bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of the first interstellar comet 2I/Borisov around perihelion: results from Indian observatories
Authors: Aravind K , Ganesh Shashikiran , Venkataramani Kumar , Sahu Devendra , Angchuk Dorje , Sivarani Thirupathi , Unni Athira
Published: January 2021

Comet 2I/Borisov is the first true interstellar comet discovered. Here, we present results from observational programs at two Indian observatories, 2 m Himalayan Chandra Telescope at the Indian Astronomical Observatory, Hanle (HCT) and 1.2 m telescope at the Mount Abu Infrared Observatory (MIRO). Two epochs of imaging and spectroscopy were carried out at the HCT and three epochs of imaging at MIRO. We found CN to be the dominant molecular emission on both epochs, 2019 November 30 and December 22, at distances of rH = 2.013 and 2.031 au, respectively. The comet was inferred to be relatively depleted in Carbon bearing molecules on the basis of low C2 and C3 abundances. We find the production rate ratio, Q(C2)/Q(CN) = 0.54 ± 0.18, pre-perihelion and Q(C2)/Q(CN) = 0.34 ± 0.12 post-perihelion. This classifies the comet as being moderately depleted in carbon chain molecules. Using the results from spectroscopic observations, we believe the comet to have a chemically heterogeneous surface having variation in abundance of carbon chain molecules. From imaging observations, we infer a dust-to-gas ratio similar to carbon chain depleted comets of the Solar system. We also compute the nucleus size to be in the range 0.18 km ≤ r ≤ 3.1 km. Our observations show that 2I/Borisov’s behaviour is analogous to that of the Solar system comets.
Giant molecular cloud catalogues for PHANGS-ALMA: methods and initial results
Authors: Rosolowsky Erik , Hughes Annie , Leroy Adam K , Sun Jiayi , Querejeta Miguel , Schruba Andreas , Usero Antonio , Herrera Cinthya N , Liu Daizhong , Pety Jérôme , Saito Toshiki , Bešlić Ivana , Bigiel Frank , Blanc Guillermo , Chevance Mélanie , Dale Daniel A , Deger Sinan , Faesi Christopher M , Glover Simon C O , Henshaw Jonathan D , Klessen Ralf S , Kruijssen J M Diederik , Larson Kirsten , Lee Janice , Meidt Sharon , Mok Angus , Schinnerer Eva , Thilker David A , Williams Thomas G
Published: January 2021

We present improved methods for segmenting CO emission from galaxies into individual molecular clouds, providing an update to the cprops algorithms presented by Rosolowsky & Leroy. The new code enables both homogenization of the noise and spatial resolution among data, which allows for rigorous comparative analysis. The code also models the completeness of the data via false source injection and includes an updated segmentation approach to better deal with blended emission. These improved algorithms are implemented in a publicly available Python package, pycprops. We apply these methods to 10 of the nearest galaxies in the PHANGS-ALMA survey, cataloguing CO emission at a common 90 pc resolution and a matched noise level. We measure the properties of 4986 individual clouds identified in these targets. We investigate the scaling relations among cloud properties and the cloud mass distributions in each galaxy. The physical properties of clouds vary among galaxies, both as a function of galactocentric radius and as a function of dynamical environment. Overall, the clouds in our target galaxies are well-described by approximate energy equipartition, although clouds in stellar bars and galaxy centres show elevated line widths and virial parameters. The mass distribution of clouds in spiral arms has a typical mass scale that is 2.5× larger than interarm clouds and spiral arms clouds show slightly lower median virial parameters compared to interarm clouds (1.2 versus 1.4).
The infancy of core-collapse supernova remnants
Authors: Gabler Michael , Wongwathanarat Annop , Janka Hans-Thomas
Published: January 2021

We present 3D hydrodynamic simulations of neutrino-driven supernovae (SNe) with the Prometheus-HotB code, evolving the asymmetrically expanding ejecta from shock breakout until they reach the homologous expansion phase after roughly one year. Our calculations continue the simulations for two red supergiant and two blue supergiant progenitors by Wongwathanarat et al., who investigated the growth of explosion asymmetries produced by hydrodynamic instabilities during the first second of the explosion and their later fragmentation by Rayleigh–Taylor instabilities. We focus on the late time acceleration and inflation of the ejecta caused by the heating due to the radioactive decay of 56Ni to 56Fe and by a new outward-moving shock, which forms when the reverse shock from the He/H-shell interface compresses the central part of the ejecta. The mean velocities of the iron-rich ejecta increase between 100 and 350 km s−1 (∼8–30 per cent), and the fastest 1 per cent of the iron accelerates by up to ∼1000 km s−1 (∼20–25 per cent). This ‘Ni-bubble effect’, known from 1D models, accelerates the bulk of the nickel in our 3D models and causes an inflation of the initially overdense Ni-rich clumps, which leads to underdense, extended fingers, enveloped by overdense skins of compressed surrounding matter. We also provide volume and surface filling factors as well as a spherical harmonics analysis to characterize the spectrum of Ni-clump sizes quantitatively. Three of our four models give volume filling factors larger than 0.3, consistent with what is suggested for SN 1987A by observations.
The MOSDEF survey: a comprehensive analysis of the rest-optical emission-line properties of z ∼ 2.3 star-forming galaxies
Authors: Runco Jordan N , Shapley Alice E , Sanders Ryan L , Topping Michael W , Kriek Mariska , Reddy Naveen A , Coil Alison L , Mobasher Bahram , Siana Brian , Freeman William R , Shivaei Irene , Azadi Mojegan , Price Sedona H , Leung Gene C K , Fetherolf Tara , de Groot Laura , Zick Tom , Fornasini Francesca M , Barro Guillermo
Published: January 2021

