bluuebunny/crossref_metadata_2025 huggingface dataset:
Crustose coralline algae display sensitivity to near future global ocean change scenarios
Authors: Britton Damon , Mundy Craig N , Noisette Fanny , McGraw Christina M , Hurd Catriona L
Published: October 2021

Most research investigating how ocean warming and acidification will impact marine species has focused on visually dominant species, such as kelps and corals, while ignoring visually cryptic species such as crustose coralline algae (CCA). CCA are important keystone species that provide settlement cues for invertebrate larvae and can be highly sensitive to global ocean change. However, few studies have assessed how CCA respond to low emission scenarios or conditions. In a laboratory experiment, we examined the responses of temperate CCA assemblages to combined warming and acidification projected under low, medium, and high emissions. Net calcification and net photosynthesis significantly declined in all emissions scenarios, while significant reductions in relative growth rates and increases in percentage bleaching were observed in the highest emission scenario. The negative responses of CCA to both low and medium emissions suggest that they may be adversely impacted by combined warming and acidification by 2030 if current emissions are sustained. This will have far reaching consequences for commercially important invertebrates that rely on them to induce settlement of larvae. These findings highlight the need to take rapid action to preserve these critical keystone species and the valuable services they provide.
Carcinoma arising within sciatic nerve endometriosis: a case report
Authors: Yahaya Adaiah , Chauhan Govind , Idowu Adeyemi , Sumathi Vaiyapuri , Botchu Rajesh , Evans Scott
Published: October 2021

Endometriosis is a common condition with significant morbidity. There have been case reports of endometrial deposits affecting the sciatic nerve. Sciatic nerve endometriosis presents with cyclical sciatica and is often difficult to diagnose as it mimics many other causes of sciatica. We report the first case of histological proven endometrial carcinoma arising in a pre-existing sciatic nerve endometriosis. This was initially managed with radiotherapy however symptoms persisted and she opted to have surgery with the aim of better symptom control and long-term prognosis.
Fungal yield from sterile specimens
Authors: Tan Shu Jin , Gardam Dianne J , Radinger Arron , Le Tam , Nure Mariyam , Boan Peter
Published: October 2021

Clinicians may not request fungal culture when it is indicated. For sterile specimens without a specific request for fungal culture, in addition to bacteriology media, we routinely incubated a Sabouraud dextrose agar (SAB) plate for 4 weeks. From 44635 sterile specimens from years 2011 to 2016, 2722 (6.1%) had fungal request. Fungi were identified from 1037 (2.3%) specimens, 292 (0.6%) from specimens with specific fungal request, 574 (1.3%) from bacteriology media, and 171 (0.4%) solely from SAB plate (of 171, 77 were deemed clinically significant and 55 were treated). Relying on request for fungal studies from sterile specimens underdiagnosed fungal infection. Routine fungal culture had a modest incremental yield at a moderately high cost.

Lay Summary

Routine fungal culture of sterile specimens had a modest incremental yield to routine bacteriology culture and specific fungal request at a moderately high financial cost.
Weak lensing mass modeling bias and the impact of miscentring
Authors: Sommer Martin W , Schrabback Tim , Applegate Douglas E , Hilbert Stefan , Ansarinejad Behzad , Floyd Benjamin , Grandis Sebastian
Published: October 2021

Parametric modeling of galaxy cluster density profiles from weak lensing observations leads to a mass bias, whose detailed understanding is critical in deriving accurate mass-observable relations for constraining cosmological models. Drawing from existing methods, we develop a robust framework for calculating this mass bias in one-parameter fits to simulations of dark matter haloes. We show that our approach has the advantage of being independent of the absolute noise level, so that only the number of haloes in a given simulation and the representativeness of the simulated haloes for real clusters limit the accuracy of the bias estimation. While we model the bias as a lognormal distribution and the haloes with a Navarro–Frenk–White profile, our method can be generalized to any bias distribution and parametric model of the radial mass distribution. We find that the lognormal assumption is not strictly valid in the presence of miscentring of haloes. We investigate the use of cluster centres derived from weak lensing in the context of mass bias, and tentatively find that such centroids can yield sensible mass estimates if the convergence peak has a signal-to-noise ratio (SNR) approximately greater than 4. In this context we also find that the standard approach to estimating the positional uncertainty of weak lensing mass peaks using bootstrapping severely underestimates the true positional uncertainty for peaks with low SNRs. Though we determine the mass and redshift dependence of the bias distribution for a few experimental setups, our focus remains providing a general approach to computing such distributions.
Dancing in the void: hydrodynamical N-body simulations of the extremely metal-poor galaxy DDO 68
Authors: Pascale R , Annibali F , Tosi M , Marinacci F , Nipoti C , Bellazzini M , Romano D , Sacchi E , Aloisi A , Cignoni M
Published: October 2021

