bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of aging on meningeal gene expression
Authors: Neutzner Melanie , Kohler Corina , Frank Stephan , Killer Hanspeter E. , Neutzner Albert 
Published: February 2023

Abstract
Background
The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal fluid-filled subarachnoid space and across the brain parenchyma via their connection to glymphatic structures. Meningeal fibroblasts lining and traversing the subarachnoid space have direct impact on the composition of the cerebrospinal fluid through endocytotic uptake as well as extensive protein secretion. In addition, the meninges are an active site for immunological processes and act as gatekeeper for immune cells entering the brain. During aging in mice, lymphatic drainage from the brain is less efficient contributing to neurodegenerative processes. Aging also affects the immunological status of the meninges, with increasing numbers of T cells, changing B cell make-up, and altered macrophage complement.

Methods
We employed RNASeq to measure gene expression and to identify differentially expressed genes in meninges isolated from young and aged mice. Using Ingenuity pathway, GO term, and MeSH analyses, we identified regulatory pathways and cellular functions in meninges affected by aging.

Results
Aging had profound impact on meningeal gene expression. Pathways related to innate as well as adaptive immunity were affected. We found evidence for increasing numbers of T and B lymphocytes and altered activity profiles for macrophages and other myeloid cells. Furthermore, expression of pro-inflammatory cytokine and chemokine genes increased with aging. Similarly, the complement system seemed to be more active in meninges of aged mice. Altered expression of solute carrier genes pointed to age-dependent changes in cerebrospinal fluid composition. In addition, gene expression for secreted proteins showed age-dependent changes, in particular, genes related to extracellular matrix composition and organization were affected.

Conclusions
Aging has profound effects on meningeal gene expression; thereby affecting the multifaceted functions meninges perform to maintain the homeostasis of the central nervous system. Thus, age-dependent neurodegenerative processes and cognitive decline are potentially in part driven by altered meningeal function.
p53 aberration and TFE3 gene amplification may be predictors of adverse prognosis in epithelioid angiomyolipoma of the kidney
Authors: Zhang Yanning , Wei Xuejing , Teng Xiaojing , Chen Guangyong 
Published: February 2023

Abstract
Background
Although epithelioid angiomyolipoma of the kidney has been studied by several groups, the reported prevalence of malignant behavior remains uncertain and there are not yet definitive predictive biomarkers. We evaluated the behavior of renal epithelioid angiomyolipoma in a consecutive series in a single institution and investigated the prognostic value of aberrant p53 expression and TFE3 gene abnormality.

Methods
We retrospectively reviewed 14 epithelioid angiomyolipomas, most with pure or close to pure epithelioid components, comprising 12 consecutive cases who had attended our institution and two consultation cases. Fluorescence in situ hybridization with TFE3 break-apart probe was performed on 14 cases. The 14 cases were also labeled for p53 and TFE3 by immunohistochemistry. All cases were followed up.

Results
Three of the epithelioid angiomyolipomas were strongly positive for TFE3 and two had a mutant expression of p53. Although no TFE3 gene rearrangement was found, the two tumors with strong TFE3 expression showed TFE3 gene amplification. Follow-up details were available for seven of the 12 consecutive cases: two of them had developed metastases and died (29%), their mean overall survival was 41 months, and both had mutant p53 expression. The two consultation cases with TFE3 gene amplification developed recurrence/metastasis within 1 year after surgery.

Conclusions
Our series study from a single institution presented the prevalence of malignant behavior in pure epithelioid angiomyolipomas, although the small number of cases with follow-up data greatly reduced the accuracy. p53 may be a prognostic marker for epithelioid angiomyolipoma. Cases with TFE3 gene amplification had poor prognoses.
HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway
Authors: Lv Jiancheng , Li Kai , Yu Hao , Han Jie , Zhuang Juntao , Yu Ruixi , Cheng Yidong , Song Qiang , Bai Kexin , Cao Qiang , Yang Haiwei , Yang Xiao , Lu Qiang 
Published: February 2023

Abstract
Background
The response rate to immunotherapy in patients with bladder cancer (BCa) remains relatively low. Considering the stable existence and important functions in tumour metabolism, the role of circRNAs in regulating immune escape and immunotherapy sensitivity is receiving increasing attention.

Methods
Circular RNA (circRNA) sequencing was performed on five pairs of BCa samples, and circFAM13B (hsa_circ_0001535) was screened out because of its remarkably low expression in BCa. Further mRNA sequencing was conducted, and the association of circFAM13B with glycolysis process and CD8+ T cell activation was confirmed. The functions of circFAM13B were verified by proliferation assays, glycolysis assays, BCa cells-CD8+ T cell co-culture assays and tumorigenesis experiment among human immune reconstitution NOG mice. Bioinformatic analysis, RNA–protein pull down, mass spectrometry, RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were performed to validate the HNRNPL/circFAM13B/IGF2BP1/PKM2 cascade.

