bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis
Authors: de Voogd Floris A , Bots Steven J , van Wassenaer Elsa A , de Jong Maria , Pruijt Maarten J , D’Haens Geert R , Gecse Krisztina B
Published: November 2023

Background

Intestinal ultrasound (IUS) is an emerging modality in monitoring disease activity in ulcerative colitis (UC). Here, we aimed to identify early IUS predictors of treatment response as evaluated by endoscopy and assessed the kinetics of IUS changes.

Methods

This prospective, longitudinal study included UC patients with endoscopic disease activity (endoscopic Mayo score [EMS] ≥2) starting anti-inflammatory treatment. Clinical scores, biochemical parameters and IUS were assessed at baseline (W0), at week 2 (W2), at W6(W6), and at the time of second endoscopy (W8-W26). Per colonic segment, endoscopic remission (EMS = 0), improvement (EMS ≤1), response (decrease in EMS ≥1), and clinical remission (Lichtiger score ≤3) were assessed and correlated with common IUS parameters. Additionally, drug-specific responsiveness of bowel wall thickness (BWT) was assessed.

Results

A total of 51 patients were included and followed, and 33 patients underwent second endoscopy. BWT was lower from W6 onward for patients reaching endoscopic improvement (3.0 ± 1.2 mm vs 4.1 ± 1.3 mm; P = .026), remission (2.5 ± 1.2 mm vs 4.1 ± 1.1 mm; P = .002), and clinical remission (3.01 ± 1.34 mm vs 3.85 ± 1.20 mm; P = .035). Decrease in BWT was more pronounced in endoscopic responders (−40 ± 25% vs −4 ± 28%; P = .001) at W8 to W26. At W6, BWT ≤3.0 mm (odds ratio [OR], 25.13; 95% confidence interval, 2.01-3.14; P = .012) and color Doppler signal (OR, 0.35; 95% confidence interval, 0.14-0.88; P = .026) predicted endoscopic remission and improvement, respectively. Submucosal layer thickness at W6 predicted endoscopic remission (OR, 0.09; P = .018) and improvement (OR, 0.14; P = .02). Furthermore, BWT decreased significantly at W2 for infliximab and tofacitinib and at W6 for vedolizumab.

Conclusions

BWT and color Doppler signal predicted endoscopic targets already after 6 weeks of treatment and response was drug specific. IUS allows close monitoring of treatment in UC and is a surrogate marker of endoscopy.
Durability of Cross-Neutralizing Antibodies 5.5 Months After Bivalent Coronavirus Disease 2019 Vaccine Booster
Authors: Rössler Annika , Knabl Ludwig , Netzl Antonia , Bante David , Borena Wegene , von Laer Dorothee , Smith Derek J , Kimpel Janine
Published: November 2023

We analyzed neutralizing antibodies in samples from ancestral + BA.1 and ancestral + BA.4/5 boosted individuals, collected around 5.5 months after booster. Titers of neutralizing antibodies generally decreased compared to a time point early after the bivalent booster immunization. This was more pronounced for individuals without infection history and for recently emerged Omicron variants.
High Risk of New HPV Infection Acquisition Among Unvaccinated Young Men
Authors: Giuliano Anna R , Palefsky Joel M , Goldstone Stephen E , Dubin Brady , Saah Alfred , Luxembourg Alain , Velicer Christine , Tota Joseph E
Published: November 2023

Background

International data on anogenital HPV infection incidence among men are limited.

Methods

Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16–27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months.

Results

IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5–4.9) and 6.8 (5.9–7.6) at penile/scrotal, and 1.2 (.8–1.6) and 1.9 (1.5–2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3–3.8) and 3.2 (2.0–4.9) at penile/scrotal, 6.8 (4.9–9.2) and 9.0 (6.9–11.6) at perineal/perianal, and 12.0 (9.4–15.1) and 16.8 (13.7–20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%).

Conclusions

A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden.

Clinical Trials Registration. NCT00090285.
Immunosuppressive Ability of Trichinella spiralis Adults Can Ameliorate Type 2 Inflammation in a Murine Allergy Model
Authors: Shi Wenjie , Xu Qinwei , Liu Yan , Hao Zhili , Liang Yue , Vallée Isabelle , You Xihuo , Liu Mingyuan , Liu Xiaolei , Xu Ning
Published: November 2023

Background

There is an increase in the global incidence of allergies. The hygiene hypothesis and the old friend hypothesis reveal that helminths are associated with the prevalence of allergic diseases. The therapeutic potential of Trichinella spiralis is recognized; however, the stage at which it exerts its immunomodulatory effect is unclear.

Methods

We evaluated the differentiation of bone marrow–derived macrophages stimulated with T spiralis excretory-secretory products. Based on an ovalbumin-induced murine model, T spiralis was introduced during 3 allergy phases. Cytokine levels and immune cell subsets in the lung, spleen, and peritoneal cavity were assessed.

