bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of Delta-8 Tetrahydrocannabinol in DUID Investigation Casework: Method Development, Validation and Application
Authors: Chan-Hosokawa Ayako , Nguyen Loan , Lattanzio Nicole , Adams Wendy R
Published: March 2021

Cannabinoid is the most frequently reported illicit drug class in Driving Under the Influence of Drugs (DUID) investigation casework. In recent years, our laboratory observed an increasing rate of overlapping peaks for the cannabinoid confirmation performed using 2D high-performance liquid chromatography (LC)--tandem mass spectrometry (MS-MS). Starting in early 2018, the incidence of unresolved interfering substances increased, contributing to a higher rate of canceled testing that peaked at 3.7% in February 2019. The observed interference demonstrates a distinctive pattern affecting the identification and quantification of both delta-9 tetrahydrocannabinol (THC) and delta-9 carboxy THC. An improved quantitative method was developed and validated to separate delta-8 and -9 isomers and their metabolites in blood. All acceptance criteria were met, with identical measurement ranges from the original method (lower limit of quantitation: 0.5 ng/mL for delta-9 THC, 1.0 ng/mL for 11-hydroxy delta-9 THC and 5.0 ng/mL for delta-9 carboxy THC). Cannabinoids were extracted from whole blood using liquid–liquid extraction, separated in a 2D LC system over a run time of 10 min and detected by an MS-MS system equipped with ESI source operating in positive ionization mode with scheduled multiple reaction mass spectrometric monitoring. The LC system consisted of a pair of Phenomenex® SecurityGuard™ C6 Phenyl (4 × 2 mm) cartridges for extracting the compounds with 5 mM ammonium formate buffer in deionized (DI) water and 0.1% formic acid in methanol as mobile phase, and a Phenomenex® Kinetex C18 column (100 × 3 mm) with 0.1% formic acid in DI water and 0.1% formic acid in methanol for LC separation at 45°C. Each set of isomers was fully resolved by the longer run-time method. To the authors’ knowledge, this is the first report of a method that successfully quantitates these primary cannabinoids in blood specimens where significant concentrations of both delta-9 and delta-8 isomers are present.
Evidence Gaps in Cancer Survivorship Care: A Report From the 2019 National Cancer Institute Cancer Survivorship Workshop
Authors: Gallicchio Lisa , Tonorezos Emily , de Moor Janet S , Elena Joanne , Farrell Margaret , Green Paige , Mitchell Sandra A , Mollica Michelle A , Perna Frank , Saiontz Nicole Gottlieb , Zhu Li , Rowland Julia , Mayer Deborah K
Published: March 2021

Today, there are more than 16.9 million cancer survivors in the United States; this number is projected to grow to 22.2 million by 2030. Although much progress has been made in describing cancer survivors’ needs and in improving survivorship care since the seminal 2006 Institute of Medicine report “From Cancer Patient to Cancer Survivor: Lost in Transition,” there is a need to identify evidence gaps and research priorities pertaining to cancer survivorship. Thus, in April 2019, the National Cancer Institute convened grant-funded extramural cancer survivorship researchers, representatives of professional organizations, cancer survivors, and advocates for a 1-day in-person meeting. At this meeting, and in a subsequent webinar aimed at soliciting input from the wider survivorship community, evidence gaps and ideas for next steps in the following 6 areas, identified from the 2006 Institute of Medicine report, were discussed: surveillance for recurrence and new cancers, management of long-term and late physical effects, management of long-term and late psychosocial effects, health promotion, care coordination, and financial hardship. Identified evidence gaps and next steps across the areas included the need to understand and address disparities among cancer survivors, to conduct longitudinal studies as well as longer-term (>5 years postdiagnosis) follow-up studies, to leverage existing data, and to incorporate implementation science strategies to translate findings into practice. Designing studies to address these broad evidence gaps, as well as those identified in each area, will expand our understanding of cancer survivors’ diverse needs, ultimately leading to the development and delivery of more comprehensive evidence-based quality care.
Neural Responses to Social Reward Predict Depressive Symptoms in Adolescent Girls During the COVID-19 Pandemic
Authors: Sequeira Stefanie L , Silk Jennifer S , Hutchinson Emily , Jones Neil P , Ladouceur Cecile D
Published: March 2021

Objective

Adolescent depression is increasing during the COVID-19 pandemic, possibly related to dramatic social changes. Individual-level factors that contribute to social functioning, such as temperament and neural reactivity to social feedback, may confer risk for or resilience against depressive symptoms during the pandemic.

Methods

Ninety-three girls (12–17 years) oversampled for high shy/fearful temperament were recruited from a longitudinal study for a follow-up COVID-19 study. During the parent study (2016–2018), participants completed a functional magnetic resonance imaging task eliciting neural activity to performance-related social feedback. Depressive symptoms were assessed during the parent study and COVID-19 follow-up (April–May 2020). In 65 participants with complete data, we examined how interactions between temperament and neural activation to social reward or punishment in a socio-affective brain network predict depressive symptoms during COVID-19.

Results

Depressive symptoms increased during COVID-19. Significant interactions between temperament and caudate, putamen, and insula activation to social reward were found. Girls high in shy/fearful temperament showed negative associations between neural activation to social reward and COVID-19 depressive symptoms, whereas girls lower in shy/fearful temperament showed positive associations.

