bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ophthalmic immune-related adverse events associated with immune checkpoint inhibitors
Authors: Gan Linyang , Chen Huan , Liu Xiaowei , Zhang Li 
Published: March 2023

PurposeTo investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and outcomes of ophthalmic irAEs.MethodsWe retrospectively reviewed the medical records of patients who received ICI therapy from January 2016 to September 2022 at Peking Union Medical College Hospital and analyzed the incidence of systemic and ophthalmic adverse effects of this therapy.ResultsOf 962 patients, 248 (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1%. The most common ICI received by the patients was pembrolizumab (373; 38.8%). Nearly half of the patients (477; 49.6%) had lung cancer. Combination therapy was associated with an increased incidence of irAEs without statistical significance. Patients with lung cancer presented with an increased incidence of total irAEs (p = 0.003) and ophthalmic irAEs (p = 0.032). Eleven patients had ophthalmic manifestations, including ophthalmoplegia (6/11), conjunctivitis (3/11), reactive cutaneous capillary endothelial proliferation (RCCEP) (1/11), and orbital inflammation (1/11). Eight patients had concomitant extra-ophthalmic irAEs. Furthermore, ICIs were discontinued in nine patients, and most ophthalmic manifestations were well controlled with topical and systemic steroids. Ten patients were treated with intravenous or oral steroids. However, cancer progression occurred in five out of eleven patients after the interruption of ICIs.ConclusionIrAEs are correlated with ICI regimens and underlying neoplasia. In our Chinese cohort, patients have a higher risk of ophthalmoplegia than uveitis. Early recognition and multidisciplinary consultation are crucial for optimal treatment of ophthalmic irAEs.
A new insight into the impact of systemic lupus erythematosus on oocyte and embryo development as well as female fertility
Authors: Mao Ruolin , Wang Xiangfei , Long Rui , Wang Meng , Jin Lei , Zhu Lixia 
Published: March 2023

BackgroundSystemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. But it’s currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it’s controversial whether SLE has an adverse effect on fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE.ObjectiveThis study was aim to investigate oocyte and embryonic development as well as ovarian reserve, and clinical outcomes in SLE patients during in vitro fertilization (IVF) treatment. By combining data on embryonic and gamete development in SLE patients, we hope to provide new insights into a comprehensive assessment of fertility in SLE patients.MethodsIn this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups.ResultsAfter PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 64.7%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both).ConclusionPatients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. Individualized fertility assessment and early fertility guidance are necessary for these special groups.
Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses
Authors: Jossi Siân E. , Arcuri Melissa , Alshayea Areej , Persaud Ruby R. , Marcial-Juárez Edith , Palmieri Elena , Di Benedetto Roberta , Pérez-Toledo Marisol , Pillaye Jamie , Channell Will M. , Schager Anna E. , Lamerton Rachel E. , Cook Charlotte N. , Goodall Margaret , Haneda Takeshi , Bäumler Andreas J. , Jackson-Jones Lucy H. , Toellner Kai-Michael , MacLennan Calman A. , Henderson Ian R. , Micoli Francesca , Cunningham Adam F. 
Published: March 2023

IntroductionVaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood.Methods and resultsHere, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (&gt;5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV.DiscussionTherefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.
Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation
Authors: Tan Yejun , Kang Jin , Li Hongli , Zhong Aifang , Liu Yaqiong , Zhang Zheyu , Huang Roujie , Cheng Xin , Peng Weijun 
Published: March 2023

