bluuebunny/crossref_metadata_2025 huggingface dataset:
On the link between nuclear star cluster and globular cluster system mass, nucleation fraction, and environment
Authors: Leaman Ryan , van de Ven Glenn
Published: August 2021

We present a simple model for the host mass dependence of the galaxy nucleation fraction (fnuc), the galaxy’s nuclear star cluster (NSC) mass, and the mass in its surviving globular clusters (MGC, obs). Considering the mass and orbital evolution of a GC in a galaxy potential, we define a critical mass limit (MGC, lim) above which a GC can simultaneously in-spiral to the galaxy centre due to dynamical friction and survive tidal dissolution, to build-up the NSC. The analytical expression for this threshold mass allows us to model the nucleation fraction for populations of galaxies. We find that the slope and curvature of the initial galaxy size–mass relation is the most important factor (with the shape of the GC mass function a secondary effect) setting the fraction of galaxies that are nucleated at a given mass. The well-defined skew-normal fnuc–Mgal observations in galaxy cluster populations are naturally reproduced in these models, provided there is an inflection in the initial size–mass relation at Mgal ∼ 109.5 M⊙. Our analytical model also predicts limits to the Mgal–MGC, tot and Mgal–MNSC relations which bound the scatter of the observational data. Moreoever, we illustrate how these scaling relations and fnuc vary if the star cluster formation efficiency, GC mass function, galaxy environment, or galaxy size–mass relation are altered. Two key predictions of our model are: (1) galaxies with NSC masses greater than their GC system masses are more compact at fixed stellar mass and (2) the fraction of nucleated galaxies at fixed galaxy mass is higher in denser environments. That a single model framework can reproduce both the NSC and GC scaling relations provides strong evidence that GC in-spiral is an important mechanism for NSC formation.
A dusty filament and turbulent CO spirals in HD 135344B - SAO 206462
Authors: Casassus Simon , Christiaens Valentin , Cárcamo Miguel , Pérez Sebastián , Weber Philipp , Ercolano Barbara , van der Marel Nienke , Pinte Christophe , Dong Ruobing , Baruteau Clément , Cieza Lucas , van Dishoeck Ewine F , Jordan Andrés , Price Daniel J , Absil Olivier , Arce-Tord Carla , Faramaz Virginie , Flores Christian , Reggiani Maddalena
Published: August 2021

Planet–disc interactions build up local pressure maxima that may halt the radial drift of protoplanetary dust, and pile it up in rings and crescents. ALMA observations of the HD 135344B disc revealed two rings in the thermal continuum stemming from ∼mm-sized dust. At higher frequencies the inner ring is brighter relative to the outer ring, which is also shaped as a crescent rather than a full ring. In near-IR scattered light images, the disc is modulated by a two-armed grand-design spiral originating inside the ALMA inner ring. Such structures may be induced by a massive companion evacuating the central cavity, and by a giant planet in the gap separating both rings, that channels the accretion of small dust and gas through its filamentary wakes while stopping the larger dust from crossing the gap. Here we present ALMA observations in the J = (2 − 1) CO isotopologue lines and in the adjacent continuum, with up to 12 km baselines. Angular resolutions of ∼0${_{.}^{\prime\prime}}$03 reveal the tentative detection of a filament connecting both rings, and which coincides with a local discontinuity in the pitch angle of the IR spiral, proposed previously as the location of the protoplanet driving this spiral. Line diagnostics suggests that turbulence, or superposed velocity components, is particularly strong in the spirals. The 12CO(2-1) 3D rotation curve points at stellocentric accretion at radii within the inner dust ring, with a radial velocity of up to ${\sim}5{{\ \rm per\ cent}}\pm 0.5{{\ \rm per\ cent}}$ Keplerian, which corresponds to an excessively large accretion rate of ${\sim}2\times 10^{-6}\, M_\odot \,$yr−1 if all of the CO layer follows the 12CO(2-1) kinematics. This suggests that only the surface layers of the disc are undergoing accretion, and that the line broadening is due to superposed laminar flows.
Dark cloud-type chemistry in photodissociation regions with moderate ultraviolet field
Authors: Kirsanova Maria S , Punanova Anna F , Semenov Dmitry A , Vasyunin Anton I
Published: August 2021

We present a study of emission lines of small hydrocarbons C2H and c-C3H2, and COMs precursors H2CO and CH3OH in order to better understand the possible chemical link between the molecular abundances and UV radiation field in photodissociation regions (PDRs). We study two PDRs around extended and compact H ii regions with G ≤ 50 Habings in the S235 star-forming complex. We find the highest abundances of both hydrocarbons on the edges of molecular clumps, while c-C3H2 is also abundant in the low-density expanding PDR around compact H ii region S235 A. We see the highest methanol column density towards the positions with the UV field G ≈ 20−30 Habings and explain them by reactive desorption from the dust grains. The $N_{\rm C_2H}/N_{\rm CH_3OH}$ ratio is lower by a factor of few or the order of magnitude in comparison with the Horsehead and Orion Bar PDRs. The ratio is similar to the value observed in hot corinos in the Perseus cloud. We conclude that ion-molecular and grain surface chemical routes rule the molecular abundances in the PDRs, and the PDRs inherit molecular abundances from the previous dark stage of molecular cloud evolution in spite of massive stars already emitting in optics.
Modified granular impact force laws for the OSIRIS-REx touchdown on the surface of asteroid (101955) Bennu
Authors: Ballouz R-L , Walsh K J , Sánchez P , Holsapple K A , Michel P , Scheeres D J , Zhang Y , Richardson D C , Barnouin O S , Nolan M C , Bierhaus E B , Connolly H C , Schwartz S R , Çelik O , Baba M , Lauretta D S
Published: August 2021

