bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholinergic regulation of cardiac pacemaker activity by L-type Cav1.3 channels
Authors: Talssi L , Bidaud I , Mangoni ME , Mesirca P 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Fondation Recherche Médicale

Introduction
The cholinergic regulation of heart rate (HR) is mediated by acetylcholine (ACh)-dependent activation of M2-receptors (M2R). Activated M2R promote release of the βγ-subunit of G-proteins to directly gate GIRK1/4 channels (underlying the cardiac IKACh current), while αi-subunits inhibit adenylate cyclase (AC) activity. AC inhibition reduces the intracellular concentration of cAMP, decreasing the activity of ion channels involved in pacemaking, including "funny" f-(HCN4) and L-type Cav1.3 calcium channels.

Purpose
To determine the role of L-type Cav1.3 channels in cholinergic regulation of heart rate.

Methods
We recorded the frequency of activation and position of pacemaker leading site in ex vivo sinus nodes and the HR of isolated Langendorff perfused hearts of mice at baseline or during ACh perfusion. We used control wild type (WT) mice, and five genetically modified mouse models: Cav1.3 knockout (KO, ablated Cav1.3-mediated L-type current), GIRK4KO (ablated IKACh current), HCN4-CNBD (selective deletion of cAMP-dependent regulation of HCN4), GIRK4KO/HCN4-CNBD and GIRK4KO/Cav1.3KO. We performed in vivo telemetric recordings of heart rate (HR) in WT and GIRK4KO/Cav1.3KO animals.

Results
Data from optical mapping experiments showed that, under basal conditions, perfusion of 3 μM ACh significantly reduced the frequency of action potentials in WT (44%), HCN4-CNBD (38%), Cav1.3KO (65%) and GIRK4KO (8%) isolated mouse sinus node tissues. ACh application did not significantly affect the frequency of action potentials recorded in tissue from GIRK4KO/HCN4-CNBD and GIRK4KO/Cav1.3KO animals. Furthermore, in all sinus nodes tested, regardless of genotype, ACh shifted the pacemaker leading site from its normal position by at least 0.7 mm.
Upon stimulation of the β-adrenergic pathway by Isoproterenol, to reproduce conditions of accentuated antagonism, 3µM ACh reduced HR in isolated hearts from WT (43.8%), HCN4-CNBD (38.7%), Cav1.3KO (25,4%), GIRK4KO (16.9%) and GIRK4KO/HCN4-CNBD (16.4%) mice. No significant HR reduction was recorded in hearts from GIRK4KO/Cav1.3KO animals.
In vivo data indicate that HR reduction induced by combined injection of Hexamethonium ( a Nicotinic acetylcholine receptor blocker) with Carbamoylcholine (CCH, M2 receptor agonist) or with 2-Chloro-N6-Cyclopentyladenosine (CCPA, A1 receptor agonist) is higher in WT than in GIRK4KO/Cav1.3KO animals (68% vs 48% CCH, and 79% vs 62% CCPA, respectively).

Conclusion
Our data indicate that L-type Cav1.3 channels are involved in cholinergic regulation of heart rate in mice. In addition, when the intracellular concentration of cAMP is elevated (i.e. under conditions of accentuated antagonism), cholinergic regulation of sinus node pacemaking is reliant on Cav1.3 and KACh channels.
The lectin LecA sensitizes the human stretch-activated channel TREK-1 but not Piezo1 and binds selectively to cardiac non-myocytes
Authors: Darkow E , Rog-Zielinska EA , Madl J , Brandel A , Siukstaite L , Omidvar R , Kohl P , Ravens U , Roemer W , Peyronnet R 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research was supported by the European Research Council (Advanced Grant CardioNECT, Project ID: #323099, PK) and a research grant from the Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin, #3091311631).
Mechanical stimuli are detected and transduced by cellular mechano-sensors, including stretch-activated ion channels (SAC). SAC are activated by stretch and changes in membrane curvature but their precise role in the heart is unclear.
The lectin LecA is a virulence factor of Pseudomonas aeruginosa and essential for bacterial cell invasion by inducing membrane curvature. We investigate whether LecA modulates SAC activity, namely TREK-1 and Piezo1 in human embryonic kidney (HEK) cells.
Confocal microscopy and electron tomography were used to follow binding dynamics of LecA, and the ion channel activity was recorded using the patch-clamp technique. Additionally, freshly isolated cardiac cells were used for studies into cell type dependency of LecA binding.
LecA binds within seconds to cell surface. Local plasma membrane invaginations are detected by 17 min of LecA exposure. LecA sensitizes TREK-1, but not Piezo1, to voltage and mechanical stimulation. In freshly isolated cardiac cells, LecA binds to non-myocytes, but not to cardiomyocytes from mouse, rabbit, pig, and human.
Our results suggest that LecA may serve as a pharmacological tool to study cardiac SAC in a cell type-preferential manner. Abstract Figure. Graphical abstract
Catalase inhibition by nitric oxide potentiates hydrogen peroxide to trigger catastrophic chromosome fragmentation in Escherichia coli
Authors: Agashe Pooja , Kuzminov Andrei 
Published: May 2021