Using hydrodynamical N-body simulations, we show that the observed structure and kinematics of the extremely metal-poor dwarf irregular galaxy DDO 68 is compatible with a merger event with at least two smaller satellite galaxies. We were able to obtain a self-consistent model that simultaneously reproduces several of its observed features, including the very asymmetric and disturbed shape of the stellar component, the overall ${\rm H\, \small {\rm I}}$ distribution and its velocity field, the arc-like stellar structure to the west, and the low surface brightness stellar stream to the north. The model implies the interaction of the main progenitor of DDO 68 with two systems with dynamical masses $7\times 10^8\, \mathrm{ M}_{\odot }$ and almost $10^8\, \mathrm{ M}_{\odot }$ – 1/20 and 1/150 times the dynamical mass of DDO 68, respectively. We show that the merger between DDO 68 and the most massive of its satellites offers a route to explain the large offset of DDO 68 from the mass–metallicity relation. Assuming that the interacting galaxies have metallicities prior to the merger compatible with those of galaxies with similar stellar masses, we provide quantitative evidence that gas mixing alone does not suffice at diluting the gas of the two components; according to our simulations, the ${\rm H\, \small {\rm II}}$ regions observed along the cometary tail trace the low metallicity of the accreted satellite rather than that of DDO 68’s main body. In this case, the mass corresponding to the low metallicity is that of the secondary body and DDO 68 becomes consistent with the mass–metallicity relation.
A persistent double nuclear structure in 3C 84
Authors: Oh Junghwan , Hodgson Jeffrey A , Trippe Sascha , Krichbaum Thomas P , Kam Minchul , Paraschos Georgios Filippos , Kim Jae-Young , Rani Bindu , Sohn Bong Won , Lee Sang-Sung , Lico Rocco , Liuzzo Elisabetta , Bremer Michael , Zensus Anton
Published: October 2021

3C 84 (NGC 1275) is the radio source at the centre of the Perseus cluster and exhibits a bright radio jet. We observed the source with the Global Millimeter VLBI Array (GMVA) between 2008 and 2015, with a typical angular resolution of ∼50 $\mu$as. The observations revealed a consistent double nuclear structure separated by ∼770 gravitational radii assuming a black hole mass of 3.2 × 108 M⊙. The region is likely too broad and bright to be the true jet base anchored in the accretion disc or black hole ergosphere. A cone and parabola were fit to the stacked (time averaged) image of the nuclear region. The data did not strongly prefer either fit, but combined with a jet/counter-jet ratio analysis, an upper limit on the viewing angle to the inner jet region of ≤35° was found. This provides evidence for a variation of the viewing angle along the jet (and therefore a bent jet) within ∼0.5 pc of the jet launching region. In the case of a conical jet, the apex is located ∼2400 gravitational radii upstream of the bright nuclear region and up to ∼600 gravitational radii upstream in the parabolic case. We found a possible correlation between the brightness temperature and relative position angle of the double nuclear components, which may indicate rotation within the jet.
FOREVER22: galaxy formation in protocluster regions
Authors: Yajima Hidenobu , Abe Makito , Khochfar Sadegh , Nagamine Kentaro , Inoue Akio K , Kodama Tadayuki , Arata Shohei , Dalla Vecchia Claudio , Fukushima Hajime , Hashimoto Takuya , Kashikawa Nobunari , Kubo Mariko , Li Yuexing , Matsuda Yuichi , Mawatari Ken , Ouchi Masami , Umehata Hideki
Published: October 2021