We analyse the rest-optical emission-line spectra of z ∼ 2.3 star-forming galaxies in the complete MOSFIRE Deep Evolution Field (MOSDEF) survey. In investigating the origin of the well-known offset between the sequences of high-redshift and local galaxies in the [O iii]λ5008/Hβ versus [N ii]λ6585/Hα (‘[N ii] BPT’) diagram, we define two populations of z ∼ 2.3 MOSDEF galaxies. These include the high population that is offset towards higher [O iii]λ5008/Hβ and/or [N ii]λ6585/Hα with respect to the local SDSS sequence and the low population that overlaps the SDSS sequence. These two groups are also segregated within the [O  iii]λ5008/Hβ versus [S ii]λλ6718,6733/Hα and the [O iii]λλ4960,5008/[O ii ]λλ3727,3730 (O32) versus ([O  iii]λλ4960,5008+[O ii]λλ3727,3730)/Hβ (R23) diagrams, which suggests qualitatively that star-forming regions in the more offset galaxies are characterized by harder ionizing spectra at fixed nebular oxygen abundance. We also investigate many galaxy properties of the split sample and find that the high sample is on average smaller in size and less massive, but has higher specific star formation rate (SFR) and SFR surface density values and is slightly younger compared to the low population. From Cloudy+BPASS photoionization models, we estimate that the high population has a lower stellar metallicity (i.e. harder ionizing spectrum) but slightly higher nebular metallicity and higher ionization parameter compared to the low population. While the high population is more α-enhanced (i.e. higher α/Fe) than the low population, both samples are significantly more α-enhanced compared to local star-forming galaxies with similar rest-optical line ratios. These differences must be accounted for in all high-redshift star-forming galaxies – not only those ‘offset’ from local excitation sequences.
Adaptive modelling of variably saturated seepage problems
Authors: Ashby B , Bortolozo C , Lukyanov A , Pryer T
Published: January 2021

In this article, we present a goal-oriented adaptive finite element method for a class of subsurface flow problems in porous media, which exhibit seepage faces. We focus on a representative case of the steady state flows governed by a nonlinear Darcy–Buckingham law with physical constraints on subsurface-atmosphere boundaries. This leads to the formulation of the problem as a variational inequality. The solutions to this problem are investigated using an adaptive finite element method based on a dual-weighted a posteriori error estimate, derived with the aim of reducing error in a specific target quantity. The quantity of interest is chosen as volumetric water flux across the seepage face, and therefore depends on an a priori unknown free boundary. We apply our method to challenging numerical examples as well as specific case studies, from which this research originates, illustrating the major difficulties that arise in practical situations. We summarise extensive numerical results that clearly demonstrate the designed method produces rapid error reduction measured against the number of degrees of freedom.
The effect of chronic intermittent hypoxia in cardiovascular gene expression is modulated by age in a mice model of sleep apnea
Authors: Castro-Grattoni Anabel L , Suarez-Giron Monique , Benitez Ivan , Tecchia Lourdes , Torres Marta , Almendros Isaac , Farre Ramon , Targa Adriano , Montserrat Josep M , Dalmases Mireia , Barbé Ferran , Gozal David , Sánchez-de-la-Torre Manuel
Published: January 2021

Study Objectives

Chronic intermittent hypoxia (CIH) is a major determinant in obstructive sleep apnea cardiovascular morbidity and this effect is influenced by age. The objective of the present study was to assess the differential molecular mechanisms at gene-level expression involved in the cardiovascular remodeling induced by CIH according to chronological age.

Methods

Two- and 18-month-old mice (N = 8 each) were subjected to CIH or normoxia for 8 weeks. Total messenger RNA (mRNA) was extracted from left ventricle myocardium and aortic arch, and gene expression of 46 intermediaries of aging, oxidative stress, and inflammation was measured by quantitative real-time polymerase chain reaction.

Results

Cardiac gene expression of Nrf2 (2.05-fold increase, p < 0.001), Sod2 (1.9-fold increase, p = 0.035), Igf1r (1.4-fold increase, p = 0.028), Mtor (1.8-fold increase, p = 0.06), Foxo3 (1.5-fold increase, p = 0.020), Sirt4, Sirt6, and Sirt7 (1.3-fold increase, p = 0.012; 1.1-fold change, p = 0.031; 1.3-fold change, p = 0.029) was increased after CIH in young mice, but not in old mice. In aortic tissue, endothelial isoform of nitric oxide synthase was reduced in young mice (p < 0.001), Nrf2 was reduced in 80% (p < 0.001) in young mice and 45% (p = 0.07) in old mice, as its downstream antioxidant target Sod2 (82% reduced, p < 0.001). IL33

Conclusions

CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a proaging process.
Intravenous versus Volatile Anesthetic Effects on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Abdominal Surgery
Authors: Li Yujuan , Chen Dongtai , Wang Hanbing , Wang Zhi , Song Furong , Li Hui , Ling Li , Shen Zhiwen , Hu Chuwen , Peng Jun , Li Weixing , Xing Wei , Pan Jiahao , Liang Hua , Zhou Qiaoling , Cai Jun , He Ziqing , Peng Shuling , Zeng Weian , Zuo Zhiyi
Published: January 2021

Background

Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur.