The OSIRIS-REx mission collected a sample from the surface of the asteroid (101955) Bennu in 2020 October. Here, we study the impact of the OSIRIS-REx Touch-and-Go Sampling Acquisition Mechanism (TAGSAM) interacting with the surface of an asteroid in the framework of granular physics. Traditional approaches to estimating the penetration depth of a projectile into a granular medium include force laws and scaling relationships formulated from laboratory experiments in terrestrial-gravity conditions. However, it is unclear that these formulations extend to the OSIRIS-REx scenario of a 1300-kg spacecraft interacting with regolith in a microgravity environment. We studied the TAGSAM interaction with Bennu through numerical simulations using two collisional codes, pkdgrav and gdc-i. We validated their accuracy by reproducing the results of laboratory impact experiments in terrestrial gravity. We then performed TAGSAM penetration simulations varying the following geotechnical properties of the regolith: packing fraction (P), bulk density, inter-particle cohesion (σc), and angle of friction (ϕ). We find that the outcome of a spacecraft-regolith impact has a non-linear dependence on packing fraction. Closely packed regolith (P ≳ 0.6) can effectively resist the penetration of TAGSAM if ϕ ≳ 28° and/or σc ≳ 50 Pa. For loosely packed regolith (P ≲ 0.5), the penetration depth is governed by a drag force that scales with impact velocity to the 4/3 power, consistent with energy conservation. We discuss the importance of low-speed impact studies for predicting and interpreting spacecraft–surface interactions. We show that these low-energy events also provide a framework for interpreting the burial depths of large boulders in asteroidal regolith.
Ancient Gene Duplications, Rather Than Polyploidization, Facilitate Diversification of Petal Pigmentation Patterns in Clarkia gracilis (Onagraceae)
Authors: Lin Rong-Chien , Rausher Mark D
Published: August 2021

It has been suggested that gene duplication and polyploidization create opportunities for the evolution of novel characters. However, the connections between the effects of polyploidization and morphological novelties have rarely been examined. In this study, we investigated whether petal pigmentation patterning in an allotetraploid Clarkia gracilis has evolved as a result of polyploidization. Clarkia gracilis is thought to be derived through a recent polyploidization event with two diploid species, C. amoena huntiana and an extinct species that is closely related to C. lassenensis. We reconstructed phylogenetic relationships of the R2R3-MYBs (the regulators of petal pigmentation) from two subspecies of C. gracilis and the two purported progenitors, C. a. huntiana and C. lassenensis. The gene tree reveals that these R2R3-MYB genes have arisen through duplications that occurred before the divergence of the two progenitor species, that is, before polyploidization. After polyploidization and subsequent gene loss, only one of the two orthologous copies inherited from the progenitors was retained in the polyploid, turning it to diploid inheritance. We examined evolutionary changes in these R2R3-MYBs and in their expression, which reveals that the changes affecting patterning (including expression domain contraction, loss-of-function mutation, cis-regulatory mutation) occurred after polyploidization within the C. gracilis lineages. Our results thus suggest that polyploidization itself is not necessary in producing novel petal color patterns. By contrast, duplications of R2R3-MYB genes in the common ancestor of the two progenitors have apparently facilitated diversification of petal pigmentation patterns.
Alpha Satellite Insertion Close to an Ancestral Centromeric Region
Authors: Giannuzzi Giuliana , Logsdon Glennis A , Chatron Nicolas , Miller Danny E , Reversat Julie , Munson Katherine M , Hoekzema Kendra , Bonnet-Dupeyron Marie-Noëlle , Rollat-Farnier Pierre-Antoine , Baker Carl A , Sanlaville Damien , Eichler Evan E , Schluth-Bolard Caroline , Reymond Alexandre
Published: August 2021

Human centromeres are mainly composed of alpha satellite DNA hierarchically organized as higher-order repeats (HORs). Alpha satellite dynamics is shown by sequence homogenization in centromeric arrays and by its transfer to other centromeric locations, for example, during the maturation of new centromeres. We identified during prenatal aneuploidy diagnosis by fluorescent in situ hybridization a de novo insertion of alpha satellite DNA from the centromere of chromosome 18 (D18Z1) into cytoband 15q26. Although bound by CENP-B, this locus did not acquire centromeric functionality as demonstrated by the lack of constriction and the absence of CENP-A binding. The insertion was associated with a 2.8-kbp deletion and likely occurred in the paternal germline. The site was enriched in long terminal repeats and located ∼10 Mbp from the location where a centromere was ancestrally seeded and became inactive in the common ancestor of humans and apes 20–25 million years ago. Long-read mapping to the T2T-CHM13 human genome assembly revealed that the insertion derives from a specific region of chromosome 18 centromeric 12-mer HOR array in which the monomer size follows a regular pattern. The rearrangement did not directly disrupt any gene or predicted regulatory element and did not alter the methylation status of the surrounding region, consistent with the absence of phenotypic consequences in the carrier. This case demonstrates a likely rare but new class of structural variation that we name “alpha satellite insertion.” It also expands our knowledge on alphoid DNA dynamics and conveys the possibility that alphoid arrays can relocate near vestigial centromeric sites.
Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation
Authors: Slepchenko Kira G , Chen Si , Counts Grace P , Corbin Kathryn L , Colvin Robert A , Nunemaker Craig S
Published: August 2021