Results

We found that T spiralis infection reduced lung inflammation, increased anti-inflammatory cytokines, and decreased Th2 cytokines and alarms. Recruitment of eosinophils, CD11b+ dendritic cells, and interstitial macrophages to the lung was significantly suppressed, whereas Treg cells and alternatively activated macrophages increased in T spiralis infection groups vs the ovalbumin group. Notably, when T spiralis was infected prior to ovalbumin challenge, intestinal adults promoted proportions of CD103+ dendritic cells and alveolar macrophages.

Conclusions

T spiralis strongly suppressed type 2 inflammation, and adults maintained lung immune homeostasis.
Economic Sanctions by Non-Democracies: A Study of Cases from China and Russia
Authors: Whang Taehee , Paik Wooyeal
Published: November 2023

Do political institutions matter in explaining how economic sanctions are used? The current understanding of sanctions imposed by non-democratic sender countries is limited in the literature, as existing theories predominantly focus on the behaviors and strategies of democratic sender countries, leaving a notable gap in systematic comprehension. Using the existing dataset on sanctions, we theoretically and empirically distinguished characteristics of sanctions by non-democracies in terms of their motivating issues, types, and objectives. We also assessed our arguments based on recent data on Chinese and Russian sanctions since 2005 and a case illustration of China's de facto sanctions on South Korea for the Terminal High Altitude Area Defense deployment beginning in 2017.
Political Theology and International Relations: From History to Emancipation
Authors: Bain William
Published: November 2023

This article elaborates an account of political theology that is both historical and critical in orientation. Whereas the historical dimension excavates theological antecedents that inform the vocabulary of international relations, the critical dimension illuminates incoherence in accepted ways of thinking and speaking about the subject. The article develops these distinct, though complementary, modes of argument to illustrate what political theology contributes to the study of international relations. Part one situates the historical mode within the broader discourse of political theology, followed in part two by a consideration of the marginal place of political theology in international relations scholarship. Part three re-reads the exception—extraordinary action that contravenes established legal or moral order—to illustrate what is at stake when analogies between divine and human deviate from the theological original. This, in turn, unlocks in part four a critical project that subverts the ubiquitous contrast between irrational (religious) belief and rational (secular) unbelief and the privilege it asserts. Political theology conceived along these lines breaks free of the parochialism of the present by denaturalizing a matrix of international relations knowledge that is anything but natural.
Exogenous salicylic acid induces defense responses in tea plants against Toxoptera aurantii (Hemiptera: Aphididae)
Authors: Jiang Wenbin , Lu Changhao , Fan Jinjuan , Wu Mengyang , Chen Wenlong , Zhao Degang , Niu Suzhen , He Yingqin
Published: November 2023

Toxoptera aurantii is one of the most destructive pests, threatening the yield and quality of tea plantations. The salicylic acid (SA)-mediated signaling pathway is vital for the induction of plant defense responses; however, its role in tea plant resistance to T. aurantii remains unclear. Thus, this study used and electrical penetration graph and monitoring of population dynamics to evaluate the effects of exogenous SA application on T. aurantii feeding behavior and population growth in tea seedlings. Moreover, the effects of SA treatment on the activities of defense-related enzymes were analyzed. Probe counts and the duration of xylem sap ingestion were significantly higher in SA-treated plants than those in the control group. The total duration of passive phloem ingestion was significantly decreased in 0.5 mmol/l SA-treated plants, and the application of 0.5, 1, and 4 mmol/l SA significantly inhibited T. aurantii population growth. In addition, the activities of polyphenol oxidase, peroxidase, and superoxide dismutase were significantly increased in the 0.5 mmol/l SA-treated plants. Overall, this study demonstrates the capacity of exogenous SA to activate defense responses against T. aurantii. These results have crucial implications for understanding the mechanisms of enhanced resistance, thereby providing a sustainable approach for managing T. aurantii.
Susceptibility of northern corn rootworm (Diabrotica barberi) populations to Cry3Bb1 and Gpp34/Tpp35Ab1 proteins in seedling and diet overlay toxicity assays
Authors: Pereira Adriano E , Huynh Man P , Paddock Kyle J , Geisert Ryan W , Calles Torrez Veronica , Knodel Janet J , Moellenbeck Daniel J , Reinders Jordan D , Meinke Lance J , Schneider Sharon K , Coudron Thomas A , Shelby Kent S , Hibbard Bruce E
Published: November 2023

The northern corn rootworm, Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae) is a major pest of maize in the United States Corn Belt. Recently, resistance to Bacillus thuringiensis (Bt) maize was reported in North Dakota and increased use of Bt maize hybrids could facilitate resistance evolution in other maize-producing states. In this study, susceptibility to Bt proteins was evaluated in wild D. barberi populations from 8 fields collected in 5 different states (Minnesota, Missouri, Nebraska, Iowa, and North Dakota). Field populations were compared to a susceptible D. barberi colony in seedling and diet toxicity assays conducted with 3 concentrations of Cry3Bb1 (0.4, 4.0, and 40.0 µg/cm2) and Gpp34/Tpp35Ab1 (previously called Cry34/35Ab1; 1.4, 14.0, and 140.0 µg/cm2). The 2019 population from Meeker Co., Minnesota (MN-2019), exhibited the lowest mortality to Cry3Bb1 and also had nominally lowest mortality to Gpp34/Tpp35Ab1 at the highest concentrations tested in diet toxicity assays. Percent second instar was also highest for larvae of the Minnesota population surviving Cry3Bb1. In seedling assays, MN and IA-2018 populations exhibited the highest proportion survival and dry weight to both proteins expressed in corn. No significant differences in mortality, percent second instar, and dry weight were observed at the highest concentration for both proteins among the populations collected in in 2020. Most D. barberi populations were still highly susceptible to Cry3Bb1 and Gpp34/Tpp35Ab1 proteins based on diet and seedling assays, but resistance appears to be developing in some D. barberi populations. Now that methods are available, resistance monitoring may also be needed for D. barberi in some regions.
Congestion and scheduling preferences of car commuters in California: estimates using big data
Authors: Kim Jinwon , Moon Jucheol
Published: November 2023

