bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosahexaenoic acid alleviates the excessive degradation of extracellular matrix in the nucleus pulposus by reducing the content of lncRNA NEAT1 to prevent the progression of intervertebral disc degeneration
Authors: Shang Liang , Ma Hui , Zhang Xiao , Mao RunZe , Ma CunYou , Ruan Zhi 
Published: February 2023

AbstractThe pathogenesis of intervertebral disc degeneration (IVDD), as a multifactorial disease, has not been fully elucidated. However, damage to the stress‐bearing system in the intervertebral disc (IVD) mediated by the excessive decomposition of extracellular matrix (ECM) in nucleus pulposus (NP) cells caused by local stimulation is widely considered the core pathological process underlying IVDD. Docosahexaenoic acid (DHA) plays a protective role in various chronic diseases. However, whether it can have such effects in IVDD has not been clearly reported. In recent years, in‐depth research on the role of long non‐coding RNA (lncRNA) nuclear‐enriched transcript 1 (NEAT1) in various diseases has continuously emerged, but such research in the field of IVD is not sufficient. In this study, tert‐butyl hydroperoxide (TBHP) was used to induce oxidative stress in human NP cells and construct a cell model of excessive ECM decomposition in vitro. A plasmid over‐expressing lncRNA NEAT1 was introduced into human NP cells to establish an NP cell model. For this specific experiment, Cell Counting Kit 8 was used to explore the timing and concentration of DHA and TBHP activity. A common gene chip platform was also used to select potential lncRNAs. Western blot and immunofluorescence assays were used to detect the expression of ECM‐related proteins in NP cells in each group. Quantitative real‐time polymerase chain reaction was used to detect the expression of lncRNA NEAT1 in NP cells in each group. On this basis, we proved that DHA alleviates excessive degradation of the ECM in NP cells in response to oxidative stress by reducing the content of lncRNA NEAT1. In conclusion, our study reveals the mechanism through which DHA relieves excessive ECM decomposition in NP cells and provides a potential new idea for the treatment of IVDD in clinical practice.
LncRNA PRKCQ‐AS1 regulates paclitaxel resistance in triple‐negative breast cancer cells through miR‐361‐5p/PIK3C3 mediated autophagy
Authors: Zheng Shurong , Fu Weida , Huang Qidi , Zhou Jieyu , Lu Kangkang , Gu Junwei , Ma Ruimin , Guo Guilong 
Published: February 2023

AbstractPaclitaxel (PTX) resistance is a key cause of chemotherapy failure in patients with triple negative breast cancer (TNBC). The aim of this study is to investigate the effect and mechanism of long non‐coding RNA (lncRNA) on the PTX resistance of TNBC cells through autophagy. MDA‐MB‐231 cells are used to induce the PTX‐resistant TNBC cell line MDA‐MB‐231.PR (MDR) by increasing dose intermittently. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to validate the mRNA levels of phosphoinositide‐3‐kinase class 3 (PIK3C3), miR‐361‐5p and lncRNA PRKCQ‐AS1 in the cells, and Western blot analysis was used to detect the protein expressions of PIK3C3, autophagy‐related, drug‐resistant and apoptosis‐related genes. MDC staining detected the formation of autophagic vacuoles. The interactions between miR‐361‐5p and PIK3C3 and between lncRNA PRKCQ‐AS1 and miR‐361‐5p were verified by dual‐luciferase assay. Cell viability, apoptosis, migration and invasion were assessed by performing MTT, flow cytometry assay, and transwell assay. The mRNA level of miR‐361‐5p and the autophagy and drug resistance levels of TNBC PTX‐resistant cells were significantly up‐regulated. miR‐361‐5p could target autophagy‐related gene PIK3C3, and overexpression of miR‐361‐5p could down‐regulate PIK3C3 protein expression and autophagy level and PTX resistance of MDR cells. LncRNA PRKCQ‐AS1 was selected through bioanalysis, and miR‐361‐5p could target lncRNA PRKCQ‐AS1. In addition, lncRNA PRKCQ‐AS1 level was up‐regulated in TNBC PTX‐resistant cells, and knockdown of lncRNA PRKCQ‐AS1 could weaken autophagy and drug resistance level and could promote cell apoptosis. Overexpression of lncRNA PRKCQ‐AS1 reversed the pro‐apoptotic effect and down‐regulation of autophagy and resistance levels was induced by miR‐361‐5p. In vivo experiments were performed to verify the role of lncRNA PRKCQ‐AS1. We demonstrate that down‐regulation of lncRNA PRKCQ‐AS1 weakened PTX resistance and promoted cell apoptosis by miR‐361‐5p/PIK3C3 mediated autophagy.
Efficient visual learning by bumble bees in virtual‐reality conditions: Size does not matter
Authors: Lafon Gregory , Paoli Marco , Paffhausen Benjamin H. , Sanchez Gabriela de Brito , Lihoreau Mathieu , Avarguès‐Weber Aurore , Giurfa Martin 
Published: February 2023