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.
Photo-activatable Ub-PCNA probes reveal new structural features of the Saccharomyces cerevisiae Polη/PCNA complex
Authors: Shen Siqi , Davidson Gregory A , Yang Kun , Zhuang Zhihao
Published: August 2021

The Y-family DNA polymerase η (Polη) is critical for the synthesis past damaged DNA nucleotides in yeast through translesion DNA synthesis (TLS). TLS is initiated by monoubiquitination of proliferating cell nuclear antigen (PCNA) and the subsequent recruitment of TLS polymerases. Although individual structures of the Polη catalytic core and PCNA have been solved, a high-resolution structure of the complex of Polη/PCNA or Polη/monoubiquitinated PCNA (Ub-PCNA) still remains elusive, partly due to the disordered Polη C-terminal region and the flexibility of ubiquitin on PCNA. To circumvent these obstacles and obtain structural insights into this important TLS polymerase complex, we developed photo-activatable PCNA and Ub-PCNA probes containing a p-benzoyl-L-phenylalanine (pBpa) crosslinker at selected positions on PCNA. By photo-crosslinking the probes with full-length Polη, specific crosslinking sites were identified following tryptic digestion and tandem mass spectrometry analysis. We discovered direct interactions of the Polη catalytic core and its C-terminal region with both sides of the PCNA ring. Model building using the crosslinking site information as a restraint revealed multiple conformations of Polη in the polymerase complex. Availability of the photo-activatable PCNA and Ub-PCNA probes will also facilitate investigations into other PCNA-containing complexes important for DNA replication, repair and damage tolerance.
A Baker’s Dozen of Top Antimicrobial Stewardship Intervention Publications in 2020
Authors: Green Sarah B , Stover Kayla R , Barber Katie , Bouchard Jeannette L , Brown Matthew L , Deri Connor R , Francis Bailey J , Gauthier Timothy P , Hayes Jillian E , Marx Ashley H , McGee Edoabasi U , Mediwala Krutika , Musgrove Rachel J , Slain Douglas , Stramel Stefanie A , Bland Christopher M , Bookstaver P Brandon
Published: August 2021

The number of articles related to antimicrobial stewardship published each year has increased significantly over the last decade. Keeping up with the literature, particularly the most innovative, well-designed, or applicable to one’s own practice area, can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network reviewed antimicrobial stewardship–related, peer-reviewed literature from 2020 that detailed actionable interventions. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for teaching and training, and to identify novel or optimized stewardship opportunities within one’s institution.
Demographic Disparities in Clinical Outcomes of COVID-19: Data From a Statewide Cohort in South Carolina
Authors: Yang Xueying , Zhang Jiajia , Chen Shujie , Olatosi Bankole , Bruner Larisa , Diedhiou Abdoulaye , Scott Cheryl , Mansaray Ali , Weissman Sharon , Li Xiaoming
Published: August 2021

Background

Current literature examining the clinical characteristics of coronavirus disease 2019 (COVID-19) patients under-represent COVID-19 cases who were either asymptomatic or had mild symptoms.

Methods

We analyzed statewide data from 280 177 COVID-19 cases from various health care facilities during March 4–December 31, 2020. Each COVID-19 case was reported using the standardized Case Report Form (CRF), which collected information on demographic characteristics, symptoms, hospitalization, and death. We used multivariable logistic regression to analyze the associations between sociodemographics and disease severity, hospitalization, and mortality.

Results

Among a total of 280 177 COVID-19 cases, 5.2% (14 451) were hospitalized and 1.9% (5308) died. Older adults, males, and Black individuals had higher odds of hospitalization and death from COVID-19 (all P < 0.0001). In particular, individuals residing in rural areas experienced a high risk of death (odds ratio [OR], 1.16; 95% CI, 1.08–1.25). Regarding disease severity, older adults (OR, 1.06; 95% CI, 1.03–1.10) and Hispanic or Latino patients (OR, 2.06; 95% CI, 1.95–2.18) had higher odds of experiencing moderate/severe symptoms, while male and Asian patients, compared with White patients, had lower odds of experiencing moderate/severe symptoms.

Conclusions

As the first statewide population-based study using data from multiple health care systems with a long follow-up period in the United States, we provide a more generalizable picture of COVID-19 symptoms and clinical outcomes. The findings from this study reinforce the fact that rural residence and racial/ethnic social determinants of health, unfortunately, remain predictors of adverse health outcomes for COVID-19 patients.
Cannabis Glandular Trichome Cell Walls Undergo Remodeling to Store Specialized Metabolites
Authors: Livingston Samuel J , Bae Eun Jeong , Unda Faride , Hahn Michael G , Mansfield Shawn D , Page Jonathan E , Samuels A Lacey
Published: August 2021

