bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective CD28 blockade impacts T cell differentiation during homeostatic reconstitution following lymphodepletion
Authors: Habib Jakob G. , Liu Danya , Crepeau Rebecca M. , Wagener Maylene E. , Ford Mandy L. 
Published: January 2023

IntroductionCostimulation blockade targeting the CD28 pathway provides improved long-term renal allograft survival compared to calcineurin inhibitors but may be limited as CTLA-4-Ig (abatacept, belatacept) blocks both CD28 costimulation and CTLA-4 coinhibition. Directly targeting CD28 while leaving CTLA-4 intact may provide a mechanistic advantage. Fc-silent non-crosslinking CD28 antagonizing domain antibodies (dAb) are currently in clinical trials for renal transplantation. Given the current standard of care in renal transplantation at most US centers, it is likely that lymphodepletion via thymoglobulin induction therapy could be used in patients treated with CD28 antagonists. Thus, we investigated the impact of T cell depletion (TCD) on T cell phenotype following homeostatic reconstitution in a murine model of skin transplantation treated with anti-CD28dAb.MethodsSkin from BALB/cJ donors was grafted onto C56BL/6 recipients which were treated with or without 0.2mg anti-CD4 and 10μg anti-CD8 one day prior to transplant and with or without 100μg anti-CD28dAb on days 0, 2, 4, 6, and weekly thereafter. Mice were euthanized six weeks post-transplant and lymphoid cells were analyzed by flow cytometry.ResultsAnti-CD28dAb reversed lymphopenia-induced differentiation of memory CD4+ T cells in the spleen and lymph node compared to TCD alone. Mice treated with TCD+anti-CD28dAb exhibited significantly improved skin graft survival compared to anti-CD28dAb alone, which was also improved compared to no treatment. In addition, the expression of CD69 was reduced on CD4+ and CD8+ T cells in the spleen and lymph node from mice that received TCD+anti-CD28dAb compared to TCD alone. While a reduced frequency of CD4+FoxP3+ T cells was observed in anti-CD28dAb treated mice relative to untreated controls, this was balanced by an increased frequency of CD8+Foxp3+ T cells that was observed in the blood and kidney of mice given TCD+anti-CD28dAb compared to TCD alone.DiscussionThese data demonstrate that CD28 signaling impacts the differentiation of both CD4+ and CD8+ T cells during homeostatic reconstitution following lymphodepletion, resulting in a shift towards fewer activated memory T cells and more CD8+FoxP3+ T cells, a profile that may underpin the observed prolongation in allograft survival.
The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass
Authors: Pan Tuo , Tuoerxun Tayierjiang , Chen Xi , Yang Cheng-Jin , Jiang Chen-Yu , Zhu Yi-Fan , Li Ze-Shi , Jiang Xin-Yi , Zhang Hai-Tao , Zhang He , Wang Ya-Peng , Chen Wei , Lu Li-Chong , Ge Min , Cheng Yong-Qing , Wang Dong-Jin , Zhou Qing 
Published: January 2023

BackgroundThe sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery.MethodsFirstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc.ResultsIn propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P&lt;0.01), bilateral pulmonary infiltrates (P&lt;0.01), oxygen index (P&lt;0.01), interleukin-6(P=0.02), procalcitonin(P&lt;0.01) and C-reactive protein(P&lt;0.01).ConclusionAdministration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB.Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.
T cell immunity ameliorates COVID-19 disease severity and provides post-exposure prophylaxis after peptide-vaccination, in Syrian hamsters
Authors: Somogyi Eszter , Kremlitzka Mariann , Csiszovszki Zsolt , Molnár Levente , Lőrincz Orsolya , Tóth József , de Waal Leon , Pattijn Sofie , Reineking Wencke , Beineke Andreas , Tőke Enikő R. 
Published: January 2023