Methods

A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery.

Results

A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups.

Conclusions

Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery.

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Greater Fibrinolysis Resistance but No Greater Platelet Aggregation in Critically Ill COVID-19 Patients
Authors: Heinz Christoph , Miesbach Wolfgang , Herrmann Eva , Sonntagbauer Michael , Raimann Florian J. , Zacharowski Kai , Weber Christian F. , Adam Elisabeth H.
Published: January 2021

Background

The hemostatic balance in patients with coronavirus disease 2019 (COVID-19) seems to be shifted toward a hypercoagulable state. The aim of the current study was to assess the associated coagulation alterations by point-of-care-diagnostics, focusing on details of clot formation and lysis in these severely affected patients.

Methods

The authors’ prospective monocentric observational study included critically ill patients diagnosed with COVID-19. Demographics and biochemical data were recorded. To assess the comprehensive hemostatic profile of this patient population, aggregometric (Multiplate) and viscoelastometric (CloPro) measures were performed in the intensive care unit of a university hospital at a single occasion. Coagulation analysis and assessment of coagulation factors were performed. Data were compared to healthy controls.

Results

In total, 27 patients (21 male; mean age, 60 yr) were included. Impedance aggregometry displayed no greater platelet aggregability in COVID-19 in comparison with healthy controls (area under the curve [AUC] in adenosine diphosphate test, 68 ± 37 U vs. 91 ± 29 U [−27 (Hodges–Lehmann 95% CI, −48 to −1); P = 0.043]; AUC in arachidonic acid test, 102 ± 54 U vs. 115 ± 26 U [−21 (Hodges–Lehmann 95% CI, −51 to 21); P = 0.374]; AUC in thrombin receptor activating peptide 6 test, 114 ± 61 U vs. 144 ± 31 U [−31 (Hodges–Lehmann 95% CI, −69 to −7); P = 0.113]). Comparing the thromboelastometric results of COVID-19 patients to healthy controls, the authors observed significant differences in maximum clot firmness in fibrin contribution to maximum clot firmness assay (37 ± 11 mm vs. 15 ± 4 mm [21 (Hodges–Lehmann 95% CI, 17 to 26); P < 0.001]) and lysis time in extrinsic activation and activation of fibrinolysis by tissue plasminogen activator assay (530 ± 327 s vs. 211 ± 80 s [238 (Hodges–Lehmann 95% CI, 160 to 326); P < 0.001]).

Conclusions

Thromboelastometry in COVID-19 patients revealed greater fibrinolysis resistance. The authors did not find a greater platelet aggregability based on impedance aggregometric tests. These findings may contribute to our understanding of the hypercoagulable state of critically ill patients with COVID-19.

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Association of Persistent Breech Presentation With External Cephalic Version Success
Authors: Lauterbach Roy , Bachar Gal , Ben-David Chen , Matanes Emad , Ginsberg Yuval , Beloosesky Ron , Ganem Nadir , Weiner Zeev , Zipori Yaniv
Published: January 2021

OBJECTIVE:

To evaluate a possible correlation between a new variable—persistent breech presentation—and the success rate of external cephalic version (ECV).

METHODS:

This was a retrospective study of ECVs performed from January 2008 through January 2019 in an Israeli tertiary care hospital. The study group included all pregnant women who underwent an ECV at or beyond 37 weeks of gestation. Persistent breech presentation was defined as persistent breech presentation during all ultrasound examinations performed between the anatomy scan at mid-pregnancy and the gestational week when ECV was attempted. Women in whom cephalic presentation was documented at least once on these ultrasound examinations were defined as not having persistent breech presentation. The primary outcome was defined as the success rate of ECV, and the secondary outcome was defined as the mode of delivery after a successful ECV.

RESULTS:

We identified 1,271 women with breech presentation during the study period. They had undergone median of five (range 2–7) ultrasound examinations. External cephalic version was attempted in 684 women (53.8%), with a success rate of 61.5%. External cephalic version succeeded in 19.6% of those with persistent breech presentation (44/224) compared with 82.0% (377/460) of those without persistent breech presentation (P<.001). Ultimately, women with persistent breech presentation and successful ECV experienced a lower rate of vaginal delivery (27.3% vs 79%, P<.001), and a higher rate of instrumental (29% vs 13%, P<.001) and cesarean deliveries (43% vs 7%, P<.001) compared with the nonpersistent breech presentation group. The rate of noninstrumental vaginal delivery among women with persistent breech presentation, regardless of ECV, was 5.4%.