This article estimates commuters’ scheduling utility function, which comprises the disutility of arriving at work earlier or later than desired (namely, the schedule-delay cost) and the disutility of travel time. The marginal rate of substitution (MRS) between the schedule delay and the travel time is about 0.85, meaning that commuters are willing to accept an extra schedule delay of about 1.2 time units (the reciprocal of 0.85) to reduce their travel time by 1 unit. For most travelers, the slope of the travel-time profile is much smaller than the estimated slope of the indifference curve (MRS). Based on our theoretical framework, where commuters choose a trip timing based on their travel-time profiles, our empirical results imply that commuters tend to arrive around their desired times bearing a small schedule-delay cost.
From backyard to backcountry: changes in mammal communities across an urbanization gradient
Authors: Hansen Christopher P , Kays Roland , Millspaugh Joshua J
Published: November 2023

Urbanization often results in biodiversity loss and homogenization, but this result is not universal and there is substantial variability in the spatiotemporal effects of urbanization on wildlife across cities and taxa. Areas with lower population and housing density are some of the fastest-growing regions in the western United States; thus, more research in these areas could offer additional insight into the effects of urbanization on wildlife and the potential importance of wild spaces in maintaining a diverse biotic community surrounding developed areas. To address this need, we conducted a study to identify the effects of urbanization (i.e. housing density) on mammals along a housing density gradient from wilderness to suburbia in Missoula, Montana. We deployed 178 motion-activated trail cameras at random sites within urban/suburban, exurban, rural, and wild regions from May to October 2019 to 2020. We identified all mammals >150 g, then evaluated how housing density influenced: (i) occupancy and (ii) species richness using multispecies occupancy models; (iii) relative abundance using Poisson models; and (iv) diel activity patterns using kernel density estimation and logistic regression. Urbanization was the strongest driver of mammal distribution, with a linear decline in mammal species richness as housing density increased. Urbanization also had strong effects on occupancy and detection rates, with larger-bodied mammals generally having stronger negative associations. Overall, mammal relative abundance was highest in suburban regions; however, this effect was largely driven by White-tailed Deer. Natural environmental factors explained most changes in mammal nocturnal activity; however, urbanization strongly affected nocturnality in some species, with Black Bear and White-tailed Deer becoming more nocturnal and Red Fox and Northern Raccoon becoming less nocturnal as housing density increased. While our study confirms that some mammals can live and thrive in developed areas, it emphasizes the importance of maintaining wild areas for those species that cannot.
Comparisons of Pediatric and Adult SARS-CoV-2-Specific Antibodies up to 6 Months after Infection, Vaccination, or Hybrid Immunity
Authors: Kim Minjun , Cheng Wesley A , Congrave-Wilson Zion , Marentes Ruiz Carolyn Jennifer , Turner Lauren , Mendieta Shirley , Jumarang Jaycee , Del Valle Jennifer , Lee Yesun , Fabrizio Thomas , Allen E Kaitlynn , Thomas Paul G , Webby Richard , Gordon Aubree , Pannaraj Pia S
Published: November 2023

Background

Characterization of longitudinal SARS-CoV-2-specific antibody responses in children following infection and vaccination is needed to inform SARS-CoV-2 vaccine policy decisions for children, which may differ from adults.

Methods

We enrolled individuals at the time of SARS-CoV-2 infection or vaccination for longitudinal serological testing and compared SARS-CoV-2-spike-specific IgG and neutralization activity in children and adults stratified by infection and vaccination status using enzyme-linked immunosorbent and virus neutralization assays.

Results

Between June 2020 and December 2022, we collected sera from 669 participants aged 40 days to 55 years, including 330 unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection, 180 vaccinated SARS-CoV-2-naïve individuals, and 159 vaccinated previously infected individuals. Half (n = 330, 49.3%) were children. SARS-CoV-2-specific IgG and neutralization activity in children < 12 years old in response to infection persisted at higher levels than those of adults through at least 6 months (spike-specific IgG levels, 2.05 [95% CI: 1.4-3.1] times higher than adults; neutralizing activity, median 88.8 vs 75.2%, respectively, p = .04). In addition, all pediatric participants had significantly higher IgG levels compared with adults at 6 months following infection or vaccination, regardless of prior infection status. Vaccine-induced SARS-CoV-2-specific IgG responses in previously infected individuals persisted at higher levels than those from infection alone at 6 months (median AUC, children 5-11 years old, 9115 vs 368; adolescents 3613 vs 475; adults 1956 vs 263, all p < .001).