BackgroundThe emergence of novel SARS-CoV-2 variants that resist neutralizing antibodies drew the attention to cellular immunity and calls for the development of alternative vaccination strategies to combat the pandemic. Here, we have assessed the kinetics of T cell responses and protective efficacy against severe COVID-19 in pre- and post-exposure settings, elicited by PolyPEPI-SCoV-2, a peptide based T cell vaccine.Methods75 Syrian hamsters were immunized subcutaneously with PolyPEPI-SCoV-2 on D0 and D14. On D42, hamsters were intranasally challenged with 102 TCID50 of the virus. To analyze immunogenicity by IFN-γ ELISPOT and antibody secretion, lymphoid tissues were collected both before (D0, D14, D28, D42) and after challenge (D44, D46, D49). To measure vaccine efficacy, lung tissue, throat swabs and nasal turbinate samples were assessed for viral load and histopathological changes. Further, body weight was monitored on D0, D28, D42 and every day after challenge.ResultsThe vaccine induced robust activation of T cells against all SARS-CoV-2 structural proteins that were rapidly boosted after virus challenge compared to control animals (~4-fold, p&lt;0.05). A single dose of PolyPEPI-SCoV-2 administered one day after challenge also resulted in elevated T cell response (p&lt;0.01). The vaccination did not induce virus-specific antibodies and viral load reduction. Still, peptide vaccination significantly reduced body weight loss (p&lt;0.001), relative lung weight (p&lt;0.05) and lung lesions (p&lt;0.05), in both settings.ConclusionOur study provides first proof of concept data on the contribution of T cell immunity on disease course and provide rationale for the use of T cell-based peptide vaccines against both novel SARS-CoV-2 variants and supports post-exposure prophylaxis as alternative vaccination strategy against COVID-19.
Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy
Authors: Guo Yangyang , Cen Kenan , Chen Qiaoqiao , Dai Ying , Mai Yifeng , Hong Kai 
Published: January 2023

IntroductionCellular senescence is a hallmark of tumors and has potential for cancer therapy. Cellular senescence of tumor cells plays a role in tumor progression, and patient prognosis is related to the tumor microenvironment (TME). This study aimed to explore the predictive value of senescence-related genes in thyroid cancer (THCA) and their relationship with the TME.MethodsSenescence-related genes were identified from the Molecular Signatures Database and used to conduct consensus clustering across TCGA-THCA. Differentially expressed genes (DEGs) were identified between the clusters used to perform multivariate Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a senescence-related signature. TCGA dataset was randomly divided into training and test datasets to verify the prognostic ability of the signature. Subsequently, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. Finally, the expression of signature genes was detected across TCGA-THCA and GSE33630 datasets, and further validated by RT-qPCR.ResultsThree senescence clusters were identified based on the expression of 432 senescence-related genes. Then, 23 prognostic DEGs were identified in TCGA dataset. The signature, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-risk THCA shows a better prognosis and higher immunotherapy response than high-risk THCA. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. The validation part demonstrated that ADAMTSL4, DOCK6, FAM111B, and SEMA6B were expressed at higher levels in the tumor tissue, whereas lower expression of MRPS10 and PSMB7 was observed.DiscussionIn conclusion, the senescence-related signature is a promising biomarker for predicting the outcome of THCA and has the potential to guide immunotherapy.
Effect of ultrasonic vibration on residual stress in plasma cladding of iron-based alloy
Authors: Lai Youbin , Yue Wenwen , Zhang Yichuan 
Published: January 2023