CONCLUSION:

Women with persistent breech presentation experienced a high rate of ECV failure and a low rate of spontaneous vaginal delivery.
Correlation of Respiratory Physiologic Parameters in Mechanically Ventilated Coronavirus Disease 2019 Patients
Authors: Saha Biplab K. , Ghalib Sana , Chieng Hau , Pezzano Chad , Lydon Darren , Feustel Paul , Smith Thomas C. , Chopra Amit
Published: January 2021

Acute respiratory distress syndrome secondary to severe acute respiratory syndrome coronavirus-2 pneumonia or coronavirus disease 2019-related acute respiratory distress syndrome is the primary cause of mortality in coronavirus disease 2019. Some studies have described the concept of “high and low” elastance coronavirus disease 2019-related acute respiratory distress syndrome and proposed individualized management for the acute respiratory distress syndrome, deviating from low tidal volume ventilation. We report simultaneously measured respiratory parameters (static lung compliance, alveolar dead space ventilation, and shunt fraction) in 14 patients with advanced coronavirus disease 2019-related acute respiratory distress syndrome. The results were consistent with typical acute respiratory distress syndrome and did not support the concept of high-type coronavirus disease 2019-related acute respiratory distress syndrome and low-type coronavirus disease 2019-related acute respiratory distress syndrome.
Evaluation of Hypertriglyceridemia in Critically Ill Patients With Coronavirus Disease 2019 Receiving Propofol
Authors: Kovacevic Mary P. , Dube Kevin M. , Lupi Kenneth E. , Szumita Paul M. , DeGrado Jeremy R.
Published: January 2021

Objectives:

To report the prevalence of, and evaluate risk factors for, the development of hypertriglyceridemia (defined as a serum triglyceride level of > 400 mg/dL) in patients with coronavirus disease 2019 who received propofol.

Design:

Single-center, retrospective, observational analysis.

Setting:

Brigham and Women’s Hospital, a tertiary academic medical center in Boston, MA.

Patients:

All ICU patients who with coronavirus disease 19 who received propofol between March 1, 2020, and April 20, 2020.

Interventions:

None.

Measurements and Main Results:

The major outcome of this analysis was to report the prevalence of, and risk factors for, the development of hypertriglyceridemia in patients with coronavirus disease 19 who received propofol. Minor outcomes included the development of acute pancreatitis and description of propofol metrics. Of the 106 patients that were included, 60 (56.6%) developed hypertriglyceridemia, with a median time to development of 46 hours. A total of five patients had clinical suspicion of acute pancreatitis, with one patient having confirmatory imaging. There was no difference in the dose or duration of propofol in patients who developed hypertriglyceridemia compared with those who did not. In the patients who developed hypertriglyceridemia, 35 patients (58.5%) continued receiving propofol for a median duration of 105 hours. Patients who developed hypertriglyceridemia had elevated levels of inflammatory markers.

Conclusions:

Hypertriglyceridemia was commonly observed in critically ill patients with coronavirus disease 2019 who received propofol. Neither the cumulative dose nor duration of propofol were identified as a risk factor for the development of hypertriglyceridemia. Due to the incidence of hypertriglyceridemia in this patient population, monitoring of serum triglyceride levels should be done frequently in patients who require more than 24 hours of propofol. Many patients who developed hypertriglyceridemia were able to continue propofol in our analysis after reducing the dose.
Autism-Focused Online Training in Shared Decision-Making: A Randomized Controlled Trial
Authors: Huffman Lynne C. , Hubner Lauren M. , Hansen Robin L.
Published: January 2021

Objective:

This medical education quasi-randomized controlled trial (quasi-RCT), involving 97 developmental-behavioral pediatrics fellows across the United States, examined differential effects of 2 autism-focused, online, interactive case-based trainings on shared decision-making (SDM).

Methods:

An intervention case provided direct teaching about SDM, addressing autism treatment options. A comparison case focused on evidence-based practice (EBP) related to medication use in autism with no specific SDM teaching. Measured outcomes included self-reported SDM and attitudes toward concordance in medication-prescribing.

Results:

After the intervention, both groups showed significantly increased SDM, but not medication-prescribing concordance (controlling for trainee level, autism patient numbers, and past SDM training).

Conclusion:

This quasi-RCT presents evidence that knowledge of SDM in care of children with autism can be enhanced by online case-based training focused either indirectly on evidence-based practice or directly on SDM. Consistent online SDM training can be provided to all trainees, irrespective of the location.
The effect of moderate intraoperative blood loss and norepinephrine therapy on sublingual microcirculatory perfusion in patients having open radical prostatectomy
Authors: Flick Moritz , Briesenick Luisa , Peine Sven , Scheeren Thomas W.L. , Duranteau Jacques , Saugel Bernd
Published: January 2021

BACKGROUND

It is not clear whether moderate intraoperative blood loss and norepinephrine used to restore the macrocirculation impair the microcirculation and affect microcirculation/macrocirculation coherence.

OBJECTIVE

We sought to investigate the effect of moderate intraoperative blood loss and norepinephrine therapy administered to treat intraoperative hypotension on the sublingual microcirculation.

