bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Effectiveness of Inhaling Different Dosage Recombinant Human Interferon α1B for Bronchiolitis in Children: a Systematic Review and Meta-Analysis
Authors: Luo Jiefeng , Yang Mengting , Zeng Linan , Pan Xiangcheng , Liu Dan , Diao Sha , Huang Liang , Chen Ting , Jia Zhi-Jun , Cheng Guo , Yu Qin , Zhang Lingli 
Published: April 2022

Purpose. To systematically evaluate the safety and effectiveness of different dosages of recombinant human interferon α1b (IFNα1b) inhaled for bronchiolitis in children. Methods. 7 databases, including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang Database, and VIP, were searched. The search time was from their inception dates to March 28, 2022. A randomized controlled trial (RCT) of 2 μg/kg IFNα1b (low dosage group) monotherapy or in combination with other drugs vs. 4 μg/kg IFNα1b (high dosage group) monotherapy or in combination with the other drugs was included. The risk of bias 2.0 evaluated the RCT’s quality, and the grading of recommendations assessment, development and evaluation (GRADE) tool was used for evaluating the overall quality of the evidence. Then, a meta-analysis was performed by RevMan 5.4. Results. A total of 13 RCTs with 1719 children were included. The meta-analysis results showed that the high dosage group was significantly shorter than the low dosage group of the duration of hospital stays (MD = −0.40, 95%CI (−0.73, −0.07),

P

= 0.02) (low quality), three depressions sign disappearing time (MD = −0.60, 95%CI (−1.05, −0.14),

P

= 0.010) (low quality), and wheeze disappearing time (MD = −0.62, 95%CI (−1.17, −0.06),  = 0.03) (low quality). There was no significant difference between the two groups in coughing disappearing time, pulmonary rales disappearing time, wheezing sound disappearing time, or adverse event rates. Conclusions. Compared with low dosage IFNα1b, high dosage IFNα1b reduces the duration of hospital stays, the disappearance time of the three depression signs, and the disappearance time of wheeze in the treatment of bronchiolitis in children. Limited by the low quality of the evidence, the conclusions still need to be supported by high-quality studies.
The Genetic Evolution of Metastasis
Authors: Rogiers Aljosja , Lobon Irene , Spain Lavinia , Turajlic Samra 
Published: April 2022

Abstract
Cancer is an evolutionary process that is characterized by the emergence of multiple genetically distinct populations or clones within the primary tumor. Intratumor heterogeneity provides a substrate for the selection of adaptive clones, such as those that lead to metastasis. Comparative molecular studies of primary tumors and metastases have identified distinct genomic features associated with the development of metastases. In this review, we discuss how these insights could inform clinical decision-making and uncover rational antimetastasis treatment strategies.
Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal
Authors: Kotsopoulos Joanne , Lubinski Jan , Gronwald Jacek , Menkiszak Janusz , McCuaig Jeanna , Metcalfe Kelly , Foulkes William D. , Neuhausen Susan L. , Sun Sophie , Karlan Beth Y. , Eisen Andrea , Tung Nadine , Olopade Olufunmilayo I. , Couch Fergus J. , Huzarski Tomasz , Senter Leigha , Bordeleau Louise , Singer Christian F. , Eng Charis , Fruscio Robert , Pal Tuya , Sun Ping , Narod Steven A. 
Published: April 2022

Abstract

Background:
The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case–control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer.

Methods:
A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer.

Results:
In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34–0.55; P &lt; 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87–1.70; P = 0.26).

Conclusions:
The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk.

Impact:
Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.
Associations of Healthcare Affordability, Availability, and Accessibility with Quality Treatment Metrics in Patients with Ovarian Cancer
Authors: Akinyemiju Tomi F. , Wilson Lauren E. , Diaz Nicole , Gupta Anjali , Huang Bin , Pisu Maria , Deveaux April , Liang Margaret , Previs Rebecca A. , Moss Haley A. , Joshi Ashwini , Ward Kevin C. , Schymura Maria J. , Berchuck Andrew , Potosky Arnold L. 
Published: April 2022