The valuable cannabinoid and terpenoid metabolites of Cannabis sativa L. are produced by floral glandular trichomes. The trichomes consist of secretory disk cells, which produce the abundant lipidic metabolites, and an extracellular storage cavity. The mechanisms of apoplastic cavity formation to accumulate and store metabolites in cannabis glandular trichomes remain wholly unexplored. Here, we identify key wall components and how they change during cannabis trichome development. While glycome and monosaccharide analyses revealed that glandular trichomes have loosely bound xyloglucans and pectic polysaccharides, quantitative immunolabeling with wall-directed antibodies revealed precise spatiotemporal distributions of cell wall epitopes. An epidermal-like identity of early trichome walls matured into specialized wall domains over development. Cavity biogenesis was marked by separation of the subcuticular wall from the underlying surface wall in a homogalacturonan and α-1,5 arabinan epitope-rich zone and was associated with a reduction in fucosylated xyloglucan epitopes. As the cavity filled, a matrix with arabinogalactan and α-1,5 arabinan epitopes enclosed the metabolite droplets. At maturity, the disk cells’ apical wall facing the storage cavity accumulated rhamnogalacturonan-I epitopes near the plasma membrane. Together, these data indicate that cannabis glandular trichomes undergo spatiotemporal remodeling at specific wall subdomains to facilitate storage cavity formation and metabolite storage.
Digital assets and property rights in insolvency
Authors: Cone Geoffrey , Bjorklund Nicholas S , Dyekman Gregory C
Published: August 2021

What happens to your Bitcoin or other cryptoassets if the custodian becomes insolvent? In the rush to investment in these alternative currencies, little attention has been paid to this consequence, not least by the custodians and exchanges themselves, as amply demonstrated by the case considered in this article. At the same time, we consider the solution to the problems presented in a number of insolvency cases around the world, by the comprehensive cryptoasset legislation introduced by the State of Wyoming, USA.
The Effect of Facilitated Tucking on the Pain Intensity Induced by Chest Tube Removal in Infants
Authors: Pouraboli Batool , Mirlashari Jila , Fakhr Aida Safaiee , Ranjbar Hadi , Ashtari Somayeh
Published: August 2021

Background:

Removal of a chest tube is a painful procedure for infants. Medications, including narcotics, are used to control pain, but nonpharmacologic interventions are also effective in reducing pain during this procedure and are not associated with adverse effects.

Purpose:

To evaluate the additive effect of facilitated tucking to the use of morphine on infant pain associated at the time of chest tube removal.

Methods:

This was a prospective, randomized control study. Sixty infants were randomized into 2 equal groups utilizing a coin flip. All infants received 0.05-mg/kg morphine 20 minutes before chest tube removal. The intervention group received facilitated tucking and the control group received standard care. Infant pain was measured using the Neonatal Infant Pain Scale. Pain was assessed at 3 time points by 2 independent evaluators: 5 minutes before, during, and 5 minutes after removal of the chest tube. Mann-Whitney and Fisher's exact (Chi-square) tests were used to compare the intervention and control groups.

Results:

Pain scores were increased during chest tube removal for both the intervention and the control groups. Compared with the control group, pain scores for infants in the intervention group were less before, during, and after chest tube removal.

Implications for Practice:

Facilitated tucking combined with morphine administration can be an effective additive intervention for pain control in infants during chest tube removal.

Implications for Research:

Evaluate the effect of the facilitated tucking on pain induced by chest tube removal in preterm infants. Preterm infants may respond differently to pain.
Preserving Wideband Tympanometry Information With Artifact Mitigation
Authors: Eberhard Kristine Elisabeth , Ravicz Michael E. , Merchant Gabrielle R. , Masud Salwa F. , Maison Stéphane F. , Neely Stephen T. , Nakajima Hideko Heidi
Published: August 2021

Objective:

Absorbance measured using wideband tympanometry (WBT) has been shown to be sensitive to changes in middle and inner ear mechanics, with potential to diagnose various mechanical ear pathologies. However, artifacts in absorbance due to measurement noise can obscure information related to pathologies and increase intermeasurement variability. Published reports frequently present absorbance that has undergone smoothing to minimize artifact; however, smoothing changes the true absorbance and can destroy important narrow-band characteristics such as peaks and notches at different frequencies. Because these characteristics can be unique to specific pathologies, preserving them is important for diagnostic purposes. Here, we identify the cause of artifacts in absorbance and develop a technique to mitigate artifacts while preserving the underlying WBT information.

Design:

A newly developed Research Platform for the Interacoustics Titan device allowed us to study raw microphone recordings and corresponding absorbances obtained by WBT measurements. We investigated WBT measurements from normal hearing ears and ears with middle and inner ear pathologies for the presence of artifact and noise. Furthermore, it was used to develop an artifact mitigation procedure and to evaluate its effectiveness in mitigating artifacts without distorting the true WBT information.

Results:

We observed various types of noise that can plague WBT measurements and that contribute to artifacts in computed absorbances, particularly intermittent low-frequency noise. We developed an artifact mitigation procedure that incorporates a high-pass filter and a Tukey window. This artifact mitigation resolved the artifacts from low-frequency noise while preserving characteristics in absorbance in both normal hearing ears and ears with pathology. Furthermore, the artifact mitigation reduced intermeasurement variability.