BackgroundPatients with diabetes mellitus (DM) have a higher incidence of malignant tumors than people without diabetes, but the underlying molecular mechanisms are still unclear.MethodsTo investigate the link between DM and cancer, we screened publicly available databases for diabetes and cancer-related genes (DCRGs) and constructed a diabetes-based cancer-associated inflammation network (DCIN). We integrated seven DCRGs into the DCIN and analyzed their role in different tumors from various perspectives. We also investigated drug sensitivity and single-cell sequencing data in colon adenocarcinoma as an example. In addition, we performed in vitro experiments to verify the expression of DCRGs and the arachidonic acid metabolic pathway.ResultsSeven identified DCRGs, including PPARG, MMP9, CTNNB1, TNF, TGFB1, PTGS2, and HIF1A, were integrated to construct a DCIN. The bioinformatics analysis showed that the expression of the seven DCRGs in different tumors was significantly different, which had varied effects on diverse perspectives. Single-cell sequencing analyzed in colon cancer showed that the activity of the DCRGs was highest in Macrophage and the lowest in B cells among all cell types in adenoma and carcinoma tissue. In vitro experiments showed that the DCRGs verified by western bolt and PEG2 verified by ELISA were all highly expressed in COAD epithelial cells stimulated by high glucose.ConclusionThis study, for the first time, constructed a DCIN, which provides novel insights into the underlying mechanism of how DM increases tumor occurrence and development. Although further research is required, our results offer clues for new potential therapeutic strategies to prevent and treat malignant tumors.
Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism
Authors: Zhu Ruizhe , Fang Yilin , Li Hongyu , Liu Ying , Wei Jing , Zhang Shuwei , Wang Liwei , Fan Rui , Wang Lingfang , Li Shengjie , Chen Tingtao 
Published: March 2023

IntroductionTest anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students.MethodsSixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students’ mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism.ResultsThe questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p &lt; 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms.ConclusionThe results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.
Persistence and distribution of dinotefuran in tree of heaven
Authors: Keyzer Justin , Lewis Phillip , McCullough Deborah G. 
Published: March 2023

Spotted lanternfly (SLF) (Lycorma delicatula (White)), an invasive planthopper discovered in Pennsylvania, U.S.A. in 2014, feeds for approximately six months by sucking phloem sap from trunks and limbs of tree of heaven, Ailanthus altissima, along with several native trees and woody vines. Basal trunk sprays of dinotefuran, a systemic neonicotinoid insecticide, are commonly used to reduce SLF densities and spread. Information on dinotefuran persistence and within-tree distribution can help identify optimal timing of annual basal trunk sprays, facilitating efficient use of available resources. We applied dinotefuran to 20 uninfested A. altissima trees in early April then periodically sampled foliage to monitor insecticide residues. Foliar dinotefuran residues averaged (± SE) 7.8 ± 1.1 and 6.3 ± 1.2 in July and August, respectively, then dropped significantly to 2.6 ± 0.5 ppm in September. In a second study, 20 A. altissima trees were similarly treated with dinotefuran basal trunk sprays in early June. Trees were felled to collect foliage and phloem from branches and the trunk in either mid-July or September. Foliar residues averaged 12.7 ± 1.3 and 14.6 ± 2.2 ppm in July and September, respectively. For trees felled in July, residues were detected in phloem collected from below the spray line on trunks of seven trees and above the spray line on three trees, averaging 8.6 ± 4.4 and 7.4 ± 2.9 ppm, respectively. In trees felled in September, phloem from below spray lines of seven trees averaged 3.7 ± 1.3 ppm but dinotefuran was not detected in phloem from above the spray line on any trees. Dinotefuran was not detected in phloem sampled from any branches in either July or September. Results suggest dinotefuran basal trunk sprays applied between late May and mid June should persist long enough to effectively control SLF late instars and adults.
Rapid and facile preparation of nanocomposite film heaters for composite manufacturing
Authors: Naseri Iman , Ashrafi Behnam , Jakubinek Michael , Martinez-Rubi Yadienka , Yourdkhani Mostafa 
Published: March 2023