AbstractRecent developments allowed establishing virtual‐reality (VR) setups to study multiple aspects of visual learning in honey bees under controlled experimental conditions. Here, we adopted a VR environment to investigate the visual learning in the buff‐tailed bumble bee Bombus terrestris. Based on responses to appetitive and aversive reinforcements used for conditioning, we show that bumble bees had the proper appetitive motivation to engage in the VR experiments and that they learned efficiently elemental color discriminations. In doing so, they reduced the latency to make a choice, increased the proportion of direct paths toward the virtual stimuli and walked faster toward them. Performance in a short‐term retention test showed that bumble bees chose and fixated longer on the correct stimulus in the absence of reinforcement. Body size and weight, although variable across individuals, did not affect cognitive performances and had a mild impact on motor performances. Overall, we show that bumble bees are suitable experimental subjects for experiments on visual learning under VR conditions, which opens important perspectives for invasive studies on the neural and molecular bases of such learning given the robustness of these insects and the accessibility of their brain.
Review of the chemical ecology of homoterpenes in arthropod–plant interactions
Authors: Gurr Geoff M. , Liu Jian , Pickett John A. , Stevenson Philip C. 
Published: February 2023

AbstractThe homoterpenes 4,8‐dimethyl‐1,3,7‐nonatriene (DMNT) and 4,8,12‐trimethyl‐1,3,7,11‐tridecatetraene (TMTT) are volatile products of plant metabolism reported from diverse plant taxa and multiple plant tissues. As such, they have a range of potential ecological functions. Here, we review the key literature to assess evidence for roles in contrasting plant–arthropod interactions. TMTT, and DMNT especially, have been reported as sometimes dominant constituents of floral scents from angiosperm taxa ranging from primitive Magnoliales to more advanced, taxonomic orders of economic significance such as Fabales and Sapindales. Although all taxa producing TMTT and DMNT in floral scents are entomophilous (‘insect pollinated’), experimental evidence for an assumed role of these homoterpenes in pollinator attraction is limited. Representing a trade‐off, in some cases, homoterpenes in floral scents have been shown to act as kairomones, attracting herbivores. Additionally, both TMTT and DMNT are released by plant foliage in response to arthropod feeding, mechanical damage simulating feeding, or even egg deposition. Evidence for a functional role in herbivore‐induced plant volatile (HIPV) blends comes from a wide range of angiosperm orders, including anemophilous (‘wind pollinated’) taxa, as well as from gymnosperms. We conclude by considering how TMTT and DMNT function in community‐level interactions and highlighting research priorities that will reveal how plants avoid trade‐offs from contrasting ecological functions of DMNT and TMTT release and how homoterpene production might be exploited to develop improved crop varieties.
The other side of emotional support: The moderating role of personality in the relations between emotionally‐valenced support elicitation experiences and strain
Authors: Hughes Ian M. , Freier Lindsey M. 
Published: February 2023

