bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and severity of immune-related hepatitis after dual checkpoint therapy is linked to younger age independent of herpes virus immunity
Authors: Zhang Zhen , Rafei-Shamsabadi David , Lehr Saskia , Buettner Nico , Diehl Rebecca , Huzly Daniela , Pinato David J , Thimme Robert , Meiss Frank , Bengsch Bertram 
Published: December 2022

Abstract
Background and Aims
Dual immune checkpoint blockade (ICB) therapy can result in immune-related-adverse events (irAE) such as ICB-hepatitis. An expansion of effector-memory (TEM) CD4 T cells associated with antiviral immunity against herpesviridae was implicated in ICB-hepatitis. Notably, these memory subsets are frequently associated with age. Here, we sought to understand baseline patient, immune and viral biomarkers associated with the development of ICB-hepatitis to identify currently lacking baseline predictors and test if an expansion of TEM or positive serology against herpesviridae can predict ICB-hepatitis.

Methods
A discovery (n = 39) and validation cohort (n = 67) of patients with advanced melanoma undergoing anti-PD-1&anti-CTLA4 combination therapy (total n = 106) were analyzed for baseline clinical characteristics, occurrence of irAE and oncological outcomes alongside serological status for CMV, EBV and HSV. Immune populations were profiled by high-parametric flow cytometry (n = 29).

Results
ICB-hepatitis occurred in 59% of patients within 100 days; 35.9% developed severe (CTCAE 3–4) hepatitis. Incidence of ICB-hepatitis was higher in the younger (< 55y: 85.7%) compared to older (> = 55y: 27.8%) age group (p = 0.0003), occured earlier in younger patients (p < 0.0001). The association of younger age with ICB-Hepatitis was also observed in the validation cohort (p = 0.0486). Incidence of ICB-hepatitis was also associated with additional non-hepatic irAE (p = 0.018), but neither positive IgG serostatus for CMV, EBV or HSV nor TEM subsets despite an association of T cell subsets with age.

Conclusion
Younger age more accurately predicts ICB-hepatitis after anti-PD-1&anti-CTLA4 checkpoint therapy at baseline compared to herpes virus serology or TEM subsets. Younger patients should be carefully monitored for the development of ICB-hepatitis.
Disruption of C/EBPβ-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain
Authors: Wu Dan , Zhang Yanqiong , Zhao Chunhui , Li Qiuyue , Zhang Junhong , Han Jiaxin , Xu Zhijian , Li Junfang , Ma Yan , Wang Ping , Xu Haiyu 
Published: December 2022

Abstract
Background
Growing evidence shows that C-Type Lectin Domain Containing 7A (Clec7a) may be involved into neuroinflammatory injury of various neurological diseases. However, its roles in neuropathic pain remain unclear.

Methods
A chronic constriction injury (CCI) rat model was constructed, and gene expression profilings in spinal cord tissues of CCI-insulted rats were detected by both microarray and RNA-seq studies. A series of bioinformatics analyses identified C/EBPβ-Clec7a to be a candidate axis involved into neuropathic pain. Then, its roles in mechanical allodynia, and pathological and molecular changes during CCI progression were determined by various gain-of-function and loss-of-function experiments in vivo and in vitro.

Results
Significant upregulation of Clec7a at both mRNA and protein levels were verified in spinal cord tissues of CCI-insulted rats. Clec7a knockdown markedly attenuated CCI-induced mechanical allodynia, obstructed Syk, ERK and JNK phosphorylation, inhibited NLRP3 inflammasome and caspase-1 activation, GSDMD cleavage, and consequently reduced the release of pro-inflammatory cytokines (all P < 0.05). Mechanically, the rat Clec7a promoter was predicted to bind with transcription factor C/EBPβ, confirmed by Luciferase assay and ChIP-qPCR. Both in vivo and in vitro assays demonstrated that C/EBPβ knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, and subsequently reduced Syk, ERK and JNK phosphorylation, NLRP3 oligomerization, caspase-1 activation, GSDMD expression and pyroptosis, which were markedly reversed by the co-transfection of Clec7a expression vector.

