bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Experience in Prioritizing Hippocampal Replay
Authors: Bendor Daniel , Gorriz Marta Huelin , Takigawa Masahiro 
Published: April 2023

Abstract
During sleep, recent memories are consolidated, whereby behavioral episodes first encoded by the hippocampus get transformed into long-term memories. However, the brain cannot consolidate every experience and much like the triage of an emergency room, the hippocampus is hypothesized to give precedence to more important memories first, and deprioritize or even skip over less relevant memories if needed. Here we examine two factors that are postulated to influence this memory triage process- 1) repetition, arising from the number of times a behavioral episode is repeated, increasing the priority to consolidate and 2) familiarity, resulting from previously experiencing a similar behavioral episode, in turn decreasing the need for further consolidation. Recording from large ensembles of hippocampal place cells while rats ran repeated spatial trajectories, and afterwards during periods of sleep, we examined how these two factors influenced replay, a hypothesized mechanism of consolidation involving the offline spontaneous reactivation of memory traces. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the rat. In contrast to this, the rate of sleep replay events decreased if the rat was more familiar with the track, arising from previously running on the same track before its most recent sleep session. Furthermore, we find that the cumulative number of awake replay events that occur during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, and provides a more parsimonious mechanism for the selectively strengthening and triaging of memories.
HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients
Authors: Naito Takeo , Shimoda Fumiko , Kakuta Yoichi , Kawai Yosuke , Shimoyama Yusuke , Moroi Rintaro , Shiga Hisashi , Nagasaki Masao , Kinouchi Yoshitaka , Masamune Atsushi 
Published: April 2023

Abstract
Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early Infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese IFX-naiveCD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The rs2097432 significantly increased the risk of early discontinuation of IFX even after being adjusted by other clinical parameters [Hazard ratio (HR) = 2.13 and P-value = 0.038]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). We confirmed the robust association of rs2097432 with IFX persistence regardless of the population. A novel genetic factor for IFX persistence was also identified using GWAS.
Pharmacy Student Attitudes to Mental Health Care: A Longitudinal Survey
Authors: Keating Dolores , McWilliams Stephen , Clarke Mary , Strawbridge Judith 
Published: April 2023

Abstract
Background

Attitudes to mental illness are an important factor in the willingness of professionals to engage in mental health care.

Aim

We sought to understand the attitudes of undergraduate pharmacy students in Ireland to severe mental illness and the provision of medicines optimisation services. Further, we aimed to understand if these attitudes changed through the course of the students’ undergraduate training.

Methods

A survey instrument was compiled using existing published research. The survey was distributed to students in their first, third and MPharm years annually between 2014 and 2019.

Results

The overall response rate to the survey was 25%. Respondents were mostly female (77.5%) and knew someone experiencing mental illness (83.2%). Notwithstanding generally positive attitudes, a sizeable proportion of students felt people with severe depression and schizophrenia were hard to talk to (29.2% vs 25.3%). Less than half of MPharm students expressed confidence and competence in caring for people with more severe mental illnesses such as bipolar disorder and schizophrenia and 29% of students would feel awkward asking someone about their antipsychotic medication. Almost two thirds (63.8%) expressed an interest in a career in mental health.

Conclusion

Irish pharmacy students have generally positive attitudes towards people with severe mental illness and provision of medicines optimisation services. Practical difficulties in conducting longitudinal research are challenging to overcome with low response rates to surveys limiting the generalisability of results. It is nonetheless encouraging that a significant proportion of our future pharmacists consider mental health care to be a potentially rewarding career option.
M6 A-mediated upregulation of HOXC10 promotes human hepatocellular carcinoma development through PTEN/AKT/mTOR signaling pathway
Authors: Li Miao , Guo Qianwen , Shi Qian , Rao Yanzhi , Dong Yixin , Chen Fangjie , Qi Xun 
Published: April 2023