Results
Low expression of circFAM13B was observed in BCa, and it was positively associated with lower tumour stage and better prognosis among patients with BCa. The function of CD8+ T cells was promoted by circFAM13B, and it could attenuate the glycolysis of BCa cells and reverse the acidic tumour microenvironment (TME). The production of granzyme B and IFN-γ was improved, and the immunotherapy (PD-1 antibodies) sensitivity was facilitated by the inhibition of acidic TME. Mechanistically, circFAM13B was competitively bound to the KH3-4 domains of IGF2BP1 and subsequently reduced the binding of IGF2BP1 and PKM2 3’UTR. Thus, the stability of the PKM2 mRNA decreased, and glycolysis-induced acidic TME was inhibited. The generation of circFAM13B was explored by confirming whether heterogeneous nuclear ribonucleoprotein L (HNRNPL) could promote circFAM13B formation via pre-mRNA back-splicing.

Conclusions
HNRNPL-induced circFAM13B could repress immune evasion and enhance immunotherapy sensitivity by inhibiting glycolysis and acidic TME in BCa through the novel circFAM13B/IGF2BP1/PKM2 cascade. Therefore, circFAM13B can be used as a biomarker for guiding the immunotherapy among patients with BCa.
RETRACTED ARTICLE: SLFN5 promotes reversible epithelial and mesenchymal transformation in ovarian cancer
Authors: Xu Qiao Ping , Deng Kui , Zhang Zhen , Shang Hongkai 
Published: February 2023

AbstractOvarian cancer is a disease with increasing incidence worldwide, and there is an urgent need for chemotherapy and biological targeted therapy. Epithelial-mesenchymal transformation (EMT) is an important initiation stage for tumor cells to acquire the ability to invade and metastasize. A growing number of findings suggest that human Schlafen family member 5(SLFN5) plays a key role in malignancy. However, the role of SLFN5 in ovarian cancer cells has not been fully elucidated. Samples were collected from patients with ovarian cancer diagnosed in Hangzhou First People's Hospital, and the expression of SLFN5 was detected by fluorescence quantitative PCR. The relationship between SLFN5 expression and the progression and malignancy of ovarian cancer was analyzed by using the expression profile data from the Cancer Genome Atlas (TCGA) database. The mRNA expression levels of SLFN5 related upstream and downstream signaling pathways were studied by fluorescence quantitative PCR. Silencing SLFN5 was performed by siRNA transfection. The expression of SLFN5 and transfer-related proteins was examined by Western blot. Transwell and wound healing experiments investigated the migration and invasion ability of ovarian cancer cells. TCGA database analysis results showed that in the population with high SLFN5 expression, compared with the group with low SLFN5 expression, OS was worse (P = 0.011). SLFN5 silencing had a significant inhibitory effect on EMT and invasion movement of ovarian cancer cells. RT-PCR method was used to detect the mRNA changes of SLFN5 in ovarian cancer tissue and adjacent tissue. It was found that the expression of SLFN5 in ovarian cancer tissue was increased, with a significant difference (P < 0.05). Together, these results suggest that SLFN5 may play a synergistic role in tumorigenesis and development of ovarian cancer cells, providing a potential target for future drug development for the treatment of ovarian cancer.
Apicomplexan haemoparasites in domestic cats in Romania
Authors: Panait Luciana Cătălina , Ionică Angela Monica , Cazan Cristina Daniela , Coroian Mircea , Diacu Ana Maria , Boncea Ana Maria , Mateescu Cosmin , Mihalca Andrei Daniel 
Published: February 2023

Abstract
Background
Apicomplexan haemoparasites are protozoans that infect a variety of domestic and wild animal species, as well as humans. Data regarding haemoprotozoans in domestic cats are limited; therefore, the aim of this study was to assess the occurrence of Babesia spp., Cytauxzoon spp., and Hepatozoon spp. in domestic cats in Romania using molecular tools.

Methods
Blood samples from 371 domestic cats were screened for the presence of piroplasmids. All samples that yielded a visible band in agarose gels were subsequently tested by specific assays targeting the 18S rDNA of Babesia spp., Cytauxzoon spp., and Hepatozoon spp. Moreover, nested PCR assays targeting mitochondrial genes of Babesia spp. were used for screening of all Babesia spp. 18S rDNA-positive samples.

Results
From the total number of sampled cats, 19.4% were positive in the PCR assay targeting piroplasmids. Babesia spp. were identified in 15.1% of cats, while 0.5% were positive for Hepatozoon spp. Molecular analyses confirmed the presence of Babesia canis. No samples were positive for Cytauxzoon spp.

