bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do state regulations on e-cigarettes have impacts on the e-cigarette prevalence?
Authors: Jun Jungmi , Kim Joon Kyoung 
Published: March 2020

BackgroundWe examine the association among five types of state regulations on electronic cigarettes (defining e-cigarettes, special tax, packaging, youth access and licensure) and initiation and current usage of e-cigarettes in 50 US states and the District of Columbia.MethodsData came from the 2017 Behavioral Risk Factor Surveillance System and the US e-cigarette regulations—50 state review by the Public Health Law Center. Logistic regressions were used to determine the odds of initiation and current use of e-cigarettes among individuals aged 18–24, 25–34 and the whole sample, adjusting for socio-demographic covariates.ResultsDespite the short history of state laws on e-cigarettes, each of the five state laws was associated with lower odds of initiation and use of e-cigarettes in the whole sample. In the 18–24 age group, only the licensure was associated with lower initiation. In the 25–34 age group, the licensure and taxation were related to lower initiation and current usage. There were significant differences of e-cigarette initiation and usage based on the number of state laws regulating e-cigarettes.ConclusionsOur analysis indicates the potential of states’ policy efforts to regulate e-cigarettes comprehensively in leading significant changes to e-cigarette prevalence in their populations.
Mortality, clinical findings, predisposing factors and treatment ofClostridioides difficilecolitis in Japanese thoroughbred racehorses
Authors: Nomura Motoi , Kuroda Taisuke , Tamura Norihisa , Muranaka Masanori , Niwa Hidekazu 
Published: March 2020

BackgroundAlthoughClostridioides difficile‐associated diseases (CDAD) is considered to be associated with colitis in horses, few studies have been performed with a focus on the characteristics of CDAD in thoroughbred racehorses.MethodsBetween 2010 and 2018, a test forC. difficilewas performed using faecal samples from 137 thoroughbred racehorses with colitis presenting with diarrhoea and fever. The mortality rate, clinical findings, predisposing factors and the selected treatments were investigated in a retrospective manner.ResultsTwenty‐four cases were diagnosed as CDAD and 113 as non‐CDAD. The mortality rate was significantly higher in the CDAD group (83 per cent) than that in the non‐CDAD group (34 per cent). The levels of serum amyloid A, blood urea nitrogen and packed cell volume at initial presentation were also significantly higher, and those of total protein and albumin were significantly lower in the CDAD group. The development of CDAD was associated with the administration of antimicrobials, surgery and hospitalisation. No significant improvement in mortality was observed for any of the selected treatment in both groups.ConclusionCDAD in thoroughbred racehorses was identified as a high mortality disease with rapid progression of systemic inflammation and deterioration of the circulatory state. Further investigation is required to improve the treatment.
Standardisation of electrocardiographic examination in corn snakes (Pantherophis guttatus)
Authors: Lewis Martyn , Bouvard Jonathan , Eatwell Kevin , Culshaw Geoff 
Published: March 2020

IntroductionCorn snakes are a very common pet reptile species, yet there is an absence of evidence‐based literature standardising collection of ECG or detailing ECG deflection morphology in the normal animal. The authors describe a well‐tolerated, reproducible technique and detail the cardiac cycle in terms of lead 2 equivalent waveforms and intervals.Animals29 adult corn snakes.Materials and methodsThis prospective study evaluated, under species‐appropriate, standardised conditions, a technique for producing standard six‐lead ECG tracings. Lead 2 equivalent cardiac cycles were described in detail and statistically analysed for sex, weight, length, heart rate and mean electrical axis.ResultsHigh‐quality tracings demonstrated common ECG characteristics for this species, including no Q, S or SV waves, prolonged PR and RT intervals, rhythmic oscillation of the baseline, short TP segments, and a right displaced mean electrical axis. An influence of sex, weight or length on heart rate and mean electrical axis was not identified.ConclusionsTo the authors’ knowledge, this is the first study to describe a standardised technique for recording ECG in significant numbers of normal corn snakes. Ranges have been provided that may be of diagnostic value or form the basis for future development of reference intervals for this species.
Neutrino elastic scattering on polarized electrons as a tool for probing the neutrino nature
Authors: Błaut A. , Sobków W. 
Published: March 2020