We present results from a new cosmological hydrodynamics simulation campaign of protocluster (PC) regions, FOREVER22: FORmation and EVolution of galaxies in Extremely overdense Regions motivated by SSA22. The simulations cover a wide range of cosmological scales using three different zoom set-ups in a parent volume of $(714.2~\rm cMpc)^{3}$: PCR (Proto-Cluster Region; V = (28.6 cMpc)3, SPH particle mass, mSPH = 4.1 × 106 M⊙, and final redshift, zend = 2.0), BCG (Brightest proto-Cluster Galaxy; V ∼ (10 cMpc)3, mSPH = 5.0 × 105 M⊙ and zend = 4.0), and First (V ∼ (3 cMpc)3, mSPH = 7.9 × 103 M⊙ and zend = 9.5) runs, that allow us to focus on different aspects of galaxy formation. In the PCR runs, we follow 10 PCs, each harbouring 1–4 SMBHs with ${\rm M_{\rm BH}}\ge 10^{9}~{\rm M_{\odot }}$. One of the PC cores shows a spatially close arrangement of seven starburst galaxies with ${\rm SFR} \gtrsim 100~{\rm {\rm M_{\odot }}~{\rm yr^{-1}}}$ each, that are dust-obscured and would appear as submillimetre galaxies with flux ≳1 mJy at $1.1~ \rm mm$ in observations. The BCG runs show that the total SFRs of haloes hosting BCGs are affected by AGN feedback, but exceed $1000~{\rm {\rm M_{\odot }}~{\rm yr^{-1}}}$ at z ≲ 6. The First runs resolve mini-haloes hosting population (Pop) III stars and we show that, in PC regions, the dominant stellar population changes from Pop III to Pop II at z ≳ 20, and the first galaxies with ${\rm SFR} \gtrsim 18~{\rm {\rm M_{\odot }}~{\rm yr^{-1}}}$ form at z ∼ 10. These can be prime targets for future observations with the James Webb Space Telescope. Our simulations successfully reproduce the global star formation activities in observed PCs and suggest that PCs can kickstart cosmic reionization.
Genome-Wide Reconstruction of Rediploidization Following Autopolyploidization across One Hundred Million Years of Salmonid Evolution
Authors: Gundappa Manu Kumar , To Thu-Hien , Grønvold Lars , Martin Samuel A M , Lien Sigbjørn , Geist Juergen , Hazlerigg David , Sandve Simen R , Macqueen Daniel J
Published: October 2021

The long-term evolutionary impacts of whole-genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologs) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnolog sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent “explosion” of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing genome-wide ohnolog divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial “wave” of rediploidization in the late Cretaceous (85–106 Ma). This was followed by a period of relative genomic stasis lasting 17–39 My, where much of the genome remained tetraploid. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnolog divergence, scaling in complexity with the number of speciation events. Using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. This study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.
CircNet 2.0: an updated database for exploring circular RNA regulatory networks in cancers
Authors: Chen Yigang , Yao Lantian , Tang Yun , Jhong Jhih-Hua , Wan Jingting , Chang Jingyue , Cui Shidong , Luo Yijun , Cai Xiaoxuan , Li Wenshuo , Chen Qi , Huang Hsi-Yuan , Wang Zhuo , Chen Weiming , Chang Tzu-Hao , Wei Fengxiang , Lee Tzong-Yi , Huang Hsien-Da
Published: October 2021

Circular RNAs (circRNAs), which are single-stranded RNA molecules that have individually formed into a covalently closed continuous loop, act as sponges of microRNAs to regulate transcription and translation. CircRNAs are important molecules in the field of cancer diagnosis, as growing evidence suggests that they are closely related to pathological cancer features. Therefore, they have high potential for clinical use as novel cancer biomarkers. In this article, we present our updates to CircNet (version 2.0), into which circRNAs from circAtlas and MiOncoCirc, and novel circRNAs from The Cancer Genome Atlas database have been integrated. In total, 2732 samples from 37 types of cancers were integrated into CircNet 2.0 and analyzed using several of the most reliable circRNA detection algorithms. Furthermore, target miRNAs were predicted from the full-length circRNA sequence using three reliable tools (PITA, miRanda and TargetScan). Additionally, 384 897 experimentally verified miRNA–target interactions from miRTarBase were integrated into our database to facilitate the construction of high-quality circRNA–miRNA–gene regulatory networks. These improvements, along with the user-friendly interactive web interface for data presentation, search, and visualization, showcase the updated CircNet database as a powerful, experimentally validated resource, for providing strong data support in the biomedical fields. CircNet 2.0 is currently accessible at https://awi.cuhk.edu.cn/∼CircNet.
miRTarBase update 2022: an informative resource for experimentally validated miRNA–target interactions
Authors: Huang Hsi-Yuan , Lin Yang-Chi-Dung , Cui Shidong , Huang Yixian , Tang Yun , Xu Jiatong , Bao Jiayang , Li Yulin , Wen Jia , Zuo Huali , Wang Weijuan , Li Jing , Ni Jie , Ruan Yini , Li Liping , Chen Yidan , Xie Yueyang , Zhu Zihao , Cai Xiaoxuan , Chen Xinyi , Yao Lantian , Chen Yigang , Luo Yijun , LuXu Shupeng , Luo Mengqi , Chiu Chih-Min , Ma Kun , Zhu Lizhe , Cheng Gui-Juan , Bai Chen , Chiang Ying-Chih , Wang Liping , Wei Fengxiang , Lee Tzong-Yi , Huang Hsien-Da
Published: October 2021

MicroRNAs (miRNAs) are noncoding RNAs with 18–26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA–target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update’s critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3′ untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.
7′,5′-alpha-bicyclo-DNA: new chemistry for oligonucleotide exon splicing modulation therapy
Authors: Evéquoz Damien , Verhaart Ingrid E C , van de Vijver Davy , Renner Wolfgang , Aartsma-Rus Annemieke , Leumann Christian J
Published: October 2021