DESIGN

Prospective observational study.

SETTING

University Medical Center Hamburg-Eppendorf, Hamburg, Germany, from November 2018 to March 2019.

PATIENTS

Thirty patients scheduled for open radical prostatectomy and 29 healthy volunteer blood donors.

INTERVENTION

Simultaneous assessment of the macrocirculation using a noninvasive finger-cuff method and the sublingual microcirculation using vital microscopy.

MAIN OUTCOME MEASURES

The main outcome measures were changes in the sublingual microcirculation caused by moderate intraoperative blood loss and norepinephrine therapy.

RESULTS

General anaesthesia decreased median [IQR] mean arterial pressure from 100 [90 to 104] to 79 [69 to 87] mmHg (P < 0.001), median heart rate from 69 [63 to 79] to 53 [44 to 62] beats per minute (P < 0.001), median cardiac index from 2.67 [2.42 to 3.17] to 2.09 [1.74 to 2.49] l min−1 m−2 (P < 0.001), and median microvascular flow index from 2.75 [2.66 to 2.85] to 2.50 [2.35 to 2.63] (P = 0.001). A median blood loss of 600 [438 to 913] ml until the time of prostate removal and norepinephrine therapy to treat intraoperative hypotension had no detrimental effect on the sublingual microcirculation: There were no clinically important changes in the microvascular flow index, the proportion of perfused vessels, the total vessel density, and the perfused vessel density. Blood donation resulted in no clinically important changes in any of the macrocirculatory or microcirculatory variables.

CONCLUSION

Moderate intraoperative blood loss and norepinephrine therapy administered to treat intraoperative hypotension have no detrimental effect on the sublingual microcirculation and the coherence between the macrocirculation and microcirculation in patients having open radical prostatectomy.
Patient-specific Extravasation Dosimetry Using Uptake Probe Measurements
Authors: Osborne Dustin , Kiser Jackson W. , Knowland Josh , Townsend David , Fisher Darrell R.
Published: January 2021

Extravasation is a common problem in radiopharmaceutical administration and can result in significant radiation dose to underlying tissue and skin. The resulting radiation effects are rarely studied and should be more fully evaluated to guide patient care and meet regulatory obligations. The purpose of this work was to show that a dedicated radiopharmaceutical injection monitoring system can help clinicians characterize extravasations for calculating tissue and skin doses. We employed a commercially available radiopharmaceutical injection monitoring system to identify suspected extravasation of 18F-fluorodeoxyglucose and 99mTc-methylene diphosphonate in 26 patients and to characterize their rates of biological clearance. We calculated the self-dose to infiltrated tissue using Monte Carlo simulation and standard MIRD dosimetry methods, and we used VARSKIN software to calculate the shallow dose equivalent to the epithelial basal-cell layer of overlying skin. For 26 patients, injection-site count rate data were used to characterize extravasation clearance. For each, the absorbed dose was calculated using representative tissue geometries. Resulting tissue-absorbed doses ranged from 0.6 to 11.2 Gy, and the shallow dose equivalent to a 10 cm2 area of adjacent skin in these patients ranged from about 0.1 to 5.4 Sv. Extravasated injections of radiopharmaceuticals can result in unintentional doses that exceed well-established radiation protection and regulatory limits; they should be identified and characterized. An external injection monitoring system may help to promptly identify and characterize extravasations and improve dosimetry calculations. Patient-specific characterization can help clinicians determine extravasation severity and whether the patient should be followed for adverse tissue reactions that may present later in time.
Preliminary Experiences with the Rexon UL-320-FDR: An Automated Thermoluminescent Dosimeter Reader with Removable Contact Heating Planchets and an Infrared Temperature Feedback System
Authors: Kuchta John R. , Thiesen Jack H. , Noey Jordan D. , Chung Long Kiu , Kearfott Kimberlee J.
Published: January 2021

The Rexon UL-320 FDR is a novel resistive-heating thermoluminescent dosimeter reader with a unique temperature measurement system and an automated dosimeter processing mechanism. The removable contact heating planchets have black-body adhesives on the back for capturing temperature information with infrared sensors. A heating cycle feedback loop ensures accurate, precise, and reproducible heating sequences. Heating rates between 0.8 and 40°C s−1 for up to 1,000 s are possible. Photomultiplier tube sensitivity and drift, dark current counts, and planchet glow were measured experimentally. Additionally, 25 LiF:Mg,Ti dosimeters were calibrated to demonstrate reader performance. Sensitivity was optimized at 1,200 V, which produced the highest reference light count to dark current count ratio while extending photomultiplier tube life. Dark current counts measured with typical time-temperature profiles for LiF:Mg,Ti were below 10 counts per channel but increased by up to 2.5% for more extreme heating cycles. Reader sensitivity drifts of up to 10% were observed during extended automated operations with typical time-temperature profiles. Total counts resulting from planchet glow decreased with faster heating rates. Calibrations performed with LiF:Mg,Ti dosimeters yielded results comparable to more established reader designs. Spikes were observed in ~3% of the glow curves from planchet dust and oil burning off at elevated temperatures. The use of N2 gas and sensitivity drift corrections are recommended to improve dosimetry performance for the UL-320 FDR reader.
Bone Mineral Density Evolution and Its Determinants in Long-term Survivors of Childhood Acute Leukemia
Authors: Tabone Marie-Dominique , Kolta Sami , Auquier Pascal , Vercasson Camille , Chastagner Pascal , Kanold Justyna , Rohrlich Pierre-Simon , Bertrand Yves , Baruchel André , Plantaz Dominique , Gandemer Virginie , Ducassou Stéphane , Petit Arnaud , Paillard Catherine , Leverger Guy , Dalle Jean-Hugues , Berbis Julie , Roux Christian , Michel Gérard
Published: January 2021

