bluuebunny/crossref_metadata_2025_split huggingface dataset:
Futibatinib Is a Novel Irreversible FGFR 1–4 Inhibitor That Shows Selective Antitumor Activity against FGFR-Deregulated Tumors
Authors: Sootome Hiroshi , Fujita Hidenori , Ito Kenjiro , Ochiiwa Hiroaki , Fujioka Yayoi , Ito Kimihiro , Miura Akihiro , Sagara Takeshi , Ito Satoru , Ohsawa Hirokazu , Otsuki Sachie , Funabashi Kaoru , Yashiro Masakazu , Matsuo Kenichi , Yonekura Kazuhiko , Hirai Hiroshi 
Published: September 2020

AbstractFGFR signaling is deregulated in many human cancers, and FGFR is considered a valid target in FGFR-deregulated tumors. Here, we examine the preclinical profile of futibatinib (TAS-120; 1-[(3S)-[4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3, 4-d] pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one), a structurally novel, irreversible FGFR1–4 inhibitor. Among a panel of 296 human kinases, futibatinib selectively inhibited FGFR1–4 with IC50 values of 1.4 to 3.7 nmol/L. Futibatinib covalently bound the FGFR kinase domain, inhibiting FGFR phosphorylation and, in turn, downstream signaling in FGFR-deregulated tumor cell lines. Futibatinib exhibited potent, selective growth inhibition of several tumor cell lines (gastric, lung, multiple myeloma, bladder, endometrial, and breast) harboring various FGFR genomic aberrations. Oral administration of futibatinib led to significant dose-dependent tumor reduction in various FGFR-driven human tumor xenograft models, and tumor reduction was associated with sustained FGFR inhibition, which was proportional to the administered dose. The frequency of appearance of drug-resistant clones was lower with futibatinib than a reversible ATP-competitive FGFR inhibitor, and futibatinib inhibited several drug-resistant FGFR2 mutants, including the FGFR2 V565I/L gatekeeper mutants, with greater potency than any reversible FGFR inhibitors tested (IC50, 1.3–50.6 nmol/L). These results indicate that futibatinib is a novel orally available, potent, selective, and irreversible inhibitor of FGFR1–4 with a broad spectrum of antitumor activity in cell lines and xenograft models. These findings provide a strong rationale for testing futibatinib in patients with tumors oncogenically driven by FGFR genomic aberrations, with phase I to III trials ongoing.Significance:Preclinical characterization of futibatinib, an irreversible FGFR1–4 inhibitor, demonstrates selective and potent antitumor activity against FGFR-deregulated cancer cell lines and xenograft models, supporting clinical evaluation in patients with FGFR-driven tumors.
NSD3-Induced Methylation of H3K36 Activates NOTCH Signaling to Drive Breast Tumor Initiation and Metastatic Progression
Authors: Jeong Ga-Young , Park Mi Kyung , Choi Hee-Joo , An Hee Woon , Park Young-Un , Choi Hyung-Jun , Park Jin , Kim Hyung-Yong , Son Taekwon , Lee Ho , Min Kyueng-Whan , Oh Young-Ha , Lee Jeong-Yeon , Kong Gu 
Published: September 2020