Antisense oligonucleotides are small pieces of modified DNA or RNA, which offer therapeutic potential for many diseases. We report on the synthesis of 7′,5′-α-bc-DNA phosphoramidite building blocks, bearing the A, G, T and MeC nucleobases. Solid-phase synthesis was performed to construct five oligodeoxyribonucleotides containing modified thymidine residues, as well as five fully modified oligonucleotides. Incorporations of the modification inside natural duplexes resulted in strong destabilizing effects. However, fully modified strands formed very stable duplexes with parallel RNA complements. In its own series, 7′,5′-α-bc-DNA formed duplexes with a surprising high thermal stability. CD spectroscopy and extensive molecular modeling indicated the adoption by the homo-duplex of a ladder-like structure, while hetero-duplexes with DNA or RNA still form helical structure. The biological properties of this new modification were investigated in animal models for Duchenne muscular dystrophy and spinal muscular atrophy, where exon splicing modulation can restore production of functional proteins. It was found that the 7′,5′-α-bc-DNA scaffold confers a high biostability and a good exon splicing modulation activity in vitro and in vivo.
A call for international research on COVID-19-induced brain dysfunctions
Authors: Valdes-Sosa Pedro A , Evans Alan C , Valdes-Sosa Mitchell J , Poo Mu-ming
Published: October 2021

COVID-19-induced brain dysfunction (CIBD) will put a strain on world health systems complicated by the heterogeneity of manifestations, which is higher than any other aspect of human biology. Neural, psychological and social causes must be disentangled for effective population-level management of CIBD. International cooperation is required in order to discover neurotechnologies appropriate for health systems.
Disruption of Hydrogen Gas Synthesis Enhances the Cellular Levels of NAD(P)H, Glycogen, Poly(3-hydroxybutyrate) and Photosynthetic Pigments Under Specific Nutrient Condition(s) in Cyanobacterium Synechocystis sp. PCC 6803
Authors: Sukkasam Nannaphat , Incharoensakdi Aran , Monshupanee Tanakarn
Published: October 2021

In photoautotrophic Synechocystis sp. PCC 6803, NADPH is generated from photosynthesis and utilized in various metabolism, including the biosynthesis of glyceraldehyde 3-phosphate (the upstream substrate for carbon metabolism), poly(3-hydroxybutyrate) (PHB), photosynthetic pigments, and hydrogen gas (H2). Redirecting NADPH flow from one biosynthesis pathway to another has yet to be studied. Synechocystis’s H2 synthesis, one of the pathways consuming NAD(P)H, was disrupted by the inactivation of hoxY and hoxH genes encoding the two catalytic subunits of hydrogenase. Such inactivation with a complete disruption of H2 synthesis led to 1.4-, 1.9-, and 2.1-fold increased cellular NAD(P)H levels when cells were cultured in normal medium (BG11), the medium without nitrate (-N), and the medium without phosphate (-P), respectively. After 49–52 d of cultivation in BG11 (when the nitrogen source in the media was depleted), the cells with disrupted H2 synthesis had 1.3-fold increased glycogen level compared to wild type of 83–85% (w/w dry weight), the highest level reported for cyanobacterial glycogen. The increased glycogen content observed by transmission electron microscopy was correlated with the increased levels of glucose 6-phosphate and glucose 1-phosphate, the two substrates in glycogen synthesis. Disrupted H2 synthesis also enhanced PHB accumulation up to 1.4-fold under -P and 1.6-fold under -N and increased levels of photosynthetic pigments (chlorophyll a, phycocyanin, and allophycocyanin) by 1.3- to 1.5-fold under BG11. Thus, disrupted H2 synthesis increased levels of NAD(P)H, which may be utilized for the biosynthesis of glycogen, PHB, and pigments. This strategy might be applicable for enhancing other biosynthetic pathways that utilize NAD(P)H.
The influence of spring warming and food chain length on plankton phenology in subtropical shallow lakes: a mesocosm study
Authors: He Hu , Ning Xiaoyu , Chen Kunquan , Li Qisheng , Han Yanqing , Huang Xiaolong , Li Kuanyi , Liu Zhengwen , Jeppesen Erik
Published: October 2021