AbstractPossibility of using the polarized electron target (PET) for testing the neutrino nature is considered. It is assumed that the incoming $$\nu _e$$νe beam is the superposition of left chiral (LC) states with right chiral (RC) ones. Consequently the non-vanishing transversal components of $$\nu _e$$νe spin polarization may appear, both T-even and T-odd. $$\nu _e$$νes are produced by the low energy monochromatic (un)polarized emitter located at a near distance from the hypothetical detector which is able to measure both the azimuthal angle and the polar angle of the recoil electrons, and/or also the energy of the outgoing electrons with a high resolution. A detection process is the elastic scattering of $$\nu _e$$νes (Dirac or Majorana) on the polarized electrons. LC $$\nu _e$$νes interact mainly by the standard $$V - A$$V-A interaction, while RC ones participate only in the non-standard $$V + A$$V+A, scalar $$S_R$$SR, pseudoscalar $$P_R$$PR and tensor $$T_R$$TR interactions. All the interactions are of flavour-conserving type (FC). We show that a distinction between the Dirac and the Majorana $$\nu _e$$νes is possible both for the longitudinal and the transversal $$\nu _e$$νe polarizations. In the first case a departure from the standard prediction of the azimuthal asymmetry of recoil electrons is caused by the interferences between the non-standard complex S and T couplings, proportional to the angular correlations (T-even and T-odd) among the polarization of the electron target, the incoming neutrino momentum and the outgoing electron momentum. It is shown that such a deviation would indicate the Dirac $$\nu _e$$νe nature and the presence of time reversal symmetry violation interactions. It is remarkable that the result is conclusive for all Majorana non-standard couplings. In the second case the azimuthal asymmetries, polar distribution and energy spectrum of scattered electrons are sensitive to the interference terms between the standard and exotic interactions, proportional to the various angular correlations among the transversal $$\nu _e$$νe spin polarization, the electron target polarization, the incoming $$\nu _e$$νe momentum and the outgoing electron momentum. In the particular case of the V–A and S couplings the precise measurement of some observables, e.g. the spectrum, can distinguish between the Dirac and the Majorana $$\nu _e$$νes as long as the incoming $$\nu _e$$νe beam has non-vanishing transversal polarization. Our model-independent study is carried out for the flavour $$\nu _e$$νe eigenstates in the relativistic $$\nu _e$$νe limit.
Repression of the Type I Interferon Pathway Underlies MYC- and KRAS-Dependent Evasion of NK and B Cells in Pancreatic Ductal Adenocarcinoma
Authors: Muthalagu Nathiya , Monteverde Tiziana , Raffo-Iraolagoitia Ximena , Wiesheu Robert , Whyte Declan , Hedley Ann , Laing Sarah , Kruspig Björn , Upstill-Goddard Rosanna , Shaw Robin , Neidler Sarah , Rink Curtis , Karim Saadia A. , Gyuraszova Katarina , Nixon Colin , Clark William , Biankin Andrew V. , Carlin Leo M. , Coffelt Seth B. , Sansom Owen J. , Morton Jennifer P. , Murphy Daniel J. 
Published: March 2020

Abstract

MYC is implicated in the development and progression of pancreatic cancer, yet the precise level of MYC deregulation required to contribute to tumor development has been difficult to define. We used modestly elevated expression of human MYC, driven from the Rosa26 locus, to investigate the pancreatic phenotypes arising in mice from an approximation of MYC trisomy. We show that this level of MYC alone suffices to drive pancreatic neuroendocrine tumors, and to accelerate progression of KRAS-initiated precursor lesions to metastatic pancreatic ductal adenocarcinoma (PDAC). Our phenotype exposed suppression of the type I interferon (IFN) pathway by the combined actions of MYC and KRAS, and we present evidence of repressive MYC–MIZ1 complexes binding directly to the promoters of the genes encodiing the type I IFN regulators IRF5, IRF7, STAT1, and STAT2. Derepression of IFN regulator genes allows pancreatic tumor infiltration by B and natural killer (NK) cells, resulting in increased survival.

Significance:
We define herein a novel mechanism of evasion of NK cell–mediated immunity through the combined actions of endogenously expressed mutant KRAS and modestly deregulated expression of MYC, via suppression of the type I IFN pathway. Restoration of IFN signaling may improve outcomes for patients with PDAC.
This article is highlighted in the In This Issue feature, p. 747
Golgi Acidification by NHE7 Regulates Cytosolic pH Homeostasis in Pancreatic Cancer Cells
Authors: Galenkamp Koen M.O. , Sosicka Paulina , Jung Michael , Recouvreux M. Victoria , Zhang Yijuan , Moldenhauer Matthew R. , Brandi Giovanni , Freeze Hudson H. , Commisso Cosimo 
Published: March 2020