AbstractHistone methyltransferase NSD3 is frequently dysregulated in human cancers, yet the epigenetic role of NSD3 during cancer development remains elusive. Here we report that NSD3-induced methylation of H3K36 is crucial for breast tumor initiation and metastasis. In patients with breast cancer, elevated expression of NSD3 was associated with recurrence, distant metastasis, and poor survival. In vivo, NSD3 promoted malignant transformation of mammary epithelial cells, a function comparable to that of HRAS. Furthermore, NSD3 expanded breast cancer-initiating cells and promoted epithelial–mesenchymal transition to trigger tumor invasion and metastasis. Mechanistically, the long isoform (full-length transcript) of NSD3, but not its shorter isoform lacking a catalytic domain, cooperated with EZH2 and RNA polymerase II to stimulate H3K36me2/3-dependent transactivation of genes associated with NOTCH receptor cleavage, leading to nuclear accumulation of NICD and NICD-mediated transcriptional repression of E-cadherin. Furthermore, mice harboring primary and metastatic breast tumors with overexpressed NSD3 showed sensitivity to NOTCH inhibition. Together, our findings uncover the critical epigenetic role of NSD3 in the modulation of NOTCH-dependent breast tumor progression, providing a rationale for targeting the NSD3–NOTCH signaling regulatory axis in aggressive breast cancer.Significance:This study demonstrates the functional significance of histone methyltransferase NSD3 in epigenetic regulation of breast cancer stemness, EMT, and metastasis, suggesting NSD3 as an actionable therapeutic target in metastatic breast cancer.
Chromothripsis in Human Breast Cancer
Authors: Bolkestein Michiel , Wong John K.L. , Thewes Verena , Körber Verena , Hlevnjak Mario , Elgaafary Shaymaa , Schulze Markus , Kommoss Felix K.F. , Sinn Hans-Peter , Anzeneder Tobias , Hirsch Steffen , Devens Frauke , Schröter Petra , Höfer Thomas , Schneeweiss Andreas , Lichter Peter , Zapatka Marc , Ernst Aurélie 
Published: September 2020

AbstractChromothripsis is a form of genome instability by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosomes. Widely assumed to be an early event in tumor development, this phenomenon plays a prominent role in tumor onset. In this study, an analysis of chromothripsis in 252 human breast cancers from two patient cohorts (149 metastatic breast cancers, 63 untreated primary tumors, 29 local relapses, and 11 longitudinal pairs) using whole-genome and whole-exome sequencing reveals that chromothripsis affects a substantial proportion of human breast cancers, with a prevalence over 60% in a cohort of metastatic cases and 25% in a cohort comprising predominantly luminal breast cancers. In the vast majority of cases, multiple chromosomes per tumor were affected, with most chromothriptic events on chromosomes 11 and 17 including, among other significantly altered drivers, CCND1, ERBB2, CDK12, and BRCA1. Importantly, chromothripsis generated recurrent fusions that drove tumor development. Chromothripsis-related rearrangements were linked with univocal mutational signatures, with clusters of point mutations due to kataegis in close proximity to the genomic breakpoints and with the activation of specific signaling pathways. Analyzing the temporal order of events in tumors with and without chromothripsis as well as longitudinal analysis of chromothriptic patterns in tumor pairs offered important insights into the role of chromothriptic chromosomes in tumor evolution.Significance:These findings identify chromothripsis as a major driving event in human breast cancer.
The Heart Failure Readmission Intervention by Variable Early Follow-up (THRIVE) Study
Authors: Lee Keane K. , Thomas Rachel C. , Tan Thida C. , Leong Thomas K. , Steimle Anthony , Go Alan S. 
Published: September 2020

Background:
In-person clinic follow-up within 7 days after discharge from a heart failure hospitalization is associated with lower 30-day readmission. However, health systems and patients may find it difficult to complete an early postdischarge clinic visit, especially during the current pandemic. We evaluated the effect on 30-day readmission and death of follow-up within 7 days postdischarge guided by an initial structured nonphysician telephone visit compared with follow-up guided by an initial clinic visit with a physician.

Methods and Results:

We conducted a pragmatic randomized trial in a large integrated healthcare delivery system. Adults being discharged home after hospitalization for heart failure were randomly assigned to either an initial telephone visit with a nurse or pharmacist to guide follow-up or an initial in-person clinic appointment with primary care physicians providing usual care within the first 7 days postdischarge. Telephone appointments included a structured protocol enabling medication titration, laboratory ordering, and booking urgent clinic visits as needed under physician supervision. Outcomes included 30-day readmissions and death and frequency and type of completed follow-up within 7 days of discharge. Among 2091 participants (mean age 78 years, 44% women), there were no significant differences in 30-day heart failure readmission (8.6% telephone, 10.6% clinic,
P
=0.11), all-cause readmission (18.8% telephone, 20.6% clinic,
P
=0.30), and all-cause death (4.0% telephone, 4.6% clinic,
P
=0.49). Completed 7-day follow-up was higher in 1027 patients randomized to telephone follow-up (92%) compared with 1064 patients assigned to physician clinic follow-up (79%,
P
<0.001). Overall frequency of clinic visits during the first 7 days postdischarge was lower in participants assigned to nonphysician telephone guided follow-up (48%) compared with physician clinic-guided follow-up (77%,
P
<0.001).

