bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare utilization is a collider: an introduction to collider bias in EHR data reuse
Authors: Weiskopf Nicole G , Dorr David A , Jackson Christie , Lehmann Harold P , Thompson Caroline A
Published: February 2023

Objectives

Collider bias is a common threat to internal validity in clinical research but is rarely mentioned in informatics education or literature. Conditioning on a collider, which is a variable that is the shared causal descendant of an exposure and outcome, may result in spurious associations between the exposure and outcome. Our objective is to introduce readers to collider bias and its corollaries in the retrospective analysis of electronic health record (EHR) data.

Target audience

Collider bias is likely to arise in the reuse of EHR data, due to data-generating mechanisms and the nature of healthcare access and utilization in the United States. Therefore, this tutorial is aimed at informaticians and other EHR data consumers without a background in epidemiological methods or causal inference.

Scope

We focus specifically on problems that may arise from conditioning on forms of healthcare utilization, a common collider that is an implicit selection criterion when one reuses EHR data. Directed acyclic graphs (DAGs) are introduced as a tool for identifying potential sources of bias during study design and planning. References for additional resources on causal inference and DAG construction are provided.
Red clover supplementation modifies rumen fermentation and promotes feed efficiency in ram lambs
Authors: Weinert-Nelson Jennifer R , Ely Donald G , Flythe Michael D , Hamilton Tracy A , May John B , Ferrell Jessica L , Hamilton Matthew C , LeeAnn Jacks Whitney , Davis Brittany E
Published: February 2023

Red clover produces isoflavones, including biochanin A, which have been shown to have microbiological effects on the rumen while also promoting growth in beef cattle. The objective was to determine if supplementation of biochanin A via red clover hay would produce similar effects on the rumen microbiota and improve growth performance of lambs. Twenty-four individually-housed Polypay ram lambs (initial age: 114 ± 1 d; initial weight: 38.1 ± 0.59 kg) were randomly assigned to one of three experimental diets (85:15 concentrate:roughage ratio; N = 8 rams/treatment): CON—control diet in which the roughage component (15.0%, w/w, of the total diet) consisted of orchardgrass hay; 7.5-RC—red clover hay substituted for half (7.5%, w/w, of the total diet) of the roughage component; and 15-RC—the entire roughage component (15.0%, w/w, of the total diet) consisted of red clover hay. Feed intake and weight gain were measured at 14-d intervals for the duration of the 56-d trial, and rumen microbiological measures were assessed on days 0, 28, and 56. Red clover supplementation impacted growth performance of ram lambs. Average daily gains (ADG) were greater in ram lambs supplemented with red clover hay (7.5-RC and 15-RC) than for those fed the CON diet (P < 0.05). Conversely, dry matter intake (DMI) was lower in 7.5-RC and 15-RC than for CON lambs (P = 0.03). Differences in ADG and DMI resulted in greater feed efficiency in ram lambs supplemented with red clover hay (both 7.5-RC and 15-RC) compared to CON (P < 0.01). Rumen microbiota were also altered by red clover supplementation. The total viable number of hyper-ammonia-producing bacteria in 7.5-RC and 15-RC decreased over the course of the experiment and were lower than CON by day 28 (P ≤ 0.04). Amylolytic bacteria were also lower in 15-RC than in CON (P = 0.03), with a trend for lower amylolytic bacteria in 7.5-RC (P = 0.08). In contrast, there was tendency for greater cellulolytic bacteria in red clover supplemented lambs than in CON (P = 0.06). Red clover supplementation also increased fiber utilization, with greater ex vivo dry matter digestibility of hay for both 7.5-RC and 15-RC compared to CON by day 28 (P < 0.03). Results of this study indicate that low levels of red clover hay can elicit production benefits in high-concentrate lamb finishing systems through alteration of the rumen microbiota.
Neutrophil activation in RSV: close encounters of the chemokined
Authors: Thwaites Ryan S
Published: February 2023

Trans-epithelial migration and physical interaction are required for full activation of neutrophils during in vitro RSV infection.
Fatty acid profiles of oomycetes (Halophytophthora and Phytopythium spp.) from Philippines mangroves
Authors: Neri Kimberly D , Devanadera Mark Kevin P , Watanabe Kenshi , Bennett Reuel M , Arafiles Kim Hazel V , Aki Tsunehiro , Dedeles Gina R
Published: February 2023