Abstract
Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.
A single-cell transcriptomic atlas characterizes molecular features in ureteritis/cystitis induced by immune checkpoint inhibitors
Authors: Qiao Guanglei , Yu Xiang , Deng Zhoufeng , Yu Wenxi , Yuan Ying , Liu Min , Liu Zimei , Zhang Yan , Chen Ying , Yu Liping , Lin Hongjian , Ma Lijun , Wu Yuquan , Huang Wentao , Liu Xin , Zhang Jianjun 
Published: April 2023

Abstract
Common immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) include dermatological, gastrointestinal, pulmonary, or endocrine side effects. Although less common than other IrAEs, IrAEs involving the urinary tract and bladder are gradually being recognized by clinicians. However, the early diagnosis and optimal management of ICI-induced ureteritis/cystitis are challenging because the underlying mechanisms remain poorly understood. Here we report the results from a comprehensive single-cell analysis of cell populations implicated in ureteritis/cystitis induced by an anti-programmed-death-1 monoclonal antibody. We observed a striking expansion of T cells with highly cytotoxic state in the ureteritis/cystitis tissue, which was accompanied by a significant decrease in epithelial cell numbers. The proportion of macrophages was also increased in the ureteritis/cystitis tissue, compared with healthy tissue. Moreover, we identified changes in the molecular features of the CXCL, TNF, NF-κB, ITGB2, and GZMB signaling pathways. Collectively, our findings provide insights into the molecular mechanisms underlying ICI-induced ureteritis/cystitis and imply that modulating T cell, macrophage, epithelial cell, and endothelial cell functions by interfering with the identified signaling pathways could help guide new therapeutic strategies.
Radiomics analysis based on CT for the prediction of pulmonary metastases in Ewing sarcoma
Authors: Liu Ying , Yin Ping , Cui Jingjing , Sun Chao , Chen Lei , Hong Nan , Li Zhentao 
Published: April 2023

Abstract
Objectives
This study aimed to develop and validate radiomics models on the basis of computed tomography (CT) and clinical features for the prediction of pulmonary metastases (MT) in patients with Ewing sarcoma (ES) within 2 years after diagnosis.
Materials and Methods
A total of 143 patients with a histopathological diagnosis of ES were enrolled in this study (114 in the training cohort and 29 in the validation cohort). The regions of interest (ROIs) were handcrafted along the boundary of each tumor on the CT and CT-enhanced (CTE) images, and radiomic features were extracted. Six different models were built, including three radiomics models (CT, CTE and ComB models) and three clinical-radiomics models (CT_clinical, CTE_clinical and ComB_clinical models). The area under the receiver operating characteristic curve (AUC), and accuracy were calculated to evaluate the different models, and DeLong test was used to compare the AUCs of the models.
Results
Among the clinical risk factors, the therapeutic method had significant differences between the MT and non-MT groups (P＜0.01). The six models performed well in predicting pulmonary metastases in patients with ES, and the ComB model (AUC: 0.866/0.852 in training/validation cohort) achieved the highest AUC among the six models. However, no statistically significant difference was observed between the AUC of the models.
Conclusions
In patients with ES, clinical-radiomics model created using radiomics signature and clinical features provided favorable ability and accuracy for pulmonary metastases prediction.
Effects of COVID-19 lockdown on hydrochemical properties of the Brahmaputra River, India
Authors: Meena Vijay , Paul Sujata , Sarma Arup Kumar , Mahanta Chandan , Bhattacharyya Krishna Gopal 
Published: April 2023