Conclusions:
Early, structured telephone follow-up after hospitalization for heart failure can increase 7-day follow-up and reduce in-person visits with comparable 30-day clinical outcomes within an integrated care delivery framework.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03524534.
Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence‐Based Recommendations
Authors: Marques Nuno , Azevedo Olga , Almeida Ana Rita , Bento Dina , Cruz Inês , Correia Emanuel , Lourenço Carolina , Lopes Luís Rocha 
Published: September 2020

Background
The emergence of specific therapies for transthyretin cardiac amyloidosis (CA) warrants the need for a systematic review of the literature.

Methods and Results
A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A systematic search was performed on MEDLINE, PubMed, and Embase databases on November 29, 2019. Studies were selected based on the following predefined eligibility criteria: English‐language randomized controlled trials (RCTs), non‐RCTs, or observational studies, which included adult patients with variant/wild‐type transthyretin‐CA, assessed specific therapies for transthyretin‐CA, and reported cardiovascular outcomes. Relevant data were extracted to a predefined template. Quality assessment was based on National Institute for Health and Care Excellence recommendations (RCTs) or a checklist by Downs and Black (non‐RCTs). From 1203 records, 24 publications were selected, describing 4 RCTs (6 publications) and 16 non‐RCTs (18 publications). Tafamidis was shown to significantly improve all‐cause mortality and cardiovascular hospitalizations and reduce worsening in 6‐minute walk test, Kansas City Cardiomyopathy Questionnaire—Overall Summary score, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) in variant/wild‐type transthyretin‐CA. Patisiran showed promising results in a subgroup analysis of patients with variant transthyretin‐CA, which have to be confirmed in RCTs. Inotersen showed conflicting results on cardiac imaging parameters. The one study on AG10 had only a 1‐month duration and cardiovascular end points were exploratory and limited to cardiac biomarkers. Limited evidence from noncomparative single‐arm small non‐RCTs existed for diflunisal, epigallocatechin‐3‐gallate (green tea extract), and doxycycline+tauroursodeoxycholic acid/ursodeoxycholic acid.

Conclusions
This systematic review of the literature supports the use of tafamidis in wild‐type and variant transthyretin‐CA. Novel therapeutic targets including transthyretin gene silencers are currently under investigation.
Residential Building Codes Do Save Energy: Evidence from Hourly Smart-Meter Data
Authors: Novan Kevin , Smith Aaron , Zhou Tianxia 
Published: September 2020

Abstract
In 1978, California adopted building codes designed to reduce the energy used for temperature control. Using a rich data set of hourly electricity consumption for 158,112 houses in Sacramento, we estimate that the average house built just after 1978 uses 8% to 13% less electricity for cooling than a similar house built just before 1978. Comparing the estimated savings to the policy's projected cost, our results suggest the policy passes a cost-benefit test. In settings where market failures prevent energy costs from being completely passed through to home prices, building codes can serve as a cost- effective tool for improving energy efficiency.
Energy Markets and Global Economic Conditions
Authors: Baumeister Christiane , Korobilis Dimitris , Lee Thomas K. 
Published: September 2020

AbstractWe evaluate alternative indicators of global economic activity and other market fundamentals in terms of their usefulness for forecasting real oil prices and global petroleum consumption. World industrial production is one of the most useful indicators. However, by combining measures from several different sources, we can do even better. Our analysis results in a new index of global economic conditions and measures for assessing future energy demand and oil price pressures. We illustrate their usefulness for quantifying the main factors behind the severe contraction of the global economy and the price risks faced by shale oil producers in early 2020.
Angers Past and Present
Authors: Rosenwein Barbara H. 
Published: September 2020