Conclusions

These data demonstrate the robust and persistent immunologic response of SARS-CoV-2 vaccination in children and emphasize the benefit of vaccination after SARS-CoV-2 infection.
Weakly supervised anomaly detection in the Milky Way
Authors: Pettee Mariel , Thanvantri Sowmya , Nachman Benjamin , Shih David , Buckley Matthew R , Collins Jack H
Published: November 2023

Large-scale astrophysics data sets present an opportunity for new machine learning techniques to identify regions of interest that might otherwise be overlooked by traditional searches. To this end, we demonstrate how Classification Without Labels (CWoLa), a weakly supervised anomaly detection method, can help identify cold stellar streams within the more than one billion Milky Way stars observed by the Gaia satellite. CWoLa operates without the use of labelled streams or knowledge of astrophysical principles. Instead, it uses a classifier to distinguish between mixed samples for which the proportions of signal and background samples are unknown. As a proof of concept, we demonstrate that this computationally lightweight strategy is able to detect both simulated streams and the known stream GD-1 in data. Originally designed for high-energy collider physics, this technique may have broad applicability within astrophysics as well as other domains interested in identifying localized anomalies.
Systematic reanalysis of KMTNet microlensing events, paper I: Updates of the photometry pipeline and a new planet candidate
Authors: Yang Hongjing , Yee Jennifer C , Hwang Kyu-Ha , Qian Qiyue , Bond Ian A , Gould Andrew , Hu Zhecheng , Zhang Jiyuan , Mao Shude , Zhu Wei , Albrow Michael D , Chung Sun-Ju , Kim Seung-Lee , Park Byeong-Gon , Han Cheongho , Jung Youn Kil , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Cha Sang-Mok , Kim Dong-Jin , Kim Hyoun-Woo , Lee Chung-Uk , Lee Dong-Joo , Lee Yongseok , Pogge Richard W , Zang Weicheng , Abe Fumio , Barry Richard , Bennett David P , Bhattacharya Aparna , Donachie Martin , Fujii Hirosane , Fukui Akihiko , Hirao Yuki , Itow Yoshitaka , Kirikawa Rintaro , Kondo Iona , Koshimoto Naoki , Silva Stela Ishitani , Li Man Cheung Alex , Matsubara Yutaka , Muraki Yasushi , Suzuki Daisuke , Tristram Paul J , Yonehara Atsunori , Ranc Clément , Miyazaki Shota , Olmschenk Greg , Rattenbury Nicholas J , Satoh Yuki , Shoji Hikaru , Sumi Takahiro , Tanaka Yuzuru , Yamawaki Tsubasa
Published: November 2023

In this work, we update and develop algorithms for KMTNet tender-love care (TLC) photometry in order to create a new, mostly automated, TLC pipeline. We then start a project to systematically apply the new TLC pipeline to the historic KMTNet microlensing events, and search for buried planetary signals. We report the discovery of such a planet candidate in the microlensing event MOA-2019-BLG-421/KMT-2019-BLG-2991. The anomalous signal can be explained by either a planet around the lens star or the orbital motion of the source star. For the planetary interpretation, despite many degenerate solutions, the planet is most likely to be a Jovian planet orbiting an M or K dwarf, which is a typical microlensing planet. The discovery proves that the project can indeed increase the sensitivity of historic events and find previously undiscovered signals.
MODOMICS: a database of RNA modifications and related information. 2023 update
Authors: Cappannini Andrea , Ray Angana , Purta Elżbieta , Mukherjee Sunandan , Boccaletto Pietro , Moafinejad S Naeim , Lechner Antony , Barchet Charles , Klaholz Bruno P , Stefaniak Filip , Bujnicki Janusz M
Published: November 2023

The MODOMICS database was updated with recent data and now includes new data types related to RNA modifications. Changes to the database include an expanded modification catalog, encompassing both natural and synthetic residues identified in RNA structures. This addition aids in representing RNA sequences from the RCSB PDB database more effectively. To manage the increased number of modifications, adjustments to the nomenclature system were made. Updates in the RNA sequences section include the addition of new sequences and the reintroduction of sequence alignments for tRNAs and rRNAs. The protein section was updated and connected to structures from the RCSB PDB database and predictions by AlphaFold. MODOMICS now includes a data annotation system, with ‘Evidence’ and ‘Estimated Reliability’ features, offering clarity on data support and accuracy. This system is open to all MODOMICS entries, enhancing the accuracy of RNA modification data representation. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.
CRISPR–dCas13a system for programmable small RNAs and polycistronic mRNA repression in bacteria
Authors: Ko Sung Cheon , Woo Han Min
Published: November 2023