Conclusions:

Unlike smoothing algorithms used in the past, our artifact mitigation specifically removes artifacts caused by noise. It does not change frequency response characteristics, such as narrow-band peaks and notches in absorbance at different frequencies that can be important for diagnosis. Also, by reducing intermeasurement variability, the artifact mitigation can improve the test–retest reliability of these measurements.
Utility and Associated Charge of Anteroposterior Radiographs in Rotational Ankle Fractures During Postoperative Follow-Up: The Results of an Orthopaedic Trauma Association Survey
Authors: Garner Matthew R. , Ptasinski Anna , Aynardi Michael C. , Mosher Timothy J. , Firoozabadi Reza
Published: August 2021

Objectives:

To evaluate the perceived utility and associated charges of the anteroposterior (AP) radiograph during rotational ankle fracture postoperative follow-up.

Design:

Survey study with charge analysis using published data at 50 orthopaedic hospitals in the United States.

Setting:

Not Applicable.

Participants:

Orthopaedic Trauma Association Members with an active email address who were invited and interested in answering a survey.

Results:

Ninety-four percent of respondents stated that they did routinely obtain an AP radiograph during rotational ankle fracture follow-up. However, 57% thought that the AP view should be eliminated from standard follow-up and only 51% found this view useful after initial treatment.

Charge Analysis:

The mean difference between a 2-view and 3-view ankle radiograph series was $102.00. Using this value and the assumption that each patient with a rotational ankle fracture gets 3 follow-up radiographs, there is the potential for a charge reduction of $306 per patient. Assuming over 134,000 rotational ankle fractures, a charge reduction of 41 million US dollars (USD) per year is possible if the AP image is routinely removed. Actual savings are likely to be less based on agreed on payer rates. Although less easy to quantify, there is also a potential reduction of radiation exposure, radiologists' interpretation time, and data storage.

Conclusions:

Routine AP radiographs should potentially be eliminated from routine postoperative ankle x-ray protocols based on this survey of experienced orthopaedic surgeons. If this specific radiograph is ordered on a case-by-case basis, then significant savings may occur.
Postoperative Prescription of Low-dose Narcotics Yields Equivalent Pain Outcomes Compared to High-dose Narcotics in Opioid-naïve Patients Undergoing Spine Surgery
Authors: Mohanty Sarthak , Shin Max , Casper David , Saifi Comron
Published: August 2021

Study Design.

Retrospective cohort study at a single institution. Patients undergoing specific, elective spinal procedures between 2012 and 2018.

Objective.

The aim of thi stsudy was to investigate the relationship between opioid prescriptions during the immediate, post-discharge period, and patient-reported pain outcomes.

Summary of Background Data.

Medically prescribed opiates contribute to the opioid crisis, manifesting in significant mortality and economic burden. Although opioids are a mainstay of pain amelioration following spinal surgery, prescription practices are heterogeneous.

Methods.

Inclusion criteria included: patients who underwent one of 10 spinal procedures (Table 1); patients with preoperative, postoperative day (POD 1, and POD 30 pain scores reported on the visual analog scale (VAS); patients discharged without a complicated perioperative course. Opioids were converted to morphine milligram equivalents per day (MME/day) using a standard reference table. χ
2, Kruskal-Wallis, and logistic regression were utilized to investigate associations between clinical variables and postoperative pain scores. Univariate and multivariable linear regression models with Stepwise selection (cut off: P = 0.05) were employed as appropriate on POD 30 VAS pain scores.

Results.

Smoking status and postoperative LOS were associated with opioid prescription doses. Patients prescribed opioids <40 MME/day, equivalent to five tablets of 5 mg oxycodone/day, showed no significant difference in POD 30 VAS score (β coefficient: 0.095, P 
= 0.752) when compared to patients who received the highest-dose opioids (>80 MME/day—equivalent to 10 tablets of 5 mg oxycodone/day). Adjusted multivariable logistic regression analysis revealed that postoperative opioid dosage/prescription was not a significant predictor of patients reporting at least 50% pain improvement, suggesting that 40 MME/day is sufficient to maintain patient satisfaction.

Conclusion.

Patients receiving the lowest dosage of opioid prescriptions with sufficient nonopiate analgesics did not report worse pain relief at POD 30 compared to those receiving higher opioid prescriptions. In light of the opioid epidemic, this study supports initial dosing recommendations by the American Society for Addiction Medicine.

Level of Evidence: 3
miR-141-3p suppresses development of clear cell renal cell carcinoma by regulating NEK6
Authors: Liu Yifei , Fu Wenqiang , Yin Feng , Xia Lianjie , Zhang Yubo , Wang Baocun , Li Tengfei , Zhang Tingting , Cheng Ling , Wei Yanbing , Gao Bin
Published: August 2021