AbstractBackground:Differential access to quality care is associated with racial disparities in ovarian cancer survival. Few studies have examined the association of multiple healthcare access (HCA) dimensions with racial disparities in quality treatment metrics, that is, primary debulking surgery performed by a gynecologic oncologist and initiation of guideline-recommended systemic therapy.Methods:We analyzed data for patients with ovarian cancer diagnosed from 2008 to 2015 in the Surveillance, Epidemiology, and End Results–Medicare database. We defined HCA dimensions as affordability, availability, and accessibility. Modified Poisson regressions with sandwich error estimation were used to estimate the relative risk (RR) for quality treatment.Results:The study cohort was 7% NH-Black, 6% Hispanic, and 87% NH-White. Overall, 29% of patients received surgery and 68% initiated systemic therapy. After adjusting for clinical variables, NH-Black patients were less likely to receive surgery [RR, 0.83; 95% confidence interval (CI), 0.70–0.98]; the observed association was attenuated after adjusting for healthcare affordability, accessibility, and availability (RR, 0.91; 95% CI, 0.77–1.08). Dual enrollment in Medicaid and Medicare compared with Medicare only was associated with lower likelihood of receiving surgery (RR, 0.86; 95% CI, 0.76–0.97) and systemic therapy (RR, 0.94; 95% CI, 0.92–0.97). Receiving treatment at a facility in the highest quartile of ovarian cancer surgical volume was associated with higher likelihood of surgery (RR, 1.12; 95% CI, 1.04–1.21).Conclusions:Racial differences were observed in ovarian cancer treatment quality and were partly explained by multiple HCA dimensions.Impact:Strategies to mitigate racial disparities in ovarian cancer treatment quality must focus on multiple HCA dimensions. Additional dimensions, acceptability and accommodation, may also be key to addressing disparities.
Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer
Authors: Mukherjee Semanti , Bandlamudi Chaitanya , Hellmann Matthew D. , Kemel Yelena , Drill Esther , Rizvi Hira , Tkachuk Kaitlyn , Khurram Aliya , Walsh Michael F. , Zauderer Marjorie G. , Mandelker Diana , Topka Sabine , Zehir Ahmet , Srinivasan Preethi , Esai Selvan Myvizhi , Carlo Maria I. , Cadoo Karen A. , Latham Alicia , Hamilton Jada G. , Liu Ying L. , Lipkin Steven M. , Belhadj Sami , Bond Gareth L. , Gümüş Zeynep H. , Klein Robert J. , Ladanyi Marc , Solit David B. , Robson Mark E. , Jones David R. , Kris Mark G. , Vijai Joseph , Stadler Zsofia K. , Amos Christopher I. , Taylor Barry S. , Berger Michael F. , Rudin Charles M. , Offit Kenneth 
Published: April 2022

Abstract

Background:
The genetic factors that modulate risk for developing lung cancer have not been fully defined. Here, we sought to determine the prevalence and clinical significance of germline pathogenic/likely pathogenic variants (PV) in patients with advanced lung cancer.

Methods:
We studied clinical and tumor characteristics of germline PV in 5,118 patients who underwent prospective genomic profiling using paired tumor–normal tissue samples in 468 cancer genes.

Results:
Germline PV in high/moderate-penetrance genes were observed in 222 (4.3%) patients; of these, 193 patients had PV in DNA damage repair (DDR) pathway genes including BRCA2 (n = 54), CHEK2 (n = 30), and ATM (n = 26) that showed high rate of biallelic inactivation in tumors. BRCA2 heterozygotes with lung adenocarcinoma were more likely to be never smokers and had improved survival compared with noncarriers. Fourteen patients with germline PV in lung cancer predisposing genes (TP53, EGFR, BAP1, and MEN1) were diagnosed at younger age compared with noncarriers, and of tumor suppressors, 75% demonstrated biallelic inactivation in tumors. A significantly higher proportion of germline PV in high/moderate-penetrance genes were detected in high-risk patients who had either a family history of any cancer, multiple primary tumors, or early age at diagnosis compared with unselected patients (10.5% vs. 4.1%; P = 1.7e−04).

Conclusions:
These data underscore the biological and clinical importance of germline mutations in highly penetrant DDR genes as a risk factor for lung cancer.

Impact:
The family members of lung cancer patients harboring PV in cancer predisposing genes should be referred for genetic counseling and may benefit from proactive surveillance.
Event Rates and Risk Factors for Recurrent Cardiovascular Events and Mortality in a Contemporary Post Acute Coronary Syndrome Population Representing 239 234 Patients During 2005 to 2018 in the United States
Authors: Steen Dylan L. , Khan Irfan , Andrade Katherine , Koumas Alexandra , Giugliano Robert P. 
Published: April 2022

Background
Patients with acute coronary syndrome (ACS) are recognized by guidelines as remaining at high risk for adverse outcomes. Evidence from contemporary, representative ACS populations in a clinical practice setting is necessary to identify subgroups and strategies for improving patient outcomes. We aimed to describe event rates and risk factors in an ACS population over prolonged follow‐up for cardiovascular end points.

