bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular immune privilege and retinal pigment epithelial cells
Authors: Du Yuxiang , Yan Bo 
Published: February 2023

AbstractThe ocular tissue microenvironment is immune-privileged and uses multiple immunosuppressive mechanisms to prevent the induction of inflammation. The retinal pigment epithelium plays an essential role in ocular immune privilege. In addition to serving as a blood barrier separating the fenestrated choriocapillaris from the retina, the retinal pigment epithelium is a source of immunosuppressive cytokines and membrane-bound negative regulators that modulate the activity of immune cells within the retina. This article reviews the current understanding of how retinal pigment epithelium cells mediate immune regulation, focusing on the changes under pathologic conditions.
Impact of COVID-19 pandemic on neuropathology service: Experience at one Canadian center
Authors: Pejhan Shervin , Tran Christopher , Driman David K , Hammond Robert , Ang Lee Cyn , Zhang Qi 
Published: January 2023

Abstract
The COVID-19 pandemic has had a significant impact on medical services. Many countries postponed nonemergent procedures to preserve hospital resources for the unprecedented situation. Surgical backlogs caused by the COVID-19 pandemic have been evaluated by different groups. However, the impact of this pandemic on pathology and specifically neuropathology (NP) services has received limited attention. In this study, we reviewed all NP reports of the London Health Sciences Centre from January 2018 (2 years before the pandemic declaration) until the end of the year 2021. Demographic information and pathology details were collected. For tumors, site, histopathology types, and WHO grading were analyzed. In nontumoral specimens, pathological diagnoses were compared in pre- and postpandemic time. The total number of NP samples reached its lowest in April 2020, corresponding to the first Ontario provincial lockdown, and fluctuated throughout the studied period. Among the different types of NP surgical specimens, muscle and epilepsy-related specimens showed a more significant reduction, compared to neoplastic specimens. In 2020, the proportion of tumor specimens from patients older than 40 years of age increased. Similarly, the proportion of high-grade glioma and brain metastasis diagnoses also increased. Lastly, we observed a marked increase in biopsies for temporal arteritis and other inflammatory lesions.
Honokiol alleviates sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis and oxidative stress
Authors: Liu Aijun , Xun Shucan , Zhou Guangzhi , Zhang Yonglin , Lin Li 
Published: January 2023

Abstract

Objective
Honokiol, a natural active compound extracted from Chinese herbal medicine, can ameliorate acute lung and kidney injury of sepsis. This study was to explore the effects of honokiol on sepsis-associated cardiac dysfunction and the underlying mechanism.

Methods
Septic mice were induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS), and septic HL-1 or AC16 cells were induced by LPS.

Results
Honokiol improved the survival and alleviated cardiac dysfunction in mice with CLP-induced sepsis. Honokiol inhibited the increased interleukin (IL) 1-β, IL-6 and tumour necrosis factor (TNF)-α in the serum and heart of CLP- and LSP-induced septic mice. Honokiol treatment reversed the increased levels of IL1-β, IL-6 and TNF-α in LPS-induced HL-1 cells. Honokiol treatment also decreased the elevated levels of IL1-β, IL-6 and TNF-α in LPS-induced AC16 cells. The increased cardiac apoptosis in CLP- and LPS-induced septic mice was alleviated by honokiol. The enhancement of oxidative stress in the heart of CLP- and LPS-induced septic mice was suppressed after honokiol administration.

