bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpelisib Efficacy without Cherry-PI3King Mutations
Authors: Tau Steven , Miller Todd W. 
Published: January 2023

SummaryThe PI3K inhibitor alpelisib is clinically approved for the treatment of metastatic estrogen receptor–positive breast cancers harboring hotspot mutations in PIK3CA, which encodes a subunit of PI3K. Prospective clinical trial results demonstrated benefit from alpelisib for the treatment of advanced ER+ breast cancers harboring PIK3CA mutations in the hotspots of exons 7, 9, and 20. However, 20% of PIK3CA mutations occur in non-hotspot regions. A recent article demonstrated that patients with cancers bearing non-hotspot PIK3CA mutations also derived benefit from alpelisib, which will inform clinical decision-making moving forward.See related article by Rugo et al., p. 1056
A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma
Authors: Chiu Daniel , Qi Jingjing , Thin Tin Htwe , Garcia-Barros Monica , Lee Brian , Hahn Mary , Mandeli John , Belani Puneet , Nael Kambiz , Rashidipour Omid , Ghatan Saadi , Hadjipanayis Constantinos G. , Yong Raymund L. , Germano Isabelle M. , Brody Rachel , Tsankova Nadejda M. , Gnjatic Sacha , Kim-Schulze Seunghee , Hormigo Adília 
Published: January 2023

Purpose:The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.Patient and Methods:Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.Results:A total of 12 patients (median age 64; range, 37–73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4–16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5–4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.Conclusions:Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.Significance:Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.
Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation
Authors: Tousif Sultan , Singh Anand P. , Umbarkar Prachi , Galindo Cristi , Wheeler Nicholas , Toro Cora Angelica , Zhang Qinkun , Prabhu Sumanth D. , Lal Hind 
Published: January 2023

Background:
The tyrosine kinase inhibitor ponatinib is the only treatment option for chronic myelogenous leukemia patients with T315I (gatekeeper) mutation. Pharmacovigilance analysis of Food and Drug Administration and World Health Organization datasets has revealed that ponatinib is the most cardiotoxic agent among all Food and Drug Administration–approved tyrosine kinase inhibitors in a real-world scenario. However, the mechanism of ponatinib-induced cardiotoxicity is unknown.

Methods:
The lack of well-optimized mouse models has hampered the in vivo cardio-oncology studies. Here, we show that cardiovascular comorbidity mouse models evidence a robust cardiac pathological phenotype upon ponatinib treatment. A combination of multiple in vitro and in vivo models was employed to delineate the underlying molecular mechanisms.

Results:
An unbiased RNA sequencing analysis identified the enrichment of dysregulated inflammatory genes, including a multifold upregulation of alarmins S100A8/A9, as a top hit in ponatinib-treated hearts. Mechanistically, we demonstrate that ponatinib activates the S100A8/A9-TLR4 (Toll-like receptor 4)-NLRP3 (NLR family pyrin domain–containing 3)-IL (interleukin)-1β signaling pathway in cardiac and systemic myeloid cells, in vitro and in vivo, thereby leading to excessive myocardial and systemic inflammation. Excessive inflammation was central to the cardiac pathology because interventions with broad-spectrum immunosuppressive glucocorticoid dexamethasone or specific inhibitors of NLRP3 (CY-09) or S100A9 (paquinimod) nearly abolished the ponatinib-induced cardiac dysfunction.

Conclusions:
Taken together, these findings uncover a novel mechanism of ponatinib-induced cardiac inflammation leading to cardiac dysfunction. From a translational perspective, our results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing ponatinib-induced cardiotoxicity.
Prescribing Trends of Oral Anticoagulants in US Patients With Cirrhosis and Nonvalvular Atrial Fibrillation
Authors: Simon Tracey G. , Schneeweiss Sebastian , Singer Daniel E. , Sreedhara Sushama Kattinakere , Lin Kueiyu Joshua 
Published: January 2023

Background
Many patients with cirrhosis have concurrent nonvalvular atrial fibrillation (NVAF). Data are lacking regarding recent oral anticoagulant (OAC) usage trends among US patients with cirrhosis and NVAF.

