bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials
Authors: Llovet Josep M. , Singal Amit G. , Villanueva Augusto , Finn Richard S. , Kudo Masatoshi , Galle Peter R. , Ikeda Masafumi , Callies Sophie , McGrath Louise M. , Wang Chunxiao , Abada Paolo , Widau Ryan C. , Gonzalez-Gugel Elena , Zhu Andrew X.
Published: April 2022

Purpose:

Ramucirumab is an effective treatment for patients with advanced hepatocellular carcinoma (aHCC) and baseline alpha-fetoprotein (AFP) ≥400 ng/mL. We aimed to identify prognostic and predictive factors of response to ramucirumab in patients with aHCC with AFP ≥400 ng/mL from the phase III REACH and REACH-2 randomized trials.

Patients and Methods:

Patients with aHCC, Child-Pugh class A with prior sorafenib treatment were randomized in REACH and REACH-2 (ramucirumab 8 mg/kg or placebo, biweekly). Meta-analysis of individual patient-level data (pooled population) from REACH (AFP ≥400 ng/mL) and REACH-2 was performed. A drug exposure analysis was conducted for those with evaluable pharmacokinetic data. To identify potential prognostic factors for overall survival (OS), multivariate analyses were performed using a Cox proportional hazards regression model. To define predictors of ramucirumab benefit, subgroup-by-treatment interaction terms were evaluated.

Results:

Of 542 patients (316 ramucirumab, 226 placebo) analyzed, eight variables had independent prognostic value associated with poor outcome (geographical region, Eastern Cooperative Oncology Group performance score ≥1, AFP >1,000 ng/mL, Child-Pugh >A5, extrahepatic spread, high neutrophil-to-lymphocyte ratio, high alkaline phosphatase and aspartate aminotransferase). Ramucirumab survival benefit was present across all subgroups, including patients with very aggressive HCC [above median AFP; HR: 0.64; 95% confidence interval (CI): 0.49–0.84] and nonviral aHCC (HR: 0.56; 95% CI: 0.40–0.79). While no baseline factor was predictive of a differential OS benefit with ramucirumab, analyses demonstrated an association between high drug exposure, treatment-emergent hypertension (grade ≥3), and increased ramucirumab benefit.

Conclusions:

Ramucirumab provided a survival benefit irrespective of baseline prognostic covariates, and this benefit was greatest in patients with high ramucirumab drug exposure and/or those with treatment-related hypertension.
Dual Fluorescence Isogenic Synthetic Lethal Kinase Screen and High-Content Secondary Screening for MUC16/CA125-Selective Agents
Authors: Rao Thapi D. , Xu Mengyao , Eng Stephanie , Yang Guangli , Manson Robin , Rosales Nestor , Kumar Raj , Veillard Irva E. , Zhou Qin , Iasonos Alexia , Ouerfelli Ouathek , Djaballah Hakim , Spriggs David R. , Yeku Oladapo O.
Published: April 2022

Significant strides have been made in the development of precision therapeutics for cancer. Aberrantly expressed glycoproteins represent a potential avenue for therapeutic development. The MUC16/CA125 glycoprotein serves as a biomarker of disease and a driver of malignant transformation in epithelial ovarian cancer. Previously, we demonstrated a proof-of-principle approach to selectively targeting MUC16+ cells. In this report, we performed a synthetic lethal kinase screen using a human kinome RNAi library and identified key pathways preferentially targetable in MUC16+ cells using isogenic dual-fluorescence ovarian cancer cell lines. Using a separate approach, we performed high-content small-molecule screening of six different libraries of 356,982 compounds for MUC16/CA125-selective agents and identified lead candidates that showed preferential cytotoxicity in MUC16+ cells. Compounds with differential activity were selected and tested in various other ovarian cell lines or isogenic pairs to identify lead compounds for structure–activity relationship (SAR) selection. Lead siRNA and small-molecule inhibitor candidates preferentially inhibited invasion of MUC16+ cells in vitro and in vivo, and we show that this is due to decreased activation of MAPK, and non–receptor tyrosine kinases. Taken together, we present a comprehensive screening approach to the development of a novel class of MUC16-selective targeted therapeutics and identify candidates suitable for further clinical development.
Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600–Mutant Tumors
Authors: Adashek Jacob J. , Menta Arjun K. , Reddy Neha K. , Desai Aakash P. , Roszik Jason , Subbiah Vivek
Published: April 2022