This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10−3). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score <−2 at the lumbar spine and 4.3% at the femoral neck level. Gender, type of leukemia, transplantation, relapse, cumulative corticosteroid doses, or growth hormone deficiency did not have any significant impact on z-score variation. Younger age at diagnosis (≤8.5 years) proved an unfavorable risk factor for z-score evolution at the lumbar spine (P = 0.041); the trend did not reach statistical significance for metabolic syndrome (P = 0.054). At the femoral neck, both were associated with unfavorable z-score evolution (P = 0.003 and 0.025, respectively). Patients treated at a younger age and those with metabolic syndrome seem to be at higher risk of bone mineral density decline and should benefit from specific interventions.
A genome-wide screen reveals microRNAs in peripheral sensory neurons driving painful diabetic neuropathy
Authors: Bali Kiran Kumar , Gandla Jagadeesh , Rangel Daniel Rojas , Castaldi Laura , Mouritzen Peter , Agarwal Nitin , Schmelz Martin , Heppenstall Paul , Kuner Rohini
Published: January 2021

Diabetes is a leading cause of peripheral neuropathy (diabetic peripheral neuropathy, DPN), and uncontrolled long-lasting hyperglycemia leads to severe complications. A major proportion of diabetics develop excruciating pain with a variable course. Mechanisms leading to painful DPN are not completely understood and treatment options limited. We hypothesized that epigenetic modulation at the level of microRNA (miRNA) expression triggered by metabolic imbalance and nerve damage regulates the course of pain development. We used clinically relevant preclinical models, genome-wide screening, in silico analyses, cellular assays, miRNA fluorescent in situ hybridization, in vivo molecular manipulations, and behavioral analyses in the current study. We identified miRNAs and their targets that critically impact on nociceptive hypersensitivity in painful DPN. Our analyses identify miR-33 and miR-380 expressed in nociceptive neurons as critical denominators of diabetic pain and miR-124-1 as a mediator of physiological nociception. Our comprehensive analyses on the putative mRNA targets for miR-33 or miR-124-1 identified a set of mRNAs that are regulated after miR-33 or miR-124-1 overexpression in dorsal root ganglia in vivo. Our results shed light on the regulation of DPN pathophysiology and implicate specific miRNAs as novel therapeutic targets for treating painful DPN.
A peptide encoded within a 5′ untranslated region promotes pain sensitization in mice
Authors: Barragan-Iglesias Paulino , Kunder Nikesh , Wanghzou Andi , Black Bryan , Ray Pradipta R. , Lou Tzu-Fang , Bryan de la Peña June , Atmaramani Rahul , Shukla Tarjani , Pancrazio Joseph J. , Price Theodore J. , Campbell Zachary T.
Published: January 2021

Translational regulation permeates neuronal function. Nociceptors are sensory neurons responsible for the detection of harmful stimuli. Changes in their activity, termed plasticity, are intimately linked to the persistence of pain. Although inhibitors of protein synthesis robustly attenuate pain-associated behavior, the underlying targets that support plasticity are largely unknown. Here, we examine the contribution of protein synthesis in regions of RNA annotated as noncoding. Based on analyses of previously reported ribosome profiling data, we provide evidence for widespread translation in noncoding transcripts and regulatory regions of mRNAs. We identify an increase in ribosome occupancy in the 5′ untranslated regions of the calcitonin gene-related peptide (CGRP/Calca). We validate the existence of an upstream open reading frame (uORF) using a series of reporter assays. Fusion of the uORF to a luciferase reporter revealed active translation in dorsal root ganglion neurons after nucleofection. Injection of the peptide corresponding to the calcitonin gene-related peptide–encoded uORF resulted in pain-associated behavioral responses in vivo and nociceptor sensitization in vitro. An inhibitor of heterotrimeric G protein signaling blocks both effects. Collectively, the data suggest pervasive translation in regions of the transcriptome annotated as noncoding in dorsal root ganglion neurons and identify a specific uORF-encoded peptide that promotes pain sensitization through GPCR signaling.
Disease Burden and Treatment Patterns Associated With Eosinophilic Esophagitis in the United States
Authors: Lu Mei , Goodwin Bridgett , Vera-Llonch Montserrat , Williams James
Published: January 2021

Goals:

This US-based, retrospective claims study aimed to investigate disease burden and treatment patterns in patients with eosinophilic esophagitis (EoE), and to compare health care resource use (HCRU) in patients with EoE and matched controls without EoE.