Currently, there have been few studies on the function and molecular mechanism of miR-141-3p in the development of clear cell renal cell carcinoma (CCRCC). This study aimed to explore the relationship between miR-141-3p and NIMA (never in mitosis, gene A)-related kinase-6 (NEK6) and investigate the role of the interaction in CCRCC cell proliferation, migration, invasion and apoptosis.Starbase database was used to predict the target gene of miR-141-3p in CCRCC and dual-luciferase reporter assay was performed to verify the targeting relationship between miR-141-3p and the target gene. Real-time quantitative PCR was conducted to detect the expression of miR-141-3p and NEK6 mRNA in cells. Western blot was carried out to detect the protein level of NEK6 in cells. Cell Counting Kit-8 assay, transwell assay and wound healing assay were conducted to detect CCRCC cell proliferation, invasion and migration abilities. Flow cytometry was performed to detect CCRCC cell apoptosis. miR-141-3p was markedly lowly expressed, and NEK6 was a target of miR-141-3p and was remarkably highly expressed in CCRCC cells. Over-expressing miR-141-3p could inhibit CCRCC cell proliferation, migration, invasion and promote apoptosis. The inhibitory effect of miR-141-3p over-expression on cell proliferation, migration and invasion was significantly weakened by over-expressing NEK6. miR-141-3p could regulate CCRCC cell proliferation, migration, invasion and apoptosis by targeting NEK6. This study lays the basis for the exploration of the molecular mechanism underlying CCRCC pathogenesis and research on targeted therapies for CCRCC.
Circ_0085495 knockdown reduces adriamycin resistance in breast cancer through miR-873-5p/integrin β1 axis
Authors: Xie Hua , Zheng Rongsheng
Published: August 2021

Circular RNAs (circRNAs) are reported to be related to cancer chemoresistance. However, the role of circ_0085495 in adriamycin (ADM) and its action mechanism has not been elucidated in breast cancer. Cell counting kit-8 was employed to detect cell viability. Quantitative real-time-PCR and western blot were performed to examine the gene and protein expression level. Flow cytometry and colony formation assay were conducted to measure cell apoptosis and proliferation. Cell migration and invasion were evaluated via transwell assay. The target association between molecules was confirmed by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Tumor xenograft assay was implemented to explore the role of circ_0085495 in vivo. Circ_0085495 and Integrin β1 were upregulated, while miR-873-5p was downregulated in ADM-resistant cells. Circ_0085495 was a stable circRNA, mainly located in the cytoplasm. Depletion of circ_0085495 repressed ADM resistance, proliferation and metastasis of ADM-resistant breast cancer cells, which was weakened by miR-873-5p inhibition or integrin β1 overexpression. Circ_0085495 sponged miR-873-5p to positively regulate integrin β1 expression. Integrin β1 knockdown also inhibited ADM resistance. Furthermore, circ_0085495 knockdown inhibited tumor growth in vivo. Circ_0085495 knockdown reduced ADM resistance in ADM-resistant cells through modulating miR-873-5p/integrin β1 axis, indicating circ_0085495 as a promising target for overcoming ADM resistance in breast cancer patients.
Downregulation of circ-SFMBT2 blocks the development of gastric cancer by targeting the miR-885-3p/CHD7 pathway
Authors: He Yuqi , Zhang Zhongliang , Wang Zinian , Jiao Yigang , Kang Qi , Li Jingzhe
Published: August 2021

Accumulating evidence insists that circular RNAs (circRNAs) play important roles in the development of human cancers, including gastric cancer. This study aimed to investigate the role of circ-SFMBT2 and provide a potential mechanism to explain its function. The expression of circ-SFMBT2, miR-885-3p and chromodomain-helicase-DNA-binding protein 7 (CHD7) mRNA was determined by quantitative real-time PCR (qRT-PCR), and the protein level of CHD7 was determined by western blot. To investigate the function of circ-SFMBT2 in vitro, the effects of circ-SFMBT2 on cell viability, colony formation, apoptosis, migration and invasion were assessed using cell counting kit-8 assay, colony formation assay, flow cytometry assay, wounding healing assay and transwell assay, respectively. The indicators of oxidative stress were assessed using matched kits. Besides, the function of circ-SFMBT2 was also investigated in animal models. The relationship between miR-885-3p and circ-SFMBT2 or CHD7 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ-SFMBT2 and CHD7 were upregulated, whereas miR-885-3p was downregulated in gastric cancer tissues and cells. In functional assay, circ-SFMBT2 knockdown suppressed gastric cancer cell viability, colony formation ability, migration, invasion and oxidative stress but induced apoptosis, and circ-SFMBT2 downregulation also blocked tumor growth in vivo. In mechanism analysis, circ-SFMBT2 regulated CHD7 expression by sponging its target miRNA, miR-885-3p. Rescue experiments manifested that miR-885-3p inhibition reversed the effects of circ-SFMBT2 knockdown, and CHD7 overexpression abolished the antitumor role of miR-885-3p overexpression. Moreover, circ-SFMBT2 knockdown inactivated the Wnt/β-catenin signaling pathway. Circ-SFMBT2 downregulation repressed the development of gastric cancer partially by controlling the miR-885-3p/CHD7 axis, which might be a novel strategy to inhibit gastric cancer progression.
A Systematic Review and Pooled Prevalence of Delirium in Critically Ill Children*
Authors: Semple Diarmaid , Howlett Moninne M. , Strawbridge Judith D. , Breatnach Cormac V. , Hayden John C.
Published: August 2021

OBJECTIVES:

Pediatric delirium is a neuropsychiatric disorder with disrupted cerebral functioning due to underlying disease and/or critical care treatment. Pediatric delirium can be classified as hypoactive, hyperactive, and mixed. This systematic review was conducted to estimate the pooled prevalence of pediatric delirium using validated assessment tools in children (Cornell Assessment of Pediatric Delirium, Pediatric Confusion Assessment Method for the ICU, PreSchool Confusion Assessment Method for the ICU, Pediatric Confusion Assessment Method for the ICU Severity Scale, and Sophia Observation Withdrawal Symptoms Pediatric Delirium scale), identify modifiable and nonmodifiable risk factors, and explore the association of pediatric delirium with clinical outcomes.