Methods and Results

Using MarketScan claims data (2012–2019), we identified patients with cirrhosis and NVAF eligible for OACs (CHA
2
DS
2
‐VASc score ≥2 [men] or ≥3 [women]). We calculated the yearly proportion of patients prescribed a direct OAC (DOAC), warfarin, or no OAC. We stratified by high‐risk features (decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease, or end‐stage renal disease). Among 32 487 patients (mean age=71.6 years, 38.5% women, 15.1% with decompensated cirrhosis, mean CHA
2
DS
2
‐VASc=4.2), 44.6% used OACs within 180 days of NVAF diagnosis, including DOACs (20.2%) or warfarin (24.4%). Compared with OAC nonusers, OAC users were less likely to have decompensated cirrhosis (18.6% versus 10.7%), thrombocytopenia (19.5% versus 12.5%), or chronic kidney disease/end‐stage renal disease (15.5% versus 14.0%). Between 2012 and 2019, warfarin use decreased by 21.0% (32.0% to 11.0%), whereas DOAC use increased by 30.6% (7.4% to 38.0%), and among all DOACs between 2012 and 2019, apixaban was the most commonly prescribed (46.1%). Warfarin use decreased and DOAC use increased in all subgroups, including in compensated and decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease/end‐stage renal disease, and across CHA
2
DS
2
‐VASc categories. Among OAC users (2012–2019), DOAC use increased by 58.9% (18.7% to 77.6%). Among DOAC users, the greatest proportional increase was with apixaban (61.2%;
P
<0.001).

Conclusions
Among US patients with cirrhosis and NVAF, DOAC use has increased substantially and surpassed warfarin, including in decompensated cirrhosis. Nevertheless, >55% of patients remain untreated, underscoring the need for clearer treatment guidance.
US Trends in Cholesterol Screening, Lipid Levels, and Lipid‐Lowering Medication Use in US Adults, 1999 to 2018
Authors: Gao Yumin , Shah Lochan M. , Ding Jie , Martin Seth S. 
Published: January 2023

Background
Understanding current trends in cholesterol screening, lipid levels, and lipid management therapies may inform health policy and practice.

Methods and Results

In 50 928 US adult National Health and Nutrition Examination Survey (NHANES) participants, trends were assessed in cholesterol screening, mean levels of total cholesterol, triglycerides, low‐density‐lipoprotein cholesterol, and lipid‐lowering medication use from 1999 through 2018. Point estimates were also calculated using the 2017 to March 2020 prepandemic data set. The age‐ and sex‐adjusted proportion of having cholesterol screened within 5 years increased from 63.2% (95% CI, 60.0–66.3) in 1999 to 2000 to 72.5% (95% CI, 69.5–75.3) in 2017 to 2018 (
P
<0.001 for linear trend). Mean total cholesterol decreased from 203.3 mg/dL (95% CI, 201.0–205.7) in 1999 to 2000 to 188.4 mg/dL in 2017 to 2018 (95% CI, 185.4–191.5) (
P
<0.001 for nonlinear trend). The mean triglyceride level decreased from 121.3 mg/dL (95% CI, 116.4–126.4) in 1999 to 2000 to 91.4 mg/dL (95% CI, 88.4–94.6) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Low‐density lipoprotein cholesterol decreased from 127.9 mg/dL (95% CI, 125.3–130.5) in 1999 to 2000 to 111.7 mg/dL (95% CI, 109.0–114.4) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Among statin‐eligible US adults, the proportion of statin use increased from 14.9% (95% CI, 12.2–17.9) in 1999 to 2000 to 27.8% (95% CI, 23.0–33.2) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Statin use increased in adults with diabetes aged 40 to 75 years from 21.4% in 1999 to 2000 to 51.9% in 2017 to 2018 (
P
<0.001 for overall linear trend). Statin use plateaued in all other groups. The proportions of using ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors were 3.7% (95% CI, 1.3–9.8) and 0.03% (95% CI, 0.01–0.15) in 2017 to March 2020, respectively.

