang Dashuai , Le Sheng , Wu Jia , Xie Fei , Li Ximei , Wang Hongfei , Zhang Anchen , Du Xinling , Huang Xiaofan 
Published: April 2022

Background
Postoperative headache (POH) is frequent after cardiac surgery; however, few studies on risk factors for POH exist. The aims of the current study were to explore risk factors related to POH after elective cardiac surgery and to establish a predictive system.

Methods and Results
Adult patients undergoing elective open‐heart surgery under cardiopulmonary bypass from 2016 to 2020 in 4 cardiac centers were retrospectively included. Two thirds of the patients were randomly allocated to a training set and one third to a validation set. Predictors for POH were selected by univariate and multivariate analysis. POH developed in 3154 of the 13 440 included patients (23.5%) and the overall mortality rate was 2.3%. Eight independent risk factors for POH after elective cardiac surgery were identified, including female sex, younger age, smoking history, chronic headache history, hypertension, lower left ventricular ejection fraction, longer cardiopulmonary bypass time, and more intraoperative transfusion of red blood cells. A nomogram based on the multivariate model was constructed, with reasonable calibration and discrimination, and was well validated. Decision curve analysis revealed good clinical utility. Finally, 3 risk intervals were divided to better facilitate clinical application.

Conclusions
A nomogram model for POH after elective cardiac surgery was developed and validated using 8 predictors, which may have potential application value in clinical risk assessment, decision‐making, and individualized treatment associated with POH.
Association Between Perioperative Adverse Cardiac Events and Mortality During One‐Year Follow‐Up After Noncardiac Surgery
Authors: Oh Ah Ran , Park Jungchan , Lee Jong‐Hwan , Kim Hara , Yang Kwangmo , Choi Jin‐ho , Ahn Joonghyun , Sung Ji Dong , Lee Seung‐Hwa 
Published: April 2022

Background
Cardiac complications are associated with perioperative mortality, but perioperative adverse cardiac events (PACEs) that are associated with long‐term mortality have not been clearly defined. We identified PACE as a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, or stroke during the 30‐day postoperative period and we compared mortality according to PACE occurrence.

Methods and Results

From January 2011 to June 2019, a total of 203 787 consecutive adult patients underwent noncardiac surgery at our institution. After excluding those with 30‐day mortality, mortality during a 1‐year follow‐up was compared. Machine learning with the extreme gradient boosting algorithm was also used to evaluate whether PACE was associated with 1‐year mortality. After excluding 1203 patients with 30‐day mortality, 202 584 patients were divided into 7994 (3.9%) patients with PACE and 194 590 (96.1%) without PACE. After an adjustment, the mortality was higher in the PACE group (2.1% versus 7.7%; hazard ratio [HR], 1.90; 95% CI, 1.74–2.09;
P
<0.001). Results were similar for 7839 pairs of propensity‐score‐matched patients (4.9% versus 7.9%; HR, 1.64; 95% CI, 1.44–1.87;
P
<0.001). PACE was significantly associated with mortality in the extreme gradient boostingmodel.

Conclusions
PACE as a composite outcome was associated with 1‐year mortality. Further studies are needed for PACE to be accepted as an end point in clinical studies of noncardiac surgery.
Seizing the Window of Opportunity Within 1 Year Postpartum: Early Cardiovascular Screening
Authors: Ackerman‐Banks Christina M. , Grechukhina Olga , Spatz Erica , Lundsberg Lisbet , Chou Josephine , Smith Graeme , Greenberg Victoria R. , Reddy Uma M. , Xu Xiao , O’Bryan Jane , Smith Shelby , Perley Lauren , Lipkind Heather S. 
Published: April 2022

Background
Our objective was to assess new chronic hypertension 6 to 12 months postpartum for those with hypertensive disorder of pregnancy (HDP) compared with normotensive participants.