Bacterial small RNAs (sRNAs) function in post-transcriptional regulatory responses to environmental changes. However, the lack of eukaryotic RNA interference-like machinery in bacteria has limited the systematic engineering of RNA repression. Here, we report the development of clustered regularly interspaced short palindromic repeats (CRISPR)-guided dead CRIPSR-associated protein 13a (dCas13a) ribonucleoprotein that utilizes programmable CRISPR RNAs (crRNAs) to repress trans-acting and cis-acting sRNA as the target, altering regulatory mechanisms and stress-related phenotypes. In addition, we implemented a modular loop engineering of the crRNA to promote modular repression of the target gene with 92% knockdown efficiency and a single base-pair mismatch specificity. With the engineered crRNAs, we achieved targetable single-gene repression in the polycistronic operon. For metabolic application, 102 crRNAs were constructed in the biofoundry and used for screening novel knockdown sRNA targets to improve lycopene (colored antioxidant) production in Escherichia coli. The CRISPR–dCas13a system will assist as a valuable systematic tool for the discovery of novel sRNAs and the fine-tuning of bacterial RNA repression in both scientific and industrial applications.
Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201
Authors: Xin Dazhuan Eric , Liao Yunfei , Rao Rohit , Ogurek Sean , Sengupta Soma , Xin Mei , Bayat Arman Esshaghi , Seibel William L , Graham Richard T , Koschmann Carl , Lu Q Richard
Published: November 2023

Background

Diffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting.

Methods

We performed a screen of compounds targeting epigenetic enzymes to identify potential inhibitors for the growth of patient-derived DIPG cells. We further carried out transcriptomic and genomic landscape profiling including RNA-seq and CUT&RUN-seq as well as shRNA-mediated knockdown to assess the effects of chaetocin and SUV39H1, a target of chaetocin, on DIPG growth.

Results

High-throughput small-molecule screening identified an epigenetic compound chaetocin as a potent blocker of DIPG cell growth. Chaetocin treatment selectively decreased proliferation and increased apoptosis of DIPG cells and significantly extended survival in DIPG xenograft models, while restoring H3K27me3 levels. Moreover, the loss of H3K9 methyltransferase SUV39H1 inhibited DIPG cell growth. Transcriptomic and epigenomic profiling indicated that SUV39H1 loss or inhibition led to the downregulation of stemness and oncogenic networks including growth factor receptor signaling and stemness-related programs; however, D2 dopamine receptor (DRD2) signaling adaptively underwent compensatory upregulation conferring resistance. Consistently, a combination of chaetocin treatment with a DRD2 antagonist ONC201 synergistically increased the antitumor efficacy.

Conclusions

Our studies reveal a therapeutic vulnerability of DIPG cells through targeting the SUV39H1–H3K9me3 pathway and compensatory signaling loops for treating this devastating disease. Combining SUV39H1-targeting chaetocin with other agents such as ONC201 may offer a new strategy for effective DIPG treatment.
HINOTORI I: The nature of rejuvenation galaxies
Authors: Tanaka Takumi S , Shimasaku Kazuhiro , Tacchella Sandro , Ando Makoto , Ito Kei , Yesuf Hassen M , Matsui Suin
Published: November 2023

We present the HINOTORI (Star Formation History Investigation To Find Rejuvenation) project to reveal the nature of rejuvenation galaxies (RGs), which are galaxies that restarted their star formation after being quiescent. As the first step of HINOTORI, we construct the largest RG sample with 1071 sources. We select these RGs from 8857 MaNGA (Mapping Nearby Galaxies at APO) survey galaxies by reconstructing their star formation histories with the Prospector spectral energy distribution fitting code. Both optical spectral data and UV to IR photometric data are used for the fitting. Using mock data, we confirm that our method can detect weak rejuvenation events that form only about $0.1$% of the total stellar mass with high completeness. The RGs account for ${\sim}10$% of the whole sample, and rejuvenation events contribute on average only about $0.1$% of the total stellar mass in those galaxies but $17$% of the cosmic star formation rate density today. Our RGs have a similar mass distribution to quiescent galaxies (QGs). However, the morphology of the RGs is more disk-like than QGs, suggesting that rejuvenation may occur selectively in disk-like QGs. Our results also suggest the possibility of multiple-time rejuvenation events in a single galaxy. Further spatially resolved analyses of integral field unit data and radio observations and comparisons to simulations are needed to identify the mechanism and the role of rejuvenation in galaxy evolution.
A major role of coumarin-dependent ferric iron reduction in strategy I-type iron acquisition in Arabidopsis
Authors: Paffrath Vanessa , Tandron Moya Yudelsy A , Weber Günther , von Wirén Nicolaus , Giehl Ricardo F H
Published: November 2023