Conclusions
From 1999 through 2018, cholesterol screening increased while mean total cholesterol, triglycerides, and low‐density lipoprotein cholesterol levels decreased, with a modest increase in statin use and low uptake of nonstatin therapy in the US population.
Dissociating the Impact of Memorability on Electrophysiological Correlates of Memory Encoding Success
Authors: Kolisnyk Matthew , Pereira April E. , Tozios Catlin J. I. , Fukuda Keisuke 
Published: January 2023

Abstract
Despite its unlimited capacity, not all visual information we encounter is encoded into visual long-term memory. Traditionally, variability in encoding success has been ascribed to variability in the types and efficacy of an individual's cognitive processes during encoding. Accordingly, past studies have identified several neural correlates of variability in encoding success, namely, frontal positivity, occipital alpha amplitude, and frontal theta amplitude, by contrasting the electrophysiological signals recorded during successful and failed encoding processes (i.e., subsequent memory). However, recent research demonstrated individuals remember and forget consistent sets of stimuli, thereby elucidating stimulus-intrinsic factors (i.e., memorability) that determine the ease of memory encoding independent of individual-specific variability in encoding processes. The existence of memorability raises the possibility that canonical EEG correlates of subsequent memory may reflect variability in stimulus-intrinsic factors rather than individual-specific encoding processes. To test this, we recorded the EEG correlates of subsequent memory while participants encoded 600 images of real-world objects and assessed the unique contribution of individual-specific and stimulus-intrinsic factors on each EEG correlate. Here, we found that frontal theta amplitude and occipital alpha amplitude were only influenced by individual-specific encoding success, whereas frontal positivity was influenced by stimulus-intrinsic and individual-specific encoding success. Overall, our results offer novel interpretations of canonical EEG correlates of subsequent memory by demonstrating a dissociable impact of stimulus-intrinsic and individual-specific factors of memory encoding success.
Sexual size monomorphism of a Pygmy Rattlesnake (Sistrurus miliarius) population in southwestern Missouri, USA
Authors: Maag Dylan , Greene Brian 
Published: January 2023

Abstract
Pitvipers are known for their sexual dimorphism in their body size with males being larger than females. One hypothesis for the increased size of males is the selective pressure from ritualistic combat between males within a species. The Pygmy Rattlesnake (Sistrurus miliarius) is a diminutive species that has not seen a lot of research outside of central Florida. This study aimed to see if a southwestern Missouri population of S. miliarius follows the typical sexual dimorphism found in pitvipers. 48 S. miliarius were captured and 27 adults were compared based on the ratios of their tail length (TL) and mass, to snout-vent length (SVL). Males had longer TL:SVL than females but were no different in their body size. Like the central Florida populations, this Missouri population doesn’t show any sexual size dimorphism. We discuss the potential implications of these findings in the context of future research and other pitviper species.
Testing the costs of defense against herbivores in ecotypes of Eruca sativa (Brassicaceae)
Authors: Barazani Oz 
Published: January 2023

Abstract
Plants of Eruca sativa from a desert population produce less vegetative biomass, flower earlier and possess higher density of trichomes than plants from a more mesic Mediterranean habitat. When eliciting plant defense mechanisms with methyl-jasmonate (MJ), trichome formation was exclusively enhanced in plants of the Mediterranean ecotype. To test the relative costs of defenses, ecologically-important traits were monitored in non-elicited plants of the two ecotypes and when defenses were induced by MJ. Opposing the expected tradeoffs of induced defense, MJ- elicitation significantly delayed bolting and flowering in plants of the desert ecotype but not in the Mediterranean ones. Moreover, MJ did not impose costs on fitness- related traits, i.e. fruit and seed production, nor differences between plants of the two ecotypes were found. It is suggested that early flowering in plants of the desert ecotype provide a mean to escape both the abiotic stressful environment as well herbivory, while induced defense in the Mediterranean ecotype was favored in habitats of more stressful biotic interactions. The results are discussed in light of the optimal defense theory and resource availability hypothesis.
Detail Enhancement of AIRS/AMSU Temperature and Moisture Profiles Using a 3D Deep Neural Network
Authors: Milstein Adam B. , Santanello Joseph A. , Blackwell William J. 
Published: January 2023