BRAF plus MEK inhibitor combinations are currently FDA-approved for melanoma, non–small cell lung cancer, and anaplastic thyroid cancer. The lack of clinical benefit with BRAF inhibition in BRAF V600–mutated colorectal cancer has prevented its tissue-agnostic drug development. We reviewed the AACR GENIE database for the prevalence of BRAF V600 mutations across tumor types. We reviewed the literature for case reports of clinical responses, outcomes in patients with BRAF V600 mutation—positive nonmelanoma malignancies who received BRAF inhibitor therapy, and data from published adult and pediatric trials. BRAF V600 mutations are prevalent across multiple nonmelanoma malignancies (>40 different tumor types), lead to oncogene addiction, and are clinically actionable in a broad range of adult and pediatric nonmelanoma rare malignancies. Continued tissue-agnostic drug development is warranted beyond the current BRAF plus MEK approved cancers.
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

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.
Clinical Efficacy and Safety of Artesimia annua-Sublingual Immunotherapy in Seasonal Allergic Rhinitis Patients Based on Different Intervention Time
Authors: Yang Jiayi , Shen Zhen , Liu Lifeng , Kang Wei , Shao Yuan , Zhang Pengfei , Quan Fang
Published: April 2022

Introduction: Artemisia is a major kind of grass pollen in Northern China that can cause multiple kinds of common allergic diseases, such as allergic rhinitis (AR), conjunctivitis, or asthma. Recently, Artemisia annua Allergens Sublingual Immunotherapy Drops have been proved effective and safe for treating seasonal AR (SAR) with or without allergic conjunctivitis patients and were available in China. We sought to further investigate the different intervention times of A. annua-sublingual immunotherapy (SLIT) for evaluating efficacy and safety in patients with SAR. Methods: A total of 88 subjects aged 18–52 years with SAR were enrolled and randomized into the SLIT group and control group. Forty-five patients received a course of SLIT with A. annua extracts along with pharmacotherapy as SLIT group and 43 patients only used symptomatic drugs as control group. Furthermore, SLIT group was randomly divided into 12–13 weeks’ pre-seasonal treatment group and 8–9 weeks’ pre-seasonal treatment group to receive different duration of SLIT before pollen season. Monosensitized and polysensitized groups were also the subgroups of SLIT group according to the sensitization status of patients. The combined symptom and medication score (CSMS), total nasal symptom score (TNSS), total medication score (TMS), visual analog score (VAS) were evaluated during the peak pollen phase in 2020 and 2021, respectively. Safety was assessed according to adverse events (AEs) reported. Results: Compared to control group, CSMS, TNSS, TMS, VAS were significantly improved during the course of SLIT (p < 0.001). Besides, clinical improvement in nasal symptoms and reduction of medication use was also observed in SLIT group, compared to the baseline value (p < 0.001). Meanwhile, we observed that there was no significant difference between monosensitized group (n = 8) and polysensitized group (n = 29), as well as 12–13 weeks’ preseasonal treatment group (n = 20) and 8–9 weeks’ pre-seasonal treatment group (n = 17) belonging to the SLIT group in clinical efficacy (p > 0.05). No severe systemic AEs were reported. Conclusions: This study proved that A. annua-SLIT can provide equivalent efficacy and safety for SAR patients under the circumstance of accepting the pre-seasonal treatment of 8–9 or 12–13 weeks, regardless of monosensitization or polysensitization.
Toxoplasma Lymphadenopathy in an Immunocompetent Host
Authors: Mandal Sanjay Kumar , Chandra Atanu , Ganguly Jacky , Chakraborty Uddalak
Published: April 2022