Numerous studies have shown that warming advances spring phenology in various ecosystems. However, few studies explicitly consider the effect of food web structure, e.g. food chain length (FCL), and most studies have focused on temperate systems. We investigated the effect of vernal warming on the spring phenology of a key herbivore, Daphnia galeata (hereafter Daphnia), and its prey, phytoplankton, in subtropical shallow aquatic mesocosms in the presence and absence of the planktivorous fish Aristichthys nobilis, simulating food chains with two or three trophic levels. The warming effect on the timing of the spring phytoplankton peak varied with the FCL. Warming led to the disappearance of the phytoplankton peak in the 2-level systems but resulted in an extensive, delayed phytoplankton peak in the 3-level systems. Irrespective of the FCL, warming did not significantly advance the timing of the Daphnia peak, although Daphnia recruited earlier under warm conditions. Both warming and FCL significantly reduced the size of the Daphnia peak. Our study suggests that spring warming affects the plankton spring phenology in subtropical shallow lakes, but the response patterns depend on the food web structure.
Using continuous directed evolution to improve enzymes for plant applications
Authors: García-García Jorge D , Van Gelder Kristen , Joshi Jaya , Bathe Ulschan , Leong Bryan J , Bruner Steven D , Liu Chang C , Hanson Andrew D
Published: October 2021

Continuous directed evolution of enzymes and other proteins in microbial hosts is capable of outperforming classical directed evolution by executing hypermutation and selection concurrently in vivo, at scale, with minimal manual input. Provided that a target enzyme’s activity can be coupled to growth of the host cells, the activity can be improved simply by selecting for growth. Like all directed evolution, the continuous version requires no prior mechanistic knowledge of the target. Continuous directed evolution is thus a powerful way to modify plant or non-plant enzymes for use in plant metabolic research and engineering. Here, we first describe the basic features of the yeast (Saccharomyces cerevisiae) OrthoRep system for continuous directed evolution and compare it briefly with other systems. We then give a step-by-step account of three ways in which OrthoRep can be deployed to evolve primary metabolic enzymes, using a THI4 thiazole synthase as an example and illustrating the mutational outcomes obtained. We close by outlining applications of OrthoRep that serve growing demands (i) to change the characteristics of plant enzymes destined for return to plants, and (ii) to adapt (“plantize”) enzymes from prokaryotes—especially exotic prokaryotes—to function well in mild, plant-like conditions.
Trade Finance and the Durability of the Dollar
Authors: Chahrour Ryan , Valchev Rosen
Published: October 2021

We propose a model in which the emergence of a single dominant currency is driven by the need to finance international trade. The model generates multiple stable steady states, each characterized by a different dominant asset, consistent with the historical durability of real-world currency regimes. The persistence of regimes is caused by a positive interaction between the returns to saving in an asset and the use of that asset for financing trade. A calibrated version of the model shows that the welfare gains of dominance are substantial, but accrue primarily during the transition to dominance. We perform several counterfactual experiments to assess potential threats to the dollar’s continued dominance.
Comomentum: Inferring Arbitrage Activity from Return Correlations
Authors: Lou Dong , Polk Christopher
Published: October 2021

We propose a novel measure of arbitrage activity to examine whether arbitrageurs can have a destabilizing effect on the stock market. We focus on stock price momentum, a classic example of a positive-feedback strategy that our theory predicts can be destabilizing. Our measure, dubbed comomentum, is the high-frequency abnormal return correlation among stocks on which a typical momentum strategy would speculate. When comomentum is low, momentum strategies are stabilizing, reflecting an underreaction phenomenon that arbitrageurs correct. When comomentum is high, the returns on momentum stocks strongly revert, reflecting prior overreaction from crowded momentum trading that pushes prices away from fundamentals.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: cohort study using data from the Clinical Practice Research Datalink Gold and Aurum
Authors: Nakafero Georgina , Grainge Matthew J , Card Tim , Taal Maarten W , Aithal Guruprasad P , Zhang Weiya , Doherty Michael , Fox Christopher P , Mallen Christian D , Abhishek Abhishek
Published: October 2021

Objective

To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results.

Methods

Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination.

Results

Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02).

Conclusion

We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments.
Post-COVID conditions—What practitioners need to know
Authors: Waterbury Susan
Published: October 2021

Up to 80% of patients have symptoms lasting 4-12 weeks or longer post infection with COVID-19. Persistent symptoms can be diverse and may include myalgia, insomnia, mobility issues, hair loss, loss of smell/taste, shortness of breath, chest pain, fatigue, cognitive impairment, and depression. More evidence will be forthcoming regarding long-term COVID-19 sequelae.
Motivation for Health Promotion in Cancer Survivors
Authors: Tock Wing Lam
Published: October 2021