Abstract
In recent decades, spaceborne microwave and hyperspectral infrared sounding instruments have significantly benefited weather forecasting and climate science. However, existing retrievals of lower-troposphere temperature and humidity profiles have limitations in vertical resolution, and often cannot accurately represent key features such as the mixed-layer thermodynamic structure and the inversion at the planetary boundary layer (PBL) top. Because of the existing limitations in PBL remote sensing from space, there is a compelling need to improve routine, global observations of the PBL and enable advances in scientific understanding and weather and climate prediction. To address this, we have developed a new 3D deep neural network (DNN) that enhances detail and reduces noise in level 2 granules of temperature and humidity profiles from the Atmospheric Infrared Sounder (AIRS)/Advanced Microwave Sounding Unit (AMSU) sounder instruments aboard NASA’s Aqua spacecraft. We show that the enhancement improves accuracy and detail including key features such as capping inversions at the top of the PBL over land, resulting in improved accuracy in estimations of PBL height.
Impact of Naples Prognostic Score at Admission on In-Hospital and Follow-Up Outcomes Among Patients with ST-Segment Elevation Myocardial Infarction
Authors: Erdogan Aslan , Genc Omer , Ozkan Eyüp , Goksu Muhammed M. , Ibisoglu Ersin , Bilen Mehmet N. , Guler Ahmet , Karagoz Ali 
Published: January 2023

The Naples prognostic score (NPS) consists of cholesterol level, albumin concentration, lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratios and reflects systemic inflammation, malnutrition, and survival for various conditions. We investigated the relationship of NPS at admission with in-hospital and follow-up outcomes among ST-segment elevation myocardial infarction (STEMI) patients. This retrospective study included 1887 consecutive patients diagnosed with STEMI and who underwent primary percutaneous coronary intervention between March 2020 and May 2022. The study population was divided by NPS into 2; low (0-1-2) and high (3-4). In-hospital adverse events and all-cause mortality rates during follow-up were extracted from the registry. The Median follow-up time was 15 months. The overall mortality rate was 14.6%. The proportions of in-hospital events that included acute respiratory failure, acute kidney injury, malignant arrhythmia, and mortality were significantly higher in the high NPS group than in the low NPS group. Compared with the baseline model, in the full model of Cox regression analysis; NPS was an independent predictor of all-cause mortality (adjusted hazard ratio (aHR): 2.49, 95%CI, 1.75-3.50, P < .001), with a significant improvement in model performance (likelihood ratio χ2, P < .001) and better calibration. In conclusion, we found an association between NPS and in-hospital and follow-up outcomes in STEMI patients.
Autoclave foaming and steam-chest molding of polypropylene/polybutene-1 blend bead foams and their crystallization and mechanical properties
Authors: Lan Xiaoqin , Huang Pengke , Chong Yunkai , Wu Fei , Su Yaozhuo , Luo Haibin , Lee Partrick C , Zheng Wenge 
Published: January 2023