Conclusions
This pre-clinical investigation reveals that C/EBPβ-Clec7a axis may be a potential target for relieving neuropathic pain through alleviating neuroinflammation, paving its way for clinical translation as a promising approach for neuropathic pain therapy.
The role of the oral microbiome in smoking-related cardiovascular risk: a review of the literature exploring mechanisms and pathways
Authors: Maki Katherine A. , Ganesan Sukirth M. , Meeks Brianna , Farmer Nicole , Kazmi Narjis , Barb Jennifer J. , Joseph Paule V. , Wallen Gwenyth R. 
Published: December 2022

AbstractCardiovascular disease is a leading cause of morbidity and mortality. Oral health is associated with smoking and cardiovascular outcomes, but there are gaps in knowledge of many mechanisms connecting smoking to cardiovascular risk. Therefore, the aim of this review is to synthesize literature on smoking and the oral microbiome, and smoking and cardiovascular risk/disease, respectively. A secondary aim is to identify common associations between the oral microbiome and cardiovascular risk/disease to smoking, respectively, to identify potential shared oral microbiome-associated mechanisms. We identified several oral bacteria across varying studies that were associated with smoking. Atopobium, Gemella, Megasphaera, Mycoplasma, Porphyromonas, Prevotella, Rothia, Treponema, and Veillonella were increased, while Bergeyella, Haemophilus, Lautropia, and Neisseria were decreased in the oral microbiome of smokers versus non-smokers. Several bacteria that were increased in the oral microbiome of smokers were also positively associated with cardiovascular outcomes including Porphyromonas, Prevotella, Treponema, and Veillonella. We review possible mechanisms that may link the oral microbiome to smoking and cardiovascular risk including inflammation, modulation of amino acids and lipids, and nitric oxide modulation. Our hope is this review will inform future research targeting the microbiome and smoking-related cardiovascular disease so possible microbial targets for cardiovascular risk reduction can be identified.
Calcitriol increases MBNL1 expression and alleviates myotonic dystrophy phenotypes in HSALR mouse models
Authors: Huang Kun , Wang Dan-Dan , Hu Wen-Bao , Zeng Wei-Qian , Xu Xia , Li Qiu-Xiang , Bi Fang-Fang , Yang Huan , Qiu Jian 
Published: December 2022

Abstract
Background
Myotonic dystrophy type 1 (DM1), one of the most common forms of adult-onset muscular dystrophy, is caused by abnormally expanded CTG repeats in the 3′ untranslated region of the DMPK gene. The CUG repeats transcribed from the expanded CTG repeats sequestrate a splicing factor, MBNL1, causing the clinical symptoms in DM1. Nowadays, only symptomatic treatments are available for DM1, and no rational therapy is available. Recently, upregulation of MBNL1 expression has been found to be one of the promising therapies for DM1.

Methods
All experiments were conducted in the C2C12 myoblasts and HSALR mice, a DM1 mouse model. Real-time PCR and western blot were used to detect the mRNA and protein level, respectively. The rotarod exercise, grip strength and hanging time were used to evaluate the muscle strength of mice.

Results
In this study, we demonstrated that calcitriol, an active form of vitamin D3, increased MBNL1 in C2C12 mouse myoblasts as well as in HSALR mice model for DM1. In HSALR mice model, calcitriol improved muscle strength, and corrected aberrant splicing in skeletal muscle. Besides, calcitriol reduced the number of central nuclei, and improved muscle histopathology in HSALR mice. In addition, we identified that calcitriol upregulated MBNL1 expression via activating the promoter of Mbnl1 in C2C12 myogenic cells.