Conclusion
These results showed that honokiol could ameliorate sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis, and oxidative stress. Honokiol is a prospective drug for sepsis-associated heart damage in the future.
Day-time-scale variability in the radio light curve of the Tidal Disruption Event AT2022cmc: confirmation of a highly relativistic outflow
Authors: Rhodes L , Bright J S , Fender R , Sfaradi I , Green D A , Horesh A , Mooley K , Pasham D , Smartt S , Titterington D J , van der Horst A J , Williams D R A 
Published: February 2023

ABSTRACTTidal disruption events (TDEs) are transient, multiwavelength events in which a star is ripped apart by a supermassive black hole. Observations show that in a small fraction of TDEs, a short-lived, synchrotron emitting jet is produced. We observed the newly discovered TDE AT2022cmc with a slew of radio facilities over the first 100 d after its discovery. The light curve from the Arcminute Microkelvin Imager Large Array radio interferometer shows day-time-scale variability which we attribute to a high brightness temperature emitting region as opposed to scintillation. We measure a brightness temperature of 2 × 1015 K, which is unphysical for synchrotron radiation. We suggest that the measured high brightness temperature is a result of relativistic beaming caused by a jet being launched at velocities close to the speed of light along our line of sight. We infer from day-time-scale variability that the jet associated with AT2022cmc has a relativistic Doppler factor of at least 16, which corresponds to a bulk Lorentz factor of at least 8, if we are observing the jet directly on axis. Such an inference is the first conclusive evidence that the radio emission observed from some TDEs is from relativistic jets because it does not rely on an outflow model. We also compare the first 100 d of radio evolution of AT2022cmc with that of the previous bright relativistic TDE,Swift J1644, and find a remarkable similarity in their evolution.
A surprising abundance of massive quiescent galaxies at 3 &lt;z&lt; 5 in the first data fromJWSTCEERS
Authors: Carnall A C , McLeod D J , McLure R J , Dunlop J S , Begley R , Cullen F , Donnan C T , Hamadouche M L , Jewell S M , Jones E W , Pollock C L , Wild V 
Published: February 2023

ABSTRACTWe report a robust sample of 10 massive quiescent galaxies at redshift, z &gt; 3, selected using the first data from the JWST Cosmic Evolution Early Release Science programme. Three of these galaxies are at 4 &lt; z &lt; 5, constituting the best evidence to date for quiescent galaxies significantly before z = 4. These extreme galaxies have stellar masses in the range log10(M*/M⊙) = 10.1–11.1, and formed the bulk of their mass around z ≃ 10, with two objects having star formation histories that suggest they had already reached log10(M*/M⊙) &gt; 10 by z ≳ 8. We report number densities for our sample, demonstrating that, based on the small area of JWST imaging so far available, previous work appears to have underestimated the number of quiescent galaxies at 3 &lt; z &lt; 4 by a factor of 3–5, due to a lack of ultra-deep imaging data at $\lambda \gt 2\, \mu$m. This result deepens the existing tension between observations and theoretical models, which already struggle to reproduce previous estimates of z &gt; 3 quiescent galaxy number densities. Upcoming wider-area JWST imaging surveys will provide larger samples of such galaxies and more robust number densities, as well as providing opportunities to search for quiescent galaxies at z &gt; 5. The galaxies we report are excellent potential targets for JWST NIRSpec spectroscopy, which will be required to understand in detail their physical properties, providing deeper insights into the processes responsible for forming massive galaxies and quenching star formation during the first billion years.
Proto-neutron star convection and the neutrino-driven wind: implications for the r-process
Authors: Nevins Brian , Roberts Luke F 
Published: February 2023

