bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region
Authors: Wang Kai‐Di , Zhu Miao‐Lin , Qin Cheng‐Jiao , Dong Rui‐Fang , Xiao Cheng‐Mei , Lin Qing , Wei Rong‐Yuan , He Xiao‐Yu , Zang Xin , Kong Ling‐Yi , Xia Yuan‐Zheng 
Published: July 2023

AbstractBackground and PurposeOsteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG's actions in osteosarcoma remain elusive, necessitating further elucidation.Experimental ApproachSingle‐stranded DNA‐binding protein 1 (SSBP1) was screened out by differential proteomic analysis. Apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial changes were assessed via flow cytometry. Western blotting and quantitative real‐time reverse transcription PCR (qRT‐PCR) were used to determine protein and gene levels. The antitumour mechanism of SNG was explored at a molecular level using chromatin immunoprecipitation (ChIP) and dual luciferase reporter plasmids.Key ResultsOur investigation revealed that SNG exerted an up‐regulated effect on SSBP1, disrupting mitochondrial function and inducing apoptosis. In‐depth analysis uncovered a mechanism whereby SNG hindered the JAK/signal transducer and activator of transcription 3 (STAT3) signalling pathway, relieved the inhibitory effect of STAT3 on SSBP1 transcription, and inhibited the downstream PI3K/Akt/mTOR signalling axis, ultimately activating apoptosis.Conclusions and ImplicationsThe study delved further into elucidating the anticancer mechanism of SNG in osteosarcoma. Notably, we unravelled the previously undisclosed apoptotic potential of SSBP1 in osteosarcoma cells. This finding holds substantial promise in advancing the development of novel anticancer drugs and identification of therapeutic targets.
Towards an emotional geoeconomics? Masculinity and emotions among Mexican and Guatemalan temporary agricultural workers in Quebec
Authors: Campos‐Flores Linamar , Martin Patricia M. 
Published: July 2023

AbstractThis article explores the emotional geographies underpinning the experiences of temporary agricultural workers who migrate yearly to fields of labour in Canada. The research is based on a transnational qualitative study in Quebec, Mexico, and Guatemala. To provide a theoretical framework for this article, we bring the concepts of geoeconomics and geographies of emotion into conversation. We then briefly present the history and evolution of temporary agricultural work, highlighting its deeply racialized and gendered nature. We argue that the mobilization and interiorization of a particular form of masculinity and emotional expression are central to both the exploitation of workers and their acceptance of their working conditions. These forms of masculinity and emotional expression are tightly bound to the workers’ role as household providers. Workers demonstrate satisfaction and pride in fulfilling their roles while negotiating an ongoing fear of job loss if they do not comply with work expectations. We argue that this represents a new form of subaltern masculinity that underpins Canadian geoeconomic strategy.
Electroacupuncture pretreatment preserves telomerase reverse transcriptase function and alleviates postoperative cognitive dysfunction by suppressing oxidative stress and neuroinflammation in aged mice
Authors: Wang Wei , Chen Chen , Wang Qiang , Ma Ji‐Guang , Li Yan‐Song , Guan Zheng , Wang Rui , Chen Xin 
Published: July 2023

AbstractBackgroundElderly patients often exhibit postoperative cognitive dysfunction (POCD), a postsurgical decline in memory and executive function. Oxidative stress and neuroinflammation, both pathological characteristics of the aged brain, contribute to this decline. This study posits that electroacupuncture (EA) stimulation, an effective antioxidant and anti‐inflammatory modality, may enhance telomerase reverse transcriptase (TERT) function, the catalytic subunit of telomerase known for its protective properties against cellular senescence and oxidative damage, to alleviate POCD in aged mice.MethodsThe animal POCD model was created by subjecting aged mice to abdominal surgery, followed by EA pretreatment at the Baihui acupoint (GV20). Postoperative cognitive function was gauged using the Morris water maze (MWM) test. Hippocampal TERT mRNA levels and telomerase activity were determined through qPCR and a Telomerase PCR ELISA kit, respectively. Oxidative stress was assessed through superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA) levels. Iba‐1 immunostaining determined the quantity of hippocampal microglia. Additionally, western blotting assessed TERT, autophagy markers, and proinflammatory cytokines at the protein level.ResultsAbdominal surgery in aged mice significantly decreased telomerase activity and TERT mRNA and protein levels, but increased oxidative stress and neuroinflammation and decreased autophagy in the hippocampus. EA‐pretreated mice demonstrated improved postoperative cognitive performance, enhanced telomerase activity, increased TERT protein expression, improved TERT mitochondrial localization, and reduced oxidative damage, autophagy dysfunction, and neuroinflammation. The neuroprotective benefits of EA pretreatment were diminished following TERT knockdown.ConclusionsOur findings underscore the significance of TERT function preservation in alleviating surgery‐induced oxidative stress and neuroinflammation in aged mice. A novel neuroprotective mechanism of EA stimulation is highlighted, whereby modulation of TERT and telomerase activity reduces oxidative damage and neuroinflammation. Consequently, maintaining TERT function via EA treatment could serve as an effective strategy for managing POCD in elderly patients.
A data‐driven approach to complement the A/T/(N) classification system using CSF biomarkers
Authors: Hernández‐Lorenzo Laura , Gil‐Moreno Maria José , Ortega‐Madueño Isabel , Cárdenas Maria Cruz , Diez‐Cirarda Maria , Delgado‐Álvarez Alfonso , Palacios‐Sarmiento Marta , Matias‐Guiu Jorge , Corrochano Silvia , Ayala José L. , Matias‐Guiu Jordi A. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: July 2023