Data Sources:

A systematic search of PubMed, EMBASE, and CINAHL databases was undertaken for full articles pertaining to pediatric delirium prevalence.

Study Selection:

No language or date barriers were set. Studies were included where the following eligibility criteria were met: study design aimed to estimate pediatric delirium prevalence arising from treatment in the intensive care setting, using a validated tool. Only randomized controlled trials, cross-sectional studies, or cohort studies allowing an estimate of the prevalence of pediatric delirium were included.

Data Extraction:

Data were extracted by the primary researcher (D.S.) and accuracy checked by coauthors.

Data Synthesis:

A narrative synthesis and pooled prevalence meta-analysis were undertaken.

CONCLUSIONS:

Pediatric delirium, as determined by the Cornell Assessment of Pediatric Delirium score, is estimated to occur in 34% of critical care admissions. Eight of 11 studies reporting on subtype identified hypoactive delirium as most prevalent (46–81%) with each of the three remaining reporting either hyperactive (44%), mixed (57%), or equal percentages of hypoactive and mixed delirium (43%) as most prevalent. The development of pediatric delirium is associated with cumulative doses of benzodiazepines, opioids, the number of sedative classes used, deep sedation, and cardiothoracic surgery. Increased time mechanically ventilated, length of stay, mortality, healthcare costs, and associations with decreased quality of life after discharge were also found. Multi-institutional and longitudinal studies are required to better determine the natural history, true prevalence, long-term outcomes, management strategies, and financial implications of pediatric delirium.
Diversity of Authors of Publications From the Canadian Critical Care Trials Group*
Authors: Mehta Sangeeta , Ahluwalia Nanki , Heybati Kiyan , Burns Karen E. A. , Owais Sawayra , Cook Deborah J. ,   for the Canadian Critical Care Trials Group
Published: August 2021

OBJECTIVES:

Diverse perspectives improve the quality of scholarly initiatives. The demographic and professional diversity of scientists who contribute to critical care research and publications has not been described for the Canadian Critical Care Trials Group. Our objective was to describe the diversity of authors of publications from the Canadian Critical Care Trials Group.

DESIGN:

We conducted a quantitative content analysis of peer-reviewed articles published on behalf of the Canadian Critical Care Trials Group.

SETTING:

All peer-reviewed articles that were published on behalf of the Canadian Critical Care Trials Group between 1994 and October 2020.

SUBJECTS:

For each publication, we recorded the study design, the number of authors, and national or international collaboration. For the lead author, the senior author, and each coauthor, we recorded the following facets of diversity: gender, professional role, medical discipline, geographic location, academic stage, and visible minority status.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 354 eligible publications; 74% (263/354) reported observational cohort studies, randomized trials, and surveys. Of 4,246 authors, 1,205 were unique individuals. The mean (sd) number of authors per publication was 12 (7.1). Of all 4,246 authors, 37% were women, and 13.7% were members of a visible minority group. Of all lead or senior authors, 40% and 34% respectively were women; 15% of lead and 10% of senior authors were members of a visible minority group. Three-quarters (73%) of publications listed authors from more than one profession, and more than half (54%) listed authors from more than one medical discipline. Nearly half of publications (45%) listed authors who were early career faculty, 33% listed authors who were trainees, and 67% listed authors who were from visible minority groups. Authors from different provinces and from different countries were listed in 67% and 40% of publications, respectively.

CONCLUSIONS:

Authors of Canadian Critical Care Trials Group publications are diverse with regard to demographic and professional characteristics.
Association Between Physical Activity, Screen Time and Sleep, and School Readiness in Canadian Children Aged 4 to 6 Years
Authors: Vanderloo Leigh M. , Omand Jessica , Keown-Stoneman Charles D. G. , Janus Magdalena , Tremblay Mark S. , Maguire Jonathon L. , Borkhoff Cornelia M. , Lebovic Gerald , Parkin Patricia , Mamdani Muhammad , Simpson Janis Randall , Duku Eric , Birken Catherine S.
Published: August 2021

Objective:

School readiness is strongly associated with a child's future school success and well-being. The primary objective of this study was to determine whether meeting 24-hour movement guidelines (national physical activity, sedentary behaviors, and sleep recommendations) was associated with school readiness measured with mean scores in each of the 5 developmental domains of the Early Development Instrument (EDI) in Canadian children aged 4 to 6 years. Secondary objectives include examining the following: (1) the association between meeting 24-hour movement guidelines and overall vulnerability in school readiness and (2) the association between meeting individual physical activity, screen use and sleep recommendations, and overall school readiness.

Methods:

A prospective cohort study was performed using data from children (aged 4–6 years) who participated in a large-scale primary care practice-based research network.

Results:

Of the 739 participants (aged 5.9 + 0.12 years) in this prospective cohort study, 18.2% met the 24-Hour Movement Guidelines. Linear regression models (adjusted for child/family demographic characteristics, number of siblings, immigration status, and annual household income) revealed no evidence of an association between meeting all 24-hour movement guidelines and any of the 5 domains of the EDI (p > 0.05). Adjusted linear regression models revealed evidence of an association between meeting screen use guidelines and the "language and cognitive development" (β = 0.16, p = 0.004) domain, and for the sleep guideline, there was a statistically significant association with the "physical health and well-being" (β = 0.23, p = 0.001), the "language and cognitive development" (β = 0.10, p = 0.003), and the "communication skills and general knowledge" (β = 0.18, p < 0.001) domain.