Methods and Results

We identified 239 234 patients in the Optum Research Database (57.2% men; mean [standard deviation] age, 69.2 [12.2] years) with evidence of an ACS hospitalization (index ACS) during January 1, 2005 through December 30, 2018. Subgroups were based on index ACS event (myocardial infarction/unstable angina and revascularization status) and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention. The 5‐year event rate for the primary end point representing nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death was 33.4% (95% CI, 33.1%–33.7%;
P
<0.001). The risk of experiencing the primary end point was ≈6‐fold higher immediately after discharge (≈40.9% annualized risk) as compared with the period 1+ years after hospitalization (≈6.4% annualized risk). Among subgroups, the 5‐year primary end point event rate was highest for myocardial infarction without revascularization and a Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention ≥4, at 47.9% (95% CI, 47.3%–48.4%;
P
<0.001) and 56.7% (95% CI, 55.9%–57.4%;
P
<0.001), respectively.

Conclusions
Patients with ACS remain at very high risk of experiencing recurrent cardiovascular events, particularly early after discharge, with identifiable subgroups at multifold higher risk of specific clinical end points.
National Trends in Use of Sodium‐Glucose Cotransporter‐2 Inhibitors and Glucagon‐like Peptide‐1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020
Authors: Adhikari Rishav , Jha Kunal , Dardari Zeina , Heyward James , Blumenthal Roger S. , Eckel Robert H. , Alexander G. Caleb , Blaha Michael J. 
Published: April 2022

Background
Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP‐1RA use by cardiologists compared with other groups of clinicians.

Methods and Results
We conducted a descriptive analysis of serial, cross‐sectional data derived from IQVIA’s National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population‐level data, to estimate monthly SGLT2is and GLP‐1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association’s Physician Masterfile to calculate average annual SGLT2is and GLP‐1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP‐1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12‐fold for SGLT2is (from 2228 to 25 815) and 4‐fold for GLP‐1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP‐1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP‐1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP‐1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP‐1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions.

Conclusions
While use of SGLT2is and GLP‐1RAs by cardiologists in the United States increased substantially over a 6‐year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.
Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data
Authors: Kwon Dayoon , Choe Young June , Kim Sun‐Young , Chun Byung Chul , Choe Seung‐Ah 
Published: April 2022

Background
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019.

Methods and Results

We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time‐stratified case‐crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 μg/m
3
) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004–1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002–1.034 at lag 0; OR, 1.022; 95% CI, 1.005–1.038 at lag 1; OR, 1.017; 95% CI, 1.001–1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2‐pollutant model and sensitivity analyses.

Conclusions
In a KD‐focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.
Mortality in Pulmonary Arterial Hypertension in the Modern Era: Early Insights From the Pulmonary Hypertension Association Registry
Authors: Chang Kevin Y. , Duval Sue , Badesch David B. , Bull Todd M. , Chakinala Murali M. , De Marco Teresa , Frantz Robert P. , Hemnes Anna , Mathai Stephen C. , Rosenzweig Erika Berman , Ryan John J. , Thenappan Thenappan , Allen Roblee , Bartolome Sonja , Benza Raymond , Cadaret Linda , Eggert Michael , Elwing Jean , Fineman Jeffrey , Foley Raymond , Ford H. James , Hirsch Russel , Grinnan James , Ivy D. Dunbar , Kawut Steven , Kennedy Jamie , Klinger James , Leary Peter , Mazimba Sula , Ramani Gautam , Raina Amresh , Runo James , Swisher John , Varghese Nidhy , White R. James , Williamson Timothy , Yung Delphine , Zamanian Roham , Zwicke Dianne 
Published: April 2022

Background
Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry).

Methods and Results

We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan‐Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment‐naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44–68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow‐up time of 489 days (281–812 days). The 1‐, 2‐, and 3‐year mortality was 8% (95% CI, 6%–10%), 16% (95% CI, 13%–19%), and 21% (95% CI, 17%–25%), respectively. When stratified into low‐, intermediate‐, and high‐risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment‐naïve patients, initial combination therapy was associated with better 1‐year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19–0.95];
P
=0.037).