Motivation for health promotion is an essential concept in health care research, as it pertains to an individual's ability to adapt to the adversity of chronic illnesses, including cancer. Adopting Rodgers’ evolutionary method of concept analysis, the objective of this article is to clarify the concept based on its existing operationalization noted in cancer survivorship literature. Through a close examination of the construction of the concept, this article facilitates the understanding of concept as it relates to the field of cancer survivorship care, which in turn helps provide guidance for developing health promotion intervention targeted at cancer survivors.
Best Practice Guidelines for Assessment and Management of Osteoporosis in Adult Patients Undergoing Elective Spinal Reconstruction
Authors: Sardar Zeeshan M. , Coury Josephine R. , Cerpa Meghan , DeWald Christopher J. , Ames Christopher P. , Shuhart Christopher , Watkins Colleen , Polly David W. , Dirschl Douglas R. , Klineberg Eric O. , Dimar John R. , Krohn Kelly D. , Kebaish Khaled M. , Tosi Laura L. , Kelly Michael , Lane Nancy E. , Binkley Neil C. , Berven Sigurd H. , Lee Nathan J. , Anderson Paul , Angevine Peter D. , Lehman Ronald A. , Lenke Lawrence G.
Published: October 2021

Study Design.

Expert consensus study.

Objective.

This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction.

Summary of Background Data.

Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes.

Methods.

A multidisciplinary panel with 18 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus.

Results.

Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared with antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months.

Conclusion.

Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.

Level of Evidence: 5
Comprehensive Review of Cardiovascular Complications of Coronavirus Disease 2019 and Beneficial Treatments
Authors: Welty Francine K. , Rajai Nazanin , Amangurbanova Maral
Published: October 2021

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed.
Mental Health and Developmental Disorder Diagnoses of Foster and Nonfoster Children Enrolled in Medicaid
Authors: Keefe Rachael J. , Cummings Angela D. L. , Greeley Christopher S. , Van Horne Bethanie S.
Published: October 2021

Objective:

This study used Medicaid claims to compare the prevalence of mental health disorders (MHDs) and developmental disorders (DDs) between foster and nonfoster youth.

Methods:

Medicaid claims data were used to identify MHDs and DDs. Diagnosis codes were categorized into 16 MHD and 8 DD groups. Children were enrolled in their respective Medicaid plan for at least 30 days and had at least 1 health care encounter generating a claim. Prevalence was compared between children in foster care and children not in foster care overall and by age group. Logistic regression was used to compare the odds of having an MHD or DD diagnosis.

Results:

Of the 8706 children in foster care, 20.1% had an MHD compared with 9.7% of the 392,815 nonfoster children. Overall, the 5 most prevalent MHD and DD conditions among foster youth were attention-deficit/hyperactivity disorder (ADHD) (11.0%), miscellaneous (9.3%), bipolar disorders (5.6%), communication disorders (5.4%), and depressive disorders (5.1%). The 5 most prevalent conditions among children not in foster care were ADHD (6.1%); communication disorders (3.0%); disruptive, impulse control, and conduct disorders (2.7%); specific learning disorders (2.5%); and trauma and stressor-related disorders (2.4%). Anxiety was significantly higher among nonfoster children. The prevalence of the most common conditions by age group is reported. Overall, children in foster care had 2.5 and 2.3 times higher odds of having an MHD or DD diagnosis, respectively.

Conclusion:

Children in foster care had significantly higher rates of mental health and DD diagnoses compared with children not in foster care.
Cardioprotective Effects of Glucagon-like Peptide-1 (9-36) Against Oxidative Injury in H9c2 Cardiomyoblasts: Potential Role of the PI3K/Akt/NOS Pathway
Authors: Nuamnaichati Narawat , Parichatikanond Warisara , Mangmool Supachoke
Published: October 2021

Glucagon-like peptide (GLP)-1(7-36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9-36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7-36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent pathway. Nevertheless, the cardioprotective effects of GLP-1(9-36) have not fully understood. The present study investigated the effects of GLP-1(9-36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cells. Here, we reported that GLP-1(9-36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9-36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating antiapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9-36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase-induced nitric oxide production. Thus, GLP-1(9-36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart via PI3K/Akt/nitric oxide synthase signaling pathway.
Lipoprotein(a) and Cardiovascular Disease: A Missing Link for Premature Atherosclerotic Heart Disease and/or Residual Risk
Authors: Melita Helen , Manolis Antonis A. , Manolis Theodora A. , Manolis Antonis S.
Published: October 2021

