bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid safety recommendations in adult palliative medicine: a North American Delphi expert consensus
Authors: Lau Jenny , Mazzotta Paolo , Whelan Ciara , Abdelaal Mohamed , Clarke Hance , Furlan Andrea D , Smith Andrew , Husain Amna , Fainsinger Robin , Hui David , Sunderji Nadiya , Zimmermann Camilla 
Published: August 2021

ObjectivesDespite the escalating public health emergency related to opioid-related deaths in Canada and the USA, opioids are essential for palliative care (PC) symptom management.Opioid safety is the prevention, identification and management of opioid-related harms. The Delphi technique was used to develop expert consensus recommendations about how to promote opioid safety in adults receiving PC in Canada and the USA.MethodsThrough a Delphi process comprised of two rounds, USA and Canadian panellists in PC, addiction and pain medicine developed expert consensus recommendations. Elected Canadian Society of Palliative Care Physicians (CSPCP) board members then rated how important it is for PC physicians to be aware of each consensus recommendation.They also identified high-priority research areas from the topics that did not achieve consensus in Round 2.ResultsThe panellists (Round 1, n=23; Round 2, n=22) developed a total of 130 recommendations from the two rounds about the following six opioid-safety related domains: (1) General principles; (2) Measures for healthcare institution and PC training and clinical programmes; (3) Patient and caregiver assessments; (4) Prescribing practices; (5) Monitoring; and (6) Patients and caregiver education. Fifty-nine topics did not achieve consensus and were deemed potential areas of research. From these results, CSPCP identified 43 high-priority recommendations and 8 high-priority research areas.ConclusionsUrgent guidance about opioid safety is needed to address the opioid crisis. These consensus recommendations can promote safer opioid use, while recognising the importance of these medications for PC symptom management.
RecombinantMycobacterium smegmatisdelivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model
Authors: Jeong Hyein , Lee So-Young , Seo Hyejun , Kim Bum-Joon 
Published: August 2021

BackgroundMacrophage migration inhibitory factor (MIF) is a pleotropic inflammatory cytokine that is overexpressed in a number of cancer types including most types of human cancer. Inhibition of MIF signaling can restore anticancer immune responses in tumor microenvironments. In this study, we aimed to develop a therapeutic vaccine capable of inhibiting tumor development by inducing anti-MIF immune responses.MethodsWe introduced a recombinantMycobacterium smegmatis(rSmeg-hMIF-hIL-7) vaccine that could deliver a fusion protein of human macrophage migration inhibitory factor (MIF) and interleukin 7, which could act as a target antigen and as an adjuvant of cancer vaccine, respectively. We checked the anticancer potential of the vaccine in a tumor-bearing mouse model.ResultsWe found that rSmeg-hMIF-hIL-7 showed enhanced oncolytic activity compared with PBS, BCG or Smeg in MC38-bearing mice, and there was an increase in the humoral and cell-mediated immune responses against MIF. rSmeg-hMIF-hIL-7 can also induce a neutralizing effect regarding MIF tautomerase activity in the serum of vaccinated mice. We also found downregulation of MIF, CD74, and CD44, which are related to the MIF signaling pathway and PI3K/Akt and MMP2/9 signaling, which are regulated by MIF in the tumor tissue of rSmeg-hMIF-hIL-7-vaccinated mice, suggesting a significant role of the anti-MIF immune response to rSmeg-hMIF-hIL-7 in its anticancer effect. In addition, rSmeg-hMIF-hIL-7 treatment led to enhanced activation of CD4+and CD8+T cells in the tumor regions of vaccinated mice, also contributing to the anticancer effect. This trend was also found in LLC-bearing and PanO2-bearing mouse models. In addition, rSmeg-hMIF-hIL-7 treatment exerted an enhanced anticancer effect with one of the immune checkpoint inhibitors, the anti-PD-L1 antibody, in a tumor-bearing mouse model.ConclusionsIn conclusion, our data showed that rSmeg-hMIF-hIL-7 exerts a strong antitumor immune response in mice, possibly by inhibiting the MIF-dependent promotion of tumorigenesis by the anti-MIF immune response and via enhanced cytotoxic T cell recruitment into tumor microenvironments. We also found that it also exerted an enhanced anticancer effect with immune checkpoint inhibitors. These results suggest that rSmeg-hMIF-hIL-7 is a potential adjuvant for cancer immunotherapy. This is the first report to prove anticancer potential of immunotherapeutic vaccine targeting immune response against MIF.
Implantable loop recorders in patients with heart disease: comparison between patients with and without syncope
Authors: Assaf Amira , Sakhi Rafi , Michels Michelle , Roos-Hesselink Jolien W , Verhagen Judith M A , Bhagwandien Rohit E , Szili-Torok Tamas , Theuns Dominic , Yap Sing-Chien 
Published: August 2021