AbstractMillions of the people in Assam- India, rely on the Brahmaputra River for survival. Hence, the assessment of the suitability of its water for drinking and agricultural use is of utmost necessity. The present research work assessed the water quality of the Brahmaputra River before and after the COVID-19 lockdown period. Eleven sampling stations along the river's course were analysed. The trend of cations and anions was observed as Ca2+> Mg2+> Na+>K+and HCO3−> SO42−> Cl−> NO3−> PO43−, both before and after the lockdown. Statistical analysis showed more deteriorated water quality after the lockdown. Chemical oxygen demand (COD) during post lockdown period was 1.4 times higher than the pre-lockdown, signifying more pollution in the post-lockdown period. Silicate and carbonate weathering was found in both periods. The drinking water quality did not improve after the lockdown and remained 'poor' for both periods. Indices used to analyse irrigation water quality were percent Sodium (Na%), Magnesium hazard (MH), Sodium Adsorption Ratio (SAR) Kelly's ratio (KR), Permeability index (PI) and Cation ratio of soil structural stability (CROSS). SAR index and Wilcox diagram depicted deteriorated water quality after the lockdown period, making it harmful for irrigation.
GABA/Baclofen Enhances Immunotherapy of Breast Cancer by Stabilizing PD-L1
Authors: Sun Xue , Xu Yanping , Lv Lei 
Published: April 2023

Abstract
The programmed death-ligand 1 (PD-L1) on the surface of tumor cells binds to the receptor programmed cell death protein 1 (PD-1) on effector T cells, thereby inhibiting the anti-tumor immune response. Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has been approved for the treatment of human cancers with lasting clinical benefit. However, many cancer patients did not respond to anti-PD-1/PD-L1 antibody blocking therapy or drugs targeting PD-1/PD-L1. Recent studies have shown that the response to PD-1/PD-L1 blockade may be related to the PD-L1 abundance of tumor cells. Therefore, it is of crucial significance to find drugs to regulate the expression of PD-L1, which can provide new strategies to improve the response rate and efficacy of PD-1/PD-L1 blocking in cancer treatment. Here, we found that GABA and baclofen, upregulates the protein level of PD-L1 by reducing the mRNA and protein levels of STUB1, a E3 ubiquitin ligase, thereby decreasing the interaction between STUB1 and PD-L1, and ultimately stabilizing PD-L1. Notably, GABA and baclofen did not affect cell proliferation in vitro, while in the treatment of breast cancer in mice, the therapeutic effect of baclofen combined with anti-PD-L1 antibody is significantly better than that of using anti-PD-L1 antibody alone by stimulating tumor infiltration of CD8+ T cells and antitumor immunity. Taken together, we unveiled a previously unappreciated role of GABA/baclofen in stabilizing PD-L1 and enhancing the immunotherapy of breast cancer.
Modulation of pancreatic tumor immunity by NKG2D T cells through MICB shedding
Authors: Toyoda Hitoshi , Kuramasu Atsuo , Hosonuma Masahiro , Murayama Masakazu , Narikawa Yoichiro , Isobe Junya , Baba Yuta , Tajima Kohei , Funayama Eiji , Shida Midori , Hirasawa Yuya , Tsurui Toshimitsu , Ariizumi Hirotsugu , Ishiguro Tomoyuki , Suzuki Risako , Kobayashi Sei , Horiike Atsushi , Hida Noriko , Sambe Takehiko , Nobe Koji , Wada Satoshi , Kobayashi Hitome , Tsuji Mayumi , Kobayashi Shinichi , Tsunoda Takuya , Inagaki Katsunori , Kiuchi Yuji , Yoshimura Kiyoshi 
Published: April 2023