Methods and Results
We performed a prospective cohort study of participants with singleton gestations and no known preexisting medical conditions who were diagnosed with HDP compared with normotensive women with no pregnancy complications (non‐HDP). Participants underwent cardiovascular risk assessment 6 to 12 months after delivery. Primary outcome was onset of new chronic hypertension at 6 to 12 months postpartum. We also examined lipid values, metabolic syndrome, prediabetes, diabetes, and 30‐year cardiovascular disease (CVD) risk. Multivariable logistic regression was performed to assess the association between HDP and odds of a postpartum diagnosis of chronic hypertension while adjusting for parity, body mass index, insurance, and family history of CVD. There were 58 participants in the HDP group and 51 participants in the non‐HDP group. Baseline characteristics between groups were not statistically different. Participants in the HDP group had 4‐fold adjusted odds of developing a new diagnosis of chronic hypertension 6 to 12 months after delivery, compared with those in the non‐HDP group (adjusted odds ratio, 4.60 [95% CI, 1.65–12.81]), when adjusting for body mass index, parity, family history of CVD, and insurance. Of the HDP group, 58.6% (n=34) developed new chronic hypertension. Participants in the HDP group had increased estimated 30‐year CVD risk and were more likely to have metabolic syndrome, a higher fasting blood glucose, and higher low‐density lipoprotein cholesterol.

Conclusions
Participants without known underlying medical conditions who develop HDP have 4‐fold increased odds of new diagnosis of chronic hypertension by 6 to 12 months postpartum as well as increased 30‐year CVD risk scores. Implementation of multidisciplinary care models focused on CVD screening, patient education, and lifestyle interventions during the first year postpartum may serve as an effective primary prevention strategy for the development of CVD.
Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity
Authors: Kingwell Bronwyn A. , Nicholls Stephen J. , Velkoska Elena , Didichenko Svetlana A. , Duffy Danielle , Korjian Serge , Gibson C. Michael 
Published: April 2022

Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90‐day post‐AMI high‐risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A‐I, which is rapidly lipidated to form high‐density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma‐derived apolipoprotein A‐I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti‐inflammatory/immune‐regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high‐risk early post‐AMI period.
Effect of Lipoprotein(a) on Stroke Recurrence Attenuates at Low LDL-C (Low-Density Lipoprotein) and Inflammation Levels
Authors: Xu Jie , Hao Xiwa , Zhan Rui , Jiang Xue , Jin Aoming , Xue Jing , Cheng Aichun , Liu Jiewen , Lin Jinxi , Meng Xia , Li Hao , Zheng Lemin , Wang Yongjun 
Published: April 2022

Background:
Lp(a) (lipoprotein(a)) contributes to cardiovascular disease mainly through proatherogenic and proinflammatory effects. Here, we aimed to evaluate whether a residual stroke risk of Lp(a) would remain when the LDL-C (low-density lipoprotein cholesterol) and inflammatory levels are maintained low.

Methods:
This prospective cohort study included 9899 patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry who had measurements of plasma Lp(a) and were followed up for 1 year. Cutoffs were set at the 50 mg/dL for Lp(a). LDL-C was corrected for Lp(a)-derived cholesterol (LDL-Cc [LDL-C corrected]) and cutoffs were set at 55 and 70 mg/dL.The threshold values of IL-6 (interleukin 6) and hsCRP (high-sensitive C-reactive protein) were the median 2.65 ng/L and 2 mg/L. Multivariable-adjusted hazard ratio (HR) were calculated using Cox regression models for each category to investigate the associations of Lp(a) with stroke recurrence within 1 year.

Results:
Among all patients, those with Lp(a) ≥50 mg/dL were at higher stroke recurrence risk than those with Lp(a) <50 mg/dL (11.5% versus 9.4%; adjusted HR, 1.20 [95% CI, 1.02–1.42]). However, the risk associated with elevated Lp(a) was attenuated in patients with LDL-Cc <55 mg/dL (high Lp(a) versus low Lp(a): 8.9% versus 9.0%; adjusted HR, 0.92 [95% CI, 0.65–1.30]) or IL-6 <2.65 ng/L (9.0% versus 7.8%; adjusted HR, 1.14 [95% CI, 0.87–1.49]). Notably, in the group with both low LDL-Cc and inflammation levels, the rate of patients with high Lp(a) did not significantly different from the rate of patients with low Lp(a; LDL-Cc <55 mg/dL and IL-6 <2.65 ng/L: 6.2% versus 7.1%; adjusted HR, 0.86 [95% CI, 0.46–1.62]; LDL-Cc <55 mg/dL and hsCRP <2 mg/L: 7.7% versus 7.6%; adjusted HR, 0.97 [95% CI, 0.57–1.66]). However, there was no interaction between the LDL-Cc, IL-6, hsCRP, and Lp(a) levels on stroke recurrence risk.