Toxoplasma infection can be congenital or acquired. Infection with Toxoplasma gondii can result in multi-organ involvement in immunocompromised patients; whereas in immunocompetent patients, it usually remains asymptomatic. Toxoplasma is a rare cause of isolated lymphadenopathy especially in immunocompetent individuals, though it is a common manifestation of this protozoal infection. We present a 27-year-old male who presented to us with isolated cervical lymphadenopathy. Histopathology and serological studies confirmed the diagnosis of toxoplasma lymphadenopathy. It usually affects the posterior cervical group of lymph nodes, but in our case, it had also affected anterior group and presented without any constitutional symptom. The patient was treated with cotrimoxazole double strength tablet once daily for 1 month and responded well.
Fertility Counseling Practices for Patients with Turner Syndrome in Pediatric Endocrine Clinics: Results of a Pediatric Endocrine Society Survey
Authors: Theroux Charleen I. , Elliott Victoria , Davis Shanlee , Crerand Canice E. , Kremen Jessica , Tishelman Amy , Hutaff-Lee Christa , Nahata Leena
Published: April 2022

Introduction: Turner syndrome (TS) is associated with a high risk of primary ovarian insufficiency. Current guidelines recommend early fertility counseling for affected youth and their families. This study assessed clinical providers’ (MD, NP, or PA) fertility counseling practices for girls with TS. Methods: TS providers were invited to complete a survey via the Pediatric Endocrine Society listserv. Descriptive statistics summarized variables of interest. Correlations were used to identify associations between barriers/practice characteristics and fertility preservation (FP) referral. Thematic analysis was used to examine qualitative responses. Results: 119 providers completed the survey. Seventy percent reported discussing fertility implications of TS routinely in pediatric care. Fifty-six percent reported often or always referring patients with spontaneous menarche to FP specialists, whereas only 19% reported often or always referring their patients without spontaneous menarche (p < 0.001). Barriers associated with FP referral frequency included unfamiliarity with FP options, belief that FP is not a possible goal for their patients, and absence of a local reproductive endocrinologist. Qualitatively, four referral barrier themes were identified: (1) questionable utility of referral, (2) lack of perceived interest among patients/families, (3) provider barriers (e.g., lack of knowledge), (4) logistical/structural barriers to accessing fertility-related care. Discussion/Conclusion: Pediatric endocrinology providers report inconsistently discussing fertility implications of TS. The frequency of referral to an FP specialist and factors/barriers affecting the decision to refer remain variable. Future research should focus on expanding provider education, addressing barriers to high-quality fertility counseling and referral for patients with TS, and investigating FP outcomes in TS.
Transportes e planos de viação no Brasil imperial
Authors: Grandi Guilherme
Published: April 2022

O contexto histórico da Independência do Brasil foi marcado por inúmeros desafios, dentre eles o estabelecimento de uma rede de vias de comunicação que integrasse o território e, assim, auxiliasse a unidade do Império brasileiro. Nesse sentido, o objetivo do presente artigo é discutir, em primeiro lugar, aspectos gerais sobre os transportes terrestre e fluvial ao longo do Primeiro Reinado (1822-1831) e da Regência (1831-1840). Em seguida, analisa-se, a partir da bibliografia especializada e de fontes primárias selecionadas, as propostas de alguns dos principais planos de viação que surgiram ao longo do período de 1869 a 1882.
O mealheiro oculto: dinâmicas econômicas entre o Norte e o Sul do Brasil no tempo da Independência
Authors: Barroso Daniel Souza
Published: April 2022

Este artigo tem como objetivo analisar a economia da Amazônia, do Nordeste e do Sul do Brasil no período da Independência. Para tal, examina as exportações e a força de trabalho escravizada dessas regiões. Propõe-se, ao final, a hipótese de que – direta ou indiretamente – as dinâmicas econômicas entre o Norte e o Sul do Brasil produziram riqueza à margem do Centro-Sul, ao responderem por grande parte das exportações e da população do país naquele contexto.
Pensamento econômico no Brasil na época da Independência
Authors: Saes Alexandre Macchione , Salomão Ivan Colangelo
Published: April 2022

O artigo discute a evolução do pensamento econômico no Brasil durante a época de sua Independência. Aproximadamente três décadas, entre os séculos XVIII e XIX, que marcam um período de transições: das independências americanas, da Revolução Francesa, da Revolução Industrial inglesa e, no que diz respeito ao pensamento econômico, da difusão das ideias da economia política clássica. No confronto entre essas ideias e a prática da economia colonial, a assimilação da economia política no Brasil realizada pela geração de d. Rodrigo de Sousa Coutinho, José da Silva Lisboa e José Bonifácio de Andrada e Silva implicou tendência contraditória de difícil conciliação entre interesses metropolitanos e coloniais e a manutenção de práticas mercantilistas em meio a concepções liberais.
Comércio interno e manufaturas nos tempos da Independência do Brasil
Authors: Ribeiro Maria Alice Rosa
Published: April 2022