Abstract
Natural killer group 2 member D ligands (NKG2DLs) are expressed as stress response proteins in cancer cells. NKG2DLs induce the activation of immune cells or tumor escape responses, depending on their expression. Human pancreatic cancer cells, Panc-1, express membrane MICA/B (mMICA/B), whereas soluble MICB (sMICB) is detected in the culture supernatant. We hypothesized that sMICB saturates NKG2D in NKG2DLow T cells and inhibits the activation signal from mMICB to NKG2D. The findings revealed that downregulation of MICB reduced sMICB, downregulated mMICB, maintained activation of NKG2DLow T cells, and inhibited activation of NKG2DHigh T cells. To maintain mMICB expression and reduce sMICB expression, we inhibited ADAM, a metalloproteinase that sheds MICB. Subsequently, the shedding of MICB was prevented by ADAM17 inhibitors, and the activation of NKG2DLow T cells was maintained. These results elucidate the mechanism of immune escape via sMICB and show promising potential for the activation of NKG2DLow T cells within the tumor microenvironment.
Functional Swiss-type experimental cheeses diet promotes beneficial effects in mice gut microbiome during homeostasis and inflammation
Authors: Carvalho Rodrigo , Rabah Houem , Carmo Fillipe Luiz Rosa , Ariute Juan Carlos , Aburjaile Flávia Figueira , Brenig Bertram , Guédon Eric , Loir Yves Le , Jan Gwénaël , Azevedo Vasco 
Published: April 2023

Abstract
Background
Nutritional interventions have been considered an alternative rationale for preventing Inflammatory Bowel Diseases. The investigation of their impact on the gut microbiota is a fundamental question since shifts in the composition of the commensal bacterial community are required for the onset and maintenance of colitis. Therefore, in this study, we investigated the effects of two types of cheeses, fermented by probiotic propionibacteria. One experimental single-strain cheese was solely fermented by Propionibacterium freudenreichii CIRM-BIA129. Another was an Emmental made in industrial conditions using the same propionic strain, in combination with Lactobacillus delbrueckii CNRZ327 and Streptococcus thermophilus LMD-9, as starters. Both kinds of cheese were tested in healthy conditions and the context of DSS-induced colitis in conventional C57BL6 mice and the gut microbiota was investigated.
Results
Based on the metagenomic analysis, our results suggest that cheese consumption, whatever the kind of cheese, did not disturb the typical microbial community, although the Emmental intake increased symbionts population as Romboutsia sp. and partially increased Akkermansia muciniphila. Furthermore, metabolic pathway reconstruction analysis suggests that A. muciniphila may produce acetate through sulfate assimilatory metabolism and may cooperate with other commensal species in tryptophan and glutamate metabolism to produce indole and gamma-aminobutyric acid. Considering the colitis context, the consumption of the Single-strain cheese restored some of the impaired microbiome metabolic functions, while Emmental cheese promoted the increase of Ligilactobacillus murinus. This bacterium presented several genes involved in producing metabolites and adhesin proteins with potential immunomodulatory activity.
Conclusions
This study concludes that the Emmental cheese effects increased the microbiota's capacity to produce metabolites involved in gut-brain axis regulation in intestinal homeostasis condition and, therefore, may represent a potential therapy for inflammatory neurodegenerative diseases. Regarding the colitis context, our results support the beneficial properties of functional Emmental cheese by suggesting possible anti-inflammatory mechanisms based on the promotion of Lg. murinus interaction with the host.
Assessment of Urbanization Impacts on Coastal Aquifer Vulnerability by Seawater Intrusion Using GIS-Based Modified GALDIT-B Model: A Case Study of South Chennai Coastal Region, Tamil Nadu, India.
Authors: Ravi Subramani , Sudalaimuthu Karuppasamy 
Published: April 2023