Mangroves create an ecological environment for a diverse assemblage of organisms, including marine and mangrove oomycetes. Halophytophthora spp., in particular, are isolated from fallen senescent mangrove leaves. Studies reported on Philippines oomycetes are mostly on their distribution and taxonomy, while fatty acid studies have not yet been fully explored. Recently, oomycetes were reported as efficient producers of various fatty acids; therefore, bioprospecting efforts are aimed at obtaining more industrially important fatty acid compounds for aquaculture, biodiesel production, and human consumption. In this study, 21 isolated oomycetes, identified as Halophytophthora spp., and two type species of Phytopythium, were grown in a broth medium containing peptone, yeast extract, glucose, and 50% seawater and incubated at room temperature for 3 weeks for fatty acid production and identification. Results revealed the presence of various fatty acids, mainly palmitic acid (C16:0), linoleic acid (C18:2n6c), oleic acid (C18:1n9c), cis-11,14,17-eicosatrienoic acid (ETA, C20:3n3), and stearic acid (C18:0), from Halophytophthora and Phytopythium isolates ranging from 2% to 30% total fatty acids. An omega-6 fatty acid, Ƴ-linolenic acid (GLA, C18:3n6), was found in Phytopythium isolates with considerably higher concentrations compared to Halophytophthoras. Further, omega-3 polyunsaturated fatty acid, cis-11,14,17-eicosatrienoic acid (ETA, C20:3n3), was detected on most oomycete isolates.
WISE J185503.7+592234: A particularly low mass ratio contact binary approaching merger
Authors: Guo Di-Fu , Li Kai , Liu Fen , Li Huai-Zhen , Liu Xin-Yi
Published: February 2023

In this paper, the total eclipsing binary WISE J185503.7+592234 (hereinafter J185503), whose mass ratio is around the mass ratio limit, was observed and investigated for the first time. The stellar atmospheric parameters of the primary (more massive) component were calculated by the spectral fitting, and the following results are obtained: Teff = 5747 ± 25 K, [Fe/H] = −0.16 ± 0.04 dex, logg = 4.78 ± 0.05 cm s−2. Although J185503 has a very small amplitude (∼ 0.17 mag in V band) and a short period (0.2800782 d), its light curves exhibit total eclipses (eclipse duration: ∼ 40 min, which is about 0.1 phase). The light curves derived from TESS exhibit some unusual behaviour, such as inversion of the O’Connell effect, exchange of occultation, and transit depths. Photometric solutions obtained from the multiband observations suggest that J185503 has a particularly low mass ratio (q = 0.0514) and a moderate contact degree of $26{{\ \rm per\ cent}}$. Based on 103 newly determined times of minimum spanning 14 yr, a secular period decrease was found, which is calculated to be dP/dt = −2.24 × 10−7 d yr−1. Through analysing the instability criterion, such as the instability separation, the instability mass ratio, and the ratio of spin angular momentum (Jspin) to the orbital angular momentum (Jorb), J185503 can be regarded as a progenitor of luminous red novae.
First on-sky demonstration of a scintillation correction technique using tomographic wavefront sensing
Authors: Hartley Kathryn E , Farley Oliver J D , Townson Matthew J , Osborn James , Wilson R W
Published: February 2023

Scintillation noise significantly limits high precision ground-based photometry of bright stars. In this paper, we present the first ever on-sky demonstration of scintillation correction. The technique uses tomographic wavefront sensing to estimate the spatial-temporal intensity fluctuations induced by high altitude optical turbulence. With an estimate of the altitudes and relative strengths of the turbulent layers above the telescope, the wavefront sensor data from multiple guide stars can be combined to estimate the phase aberrations of the wavefront at each altitude through the use of a tomographic algorithm. This 3D model of the phase aberrations can then be used to estimate the intensity fluctuations across the telescope pupil via Fresnel propagation. The measured photometric data for a given target within the field of view can then be corrected for the effects of scintillation using this estimate in post-processing. A simple proof-of-concept experiment using a wavefront sensor and a stereo-SCIDAR turbulence profiler attached to the 2.5 m Isaac Newton Telescope was performed for a range of exposure times using the Orion Trapezium cluster as the reference stars. The results from this on-sky demonstration as well as simulations estimating the expected performance for a full tomographic AO system with laser guide stars are presented. On-sky, the scintillation index was reduced on average by a factor of 1.9, with a peak of 3.4. For a full tomographic system, we expect to achieve a maximum reduction in the scintillation index by a factor of ∼25.
Triggered Population III star formation: the effect of H2 self-shielding
Authors: Chiaki Gen , Wise John H
Published: February 2023

The multiplicity of metal-free (Population III) stars may influence their feedback efficiency within their host dark matter haloes, affecting subsequent metal enrichment and the transition to galaxy formation. Radiative feedback from massive stars can trigger nearby star formation in dense self-shielded clouds. In model radiation self-shielding, the H2 column density must be accurately computed. In this study, we compare two local approximations based on the density gradient and Jeans length with a direct integration of column density along rays. After the primary massive star forms, we find that no secondary stars form for both the direct integration and density gradient approaches. The approximate method reduces the computation time by a factor of 2. The Jeans length approximation overestimates the H2 column density by a factor of 10, leading to five numerically enhanced self-shielded, star-forming clumps. We conclude that the density gradient approximation is sufficiently accurate for larger volume galaxy simulations, although one must still caution that the approximation cannot fully reproduce the result of direct integration.
Chemodynamical ages of small-scale kinematic structures of the galactic disc in the solar neighbourhood from ∼250 000 K and M dwarfs
Authors: Medan Ilija , Lépine Sébastien
Published: February 2023