Abstract
Hydrogen peroxide (H2O2, HP) is a universal toxin that organisms deploy to kill competing or invading cells. Bactericidal action of H2O2 presents several questions. First, the lethal H2O2 concentrations in bacterial cultures are 1000x higher than, for example, those calculated for the phagosome. Second, H2O2-alone kills bacteria in cultures either by mode-one, via iron-mediated chromosomal damage, or by mode-two, via unknown targets, but the killing mode in phagosomes is unclear. Third, phagosomal H2O2 toxicity is enhanced by production of nitric oxide (NO), but in vitro studies disagree: some show NO synergy with H2O2 antimicrobial action, others instead report alleviation. To investigate this “NO paradox,” we treated Escherichia coli with various concentrations of H2O2-alone or H2O2+NO, measuring survival and chromosome stability. We found that all NO concentrations make sublethal H2O2 treatments highly lethal, via triggering catastrophic chromosome fragmentation (mode-one killing). Yet, NO-alone is not lethal, potentiating H2O2 toxicity by blocking H2O2 scavenging in cultures. Catalases represent obvious targets of NO inhibition, and catalase-deficient mutants are indeed killed equally by H2O2-alone or H2O2+NO treatments, also showing similar levels of chromosome fragmentation. Interestingly, iron chelation blocks chromosome fragmentation in catalase-deficient mutants without blocking H2O2-alone lethality, indicating mode-two killing. In fact, mode-two killing of WT cells by much higher H2O2 concentrations is transiently alleviated by NO, reproducing the “NO paradox.” We conclude that NO potentiates H2O2 toxicity by promoting mode-one killing (via catastrophic chromosome fragmentation) by otherwise static low H2O2 concentrations, while transiently suppressing mode-two killing by immediately lethal high H2O2 concentrations.
Retroperitoneal necrotizing fasciitis with the involvement of the anterior abdominal wall following perianal abscess
Authors: Abebe Metasebia W , Nigussie Mary Mesfin 
Published: May 2021

Abstract
Necrotizing fasciitis (NF) is a life-threatening infection, which requires immediate debridement and broad-spectrum antibiotic treatment. Delay in prompt diagnosis and operative debridement is associated with significant morbidity and mortality. Retroperitoneal NF is a rare condition whereby the infection within the pelvis or retroperitoneum rapidly expands over the fascial planes to involve the anterior abdominal wall (AW), the thighs and the buttocks. It presents a challenge for surgical access due to the anatomic depth of the structures and may result in extensive soft tissue loss requiring complex AW reconstruction for closure. The case discussed here is a 43-year-old female with a perianal abscess that progressed to retroperitoneal and anterior AW NF with intra-peritoneal abscess collection requiring bilateral tensor fascia-lata graft for the closure of the anterior AW fascia defect.
Digitalizing experiential celebrations in the early modern civic space: A methodological investigation of augmented reality as an interpretative tool
Authors: Guidicini Giovanna 
Published: May 2021

Abstract
This article investigates the methodological suitability of Virtual and Augmented Reality (VR and AR) to the recreation of early modern civic spectacles. These are presented as instances of controlled engagement of a (royal) user with a civic space temporarily ‘augmented’ by the engaging superimposition of structures, performances, and haptic experiences – hence fulfilling Ronald Azuma’s definition of AR. The writings of theorists of space and Cross Reality innovators provide the basis for a comparative discussion of practical applications of VR and AR in history-related fields (archaeology, history, education, and gaming and entertainment). For their methodological similarities to civic festivals in addressing the complexity of human experiences in augmented spaces, AR-based virtual reconstructions are demonstrated to be cognate and ductile investigative tools.
The Dark Energy Survey supernova programme: modelling selection efficiency and observed core-collapse supernova contamination
Authors: Vincenzi M , Sullivan M , Graur O , Brout D , Davis T M , Frohmaier C , Galbany L , Gutiérrez C P , Hinton S R , Hounsell R , Kelsey L , Kessler R , Kovacs E , Kuhlmann S , Lasker J , Lidman C , Möller A , Nichol R C , Sako M , Scolnic D , Smith M , Swann E , Wiseman P , Asorey J , Lewis G F , Sharp R , Tucker B E , Aguena M , Allam S , Avila S , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Choi A , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Doel P , Everett S , Ferrero I , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gutierrez G , Hollowood D L , Honscheid K , Hoyle B , James D J , Kuehn K , Kuropatkin N , Maia M A G , Martini P , Menanteau F , Miquel R , Morgan R , Palmese A , Paz-Chinchón F , Plazas A A , Romer A K , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Soares-Santos M , Suchyta E , Tarle G , Thomas D , To C , Varga T N , Walker A R , Wilkinson R D , (DES Collaboration)  
Published: May 2021