ObjectivePatients with heart disease are at increased risk for sudden cardiac death. Guidelines recommend an implantable loop recorder (ILR) for symptomatic patients when symptoms are sporadic and possibly arrhythmia-related. In clinical practice, an ILR is mainly used in patients with unexplained syncope. We aimed to compare the clinical value of an ILR in patients with heart disease and a history of syncope versus those with non-syncopal symptoms.MethodsIn this observational single-centre study, we included symptomatic patients with heart disease who received an ILR. The primary endpoint was an actionable event which was defined as an arrhythmic event leading to a change in clinical management. The secondary endpoint was an event leading to device implantation.ResultsOne hundred and twenty patients (mean age 47±17 years, 49% men) were included. The underlying disease substrate was inherited cardiomyopathy (31%), congenital heart disease (28%), channelopathy (23%) and other (18%). Group A consisted of 43 patients with prior syncope and group B consisted of 77 patients with palpitations and/or near-syncope. The median follow-up duration was 19 months (IQR 8–36). The 3-year cumulative event rate was similar between groups with regard to the primary endpoint (38% vs 39% for group A and B, respectively, logrank p=0.54). There was also no difference in the 3-year cumulative rate of device implantation (21% vs 13% for group A and B, respectively, logrank p=0.65).ConclusionIn symptomatic patients with heart disease, there is no difference in the yield of an ILR in patients presenting with or without syncope.
When the balloon goes up, blood transfusion goes down: a pilot study of REBOA in placenta accreta spectrum disorders
Authors: Ioffe Yevgeniya J M , Burruss Sigrid , Yao Ruofan , Tse Beverly , Cryer Alicia , Mukherjee Kaushik , Hong Linda J 
Published: August 2021

BackgroundPatients with placenta accreta spectrum (PAS) disorders often suffer massive hemorrhage during cesarean hysterectomies (CHyst). A novel strategy to decrease blood loss and minimize perioperative morbidity associated with PAS is utilization of ER-REBOA Catheter intraoperatively. In this study, we explore the use of ER-REBOA Catheter during CHyst with the goal of minimizing perioperative morbidity and packed red blood cell (PRBC) transfusions.MethodsWe conducted a retrospective case–control study at a regional referral center of consecutive patients with PAS undergoing CHyst. The primary outcomes were PRBC transfusions of ≥4 units. Secondary outcomes included surgical intensive care unit admissions, postoperative length of stay (LOS), postoperative ileus, and vascular complication rate. We also explored utilization of manual palpation and omission of precesarean fluoroscopy for resuscitative endovascular balloon occlusion of the aorta (REBOA) placement verification in distal aortic zone 3.Results90 patients were included in the study. REBOA and non-REBOA cases were similar in clinicodemographic characteristics. 17.7% of REBOA cases received ≥4 units of PRBC compared with 49.3% of non-REBOA cases (p=0.03). Zero REBOA patients developed postoperative ileus, whereas 18 (25%) non-REBOA patients did (p=0.02). LOS was reduced in the REBOA group. Postplacement fluoroscopy was omitted in all REBOA cases. Two postoperative arterial thrombotic events (2 of 19, 11% of REBOA patients) were identified in the REBOA group, one requiring a thrombectomy (1 of 19, 5%).DiscussionDecrease in blood transfusions of ≥4 units of PRBC is demonstrated when ER-REBOA Catheter is placed in distal aortic zone 3 during CHyst performed for severe PAS disorders. The incidence of postoperative ileus and LOS are reduced in the ER-REBOA Catheter group. Placement and utilization of ER-REBOA Catheter during CHyst may be feasible without fluoroscopy when manual placement verification is performed by an experienced operator. Protocol modifications focusing on reducing thrombotic rate are ongoing.Level of evidenceIV.
Characterizing entanglement and measurement’s uncertainty in neutrino oscillations
Authors: Li Li-Juan , Ming Fei , Song Xue-Ke , Ye Liu , Wang Dong 
Published: August 2021

