bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC
Authors: Jung Hyun Ae , Lim Jinyeong , Choi Yoon-La , Lee Se-Hoon , Joung Je-Gun , Jeon Yeong Jeong , Choi Jae Won , Shin Sumin , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Zo Jae Ill , Shim Young Mog , Park Sehhoon , Sun Jong-Mu , Ahn Jin Seok , Ahn Myung-Ju , Han Joungho , Park Woong-Yang , Kim Jhingook , Park Keunchil 
Published: July 2022

Abstract

Purpose:
In early-stage, EGFR mutation–positive (EGFR-M+) non–small cell lung cancer (NSCLC), surgery remains the primary treatment, without personalized adjuvant treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized adjuvant strategies in resected early-stage EGFR-M+ NSCLC.

Experimental Design:
From January 2008 to August 2020, a total of 2,340 patients with pathologic stage (pStage) IB–IIIA, non-squamous NSCLC underwent curative surgery. To identify clinicopathologic risk factors, 1,181 patients with pStage IB–IIIA, common EGFR-M+ NSCLC who underwent surgical resection were analyzed. To identify molecular risk factors, comprehensive genomic analysis was conducted in 56 patients with matched case–controls (pStage II and IIIA and type of EGFR mutation).

Results:
Median follow-up duration was 38.8 months (0.5–156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. Median RFS was 73.5 months [95% confidence interval (CI), 62.1–84.9], 48.7 months (95% CI, 41.2–56.3), and 22.7 months (95% CI, 19.4–26.0) for pStage IB, II, and IIIA, respectively (P &lt; 0.001). In multivariate analysis of clinicopathologic risk factors, pStage, micropapillary subtype, vascular invasion, and pleural invasion, and pathologic classification by cell of origin (type II pneumocyte-like tumor cell vs. bronchial surface epithelial cell–like tumor cell) were associated with RFS. As molecular risk factors, the non-terminal respiratory unit (non-TRU) of the RNA subtype (HR, 3.49; 95% CI, 1.72–7.09; P &lt; 0.01) and TP53 mutation (HR, 2.50; 95% CI, 1.24–5.04; P = 0.01) were associated with poor RFS independent of pStage II or IIIA. Among the patients with recurrence, progression-free survival of EGFR-tyrosine kinase inhibitor (TKI) in those with the Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) mutation signature was inferior compared with that of patients without this signature (8.6 vs. 28.8 months; HR, 4.16; 95% CI, 1.28–13.46; P = 0.02).

Conclusions:
The low-risk group with TRU subtype and TP53 wild-type without clinicopathologic risk factors might not need adjuvant EGFR-TKIs. In the high-risk group, with non-TRU subtype and/or TP 53 mutation, or clinicopathologic risk factors, a novel adjuvant strategy of EGFR-TKI with others, e.g., chemotherapy or antiangiogenic agents needs to be investigated. Given the poor outcome to EGFR-TKIs after recurrence in patients with the APOBEC mutation signature, an alternative adjuvant strategy might be needed.
circ_0041732 Promotes Breast Cancer Progression
Authors: Ye Guolin , He Suqun , Pan Ruilin , Zhu Lewei , Zhou Dan , Cai Genxi , Chen Peixian 
Published: July 2022

Abstract

Breast cancer is quite a prevalent cancer worldwide, and it is the leading cause of cancer-related deaths among female populations worldwide. Increasingly more efforts have been made in exploration of circular RNA functions in various malignancies. In this study, the primary target was to verify the putative influences of circ_0041732 on breast cancer progression and the corresponding regulatory mechanism. In addition to measurement of RNAs and proteins, functional assays were done to examine the changes in cell proliferation and cell cycle, and the potential association among genes was investigated by mechanism assays. According to experimental results, significant upregulation of circ_0041732 was confirmed in breast cancer tissues and cell lines. E2F4 was proved to transcriptionally modulate circ_0041732. Moreover, circ_0041732 was validated to accelerate breast cancer cell proliferation and impede G2–M arrest and cell apoptosis, and the oncogenic role of circ_0041732 in breast cancer was further verified via in vivo experiments. circ_0041732 could sponge miR-541-3p to enhance expression levels of RelA and GLI4, thus activating NFκB and Hedgehog pathways and affecting breast cancer cell proliferation, cell cycle, and apoptosis. In all, E2F4-mediated circ_0041732 could activate RelA/NFκB and GLI4/Hedgehog signaling pathways via modulation on miR-541-3p/RelA/GLI4 to promote breast cancer progression.