ABSTRACT
The analysis of current and future cosmological surveys of Type Ia supernovae (SNe Ia) at high redshift depends on the accurate photometric classification of the SN events detected. Generating realistic simulations of photometric SN surveys constitutes an essential step for training and testing photometric classification algorithms, and for correcting biases introduced by selection effects and contamination arising from core-collapse SNe in the photometric SN Ia samples. We use published SN time-series spectrophotometric templates, rates, luminosity functions, and empirical relationships between SNe and their host galaxies to construct a framework for simulating photometric SN surveys. We present this framework in the context of the Dark Energy Survey (DES) 5-yr photometric SN sample, comparing our simulations of DES with the observed DES transient populations. We demonstrate excellent agreement in many distributions, including Hubble residuals, between our simulations and data. We estimate the core collapse fraction expected in the DES SN sample after selection requirements are applied and before photometric classification. After testing different modelling choices and astrophysical assumptions underlying our simulation, we find that the predicted contamination varies from 7.2 to 11.7 per cent, with an average of 8.8 per cent and an r.m.s. of 1.1 per cent. Our simulations are the first to reproduce the observed photometric SN and host galaxy properties in high-redshift surveys without fine-tuning the input parameters. The simulation methods presented here will be a critical component of the cosmology analysis of the DES photometric SN Ia sample: correcting for biases arising from contamination, and evaluating the associated systematic uncertainty.
Constraints on variation in the speed of light based on gravitational constant constraints
Authors: Eaves R E 
Published: May 2021

ABSTRACT
We consider the possibility of a varying speed of light based on a unit of length defined with a rigid rod or atomic standard. The reference for comparison is the international standard for the meter based on the transit of light, defined so that c is constant. If these two units do not correspond over time, then the gravitational constant G as measured with each will not be in agreement. We relate changes in the speed of light in atomic units of length to changes in G measured in the two systems. Reported experimental data that constrain yearly changes in G are sufficient to bound changes in c. Experimental constraints on $|\dot{G}/G|$ based on spacecraft microwave ranging and on helioseismology indicate that presently $|{\dot{c}/c}|\le .55 \times 10^{-12}\, \textrm {yr}^{-1}$. If this result is extended in epoch by relating c to a power of the scale factor, an, then variation in c is constrained by |n| &lt; .0080. The approach is distinct from other efforts to constrain $\dot{c}$ in being based on data from within the Solar system instead of cosmological observations. A relationship between c and the fine-structure constant is identified that potentially provides tighter constraints.
Helium enrichment during classical nova outbursts
Authors: Guo Yunlang , Wu Chengyuan , Wang Bo 
Published: May 2021

ABSTRACT
Nova outbursts play an important role in the chemical evolution of Galaxy, especially they are the main source of synthetic $^{13}\rm C$, $^{15}\rm N$, $^{17}\rm O$, and some radioactive isotopes like $^{22}\rm Na$ and $^{26}\rm Al$. The enrichment of He in nova ejecta indicates that the accreted material may mix with the He-shell (He-mixing). The purpose of this work is to investigate how the He-mixing affects the nova outbursts in a systematic way. We evolved a series of accreting WD models, and found that the mass fraction of H and He in nova ejecta can be influenced by different He-mixing fractions significantly. We also found that both the nova cycle duration and ejected mass increase with the He-mixing fractions. Meanwhile, the nuclear energy generation rate of p–p chains decreases with the He-mixing fraction during the nova outbursts, whereas the CNO-cycle increases. This work can reproduce the chemical abundances in the ejecta of some representative novae, such as GQ Mus, ASASSN-18fv, HR Del, T Aur, and V443 Sct. This implies that the He-mixing process cannot be neglected when studying nova outbursts. This study also develops a He-mixing meter (i.e. $\rm He/H$) that can be used to estimate the He-mixing fraction in classical nova systems.
$t \to 0$
extrapolation function in the small flow time expansion method for the energy–momentum tensor
Authors: Suzuki Hiroshi , Takaura Hiromasa 
Published: May 2021