AbstractAimsThe AT(N) classification system not only improved the biological characterization of Alzheimer's disease (AD) but also raised challenges for its clinical application. Unbiased, data‐driven techniques such as clustering may help optimize it, rendering informative categories on biomarkers' values.MethodsWe compared the diagnostic and prognostic abilities of CSF biomarkers clustering results against their AT(N) classification. We studied clinical (patients from our center) and research (Alzheimer's Disease Neuroimaging Initiative) cohorts. The studied CSF biomarkers included Aβ(1–42), Aβ(1–42)/Aβ(1–40) ratio, tTau, and pTau.ResultsThe optimal solution yielded three clusters in both cohorts, significantly different in diagnosis, AT(N) classification, values distribution, and survival. We defined these three CSF groups as (i) non‐defined or unrelated to AD, (ii) early stages and/or more delayed risk of conversion to dementia, and (iii) more severe cognitive impairment subjects with faster progression to dementia.ConclusionWe propose this data‐driven three‐group classification as a meaningful and straightforward approach to evaluating the risk of conversion to dementia, complementary to the AT(N) system classification.
The associations of sodium‐glucose cotransporter‐2 inhibitors versus dipeptidyl peptidase‐4 inhibitors as add‐on to metformin with fracture risk in patients with type 2 diabetes mellitus
Authors: van Hulten Veerle , Driessen Johanna H. M. , Starup‐Linde Jakob K. , Al‐Mashhadi Zheer K. , Viggers Rikke , Klungel Olaf H. , Souverein Patrick C. , Vestergaard Peter , Stehouwer Coen D. A. , van den Bergh Joop P. 
Published: July 2023

AbstractAimTo investigate whether sodium‐glucose cotransporter‐2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitor use as add‐on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs).MethodsA cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first‐ever prescription for a DPP‐4 inhibitor or an SGLT2 inhibitor as add‐on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP‐4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP‐4 inhibitor use.ResultsA total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP‐4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP‐4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91‐1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64‐1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age.ConclusionUse of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP‐4 inhibitor use.
Safety of sodium‐glucose co‐transporter‐2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes
Authors: Park Sohee , Jeong Han Eol , Bea Sungho , Yu Oriana H. Y. , Cho Young Min , You Seng Chan , Man Kenneth K. C. , Shin Ju‐Young 
Published: July 2023

AbstractAimTo assess the risk of amputation associated with sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU).Materials and MethodsWe conducted an active comparator, new‐user cohort study using Korea's nationwide claims data (2015‐2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase‐4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU‐, (3) CVD‐/DU+ and (4) CVD‐/DU‐. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models.ResultsWe identified 219 900 PS‐matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU‐, n = 26 092; CVD‐/DU+, n = 26 894; and CVD‐/DU‐, n = 155 195), with well‐balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14‐0.90), CVD+/DU‐ (0.45, 0.21‐0.99) and CVD‐/DU‐ (0.48, 0.33‐0.70), but not in CVD‐/DU+ (0.54, 0.26‐1.12). Consistent trends in estimates were found across various sensitivity analyses.ConclusionsInitiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high‐risk patients with type 2 diabetes.
Handedness effects on imagery of dominant‐ versus non‐dominant‐hand movements: An electroencephalographic investigation
Authors: Lambert Kathryn J. M. , Chen Yvonne Y. , Donoff Christopher , Elke Jonah , Madan Christopher R. , Singhal Anthony 
Published: July 2023