Abstract

abstract
Cancer cells reprogram their metabolism to meet elevated energy demands and favor glycolysis for energy production. This boost in glycolytic flux supports proliferation, but also generates acid in the form of hydrogen ions that must be eliminated from the cytoplasm to maintain the alkaline intracellular pH (pHi) associated with transformation. To cope with acid production, tumor cells employ ion transport systems, including the family of sodium–hydrogen exchangers (NHE). Here, we identify NHE7 as a novel regulator of pHi in pancreatic ductal adenocarcinoma (PDAC). We determine that NHE7 suppression causes alkalinization of the Golgi, leading to a buildup of cytosolic acid that diminishes tumor cell fitness mainly through the dysregulation of actin. Importantly, NHE7 knockdown in vivo leads to the abrogation of tumor growth. These results identify Golgi acidification as a mechanism to control pHi and point to the regulation of pHi as a possible therapeutic vulnerability in PDAC.

Significance:
NHE7 regulates cytosolic pH through Golgi acidification, which points to the Golgi as a “proton sink” for metabolic acid. Disruption of cytosolic pH homeostasis via NHE7 suppression compromises PDAC cell viability and tumor growth.
See related commentary by Ward and DeNicola, p. 768.
This article is highlighted in the In This Issue feature, p. 747
Association of Heart Rate Variability With Cognitive Performance: The Multi‐Ethnic Study of Atherosclerosis
Authors: Schaich Christopher L. , Malaver Diego , Chen Haiying , Shaltout Hossam A. , Zeki Al Hazzouri Adina , Herrington David M. , Hughes Timothy M. 
Published: March 2020

Background

Heart rate variability (
HRV
) is associated with vascular risk factors for dementia, but whether
HRV
is associated with specific domains of cognitive performance is unclear.

Methods and Results

In the Multi‐Ethnic Study of Atherosclerosis (N=3018; mean age 59.3±9.2 years), we assessed the relationship of 10‐second
HRV
to scores on tests of global cognitive performance (Cognitive Abilities Screening Instrument), processing speed (Digit Symbol Coding), and working memory (Digit Span).
HRV
was computed as the SD of normal‐normal intervals (SDNN) and root mean square of successive differences (RMSSD) at Exam 1 (2000–2002) and Exam 5 (2010–2012). Cognitive tests were administered at Exam 5. We report regression coefficients (β [95% CI]) representing cognitive test score change per 2‐fold increase in
HRV
. After adjustment for age, race/ethnicity, sex, education, apolipoprotein E genotype, and cardiovascular risk factors and incident disease, higher Exam 1 (β=0.37 [0.06, 0.67]) and Exam 5 (β=0.31 [0.04, 0.59]) SDNN were associated with better Cognitive Abilities Screening Instrument performance. Higher Exam 1 (β=0.80 [0.17, 1.43]) and Exam 5 (β=0.63 [0.06, 1.20])
SDNN
, and Exam 5 RMSSD (β=0.54 [0.01, 1.08]) were associated with better Digit Symbol Coding performance. Finally, higher Exam 5 SDNN was associated with better Digit Span performance (β=0.17 [0.01, 0.33]). Associations were attenuated after adjustment for resting heart rate.

Conclusions

Higher
HRV
is generally associated with better cognitive performance in this multi‐ethnic cohort of aging adults, and further study of the relationship of autonomic function to cognition is warranted.
Associations of Benzodiazepine With Adverse Prognosis in Heart Failure Patients With Insomnia
Authors: Sato Yu , Yoshihisa Akiomi , Hotsuki Yu , Watanabe Koichiro , Kimishima Yusuke , Kiko Takatoyo , Kanno Yuki , Yokokawa Tetsuro , Abe Satoshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika 
Published: March 2020

Background
The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF).

Methods and Results

This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z‐drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for
HF
and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years;
P
=0.010), had a higher prevalence of depression (17.4% versus 8.9%;
P
<0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%;
P
=0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/
dL
;
P
=0.001), sodium (139.0 versus 140.0
mE
q/L;
P
=0.018), and albumin (3.7 versus 3.9 g/
dL
;
P
=0.003). Kaplan‐Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for
HF
, log‐rank
P
=0.001; cardiac death, log‐rank
P
=0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for
HF
(hazard ratio, 1.530; 95% CI, 1.025–2.284;
P
=0.038). Furthermore, rehospitalization for
HF
was higher in the benzodiazepine group after propensity score matching (log‐rank
P
=0.036).