Many non-graminaceous species release various coumarins in response to iron (Fe) deficiency. However, the physiological relevance of these coumarins remains poorly understood. Here, we show that the three enzymes leading to sideretin biosynthesis co-exist in Arabidopsis (Arabidopsis thaliana) epidermal and cortical cells and that the shift to fraxetin at alkaline pH depends on MYB72-mediated repression of CYTOCHROME P450, FAMILY 82, SUBFAMILY C, POLYPEPTIDE 4 (CYP82C4). In vitro, only fraxetin and sideretin can reduce part of the Fe(III) that they mobilize. We demonstrate that coumarin-mediated Fe(III) reduction is critical under acidic conditions, as fraxetin and sideretin can complement the Fe(III)-chelate reductase mutant ferric reduction oxidase 2 (fro2), and disruption of coumarin biosynthesis in fro2 plants impairs Fe acquisition similar to in the Fe(II) uptake-deficient mutant iron-regulated transporter 1 (irt1). Disruption of sideretin biosynthesis in a fro2 cyp82C4-1 double mutant revealed that sideretin is the dominant chemical reductant that functions with FRO2 to mediate Fe(II) formation for root uptake. At alkaline pH, Fe(III) reduction by coumarins becomes almost negligible but fraxetin still sustains high Fe(III) mobilization, suggesting that its main function is to provide chelated Fe(III) for FRO2. Our study indicates that strategy-I plants link sideretin and fraxetin biosynthesis and secretion to external pH to recruit distinct coumarin chemical activities to maximize Fe acquisition according to prevailing soil pH conditions.
A pan-SARS-CoV-2-specific soluble angiotensin-converting enzyme 2-albumin fusion engineered for enhanced plasma half-life and needle-free mucosal delivery
Authors: Benjakul Sopisa , Anthi Aina Karen , Kolderup Anette , Vaysburd Marina , Lode Heidrun Elisabeth , Mallery Donna , Fossum Even , Vikse Elisabeth Lea , Albecka Anna , Ianevski Aleksandr , Kainov Denis , Karlsen Karine Flem , Sakya Siri Aastedatter , Nyquist-Andersen Mari , Gjølberg Torleif Tollefsrud , Moe Morten C , Bjørås Magnar , Sandlie Inger , James Leo C , Andersen Jan Terje
Published: November 2023

Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants.
Probing Multiple Transplant Delivery Routes of CD+34 Stem Cells for Promoting Behavioral and Histological Benefits in Experimental Ischemic Stroke
Authors: Lee Jea-Young , Cho Justin , D’Egidio Francesco , Vignon Christine , Streefkerk Hendrik , de Kalbermatten Matthieu , Garitaonandia Ibon , Borlongan Cesar V
Published: November 2023

Stroke is a leading cause of death in the US and around the world but with limited treatment options. Survivors often present with long-term cognitive and neurological deficits. Stem cell-based therapy has emerged as a potential treatment for stroke. While stem cell transplantation in stroke has reached clinical trials, mostly safety outcomes have been reported with efficacy readouts warranting more studies. In an effort to optimize the stem cell regimen for stroke, here we conducted vis-a-vis comparison of different routes of transplantation, namely, intracerebral, intraarterial, and intranasal delivery of expanded human CD34 + stem cells, called ProtheraCytes, in the established stroke model of transient middle cerebral artery occlusion (MCAO) using adult Sprague-Dawley rats. After adjusting for the dose and subacute timing of cell delivery, animals were randomly assigned to receive either ProtheraCytes or vehicle. Motor and neurological assays from days 7 to 28 post-stroke revealed significant functional recovery across all 3 delivery routes of ProtheraCytes compared to vehicle-treated stroke rats. Additionally, ProtheraCytes-transplanted stroke rats displayed significantly reduced infarct size and cell loss in the peri-infarct area coupled with enhanced neurogenesis and angiogenesis compared to vehicle-treated stroke rats. These results highlight the safety and efficacy of transplanting ProtheraCytes, including via the minimally invasive intranasal route, in conferring robust and stable behavioral and histological positive outcomes in experimental stroke.
National health insurance scheme improves access and optimization of antimicrobial use in the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
Authors: Obadare Temitope O , Ogundipe Taiwo O , Adeyemo Adeyemi T , Aboderin Caleb M , Abiola Doyin R , Sule Naheemot O , Aboderin Aaron O
Published: November 2023

Background

Nigeria instituted the National Health Insurance Scheme (NHIS) for universal health coverage. This study compared the NHIS and out-of-pocket (OOP) antibiotic prescribing with the World Health Organization (WHO) optimal values.

Methods

A total of 2190 prescription forms from the NHIS and OOP were included in this study conducted at Obafemi Awolowo University Teaching Hospitals Complex, Nigeria from January 2021 to December 2022 and analysed using WHO drug prescribing guidelines.

Results

The average number of drugs per encounter was higher in the NHIS prescribing (χ2=58.956, p=0.00) than in OOP prescribing. The percentage of encounters with an antibiotic prescribed is higher in NHIS prescribing (χ2=46.034, p=0.000) than in OOP prescribing. The percentage of parenteral antibiotic prescribing is higher in OOP prescribing (χ2=25.413, p=0.000) than in NHIS prescribing. The percentage of antibiotic prescribed from the National Essential Medicine List is higher in NHIS prescribing (χ2=8.227, p=0.000) as well as the antibiotics prescribed from the Access category of the WHO Access, Watch and Reserve (AWaRe) Classification of antibiotics (χ2=23.946, p=0.000) when compared with OOP prescribing.