Conclusion
Our study suggests that calcitriol is a potential pharmacological strategy for DM1 that enhances MBNL1 expression.
Targeting macrophages: a novel treatment strategy in solid tumors
Authors: Liu Mengmeng , Liu Lina , Song Yongping , Li Wei , Xu Linping 
Published: December 2022

AbstractIn the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.
Exposure to violence is associated with decreased neural connectivity in emotion regulation and cognitive control, but not working memory, networks after accounting for socioeconomic status: a preliminary study
Authors: Mattheiss Samantha R. , Levinson Hillary , Rosenberg-Lee Miriam , Graves William W. 
Published: December 2022

AbstractPrevious research has demonstrated behavioral and neural differences associated with experiencing adversity. However, adversity is unlikely to be a monolithic construct, and we expect that examining effects of more specific components such as exposure to violence in the home community will yield more concretely interpretable results. Here we account for effects of low socioeconomic status (SES) to examine the specific effects of exposure to violence on functional connectivity between brain areas known to be related to emotion regulation and working memory. Decreased resting state functional connectivity for individuals exposed to high compared to low levels of violence during childhood was predicted for two sets of areas: (1) bilateral amygdala with anterior medial regions involved in cognitive control of emotion, and (2) the right dorsolateral prefrontal cortex (dlPFC) with frontal and parietal regions implicated in working memory. Consistent with our predictions, increasing exposure to violence was related to decreased resting state functional connectivity between the right amygdala and anterior cingulate cortex, even after accounting for SES. Also after accounting for SES, exposure to violence was related to reductions in connectivity between the right dlPFC and frontal regions, but not with parietal regions typically associated with working memory. Overall, this pattern suggests increased exposure to violence in childhood is associated with reduced connectivity among key areas of the circuitry involved in emotion regulation and cognitive control, but not working memory. These results offer insight into the neural underpinnings of behavioral outcomes associated with exposure to violence, laying the foundation for ultimately designing interventions to address the effects of such exposure.
Occupational safety practice among metal workers in Bangladesh: a community-level study
Authors: Islam Farhin , Alam MR , Mamun SM Abdullah AL , Hossain Mohammad Sorowar 
Published: December 2022

Abstract
Background
The overall information on occupational health and safety (OHS)-related knowledge and workplace practices are scarce in Bangladesh. This study aimed to (i) examine the prevalence of occupational injuries, (ii) explore the level of OHS-related knowledge and practice among workers and associated factors, and (iii) investigate the socioeconomic factors and OHS-related knowledge and practice scores as determinants of injury among metal workers at a community setting in Bangladesh.

Methods
This was a cross-sectional study conducted on all the functional metal workshops in a community of a town. The sociodemographic characteristics, history of injury and its consequences, and the state of knowledge and practice were measured using descriptive statistics. Univariate and multivariate analyses were used to measure the association between practice scores and sociodemographic factors and knowledge. Logistic regression was conducted to get the odds ratio of getting injured.

Results
A high annual rate (82.9%) of occupational injuries was documented in a one-year timeframe and the majority (81.1%) of injured workers lost more than three working days (median 20 days). Workers working in workshops with more than three workers were 3.3 times more likely to be injured [AOR = 3.33, 95% CI = 1.16, 9.58] compared to the workers in factories with one to three workers. Most of the workers had the basic knowledge related to OHS but the mean practice score was very low, 1.86 (SD 1.17). Higher education, lower monthly family income, and being an owner significantly led to higher practice scores.

Conclusions
The OHS-related knowledge was not properly translated into good workplace practices in small informal metal workshops because of the absence of implementation of OHS policies and monitoring by the relevant authority. Government should support the informal metal working sector to increase awareness and skills for the prevention and proper management of injuries and risks, and to ensure access to safety equipment and a safe environment.
A simple and robust method for isolating and analyzing chromatin-bound RNAs in Arabidopsis
Authors: Zhang Qiqi , Zhao Fengli , Wu Zhe , Zhu Danling 
Published: December 2022

Abstract
Background
Chromatin-bound RNAs are the primary product of transcription that undergo on-chromatin processing such as capping, splicing, and polyadenylation. These processing steps then determine the fate of RNAs. Albeit its vital importance, a simple and robust method for isolating different fractions of chromatin-bound RNAs is missing in plants.