AbstractRecent organizational research has begun focusing on alternative perspectives of the social support dynamic. One of these perspectives is the potential support provider perspective, which captures the social support dynamic from the view of employees put in position to potentially provide social support. Empirical findings concerning this perspective are scant and thus warrant additional research. The present study, using a large, occupationally heterogenous two‐wave sample (N = 447), further explored relations between strain and support elicitation experiences that are emotionally‐valenced, or SEE‐E, from the potential support provider perspective. The role of individual differences in influencing these relations was also investigated. Using hierarchical regression, we found that SEE‐E was related to key forms of psychological (work‐related burnout), behavioral (hostility), and physiological (the presence of physical symptoms) strain. Furthermore, we found that higher levels of agreeableness strengthened the relations between SEE‐E and work‐related burnout, and higher levels of conscientiousness weakened the relations between SEE‐E and hostility. Results from this study contribute to the nascent findings surrounding the potential support provider perspective of the workplace social support dynamic and further demonstrate the importance of individual differences to stressor‐strain dynamics.
Glycochenodeoxycholate and glycodeoxycholate 3‐O‐glucuronides, but not hexadecanedioate and tetradecanedioate, detected weak inhibition of OATP1B caused by GDC‐0810 in humans
Authors: Yoshida Kenta , Jaochico Allan , Mao Jialin , Sangaraju Dewakar 
Published: February 2023

Endogenous biomarkers of drug transporters are promising tools to evaluate in vivo transporter function and potential alterations in the pharmacokinetics of their substrates. We have previously reported that coproporphyrin I/III captured the weak inhibition of OATP1B transporters by GDC‐0810. In this study, we measured plasma concentrations of additional biomarkers, namely fatty acids, bile acids and their sulphate or glucuronide conjugates in the presence and absence of GDC‐0810. Concentrations of hexadecanedioate and tetradecanedioate did not increase in the presence of GDC‐0810. Among bile acids and their conjugates, glycochenodeoxycholate and glycodeoxycholate 3‐O‐glucuronides (GCDCA‐3G and GDCA‐3G) showed Cmax increases with geometric mean ratio (95% confidence interval) of 1.58 (1.13‐2.22) and 1.49 (1.21‐1.83), consistent with previous reports from low‐dose rifampin co‐administration and pharmacogenetic studies. These results suggest that GCDCA‐3G and GDCA‐3G are two more promising biomarkers that may capture weak OATP1B inhibition in addition to coproporphyrin I/III.
BC Clinical impact of medication reviews with follow‐up in cardiovascular older patients in primary care: A cluster‐randomized controlled trial
Authors: Martínez‐Mardones Francisco , Benrimoj Shalom I. , Ahumada‐Canale Antonio , Plaza‐Plaza Jose C. , Garcia‐Cardenas Victoria 
Published: February 2023

AimsCardiovascular diseases (CVD) are the primary cause of death in Chile. Pharmacist‐led medication review with follow‐up (MRF) has improved CVD risk factors control in Europe and North America. However, their healthcare systems differ from Chile's, precluding generalizability. This trial aimed to determine the effect of MRF on CVD risk factor control among older patients with polypharmacy attending public primary care centres in Chile.MethodsA cluster‐randomized controlled trial was conducted in 24 centres. Patients older than 65 years with moderate‐to‐high CVD risk, five or more medications, hypertension, type 2 diabetes or dyslipidaemia, received MRF in addition to usual care or usual care alone for 12 months. Primary outcome measures were clinical goal achievement for hypertension, type 2 diabetes and dyslipidaemia, as well as medication adherence, medication number and CVD risk score. Adjusted generalized estimating equations were used, with odds ratios (ORs) for binary measures and mean differences for continuous measures.ResultsIn total, 324 patients from 12 centres (174 MRF group, 150 usual care group, six centres each) received four pharmacist visits. Significant improvements were found for goal achievement in hypertension (OR 4.37, 95% confidence interval [CI] 2.54 to 7.51, P = .001), LDL cholesterol (OR 3.67, 95% CI 2.13 to 6.33, P = .001), type 2 diabetes (OR 6.97, 95% CI 3.69 to 13.2, P = .001), medication adherence (OR 6.60, 95% CI 1.36 to 31.9, P = .022), medications number (−0.86, 95% CI −1.14 to −0.58, P < .001) and CVD risk score (−2.27, 95% CI −2.84 to −1.69, P < .001).ConclusionPharmacist‐led medication review with follow‐up improved cardiovascular disease risk factor control and medication adherence. This study supports pharmacists' inclusion in primary care teams.
Evaluation of important human CYP450 isoforms and P‐glycoprotein phenotype changes and genotype in type 2 diabetic patients, before and after intensifying treatment regimen using Geneva cocktail
Authors: Neyshaburinezhad Navid , Shirzad Nooshin , Rouini Mohammadreza , Namazi Soha , Khoshayand Mohammadreza , Esteghamati Alireza , Nakhjavani Manouchehr , Ghasim Hengameh , Gloor Yvonne , Daali Youssef , Ardakani Yalda H. 
Published: February 2023