Materials and Methods:

Patients with a diagnosis of EoE and ≥12 months of prediagnosis data were identified from the Truven Health MarketScan Research databases (January 2008 to September 2016) and followed up from the diagnosis date until termination of eligibility for a health plan. Patient clinical characteristics and HCRU were recorded in the 12 months before diagnosis; HCRU and treatment patterns were recorded during follow-up. HCRU in patients with EoE and matched controls was compared during the 12-month postdiagnosis period.

Results:

Among the 23,003 patients with EoE (mean age: 34.3 y; 64.8% male), gastroesophageal reflux disease was the most common prediagnosis condition (34.6%). After diagnosis, the most common off-label, first-line treatments were proton pump inhibitor monotherapy (52.8%) and topical corticosteroid monotherapy (21.5%). Overall, 3336 patients (14.5%) received at least 3 lines of off-label pharmacotherapy. Outpatient visits (recorded in 99.9% of patients on and postdiagnosis) were most frequently to gastroenterologists/pediatric gastroenterologists (49.5% prediagnosis, 72.6% on and postdiagnosis). Inpatient admissions and outpatient and emergency room visits were more likely in patients with EoE than in matched controls (P<0.0001).

Conclusions:

Patients with EoE in the USA experience a high disease burden both before and after diagnosis, which requires significant HCRU. Our findings highlight the unmet need for adequate control of EoE-related symptoms.
Primary cystic and solid neuroendocrine tumor of the retroperitoneum
Authors: Shi Dan , Dong Guo-Qiu , Shen Ke-Ren , Pan Yao , Wei Shu-Mei , Chen Ying , Yu Ri-Sheng
Published: January 2021

Rationale:

Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs.

Patient concerns:

A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup.

Diagnoses:

The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery.

Interventions:

The patient underwent resection of the large retroperitoneal tumor.

Outcomes:

The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment.

Lessons subsections:

When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.
Adenylate kinase 7 is a prognostic indicator of overall survival in ovarian cancer
Authors: Zhang Xue-ying , Zhou Li-li , Jiao Yan , Li Yan-qing , Guan Yi-nuo , Zhao Yue-chen , Zheng Lian-wen
Published: January 2021

Ovarian cancer (OC), a common malignant heterogeneous gynecological tumor, is the primary cause of cancer-related death in women worldwide. Adenylate kinase (AK) 7 belongs to the adenylate kinase (AK) family and is a cytosolic isoform of AK. Recent studies have demonstrated that AK7 is expressed in several human diseases, including cancer. However, there is a scarcity of reports on the relationship between AK7 and OC. Here, we compared the expression of AK7 in normal and cancerous ovarian tissues from The Cancer Genome Atlas database and used the c2 test to assess the correlation between AK7 levels and the clinical symptoms of OC. Finally, the prognostic significance of AK7 in OC was determined using the Kaplan–Meier analyses and Cox regression and performed gene set enrichment analysis to detect any relevant signaling pathways. We found that AK7 levels were substantially downregulated in OC than that in normal ovarian tissues (P < .001). Low AK7 levels were related to the patients’ age (P = .0093) in OC. The median overall survival (OS) of patients with low AK7-expressing OC was shorter than patients with high AK7-expressing OC (P = .019). The Cox regression analysis (multivariate) identified low AK7 levels were independently related to the prognosis of OC (HR 1.34; P = .048). Our study demonstrated that the downregulated levels of AK7 could serve as an independent prognostic indicator for the OS in OC. Additionally, gene set enrichment analysis revealed that EMT, apical junction, TGF-b signaling, UV response, and myogenesis were associated in the low AK7 expression phenotype (NOM P < .05).
Infantile hepatic hemangioma misdiagnosed by prenatal ultrasonography
Authors: Jin Ya , Li Lin , Yang Fan
Published: January 2021

Rationale:

The drastic differences in treatment and prognosis of infantile hepatic hemangioma (IHH) and hepatoblastoma (HBL) make accurate prenatal diagnosis imperative. The retrospective comparisons of ultrasonic features between fetal IHH and HBL have been reported before, but clinically, the differential diagnosis in utero is very difficult and can lead to prenatal misdiagnosis.

Patient concerns:

A 27-year-old woman at 30 gestational weeks underwent the routine prenatal examination. A heterogeneous solid mass of the fetus, with close relationship to the liver, was recognized by ultrasound.

Diagnosis:

A diagnosis of HBL was highly considered.

Interventions:

The fetus was aborted and the autopsy was performed.

Outcomes:

The histological outcome was IHH.

Lessons:

The prognosis of fetal IHH and HBL is very different, so an accurate diagnosis prenatally is crucial and indispensable. The radiologist and clinician should differentiate between IHH and HBL, especially since the fetus can have serious complications.
Model establishment of prognostic-related immune genes in laryngeal squamous cell carcinoma
Authors: Sun Ming , Chen Sihan , Fu Min
Published: January 2021

Background:

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck in the world. At present, the treatment methods include surgery, radiotherapy, and chemotherapy, but the 5-year survival rate is still not ideal and the quality of life of the patients is low. Due to the relative lack of immunotherapy methods, this study aims to build a risk prediction model of related immune genes, which can be used to effectively predict the prognosis of laryngeal cancer patients, and provide targets for subsequent immunotherapy.