To explore the effect of ultrasonic vibration power and frequency on the residual stress of single-channel iron-based alloy plasma cladding, the single-factor ultrasonic vibration plasma cladding test was designed, and ten groups of single-channel iron-based alloy cladding samples under different process parameters were studied. The drilling method was used to measure the residual stress of the substrate at the beginning, middle and tail positions of each sample cladding layer. The residual stress of the substrate was analyzed and the significant characteristics of the effect of ultrasonic vibration power and frequency on the residual stress at different positions were explored using variance analysis. The results show that the residual stress is significantly reduced after applying ultrasonic waves. When the ultrasonic frequency is constant and the ultrasonic power is 240 W, the residual stress of the formed sample is the smallest. Compared with the unapplied ultrasonic assistance, the residual stress in the X direction is reduced by 62.56%, and the residual stress in the Y direction is reduced by 63.23%. When the ultrasonic power is constant and the ultrasonic frequency is 28 kHz, the residual stress of the formed sample is the smallest. Compared with the unapplied ultrasonic assistance, the residual stress in the X direction is reduced by 17.23%, and the residual stress in the Y direction is reduced by 19.79%. The ultrasonic power significantly affects the middle part of the substrate, and the ultrasonic frequency significantly affects each point of the substrate.
Uveal melanoma incidence trends in Canada: 1992–2010 vs. 2011–2017
Authors: Conte Santina , Lagacé François , Ghazawi Feras M. , Cattelan Leila , Nath Siddharth , Dhillon Jobanpreet , Nedjar Hacene , Rahme Elham , Sasseville Denis , Burnier Miguel N. , Litvinov Ivan V. 
Published: January 2023

Background/aimsUveal melanoma is the most common type of non-cutaneous melanoma and the most common ocular malignancy in the adult population, especially affecting Caucasians (98% of cases). Despite its low incidence rate, we have noted increasing incidence trends in recent years.MethodsWe analyzed uveal melanoma incidence data using the Canadian Cancer Registry (CCR) for 2011–2017 years. The data was examined using the International Classification of Diseases for Oncology, Third Edition, codes for all uveal melanoma subtypes. The data for 2011–2017 was then compared to previously published work by our research group for uveal melanoma incidence in Canada between 1992 and 2010 using the same methodology.ResultsBetween 2011 and 2017, 1,215 patients were diagnosed with uveal melanoma, 49% of whom were females. The percentage distribution of uveal melanoma between the sexes was similar between 1992–2010 and 2011–2017, whereby of the 2,215 diagnoses of uveal melanoma in 1992–2010, 47.9% were females. The change in the incidence rate for this cancer has doubled between 1992–2010 and 2011–2017, from 0.074 to 0.15 cases per million individuals per year. Our study documents that the Canadian 2011–2017 age-standardized incidence rate (ASIR) for uveal melanoma against the World Health Organization (WHO) 2000–2025 world population standard was 5.09 cases per million individuals per year (95% confidence interval, 4.73–5.44), as compared with the 1992–2010 rate of 3.34 cases per million individuals per year (95% confidence interval, CI 3.20 to 3.47).ConclusionThis work demonstrates an ongoing, steady increase in uveal melanoma incidence in Canada in recent years.
Effects of maternal characteristics and medical history on first trimester biomarkers for preeclampsia
Authors: Torres-Torres Johnatan , Espino-y-Sosa Salvador , Villafan-Bernal Jose Rafael , Orozco-Guzman Luis Enrique , Solis-Paredes Juan Mario , Estrada-Gutierrez Guadalupe , Martinez-Cisneros Romeo Adalid , Mateu-Rogell Paloma , Acevedo-Gallegos Sandra , Martinez-Portilla Raigam Jafet 
Published: January 2023