Conclusions

Girls high in shy/fearful temperament with reduced neural activation to social reward may be less likely to engage socially, which could be detrimental during the pandemic when social interactions are limited. In contrast, girls lower in shy/fearful temperament with heightened neural reactivity to social reward may be highly motivated to engage socially, which could also be detrimental with limited social opportunities. In both cases, improving social connection during the pandemic may attenuate or prevent depressive symptoms.
Did Zika virus attenuation or increased virulence lead to the emergence of congenital Zika syndrome?
Authors: Lambrechts Louis
Published: March 2021

The global emergence of Zika revealed the unprecedented ability of a mosquito-borne virus to cause severe congenital abnormalities. Recent studies indicate that the ability to harm fetuses is not a novel feature of Zika virus. Counter-intuitively, it may have in fact recently ‘attenuated’ from killing embryos to causing birth defects.
Trends of the global, regional and national incidence of malaria in 204 countries from 1990 to 2019 and implications for malaria prevention
Authors: Liu Qiao , Jing Wenzhan , Kang Liangyu , Liu Jue , Liu Min
Published: March 2021

Background

Malaria is a life-threatening disease worldwide, but lacks studies on its incidence at the global level. We aimed to describe global trends and regional diversities in incidence of malaria infection, to make global tailored implications for malaria prevention.

Methods

We used the data from the Global Burden of Disease Study 2019. The age-standardized incidence rate (ASR) and absolute number of malaria episodes showed the epidemic status of malaria infection. The estimated annual percentage change of ASR and changes in malaria episodes quantified the malaria incidence trends. The connection between ASRs and traveller number indicated infection risk for travellers.

Results

Globally, the malaria ASR decreased by an average 0.80% (95% confidence interval 0.58–1.02%) per year from 1990 to 2019; however, it slightly increased from 3195.32 per 100 000 in 2015 to 3247.02 per 100 000 in 2019. The incidence rate of children under 5 was higher than other age groups. A total of 40 countries had higher ASRs in 2019 than in 2015, with the largest expansion in Cabo Verde (from 2.02 per 100 000 to 597.00 per 100 000). After 2015, the ASRs in high-middle, middle and low-middle Socio-demographic Index regions began to rise and the uptrends remained in 2019. Central, Western and Eastern Sub-Saharan Africa had the highest ASRs since 1990, and traveller number in Eastern and Western Sub-Saharan Africa increased by 31.24 and 7.58%, respectively, from 2017 to 2018. Especially, most countries with ASR over 10 000 per 100 000 had increase in traveller number from 2017 to 2018, with the highest change by 89.56% in Mozambique.

Conclusions

Malaria is still a public health threat for locals and travellers in Sub-Saharan Africa and other malaria-endemic areas, especially for children under 5. There were unexpected global uptrends of malaria ASRs from 2015 to 2019. More studies are needed to achieve the goal of malaria elimination.
NGC 6611 601: a hot pre-main-sequence spectroscopic binary containing a centrifugal magnetosphere host star
Authors: Shultz M E , Alecian E , Petit V , Bagnulo S , Böhm T , Folsom C P , Wade G A ,   the MiMeS Collaboration
Published: March 2021

W 601 (NGC 6611 601) is one of the handful of known magnetic Herbig Ae/Be stars. We report the analysis of a large data set of high-resolution spectropolarimetry. The star is a previously unreported spectroscopic binary, consisting of two B2 stars with a mass ratio of 1.8, masses of 12 and 6.2 M⊙, in an eccentric 110-d orbit. The magnetic field belongs to the secondary, W 601 B. The H α emission is consistent with an origin in W 601 B’s centrifugal magnetosphere; the star is therefore not a classical Herbig Be star in the sense that its emission is not formed in an accretion disc. However, the low value of log g = 3.8 determined via spectroscopic analysis and the star’s membership in the young NGC 6611 cluster are most consistent with it being on the pre-main sequence. The rotational period inferred from the variability of the H α line and the longitudinal magnetic field 〈Bz〉 is 1.13 d. Modelling of Stokes V and 〈Bz〉 indicates a surface dipolar magnetic field Bd between 6 and 11 kG. With its strong emission, rapid rotation, and strong surface magnetic field, W 601 B is likely a precursor to H α-bright magnetic B-type stars such as σ Ori E. By contrast, the primary is an apparently non-magnetic (Bd < 300 G) pre-main-sequence early B-type star. In accordance with expectations from magnetic braking, the non-magnetic primary is apparently more rapidly rotating than the magnetic star.
QPOs and Orbital elements of X-ray binary 4U 0115+63 during the 2017 outburst observed by Insight-HXMT
Authors: Ding Y Z , Wang W , Zhang P , Bu Q C , Cai C , Cao X L , Zhi C , Chen L , Chen T X , Chen Y B , Chen Y , Chen Y P , Cui W W , Du Y Y , Gao G H , Gao H , Ge M Y , Gu Y D , Guan J , Guo C C , Han D W , Huang Y , Huo J , Jia S M , Jiang W C , Jin J , Kong L D , Li B , Li C K , Li G , Li T P , Li W , Li X , Li X B , Li X F , Li Z W , Liang X H , Liao J Y , Liu B S , Liu C Z , Liu H X , Liu H W , Liu X J , Lu F J , Lu X F , L Q , T L , Ma R C , Ma X , Meng B , Nang Y , Nie J Y , Qu J L , Ren X Q , Sai N , Song L M , Song X Y , Sun L , Tan Y , Tao L , Tuo Y L , Wang L J , Wang P J , Wang W S , Wang Y S , Wen X Y , Wu B Y , Wu B B , Wu M , Xiao G C , Xiao S , Xiong S L , Xu Y P , Yang R J , Yang S , Yang Y J , Yi Q B , Yin Q Q , You Y , Zhang F , Zhang H M , Zhang J , Zhang P , Zhang S , Zhang S N , Zhang W C , Zhang W , Zhang Y F , Zhang Y H , Zhao H S , Zhao X F , Zheng S J , Zheng Y G , Zhou D K
Published: March 2021