Abstract
Seawater intrusion into groundwater aquifers is a growing global concern due to factors such as groundwater exploitation, rising sea levels, and climate change. This study focuses on the Chennai south coastal region and incorporates an urban sprawl perspective to delineate vulnerable zones of seawater intrusion into littoral aquifers. The study uses land use/land cover (LULC) classification to measure the expansion of impervious surfaces in the region from 2000 to 2020. The GALDIT-B model is modified and performed using the Geographic Information System (GIS) based -Analytical Heirarchy Process (AHP) to assign weights and ratings to each factor. The resulting model identifies five categories of vulnerable zones, ranging from very high to very low, based on factors such as groundwater level and the impact of existing seawater intrusion. The study found that the coastal and deltaic geomorphological formations in the region, which consist of clayey and sandy aquifer regions with built-up areas, are the most vulnerable to saltwater intrusion. The vulnerability of the very high vulnerable zone increased by 6% between pre-monsoon 2000 and pre-monsoon 2010 and by 16% between pre-monsoon 2010 and pre-monsoon 2020. The model was cross-validated using major hydrochemical parameters and the hydrochemical facies evolution (HFE) diagram of groundwater elements. The highest concentration of NaCl was found in the extremely vulnerable zones. The Piper trilinear diagram was used to identify the presence of saltwater in coastal aquifers. The modified GALDIT-B model is a useful tool for decision-makers involved in the development of coastal urbanization.
Textbook Outcome Contributes to Long-Term Prognosis in Elderly Colorectal Cancer patients
Authors: Maeda Yuto , Iwatsuki Masaaki , Mitsuura Chisho , Morito Atsushi , Ohuchi Mayuko , Kosumi Keisuke , Eto Kojiro , Ogawa Katsuhiro , Baba Yoshifumi , Iwagami Shiro , Miyamoto Yuji , Yoshida Naoya , Baba Hideo 
Published: April 2023

Abstract
Purpose
Textbook outcome (TO) has been used to define achievement of multiple “ideal” or “optimal” surgical and postoperative quality measures from the patient’s perspective. However, TO has not been reported for their impact on survival in elderly, including CRC surgery. This study determined whether TO is associated with long-term outcomes after curative colorectomy in patients with colorectal cancer (CRC).
Methods
Patient who underwent curative surgery over 75 years old for CRC between March 2005 and December 2016. TO included five separate: surgery within 6 weeks, radical resection, Lymph node (LN) yield ≥ 12, no stoma, and no adverse outcome. When all 5 short-term quality of care parameters were realized, TO was achieved (TO). If any one of the 5 parameters was not met, the treatment was not considered TO (nTO).
Results
TO was realized in 80 patients (43.0%). Differences in surgical-related characteristics, and pathological characteristics according to TO had no statistically significant differences in baseline characteristics, except for Lymph node dissection. The Kaplan–Meier curves for OS and RFS association between TO and nTO had significantly poor 5-year OS and 5-year RFS compared with the TO groups (OS, 77.8% vs. 60.8%, P < 0.01; RFS, 69.6% vs. 50.8%, P = 0.01). In the multivariate analysis, nTO was an independent predictive factor for worse OS (HR, 2.04; 95% confidence interval (CI), 1.175–3.557; P = 0.01) and RFS (HR, 1.72; 95% CI, 1.043–2.842; P = 0.03).
Conclusions
TO can be a useful predictor for postoperative morbidity and prognosis after curative colorectomy for CRC.
Garlic exosomes alleviate dextran sodium sulfate-induced colitis, in which peu-MIR2916-p3 acts as a key component boosting the growth of anti-colitis Bacteroides thetaiotaomicron
Authors: Wang Xiaoyuan , Liu Yueyue , Dong Xinyue , Duan Tianchi , Wang Chennan , Wang Lu , Yang Xingbin , Tian Honglei , Li Ting 
Published: April 2023

AbstractBackground:Recently, plant-derived exosome-like nanoparticles (ELNs) have drawn much attention for oral prevention and treatment of colonic diseases. However, the roles of ELNs derived from garlic (Allium sativumL.)., which is widely documented for treating dysentery in Chinese medicine, on colitis remain largely unknown.Results:We demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) trafficking large amounts of functional proteins and miRNAs, stably roam in the gut and confer protection against ulcerative colitis. In DSS-induced colitis mice, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in whichBacteroidesserved as the dominant respondent genus upon GELNs treatment. Of note, peu-MIR2916-p3, one of the most abundant miRNAs in GELNs, specifically promoted the growth ofBacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effect on colitis.Conclusion:Our findings provide new insights for the application of GELNs and highlight the potential of GELNs as natural nanotherapeutic agents for preventing and treating ulcerative colitis.