AbstractMental representations of our bodies are thought to influence how we interact with our surroundings. We can examine these mental representations through motor imagery, the imagination of movement using scalp EEG recordings. The visual modality of motor imagery emphasises ‘seeing’ the imagined movement and is associated with increased activity in the alpha rhythm (8–14 Hz) measured over the occipital regions. The kinaesthetic modality emphasises ‘feeling’ the movement and is associated with decreased activity in the mu rhythm (8–14 Hz) measured over the sensorimotor cortices. These two modalities can be engaged in isolation or together. We recorded EEG activity while 37 participants (17 left‐hand dominant) completed an objective hand motor imagery task. Left‐handers exhibited significant activity differences between occipital and motor regions only during imagery of right‐hand (non‐dominant‐hand) movements. This difference was primarily driven by less oscillatory activity in the mu rhythm, which may reflect a shift in imagery strategy wherein participants placed more effort into generating the kinaesthetic sensations of non‐dominant‐hand imagery. Spatial features of 8–14 Hz activity generated from principal component analysis (PCA) provide further support for a strategy shift. Right‐handers also exhibited significant differences between alpha and mu activity during imagery of non‐dominant movements. However, this difference was not primarily driven by either rhythm, and no differences were observed in the group's PCA results. Together, these findings indicate that individuals imagine movement differently when it involves their dominant versus non‐dominant hand, and left‐handers may be more flexible in their motor imagery strategies.
Effect of current direction and muscle activation on motor cortex neuroplasticity induced by repetitive paired‐pulse transcranial magnetic stimulation
Authors: Sasaki Ryoki , Liao Wei‐Yeh , Opie George M. , Semmler John G. 
Published: July 2023

AbstractRepetitive paired‐pulse transcranial magnetic stimulation (TMS) at indirect (I)‐wave periodicity (iTMS) can increase plasticity in primary motor cortex (M1). Both TMS coil orientation and muscle activation can influence I‐wave activity, but it remains unclear how these factors influence M1 plasticity with iTMS. We therefore investigated the influence of TMS coil orientation and muscle activation on the response to iTMS. Thirty‐two young adults (24.2 ± 4.8 years) participated in three experiments. Each experiment included two sessions using a modified iTMS intervention with either a posterior–anterior orientation (PA) or anterior–posterior (AP) coil orientation over M1. Stimulation was applied in resting (Experiments 1 and 3) or active muscle (Experiments 2 and 3). Effects of iTMS on M1 excitability were assessed by recording motor evoked potentials (MEPs) and short‐interval intracortical facilitation (SICF) with PA and AP orientations in both resting (all experiments) and active (Experiment 2) muscle. For the resting intervention, MEPs were greater after AP iTMS (Experiment 1, P = .046), whereas SICF was comparable between interventions (all P > .10). For the active intervention, responses did not vary between PA and AP iTMS (Experiment 2, all P > .14), and muscle activation reduced the effect of AP iTMS during the intervention (Experiment 3, P = .002). Coil orientation influenced the MEP response after iTMS, and muscle activation reduced the response during iTMS. While this suggests that AP iTMS may be beneficial in producing a neuroplastic modulation of I‐wave circuits in resting muscle, further exploration of factors such as dosing is required.
Soil properties of vineyards on arkoses as a basis to understand their suitability and optimum performance
Authors: Jiménez‐Ballesta R. , Bravo S. , Pérez‐de‐los‐Reyes C. , Amorós J. A. , García‐Navarro F. J. 
Published: July 2023