Result
Here, we describe our updated method and the associated step-by-step protocol for chromatin-bound RNAs isolation in A. thaliana. The chromatin-bound RNAs isolation is based on the 1 M UREA wash that removes the majority of non-chromatin-associated proteins from the nucleus, as previously developed in mammalian cells. On-demand, the isolated chromatin-bound RNAs can be either used directly for gene-specific analysis or subject to further rRNA removal and also the optional polyadenylated RNA removal, followed by high-throughput sequencing. Detailed protocols for these procedures are also provided. Comparison of sequencing results of chromatin-bound RNAs with and without polyadenylated RNA removal revealed that a small fraction of CB-RNAs is polyadenylated but not yet fully spliced, representing RNA-processing intermediate on-chromatin.

Conclusion
This optimized chromatin-bound RNAs purification method is simple and robust and can be used to study transcription and its-coupled RNA processing in plants.
School-based harm reduction with adolescents: a pilot study
Authors: Fischer Nina Rose 
Published: December 2022

AbstractA pilot study of Safety First: Real Drug Education for Teens showed significant results pre to post curriculum with high school freshmen. Negative outcomes of drug education are linked to a failure to engage students because of developmentally inappropriate materials that include activities that have no relevance to real experiences of young people. The few harm reduction studies showed increased student drug related knowledge. Students were less likely to consume substances, and less likely to consume to harmful levels. More studies are necessary to evidence harm reduction efficacy in the classroom. The goal of this study was to measure harm reduction knowledge and behaviors, including drug policy advocacy, before and after Safety First. Data were analyzed using McNemar’s test, ANOVA, linear regression,t-tests and thematic coding. Survey results, corroborated by the qualitative findings, showed a significant increase (p < .05) in high school freshmen harm reduction knowledge and behaviors in relationship to substance use pre to post Safety First. This increase related to a decrease in overall substance use. Harm reduction is often perceived as a controversial approach to substance use. These findings have implications for further study of what could be a promising harm reduction-based substance use intervention with teens.
Clinical and sonographic improvement of developmental dysplasia of the hip: analysis of 948 patients
Authors: Bakti Karim , Lankinen Vilma , Helminen Mika , Välipakka Jarmo , Laivuori Hannele , Hyvärinen Anna 
Published: December 2022

Abstract
Background
Developmental dysplasia of the hip is a common condition, which varies in severity. Abduction treatment is widely used to correct the development of the hips, but mild forms of DDH can also recover spontaneously. The purpose of this study was to evaluate factors affecting the rate of improvement of developmental dysplasia of the hip, and evaluate any risk factors slowing the process.

Material and methods
The study population consisted of patients diagnosed with DDH in Tampere University hospital in the years 1998–2018. Data were retrospectively collected, and associations between clinical variables and rate of improvement were analyzed. Alpha angles were assessed monthly, and associations between risk factors and improvement of alpha angles were studied. A total of 948 patients were included in the analysis.

Results
More severe first status of the hips was associated with faster improvement in dynamic ultrasound compared to milder DDH in univariate design in first 3 months of age; in the multivariable design, Ortolani positivity was conversely associated with lower alpha angles in 1-month follow-up. Immediate abduction treatment was associated with faster recovery rate compared to delayed abduction or watchful waiting. Female sex and positive family history were associated with slower rate of improvement and lower alpha angles. In multivariable design, female sex, positive family history and treatment strategy remained statistically significant as initiation time of the treatment explained the first found association of clinical hip status and the recovery rate after 2 months of age.