Lipoprotein(a) or lipoprotein “little a” [Lp(a)] is an under-recognized causal risk factor for cardiovascular (CV) disease (CVD), including coronary atherosclerosis, aortic valvular stenosis, ischemic stroke, heart failure, and peripheral arterial disease. Elevated plasma Lp(a) (≥50 mg/dL or ≥100 nmol/L) is commonly encountered in almost 1 in 5 individuals and confers a higher CV risk compared with those with normal Lp(a) levels, although such normal levels have not been generally agreed upon. Elevated Lp(a) is considered a cause of premature and accelerated atherosclerotic CVD. Thus, in patients with a positive family or personal history of premature coronary artery disease (CAD), Lp(a) should be measured. However, elevated Lp(a) may confer increased risk for incident CAD even in the absence of a family history of CAD, and even in those who have guideline-lowered LDL cholesterol (<70 mg/dL) and continue to have a persisting CV residual risk. Thus, measurement of Lp(a) will have a significant clinical impact on the assessment of atherosclerotic CVD risk, and will assume a more important role in managing patients with CVD with the advent and clinical application of specific Lp(a)-lowering therapies. Conventional therapeutic approaches like lifestyle modification and statin therapy remain ineffective at lowering Lp(a). Newer treatment modalities, such as gene silencing via RNA interference with use of antisense oligonucleotide(s) or small interfering RNA molecules targeting Lp(a), seem very promising. These issues are herein reviewed, accumulated data are scrutinized, meta-analyses and current guidelines are tabulated, and Lp(a)-related CVDs and newer therapeutic modalities are pictorially illustrated.
Exclusion of left atrial appendage: effects beyond thromboembolic prevention
Authors: Bai Rong , Zawaneh Michael , Weiss Peter J. , Su Wilber W.
Published: October 2021

Purpose of review

This review aims to summarize the nonthromboembolic prevention effects of left atrial appendage exclusion (LAAE).

Recent findings

Left atrial appendage (LAA) secretes multiple hormones; regulates blood volume and pressure; and generates trigger activities. Exclusion of the LAA by different techniques may lead to downstream effects including changes in blood pressure and cardiac performance, improvement of outcome of atrial fibrillation (AF) ablation, and alteration of metabolism.

LAAE procedures not only prevent thromboembolic events in patients with AF, but rather may bring additional benefits or side-effect to patients undergoing LAAE.
Development of the Novel Pneumonia Risk Score to Predict Radiographic Pneumonia in Children
Authors: Lipsett Susan C. , Hirsch Alexander W. , Monuteaux Michael C. , Bachur Richard G. , Neuman Mark I.
Published: October 2021

Background:

The diagnosis of pneumonia in children is challenging, given the wide overlap of many of the symptoms and physical examination findings with other common respiratory illnesses. We sought to derive and validate the novel Pneumonia Risk Score (PRS), a clinical tool utilizing signs and symptoms available to clinicians to determine a child’s risk of radiographic pneumonia.

Methods:

We prospectively enrolled children 3 months to 18 years in whom a chest radiograph (CXR) was obtained in the emergency department to evaluate for pneumonia. Before CXR, we collected information regarding symptoms, physical examination findings, and the physician-estimated probability of radiographic pneumonia. Logistic regression was used to predict the presence of radiographic pneumonia, and the PRS was validated in a distinct cohort of children with suspected pneumonia.

Results:

Among 1181 children included in the study, 206 (17%) had radiographic pneumonia. The PRS included age in years, triage oxygen saturation, presence of fever, presence of rales, and presence of wheeze. The area under the curve (AUC) of the PRS was 0.71 (95% confidence interval [CI]: 0.68–0.75), while the AUC of clinician judgment was 0.61 (95% CI: 0.56–0.66) (P < 0.001). Among 2132 children included in the validation cohort, the PRS demonstrated an AUC of 0.69 (95% CI: 0.65–0.73).

Conclusions:

In children with suspected pneumonia, the PRS is superior to clinician judgment in predicting the presence of radiographic pneumonia. Use of the PRS may help efforts to support the judicious use of antibiotics and chest radiography among children with suspected pneumonia.
Call to action: treating dry eye disease and setting the foundation for successful surgery
Authors: Donaldson Kendall , Parkhurst Gregory , Saenz Bobby , Whitley Walter , Williamson Blake , Hovanesian John
Published: October 2021

Dry eye disease (DED) is a common disease that can reduce the quality of life. Prevalence estimates vary but have been reported to be as high as 60% in some populations. Diagnosis is complicated by a multifactorial etiology and a disconnection between clinical signs and patient-reported symptomatology. Critically, preexisting DED can exacerbate postoperative dry eye symptoms and reduce patient satisfaction after ocular surgery, highlighting the value of thorough evaluation and screening for signs and symptoms of DED in preparation for ocular surgery. This article reviewed predisposing and exacerbating factors for DED and presented an argument for the importance of adequately treating DED prior to surgery, from the perspective of both the patient and the provider. It briefly reviewed currently available methodologies and emphasized the utility of multimodal diagnosis and treatment algorithms to optimize outcomes and patient satisfaction.
Comparison of refractive and visual outcomes between image-guided system–assisted small-incision lenticule extraction and wavefront-optimized FS-LASIK in treatment of high astigmatism
Authors: Kose Bulent
Published: October 2021

Purpose:

To compare the refractive and visual results of image-guided system–assisted small-incision lenticule extraction (IGA-SMILE) and wavefront-optimized femtosecond laser in situ keratomileusis (FS-LASIK) in the treatment of high astigmatism.