AbstractThe present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P‐glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non‐T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL‐1β and IL‐6), genotypes, diabetes and demographic‐related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform‐specific manner.
Development and validation of a patient‐reported outcome measure to assess symptom burden after chimeric antigen receptor T‐cell therapy
Authors: Wang Xin Shelley , Srour Samer A. , Mendoza Tito , Whisenant Meagan , Subbiah Ishwaria , Gonzalez Elizabeth , Kamal Mona , Shen Shu‐En , Cleeland Charles , Kebriaei Partow , Rezvani Katayoun , Neelapu Sattva , Ahmed Sairah , Shpall Elizabeth 
Published: February 2023

SummaryThis cross‐sectional study aimed to develop and validate a patient‐reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T‐cell therapy, the MD Anderson Symptom Inventory (MDASI‐CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single‐item quality‐of‐life (QoL) measure and Patient‐Reported Outcomes Measurement Information System‐29 (PROMIS‐29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI‐CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, sexual dysfunction, and diarrhoea with high internal consistency (Cronbach's alpha: MDASI Core, 0.865; MDASI Interference, 0.915; CAR‐T module, 0.746). The MDASI‐CAR has excellent known‐group validity that was demonstrated by differentiate patients based on patient's performance status (Cohen's d for MDASI core = −1.008, interference = −0.771, module = −0.835). Criterion validity was demonstrated by the significant correlations between the MDASI‐CAR composite score, the single QoL item and the relevant domains on PROMIS‐29 (all p < 0.05). This study established the MDASI‐CAR module as a reliable and valid PRO tool for monitoring symptom burden after CAR T‐cell therapy in patients with haematological malignancies. The findings need to be validated with a longitudinal design.
The heparan sulfate mimetic Muparfostat aggravates steatohepatitis in obese mice due to its binding affinity to lipoprotein lipase
Authors: Zhang Jia , Li Kai , Sun Hao‐Ran , Sun Shao‐Kun , Zhu Ya‐Ting , Ge Yu‐Ting , Wu Yu‐Xuan , Zhou Qin‐Yao , Li Guan‐Ting , Chang Xiao‐Ai , Sun Peng , Ding Ying , Han Xiao 
Published: February 2023

Background and PurposeHeparanase is the only confirmed endoglycosidase that cleaves heparan sulfate (HS), a ubiquitous glycosaminoglycan with various essential roles in multiple pathological processes. Thus, the development of heparanase inhibitors has become an attractive strategy for drug discovery, especially in tumour therapy, in which HS mimetics are the most promising compounds. The various biological effects of heparanase also suggest a role for HS mimetics in many non‐cancer indications, such as type 1 diabetes. However, the potential benefits of HS mimetics in obesity‐related type 2 diabetes have not been elucidated.Experimental ApproachIn this study, we investigated muparfostat (PI‐88), a developed HS mimetic currently enrolled in Phase III clinical trials, in obese mouse models and in vitro cultured murine hepatocytes.Key ResultsDaily administration of muparfostat for 4 weeks caused hyperlipidaemia and aggravated hepatic steatosis in obese mice models, but not in lean animals. In cultured hepatocytes, muparfostat did not alter lipid accumulation. Acute tests suggested that muparfostat binds to lipoprotein lipase in competition with HS on vascular endothelial cell surfaces, thereby reducing the degradation of circulating triglycerides by lipoprotein lipase and subsequent uptake of fatty acids into vascular endothelial cells and causing hyperlipidaemia. This hyperlipidaemia aggravates hepatic steatosis and causes liver injury in muparfostat‐treated obese mice.Conclusions and ImplicationsThe binding activity of HS mimetics to lipoprotein lipase should be investigated as an additional pharmacological effect during heparanase inhibitor drug discovery. This study also provides novel evidence for an increased risk of drug‐induced liver injury in obese individuals.
A rift‐scale view at strain partitioning during multiphase rifting: Insights from the Hailar Basin, northeast Asia
Authors: Wu Lulu , Shen Chuanbo , Paton Douglas A. , Hou Yanping , Mortimer Estelle J. , Mei Lianfu , Sun Rongyao , Zeng Xiaowei , Shi Guanzhong 
Published: February 2023