AbstractSince neutrino oscillations (NOs) show nonclassical features with the Leggett–Garg inequality and exhibit potential applications in quantum information processing and telecommunications, in order to further reveal quantum properties of the NO systems, we herein focus on investigating entanglement and entropic uncertainty relation in the context of three-flavor NOs. Specifically, we take advantage of three different types of entanglement measures to characterize quantum resources originating from NO systems, and examine the hierarchical relationship among them. Moreover, we analyze the experiment data from different neutrino sources including Daya Bay (0.5 and 1.6 km) and MINOS+ (735 km) collaborations in comparison with our theoretical results. We find that the dynamical evolution of both the entropic uncertainty and entanglement of system shows non-monotonicity, and the experimental results coincide with our theoretical prediction very well. Interestingly, it shows that neutrinos always maintain quantum properties during oscillation process. More importantly, we reveal that the variation of the uncertainty is almost anti-correlated with that of the entanglement of system. Therefore, the nature of entanglement and uncertainty in NOs can be explored in the practical experiment when the three-flavor neutrino states are treated as three-qubit ones, which might be useful for the potential NO-based applications on prospective quantum information processing.
Particle identification at FCC-ee
Authors: Wilkinson Guy 
Published: August 2021

AbstractEquipping an experiment at FCC-ee with particle identification (PID) capabilities, in particular the ability to distinguish between hadron species, would bring great benefits to the physics programme. Good PID is essential for precise studies in quark flavour physics and is also a great asset for many measurements in tau, top, and Higgs physics. The requirements placed by flavour physics and these other applications are surveyed, with an emphasis on the momentum range over which PID is necessary. Possible solutions are discussed, including classical RICH counters, time-of-flight systems, and dE/dx and cluster counting. Attention is paid to the impact on the global detector design that including PID capabilities would imply.
Heavy-quark opportunities and challenges at FCC-ee
Authors: Monteil Stéphane , Wilkinson Guy 
Published: August 2021

AbstractThe abundant production of beauty and charm hadrons in the $$5 \times 10^{12}$$

5
×

10
12

$$Z^0$$

Z
0

decays expected at FCC-ee offers outstanding opportunities in flavour physics that in general exceed those available at Belle II and are complementary to the heavy-flavour programme of the LHC. A wide range of measurements will be possible in heavy-flavour spectroscopy, rare decays of heavy-flavoured particles and $$C\!P$$

C

P

-violation studies, which will benefit from the low-background experimental environment, the high Lorentz boost and the availability of the full spectrum of hadron species. This essay first surveys the important questions in heavy-flavour physics and assesses the likely theoretical and experimental landscape at the turn-on of FCC-ee. From this certain, measurements are identified where the impact of FCC-ee will be particularly important. A full exploitation of the heavy-flavour potential of FCC-ee places specific constraints and challenges on detector design, which in some cases are in tension with those imposed by the other physics goals of the facility. These requirements and conflicts are discussed.
Development and Validation of Industry 4.0 Readiness Scale — A Formative Model
Authors: Hajoary Pinosh Kumar 
Published: August 2021