Settings:

Osmangazi Aritmi Hospital, Bursa, Turkey.

Design:

Retrospective.

Methods:

This retrospective case-matched study included 64 eyes that had undergone IGA-SMILE and 64 eyes that had undergone wavefront-optimized FS-LASIK. The mean preoperative myopia and astigmatism were −4.05 ± 1.98 diopter (D) and 3.11 ± 1.06 D in the IGA-SMILE group and −4.21 ± 2.23 D and −3.15 ± 0.62 D in the FS-LASIK group, respectively. One year later, visual and refractive results were compared in the groups. Vector analysis based on Alpins method was performed to evaluate astigmatic treatment.

Results:

128 eyes of 128 patients were included in this study. At 1 year, the residual astigmatism was −0.21 ± 0.25 D in the IGA-SMILE group and −0.21 ± 0.24 D in the FS-LASIK group (P = .305). In the IGA-SMILE group, 57 eyes (89.1%) achieved uncorrected distance visual acuity of 20/20 or better, as did 56 eyes (85.9%) in the FS-LASIK group. Vector analysis results demonstrated that the difference vectors were 0.22 ± 0.24 D and 0.21 ± 0.22 D (P = .230), the correction indexes were 0.95 ± 0.08 and 0.95 ± 0.08 (P = .239), and the indices of success were 0.08 ± 0.09 and 0.08 ± 0.09 (P = .248) in the IGA-SMILE and the FS-LASIK groups, respectively.

Conclusions:

The combination of an image-guided system with SMILE resulted in high efficacy and safety indices that were comparable with FS-LASIK surgery.
Tale of Two Alopecias: Alopecia Areata and Central Centrifugal Cicatricial Alopecia Occurring in the Same Patient
Authors: See Sharlene Helene C. , Tan Timothy L. , Aderibigbe Oyinade , Yazdan Pedram
Published: October 2021

Introduction:

Scarring and non-scarring alopecias have rarely been described to occur together in the same patient. Distinguishing these two different types of alopecia is important as treatment and prognosis can be different.

Case presentation:

Here, we report the first case of simultaneous alopecia areata (AA) and central centrifugal cicatricial alopecia (CCCA) in a 35-year-old woman. New alopecic patches were noted on her frontal and vertex scalp. Biopsy of the frontal scalp revealed miniaturized hair follicles and dense lymphocytic infiltrate surrounding the hair bulbs, consistent with AA; while biopsy of the vertex scalp revealed decreased hair follicles, perifollicular fibroplasia with eccentric atrophy of the follicular epithelium, and premature desquamation of the inner root sheath at the level of the lower isthmus, consistent with CCCA.

Discussion:

Proposed mechanisms of these two alopecia types occurring together include loss of immune privilege, genetic predisposition, as well as unknown external factors that trigger an autoimmune lymphocytic response. Most recently, the peptidylarginine deiminase type III gene has been implicated in both diseases. Although treatment options can overlap between the two diseases, treatment response can differ and CCCA tends to have a worse prognosis.

Conclusion:

Awareness of this concomitant presentation of two alopecic types is important for appropriate treatment and prognostication.
Lichen Planus Pigmentosus Inversus: Two Case Reports
Authors: Lee Se Hoon , Cho Minah , Han Yu Jin , Woo Yu Ri , Cho Sang Hyun , Lee Jeong Deuk , Kim Hei Sung
Published: October 2021

Introduction:

Lichen planus pigmentosus inversus (LPPI) is a rare a rare variant of lichen planus characterized by hyperpigmented patches with predominating localization in intertriginous areas. Due to its rarity, only a few LPPI cases are reported.

We herein describe two rare cases of LPPI.

Case presentation:

The two patients were all with a brownish macular lesion on the intertriginous area. A diagnosis of LPPI was made based on their clinical manifestations, dermoscopic features, and histopathologic features, which revealed an interface change, lichenoid infiltration, and pigmentary incontinence.

Discussion:

LPPI is pruritic or asymptomatic, hyperpigmented macules and patches on the flexural folds. The axillae and flanks were the most commonly affected areas, followed by the groin and genitalia. About half of the female patients had inframammary fold lesions. LPPI shows higher female predominance than Lichen planus pigmentosus. There were fewer cases that lasted more than 3 years compared to LPP.

Conclusion:

LPPI is a rare variant of lichen planus, with a locational characteristic and female predominance. Therefore, in the case of a pigmented disease occurring in the flexural folds, it should be placed in the differential diagnosis.