ABSTRACT
The neutrino-driven wind from proto-neutron stars is a proposed site for r-process nucleosynthesis, although most previous work has found that a wind heated only by neutrinos cannot produce the third r-process peak. However, several groups have noted that introducing a secondary heating source within the wind can change the hydrodynamic conditions sufficiently for a strong r-process to proceed. One possible secondary heating source is gravito-acoustic waves, generated by convection inside the proto-neutron star. As these waves propagate into the wind, they can both accelerate the wind and shock and deposit energy into the wind. Additionally, the acceleration of the wind by these waves can reduce the total number of neutrino captures and thereby reduce the final electron fraction of the wind. In neutron rich conditions, all of these effects can make conditions more favourable for r-process nucleosynthesis. Here, we present a systematic investigation of the impact of these convection-generated gravito-acoustic waves within the wind on potential nucleosynthesis. We find that wave effects in the wind can generate conditions favourable for a strong r-process, even when the energy flux in the waves is a factor of 10−4 smaller than the total neutrino energy flux and the wind is marginally neutron rich. Nevertheless, this depends strongly on the radius at which the waves become non-linear and form shocks. We also find that both entropy production after shock formation and the acceleration of the wind due to stresses produced by the waves prior to shock formation impact the structure and nucleosynthesis of these winds.
Deciphering the Genetic Basis of Silkworm Cocoon Colors Provides New Insights into Biological Coloration and Phenotypic Diversification
Authors: Lu Yaru , Luo Jiangwen , An Erxia , Lu Bo , Wei Yinqiu , Chen Xiang , Lu Kunpeng , Liang Shubo , Hu Hai , Han Minjin , He Songzhen , Shen Jianghong , Guo Dongyang , Bu Nvping , Yang Ling , Xu Wenya , Lu Cheng , Xiang Zhonghuai , Tong Xiaoling , Dai Fangyin 
Published: January 2023

AbstractThe genetic basis of phenotypic variation is a long-standing concern of evolutionary biology. Coloration has proven to be a visual, easily quantifiable, and highly tractable system for genetic analysis and is an ever-evolving focus of biological research. Compared with the homogenized brown-yellow cocoons of wild silkworms, the cocoons of domestic silkworms are spectacularly diverse in color, such as white, green, and yellow-red; this provides an outstanding model for exploring the phenotypic diversification and biological coloration. Herein, the molecular mechanism underlying silkworm green cocoon formation was investigated, which was not fully understood. We demonstrated that five of the seven members of a sugar transporter gene cluster were specifically duplicated in the Bombycidae and evolved new spatial expression patterns predominantly expressed in silk glands, accompanying complementary temporal expression; they synergistically facilitate the uptake of flavonoids, thus determining the green cocoon. Subsequently, polymorphic cocoon coloring landscape involving multiple loci and the evolution of cocoon color from wild to domestic silkworms were analyzed based on the pan-genome sequencing data. It was found that cocoon coloration involved epistatic interaction between loci; all the identified cocoon color-related loci existed in wild silkworms; the genetic segregation, recombination, and variation of these loci shaped the multicolored cocoons of domestic silkworms. This study revealed a new mechanism for flavonoids-based biological coloration that highlights the crucial role of gene duplication followed by functional diversification in acquiring new genetic functions; furthermore, the results in this work provide insight into phenotypic innovation during domestication.
Plasticity and Stereotypic Rewiring of the Transcriptome Upon Bacterial Evolution of Antibiotic Resistance
Authors: Grézal Gábor , Spohn Réka , Méhi Orsolya , Dunai Anett , Lázár Viktória , Bálint Balázs , Nagy István , Pál Csaba , Papp Balázs 
Published: January 2023

Abstract
Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.
The impact of nucleosome structure on CRISPR/Cas9 fidelity
Authors: Handelmann Christopher R , Tsompana Maria , Samudrala Ram , Buck Michael J 
Published: February 2023

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR) Cas system is a powerful tool that has the potential to become a therapeutic gene editor in the near future. Cas9 is the best studied CRISPR system and has been shown to have problems that restrict its use in therapeutic applications. Chromatin structure is a known impactor of Cas9 targeting and there is a gap in knowledge on Cas9’s efficacy when targeting such locations. To quantify at a single base pair resolution how chromatin inhibits on-target gene editing relative to off-target editing of exposed mismatching targets, we developed the gene editor mismatch nucleosome inhibition assay (GEMiNI-seq). GEMiNI-seq utilizes a library of nucleosome sequences to examine all target locations throughout nucleosomes in a single assay. The results from GEMiNI-seq revealed that the location of the protospacer-adjacent motif (PAM) sequence on the nucleosome edge drives the ability for Cas9 to access its target sequence. In addition, Cas9 had a higher affinity for exposed mismatched targets than on-target sequences within a nucleosome. Overall, our results show how chromatin structure impacts the fidelity of Cas9 to potential targets and highlight how targeting sequences with exposed PAMs could limit off-target gene editing, with such considerations improving Cas9 efficacy and resolving current limitations.
eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation
Authors: Schmidt Tobias , Dabrowska Adrianna , Waldron Joseph A , Hodge Kelly , Koulouras Grigorios , Gabrielsen Mads , Munro June , Tack David C , Harris Gemma , McGhee Ewan , Scott David , Carlin Leo M , Huang Danny , Le Quesne John , Zanivan Sara , Wilczynska Ania , Bushell Martin 
Published: February 2023