Implications:
E2F4-mediated circ_0041732 upregulation resulted in the activation of NFκB and Hedgehog pathways via sponging miR-541-3p and enhancing expression levels of RelA and GLI4, thus affecting breast cancer cell proliferation, cell cycle, and cell apoptosis.
Association of Smartphone‐Recorded Steps Over Years and Change in Cardiovascular Risk Factors Among Working‐Age Adults
Authors: Hamaya Rikuta , Mori Masaki , Miyake Kuniaki , Lee I‐Min 
Published: July 2022

Background
Few data exist on long‐term steps and their relation to changes in cardiovascular disease risk factors. We aimed to examine the associations using long‐term smartphone‐recorded steps.

Methods and Results
The present analysis made use of data from 2 national databases and a commercial app database. We evaluated the associations between smartphone‐recorded daily steps over 2 years and 2‐year changes in the cardiovascular disease risk factors. A total of 15 708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. After adjustment for potential confounders, differences in weight were almost linearly associated with 2‐year steps in men (estimate [SE] per 1000 steps/d: −0.33 [0.029] kg), and inversely related only above 5000 steps/d in women (−0.18 [0.054] kg). An inverse linear association with systolic blood pressure was observed in men (−0.34 [0.097] mm Hg) but not in women. Greater steps were associated with change in high‐density lipoprotein cholesterol and triglycerides (0.61 [0.068] and −3.4 [0.61] mg/dL in men; 0.64 [0.17] and −2.3 [0.67] mg/dL in women), while changes in low‐density lipoprotein cholesterol were evident in men only (−0.59 [0.17] mg/dL). A significant negative association with hemoglobin A1c was observed only in women (−0.012 [0.0043] %).

Conclusions
In a large cohort of Japanese adults, smartphone‐recorded steps over years were associated with beneficial changes in cardiovascular disease risk factors, with some differences between men and women in the associational patterns. The findings support the benefit of long‐term physical activity for cardiovascular disease health and suggest a useful role of smartphone‐recorded steps for monitoring cardiovascular disease risk over the long term.
Serum Neurofilament Light Chain in Patients With Atrial Fibrillation
Authors: Sjölin Karl , Aulin Julia , Wallentin Lars , Eriksson Niclas , Held Claes , Kultima Kim , Oldgren Jonas , Burman Joachim 
Published: July 2022

Background
Atrial fibrillation (AF) is associated with stroke and MRI features of cerebral tissue damage but its impact on levels of serum neurofilament light chain (sNFL), an established biochemical marker of neuroaxonal damage, is unknown.

Methods and Results

In this observational study, sNFL was analyzed in 280 patients with AF and 280 controls without AF matched for age, sex, and diabetes status within the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. None of the patients had a history of previous stroke or transient ischemic attack. Patients with a diagnosis of AF were divided into two groups based on if they were in AF rhythm at the time of blood sampling (AF ECG+, n=74), or not (AF ECG−, n=206). Multiple linear regression analysis was performed to adjust for clinical risk factors. In patients with AF, the levels of sNFL were 15% (AF ECG+) and 10% (AF ECG−) higher than in the control group after adjustment for clinical risk factors,
P
=0.047 and 0.04, respectively. There was no association between anticoagulation treatment and sNFL levels.

Conclusions
sNFL was elevated in patients with AF compared with matched controls without AF. Ongoing AF rhythm was associated with even higher levels of sNFL than in patients with a diagnosis of AF but currently not in AF rhythm. Anticoagulation treatment did not affect sNFL levels.