Conclusions

Prescribing indicators show better performances with NHIS antibiotic prescribing and are closer to the WHO-recommended optimal values than in OPP prescribing. Hence NHIS prescribing can be an easy target for hospital antibiotic stewardship intervention for optimal antibiotic prescribing.
Too old to be creative? An age bias in creativity judgment
Authors: Oh Ga-Eun (Grace) , Jeong Inseong , Wang Mo , North Michael S , Choi Yeeun
Published: November 2023

Building on prior literature on social judgment and age stereotypes, we investigate whether age bias exists in creativity judgment and, if so, how it emerges and to what extent it persists. One archival data study (Study 1) and 5 recruitment scenario experiments (Studies 2–5) provide evidence that people persistently evaluate the creativity of an older person more negatively compared to that of a younger person. This age bias in creativity judgment remained even when a creative job feature that is positively associated with older people (i.e., requiring convergent vs. divergent thinking) was highlighted (Study 3) and when a worker demonstrated creative performance (Study 4). Furthermore, by testing the moderating role of age stereotypes, we found that age stereotypes in the adaptability dimension specifically contributed to this bias: those who believe that older people are not adaptable at work tend to exhibit age-biased creativity judgments (Studies 5a and 5b). Understanding the persistence of age bias in creativity judgment and its processes helps raise awareness of it in the workplace. Our findings also call for future investigations into effective strategies to attenuate such biases in the workplace.
The NLN/Jonas Ten-Year Story: Perceptions of Nurse Educator Scholars
Authors: Patterson Barbara , Thomas Dreifuerst Kristina , McGuire Amy
Published: November 2023

The aim of the NLN/Jonas Scholars Program is to support doctoral nursing students whose program of research focuses on research in nursing education. As a 10-year review, 23 nursing students pursuing a doctorate participated in focus groups with the goal of describing the influence of a year-long mentoring program on their career trajectory. Analysis of the data revealed two themes: having someone believe in me and my research topic and being mentored and learning to mentor others. The findings support that being skilled in conducting pedagogical research with mentorship advances nursing education practice, scholarship, and leadership.
Thirty-day Outcomes of First-in-man Implantation of a Novel Transcatheter Edge-to-edge Mitral Repair System in Patients With Severe Mitral Regurgitation
Authors: Xu Kai , Wang Yan , Chen Shaoliang , Pan Xiangbin , He Ben , Zhang Ruiyan , Wang Bin , Zhang Junjie , Zhu Zhengbin , Wang Bin , Zhu Da , Han Yaling
Published: November 2023

Objectives:

The aim of this multicenter, prospective, single-arm pilot study (ClinicalTrials.gov number: NCT05040074) was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system, SQ-Kyrin®-M Clip (Shenqi Medical, Shanghai, China), in patients with severe mitral regurgitation (MR).

Methods:

The heart team considered patients from 5 centers in China with clinically significant functional mitral regurgitation ≥3+ despite optimal medical therapy or degenerative mitral regurgitation ≥3+ with high surgical risk as candidates for transcatheter repair. All patients received transcatheter edge-to-edge mitral valve repair under general anesthesia. The primary outcome was technical success, which included all of the following measured at the exit from the catheterization laboratory: (1) absence of procedural mortality; (2) successful access, delivery, and retrieval of the device delivery system; (3) successful deployment and correct positioning of the first intended device; and (4) no emergency surgery or reintervention related to the device or access procedure. The secondary outcomes included all-cause mortality, serious adverse events, device success, and procedural success 30 d after the intervention.

Results:

From June 2021 to December 2021, 18 patients were enrolled in this study with age (75.7 ± 7.4) years. Fifteen patients had MR 4+, while 3 had MR 3+. Technical success was achieved in all patients, including 6 degenerative mitral regurgitation and 12 functional mitral regurgitation patients. There was no all-cause mortality at 30 d. One patient had single leaflet device attachment within 30 d, which was regarded as a serious adverse event, and the patient was successfully treated with reintervention by implanting another clip. Another patient’s transmitral gradient was 6 mmHg (>5 mmHg), with an effective orifice area of 2.57 cm2 after the procedure. Sixteen patients had device success and procedural success at 30 d postoperation. Fourteen patients had MR 1+, 3 had MR 2+, and only 1 patient had MR 3 + 30 d after the procedure.

Conclusions:

The results of this feasibility study showed the efficacy and safety of the SQ-Kyrin®-M device in the Chinese population with severe MR, laying a solid foundation for a subsequent large-scale confirmatory study.
Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs
Authors: Hu Yan-Xia , Diao Li-Ting , Hou Ya-Rui , Lv Guo , Tao Shuang , Xu Wan-Yi , Xie Shu-Juan , Ren Ya-Han , Xiao Zhen-Dong
Published: November 2023

Background and Aims:

Pseudouridine is a prevalent RNA modification and is highly present in the serum and urine of patients with HCC. However, the role of pseudouridylation and its modifiers in HCC remains unknown. We investigated the function and underlying mechanism of pseudouridine synthase 1 (PUS1) in HCC.