We combine photometric metallicities with astrometry from Gaia DR3 to examine the chemodynamic structure of ∼250 000 K dwarfs in the solar neighbourhood (SN). In kinematics, we observe ridges/clumps of ‘kinematic groups’, like studies of more massive main-sequence stars. Here, we note clear differences in both metallicity and vertical velocity as compared with the surrounding regions in velocity space and hypothesize this is due to differences in mean age. To test this, we develop a method to estimate the age distribution of subpopulations of stars. In this method, we use GALAH data to define probability distributions of W versus [M/H] in age bins of 2 Gyr and determine optimal age distributions as the best-fitting weighted sum of these distributions. This process is then validated using the GALAH subset. We estimate the probable age distribution for regions in the kinematic plane, where we find significant substructure that is correlated with the kinematic groups. Most notably, we find an age gradient across the Hercules streams that is correlated with birth radius. Finally, we examine the bending and breathing modes as a function of age. From this, we observe potential hints of an increase in the bending amplitude with age, which will require further analysis in order to confirm it. This is one of the first studies to examine these chemodynamics in the SN using primarily low-mass stars and we hope these findings can better constrain dynamical models of the Milky Way due to the increase in resolution the sample size provides.
Cortical microtubules contribute to division plane positioning during telophase in maize
Authors: Bellinger Marschal A , Uyehara Aimee N , Allsman Lindy , Martinez Pablo , McCarthy Michael C , Rasmussen Carolyn G
Published: February 2023

Cell divisions are accurately positioned to generate cells of the correct size and shape. In plant cells, the new cell wall is built in the middle of the cell by vesicles trafficked along an antiparallel microtubule and a microfilament array called the phragmoplast. The phragmoplast expands toward a specific location at the cell cortex called the division site, but how it accurately reaches the division site is unclear. We observed microtubule arrays that accumulate at the cell cortex during the telophase transition in maize (Zea mays) leaf epidermal cells. Before the phragmoplast reaches the cell cortex, these cortical-telophase microtubules transiently interact with the division site. Increased microtubule plus end capture and pausing occur when microtubules contact the division site-localized protein TANGLED1 or other closely associated proteins. Microtubule capture and pausing align the cortical microtubules perpendicular to the division site during telophase. Once the phragmoplast reaches the cell cortex, cortical-telophase microtubules are incorporated into the phragmoplast primarily by parallel bundling. The addition of microtubules into the phragmoplast promotes fine-tuning of the positioning at the division site. Our hypothesis is that division site-localized proteins such as TANGLED1 organize cortical microtubules during telophase to mediate phragmoplast positioning at the final division plane.
Low-phosphorus concentrations and important ferric hydroxide scavenging in Archean seawater
Authors: Rego Eric Siciliano , Busigny Vincent , Lalonde Stefan V , Rossignol Camille , Babinski Marly , Philippot Pascal
Published: February 2023

The availability of nutrients in seawater, such as dissolved phosphorus (P), is thought to have regulated the evolution and activity of microbial life in Earth's early oceans. Marine concentrations of bioavailable phosphorus spanning the Archean Eon remain a topic of debate, with variable estimates indicating either low (0.04 to 0.13 μM P) or high (10 to 100 μM P) dissolved P in seawater. The large uncertainty on these estimates reflects in part a lack of clear proxy signals recorded in sedimentary rocks. Contrary to some recent views, we show here that iron formations (IFs) are reliable recorders of past phosphorus concentrations and preserved a primary seawater signature. Using measured P and iron (Fe) contents in Neoarchean IF from Carajás (Brazil), we demonstrate for the first time a clear partitioning coefficient relationship in the P-Fe systematics of this IF, which, in combination with experimental and Archean literature data, permits us to constrain Archean seawater to a mean value of 0.063 ± 0.05 μM dissolved phosphorus. Our data set suggests that low-phosphorus conditions prevailed throughout the first half of Earth's history, likely as the result of limited continental emergence and marine P removal by iron oxyhydroxide precipitation, supporting prior suggestions that changes in ancient marine P availability at the end of the Archean modulated marine productivity, and ultimately, the redox state of Earth's early oceans and atmosphere.