Trial Registration

ClinicalTrials.gov
NCT00799903.
The Role of Anthropogenic Aerosol Forcing in the 1850–1985 Strengthening of the AMOC in CMIP6 Historical Simulations
Authors: Robson Jon , Menary Matthew B. , Sutton Rowan T. , Mecking Jenny , Gregory Jonathan M. , Jones Colin , Sinha Bablu , Stevens David P. , Wilcox Laura J. 
Published: July 2022

Abstract
Previous work has shown that anthropogenic aerosol (AA) forcing drives a strengthening in the Atlantic meridional overturning circulation (AMOC) in CMIP6 historical simulations over 1850–1985, but the mechanisms have not been fully understood. Across CMIP6 models, it is shown that there is a strong correlation between surface heat loss over the subpolar North Atlantic (SPNA) and the forced strengthening of the AMOC. Despite the link to AA forcing, the AMOC response is not strongly related to the contribution of anomalous downwelling surface shortwave radiation to SPNA heat loss. Rather, the spread in AMOC response is primarily due to the spread in turbulent heat loss. We hypothesize that turbulent heat loss is larger in models with strong AA forcing because the air advected over the ocean is colder and drier, in turn because of greater AA-forced cooling over the continents upwind, especially North America. The strengthening of the AMOC also feeds back on itself positively in two distinct ways: by raising the sea surface temperature and hence further increasing turbulent heat loss in the SPNA, and by increasing the sea surface density across the SPNA due to increased northward transport of saline water. A comparison of key indices suggests that the AMOC response in models with strong AA forcing is not likely to be consistent with observations.
Quantifying Cross-Shelf Transport in the East Australian Current System: A Budget-Based Approach
Authors: Malan Neil , Roughan Moninya , Stanley Geoffrey J. , Holmes Ryan , Li Junde 
Published: July 2022

Abstract
Cross-shelf transport plays an important role in the heat, salt, and nutrient budgets of the continental shelf. In this study, we quantify cross-shelf volume transport and explore its dynamics within a high-resolution (2.5–6 km) regional ocean model of the East Australian Current (EAC) System, a western boundary current with a high level of mesoscale eddy activity. We find that the largest time-mean cross-shelf flows (>4 Sv per 100 km; 1 Sv ≡ 106 m3 s−1) occur inshore of the coherent western boundary current, between 26° and 30°S, while the strongest time-varying flows occur in the EAC southern extension, poleward of 32°S, associated with mesoscale eddies. Using a novel diagnostic equation derived from the momentum budget we show that the cross-shelf transport is dominated by the baroclinic and geostrophic component of the velocities, as the EAC jet is relatively free to flow over the variable shelfbreak topography. However, topographic interactions are also important and act through the bottom pressure torque term as a secondary driver of cross-shelf transport. The importance of topographic interaction also increases in shallower water inshore of the coherent jet. Downstream of separation, cross-shelf transport is more time-varying and associated with the interaction of mesoscale eddies with the shelf. The identification of the change in nature and drivers of cross-shelf transport in eddy versus jet dominated regimes may be applicable to understanding cross-shelf transport dynamics in other boundary current systems.

Significance Statement
Cross-shelf transport, i.e., the movement of water from the open ocean on or off the continental shelf, is not reported often as it is difficult to measure and model. We demonstrate a simple but effective method to do this and, using an ocean model, apply it to the East Australian Current System and show what drives it. The results show two distinct regimes, which differ depending on which part of the current system you are in. Our results help to place observations of cross-shelf transport in better context and provide a framework within which to consider the transport of other things such as heat and carbon from the open ocean to the continental shelf.
Crescent-Shaped Low-Temperature Distribution along the Convex Topography in the Southeastern Edge of Taiwan Bank in Summer
Authors: Lee Hung-Jen , Lee Ming-An , Ho Chia-Ying , Hsu Po-Chun , Wang Yi-Chen 
Published: July 2022

Abstract
Various physical mechanisms of ocean upwelling usually occur near or along coastal regions worldwide. Five upwelling zones of unequal intensity are found around the Taiwan Strait, and the Taiwan Bank (TB) upwelling zone has the most prominent characteristics of low temperature. In this study, satellite images, shipboard ADCPs (acoustic Doppler current profilers), and CTDs (conductivity–temperature–depth measures) were analyzed to investigate the processes of cold water upwelling around the TB shoaling zone. In addition, the MITgcm numerical model and the flexible cubic spline technique were also employed, allowing us to better understand those processes. The model results suggested that a combination of Ekman transport and the centrifugal force, driven by the geostrophic South China Sea Warm Current (SCSWC), constitutes a physical mechanism to contribute the vigorous upwelling in the TB shoal zone. The upwelling is largely driven by Ekman transport. However, the centrifugal force may explain why the upwelling with a crescent-shaped distribution of low temperatures along the convex topography of the southeastern edge of the TB shoaling zone is more prominent than expected, as it tends toward the so-called gradient wind balance. Sudden relaxation of the friction force occurred because of the very sharp shelf break (20–60 m) and steep slope topography; a discontinuous velocity zone around the shelf break could also lead to vigorous cold water upwelling.