Abstract
Thomas Dixon makes the important point that modern anger is nothing like the seemingly parallel phenomena (ira, mênis and so on) of the past. He proposes to show how different it is by employing what he calls an anatomical-genealogical approach – tracing components of the present idea of anger to their antecedents. He criticises my own work on anger as ahistorical because I use the singular term rather than the plurals that the subject demands. I find his critique unconvincing and his approach problematic. I suggest that we explore past notions of anger (and other emotions as well) in their own lived contexts rather than by separate components.
Severe Convective Storms across Europe and the United States. Part II: ERA5 Environments Associated with Lightning, Large Hail, Severe Wind, and Tornadoes
Authors: Taszarek Mateusz , Allen John T. , Púčik Tomáš , Hoogewind Kimberly A. , Brooks Harold E. 
Published: September 2020

AbstractIn this study we investigate convective environments and their corresponding climatological features over Europe and the United States. For this purpose, National Lightning Detection Network (NLDN) and Arrival Time Difference long-range lightning detection network (ATDnet) data, ERA5 hybrid-sigma levels, and severe weather reports from the European Severe Weather Database (ESWD) and Storm Prediction Center (SPC) Storm Data were combined on a common grid of 0.25° and 1-h steps over the period 1979–2018. The severity of convective hazards increases with increasing instability and wind shear (WMAXSHEAR), but climatological aspects of these features differ over both domains. Environments over the United States are characterized by higher moisture, CAPE, CIN, wind shear, and midtropospheric lapse rates. Conversely, 0–3-km CAPE and low-level lapse rates are higher over Europe. From the climatological perspective severe thunderstorm environments (hours) are around 3–4 times more frequent over the United States with peaks across the Great Plains, Midwest, and Southeast. Over Europe severe environments are the most common over the south with local maxima in northern Italy. Despite having lower CAPE (tail distribution of 3000–4000 J kg−1 compared to 6000–8000 J kg−1 over the United States), thunderstorms over Europe have a higher probability for convective initiation given a favorable environment. Conversely, the lowest probability for initiation is observed over the Great Plains, but, once a thunderstorm develops, the probability that it will become severe is much higher compared to Europe. Prime conditions for severe thunderstorms over the United States are between April and June, typically from 1200 to 2200 central standard time (CST), while across Europe favorable environments are observed from June to August, usually between 1400 and 2100 UTC.
Smart phone usage, sleep quality and depression in university students
Authors: Kaya Fadime , Bostanci Daştan Nihal , Durar Erkan 
Published: September 2020

Background: The smart phone contains various mobile applications specifically targeting their contents, such as information, messages, e-mail, education and entertainment towards youths. Problematic and excessive smart phone usage can cause many health problems including anxiety, depression and sleep disorders. Aims: The aim of this study is to analyse the relationship between smart phone usage, sleep quality and depression. Methods: Eight hundred and four students who owned smart phones were given the Information Form, Smart Phone Addiction Scale-Short Version, Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI). The descriptive statistics, independent sample t-test, one-way ANOVA, correlation analysis and multivariate regression analysis were used for analysis data. Results: The mean age of the students in the sample was 20.93 ± 2.44. It comprised female (65.0%) and male (35.0%) students. All of the students used smart phones. The daily smart phone usage duration was 7.85 ± 4.55 hour. According to the multivariate linear regression analysis results, significant relationships were statistically determined in the positive way between the smart phone addiction and PSQI point ( p  < .01) and BDI point ( p  < .01). Conclusion: Consequently, a relationship exists between smart phone usage, poor sleep quality and depressive symptoms in university students. The university students, whose depression point is high and sleep quality is poor, should be followed up with regarding the smart phone addiction.
Positional Installation of Intranasal Corticosteroids in the Treatment of Chronic Rhinosinusitis: A Systematic Review of the Literature
Authors: Cummings Emily L. , Fassas Scott N. , Sykes Kevin J. , Sisson Amy , Chiu Alexander G. , Fox Meha G. 
Published: September 2020