Conclusions

Benzodiazepine is associated with higher risk of rehospitalization for
HF
compared with Z‐drugs in patients with
HF
.
Renal Fibrosis Is Significantly Attenuated Following Targeted Disruption of
Cd40
in Experimental Renal Ischemia
Authors: Zhang Shungang , Breidenbach Joshua D. , Khalaf Fatimah K. , Dube Prabhatchandra R. , Mohammed Chrysan J. , Lad Apurva , Stepkowski Stanislaw , Hinds Terry D. , Kumarasamy Sivarajan , Kleinhenz Andrew , Tian Jiang , Malhotra Deepak , Kennedy David J. , Cooper Christopher J. , Haller Steven T. 
Published: March 2020

Background

Renal artery stenosis is a common cause of renal ischemia, contributing to the development of chronic kidney disease. To investigate the role of local
CD
40 expression in renal artery stenosis, Goldblatt 2‐kidney 1‐clip surgery was performed on hypertensive Dahl salt‐sensitive rats (S rats) and genetically modified S rats in which
CD
40 function is abolished (
Cd40

mutant

).

Methods and Results

Four weeks following the 2‐kidney 1‐clip procedure,
Cd40

mutant

rats demonstrated significantly reduced blood pressure and renal fibrosis in the ischemic kidneys compared with S rat controls. Similarly, disruption of Cd40 resulted in reduced 24‐hour urinary protein excretion in
Cd40

mutant

rats versus S rat controls (46.2±1.9 versus 118.4±5.3 mg/24 h;
P
<0.01), as well as protection from oxidative stress, as indicated by increased paraoxonase activity in
Cd40

mutant

rats versus S rat controls (
P
<0.01). Ischemic kidneys from
Cd40

mutant

rats demonstrated a significant decrease in gene expression of the profibrotic mediator, plasminogen activator inhibitor‐1 (
P
<0.05), and the proinflammatory mediators, C‐C motif chemokine ligand 19 (
P
<0.01), C‐X‐C Motif Chemokine Ligand 9 (
P
<0.01), and interleukin‐6 receptor (
P
<0.001), compared with S rat ischemic kidneys, as assessed by quantitative
PCR
assay. Reciprocal renal transplantation documented that
CD
40 exclusively expressed in the kidney contributes to ischemia‐induced renal fibrosis. Furthermore, human
CD
40‐knockout proximal tubule epithelial cells suggested that suppression of
CD
40 signaling significantly inhibited expression of proinflammatory and ‐fibrotic genes.

Conclusions

Taken together, our data suggest that activation of
CD
40 induces a significant proinflammatory and ‐fibrotic response and represents an attractive therapeutic target for treatment of ischemic renal disease.
Deep Learning–Based Algorithm for Detecting Aortic Stenosis Using Electrocardiography
Authors: Kwon Joon‐Myoung , Lee Soo Youn , Jeon Ki‐Hyun , Lee Yeha , Kim Kyung‐Hee , Park Jinsik , Oh Byung‐Hee , Lee Myong‐Mook 
Published: March 2020

Background

Severe, symptomatic aortic stenosis (
AS
) is associated with poor prognoses. However, early detection of
AS
is difficult because of the long asymptomatic period experienced by many patients, during which screening tools are ineffective. The aim of this study was to develop and validate a deep learning–based algorithm, combining a multilayer perceptron and convolutional neural network, for detecting significant
AS
using ECGs.

Methods and Results

This retrospective cohort study included adult patients who had undergone both
ECG
and echocardiography. A deep learning–based algorithm was developed using 39 371
ECG
s. Internal validation of the algorithm was performed with 6453
ECG
s from one hospital, and external validation was performed with 10 865
ECG
s from another hospital. The end point was significant
AS
(beyond moderate). We used demographic information, features, and 500‐Hz, 12‐lead
ECG
raw data as predictive variables. In addition, we identified which region had the most significant effect on the decision‐making of the algorithm using a sensitivity map. During internal and external validation, the areas under the receiver operating characteristic curve of the deep learning–based algorithm using 12‐lead
ECG
for detecting significant
AS
were 0.884 (95% CI, 0.880–0.887) and 0.861 (95% CI, 0.858–0.863), respectively; those using a single‐lead
ECG
signal were 0.845 (95% CI, 0.841–0.848) and 0.821 (95% CI, 0.816–0.825), respectively. The sensitivity map showed the algorithm focused on the T wave of the precordial lead to determine the presence of significant
AS
.