In this paper, we presented a detailed timing analysis of a prominent outburst of 4U 0115+63 detected by Insight-HXMT in 2017 August. The spin period of the neutron star was determined to be 3.61398 ± 0.00002 s at MJD 57978. We measured the period variability and extract the orbital elements of the binary system. The angle of periastron evolved with a rate of $0.048^\circ \pm 0.003^\circ \rm \, yr^{-1}$. The light curves are folded to sketch the pulse profiles in different energy ranges. A multi-peak structure in 1-10 keV is clearly illustrated. We introduced wavelet analysis into our data analysis procedures to study QPO signals and perform a detailed wavelet analysis in many different energy ranges. Through the wavelet spectra, we report the discovery of a QPO at the frequency ∼10 mHz. In addition, the X-ray light curves showed multiple QPOs in the period of ∼16 − 32 s and ∼67 − 200 s. We found that the ∼100 s QPO was significant in most of the observations and energies. There exist positive relations between X-ray luminosity and their Q-factors and S-factors, while the QPO periods have no correlation with X-ray luminosity. In wavelet phase maps, we found that the pulse phase of ∼67 − 200 s QPO drifting frequently while the ∼16 − 32 s QPO scarcely drifting. The dissipation of oscillations from high energy to low energy was also observed. These features of QPOs in 4U 0115+63 provide new challenge to our understanding of their physical origins.
BRITE observations of ν Centauri and γ Lupi, the first non-eclipsing members of the new class of nascent binaries
Authors: Jerzykiewicz M , Pigulski A , Michalska G , Moździerski D , Ratajczak M , Handler G , Moffat A F J , Pablo H , Popowicz A , Wade G A , Zwintz K
Published: March 2021

Results of an analysis of the BRITE-Constellation and Solar Mass Ejection Imager photometry and radial-velocity observations, archival and new, of two single-lined spectroscopic binary (SB) systems ν Centauri and γ Lupi are reported. In the case of γ Lup AB, a visual binary, an examination of the light-time effect shows that component A is the SB. Both ν Cen and γ Lup exhibit light variations with the orbital period. The variations are caused by the reflection effect, i.e. heating of the secondary’s hemisphere by the early-B main sequence (MS) primary component’s light. The modelling of the light curves augmented with the fundamental parameters of the primary components obtained from the literature photometric data and Hipparcos parallaxes, shows that the secondary components are pre-MS stars, in the process of contracting on to the MS. ν Cen and γ Lup A are thus found to be non-eclipsing counterparts of the B2 IV eclipsing binary (and a β Cephei variable) 16 (EN) Lac, the B5 IV eclipsing binary (and an SPB variable) μ Eri, and the recently discovered Large Magellanic Cloud nascent eclipsing binaries.
The completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: a multitracer analysis in Fourier space for measuring the cosmic structure growth and expansion rate
Authors: Zhao Gong-Bo , Wang Yuting , Taruya Atsushi , Zhang Weibing , Gil-Marín Héctor , de Mattia Arnaud , Ross Ashley J , Raichoor Anand , Zhao Cheng , Percival Will J , Alam Shadab , Bautista Julian E , Burtin Etienne , Chuang Chia-Hsun , Dawson Kyle S , Hou Jiamin , Kneib Jean-Paul , Koyama Kazuya , du Mas des Bourboux Hélion , Mueller Eva-Maria , Newman Jeffrey A , Peacock John A , Rossi Graziano , Ruhlmann-Kleider Vanina , Schneider Donald P , Shafieloo Arman
Published: March 2021

We perform a joint BAO and RSD analysis using the eBOSS DR16 LRG and ELG samples in the redshift range of z ∈ [0.6, 1.1], and detect an RSD signal from the cross-power spectrum at a ∼4σ confidence level, i.e., fσ8 = 0.317 ± 0.080 at zeff = 0.77. Based on the chained power spectrum, which is a new development in this work to mitigate the angular systematics, we measure the BAO distances and growth rate simultaneously at two effective redshifts, namely, DM/rd (z = 0.70) = 17.96 ± 0.51, DH/rd (z = 0.70) = 21.22 ± 1.20, fσ8 (z = 0.70) = 0.43 ± 0.05, and DM/rd (z = 0.845) = 18.90 ± 0.78, DH/rd (z = 0.845) = 20.91 ± 2.86, fσ8 (z = 0.845) = 0.30 ± 0.08. Combined with BAO measurements including those from the eBOSS DR16 QSO and Lyman-α sample, our measurement has raised the significance level of a non-zero ΩΛ to ∼11σ. The data product of this work is publicly available at https://github.com/icosmology/eBOSS_DR16_LRGxELG and https://www.sdss.org/science/final-bao-and-rsd-measurements/.
BART Cancer: a web resource for transcriptional regulators in cancer genomes
Authors: Thomas Zachary V , Wang Zhenjia , Zang Chongzhi
Published: March 2021

Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10000 gene expression profiling RNA-seq datasets from TCGA with over 7000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.
Process-Outcome Associations in an Interdisciplinary Treatment for Chronic Pain and Comorbid Mental Disorders Based on Acceptance and Commitment Therapy
Authors: Ohse Ludwig , Burian Ronald , Hahn Eric , Burian Hanna , Ta Thi Minh Tam , Diefenbacher Albert , Böge Kerem
Published: March 2021

Objective

Numerous studies support the effectiveness of acceptance and commitment therapy (ACT) for chronic pain, yet little research has been conducted about its underlying mechanisms of change, especially regarding patients with comorbid mental disorders. The present investigation addressed this issue by examining associations of processes targeted by ACT (pain acceptance, mindfulness, psychological flexibility) and clinical outcomes (pain intensity, somatic symptoms, physical health, mental health, depression, general anxiety).

Subjects

Participants were 109 patients who attended an ACT-based interdisciplinary treatment program for chronic pain and comorbid mental disorders in a routine care psychiatric day hospital.

Methods

Pre- to posttreatment differences in processes and outcomes were examined with Wilcoxon signed-rank tests and effect size r. Associations between changes in processes and changes in outcomes were analyzed with correlation and multiple regression analyses.

Results

Pre- to posttreatment effect sizes were mostly moderate to large (r between 0.21 and 0.62). Associations between changes in processes and changes in outcomes were moderate to large for both, bivariate correlations (r between 0.30 and 0.54) and shared variances accounting for all three processes combined (R2 between 0.21 and 0.29).

Conclusion

The present investigation suggests that changes in pain acceptance, mindfulness, and psychological flexibility are meaningfully associated with changes in clinical outcomes. It provides evidence on particular process-outcome associations that had not been investigated in this way before. The focus on comorbid mental disorders informs clinicians about a population of chronic pain patients who often have a severe course of illness and have seldom been studied.
Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals
Authors: Anteraper Sheeba Arnold , Guell Xavier , Collin Guusje , Qi Zhenghan , Ren Jingwen , Nair Atira , Seidman Larry J , Keshavan Matcheri S , Zhang Tianhong , Tang Yingying , Li Huijun , McCarley Robert W , Niznikiewicz Margaret A , Shenton Martha E , Stone William S , Wang Jijun , Whitfield-Gabrieli Susan
Published: March 2021

Objective

The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia.

Methods

We used the magnetic resonance imaging (MRI) dataset from the Shanghai At Risk for Psychosis study that included subjects at high risk to develop schizophrenia (N = 144), with longitudinal follow-up to determine which subjects developed a psychotic episode within 1 year of their functional magnetic resonance imaging (fMRI) scan (converters N = 23). Analysis used the 3 functional parcels (default-mode, salience-motor, and visual territory) from the DN as seed regions of interest for whole-brain RsFc analysis.

Results

RsFc analysis revealed abnormalities at baseline in high-risk individuals who developed psychosis, compared to high-risk individuals who did not develop psychosis. The nature of the observed abnormalities was found to be anatomically specific such that abnormal RsFc was localized predominantly in cerebral cortical networks that matched the 3 functional territories of the DN that were evaluated.

Conclusions

We show for the first time that abnormal RsFc of the DN may precede the onset of psychosis. This new evidence highlights the role of the cerebellum as a potential target for psychosis prediction and prevention.
Who was Ever ‘a Fisherman’? Revisiting Paul Thompson’s Living the Fishing
Authors: Taylor Becky
Published: March 2021

This article revisits Paul Thompson’s major oral history project of Britain’s early twentieth-century fishing industry, situating it within the emergence of oral history as a practice in the 1960s and 1970s, and interrogating assumptions over the fixed category of ‘fisherman’ which informed the original research. Through a detailed look at interviews collected with those involved in the herring fishing of East Anglia and north-east Scotland, it finds that Thompson and his colleagues were still as informed by social science interviewing practices as they were oral history as an evolving methodology, and framed their approach at a time when fixed worker identities were taken as given. Revisiting the transcripts with a different set of research questions revealed how ‘fishermen’ moved in and out of fishing, with ‘farmworkers’ equally being found as regularly employed on boats. Thus the article argues that instead of fixed and life-long fisher identities, precarity, migration and seasonality were key features of many fishers’ involvement in the herring industry. Through focussing on mobility – across place and types of employment – this piece also reveals the central role of personal preference and intimate decision-making in mediating individuals’ choices to ‘follow the herring’.
Protective effects of baicalin in a Caenorhabditis elegans model of Parkinson’s disease
Authors: Ma Jing , Wang Ranran , Chen Ting , Jiang Shaowei , Xu Ajing
Published: March 2021