Conclusion:

Early lifestyle interventions targeting screen use and sleep may be beneficial for improving a child's readiness for school.
Risk factors predisposing to acute stroke in India: a prospective study
Authors: Ram C. Venkata S. , Kumar Sudhir , Renjen Pushpendra Nath , Kumar G. Praveen , Swaminathan Jayanthi , Reddy C. Rajesh , Kondati Sathyanarayana , Sharma Mukesh , Selvan V.L. Arul , Sundaram Meenakshi , Vasudevan Anupama , Lackland Daniel
Published: August 2021

Background:

Stroke is an important neurological disorder with significant morbidity and mortality. In India, the risk factors for stroke (obesity, diabetes mellitus, alcoholism, hypertension, and sedentary lifestyle) are mounting with economic growth and increasing the disease burden.

Objective:

To assess the severity and risk factors of stroke in India and identify any new predisposing factors.

Methods:

A multicentric (six tertiary care hospitals across India) prospective observational study (from September 2016 to July 2017) was conducted on 526 stroke patients, presenting within the first 24 h to examine the risk factors for ischemic and hemorrhagic strokes. Severity was determined using the National Institutes of Health Stroke Scale (NIHSS).

Results:

Predominantly male (72.3%), 75% of the sample was >50 years old, with a mean body mass index (BMI) of 25.8 ± 4.3 kg/m2 and 14.6% obese patients. Hypertension and diabetes mellitus were the commonest comorbidities, followed by a history of ischemic heart disease and familial history of stroke. 20.5% of patients had mild strokes, 57.4% had moderate, 8.4% experienced moderate-severe strokes, whereas 7.2% had severe strokes. Regarding the admission diagnoses, 56.8% were ischemic, 18.6% were hemorrhagic, 1.1% had a transient ischemic attack, 6.6% suffered recurrent strokes, and 17% were other forms.

Conclusion:

The foremost risk factors for stroke in India, hypertension and diabetes, need to be controlled and treated like other global high-risk populations for stroke prevention. The NIHSS scores highlight the relationship between risk factors and stroke severity.
Socioeconomic disparities and risk of hypertension among older Americans: the Health and Retirement Study
Authors: Neufcourt Lola , Zins Marie , Berkman Lisa F. , Grimaud Olivier
Published: August 2021

Background:

Reducing hypertension represents a critical point of intervention to lower the burden of cardiovascular disease worldwide. Although the relationship between lower socioeconomic status and higher rates of hypertension is well documented, most of the evidence comes from prevalence studies involving young adult population.

Aim:

To investigate the independent association of wealth, education and income with incident hypertension among older adults living in the United States.

Methods:

This cohort study included 16 587 individuals aged 50 years and older, free of hypertension and cardiovascular disease at baseline from the Health and Retirement Study over the period 1992–2014. We used Cox proportional hazards models to examine longitudinal associations between wealth, education, and income at baseline and self-reported diagnosis of incident hypertension.

Results:

During a median follow-up of 7.8 years, 6817 participants declared an occurrence of hypertension (incidence rate: 45.3 [95% confidence interval (CI) = 44.2–46.4] per 1000 person-years). Overall, those in low as compared with high socioeconomic status groups had a higher risk of developing hypertension in late life. In particular, adjusted hazard ratios [95% CI] across decreasing wealth quartiles were 1.0 (reference), 0.97 [0.88–1.08], 1.17 [1.05–1.30], and 1.20 [1.07–1.35] in men, and 1.0 (reference), 1.28 [1.17–1.41], 1.21 [1.09–1.33], and 1.28 [1.16–1.42] in women. In multivariate analyses, wealth remained strongly associated with incident hypertension among women after accounting for other socioeconomic, behavioral and anthropometric risk factors.

Conclusions:

Socioeconomic status, especially wealth, is a strong independent predictor of incident hypertension in older adults. Our findings support population-based interventions tailored to those in disadvantaged socioeconomic groups to reduce the risk of hypertension.
Operational Stress Control Service
Authors: Martindale Sarah L. , Shura Robert D. , Cooper Marc A. , Womack Sheila F. , Hurley Robin A. , Vair Christina L. , Rowland Jared A.
Published: August 2021

Objective:

This manuscript details the methods, outcomes, and lessons learned from a successful multi-dimensional, interdisciplinary, institutional response to HCW well-being during the COVID-19 pandemic.

Methods:

Operational Stress Control Service (OSCS) is a model for the prevention and management of stress and trauma implemented within an occupational system. Communication, Employee Wellness, and Intervention were targeted program aspects, adapted from an established US military protocol.

Results:

Since April 2020, OSCS has received 4660 unique survey responses; reached 1007 employees in-person; informed 125 leadership-hosted videoconferences; and assisted 13 departments with grief and morale-related challenges.

Conclusions:

OSCS improved communication across the organization and allowed for rapid deployment of solutions to maintain effective operations. Results highlight the benefit of multiple avenues of frequent, bottom-up, and top-down communication. Creating such services during times of normalcy might be considered in preparation for future crisis.