Nanocomposite film heaters are promising for out-of-oven (OoO) and energy-efficient curing of fiber-reinforced polymer composites. However, the current techniques for manufacturing nanocomposite film heaters are intensive in terms of time and energy and require expensive resources. In this work, we present a facile and rapid approach for preparation of nanocomposite film heaters with excellent heat generation properties based on a frontally polymerizable resin system. This approach enables rapid fabrication of nanocomposite films within a few minutes and without the need for using expensive equipment, making it suitable for mass production of nanocomposite film heaters. Various characterization techniques are used to determine the morphology, composition, and mechanical properties of nanocomposite films. The electrothermal performance of nanocomposite film heaters are then evaluated under various conditions. Nanostructured heaters exhibit excellent Joule heating properties, where temperatures as high as ∼132°C can be reached within only 2 min using a low input power density of ∼2 W cm−2. Finally, a nanocomposite film heater is used for OoO curing of a small composite panel with minimal energy consumption. Using this approach, 0.1 MJ of energy is consumed during the 4-h cure cycle of a commercial prepreg system, which would otherwise require at least 40.5 MJ of energy to cure using a convection oven.
The integrated stress response is activated in the salivary glands of Sjögren’s syndrome patients
Authors: Carvajal Patricia , Bahamondes Verónica , Jara Daniela , Castro Isabel , Matus Soledad , Aguilera Sergio , Molina Claudio , González Sergio , Hermoso Marcela , Barrera María-José , González María-Julieta 
Published: March 2023

IntroductionPrimary Sjögren’s syndrome (SS) is an autoimmune exocrinopathy that affects the structure and function of salivary and lachrymal glands. Labial salivary gland (LSG) acinar cells from SS patients lose cellular homeostasis and experience endoplasmic reticulum and oxidative stress. The integrated cellular stress response (ISR) is an adaptive pathway essential for restoring homeostasis against various stress-inducing factors, including pro-inflammatory cytokines, and endoplasmic reticulum and oxidative stress. ISR activation leads eIF2α phosphorylation, which transiently blocks protein synthesis while allowing the ATF4 expression, which induces a gene expression program that seeks to optimize cellular recovery. PKR, HRI, GCN2, and PERK are the four sentinel stress kinases that control eIF2α phosphorylation. Dysregulation and chronic activation of ISR signaling have pathologic consequences associated with inflammation.MethodsHere, we analyzed the activation of the ISR in LSGs of SS-patients and non-SS sicca controls, determining the mRNA, protein, and phosphorylated-protein levels of key ISR components, as well as the expression of some of ATF4 targets. Moreover, we performed a qualitative characterization of the distribution of ISR components in LSGs from both groups and evaluated if their levels correlate with clinical parameters.ResultsWe observed that the four ISR sensors are expressed in LSGs of both groups. However, only PKR and PERK showed increased expression and/or activation in LSGs from SS-patients. eIF2α and p-eIF2α protein levels significantly increased in SS-patients; meanwhile components of the PP1c complex responsible for eIF2α dephosphorylation decreased. ATF4 mRNA levels were decreased in LSGs from SS-patients along with hypermethylation of the ATF4 promoter. Despite low mRNA levels, SS-patients showed increased levels of ATF4 protein and ATF4-target genes involved in the antioxidant response. The acinar cells of SS-patients showed increased staining intensity for PKR, p-PKR, p-PERK, p-eIF2α, ATF4, xCT, CHOP, and NRF2. Autoantibodies, focus score, and ESSDAI were correlated with p-PERK/PERK ratio and ATF4 protein levels.DiscussionIn summary, the results showed an increased ISR activation in LSGs of SS-patients. The increased protein levels of ATF4 and ATF4-target genes involved in the redox homeostasis could be part of a rescue response against the various stressful conditions to which the LSGs of SS-patients are subjected and promote cell survival.
Drug repositioning prediction for psoriasis using the adverse event reporting database
Authors: Ko Minoh , Oh Jung Mi , Kim In-Wha 
Published: March 2023