Expanded polypropylene (EPP) foams have showed wide applications in our daily life, such as automotive and packaging. Usually, autoclave foaming combined with steam-chest molding is the main artwork to prepare the high-precision EPP foam products. However, the foaming behavior of EPP and the excessive pressure required for molding still need to be further improved, which is great significance for energy saving and cost saving, etc. Herein, this study finds that adding a certain amount of polybutene-1 (PB-1) into the PP can help to reduce the temperature and pressure required for foaming/molding, and to broaden the foaming temperature. For example, in order to make the foam beads bonding well and with the expansion ratio of 20, the molding pressure should be higher than 2.7 bar for Neat PP foams, but just 1.5 bar for PP/PB-1 mixtures. Moreover, the effects of PB-1 content on the crystallization properties and foaming/molding behaviors of the PP/PB-1 bead foams are illustrated, and then the mechanical properties are also studied. Furthermore, the low-pressure foaming strategy presented here is beneficial for reducing the barriers of energy consumption and promoting the development of new bead foam materials.
Application of electrolaminates for the development of biomimetic morphing unmanned aerial vehicles
Authors: Kornbluh Roy , Kirkwood Gordon , West Mark , Hanna Yohanna , Spedding Geoffrey , Kudva Jay 
Published: January 2023

Morphing aircraft offer the promise of performance that can be optimized for a range of flight profiles. But such capability places challenging demands on the morphing system that cannot easily be met with conventional actuators or smart materials. Electrolaminates use electrostatic forces controlled by the application of a voltage (typically high-voltage but extremely low-current) to controllably bond or unbond layers of a laminated composite structure together. Such on-demand bonding can be used to effectively change the stiffness of the structure or control elongation or twist of the structure. This technology has multiple benefits compared to other smart material or conventional actuator-driven approaches; it is thin and light, has very low energy requirements, and offers rapid response capabilities controlled by simple electronics. These capabilities can enable bio-inspired morphing with large numbers of degrees of freedom and high spatial resolution. We designed, fabricated, and tested a fully functional morphing-wing unmanned aerial vehicle (UAV) with telescoping wings and a splaying, bird-like tail enabled by electrolaminates. Key features of the current UAV configuration include: a variable wingspan of 1.2–2.4 m with a corresponding change in the wing area of nearly a factor of four; no vertical tail; and a horizontal tail area variable by a factor of three. The ability to asymmetrically control the tail area allows for independent pitch and body circulation control. The tail area is changed by a separate electrolaminate clamping mechanism. The variable-area tail uses ‘feathers’ that can be overlapped or splayed as needed. The practical shape-changing is enabled by electrolaminate materials that can rapidly lock the orientation of the feathers. The electrolaminate clutches support more than 5 nm of torque and are sufficient to resist expected flight loads. We also designed, fabricated, and tested other morphing-wing designs enabled by electrolaminate technology to create a wing with smoothly sliding skin that is capable of changing chord and camber with a single linear actuator. Our results suggest that electrolaminates can practically enable bio-inspired, small (Group 1 and 2) morphing UAVs.
Healing large Traumatic Tympanic Membrane Perforations Using Vaseline Gauze and Gelfoam Patching Alone
Authors: Zong Huiqin , Lou Zhengcai 
Published: January 2023

Objective The aim of this study was to evaluate the effect of vaseline gauze (VG) patching on the treatment of large traumatic perforation of tympanic membrane (TM). Material and methods 90 patients with traumatic perforation larger than 25% of the TM were randomly allocated into the control group of observation only, VG group, and Gelfoam patch alone group. The closure rate and closure time among the 3 groups were compared at 3 months. Results In total, 82 large traumatic perforations were analyzed in this study. The closure rates in the control, VG, and gelfoam patch groups were 84.6%, 100.0%, and 89.3%, respectively ( P = 0.637). Post-hoc multiple comparisons showed that the difference between the control and VG groups was significant ( P = 0.047), but the difference wasn’t significant between gelfoam alone and control groups ( P = 0.699) or VG groups ( P = 0.236). The mean closure times were 5.41 ± 1.47, 2.14 ± 0.93, and 3.00 ± 0.62 weeks for the control, VG, and gelfoam patch groups, respectively ( P < 0.001). Post-hoc multiple comparisons showed that the difference was significant between the control and VG groups ( P < 0.001) or gelfoam alone group ( P < 0.001) or VG and gelfoam groups ( P < 0.05). Conclusions VG improved the closure rate and shortened the closure time compared with observation only, which could be an effective patch material for repairing traumatic lager perforations in the outpatient setting, which is readily available and convenient.