Objectives: First-line treatment of chronic rhinosinusitis includes topical corticosteroids aimed at decreasing inflammation of sinonasal mucosa. No guidelines exist regarding the effect of head position during administration of corticosteroids. We hypothesize certain positions enhance delivery to the paranasal sinuses, with further improvement in delivery after sinus surgery. Methods: A systematic review of the literature was conducted using Medline Ovid, Embase, Scopus, and Cochrane databases. All studies evaluating intranasal medications administered in 2 or more head positions were included. Study population, head position(s), method/volume of delivery, and outcome metrics were recorded. Results: Twenty-four studies compared head positions and their role in distribution of intranasal medication. Of 12 papers studying surgically naive subjects, 6 found improvement in delivery to specific sinonasal regions (middle meatus; lateral, superior, or posterior nasal cavity) and/or symptomatic improvement, in the lying head back (LHB) or head down and forward (HDF) positions, but only 3 reached statistical significance. Of 12 papers studying surgically altered patients, 10 found delivery improved in the HDF, LHB, and head forward 45° or 90° positions. Of 5 studies of extended frontal sinus procedures (Draf IIb/III), a majority found distribution to the frontal sinus improved with the head forward 90° position. Patients found the HDF position most uncomfortable. Conclusions: Studies found no statistically significant difference in distribution to unoperated sinuses among different head positions. A minority of studies supported the use of the LHB and HDF positions. This suggests that in surgically naive patients, intranasal corticosteroid delivery to sinonasal regions and/or symptomatic improvement may be best achieved with the sinuses positioned inferior to the delivery device. Surgery improved distribution to the paranasal sinuses regardless of head position, although tilting the head forward 90° was particularly effective in delivery to the frontal sinus after extended frontal sinus procedures.
Adolescent physical activity-related injuries in school physical education and leisure-time sports
Authors: Sollerhed Ann-Christin , Horn Axel , Culpan Ian , Lynch James 
Published: September 2020

Objective The aims of this study were to investigate the prevalence of sports injuries in school physical education (PE) and leisure-time sports among 1011 15- to 16-year-old adolescents in relation to physical activity, and to examine goal orientation. Methods A survey was used with additional narrative descriptions. Results There was a higher prevalence of injuries in leisure time (645/993 = 65%) than in PE (519/998 = 52%). Two groups with high PE injury rates were identified: a) highly active (258/998 = 26%) in both school PE and leisure-time sports and b) highly inactive (180/998 = 18%) in both contexts. There were no differences between girls and boys. Task-oriented adolescents were more prone to injury. Conclusions The high prevalence of injuries in PE appears to have two mechanisms: renewed inadequately recovered leisure-time injuries among highly active adolescents, and injuries among fragile inactive adolescents unfamiliar with exercise. PE educators of these two groups with different injury patterns have a considerable didactic challenge. Knowledge of inadequately recovered injuries and consideration of the high volume and intensity of early sport-specific training in children and adolescents are important parameters in the design of lesson plans for PE.
Expression of CUE domain containing 2 protein in serous ovarian cancer tissue: predicting disease-free and overall survival of patients
Authors: Lingyun Hu , Ailing Li , Yali Li , Yanqin You , Jing Ning 
Published: September 2020

Objective The aim of this study was to predict disease-free (DFS) and overall (OS) survival of cancer patients through expression of CUE domain containing 2 (CUEDC2) protein. Methods In this retrospective study, we investigated CUEDC2 expression in 75 serous ovarian cancer tissues and 34 tubal fimbria tissues by immunohistochemistry. Chemoresistance was analyzed using clinical follow-up data. Results CUEDC2 expression scores were 1.35 ± 0.60, 1.54 ± 0.57, 1.78 ± 0.71, and 2.13 ± 0.27 for International Federation of Gynecology and Obstetrics (FIGO) stages I, II, III, and IV tissues, respectively, indicating that CUEDC2 expression increased with stage and that scores differed between patients with early and advanced cancers. We found no differences in CUEDC2 expression for tissues with low, medium, and high differentiation. CUEDC2 expression was unrelated to patient age, pathological grade, or presence or absence of lymph node metastasis, but was related to tumor stage. For CUEDC2-positive patients, median DFS and OS survival were 32.6 and 54.3 months, respectively. For CUEDC2-negative patients, median DFS and OS were 51.9 and 63.5 months, respectively. Expression of CUEDC2 was correlated with DFS but not OS. Conclusion CUEDC2 is highly expressed in ovarian cancer tissues and is related to tumor stage and DFS.