Significance Statement
Extensive data concerning the Taiwan Bank (TB) shoaling zone have been collected in the past decade in an attempt to improve understanding of the process of cold water upwelling in the area. Because the Kuroshio invades the South China Sea from the east, and the South China Sea Warm Current flows northeastward around the southeastern edge of the TB, water circulation in and around the sandbar is very complicated. Thus, we expanded our model range from small to large scale to avoid the open boundary settings of small-scale model (including the temperature and salinity fields, wind stress, and the model driving forces), which were not easy to set up. Thus, we used a large-scale, high-resolution circulation model to study a small-scale ocean region. Physical processes of this upwelling can finally be verified in the small-scale region. To compensate for the insufficient resolution of the large-scale numerical model, our strategy was to utilize the flexible cubic spline technique to resolve the curvature of the markedly meandering currents. In light of scale analysis, the results showed that in addition to the critical contribution of Ekman transport to the upwelling, the effects of centrifugal forces on upwelling in the TB shoal zone need to be considered.
Diagnostics of Tropical Variability for Numerical Weather Forecasts
Authors: Gehne Maria , Wolding Brandon , Dias Juliana , Kiladis George N. 
Published: July 2022

Abstract
Tropical precipitation and circulation are often coupled and span a vast spectrum of scales from a few to several thousands of kilometers and from hours to weeks. Current operational numerical weather prediction (NWP) models struggle with representing the full range of scales of tropical phenomena. Synoptic to planetary scales are of particular importance because improved skill in the representation of tropical larger-scale features such as convectively coupled equatorial waves (CCEWs) has the potential to reduce forecast error propagation from the tropics to the midlatitudes. Here we introduce diagnostics from a recently developed tropical variability diagnostics toolbox, where we focus on two recent versions of NOAA’s Unified Forecast System (UFS): operational GFSv15 forecasts and experimental GFSv16 forecasts from April to October 2020. The diagnostics include space–time coherence spectra to identify preferred scales of coupling between circulation and precipitation, pattern correlations of Hovmöller diagrams to assess model skill in zonal propagation of precipitating features, CCEW skill assessment, plus a diagnostic aimed at evaluating moisture–convection coupling in the tropics. Results show that the GFSv16 forecasts are slightly more realistic than GFSv15 in their coherence between precipitation and model dynamics at synoptic to planetary scales, with modest improvements in moisture convection coupling. However, this slightly improved performance does not necessarily translate to improvements in traditional precipitation skill scores. The results highlight the utility of these diagnostics in the pursuit of better understanding of NWP model performance in the tropics, while also demonstrating the challenges in translating model advancements into improved skill.
Impact of Increased Enoxaparin Dosing on Anti-Xa Levels for Venous Thromboembolism Prophylaxis in Trauma Patients
Authors: Bellfi Lillian T. , Zimmerman S. Anthony , Boudreau Ryan , Mosier Willard , Smith Alison , Rueb Nicole , Hunt John P. , Stuke Lance , Greiffenstein Patrick , Schoen Jonathan , Marr Alan 
Published: July 2022