Classification: Physical Sciences, Earth, Atmospheric and Planetary Sciences
Effects of fat source and level on growth performance and carcass characteristics of commercial finishing pigs
Authors: Bromm Jenna J , Tokach Mike D , Woodworth Jason C , Goodband Robert D , DeRouchey Joel M , De Jong Jon A , Berg Kiah M , Pohlen Courtney L , Gebhardt Jordan T
Published: February 2023

Two experiments evaluated different fat sources and levels on growth performance, carcass characteristics, and economic impact in commercial finishing pigs. In experiment 1, 2,160 pigs (337 × 1,050, PIC; initially 37.3 ± 0.93 kg) were used. Pens of pigs were blocked by initial body weight and randomly assigned to one of four dietary treatments. Three of the four dietary treatments included: 0%, 1%, and 3% choice white grease. The final treatment contained no added fat until pigs were approximately 100 kg, and then a diet containing 3% fat was fed until marketing. Experimental diets were fed over four phases and were corn–soybean meal based with 40% distillers dried grains with solubles. Overall, increasing choice white grease decreased (linear, P = 0.006) average daily feed intake (ADFI) and increased (linear, P = 0.006) G:F. Pigs fed 3% fat only during the late-finishing phase (~100 to 129 kg) had similar G:F compared to pigs fed 3% for the entire study during the late-finishing phase, and intermediate G:F overall. Increasing fat tended to increase (linear, P = 0.068) hot carcass weight (HCW). Feed cost increased (linear, P ≤ 0.005) and income over feed cost decreased (linear, P ≤ 0.041) as choice white grease increased. In Experiment 2, 2,011 pigs (PIC 1,050 × DNA 600; initially 28.3 ± 0.53 kg) were used. Pens of pigs were blocked by location in the barn and randomly assigned to one of five dietary treatments arranged in a 2 × 2 + 1 factorial with main effects of fat source (choice white grease or corn oil) and level (1% or 3% of the diet) and a control diet with no added fat. Overall, increasing fat, regardless of source, increased (linear, P < 0.001) average daily gain (ADG), decreased (linear, P = 0.013) ADFI, and increased (linear, P < 0.001) G:F. Increasing fat increased (linear, P ≤ 0.016) HCW, carcass yield, and backfat depth. There was a fat source × level interaction (P < 0.001) in carcass fat iodine value (IV), where IV increased to a greater extent in pigs fed corn oil with only a small increase in IV in pigs fed diets with choice white grease. In conclusion, these experiments suggest that increasing fat from 0% to 3%, regardless of source, produced variable responses in ADG but consistently improved G:F. Increasing fat increased HCW, carcass yield, and backfat depth, but feeding diets containing corn oil increased carcass IV. With the ingredient prices used, the improvement in growth performance did not justify the extra diet cost from increasing fat from 0% to 3% in most situations.
Diagnostic Guide: Fusarium Head Blight of Cereal Grains
Authors: Hagerty C. H. , Namdar G. F. , Rivedal H. M. , Wen N. , Yin C.
Published: February 2023

Fusarium head blight (FHB) is a devastating disease of wheat ( Triticum aestivum) worldwide. This disease is caused by Fusarium species including Fusarium graminearum Schwabe sensu stricto, F. culmorum (Wm. G. Sm.) Sacc., and F. pseudograminearum O'Donnell & T. Aoki . This diagnostic guide provides information on the pathogen, signs and symptoms of disease, host range, and geographic distribution. A discussion of the mycotoxins produced by the pathogens, as well as management strategies, is also presented. Proper diagnosis will allow practitioners greater opportunity to adequately control FHB disease.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
A Perspective on Current Therapeutic Molecule Screening Methods Against ‘Candidatus Liberibacter asiaticus’, the Presumed Causative Agent of Citrus Huanglongbing
Authors: Kennedy John Paul , Wood Kimberly , Pitino Marco , Mandadi Kranthi , Igwe David O. , Shatters Robert G. , Widmer Timothy L. , Niedz Randall , Heck Michelle
Published: February 2023

Huanglongbing (HLB), referred to as citrus greening disease, is a bacterial disease impacting citrus production worldwide and is fatal to young trees and mature trees of certain varieties. In some areas, the disease is devastating the citrus industry. A successful solution to HLB will be measured in economics: citrus growers need treatments that improve tree health, fruit production, and most importantly, economic yield. The profitability of citrus groves is the ultimate metric that truly matters when searching for solutions to HLB. Scientific approaches used in the laboratory, greenhouse, or field trials are critical to the discovery of those solutions and to estimate the likelihood of success of a treatment aimed at commercialization. Researchers and the citrus industry use a number of proxy evaluations of potential HLB solutions; understanding the strengths and limitations of each assay, as well as how best to compare different assays, is critical for decision-making to advance therapies into field trials and commercialization. This perspective aims to help the reader compare and understand the limitations of different proxy evaluation systems based on the treatment and evaluation under consideration. The researcher must determine the suitability of one or more of these metrics to identify treatments and predict the usefulness of these treatments in having an eventual impact on citrus production and HLB mitigation. As therapies advance to field trials in the next few years, a reevaluation of these metrics will be useful to guide future research efforts on strategies to mitigate HLB and vascular bacterial pathogens in other perennial crops.
Diagnostic Molecular Markers for Identification of Different Races and a Pathotype of Columbia Root Knot Nematode
Authors: Hu Shengwei , Franco Jessica , Bali Sapinder , Chavoshi Sam , Brown Charles , Mojtahedi Hassan , Quick Rich , Cimrhakl Launa , Ingham Russell , Gleason Cynthia , Sathuvalli Vidyasagar
Published: February 2023