The purpose of this paper is to develop a suitable formative scale for Industry 4.0 readiness assessment and validate in the Indian steel manufacturing sector. For this, a literature review was undertaken to identify the relevant dimensions and items to assess the Industry 4.0 readiness at micro-level. Further, a pilot study and content validity were undertaken with experts from the industry and academia to find out the relevance of the dimensions and their items. The index thus developed was administered among top-level managers from steel manufacturing organizations and the data was analyzed using PLS-SEM. The findings revealed the most important parameters — strategy & organization; business model; manufacturing & operations; supply chain; products & services along with 21 indicators to be significant in all cases to assess Industry 4.0 readiness.
A Universal Positioning System for Coupling Characterization of SEM and AFM
Authors: Liu Jinchao , Wang Andi , Yang Ji , Yin Shiheng , Yang Xianfeng 
Published: August 2021

Hyphenated techniques, providing comprehensive information in various aspects such as constituent, structure, functional group, and morphology, play an important role in scientific research. Nowadays, coupling characterization of the same position in microscale is in great need in the field of nanomaterial research and exploration. In this article, a new hyphenated technique was developed to facilitate the coupling characterization of atomic force microscope (AFM) and scanning electron microscope (SEM) by designing a universal positioning system. The system consisted of a specimen holder with coordinate grids and a software for converting the coordinate values of the same point to fit SEM, specimen holder, and AFM system. In working condition, the coordinates of the labeled points and target position were firstly extracted from the SEM operation software, then converted into the numerical values adapted to the specimen holder itself, and finally transformed into the coordinates matching the AFM system. The experimental result showed that a retrieving rate of 96% was achieved for a spherical target with a diameter of 1 μm in a

30

μ
m
×
30

μ
m

square. The hyphenated technique is a universal, accurate, efficient, and financially feasible method in microanalysis field and has great application potential.
Correlation between Imaging Morphological Findings and Laboratory Biomarkers in Patients with Diabetic Macular Edema
Authors: Dimitriou Eleni , Sergentanis Theodoros N. , Lambadiari Vaia , Theodossiadis George , Theodossiadis Panagiotis , Chatziralli Irini 
Published: August 2021

Purpose. To investigate the potential association between peripheral blood biomarkers and morphological characteristics of retinal imaging in patients with diabetic macular edema (DME). Methods. Participants in this cross-sectional study were 36 consecutive patients (36 eyes) with treatment-naïve DME, who underwent spectral domain-optical coherence tomography (SD-OCT), fundus photography, and fundus fluorescein angiography (FFA). In addition, peripheral blood samples were taken to evaluate full blood count and biochemical parameters. Correlation between imaging characteristics and laboratory parameters was examined. Results. Eyes with central subfield thickness greater than 405 μm presented significantly higher neutrophils/lymphocytes (

p
=
0.043

) and higher lipoprotein (a) compared to eyes with

CST
<
405

μ
m

(

p
=
0.003

). Presence of hyperreflective foci on SD-OCT was associated with significantly higher white blood cell count (

p
=
0.028

). Ellipsoid zone disruption was associated with significantly lower hematocrit (

p
=
0.012

), hemoglobin (

p
=
0.009

), and red blood cell count (

p
=
0.026

), as well as with higher lipoprotein (a) (

p
=
0.015

). Macular ischemia on FFA was associated with significantly higher monocytes (

p
=
0.027

) and monocytes/HDL (

p
=
0.019

). No significant associations were found between laboratory parameters and subretinal fluid, intraretinal fluid, exudates, cysts, disorganization of inner retinal layers, epiretinal membrane, and external limiting membrane condition. Conclusion. Specific imaging morphological characteristics were found to be associated with laboratory parameters in patients with DME. These findings may shed light on the pathophysiology of DME and its correlation with the development of specific clinical signs.
Biventricular Global Function Index Is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot
Authors: Alsaied Tarek , Geva Tal , Graf Julia A. , Sleeper Lynn A. , Marie Valente Anne 
Published: August 2021

Introduction:
Cardiac magnetic resonance (CMR) derived biventricular global function index (BVGFI) is a new CMR parameter that integrates biventricular volumes, mass, and function using clinically available CMR parameters. The associations of BVGFI with clinical outcomes in repaired tetralogy of Fallot are unknown.