Parkinson’s disease (PD) is a common neurodegenerative disorder of the central nervous system. However, the pathogenetic mechanisms of PD are far from understood. The aim of this study was to determine the protective effect of baicalin in a Caenorhabditis elegans model of PD. C. elegans worms were stimulated for 24 h with 6-hydroxydopamine (6-OHDA, 50 mM) and treated with or without baicalin (1, 10, or 100 μM). At all tested concentrations, baicalin improved the reversal and omega turn behavioral phenotypes, as well as the survival, of 6-OHDA-stimulated worms. It also inhibited 6-OHDA-induced oxidative stress by decreasing malondialdehyde levels, increasing superoxide dismutase, glutathione reductase, catalase, and glutathione levels and up-regulating mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, daf-2, and daf-16. Additionally, it significantly decreased the expression of the apoptosis-related gene ced-3 and increased that of the anti-apoptosis-related gene ced-9. The expression levels of cleaved caspase-3 and B-cell lymphoma 2 in 6-OHDA-treated worms were reversed by baicalin. Apoptosis was suppressed by 6-OHDA in loss-of-function strains via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, the apoptotic effects of 6-OHDA were blocked in sek-1 and pmk-1 mutants. Finally, the mRNA expression of sek-1 and pmk-1 and the protein expression of p38 MAPK and stress-activated protein kinase/extracellular signal-regulated kinase 1 were up-regulated by 6-OHDA and reversed by baicalin. Baicalin may protect against 6-OHDA injury by inhibiting apoptosis and decreasing oxidative stress through the p38 MAPK signaling pathway.
Eucyon khoikhoisp. nov. (Carnivora: Canidae) from Langebaanweg ‘E’ Quarry (early Pliocene, South Africa): the most complete African canini from the Mio-Pliocene
Authors: Valenciano Alberto , Morales Jorge , Govender Romala
Published: March 2021

A new medium-sized canid, Eucyon khoikhoi sp. nov., is described from the early Pliocene site of Langebaanweg ‘E’ Quarry (South Africa). It possesses a robust dentition with large upper- and lower-second molars, an m1 talonid without a transverse cristid between the entoconid and the hypoconid, and a well-developed hypoconulid shelf. Our cladistic analysis of the earliest better-known African canini, places E. khoikhoi as the most basal taxon of an African clade composed of E. wokari, ?Nyctereutes barryi, ?Schaeffia mohibi and Schaeffia adusta (living side-striped jackal). We suggest an alternative arrangement for the poorly known East African E. intrepidus from the Late Miocene and E. kuta from the Middle Pliocene. Eucyon intrepidus could belong to the same clade as E. khoikhoi, unlike E. kuta, whose dentition suggests a closer relation with the Lupulella group. Thus, these results support the paraphyly of Eucyon, demonstrating the need for an in-depth review of the genus. Eucyon khoikhoi has a body mass comparable to E. kuta and the European E. debonisi and E. monticinensis. We conclude that E. khoikhoi may have had a comparable role in the ecosystem to the extant hypocarnivorous S. adusta.
Genetic deletion of CMG2 exacerbates systemic‐to‐pulmonary shunt‐induced pulmonary arterial hypertension
Authors: Meng Liukun , Yuan Wen , Chi Hongjie , Han Ruijuan , Zhang Yeping , Pan Xiangbin , Meng Jian , Liu Ying , Song Jiawei , Zhong Jiuchang , Liu Xiaoyan
Published: March 2021

Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD‐PAH) with systemic‐to‐pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene‐2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS‐induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS‐induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2−/− rats exhibited more severe PAH and pulmonary vascular remodeling than wild‐type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next‐generation sequencing and subsequent validation results suggested that PI3K‐AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2−/− rat lungs. Our work identified a novel role for CMG2 in SPS‐induced PAH based on the findings that CMG2 deficiency exacerbates SPS‐induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD‐PAH.
ω3 fatty acid metabolite, 12‐hydroxyeicosapentaenoic acid, alleviates contact hypersensitivity by downregulation of CXCL1 and CXCL2 gene expression in keratinocytes via retinoid X receptor α
Authors: Saika Azusa , Nagatake Takahiro , Hirata So‐ichiro , Sawane Kento , Adachi Jun , Abe Yuichi , Isoyama Junko , Morimoto Sakiko , Node Eri , Tiwari Prabha , Hosomi Koji , Matsunaga Ayu , Honda Tetsuya , Tomonaga Takeshi , Arita Makoto , Kabashima Kenji , Kunisawa Jun
Published: March 2021

ω3 fatty acids show potent bioactivities via conversion into lipid mediators; therefore, metabolism of dietary lipids is a critical determinant in the properties of ω3 fatty acids in the control of allergic inflammatory diseases. However, metabolic progression of ω3 fatty acids in the skin and their roles in the regulation of skin inflammation remains to be clarified. In this study, we found that 12‐hydroxyeicosapentaenoic acid (12‐HEPE), which is a 12‐lipoxygenase metabolite of eicosapentaenoic acid, was the prominent metabolite accumulated in the skin of mice fed ω3 fatty acid‐rich linseed oil. Consistently, the gene expression levels of Alox12 and Alox12b, which encode proteins involved in the generation of 12‐HEPE, were much higher in the skin than in the other tissues (eg, gut). We also found that the topical application of 12‐HEPE inhibited the inflammation associated with contact hypersensitivity by inhibiting neutrophil infiltration into the skin. In human keratinocytes in vitro, 12‐HEPE inhibited the expression of two genes encoding neutrophil chemoattractants, CXCL1 and CXCL2, via retinoid X receptor α. Together, the present results demonstrate that the metabolic progression of dietary ω3 fatty acids differs in different organs, and identify 12‐HEPE as the dominant ω3 fatty acid metabolite in the skin.
Lack of peptide YY signaling in mice disturbs gut microbiome composition in response to high‐fat diet
Authors: Farzi Aitak , Ip Chi Kin , Reed Felicia , Enriquez Ronaldo , Zenz Geraldine , Durdevic Marija , Zhang Lei , Holzer Peter , Herzog Herbert
Published: March 2021