Conclusions
Mortality in the intermediate‐ and high‐risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.
CELER: A 365-Participant Corpus of Eye Movements in L1 and L2 English Reading
Authors: Berzak Yevgeni , Nakamura Chie , Smith Amelia , Weng Emily , Katz Boris , Flynn Suzanne , Levy Roger 
Published: April 2022

Abstract
We present CELER (Corpus of Eye Movements in L1 and L2 English Reading), a broad coverage eye-tracking corpus for English. CELER comprises over 320,000 words, and eye-tracking data from 365 participants. Sixty-nine participants are L1 (first language) speakers, and 296 are L2 (second language) speakers from a wide range of English proficiency levels and five different native language backgrounds. As such, CELER has an order of magnitude more L2 participants than any currently available eye movements dataset with L2 readers. Each participant in CELER reads 156 newswire sentences from the Wall Street Journal (WSJ), in a new experimental design where half of the sentences are shared across participants and half are unique to each participant. We provide analyses that compare L1 and L2 participants with respect to standard reading time measures, as well as the effects of frequency, surprisal, and word length on reading times. These analyses validate the corpus and demonstrate some of its strengths. We envision CELER to enable new types of research on language processing and acquisition, and to facilitate interactions between psycholinguistics and natural language processing (NLP).
Linear Inverse Modeling of Large-Scale Atmospheric Flow Using Optimal Mode Decomposition
Authors: Kwasniok Frank 
Published: April 2022

Abstract
Linear inverse modeling or principal oscillation pattern (POP) analysis is a widely applied tool in climate science for extracting from data dominant spatial patterns together with their dynamics as approximated by a linear Markov model. The system is projected onto a principal linear subspace and the system matrix is estimated from data. The eigenmodes of the system matrix are the POPs, with the eigenvalues providing their decay time scales and oscillation frequencies. Usually, the subspace is spanned by the leading principal components (PCs) and empirical orthogonal functions (EOFs). Outside of climate science, this procedure is now more commonly referred to as dynamic mode decomposition (DMD). Here, we use optimal mode decomposition (OMD) to address the full linear inverse modeling problem of simultaneous optimization of the principal subspace and the linear operator. The method is illustrated on two pedagogical examples and then applied to a three-level quasigeostrophic atmospheric model with realistic mean state and variability. The OMD models significantly outperform the EOF/DMD models in predicting the time evolution of the large-scale flow modes. The advantage of the OMD models stems from finding more persistent modes as well as from better capturing the nonnormality of the linear operator and the associated nonmodal growth. The dynamics of the large-scale flow modes turn out to be markedly non-Markovian and the OMD modes are superior to the EOF/DMD modes also in a modeling setting with a higher-order vector autoregressive process. The OMD modes could also be used as basis functions for a nonlinear dynamical model although they are not optimized for that purpose. Potential applications of the OMD method in weather and climate science include ENSO or MJO prediction, reduced-rank data assimilation, and generation of initial perturbations for ensemble prediction.
Human Influence on Seasonal Precipitation in Europe
Authors: Christidis Nikolaos , Stott Peter A 
Published: April 2022

Abstract
The response of precipitation to global warming is manifest in the strengthening of the hydrological cycle but can be complex on regional scales. Fingerprinting analyses have so far detected the effect of human influence on regional changes of precipitation extremes. Here we examine changes in seasonal precipitation in Europe since the beginning of the twentieth century and use an ensemble of new climate models to assess the role of different climatic forcings, both natural and anthropogenic. We find that human influence gives rise to a characteristic pattern of contrasting trends, with drier seasons in the Mediterranean basin and wetter over the rest of the continent. The trends are stronger in winter and weaker in summer, when drying is more spatially widespread. The anthropogenic signal is dominated by the response to greenhouse gas emissions, but is also weakened, to some extent, by the opposite effect of anthropogenic aerosols. Using a formal fingerprinting attribution methodology, we show here for the first time that the effects of the total anthropogenic forcing, and also of its greenhouse gas component, can be detected in observed changes of winter precipitation. Greenhouse gas emissions are also found to drive an increase in precipitation variability in all seasons. Moreover, the models suggest that human influence alters characteristics of seasonal extremes, with the frequency of high precipitation extremes increasing everywhere except the Mediterranean basin, where low precipitation extremes become more common. Regional attribution information contributes to the scientific basis that can help European citizens build their climate resilience.