Methods:
Patients with repaired tetralogy of Fallot who had a CMR before the occurrence of a composite outcome of death, resuscitated sudden death, or sustained ventricular tachycardia were studied. BVGFI was calculated as the average of right and left GFI. GFI was defined as (ventricular stroke volume×100)/(ventricular mean cavity volume + total ventricular myocardial volume). Ventricular mean cavity volume was defined as ([end-diastolic + end-systolic volume]/2). Cox multivariable regression analysis and classification and regression tree methodology were used.

Results:

Of the 736 eligible subjects (mean age at CMR 25.4±14.5 years), with a median follow-up of 28 months, 55 subjects (7.4%) reached the composite outcome (46 deaths and 9 sustained ventricular tachycardia). Independent associations with the composite outcome were as follows: BVGFI <37 (hazard ratio, 2.52;
P
=0.004), right ventricular end-systolic volume index >85 mL/m
2
(hazard ratio, 3.25;
P
<0.001), atrial tachycardia (hazard ratio, 2.03;
P
=0.021), and age at repair >2.5 years (hazard ratio, 3.37;
P
<0.001). Classification and regression tree analysis identified BVGFI as the most discriminatory CMR parameter associated with a high risk for adverse outcomes.

Conclusions:
BVGFI, a novel CMR-derived imaging biomarker combining biventricular volumes, mass, and function, may improve risk stratification for adverse clinical outcomes in patients with repaired tetralogy of Fallot.
miR‐133a Replacement Attenuates Thoracic Aortic Aneurysm in Mice
Authors: Akerman Adam W. , Collins Elizabeth N. , Peterson Andrew R. , Collins Lauren B. , Harrison Jessica K. , DeVaughn Amari , Townsend Jaleel M. , Vanbuskirk Rebecca L. , Riopedre‐Maqueira Jessica , Reyes Ailet , Oh Joyce E. , Raybuck Charles M. , Jones Jeffrey A. , Ikonomidis John S. 
Published: August 2021

Background
Thoracic aortic aneurysms (TAAs) occur because of abnormal remodeling of aortic extracellular matrix and are accompanied by the emergence of proteolytically active myofibroblasts. The microRNA miR‐133a regulates cellular phenotypes and is reduced in clinical TAA specimens. This study tested the hypothesis that miR‐133a modulates aortic fibroblast phenotype, and overexpression by lentivirus attenuates the development of TAA in a murine model.

Methods and Results
TAA was induced in mice. Copy number of miR‐133a was reduced in TAA tissue and linear regression analysis confirmed an inverse correlation between aortic diameter and miR‐133a. Analyses of phenotypic markers revealed an mRNA expression profile consistent with myofibroblasts in TAA tissue. Fibroblasts were isolated from the thoracic aortae of mice with/without TAA. When compared with controls, miR‐133a was reduced, migration was increased, adhesion was reduced, and the ability to contract a collagen disk was increased. Overexpression/knockdown of miR‐133a controlled these phenotypes. After TAA induction in mice, a single tail‐vein injection of either miR‐133a overexpression or scrambled sequence (control) lentivirus was performed. Overexpression of miR‐133a attenuated TAA development. The pro‐protein convertase furin was confirmed to be a target of miR‐133a by luciferase reporter assay. Furin was elevated in this murine model of TAA and repressed by miR‐133a replacement in vivo resulting in reduced proteolytic activation.

Conclusions
miR‐133a regulates aortic fibroblast phenotype and over‐expression prevented the development of TAA in a murine model. These findings suggest that stable alterations in aortic fibroblasts are associated with development of TAA and regulation by miR‐133a may lead to a novel therapeutic strategy.
Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH‐2
Authors: Miwa Kaori , Koga Masatoshi , Fukuda‐Doi Mayumi , Yamamoto Haruko , Tanaka Kanata , Yoshimura Sohei , Ihara Masafumi , Qureshi Adnan I. , Toyoda Kazunori 
Published: August 2021

Background
To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes.

Methods and Results
In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%.

Conclusions
Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH.

Registration

URL:
https://www.clinicaltrials.gov
; Unique Identiﬁer: NCT01176565.