Conclusions

The deep learning–based algorithm demonstrated high accuracy for significant
AS
detection using both 12‐lead and single‐lead
ECG
s.
Risk‐Standardizing Rates of Return of Spontaneous Circulation for In‐Hospital Cardiac Arrest to Facilitate Hospital Comparisons
Authors: Chan Paul S. , Tang Yuanyuan ,   for the American Heart Association's Get With the Guidelines‐Resuscitation Investigators
Published: March 2020

Background
Sustained return of spontaneous circulation (ROSC) is the most proximal and direct assessment of acute resuscitation quality in hospitals. However, validated tools to benchmark hospital rates for ROSC after in‐hospital cardiac arrest currently do not exist.

Methods and Results

Within the national Get With The Guidelines‐Resuscitation registry, we identified 83 206 patients admitted from 335 hospitals from 2014 to 2017 with in‐hospital cardiac arrest. Using hierarchical logistic regression, we derived and validated a model for ROSC, defined as spontaneous and sustained ROSC for ≥20 consecutive minutes, from 24 pre‐arrest variables and calculated rates of risk‐standardized ROSC for in‐hospital cardiac arrest for each hospital. Overall, rates of ROSC were 72.0% and 72.7% for the derivation and validation cohorts, respectively. The model in the derivation cohort had moderate discrimination (C‐statistic 0.643) and excellent calibration (
R
2
of 0.996). Seventeen variables were associated with ROSC, and a parsimonious model retained 10 variables. Before risk‐adjustment, the median hospital ROSC rate was 70.5% (interquartile range: 64.7–76.9%; range: 33.3–89.6%). After adjustment, the distribution of risk‐standardized ROSC rates was narrower: median of 71.9% (interquartile range: 68.2–76.4%; range: 42.2–84.6%). Overall, 56 (16.7%) of 335 hospitals had at least a 10% absolute change in percentile rank after risk standardization: 27 (8.0%) with a ≥10% negative percentile change and 29 (8.7%) with a ≥10% positive percentile change.

Conclusions
We have derived and validated a model to risk‐standardize hospital rates of ROSC for in‐hospital cardiac arrest. Use of this model can support efforts to compare acute resuscitation survival across hospitals to facilitate quality improvement.
Seneca on the Death of M. Livius Drusus (De brevitate vitae 6.1-2)
Authors: Currie Michelle 
Published: March 2020

Abstract
The account of M. Livius Drusus in Seneca’s dialogue De brevitate vitae significantly departs from other versions by suggesting that Drusus’ death may have been a suicide rather than an assassination. The inspiration for Seneca’s reworking of the scene lies with Stoicism’s expectations for choosing and implementing suicide. Drusus’ role in the dialogue is to provide a cautionary illustration of the problems of neglecting true otium and the philosophical pursuits it entails. Seneca portrays Drusus disregarding Stoic conventions for suicide in order to reinforce his broader philosophical failings. The author therefore significantly breaks with historiographical tradition in order to make a more effective philosophical argument.
Efficacy and safety of high-intensity focused ultrasound (HIFU) for treating benign thyroid nodules: a systematic review and meta-analysis
Authors: Chung Sae Rom , Baek Jung Hwan , Suh Chong Hyun , Choi Young Jun , Lee Jeong Hyun 
Published: March 2020

Background High-intensity focused ultrasound (HIFU) is an emerging thermal ablation technique that has been successfully applied to various benign thyroid nodules. Purpose To evaluate the efficacy and safety of HIFU for the treatment of benign thyroid nodules. Material and Methods The Ovid-MEDLINE and EMBASE databases were searched up to 9 July 2018 for studies describing the use of HIFU to treat benign thyroid nodules. We included studies that have outcomes with sufficient detail to evaluate the volume reduction rate (VRR). The pooled proportions of VRR ≥50% and pooled VRR at one, three, and six months after HIFU were assessed using random-effects modeling. Heterogeneity among studies was determined using Chi-square statistics for pooled estimates and the inconsistency index I2. Results Seven studies were included in the systematic review and four in the meta-analysis. The pooled VRR at one, three, and six months after HIFU were 17.59 (95% confidence interval [CI] 12.56–22.62), 48.93 (95% CI 42.20–55.66), and 60.43 (95% CI 51.88–68.98). The pooled proportions of VRR ≥50% at six months after HIFU were 75% (95% CI 53–89; I2=73.6%). There were no major complications of HIFU. Conclusion HIFU may be a safe and effective treatment modality for benign thyroid nodules, especially for small nodules.