Conclusions
The high infection rates of domestic cats with Babesia spp. and the need for species differentiation highlight the importance of mitochondrial genes as targets for molecular protocols.
The performance of the MODY calculator in a non-Caucasian, mixed-race population diagnosed with diabetes mellitus before 35 years of age
Authors: Santomauro Augusto Cezar , Magalhães Áurea Luiza Fernandes , Motta Flávia Tedesco , de Santana Lucas Santos , Franco Pedro Campos , de Freitas Silvia Maria , Sanchez Jeniffer Johana Duarte , Costa-Riquetto Aline Dantas , Teles Milena G. 
Published: February 2023

Abstract
Background
A maturity-onset diabetes of the young (MODY) calculator has been described and validated for use in European Caucasians. This study evaluated its performance in Brazilians diagnosed with diabetes mellitus (DM) before 35 years of age.

Methods
The electronic records of 391 individuals were reviewed in 2020 at the diabetes clinic of a quaternary hospital in São Paulo were analyzed: 231 with type 1 DM (T1DM), 46 with type 2 (T2DM) and 114 with MODY. The MODY calculator was applied to the three groups. A receiver operating characteristic curve was calculated to obtain cut-off points for this population.

Results
The principal differences between the MODY and the T1DM and T2DM groups were body mass index, a positive family history of diabetes and mean HbA1c level. Age at diagnosis in the MODY group was only significantly different compared to the T2DM group. Specificity and sensitivity were good for the cut-off points of 40%, 50% and 60%, with the accuracy of the model for any of these cut-off points being > 95%.

Conclusion
The capacity of the calculator to identify Brazilian patients with MODY was good. Values ≥ 60% proved useful for selecting candidates for MODY genetic testing, with good sensitivity and specificity.
Aberrant JAK-STAT signaling-mediated chromatin remodeling impairs the sensitivity of NK/T-cell lymphoma to chidamide
Authors: Chen Jinghong , Zuo Zhixiang , Gao Yan , Yao Xiaosai , Guan Peiyong , Wang Yali , Li Zhimei , Liu Zhilong , Hong Jing Han , Deng Peng , Chan Jason Yongsheng , Cheah Daryl Ming Zhe , Lim Jingquan , Chai Kelila Xin Ye , Chia Burton Kuan Hui , Pang Jane Wan Lu , Koh Joanna , Huang Dachuan , He Haixia , Sun Yichen , Liu Lizhen , Liu Shini , Huang Yuhua , Wang Xiaoxiao , You Hua , Saraf Sahil Ajit , Grigoropoulos Nicholas Francis , Li Xiaoqiu , Bei Jinxin , Kang Tiebang , Lim Soon Thye , Teh Bin Tean , Huang Huiqiang , Ong Choon Kiat , Tan Jing 
Published: February 2023

Abstract
Background
Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. However, its therapeutic efficacy in NKTL remains unclear.

Methods
We performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohistochemistry (IHC) was used to validate the predictive biomarkers in tumors from the clinical trial.

Results
We demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanistically, our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect in vitro and in vivo. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of the JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide.

Conclusions
Our study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL.

Trial registration: ClinicalTrials.gov, NCT02878278. Registered 25 August 2016, https://clinicaltrials.gov/ct2/show/NCT02878278
Using random forest to predict antimicrobial minimum inhibitory concentrations of nontyphoidal Salmonella in Taiwan
Authors: Wang Chia-Chi , Hung Yu-Ting , Chou Che-Yu , Hsuan Shih-Ling , Chen Zeng-Weng , Chang Pei-Yu , Jan Tong-Rong , Tung Chun-Wei 
Published: February 2023

AbstractAntimicrobial resistance (AMR) is a global health issue and surveillance of AMR can be useful for understanding AMR trends and planning intervention strategies. Salmonella, widely distributed in food-producing animals, has been considered the first priority for inclusion in the AMR surveillance program by the World Health Organization (WHO). Recent advances in rapid and affordable whole-genome sequencing (WGS) techniques lead to the emergence of WGS as a one-stop test to predict the antimicrobial susceptibility. Since the variation of sequencing and minimum inhibitory concentration (MIC) measurement methods could result in different results, this study aimed to develop WGS-based random forest models for predicting MIC values of 24 drugs using data generated from the same laboratories in Taiwan. The WGS data have been transformed as a feature vector of 10-mers for machine learning. Based on rigorous validation and independent tests, a good performance was obtained with an average mean absolute error (MAE) less than 1 for both validation and independent test. Feature selection was then applied to identify top-ranked 10-mers that can further improve the prediction performance. For surveillance purposes, the genome sequence-based machine learning methods could be utilized to monitor the difference between predicted and experimental MIC, where a large difference might be worthy of investigation on the emerging genomic determinants.
Prediction model of agricultural water quality based on optimized logistic regression algorithm
Authors: Gai RongLi , Zhang Hao 
Published: February 2023