AbstractAltered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs specifically activate eIF4A1 unwinding allowing local RNA structural rearrangement and translation of eIF4A1-dependent mRNAs in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain AG-rich motifs within their 5’UTR which specifically activate eIF4A1 unwinding of local RNA structure to facilitate translation. This mode of eIF4A1 regulation is used by mRNAs encoding components of mTORC-signalling and cell cycle progression, and renders these mRNAs particularly sensitive to eIF4A1-inhibition. Mechanistically, we show that binding of eIF4A1 to AG-rich sequences leads to multimerization of eIF4A1 with eIF4A1 subunits performing distinct enzymatic activities. Our structural data suggest that RNA-binding of multimeric eIF4A1 induces conformational changes in the RNA resulting in an optimal positioning of eIF4A1 proximal to the RNA duplex enabling efficient unwinding. Our data proposes a model in which AG-motifs in the 5’UTR of eIF4A1-dependent mRNAs specifically activate eIF4A1, enabling assembly of the helicase-competent multimeric eIF4A1 complex, and positioning these complexes proximal to stable localised RNA structure allowing ribosomal subunit scanning.
Clostridioides difficileBinary Toxin Binding Component Increases Virulence in a Hamster Model
Authors: Simpson Morgan , Bilverstone Terry , Leslie Jhansi , Donlan Alexandra , Uddin Md Jashim , Petri William A , Marin Natasha , Kuehne Sarah , Minton Nigel P , Petri William A 
Published: January 2023

AbstractBackgroundClostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection.MethodsTo determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness.ResultsAlthough expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection.ConclusionsOverall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection.
Factors Associated With Long COVID Symptoms in an Online Cohort Study
Authors: Durstenfeld Matthew S , Peluso Michael J , Peyser Noah D , Lin Feng , Knight Sara J , Djibo Audrey , Khatib Rasha , Kitzman Heather , O’Brien Emily , Williams Natasha , Isasi Carmen , Kornak John , Carton Thomas W , Olgin Jeffrey E , Pletcher Mark J , Marcus Gregory M , Beatty Alexis L 
Published: February 2023

AbstractBackgroundFew prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID.MethodsIn March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise.ResultsOf 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents’ mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20–1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02–2.63), preinfection depression (OR, 1.08; 95% CI, 1.01–1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15–0.90) were associated with Long COVID symptoms.ConclusionsVariant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms.
The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment
Authors: Tse Natalie , Parks Ruth M , Holmes Holly M , Cheung Kwok-Leung 
Published: January 2023

AbstractBackgroundPolypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status.MethodsA total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision.ResultsPolypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P &lt; .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases.ConclusionsThis work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.
Gradability and Comparison in Kannada
Authors: Herur Sindhu , Amritavalli R. 
Published: January 2023

Abstract
Gradable nouns participate in comparison without the need for a quantifier to project a degree head. Case, genitive, or dative (and of in English) can function to project a degree head; bare property concept nouns in the dative subject construction are not gradable, but their dative/genitive-marked counterparts are. Thus, one source for a category of adjectives from a universal two-category lexical base (N, V) is by the absorption of N into a degree case-head. Taking also have as be which absorbs the dative case, the stability of morphological case in Dravidian explains the lack of have and the paucity of adjectives, and thus, the inevitability of the dative subject construction.