Conclusions:
Increased Lp(a) was significantly associated with stroke recurrence risk in patients with ischemic stroke/transient ischemic attack. However, at low LDL-Cc or IL-6 levels, the elevated Lp(a) -associated stroke recurrence risk was attenuated in a secondary prevention setting.
TopiOCQA: Open-domain Conversational Question Answering with Topic Switching
Authors: Adlakha Vaibhav , Dhuliawala Shehzaad , Suleman Kaheer , de Vries Harm , Reddy Siva 
Published: April 2022

Abstract
In a conversational question answering scenario, a questioner seeks to extract information about a topic through a series of interdependent questions and answers. As the conversation progresses, they may switch to related topics, a phenomenon commonly observed in information-seeking search sessions. However, current datasets for conversational question answering are limiting in two ways: 1) they do not contain topic switches; and 2) they assume the reference text for the conversation is given, that is, the setting is not open-domain. We introduce TopiOCQA (pronounced Tapioca), an open-domain conversational dataset with topic switches based on Wikipedia. TopiOCQA contains 3,920 conversations with information-seeking questions and free-form answers. On average, a conversation in our dataset spans 13 question-answer turns and involves four topics (documents). TopiOCQA poses a challenging test-bed for models, where efficient retrieval is required on multiple turns of the same conversation, in conjunction with constructing valid responses using conversational history. We evaluate several baselines, by combining state-of-the-art document retrieval methods with neural reader models. Our best model achieves F1 of 55.8, falling short of human performance by 14.2 points, indicating the difficulty of our dataset. Our dataset and code are available at https://mcgill-nlp.github.io/topiocqa.
Corybas kaiganganianus (Orchidaceae), a new, rare helmet orchid from Samar Island, Philippines
Authors: DELOS ANGELES MARJORIE D. , BUOT JR. INOCENCIO E. , MORAN CECILIA B. , ROBINSON ALASTAIR S. , TANDANG DANILO N. 
Published: April 2022

Corybas Salisbury (1807: t. 83) comprises approximately 120 highly distinctive and diminutive terrestrial and lithophytic species widely distributed from India to the western Pacific (Pridgeon et al. 2001, Aldrich & Haggins 2008, Chung & Hsu 2008, Chantanaorrapint & Chantanaorrapint 2016, Govaerts et al. 2019). The Philippines has six Corybas species (Pelser et al., 2011): C. boholensis Tandang, Bustamante, Reyes & Lyon (2020a: 261), Bohol, Visayas;, C. circinatus Tandang & Bustamante (2020b: 135), central Palawan; C. geminigibbus Smith (1927: 13), Mt. Victoria, Palawan; C. laceratus Williams (1937: 54), Rizal Prov., Luzon; C. merrillii (Ames) Ames (1908: 42), Mt. Mariveles, Luzon; and C. ramosianus Dransfield in Dransfield et al. (1986: 611), Ilocos Norte Prov., Luzon. Corybas is often overlooked and understudied owing to its diminutive size and ephemeral flowers (Tandang et al. 2020a), and ongoing explorations of the Philippine Archipelago have demonstrated the merit of this observation, with several species having been newly documented and described in recent years from areas that are known to have been botanized in the past.
Ecocene Politics
Authors: Tănăsescu Mihnea 
Published: April 2022