O artigo discute o tema do comércio interno e das manufaturas na época da Independência. Na primeira parte abordamos o comércio interno – o tráfico de escravizados, distinguindo os negociantes do comércio atlântico daqueles que atuavam na distribuição de escravizados no mercado interno. Tratamos do comércio de abastecimento de alimentos e de manufaturados comuns transacionados pelos tropeiros e pelas vendas, e do comércio de manufaturados importados mais sofisticados. Na segunda parte, o foco recai sobre a produção manufatureira, a indústria artesanal doméstica, baseada no beneficiamento de matérias-primas, algodão, alimentos e bebidas, cerâmica, olaria, etc. Por fim, é tratada uma das mais importantes atividades industriais, as fábricas de ferro, a siderurgia.
Fiscalidade no Brasil Império: a manutenção de privilégios e o legado da desigualdade
Authors: Galvão Luciana Suarez , Hanley Anne Gerard
Published: April 2022

O presente artigo analisa o legado tributário colonial e as primeiras ações do Brasil como nação independente na reestruturação de seu sistema fiscal, na separação das rendas e na definição das competências tributárias das várias instâncias governamentais. Defendemos que a retórica do liberalismo e a falta de planejamento levaram ao estabelecimento de um sistema tributário que manteve os privilégios da elite política e econômica, tendo como base o recolhimento de impostos indiretos sobre toda uma população socialmente desigual. A mesma falta de planejamento acabou por deixar províncias, e em especial municípios, com grande parte da responsabilidade sobre o provimento de bens públicos, mas sem a adequada provisão de rendas para isso. Combinados, esses aspectos comprometeram de maneira significativa o desenvolvimento econômico de longo prazo, agravando ainda mais a disparidade social.
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.
Establishing a National Cardiovascular Disease Surveillance System in the United States Using Electronic Health Record Data: Key Strengths and Limitations
Authors: Williams Brent A. , Voyce Stephen , Sidney Stephen , Roger Véronique L. , Plante Timothy B. , Larson Sharon , LaMonte Michael J. , Labarthe Darwin R. , DeBarmore Bailey M. , Chang Alexander R. , Chamberlain Alanna M. , Benziger Catherine P.
Published: April 2022

Cardiovascular disease surveillance involves quantifying the evolving population‐level burden of cardiovascular outcomes and risk factors as a data‐driven initial step followed by the implementation of interventional strategies designed to alleviate this burden in the target population. Despite widespread acknowledgement of its potential value, a national surveillance system dedicated specifically to cardiovascular disease does not currently exist in the United States. Routinely collected health care data such as from electronic health records (EHRs) are a possible means of achieving national surveillance. Accordingly, this article elaborates on some key strengths and limitations of using EHR data for establishing a national cardiovascular disease surveillance system. Key strengths discussed include the: (1) ubiquity of EHRs and consequent ability to create a more “national” surveillance system, (2) existence of a common data infrastructure underlying the health care enterprise with respect to data domains and the nomenclature by which these data are expressed, (3) longitudinal length and detail that define EHR data when individuals repeatedly patronize a health care organization, and (4) breadth of outcomes capable of being surveilled with EHRs. Key limitations discussed include the: (1) incomplete ascertainment of health information related to health care–seeking behavior and the disconnect of health care data generated at separate health care organizations, (2) suspect data quality resulting from the default information‐gathering processes within the clinical enterprise, (3) questionable ability to surveil patients through EHRs in the absence of documented interactions, and (4) the challenge in interpreting temporal trends in health metrics, which can be obscured by changing clinical and administrative processes.
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

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.
Studies on Neotropical crickets: Mellogryllus mutus n. gen. et n. sp., an intriguing new genus and species of cricket of the Miogryllae Group (Orthoptera: Gryllidae: Gryllinae: Gryllini: Brachytrupina) from the Brazilian Atlantic Forest
Authors: CADENA-CASTAÑEDA OSCAR J. , TAVARES GUSTAVO COSTA , FERNANDES JOSÉ ANTÔNIO MARIN
Published: April 2022