AbstractAiming at the problem that the linear regression of the traditional linear water quality prediction model is not robust enough and the prediction accuracy cannot be guaranteed in the presence of interference, this paper proposes an agricultural water quality prediction model based on the Momentum algorithm to optimize the logistic regression algorithm (LRM algorithm). The model uses the Momentum algorithm to optimize the logistic regression algorithm to quickly adjust the misclassified samples. When the object encounters a local optimum in the process of falling, the introduction of momentum makes it easy for the next update to jump out of the local optimum with the help of the last large gradient. In this paper, the performance of the proposed model is evaluated on 4 real data sets. The experimental results show that the LRM algorithm proposed in this paper improves the prediction accuracy of the existing algorithm by an average of 1.11 percentage points.Compared with KNN and other traditional prediction algorithms, LRM not only speeds up the convergence rate of the algorithm, but also reduces the steady-state error and improves the prediction accuracy of water quality, suitable for data mining of complex water quality data, The experiment verifies the feasibility of this method in predicting the actual agricultural water quality and even in predicting and warning the residents drinking water.
A Hardy–Hilbert-type integral inequality involving two multiple upper-limit functions
Authors: Luo Ricai , Yang Bicheng , He Leping 
Published: February 2023

AbstractBy means of the weight functions, the idea of introducing parameters and the technique of real analysis, a new Hardy–Hilbert-type integral inequality with the homogeneous kernel$\frac{1}{(x + y)^{\lambda}}\ (\lambda > 0)$1(x+y)λ(λ>0)involving two multiple upper-limit functions is obtained. The equivalent statements of the best possible constant factor related to the beta and gamma functions are considered. As applications, the equivalent forms and the case of a nonhomogeneous kernel are deduced. Some particular inequalities and the operator expressions are provided.
Efficacy of mindfulness and goal setting interventions for increasing resilience and reducing smoking in lower socio-economic groups: randomised controlled trial protocol
Authors: De Zylva Reece , Mortimer Elissa , Miller Emma , Tsourtos George , Lawn Sharon , Wilson Carlene , Karnon Jonathan , Woodman Richard , Ward Paul 
Published: February 2023

Abstract
Background
Smoking and resulting health problems disproportionately impact low socioeconomic status (SES) individuals. Building resilience presents an approach to ‘closing the gap’. Mindfulness-based interventions and setting realistic goals are preferred in low socioeconomic communities. We aim to test if these interventions, delivered online and consolidated with peer support offered via ex-smokers, are successful in promoting smoking cessation and resilience. Our conceptualisation of resilience encompasses the inner capacity/skills and external resources (e.g., social support) which smokers utilise to bounce back from adversity. We include a process evaluation of barriers/facilitators to interventions and cost-effectiveness analysis (from health system perspective).

Methods
We plan a four-arm parallel 12-month RCT with a 6-month follow-up to test the efficacy of three group-based interventions each followed by peer support. Arm 1: mindfulness-integrated cognitive behavioural therapy; Arm 2: mindfulness training; Arm 3: setting realistic goals; Arm 4: active control group directed to quit services. All interventions will be administered online. Participants are adult smokers in Australia (N = 812) who have an average weekly household income less than $457AUD or receive welfare benefits. Group-based interventions will occur over 6 months, followed by 6 months of forum-based peer support. Primary outcome: self-reported 14-day period prevalence of smoking abstinence at 6 months, with remote biochemical verification of saliva cotinine (< 30 ng/mL). Secondary outcomes include: internal resilience (Connor-Davidson Resilience Scale-25); external resilience (ENRICHD social support tool); quality adjusted life years (EQ-5D-5L); self-efficacy for smoking abstinence (Smoking-Abstinence Self-Efficacy Questionnaire); motivation to quit smoking (Biener and Abrams Contemplation Ladder); nicotine dependence (Fagerstrom Test for Nicotine Dependency); equanimity (Equanimity Scale-16); stress (Perceived Stress Scale-10); goal assessment/attainment (Problems and Goals Assessment Scale).

Discussion
This study is the first to compare resilience interventions for low SES smokers which have been identified by them as acceptable. Our various repeated measures and process evaluation will facilitate exploration of mechanisms of impact. We intervene within the novel framework of the Psychosocial Model of Resilience, applying a promising paradigm to address a critical and inequitable public health problem.
Trial registration Australian New Zealand Clinical Trials Registry ID: ACTRN12621000445875, registered 19 April 2021 (https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381007&isReview=true). The Universal Trial Number is U1111-1261–8951