Conclusion
Female sex and positive family history might be independent risk factors for slower recovery in DDH before 6 months of age. These children might need special attention in their follow-up plans and abduction treatment.
Semisynthetic aurones A14 protects against T-cell acute lymphoblastic leukemia via suppressing proliferation and inducing cell cycle arrest with apoptosis
Authors: Wang Meng , Li Lisi , Fan Tengyun , Cao Lixue , Zhang Jiayi , Li Shuang , Liu Chunming , Liu Xifu 
Published: December 2022

Abstract
Background
Acute lymphoblastic leukemia is an aggressive neoplasm and seriously threatens human health. A14 is one kind of semisynthetic aurone that exhibits the capability to inhibit prostate cancer, but little is known about the role of A14 on T-cell acute lymphoblastic leukemia.

Methods
Firstly, the effects of A14 on the ability of leukemia cells to proliferate were measured by Vi-cell counter. Then, we detected the cell cycle and apoptosis by flow cytometry and characterized the related protein expression using immunoblotting. In addition, we constructed stable luciferase expressing cell lines for use in a cell derived xenograft mouse model to measure the effect of A14 on T-cell acute lymphoblastic leukemia.

Results
Results exhibited that A14 markedly suppressed cell proliferation and induced G2/M phase arrest along with cell cycles regulating proteins changes. A14 led to apoptosis in leukemia cells, at least partly, through the cytochrome c signaling pathway. Experiments in cell derived xenograft mouse model also showed that A14 markedly ameliorated the survival rate.

Conclusions
The present study revealed that semisynthetic aurones A14 can effectively protect against T-cell acute lymphoblastic leukemia progression both in vitro and in vivo, indicating the capability of A14 as a promising drug for the treatment of T-cell acute lymphoblastic leukemia.
A retrospective study of 18 children with subcutaneous panniculitis-like T-cell lymphoma: multidrug combination chemotherapy or immunomodulatory therapy?
Authors: Duan Yanlong , Gao Huixia , Zhou Chunju , Jin Ling , Yang Jing , Huang Shuang , Zhang Meng , Zhang Yonghong , Wang Tianyou 
Published: December 2022

Abstract
Background
Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare, cytotoxic T-cell lymphoma with which some patients have accompanying hemophagocytic syndrome (HPS). There is currently no standard treatment regimen. In the past, the most commonly used treatment was multidrug chemotherapy. In contrast, numerous case reports or small series suggest that immunosuppressive drugs could also be effective for some patients. Since this NHL subtype is extremely rare in children and adolescents, to improve the understanding of this disease and standardize its rational treatment, we retrospectively summarized the treatment regimens of 18 pathologically diagnosed children with SPTCL to compare the clinical efficacy of multidrug chemotherapy and immunomodulatory therapy.

Results
The median age of onset was 11.1 years. Painless subcutaneous nodules or skin patchy lesions were found in all patients, most commonly involving the lower extremities and/or trunk. Before January 1, 2019, the treatment was mainly chemotherapy, and 10 patients were initially treated with chemotherapy, among whom was one patient who progressed during initial treatment, was voluntarily discharged and was subsequently lost to follow-up, one patient who died of disease progression, and the remaining 8 patients who all achieved sustained remission, with a complete remission (CR) rate of 80% (8/10). Corticosteroids combined with cyclosporine A or ruxolitinib were the most common initial immunosuppressive agents at our center after January 1, 2019 and had a CR rate of 71.4% (5/7). In addition, 1 patient achieved partial remission (PR) during follow-up, and one had autologous hematopoietic stem cell transplantation (AHSCT) after 4 months of drug withdrawal. There were 7 patients (38.9%, one case in chemotherapy group and six cases in immunotherapy group) with HPS and 4/5 screened patients (80%) with positive HAVCR2 gene mutations. The median follow-up was 17 months.

Conclusion
The prognosis of SPTCL is relatively good. Previous multi-drug and long-term chemotherapy treatment has clear efficacy, and recent immunomodulatory therapy as pre-chemotherapy therapy can also benefit patients.