Abstract
We theoretically clarify the functional form to be used in $t \to 0$ extrapolation in the small flow time expansion method for the energy–momentum tensor (EMT), which facilitates lattice simulation of the EMT based on the gradient flow. We argue that in the $t \to 0$ extrapolation analysis, lattice data should be fitted by a power function in $g(\mu(t))$, the flow time dependent running coupling, where the power is determined by the perturbation order we consider. From actual lattice data, we confirm the validity of the extrapolation function. Using the new extrapolation function, we present updated lattice results for thermodynamics quantities in quenched QCD; our results are consistent with the previous study [T. Iritani et al., Prog. Theor. Exp. Phys. 2019, 023B02 (2019)] but we obtain smaller errors due to the reduction of systematic errors.
The role of religiosity in COVID-19 vaccine hesitancy
Authors: Garcia Louiegi L , Yap John Federick C 
Published: May 2021

Abstract
With the surge of COVID-19 cases worldwide, it is essential that vaccination be prioritized to facilitate herd immunity. However, there is vaccine hesitancy reflected in religiosity. This correspondence aims to understand religiosity as a factor that plays a role in vaccination hesitancy. Medical and scientifically sound evidence is influenced by religious beliefs resulting in varied responses toward getting vaccinated such as vaccination hesitancy.
Darwin’s ‘struggle for life’, suffering and incompetence recognition: a philoscientific perspective on COVID-19 crisis
Authors: Pacaol Niñoval F 
Published: May 2021

Abstract
Many of the academic papers that discussed the COVID-19 pandemic sought to present a reasonable analysis of the crisis and its underlying implications in government policies (for social and environmental reformations) and individual actions either in the present context or future. This paper attempted to contextualize the COVID-19 crisis through the lens of the Darwinian struggle for life and the philosophical notion of suffering while stressing the importance of defects admission. Generally, the author argues that these concepts are the primary roots of other dimensions of COVID-19-related studies.
Parkinson Disease, Dysphagia, and Cervical Spine Surgery
Authors: Avila Mauricio J. , Aguilar-Salinas Pedro , Burket Aaron R. , Dumont Travis M. 
Published: May 2021

Study Design:
An analysis of a National Database.

Objective:
The objective of this study was to evaluate the rate of dysphagia for Parkinson disease (PD) patients undergoing cervical spine surgery for cervical myelopathy.

Summary of Background Data:
Cervical spondylotic myelopathy (CSM) is an increasingly common problem in the aging population. Several surgical options exist to treat this condition including anterior, posterior and combined surgical approaches. Each approach carries its own set of postoperative complications. Little is known of the of outcomes after cervical spine surgery in PD.

Materials and Methods:
The National Inpatient sample was queried 1998 to 2016, all elective admissions with CSM were identified. Surgical treatments were identified as either: anterior cervical discectomy and fusion (ACDF), posterior laminectomies, posterior cervical fusion or combined anterior/posterior surgery. Preexisting PD was identified. Endpoints included mortality, length of stay (LOS), swallowing dysfunction measured by placement of feeding tube (NGT), and postprocedure pneumonia.

Results:
A total of 73,088 patients underwent surgical procedures for CSM during the study period. Of those, 552 patients (7.5%) had concomitant PD. The most common procedure was ACDF. Patients with PD had a higher rate of dysphagia (NGT placement) after surgery compared with those without PD (P<0.001). Multiple regression analysis showed that PD patients had a higher risk of having NGT placement or developing pneumonia [odds ratio 2.98 (1.7-5.2), P<0.001] after surgery.
Patients with PD who underwent ACDF, posterior laminectomies or posterior cervical fusion had a longer LOS compared with those who did not have PD (P<0.001). There was no difference in LOS for patients who underwent combined anterior/posterior surgery. Inpatient mortality was higher in patients with PD who underwent ACDF or combined surgery (P<0.001).

Conclusions:
While ACDF is the most commonly performed procedure for CSM in patients with PD, it is associated with longer LOS, higher incidence of postoperative dysphagia, and postprocedural pneumonia, as well as higher inpatient mortality compared with posterior cervical procedures.