AbstractThe spatial strain variations while continental lithospheric extension progresses and leads to either a failed rift basin or a fully rifted passive margins have been extensively studied. However, determining the spatial kinematics of rift basins throughout their entire temporal evolution at rift scale is often difficult due to the sparsity of spatial data coverage; this limits our current understanding of rift evolution and our ability to ascertain the controlling factors on basin development. This study uses extensive high‐quality 2D and 3D seismic reflection data and borehole data from the Hailar Basin (northeast Asia) to investigate the spatial strain variations that occurred during multiphase rifting at both high resolution and rift scale. By coupling fault evolution and depocenter analysis, we demonstrate that the Hailar Basin experienced complex strain partitioning with a progressively eastward migration of strain and eventual strain localization onto rift axis. This strain localization occurred in the area that had been dominated by syn‐rift sagging. We propose that the observed eastward strain migration has been driven by the multiphase rollback of the Paleo‐Pacific slab. Contrastingly, during the final rift phase, crustal rheology played the dominant role in rift development, while the influence of geodynamic processes significantly decreased, resulting in the cessation of the eastward rift migration and the ultimate strain localization. This pattern of strain migration and localization is likely to be applicable to other multiphase rifts where the main controlling factors varied through time.
Autological platelet‐rich fibrin sealant for anterior horseshoe anal fistula in female patient: A video vignette
Authors: Churina Yuliya , Tsugulya Petr , Vasilyev Alexandr , Medkova Yulia , Tsarkov Petr 
Published: February 2023

AbstractIntroductionNowadays many techniques have been developed for the treatment of complex anorectal fistulas. Biological substances are used for minimally invasive treatment of anorectal fistulas, especially for complex anal fistulas. Insertion of autological fibrin substance into the fistula tract is one of the types of such procedures.Clinical caseHere, we present a case of insertion of platelet‐rich fibrin sealant into a horseshoe fistula in a female patient. The follow‐up period was 10 months with no signs of clinical or MRI recurrence.
Cannabis use and gastrointestinal tract illnesses: The National Health and Nutrition Examination Surveys, 2005–2018
Authors: Vanderziel Alyssa , Alshaarawy Omayma 
Published: February 2023

AbstractIntroductionThe antiemetic properties of cannabis have motivated its use in the management of chemotherapy‐induced nausea and vomiting. Conversely, case reports of intractable vomiting among heavy cannabis users have increasingly appeared in the literature. Studies on cannabis and gastrointestinal tract (GIT) health are scare. Here, we use data for the National Health and Nutrition Examination Surveys (NHANES, 2005–2018) to estimate the association between cannabis use and GIT illness.MethodsThe study sample included non‐pregnant adult NHANES participants (20–59 years) without history of cancer or HIV (n = 18,753). Cannabis use was categorised into never, former (0 day in the past 30 days), infrequent (1–2 days), occasional (3–19 days) and frequent (20–30 days) use. Recent GIT illness was defined as experiencing GIT illness with vomiting or diarrhoea that started in the 30 days prior to NHANES. Logistic regression was used to regress GIT illness on cannabis use, adjusting for potential confounders.ResultsCompared to never use, frequent cannabis use was associated with higher odds of GIT illness (OR = 1.4; 95% confidence interval 1.04, 1.9). There were no associations between former, infrequent or occasional cannabis use and GIT illness.Discussion and ConclusionsFrequent cannabis use is associated with GIT illnesses in a large cross‐sectional study of US residents. It is possible that frequent cannabis use adversely affects GIT health, consistent with clinical case reports. Alternatively, patients with GIT illness might self‐medicate with cannabis given its antiemetic properties. Prospective studies are needed to understand the effects of cannabis use on GIT health.