A new monotypic genus, Mellogryllus mutus n. gen. et n. sp., is described from the dense ombrophilous forests of the Brazilian coastal Atlantic Forest. This new genus is included within the genus-group Miogryllae due to the structure of the male genitalia. The key for the genera of the Group Miogryllae is also updated. Finally, the morphological particularities of Mellogryllus n. gen. are discussed, such as the presence or absence of tympanum in the different sexes, variation in the number of spurs on the legs, and the modification of the first pair of legs for underground life.
Notes on the genus Micromorphus Mik (Diptera: Dolichopodidae) and the uncertain identity of its type species, M. albipes (Zetterstedt)
Authors: BICKEL DANIEL J.
Published: April 2022

Micromorphus albipes (Zetterstedt), the type species of the genus Micromorphus Mik (Diptera: Dolichopodidae), was based on a female collected in Sweden. Diagnostic males have not been directly associated with the species, even though at least three distinct congeners based on male genitalia occur in northern Europe. Despite being inadequately described, the name has been applied to species in the New World, New Zealand and Nepal. Micromorphus albipes is demonstrated not to occur in the New World, and Micromorphus caudatus (Aldrich), new status, is redescribed and regarded as the valid name for these incorrect identifications. The records of Micromorphus albipes from New Zealand and Nepal are also unsubstantiated. As well, the enigmatic Central American Micromorphus micidus Parent is redescribed and figured. The genus Micromorphus as a whole is discussed.
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.
1. Introduction
Authors: Tănăsescu Mihnea
Published: April 2022

This chapter introduces the concept of the Ecocene. Offered as an alternative to the Anthropocene, it argues that the new era is largely determined by the way in which ecological processes themselves have come to matter in politics. We live, in other words, in the age of ecology, not the human age. The concept of ecology is developed in terms of the ideas of chance, change, and locality. The chapter attends to the ways in which a conception of Ecocene politics can help an increasing number of social groups to live with tragedy and the increasing loss that will define countless futures.
4. Renovative Practice
Authors: Tănăsescu Mihnea
Published: April 2022

The concepts of nature restoration, conservation, and rewilding are developed in relation to each other and to the politics of the Ecocene. Different practical models are presented and related to the ideas of reciprocity and responsibility discussed in the next parts of the book. The chapter proposes the idea of ritual as key to understanding restoration in relational ways.
6. Ecopolitical Ethics, Part II
Authors: Tănăsescu Mihnea
Published: April 2022

The concept of responsibility is developed as another key aspect of political ethics. It is considered as applicable to human relations only. However, being responsible for fellow humans supposes the practice of ecological restoration, without which human well-being is impossible. Along with the previous chapters, the idea of Ecocene politics is fleshed out in greater detail.
Intermezzo II
Authors: Tănăsescu Mihnea
Published: April 2022

The chapter compares the story of a tree in the North Island of Aotearoa, New Zealand with the plight of olive trees in Puglia. In doing so, it shows the common threads that tragedy can weave, and ponders the possibility of new, intergenerational responsibilities.
7. Mutualism
Authors: Tănăsescu Mihnea
Published: April 2022

This last substantive chapter presents the idea of mutualism as partially uniting the concepts developed throughout the book. It is weaved with arguments from both the biological sciences and anarchist political thought. It returns one last time to Māori philosophy, allying it with practices of ecological restoration. Mutualism brings the examination of a politics fit for the new era to a close.
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.
Price Transparency for Primary Care Office Visits and Routine Tests: Results From a 2016 Audit Study
Authors: Batra Anchita , Candon Molly
Published: April 2022

Introduction: Price transparency is a central component of the shift from volume to value in healthcare delivery. Price transparency in primary care, the most common point of contact with the healthcare system for patients in the U.S., has not been widely studied.

Methods: Using an audit study across 10 states in 2016, we examined the characteristics of primary care practices that were able to provide price information for office visits and routine tests.

Results: Most primary care practices were able to disclose some price information for office visits and routine tests. Results indicate that larger, integrated primary care practices in urban areas and in areas with a higher percentage of minority residents were less likely to provide prices than smaller, standalone practices.

Conclusion: These findings suggest that future efforts to increase price transparency in primary care should be tailored to practice characteristics, including practice location and whether the practice is embedded in an integrated health system.