Introduction Venous thromboembolism (VTE) contributes to significant morbidity in trauma patients while increasing hospital costs and length of stay. Standard trauma prophylaxis dosing with enoxaparin 30 mg twice daily may be inadequate to prevent VTEs. The objective of this study was to compare standard dosing of enoxaparin to an increased dose of enoxaparin 40 mg twice daily for trauma patients. We hypothesized that increasing thromboprophylaxis dosing leads to an increase in therapeutic anti-Xa levels and reduced VTE rates. Methods A retrospective study was performed from January 2020 to June 2021 at a Level I trauma center, following implementation of an increased enoxaparin dosing strategy. Patients with increased enoxaparin dosing were compared with those who received standard dosing. The primary outcome evaluated was the incidence of subtherapeutic anti-Xa levels. Secondary outcomes evaluated VTE rates and clinically significant bleed. Results A total of 204 trauma patients were identified. Ninety-one patients received an increased enoxaparin dose compared to 113 who received standard dosing. The baseline demographics of both groups were similar ( P > .05). Subtherapeutic levels were higher with standard dosing compared to the increased dose (50 vs 22%, P = .003). Higher VTE rates were observed with standard dosing compared to higher dosing (6.2 vs 3.3%) but with a lower incidence of major bleed (1.8 vs 4.4%). Overall annual VTE rates decreased from 1.6 to 1.3% after implementation of the increased dosing regimen. Conclusions This study demonstrated that an increased dosing strategy decreased rates of subtherapeutic anti-Xa levels and trended toward lower overall VTE rates in trauma.
Sex-specific differences in 30-day outcomes following primary total hip replacement in 86,684 patients
Authors: Chaudhry Harman , Ekhtiari Seper , Ravi Bheeshma , Wadey Veronica , Tomescu Sebastian , Murnaghan John , Mundi Raman 
Published: July 2022

Introduction: Although differential outcomes based on sex are widespread in medicine and surgery, evaluation of sex-specific differences in the field of orthopaedic surgery in general – and arthroplasty in particular – are lacking. We hypothesised that morbidly obese male and female patients would have differing risks of surgical complications following primary total hip replacement. Methods: We reviewed data contained within the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database from 2015 through 2018, inclusive. A multivariable binary logistic regression model was used to determine the adjusted odds ratios (OR) of relevant variables on primary and secondary outcomes. Results: A total of 86,684 patients undergoing THR were identified, of whom 9972 patients (4095 male and 5877 female) were morbidly obese. Among morbidly obese patients, odds of surgical site infection were higher in females than males within 30 days of surgery (adjusted OR 1.40; 95% CI, 1.10–1.79; p = 0.007). This comprised the odds of both superficial infection (1.8% vs. 1.1%, adjusted OR 1.67; 95% CI, 1.16–2.40; p = 0.006) and deep infection (1.9% vs. 1.4%, adjusted OR 1.22; 95% CI, 0.88–1.68; p = 0.24). Unexpected return to the operating room (i.e., reoperation) within 30 days of the surgical procedure was also higher among females than males (4.2% vs. 3.1%, adjusted OR 1.38, 95% CI, 1.10–1.71, p = 0.005). There were no differences between male and female patients in the non-obese cohort. Conclusions: Among patients with morbid obesity, the risk of surgical site infection and reoperation within the first 30 days is greater in women as compared to men. Future research must address whether this early increased risk among morbidly obese women persists in the longer term, and whether it results in compromised function or quality of life.
Transradial access for cerebral angiography and neurointerventional procedures: A meta-analysis and systematic review
Authors: Rentiya Zubir S. , Kuhn Anna Luisa , Hutnik Robert , Shazeeb Mohammed Salman , De Leacy Reade A. , Goldman Daryl , Singh Jasmeet , Puri Ajit S. 
Published: July 2022

Purpose: Transradial access (TRA) for diagnostic and interventional neurointerventional procedures has recently gained traction over transfemoral access (TFA) in the neurointerventional community. This meta-analysis aims to assess and summarize the utility of TRA in cerebral angiography and neurointerventional procedures. Methods: A systematic literature review was performed utilizing Pubmed, Embase, and Scopus databases. Using PRISMA guidelines, records were extracted with the following search terms: transradial approach, transradial access, radial access, cerebral angiogram, cerebral angiography, neurointervention, and neuroendovascular. The primary outcomes assessed were case success rate, complication rate, and crossover rate from TRA to TFA. Secondary analysis was performed on procedure time, fluoroscopy time, fluoroscopy time per vessel (diagnostic procedures only), contrast dose, radial artery diameter, distal radial artery diameter, and patient preference for TRA over TFA. Results: Sixty-two full-text articles were analyzed for this meta-analysis, representing 12,927 diagnostic and interventional TRA access patients. Our analysis revealed a combined diagnostic and interventional case success rate of 95.9% and complication rate of 3.5%, with crossover to TFA occurring in 4.9% of cases. Conclusion: This meta-analysis demonstrates that TRA access for diagnostic angiography and neurointerventional procedures is a safe and effective approach, though determining a true complication rate is challenging as the definition of TRA complications has changed in various publications over time.