ObjectiveTo identify and quantify the effects of maternal characteristics and medical history on the distribution of Placental Growth Factor (PlGF), mean arterial pressure (MAP), and Uterine Artery Mean Pulsatility Index (UtA-PI); and to standardize the expected values for these biomarkers in the first trimester to create unique multiples of the median (MoMs) for Latin-American population.MethodsThis is a prospective cohort built exclusively for research purposes of consecutive pregnant women attending their first-trimester screening ultrasound at a primary care center for the general population in Mexico City between April 2019 and October 2021. We excluded fetuses with chromosomal abnormalities, major fetal malformations, and women delivering in another care center. Linear regression was used on log-transformed biomarkers to assess the influence of maternal characteristics on non-preeclamptic women to create MoM.ResultsOf a total of 2,820 pregnant women included in the final analysis, 118 (4.18%) developed PE, of which 22 (0.78%) delivered before 34 weeks of gestation, 74 (2.62%) before 37 weeks, and 44 (1.56%) from 37 weeks gestation. Characteristics that significantly influenced PLGF were fetal crown rump length (CRL), maternal age, nulliparity, body mass index (BMI), chronic hypertension, Lupus, spontaneous pregnancy, polycystic ovary syndrome (PCOS), hypothyroidism, preeclampsia (PE) in a previous pregnancy, and mother with PE. MAP had significant influence from CRL, maternal age, PE in a previous pregnancy, induction of ovulation, a mother with PE, chronic hypertension, BMI, and hypothyroidism. UtA-PI was influenced by CRL, maternal age, a mother with PE, chronic hypertension, and gestational diabetes mellitus (GDM) in a previous pregnancy.ConclusionPopulation-specific multiples of the median (MoMs) for PlGF, MAP, and UtA-PI in the first trimester adequately discriminate among women developing preeclampsia later in pregnancy.
Optic nerve sheath fenestration for visual impairment in cerebral venous diseases
Authors: Xue Xiao , Zhou Chen , Gao Yuan , Ji Xunming , Zhang Xuxiang 
Published: January 2023

ObjectiveVisual impairment is the most common clinical feature of cerebral venous sinus occlusion or cerebral venous thrombosis-induced intracranial hypertension, which can result in optic atrophy, leading to irreversible vision loss, visual field defections, and finally, permanent blindness. Papilledema is a typical early pathophysiological alteration in visual impairment. Optic nerve sheath fenestration (ONSF) has become increasingly accepted as an option to prevent or halt progressive visual loss owing to its low risk and complications. The objective of this study is to review the latest research progress on ONSF for the treatment of visual impairment related to cerebral venous diseases.MethodsStudy were searched following PRISMA guidelines based on three electronic databases (Pubmed, Embase and Medline-Ovid). We used the following keywords and variations as keywords to identify studies: “optic nerve sheath fenestration, papilledema, cerebral venous diseases, cerebral venous stenosis, cerebral venous thrombosis, idiopathic intracranial hypertension”. The publication date of studies was restricted between 1,872.1.1 and 2,021.12.31. The application of ONSF in papilledema due to cerebral venous diseases is reviewed. Additionally, the common surgical approaches as well as advantages and disadvantages are also described graphically.ResultsWith the improvement of specific details of the ONSF procedure and surgical instruments, complications of ONSF have reduced and its safety has been significantly improved, although the number of clinically investigated cases in the literature remains low.ConclusionWe recommend that ONSF should be considered as an imperative alternative to reduce or delay the visual morbidity of cerebral venous diseases, although there is yet no consensus on the optimal surgical timing.
Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer’s disease
Authors: Frederiksen Kristian Steen , Jensen Camilla Steen , Høgh Peter , Gergelyffy Robert , Waldemar Gunhild , Andersen Birgitte Bo , Gottrup Hanne , Vestergaard Karsten , Wermuth Lene , Søndergaard Helle Bach , Sellebjerg Finn , Hasselbalch Steen Gregers , Simonsen Anja Hviid 
Published: January 2023

IntroductionAerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration.ObjectiveTo investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD).MethodsThis is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer’s disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention.ResultsA total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline −1.16, p = 0.09].ConclusionThe findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration.Clinical trial registrationclinicaltrials.gov, identifier NCT01681602.
Association between the uric acid to high density lipoprotein cholesterol ratio and alanine transaminase in Chinese short stature children and adolescents: A cross-sectional study
Authors: Li Guangxin , Zhao Qianqian , Zhang Xinran , Ban Bo , Zhang Mei 
Published: January 2023