IntroductionInverse signals produced from disproportional analyses using spontaneous drug adverse event reports can be used for drug repositioning purposes. The purpose of this study is to predict drug candidates using a computational method that integrates reported drug adverse event data, disease-specific gene expression profiles, and drug-induced gene expression profiles.MethodsDrug and adverse events from 2015 through 2020 were downloaded from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), information component (IC) and empirical Bayes geometric mean (EBGM) were used to calculate the inverse signals. Psoriasis was selected as the target disease. Disease specific gene expression profiles were obtained by the meta-analysis of the Gene Expression Omnibus (GEO). The reverse gene expression scores were calculated using the Library of Integrated Network-based Cellular Signatures (LINCS) and their correlations with the inverse signals were obtained.ResultsReversal genes and the candidate compounds were identified. Additionally, these correlations were validated using the relationship between the reverse gene expression scores and the half-maximal inhibitory concentration (IC50) values from the Chemical European Molecular Biology Laboratory (ChEMBL).ConclusionInverse signals produced from a disproportional analysis can be used for drug repositioning and to predict drug candidates against psoriasis.
Impact of oestrus synchronization devices on ewes vaginal microbiota and artificial insemination outcome
Authors: Reinoso-Peláez Edgar L. , Saura María , González-Recio Óscar , González Carmen , Fernández Almudena , Peiro-Pastor Ramón , López-García Adrián , Saborío-Montero Alejandro , Calvo Jorge H. , Ramón Manuel , Serrano Malena 
Published: March 2023

IntroductionThe low pregnancy rate by artificial insemination in sheep represents a fundamental challenge for breeding programs. In this species, oestrus synchronization is carried out by manipulating hormonal regimens through the insertion of progestogen intravaginal devices. This reproductive strategy may alter the vaginal microbiota affecting the artificial insemination outcome.MethodsIn this study, we analyzed the vaginal microbiome of 94 vaginal swabs collected from 47 ewes with alternative treatments applied to the progesterone-releasing intravaginal devices (probiotic, maltodextrin, antibiotic and control), in two sample periods (before placing and after removing the devices). To our knowledge, this is the first study using nanopore-based metagenome sequencing for vaginal microbiome characterization in livestock.ResultsOur results revealed a significant lower abundance of the genera Oenococcus (Firmicutes) and Neisseria (Proteobacteria) in pregnant compared to non-pregnant ewes. We also detected a significant lower abundance of Campylobacter in the group of samples treated with the probiotic.DiscussionAlthough the use of probiotics represents a promising practice to improve insemination results, the election of the suitable species and concentration requires further investigation. In addition, the use of progestogen in the synchronization devices seemed to increase the alpha-diversity and decrease the abundance of harmful microorganisms belonging to Gammaproteobacteria and Fusobacteriia classes, suggesting a beneficial effect of their use.
Studying pulmonary fibrosis due to microbial infection via automated microscopic image analysis
Authors: Chen Yajie , He Henghui , Luo Licheng , Liu Kangyi , Jiang Min , Li Shiqi , Zhang Xianqi , Yang Xin , Liu Qian 
Published: March 2023

IntroductionPulmonary fibrosis is a consequential complication of microbial infections, which has notably been observed in SARS-CoV-2 infections in recent times. Macrophage polarization, specifically the M2-type, is a significant mechanism that induces pulmonary fibrosis, and its role in the development of Post- COVID-19 Pulmonary Fibrosis is worth investigating. While pathological examination is the gold standard for studying pulmonary fibrosis, manual review is subject to limitations. In light of this, we have constructed a novel method that utilizes artificial intelligence techniques to analyze fibro-pathological images. This method involves image registration, cropping, fibrosis degree classification, cell counting and calibration, and it has been utilized to analyze microscopic images of COVID-19 lung tissue.MethodsOur approach combines the Transformer network with ResNet for fibrosis degree classification, leading to a significant improvement over the use of ResNet or Transformer individually. Furthermore, we employ semi-supervised learning which utilize both labeled and unlabeled data to enhance the ability of the classification network in analyzing complex samples. To facilitate cell counting, we applied the Trimap method to localize target cells. To further improve the accuracy of the counting results, we utilized an effective area calibration method that better reflects the positive density of target cells.ResultsThe image analysis method developed in this paper allows for standardization, precision, and staging of pulmonary fibrosis. Analysis of microscopic images of COVID-19 lung tissue revealed a significant number of macrophage aggregates, among which the number of M2-type macrophages was proportional to the degree of fibrosis.DiscussionThe image analysis method provids a more standardized approach and more accurate data for correlation studies on the degree of pulmonary fibrosis. This advancement can assist in the treatment and prevention of pulmonary fibrosis. And M2-type macrophage polarization is a critical mechanism that affects pulmonary fibrosis, and its specific molecular mechanism warrants further exploration.