Level of Evidence:
Level III.
Propofol, Ketamine, and Etomidate as Induction Agents for Intubation and Outcomes in Critically Ill Patients: A Retrospective Cohort Study
Authors: Wan Chun , Hanson Andrew C. , Schulte Phillip J. , Dong Yue , Bauer Philippe R. 
Published: May 2021

IMPORTANCE:
Propofol, ketamine, and etomidate are common anesthetic agents for induction of anesthesia in the ICU. The choice between these agents is complex and may not depend solely upon severity of illness.

OBJECTIVES:
To evaluate the association between the administration of propofol, ketamine, and etomidate and ICU, hospital mortality, and length of stay.

DESIGN, SETTING, AND PARTICIPANTS:
Retrospective single-center cohort study. ICUs in a tertiary medical center, between January 01, 2012, and December 31, 2017. Critically ill adult patients given a single IV anesthetic for intubation.

MAIN OUTCOME AND MEASURES:
Primary outcomes were ICU and hospital mortality. Secondary outcomes were ICU- and hospital-free days through 28 days. An inverse probability of treatment weighed approach was used. The propensity score was estimated using a generalized logit model as a function of patient characteristics, admission source, ICU type, readmission status, length of ICU stays prior to intubation, and acute physiology score. Mortality outcomes were assessed with weighted logistic regression and -free days assessed by weighted linear regression with Bonferroni correction for pairwise comparisons.

RESULTS:
Of 2,673 patients, 36% received propofol, 30% ketamine and 34% etomidate. Overall ICU and hospital mortality were 19% and 29%, respectively. Patients given ketamine had higher odds of ICU mortality (1.45; [95% CI, 1.07–1.94]; p = 0.015) and patients given etomidate had higher odds of ICU mortality (1.87; 1.40–2.49; p < 0.001), hospital mortality (1.43; 1.09–1.86; p = 0.009), and less ICU-free days (–2.10; –3.21 to –1.00; p < 0.001) than those given propofol. Patients given ketamine and etomidate had similar odds of hospital mortality (1.06; 0.80–1.42; p = 0.761) and similar hospital-free days (0.30; –0.81 to 1.40; p = 0.600).

CONCLUSIONS AND RELEVANCE:
Compared with ketamine and etomidate, propofol was associated with better outcome in critically ill patients undergoing anesthesia for intubation. Even after adjusting for severity of illness prior to intubation, residual confounders cannot be excluded.
Clinical Impact of Oral Intake in Second-line or Third-line Chemotherapy for 589 Patients With Advanced Gastric Cancer
Authors: Ogata Takatsugu , Narita Yukiya , Kumanishi Ryosuke , Nakazawa Taiko , Matsubara Yuki , Kato Kyoko , Nozawa Kazuki , Honda Kazunori , Masuishi Toshiki , Bando Hideaki , Kadowaki Shigenori , Ando Masashi , Tajika Masahiro , Muro Kei 
Published: May 2021

Objectives:
Insufficient oral intake in advanced gastric cancer (AGC) limits the use of several drugs. We aimed to determine the oral intake status of patients with AGC during later-line chemotherapy.

Materials and Methods:
We retrospectively evaluated data of patients with AGC who experienced disease progression during first-line chemotherapy administered from January 2012 to December 2018 in a single institution. We defined “insufficient oral intake” as requiring daily intravenous fluids or hyperalimentation. Multivariate logistic regression was performed to identify oral intake-related factors.

Results:
Among 589 included patients, at disease progression during first-line, second-line, and third-line chemotherapy, 78.3% (461), 53.3% (314), and 30.4% (179) of patients, respectively, exhibited sufficient oral intake. Fourth-line chemotherapy was initiated for 22.2% (131) of patients, with 20.0% (118) exhibiting sufficient oral intake. During second-line and third-line chemotherapy, 11/67 (16%) and 2/39 (5%) patients, respectively, exhibited improvements in oral intake; 85/428 (19.9%) and 70/259 (27.0%), respectively, exhibited deteriorations in oral intake. Factors correlated to deterioration in oral intake during second-line chemotherapy were poor Eastern Cooperative Oncology Group Performance Status (odds ratio, 4.32; P<0.001), moderate or severe ascites (1.96; P=0.045), peritoneal metastasis (2.12; P=0.029), prior palliative surgery (3.41; P=0.003), and high neutrophil-to-lymphocyte ratio (3.09; P<0.001); those correlated to deterioration in oral intake during third-line chemotherapy were poorly differentiated pathology (2.52; P=0.025) and high neutrophil-to-lymphocyte ratio (2.65; P=0.006).

Conclusion:
As later-line chemotherapy is ineffective in improving oral intake in patients with AGC, careful adaptation of regimens is required for patients at risk for impaired oral intake.