Methods:

We collected the 111 cases of laryngeal squamous cell carcinoma and 12 matched normal samples in the The Cancer Genome Atlas Database (TCGA) gene expression quantification database. The differentially expressed related immune genes were screened by R software version 3.5.2. The COX regression model of immune related genes was constructed, and the sensitivity and specificity of the model were evaluated. The risk value was calculated according to the model, and the risk curve was drawn to verify the correlation between related immune genes, risk score, and clinical traits.

Results:

We selected 8 immune-related genes that can predict the prognosis of LSCC in a COX regression model and plotted the Kaplan–Meier survival curve. The 5-year survival rate of the high-risk group was 16.5% (95% CI: 0.059–0.459), and that of the low-risk group was 72.9% (95% CI: 0.555–0.956). The area under the receiver operating characteristic (ROC) curve was used to confirm the accuracy of the model (AUG = 0.887). After univariate and multivariate regression analysis, the risk score can be used as an independent risk factor for predicting prognosis. The risk score (P = .021) was positively correlated with the clinical Stage classification.

Conclusion:

We screened out 8 immune genes related to prognosis: RBP1, TLR2, AQP9, BTC, EPO, STC2, ZAP70, and PLCG1 to construct risk value models, which can be used to speculate the prognosis of the disease and provide new targets for future immunotherapy.
The effects of ACEI/ARB, aldosterone receptor antagonists and statins on preventing recurrence of atrial fibrillation
Authors: Jia Qiulei , Han Wenbing , Shi Shuqing , Hu Yuanhui
Published: January 2021

Background:

Atrial fibrillation (AF) is one of the most common arrhythmias, and is high relative to cardiovascular morbidity and mortality. AF-related complications and treatment costs bring about huge health burden, therefore the prevention recurrence of AF is imperative. “Upstream therapy” refers to the use of non-antiarrhythmic drugs (non-AADs) that modify the atrial substrate or target-specific mechanisms of AF to prevent the occurrence or recurrence of the arrhythmia. RAAS Blockers, aldosterone receptor antagonists and statins have an effect on preventing recurrence of atrial fibrillation. This protocol is designed for systematic review and network meta-analysis, which will assess comparative effects and safety of various non-antiarrhythmic drugs in preventing recurrence of atrial fibrillation.

Methods:

The Cochrane Library, MEDLINE, EMBASE, ClinicalTrials.gov will be searched from inception to Aug 31, 2020 to identify relevant studies. The Cochrane “Risk of bias” tool will be used to assess the methodological quality of eligible studies. The pair-wise meta-analysis will be performed by STATA 14.0 software. The network meta-analysis will be implemented in a Bayesian framework using Win BUGS 1.4.3 and the package “gemtc” V.0.8.1 of R-3.6.2 software. The network plots will be drawn using STATA 14.0 software. A comparison-adjusted funnel plot will be used to assess the publication bias using STATA 14.0 software. Quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results:

The results of this network meta-analysis will determine the preventive effect and rank ordering of these interventions for recurrence of AF. The report will follow the PRISMA checklist for network meta-analysis.

Conclusion:

This network meta-analysis will provide comprehensive evidence-based information in clinical practice.

Inplasy registration number:

INPLASY202090004.
Accelerating Research on Suicide Risk and Prevention in Women Veterans Through Research-Operations Partnerships
Authors: Hoffmire Claire A. , Denneson Lauren M. , Monteith Lindsey L. , Dichter Melissa E. , Gradus Jaimie L. , Cappelletti Maurand M. , Brenner Lisa A. , Yano Elizabeth M.
Published: January 2021

Background:

Suicide rates for women veterans are increasing faster than for nonveterans. The 2017 suicide rate for women veterans was more than double that for women nonveterans. However, research to inform improved suicide prevention for women veterans is scant.

Objectives:

To accelerate research on women veterans’ unique risks and resiliencies for suicide, the Department of Veterans Affairs (VA) Women’s Health Research Network launched a Women Veterans Suicide Prevention Research Work Group to target technical support for researchers, promote collaboration with national VA program offices, and ultimately increase dissemination and translation of research into clinical practice, public health strategies, and policies. The objective of this paper is to report on the process and outcomes of the Work Group’s strategic planning efforts to identify and fill gaps in suicide prevention research among women veterans.

Methods:

An in-person meeting of 20 researchers and operational leaders was convened to summarize existing research evidence and identify research priorities and challenges.

Results:

Research priorities included civilian reintegration, community connections, psychosocial stressors (eg, social determinants of health) and trauma, risk assessment, clinical interventions, upstream prevention, and health care access. The importance of increasing evidence on gender differences and for women veterans not using VA health care was emphasized.

Conclusions:

Research to inform suicide prevention tailored to meet women veterans’ needs is essential; however, many priorities and challenges remain unaddressed. Although Work Group efforts have achieved funding gains, further work to formalize, promote and meet the demands of a suicide prevention research agenda for women veterans requires is ongoing focus.