Peptide YY (PYY), produced by endocrine L cells in the gut, is known for its critical role in regulating gastrointestinal functions as well as satiety. However, how these processes are integrated with maintaining a healthy gut microbiome composition is unknown. Here, we show that lack of PYY in mice leads to distinct changes in gut microbiome composition that are diet‐dependent. While under chow diet only slight differences in gut microbiome composition could be observed, high‐fat diet (HFD) aggravated these differences. Specifically an increased abundance of the Bacteroidetes phylum with a corresponding decrease of the Firmicutes/Bacteroidetes ratio could be detected in Pyy‐knockout (KO) mice in response to HFD. Detailed analysis of the Bacteroidetes phylum further revealed that the Alistipes genus belonging to the Rikenellaceae family, the Parabacteroides belonging to the Tannerellaceae family, as well as Muribaculum were increased in Pyy‐KO mice. In order to investigate whether these changes are associated with changed markers of gut barrier and immunity, we analyzed the colonic expression of various pro‐inflammatory cytokines, as well as tight junction proteins and mucin 2, and identified increased mRNA expression of the tight junction proteins Cldn2 and Ocel1 in Pyy‐KO mice, while pro‐inflammatory cytokine expression was not significantly altered. Together these results highlight a critical gene‐environment interaction between diet and the gut microbiome and its impact on homeostasis of the intestinal epithelium under conditions of reduced PYY signaling which is commonly seen under obese conditions.
Lnc‐ing pluripotency maintenance and early differentiation in human pluripotent stem cells
Authors: Lu Pei , Li Mao , Zhang Donghui , Jiang Wei
Published: March 2021

Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self‐renewal or differentiation is under the exquisite control of the gene regulatory network, which is composed of transcription factors, signaling pathways, metabolic factors, chromatin or histone modifiers, miRNAs, and lncRNAs. Growing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in epigenetic, transcriptional, and posttranscriptional gene regulation during the cell fate determination of pluripotent stem cells. Here, we summarize recent reports of lncRNA functions in pluripotency maintenance/exit and the early germ layer specification of human pluripotent stem cells. We also illustrate four major lncRNA functional mechanisms according to different types of cofactors: chromatin or histone modifiers, transcription factors, canonical and noncanonical RNA‐binding proteins, and miRNAs. Further understanding of lncRNA‐based regulation will provide more insights into the drivers manipulating cell fate and promote the therapeutic and research potential of human embryonic and induced pluripotent stem cells.
Insulin signaling is an essential regulator of endometrial proliferation and implantation in mice
Authors: Sekulovski Nikola , Whorton Allison E. , Shi Mingxin , Hayashi Kanako , MacLean James A.
Published: March 2021

Insulin signaling is critical for the development of preovulatory follicles and progression through the antral stage. Using a conditional knockout model that escapes this blockage, we recently described the role of insulin signaling in granulosa cells during the periovulatory window in mice lacking Insr and Igf1r driven by Pgr‐Cre. These mice were infertile, exhibiting defects in ovulation, luteinization, steroidogenesis, and early embryo development. Herein, we demonstrate that while these mice exhibit normal uterine receptivity, uterine cell proliferation and decidualization are compromised resulting in complete absence of embryo implantation in uteri lacking both receptors. While the histological organization of double knockout mice appeared normal, the thickness of their endometrium was significantly reduced. This was supported by the reduced proliferation of both epithelial and stromal cells during the preimplantation stages of pregnancy. Expression and localization of the main drivers of uterine proliferation, ESR1 and PGR, was normal in knockouts, suggesting that insulin signaling acts downstream of these two receptors. While AKT/PI3K signaling was unaffected by insulin receptor ablation, activation of p44/42 MAPK was significantly reduced in both single and double knockout uteri at 3.5 dpc. Overall, we conclude that both INSR and IGF1R are necessary for optimal endometrial proliferation and implantation.
CaMKIIδ is upregulated by pro‐inflammatory cytokine IL‐6 in a JAK/STAT3‐dependent manner to promote angiogenesis
Authors: O'Brien Brendan J. , Singer Harold A. , Adam Alejandro P. , Ginnan Roman G.
Published: March 2021

Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a ubiquitous serine threonine kinase with established roles in physiological and pathophysiological vascular remodeling. Based on our previous study demonstrating that CaMKIIδ promotes thrombin‐induced endothelial permeability and recent reports that CaMKII may contribute to inflammatory remodeling in the heart, we investigated CaMKIIδ‐dependent regulation of endothelial function downstream of an interleukin‐6 (IL‐6)/JAK/STAT3 signaling axis. Upon treatment with IL‐6 and its soluble receptor (sIL‐6r), CaMKIIδ expression is significantly induced in HUVEC. Using pharmacological inhibitors of JAK and siRNA targeting STAT3, we demonstrated that activation of STAT3 is sufficient to induce CaMKIIδ expression. Under these conditions, rather than promoting IL‐6‐induced permeability, we found that CaMKIIδ promotes endothelial cell migration as measured by live cell imaging of scratch wound closure and single‐cell motility analysis. In a similar manner, endothelial cell proliferation was attenuated upon knockdown of CaMKIIδ as determined by growth curves, cell cycle analysis, and capacitance of cell‐covered electrodes as measured by ECIS. Using inducible endothelial‐specific STAT3 knockout mice, we demonstrate that STAT3 signaling promotes developmental angiogenesis in the neonatal mouse retina assessed at postnatal day 6. CaMKIIδ expression in retinal endothelium was attenuated in these animals as measured by qPCR. STAT3's effects on angiogenesis were phenocopied by the endothelial‐specific knockout of CaMKIIδ, with significantly reduced vascular outgrowth and number of junctions in the developing P6 retina. For the first time, we demonstrate that transcriptional regulation of CaMKIIδ by STAT3 promotes endothelial motility, proliferation, and in vivo angiogenesis.
Successful Salvage of a Lower Extremity Local Flap Using Multiple Negative Pressure Modalities
Authors: Gabriel Allen , Pfaffenberger Maci , Eldenburg Elizabeth
Published: March 2021

Wounds from orthopedic limb reconstruction are often difficult to heal due to the surgery, patient comorbidities, or a combination of these factors. The role of negative pressure wound therapy (NPWT) modalities in the perioperative management of patients with complex lower extremity wounds is evolving. Here, we present a case study using adjunctive NPWT with instillation and a dwell time, standard NPWT, and closed-incision negative pressure therapy (ciNPT) to manage a complex lower extremity wound. The patient was a 51-year-old man who presented with severe scarring of the lower extremity and infection following plate osteosynthesis of a tibial shaft fracture. Following lower extremity reconstruction, the patient received 5 days of NPWT with instillation and a dwell time with cycles that consisted of instilling normal saline with a 1-second dwell time, followed by 2 hours of continuous negative pressure at −125 mm Hg. The wound is then covered with an adjacent local tissue flap, which showed signs of vascular complication. ciNPT is applied over the flap incision for 7 days, which resulted in restored normal coloration; ciNPT is continued for another 7 days. A skin substitute is applied over the flap donor site, followed by NPWT using a silver foam dressing. Dressing changes are performed weekly for 4 weeks. At 8 weeks postsurgery, a skin graft is applied over the donor site. In this case, adjunctive use of multiple NPWT modalities resulted in a completely healed wound within 12 months with no complications.
Sacral and Rectal Necrosis after Carbon Ion Radiotherapy Reconstructed with Transpelvic Rectus Abdominis Flap
Authors: Atomura Daisuke , Makiguchi Takaya , Nakamura Hideharu , Yamatsu Yukie , Osone Katsuya , Motegi Yoko , Ogawa Hiroomi , Shirabe Ken , Yokoo Satoshi
Published: March 2021

Carbon ion radiotherapy (CIRT) has been used for malignant tumors that are difficult to excise surgically, such as sacral chordoma, and the success of its outcomes is attributable to the high dose concentration and biological effects. CIRT has produced successful clinical outcomes, and it is considered to have fewer adverse effects on surrounding normal tissues; moreover, complications have been rarely reported. We describe a 75-year-old woman with a full-thickness sacral defect, who had received CIRT for sacral chordoma 3 years earlier. Computed tomography showed sacral bone destruction, and a colonoscopy revealed rectal necrosis. Rectectomy in addition to sacral bone resection was necessary, which resulted in a huge sacral defect of slightly anxious viability. We performed reconstruction of the sacral defect by using pedicled vertical rectus abdominis myocutaneous (VRAM) flap, obliterating sacral defects and intrapelvic dead space that occurred after rectectomy. Six months after surgery, the wound had healed well, and no complication was observed. Sacral complications after CIRT may affect surrounding normal tissues such as the rectum, and it would be difficult to reconstruct the resulting complications. The vertical rectus abdominis myocutaneous flap is considered useful for the simultaneous obliteration of sacral defects and intrapelvic dead space after CIRT.
Sternotomy Wound Closure: Equivalent Results with Less Surgery
Authors: Atwez Abdelaziz , Friedman Harold I. , Durkin Martin , Gilstrap Jarom , Mujadzic Mirsad , Chen Elliott
Published: March 2021

Background:

Mediastinitis after a median sternotomy can be life-threatening. The advent of pedicle flap–based treatment has resulted in an improvement in both morbidity and mortality. However, significant morbidities can still occur following the use of flaps for sternal closure, particularly in patients with comorbidities. To minimize an extensive surgical dissection, we modified our approach to reconstruction using a modified subpectoral approach, leaving the overlying skin attached. This technique focuses primarily on controlling wound tension rather than on maximal muscle coverage. This study is a retrospective review of 58 consecutive patients treated with this approach, by a single surgeon.