Anchored in the diverse ecological practices of communities in southern Italy and Aotearoa/New Zealand, this book devises a unique and considered theoretical response to the shortcomings of global politics in the Ecocene—a new temporal epoch characterised by the increasingly frequent intrusion of ecological processes into political life.
Dismantling the use of the term ‘Anthropocene’ as a descriptor for our current ecological and political paradigm, this bold and resolutely original contribution proposes a restorative ethics of mutualism. An emancipatory theory intended to re-invigorate human agency in the face of contemporary ecological challenges, it posits an effective means to combat the environmental destruction engendered by modernity.
Using ecology alongside European moral and Māori philosophies to re-conceptualise the ecological remit of politics, this book’s granular approach questions the role played by contemporary political ontologies in the separation of humans and environments, offering an in-depth view of their renewed interrelation under mutualism.
Ecocene Politics will be essential to researchers and students in the fields of politics, philosophy, sociology, anthropology, and geography. It will be of further interest to those working in the fields of political ecology, environmental humanities, and Anthropocene studies, as well as to general readers seeking a theoretical approach to the political issues posed by current ecological crises.
Mental health symptoms in children and adolescents during COVID-19 in Australia
Authors: Sicouri Gemma , March Sonja , Pellicano Elizabeth , De Young Alex C , Donovan Caroline L , Cobham Vanessa E , Rowe Arlen , Brett Simon , Russell Jeremy K , Uhlmann Laura , Hudson Jennifer L 
Published: April 2022

Objective: COVID-19 has led to disruptions to the lives of Australian families through social distancing, school closures, a temporary move to home-based online learning, and effective lockdown. Understanding the effects on child and adolescent mental health is important to inform policies to support communities as they continue to face the pandemic and future crises. This paper sought to report on mental health symptoms in Australian children and adolescents during the initial stages of the pandemic (May to November 2020) and to examine their association with child/family characteristics and exposure to the broad COVID-19 environment. Methods: An online baseline survey was completed by 1327 parents and carers of Australian children aged 4 to 17 years. Parents/carers reported on their child’s mental health using five measures, including emotional symptoms, conduct problems, hyperactivity/inattention, anxiety symptoms and depressive symptoms. Child/family characteristics and COVID-related variables were measured. Results: Overall, 30.5%, 26.3% and 9.5% of our sample scored in the high to very high range for emotional symptoms, conduct problems and hyperactivity/inattention, respectively. Similarly, 20.2% and 20.4% of our sample scored in the clinical range for anxiety symptoms and depressive symptoms, respectively. A child’s pre-existing mental health diagnosis, neurodevelopmental condition and chronic illness significantly predicted parent-reported child and adolescent mental health symptoms. Parental mental health symptoms, having a close contact with COVID-19 and applying for government financial assistance during COVID-19, were significantly associated with child and adolescent mental health symptoms. Conclusion: Our findings show that Australian children and adolescents experienced considerable levels of mental health symptoms during the initial phase of COVID-19. This highlights the need for targeted and effective support for affected youth, particularly for those with pre-existing vulnerabilities.
Evaluating level of specificity and discrepancy of normative referents for condom promotion
Authors: Firkey Madison K , Sheinfil Alan Z , Woolf-King Sarah E 
Published: April 2022

Objective: College students are among the age-group most affected by sexually transmitted infections, yet few evidence-based interventions have proved effective in increasing college student condom use. The goal of this study was to determine which combination of referent proximity and width of discrepancy between perceived and actual norms within a normative feedback intervention produced the greatest motivation to increase condom use among US college students. Design: A 2 (proximity) × 2 (width of discrepancy) × 2 (gender) randomised-factorial experiment was conducted. Setting: Sexually active college students ( N = 212; 50.5% female; 70.4% White) were recruited via Amazon Mechanical Turk, an online labour market. Method: Participants were randomised, stratified by gender, to one of four sham feedback conditions: proximal referent wide discrepancy, proximal referent narrow discrepancy, distal referent wide discrepancy and distal referent narrow discrepancy. Following delivery of the feedback, participants completed measures assessing their willingness to change their condom use. Results: A three-way factorial analysis of covariance revealed a significant interaction between referent proximity and width of discrepancy ( F = 7.88, p = .005, [Formula: see text]), such that the effect of proximity on willingness to use condoms was greater in the narrow, compared with wide, discrepancy condition. Conclusion: Findings from this study indicate that it may be beneficial to assess students’ perceptions of their peers’ sexual behaviour before selecting the reference group to include within normative feedback. This is the first study to demonstrate that the importance of selecting referents within normative feedback may be dependent on the accuracy of students’ perceptions.