Columbia root-knot nematode, Meloidogyne chitwoodi, parasitizes potato plants and causes visible small brown dots in the tuber flesh that dramatically reduce the market value of the crop. In the Pacific Northwest, two races of M. chitwoodi, Race 1 and Race 2, and a pathotype, Race 1Roza, exist. The races and pathotype of M. chitwoodi are primarily differentiated based on host tests. Currently, M. chitwoodi can be differentiated from M. hapla and other Meloidogyne spp. based on morphology and molecular markers; however, the different pathotypes of M. chitwoodi cannot be differentiated using the aforementioned techniques. Based on the in silico genome comparison of M. chitwoodi Race 1, Race 2, and Race 1Roza, we developed diagnostic molecular markers that could successfully differentiate between M. chitwoodi races and the pathotype. We also developed three race-specific markers that can specifically amplify Race 1, Race 2, or Race 1Roza. Overall, we have potential markers that can successfully differentiate the two races and one pathotype of M. chitwoodi through simplex PCR, which has a potential application in plant disease diagnostics.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Diversity Profiling and the Distribution of Pathotypes and Mating Types in Indian Isolates of Ascochyta rabiei Causing Ascochyta Blight of Chickpea
Authors: Manjunatha Lakshmaiah , Uppala Leela Saisree , Mahesha Hunsur S. , Konda Aravinda Kumar , Rani Upasana , Singh Shailendra , Singh Narendra Pratap , Kumar Yogesh
Published: February 2023

The prevalence and distribution of pathotypes and mating types of Ascochyta rabiei (Pass.) Labr. were evaluated during the winter (October to March) seasons of 2017-18 and 2018-19. Forty-five A. rabiei isolates were obtained from six different states. From the survey results, the state of Punjab recorded the highest disease rating (Rating 9) compared with other chickpea-growing areas. The β-tubulin gene was amplified (330 bp) from all the isolates, and sequence analysis was performed. The phylogenetic tree produced by cluster analysis of β-tubulin gene sequences differentiated the 44 A. rabiei isolates . Using multiplex PCR, mating types were identified. From the mating type (MAT) study of all the A. rabiei isolates, amplification was observed at the 490-bp size, which corresponds to mating type 2 (MAT1-2). The four pathotypes (I, II, III, IV) and six physiological races were delineated based on the differential reaction of the disease. The most widely distributed pathotype was pathotype III (52.27%) among the surveyed regions of North Indian states, except Uttarakhand (where only pathotype II was recorded), followed by the least aggressive pathotype I (22.7%), highly aggressive pathotype IV (15.9%), and aggressive pathotype II (9.1%). Among the six physiological races identified, the most common races were race 5 (25%), followed by race 1 (22.73%), race 6 (18.18%), race 4 (18.18%), race 3 (9.09%), and race 2 (6.82%). Because of the prevalence of a single mating type among the surveyed locations in India, we opine that there may be less diversity in A. rabiei compared with isolates reported from other countries. However, to substantiate this conclusion, evaluation of more isolates of A. rabiei is required.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The homeostatic function of Regnase‐2 restricts neuroinflammation
Authors: Sowinska Weronika , Wawro Mateusz , Biswas Debolina D. , Kochan Jakub , Pustelny Katarzyna , Solecka Aleksandra , Gupta Angela S. , Mockenhaupt Karli , Polak Jarosław , Kwinta Borys , Kordula Tomasz , Kasza Aneta
Published: February 2023

The precise physiological functions and mechanisms regulating RNase Regnase‐2 (Reg‐2/ZC3H12B/MCPIP2) activity remain enigmatic. We found that Reg‐2 actively modulates neuroinflammation in nontransformed cells, including primary astrocytes. Downregulation of Reg‐2 in these cells results in increased mRNA levels of proinflammatory cytokines IL‐1β and IL‐6. In primary astrocytes, Reg‐2 also regulates the mRNA level of Regnase‐1 (Reg‐1/ZC3H12A/MCPIP1).Reg‐2is expressed at high levels in the healthy brain, but its expression is reduced during neuroinflammation as well as glioblastoma progression. This process is associated with the upregulation ofReg‐1. Conversely, overexpression of Reg‐2 is accompanied by the downregulation ofReg‐1in glioma cells in a nucleolytic NYN/PIN domain‐dependent manner. Interestingly, low levels ofReg‐2and high levels ofReg‐1correlate with poor‐glioblastoma patients' prognoses. WhileReg‐2restricts the basal levels of proinflammatory cytokines in resting astrocytes, its expression is reduced in IL‐1β‐activated astrocytes. Following IL‐1β exposure, Reg‐2 is phosphorylated, ubiquitinated, and degraded by proteasomes. Simultaneously, theReg‐2transcript is destabilized by tristetraprolin (TTP) andReg‐1through the AREs elements and conservative stem‐loop structure present in its 3′UTR. Thus, the peer‐control loop, of Reg‐1 and Reg‐2 opposing each other, exists. The involvement of TTP inReg‐2mRNA turnover is confirmed by the observation that high TTP levels correlate with the downregulation of theReg‐2expression in high‐grade human gliomas. Additionally, obtained results reveal the importance of Reg‐2 in inhibiting human and mouse glioma cell proliferation. Our current studies identify Reg‐2 as a critical regulator of homeostasis in the brain.
An outpatient pain plan and ED pain pathway for adults with sickle cell disease
Authors: Mercado Stephanie Harris
Published: February 2023