Methods:

Fifty-eight consecutive patients treated between 2008 and 2019 were included. All patients received the same procedure regardless of the degree of illness, the extent of tissue loss, and the size of sternal defect. Treatment included thorough debridement, with total sternectomy (if required); limited dissection of the pectoralis major muscle off the chest wall to the level of the pectoralis minor without skin and subcutaneous undermining; no release of the insertion of the pectoralis or use of the rectus abdominis; and midline closure over drains connected to wall suction to obliterate dead space.

Results:

Reoperations were required in 7 patients (12%). Of these, only 4 (6.9%) were related to continued sternal osteomyelitis. The other reoperations were for hematoma evacuation, breast fat necrosis, and skin necrosis. There were no operative mortalities.

Conclusion:

Chest closure using minimal dissection and tension release is safe, efficient, and associated with a complication rate equivalent to more extensive procedures reported in the literature despite significant comorbidities.
Improvements in Cleft Lip Aesthetics with the Fisher Repair Compared to the Mohler Repair
Authors: Mittermiller Paul A. , Martin Shanique , Johns Dana N. , Perrault David , Jablonka Eric M. , Khosla Rohit K.
Published: March 2021

Background:

The extended Mohler rotation-advancement repair and the Fisher anatomic subunit repair are commonly used for the surgical correction of unilateral cleft lip. The rotation-advancement repair was the initial technique of choice by the senior surgeon. However, due to recurring suboptimal aesthetic results, the senior surgeon transitioned to the anatomic subunit repair. This study was performed to compare the outcomes of the rotation-advancement repair and the anatomic subunit repair.

Methods:

A retrospective study of all consecutive patients undergoing unilateral cleft lip repair by the senior author between 2009 and 2016 was conducted. Demographic data, the presence of scar shortening/contraction, hypertrophy, widening, and revision rates were recorded.

Results:

There were 68 patients identified for inclusion. Thirty-four patients had a rotation-advancement repair and 35 had an anatomic subunit repair. Twelve patients (36%) with the rotation-advancement repair and 1 patient (2.9%) with the subunit repair required anterior lip revision (P < 0.001). Conversely, 2 patients (6.1%) with the rotation-advancement repair and 13 patients (37.1%) with the subunit repair required minor debulking of excess red vermilion fullness (P < 0.005).

Conclusions:

Transitioning from the rotation-advancement repair to the anatomic subunit repair has resulted in improved lip aesthetics with decreased incidence of scar contracture, hypertrophy, and widening as evidenced by a decrease in the revision rate for these suboptimal scars. However, the rate of debulking procedures of the red vermilion did increase early in the adoption of the anatomic subunit repair, requiring minor modifications in the technique.
Rhomboid Flap for Large Cutaneous Trunk Defect
Authors: Kang Ajaipal S. , Kang Kevin S.
Published: March 2021

Resection of large cutaneous malignancies may result in substantial skin defects. Often, skin grafting is a first-line option for reconstruction of such defects but may be limited by poor cosmetic outcomes and incomplete graft acceptance. Accordingly, skin flaps, tissue rearrangement techniques, and more complex procedures may be needed. This case report presents the successful use of a rhomboid flap for reconstruction of a 20 × 19 cm2-sized trunk skin defect left after a squamous cell cancer resection. The flap was quickly and easily fashioned, did not require any special instruments, and resulted in a good cosmetic outcome. There were no major wound complications despite postoperative radiation therapy. At 1-year follow-up, the flap healed completely with excellent contour, texture, thickness, color match, and complete patient satisfaction. In the past, rhomboid flaps have been used for small defects. This case is a unique example of a versatile and successful rhomboid flap reconstruction of an extremely large defect, instead of a more complicated reconstructive option.
Three-dimensional Printing in Plastic Surgery: Current Applications, Future Directions, and Ethical Implications
Authors: Lynn Alex Q. , Pflibsen Lacey R. , Smith Anthony A. , Rebecca Alanna M. , Teven Chad M.
Published: March 2021

Background:

Three-dimensional printing (3DP) is a rapidly advancing tool that has revolutionized plastic surgery. With ongoing research and development of new technology, surgeons can use 3DP for surgical planning, medical education, biological implants, and more. This literature review aims to summarize the currently published literature on 3DP’s impact on plastic surgery.

Methods:

A literature review was performed using Pubmed and MEDLINE from 2016 to 2020 by 2 independent authors. Keywords used for literature search included 3-dimensional (3D), three-dimensional printing (3DP), printing, plastic, surgery, applications, prostheses, implants, medical education, bioprinting, and preoperative planning. All studies from the database queries were eligible for inclusion. Studies not in English, not pertaining to plastic surgery and 3DP, or focused on animal data were excluded.

Results:

In total, 373 articles were identified. Sixteen articles satisfied all inclusion and exclusion criteria, and were further analyzed by the authors. Most studies were either retrospective cohort studies, case reports, or case series and with 1 study being prospective in design.

Conclusions:

3DP has consistently shown to be useful in the field of plastic surgery with improvements on multiple aspects, including the delivery of safe, effective methods of treating patients while improving patient satisfaction. Although the current technology may limit the ability of true bioprinting, research has shown safe and effective ways to incorporate biological material into the 3D printed scaffolds or implants. With an overwhelmingly positive outlook on 3DP and potential for more applications with updated technology, 3DP shall remain as an effective tool for the field of plastic surgery.