ObjectiveUric acid to high-density lipoprotein cholesterol ratio (UHR), the ratio of uric acid to high-density lipoprotein cholesterol, is a newly proposed marker of metabolic abnormalities. There are few previous studies directly investigating the relationship between UHR and alanine aminotransferase (ALT), especially in short stature populations, however, short stature children and adolescents are more likely to have metabolic disorders. This research aimed to investigate the relationship between the UHR and ALT in children and adolescents with short stature.MethodsIn this cross-sectional analysis, the clinical data of 1,510 children with height below −2 SD who were evaluated at the Department of Endocrinology, Affiliated Hospital of Jining Medical University from 1 March 2013 to 31 December 2021, were selected. Anthropometric and biochemical indicators were measured. The relationship between UHR and ALT was analysed.ResultsThe univariate analysis results showed that UHR was positively associated with ALT (β = 0.43, P &lt; 0.0001). Furthermore, after adjusting for possible confounding factors, a non-linear relationship was detected between UHR and ALT through smooth curve fitting, and the inflection point of UHR was 10.93% after multivariate piecewise linear regression analysis. ALT increased with UHR elevation when the UHR was greater than 10.93% (β = 0.69, 95% CI 0.39, 0.98; P &lt; 0.0001). However, we did not observe a significant relationship when the UHR was less than 10.93% (P = 0.9229).ConclusionOur study demonstrated that in Chinese children and adolescents with short stature, UHR may be associated with the regulation of ALT levels, and this relationship merits further investigation.
Associations between dietary intake, physical activity, and obesity among public school teachers in Jeddah, Saudi Arabia
Authors: Almoraie Noha M. , Shatwan Israa M. , Althaiban Maha A. , Hanbazaza Mahitab A. , Wazzan Huda A. , Aljefree Najlaa M. 
Published: January 2023

ObjectiveWe aimed to assess the dietary intake of certain food groups in a representative sample of public-school teachers living in Jeddah city. We also, examined the association of dietary intake with physical activity and obesity among schoolteachers.MethodsThe study was a cross-sectional online survey, conducted among 640 (177 male, 463 female) schoolteachers aged between 20 and 62 years old and working in public primary, intermediate, and high schools in Jeddah. Measurements included gender, weight, height, body mass index (BMI), health problems, and lifestyle behaviours, including physical activity levels, smoking status, and dietary intake.ResultsBased on gender, number of non-smoking women (94%) was higher than number of non-smoking men (57.1%) (P &lt; 0.001). However, men were more active than women (P = 0.03). Regarding BMI, there were more overweight men than women, while obese women numbered more than men (P = 0.003). There was no significant difference in dietary intake between men and women except that men consumed more soft drinks than women (P = 0.002). Lower physically active schoolteachers were less likely to consume salad (OR = 0.6, 95% CI 0.4–0.9; P = 0.02), vegetables (OR = 0.6, 95% CI 0.3–0.9; P = 0.01), beans and legumes (OR = 0.4, 95% CI 0.2–0.7; P = 0.005), wholegrain bread (OR = 0.6, 95% CI 0.4–0.9; P = 0.03), dairy products (OR = 0.6, 95% CI 0.4–0.9; P = 0.01), snacks (OR = 0.5, 95% CI 0.2–0.8; P = 0.01), and fish (OR = 0.4, 95% CI 0.2–0.9; P = 0.04) compared to those with high levels of physical activity. Only fruit intake was considered statistically significant (OR = 0.4, 95% CI 0.3–0.7; P = 0.003). The study found a relationship between the BMI of schoolteachers and food intake. Obese schoolteachers had lower consumption of fruits (OR = 0.3, 95% CI 0.2–0.7; P = 0.007) and white meat (OR = 0.5, 95%CI 0.3–0.9; P = 0.03) than schoolteachers in the normal weight group.ConclusionThe high prevalence of physical activity, dietary intake and body weight among Saudi teachers is a major public health concern. The present study identified several lifestyle factors associated with body weight that may represent valid targets for the prevention and management of obesity among Saudi school teachers. Promoting active lifestyles and healthy diets would be primary targets for obesity prevention.