Sickle cell disease (SCD), one of the most common inherited diseases, is associated with lifetime morbidity and reduced life expectancy. In the United States, SCD primarily affects Black patients and, to a lesser degree, those of Hispanic descent. These populations are known to have healthcare disparities related to lower socioeconomic status, limited access to healthcare, and racial bias. The quality-adjusted life expectancy of patients with SCD is less than 35 years, because of progressive complications of the disease. The most common complication is severe episodic pain related to vaso-occlusive ischemic events. Despite guidelines, pain management often is delayed as patients struggle with resistance from clinicians based on concerns over opioid use or abuse, overdose, or drug-seeking behavior. Effective pain management can be accomplished with collaboration between clinicians and patients, a documented outpatient pain management plan, and when necessary, an ED clinical pain pathway for acute SCD pain management.
The complexity in DNA methylation analysis of allergic diseases
Authors: Legaki Evangelia , Taka Styliani , Papadopoulos Nikolaos G.
Published: February 2023

Purpose of review

This review aims to report all the recent studies that are implicated in DNA methylation analysis in the field of allergy and to underline the complexity of the study methodologies and results.

Recent findings

Although the growing number of DNA methylation studies have yet to point to a specific mechanism, herein we provide an overview of the majority of pathways considered to be implicated and highlight particular genes, like KNH2, ATPAF2 and ZNF385A, for their potential as biomarkers.

The epigenetic profile of respiratory allergic diseases, and particularly DNA methylation, has been investigated in various populations, so as to gain a better understanding of its role in pathogenesis. Through our analysis, multiple links are presented between differential DNA methylation loci and IgE sensitization, lung functionality and severity of the disease. Additionally, associations of this epigenetic change with maternal asthma, age, sex and environmental factors are described, thus uncovering specific gene families that, after further examination could be used as methylation biomarkers in cases of allergic disease.
Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type– and Sex-specific Effects during Development in Mice
Authors: Song Shao-yong , Peng Ke , Meng Xiao-wen , Shan Xi-sheng , Chen Qing-cai , Zhao Wei-ming , Shen Biyu , Qiu Hong , Liu Hong , Liu Hua-yue , Ji Fu-hai
Published: February 2023

Background

Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell type–specific information after sevoflurane exposure limits the mechanistic understanding of these effects. In this study, the authors tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type–specific effects in mice of both sexes.

Methods

Neonatal mice were exposed to 3% sevoflurane for 2 h at postnatal days 6, 8, and 10 and analyzed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. The Morris Water Maze test was performed to test neurocognitive function.

Results

The authors found sex-specific distribution of hippocampal cell types in control mice alongside cell type– and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice after sevoflurane exposure regarding the proportions of cornu ammonis 1 neurons (control vs. sevoflurane, males: 79.9% vs. 32.3%; females: 27.3% vs. 24.3%), dentate gyrus (males: 4.2% vs. 23.4%; females: 36.2% vs. 35.8%), and oligodendrocytes (males: 0.6% vs. 6.9%; females: 5.9% vs. 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand–receptor pairs in the cornu ammonis 1, cornu ammonis 3, and dente gyrus trisynaptic circuit (control vs. sevoflurane, cornu ammonis 1–cornu ammonis 3: 18 vs. 42 in males and 15 vs. 21 in females; cornu ammonis 1–dentate gyrus: 21 vs. 35 in males and 12 vs. 20 in females; cornu ammonis 3–dentate gyrus: 25 vs. 45 in males and 17 vs. 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased cornu ammonis 1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes.

Conclusions

This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and nonneuronal cell type– and sex-specific effects of sevoflurane during development.