AbstractThe study of the soil properties and geochemistry of vineyard soils of the Méntrida Protected Designation of Origin (PDO) (central Spain) was performed to better understand the role of soil as a terroir component and to contribute to sustainable vineyard management. Soil physico‐chemical characteristics were determined, along with the content of trace elements (by placing emphasis on rare earths) in topsoils and subsoils. The dominant soil types were Inceptisols, Alfisols and Entisols (USDA soil classificacion), i.e., Cambisols, Luvisols and Regosols in the World Reference Base for Soil Resources (WRB) system. They were all deep and well‐structured. Our findings reveal that soil‐available nitrogen (N) ranged from 0.03 to 0.21 (%), with soil‐available phosphorus (P) ranging from 0.20 to 40.50 (mg·kg−1). pH had a mean of 6.33 (range: 4.4–8.7) in the ten observations, and a degree of mesotrophic saturation in bases (V%), except in one that had a 100% value (soils where carbonates were absent, save exceptional cases). A medium to high cation exchange capacity (CEC) was found (range: 9.8–38.3 cmol·kg−1). The mean values of elements' contents were (mg·kg−1): Sc 14.8, V 32.13, Cr 23.09, As 4.01, Ni 8.57, Cu 6.43, Zn 30.13, Rb 143.49, Sr 63.03, Y 15.39, Ba 374,44, La 25.87, Ce 43.77, Pb 22.25, Nd 21.28. They decreased in this order: Ba > Rb > Sr > Ce > V > Zn > La > Cr > Pb > Nd > Y > Sc > Cu > As. The results confirm the importance of soils for the PDO, with an optimum condition to produce grapevine quality laying the foundations to obtain a good wine. Our findings provide insights into the importance of pedological properties for regulating soil nutrient availability across soil types, and support soil resource utilization management in regional viticulture.
Stalevo®: A pioneering treatment for OFF periods in Parkinsons disease
Authors: Jenner Peter 
Published: July 2023

AbstractEnzymatic metabolism is the key determinant of the overall bioavailability, brain penetration, and efficacy of levodopa in the treatment of Parkinsons disease (PD). Enzyme inhibitors in the form of peripheral dopa‐decarboxylase inhibitors and monoamine oxidase type‐B inhibitors have been successfully employed to maximize the utility of levodopa in both early‐ and late‐stage PD. However, another major pathway of the peripheral metabolism of levodopa through catechol‐O‐methyltransferase (COMT) remains unchecked by those measures. Consequently, this becomes a major factor in determining the extent of delivery to the brain. The introduction of tolcapone as a potent and effective peripheral and central COMT inhibitor was frustrated by the emergence of hepatic toxicity. Only with the subsequent introduction of entacapone as an effective inhibitor of peripheral COMT activity has it become possible to fully control the peripheral metabolism of levodopa and to optimize its delivery to the brain. At a single‐dose level of 200 mg, the efficacy of entacapone in reducing OFF time and increasing ON time has led to its widespread use for the treatment of "wearing off". To maximize the efficacy of entacapone and to time‐lock its pharmacokinetic profile to that of levodopa, a triple combination of levodopa, carbidopa, and entacapone in the form of Stalevo® that allowed for flexibility in levodopa dosing was introduced early in the 21st century. This pioneering development has been successfully used worldwide for the past 20 years. This review considers the role of all three classes of enzyme inhibitors in PD medicine.
Wrist‐worn smartwatch and predictive models for seizures
Authors: Pipatpratarnporn Waroth , Muangthong Wichuta , Jirasakuldej Suda , Limotai Chusak 
Published: July 2023

AbstractObjectiveThis study was undertaken to describe extracerebral biosignal characteristics of overall and various seizure types as compared with baseline physical activities using multimodal devices (Empatica E4); develop predictive models for overall and each seizure type; and assess diagnostic performance of each model.MethodsWe prospectively recruited patients with focal epilepsy who were admitted to the epilepsy monitoring unit for presurgical evaluation during January to December 2020. All study participants were simultaneously applied gold standard long‐term video‐electroencephalographic (EEG) monitoring and an index test, E4. Two certified epileptologists independently determined whether captured events were seizures and then indicated ictal semiology and EEG information. Both were blind to multimodal biosignal findings detected by E4. Biosignals during 5‐min epochs of both seizure events and baseline were collected and compared. Predictive models for occurrence overall and of each seizure type were developed using a generalized estimating equation. Diagnostic performance of each model was then assessed.ResultsThirty patients had events recorded and were recruited for analysis. One hundred eight seizure events and 120 baseline epochs were collected. Heart rate (HR), acceleration (ACC), and electrodermal activity (EDA) but not temperature were significantly elevated during seizures. Cluster analysis showed trends of greatest elevation of HR and ACC in bilateral tonic–clonic seizures (BTCs), as compared with non‐BTCs and isolated auras. HR and ACC were independent predictors for overall seizure types, BTCs, and non‐BTCs, whereas only HR was a predictor for isolated aura. Diagnostic performance including sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve of the predictive model for overall seizures were 77.78%, 60%, and .696 (95% confidence interval = .628–.764), respectively.SignificanceMultimodal extracerebral biosignals (HR, ACC, EDA) detected by a wrist‐worn smartwatch can help differentiate between epileptic seizures and normal physical activities. It would be worthwhile to implement our predictive algorithms in commercial seizure detection devices. However, larger studies to externally validate our predictive models are required.