Approach and Results:

By analyzing the TCGA data set, PUS1 was found to be significantly upregulated in human HCC specimens and positively correlated with tumor grade and poor prognosis of HCC. Knockdown of PUS1 inhibited cell proliferation and the growth of tumors in a subcutaneous xenograft mouse model. Accordingly, increased cell proliferation and tumor growth were observed in PUS1-overexpressing cells. Furthermore, overexpression of PUS1 significantly accelerates tumor formation in a mouse HCC model established by hydrodynamic tail vein injection, while knockout of PUS1 decreases it. Additionally, PUS1 catalytic activity is required for HCC tumorigenesis. Mechanistically, we profiled the mRNA targets of PUS1 by utilizing surveying targets by apolipoprotein B mRNA-editing enzyme 1 (APOBEC1)-mediated profiling and found that PUS1 incorporated pseudouridine into mRNAs of a set of oncogenes, thereby endowing them with greater translation capacity.

Conclusions:

Our study highlights the critical role of PUS1 and pseudouridylation in HCC development, and provides new insight that PUS1 enhances the protein levels of a set of oncogenes, including insulin receptor substrate 1 (IRS1) and c-MYC, by means of pseudouridylation-mediated mRNA translation.
Whole-genome methylation profiling reveals regions associated with painful temporomandibular disorders and active recovery processes
Authors: Ao Xiang , Parisien Marc , Fillingim Roger B. , Ohrbach Richard , Slade Gary D. , Diatchenko Luda , Smith Shad B.
Published: November 2023

Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexplained heritability may be because of DNA methylation, an epigenetic phenomenon, we measured genome-wide DNA methylation using the Illumina MethylationEPIC platform with blood samples from participants in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Associations with chronic TMD used methylation data from 496 chronic painful TMD cases and 452 TMD-free controls. Changes in methylation between enrollment and a 6-month follow-up visit were determined for a separate sample of 62 people with recent-onset painful TMD. More than 750,000 individual CpG sites were examined for association with chronic painful TMD. Six differentially methylated regions were significantly (P < 5 × 10−8) associated with chronic painful TMD, including loci near genes involved in the regulation of inflammatory and neuronal response. A majority of loci were similarly differentially methylated in acute TMD consistent with observed transience or persistence of symptoms at follow-up. Functional characterization of the identified regions found relationships between methylation at these loci and nearby genetic variation contributing to chronic painful TMD and with gene expression of proximal genes. These findings reveal epigenetic contributions to chronic painful TMD through methylation of the genes FMOD, PM20D1, ZNF718, ZFP57, and RNF39, following the development of acute painful TMD. Epigenetic regulation of these genes likely contributes to the trajectory of transcriptional events in affected tissues leading to resolution or chronicity of pain.
Factors Influencing Sleep Disturbances in Adolescent Smokers in South Korea
Authors: Kim Sung Reul , Kim Ji Young , Kim Hyun Kyung , Kim Hye Young
Published: November 2023

This study aimed to describe sleep disturbances and identify associated factors in adolescent smokers in South Korea. This study adopted a cross-sectional design and recruited 520 students aged 12–17 years from 35 schools to participate in a smoking cessation program. To compare demographic, smoking-related, psychological, and problem behavior characteristics between adolescent smokers with sleep disturbances and without sleep disturbances, chi-square tests and independent t tests were used. Logistic regression analysis was performed to identify the factors associated with sleep disturbances in adolescent smokers. Approximately 45.8% of adolescent smokers reported sleep disturbances. Sleep disturbances were more frequent among girls than among boys and more frequent among high school students than among middle school students. Other factors included cigarette use within 1 month, nicotine dependence, smoking cessation self-efficacy, depression, Internet addiction, and suicidal ideation. Gender (girls), school level (high school), depression, Internet addiction, and daily cigarette use (11 or more cigarettes) were significantly associated with sleep disturbances in adolescent smokers. To improve the sleep quality of adolescent smokers, health professionals should focus on sleep disturbances and associated factors and develop appropriate intervention programs.
Closing the Opioid Treatment Gap Through Advance Practice Nursing Activation
Authors: Tierney Matthew , Castillo Elizabeth , Leonard Adam , Huang Emily
Published: November 2023

Introduction

Buprenorphine, an effective medication for opioid use disorder (MOUD), reduces opioid-related harms including overdose, but a significant gap exists between MOUD need and treatment, especially for marginalized populations. Historically, low MOUD treatment capacity is rising, driven by advanced practice registered nurses (APRNs). A graduate nursing course was designed to increase equitable buprenorphine treatment delivery by APRNs. We report on baseline findings of a curriculum evaluation study with a pretest–posttest design.

Design

Computerized surveys assessed trainee satisfaction with the course, trainee knowledge for providing MOUD, and trainee satisfaction in working with people who use drugs.

Methods

Quantitative survey results utilizing Likert scales are presented.

Results

Baseline precourse surveys revealed less than half (44%) of APRN students agreed/strongly agreed that they had a working knowledge of drugs and drug-related problems and 37% agreed/strongly agreed that they knew enough about the causes of drug problems to carry out their roles when working with people who use drugs. Approximately two thirds of APRN students agreed/strongly agreed that they want to work with people who use drugs (63%), that it is satisfying to work with people who use drugs (66%), and that it is rewarding to work with people who use drugs (63%). Nearly all students reported high satisfaction with the course.

Conclusion

APRN students reported high satisfaction with a novel course grounded in health equity that has potential to reduce health disparities and accelerate the closure of the MOUD treatment gap, particularly for racial/ethnic minorities, rural populations, and transition-age youth.