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Management of Segmental Tibial Bone Defects With the Magnetic Motorized Intramedullary Transport Nail: A Case Series
Authors: Geiger Erik J. , Geffner Adam D. , Rozbruch S. Robert , Fragomen Austin T.
Published: February 2023

Critical-sized bone defects in the tibia can arise as sequelae of trauma, infection, tumor, or the treatment of congenital limb deficiencies. Treatment of these defects often requires bone transport, which has traditionally been accomplished using circular external fixators. The development of a bone transport nail facilitated tibia reconstruction through distraction osteogenesis using an all-internal device, thus avoiding the complications associated with chronic external fixation. Given the rarity of these cases, few studies have been published on the reconstruction outcomes using this implant. We sought to investigate the bone healing indices (including regenerate consolidation and time to docking site union) associated with the use of a magnetically controlled all-internal bone transport nail for the reconstruction of 4 patients treated for posttraumatic tibial bone loss. Perioperative and device-related complications are also reported.
Cephalomedullary Nailing of Unstable Geriatric Intertrochanteric Fractures on a Traction Table Combined With Percutaneous Reduction Techniques Is Safe and Results in a Low Rate of Cutout
Authors: Somasundaram Vivek , Owen Aaron R. , Hidden Krystin A. , Barlow Jonathan D. , Cross William W. , Sems Stephen A. , Yuan Brandon J.
Published: February 2023

Objectives:

To describe a reproducible technique for reduction assessment and percutaneous reduction of unstable intertrochanteric fractures treated with a cephalomedullary nail on a traction table.

Design:

Retrospective cohort study.

Setting:

Level-1 trauma center.

Patients:

Two-hundred 20 consecutive patients with intertrochanteric fractures.

Intervention:

Initial closed reduction performed on a traction table. Accessory incisions were used to facilitate a reduction in 77 patients (35%). All fractures were stabilized with a cephalomedullary nail.

Main Outcome Measurements:

Radiographic outcome including union, cutout, and fracture collapse (FC). Surgical outcomes including infection and hematoma were also reported.

Results:

Mechanical complications (nonunion, cutout, and varus collapse) occurred in 8.8% of patients at 1 year. Eleven of 13 patients who developed these complications had either suboptimal implant placement (tip-to-apex distance >25 mm) or a varus reduction. There was no difference in the incidence of reoperation, nonunion, lag screw cutout, or posttraumatic arthritis based on the use of an accessory incision for fracture reduction. There was a significant increase in FC in patients who received an accessory incision (6.8 mm vs. 5.4 mm, P = 0.04). One patient (1%) developed a hematoma in the accessory incision cohort, and 1 patient (0.7%) who did not have an accessory incision developed a postoperative infection.

Conclusions:

The current study suggests utilization of accessory incisions assist in reduction is safe and is associated with a low rate of complications. The surgeon should prioritize fracture reduction and optimal implant placement and not hesitate to use an accessory incision to assist with fracture reduction.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Effect of inferior vena cava respiratory variability-guided fluid therapy after laparoscopic hepatectomy: a randomized controlled clinical trial
Authors: Ji Jingjing , Ma Qian , Tian Yali , Shi Xueduo , Chen Luning , Zhu Xinhua , Yu Decai , Qiu Yudong , Li Bingbing
Published: February 2023

Background:

After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU).

Methods:

This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy.

Results:

Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9–36.7] mg/L vs. 44.8 [95%CI: 26.9–63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D-lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups.

Conclusion:

Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR.

Trial Registration:

ChiCTR-INR-17013093.
Development of a nicotine aerosol self-administration model in rats and the effects of e-liquid flavors
Authors: Marusich Julie A. , Palmatier Matthew I.
Published: February 2023

Electronic nicotine delivery system (ENDS) use is maintained by the positive reinforcement associated with preferred flavors. These flavors become conditioned reinforcers through pairings with primary reinforcers. This study sought to extend prior research with intravenous nicotine self-administration and develop a more ecologically valid preclinical model of aerosol self-administration in rats that incorporated flavors paired with sucrose. Rats were first trained to respond for oral sucrose with or without raspberry flavor to establish the flavor as a conditioned reinforcer for some groups. Rats were then exposed to aerosol self-administration. All groups responded for raspberry-flavored aerosol with or without nicotine. Rats responded more for raspberry flavored sucrose than unflavored sucrose. Despite raspberry increasing responding for sucrose, the flavor did not function as a conditioned reinforcer during aerosol self-administration and did not increase responding for nicotine. Throughout the aerosol self-administration phase, most groups responded more on the active than inactive lever, and some groups increased their response when the fixed ratio value was increased. At the end of the study, rats in nicotine groups earned similar or fewer aerosol deliveries than rats in vehicle groups. Aerosolized nicotine did not function as a reinforcer in this study, whereas aerosolized raspberry flavor may have maintained self-administration. Further preclinical investigation is needed to articulate the impact of flavors on ENDS use and whether they offset some aversive effects of nicotine or maintain responding on their own. If flavors reduce some aversive effects of self-administered nicotine, then policies to regulate flavors in e-liquids are prudent.
Artificial Intelligence and Machine Learning Approaches to Facilitate Therapeutic Drug Management and Model-Informed Precision Dosing
Authors: Poweleit Ethan A. , Vinks Alexander A. , Mizuno Tomoyuki
Published: February 2023

Background:

Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) approaches for supporting clinical research and support is increasing. However, AI and ML applications for precision dosing have been evaluated only recently. Given the capability of ML to handle multidimensional data, such as from electronic health records, opportunities for AI and ML applications to facilitate TDM and MIPD may be advantageous.

Methods:

This review summarizes relevant AI and ML approaches to support TDM and MIPD, with a specific focus on recent applications. The opportunities and challenges associated with this integration are also discussed.

Results:

Various AI and ML applications have been evaluated for precision dosing, including those related to concentration or exposure prediction, dose optimization, population pharmacokinetics and pharmacodynamics, quantitative systems pharmacology, and MIPD system development and support. These applications provide an opportunity for ML and pharmacometrics to operate in an integrated manner to provide clinical decision support for precision dosing.

Conclusions:

Although the integration of AI with precision dosing is still in its early stages and is evolving, AI and ML have the potential to work harmoniously and synergistically with pharmacometric approaches to support TDM and MIPD. Because data are increasingly shared between institutions and clinical networks and aggregated into large databases, these applications will continue to grow. The successful implementation of these approaches will depend on cross-field collaborations among clinicians and experts in informatics, ML, pharmacometrics, clinical pharmacology, and TDM.
Lifetime history of interpersonal partner violence is associated with insomnia among midlife women veterans
Authors: Goldstein Lizabeth A. , Jakubowski Karen P. , Huang Alison J. , Seal Karen H. , Maguen Shira , Inslicht Sabra S. , Byers Amy L. , Gibson Carolyn J.
Published: February 2023

Objective

Over a third of women in the United States report a lifetime history of intimate partner violence. Although a recent review found that intimate partner violence is related to poor subjective sleep, the majority of studies involved reproductive-aged women and used suboptimal measures of interpersonal violence and/or insomnia. We examined the relationship between lifetime intimate partner violence and current clinical insomnia in a cross-sectional sample of midlife women veterans.

Methods

Cross-sectional data were drawn from the Midlife Women Veterans Health Survey. Women Veterans (N = 232) aged 45 to 64 years enrolled in Department of Veterans Affairs health care in Northern California completed an adapted version of the Extended-Hurt, Insult, Threaten, Scream to assess lifetime history of intimate partner violence (screening threshold score and any physical, sexual, and psychological intimate partner violence) and the Insomnia Severity Index to assess current insomnia.

Results

In multivariable analyses, lifetime history of intimate partner violence was associated with twofold to fourfold odds of current clinical insomnia, including overall intimate partner violence (odds ratio, 3.24; 95% confidence interval, 1.57‐6.69), physical intimate partner violence (odds ratio, 2.01; 95% confidence interval, 1.09‐3.70), psychological intimate partner violence (odds ratio, 3.98; 95% confidence interval, 2.06‐7.71), and sexual intimate partner violence (odds ratio, 2.09; 95% confidence interval, 1.08‐4.07).

Conclusions

Lifetime history of intimate partner violence is common and may be associated with clinical insomnia during midlife. Findings highlight the importance of screening midlife women for intimate partner violence and recognizing the potential role of this traumatic exposure on women's health.
Neurodevelopment in the Congenital Heart Disease Population as Framed by the Life Course Health Development Framework
Authors: Smith Lindsay M. , Harrison Tondi M.
Published: February 2023

Background

Adverse neurodevelopment is a common comorbidity associated with congenital heart disease (CHD). The consequences of adverse neurodevelopment are seen across the life course. The cause of adverse neurodevelopment is multifactorial, and use of a life course perspective can assist with understanding and enhancing neurodevelopment in individuals with CHD.

Purpose

The purposes of this article are to (1) apply the Life Course Health Development framework to neurodevelopment in the population with CHD and (2) discuss how exposure to the pediatric cardiac intensive care unit (PCICU) environment during infancy is a point of intervention for improving neurodevelopmental outcomes.

Conclusion

Individuals with CHD are at an increased risk for adverse neurodevelopment across the life course. The PCICU environment is a point of intervention for improving neurodevelopmental outcomes. Stress can lead to changes in brain structure and function that are associated with negative outcomes in terms of outward behavioral and functional capacity, and the PCICU environment is a source of stressful stimuli. Infancy is a period of rapid brain growth, and the brain is more susceptible to stress during this period of the life course, putting infants receiving care in the PCICU at an increased risk of adverse neurodevelopment.

Clinical Implications

Interventions to support optimal neurodevelopment should focus on the PCICU environment during infancy. Developmentally supportive care models should be explored as a means of modifying the PCICU environment. In addition, more research is needed on the relationship between the PCICU and neurodevelopment. The conceptual model introduced can serve as a starting point for this research.