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Reversible Isomerization of Stiff-Stilbene by an Oriented External Electric Field
Identifying factors that underpin student decisions to pursue the Doctor of Pharmacy degree at Atlantic Canadian Universities: Protocol for a mixed methods study
Several international studies have investigated academic decision-making in higher education, but there is limited research on students’ choice to study pharmacy in the Canadian context. While there is some variation across jurisdictions, decisions to enroll in a particular degree program fall into several decision-making domains (e.g., personal, family, institutional, social, and economic). These findings have been theorized in various ways, for example, through social cognitive theory and social reproduction theory. The purpose of this study is to gain a better understanding of the personal, family, institutional, social, and economic factors that underpin student decisions to pursue the Doctor of Pharmacy (PharmD) degree at Atlantic Canadian Universities and to explore barriers to pursuing a pharmacy degree. The proposed study uses an explanatory sequential mixed-methods design consisting of a quantitative survey followed by qualitative interviews. All entry-to-practice PharmD students and graduates in Atlantic Canada are eligible to participate. The survey consists of several Likert scale questions associated with five decision-making domains, as well as several socio-demographic questions. Descriptive statistics and frequency counts will be used to describe the data; differences across decision-making domains, by gender and other demographic groupings, will be analyzed using inferential statistics. Semi-structured interviews with a sample of 12 to 15 participants will be conducted to further understand and explain the quantitative results. We will engage in thematic analysis of qualitative data. The findings of this research will provide insight into the decision-making patterns and socio-demographic characteristics of students who have chosen to pursue a PharmD. Important information will be gathered to inform health professional education and workforce planning, which we believe will contribute to improving healthcare resource capacity and patient outcomes in Atlantic Canada. The results of this project will also inform future recruitment strategies and admission criteria and support educators in the secondary school system in providing evidence-informed career counselling advice for students interested in pursuing a degree in pharmacy. The findings of this study may also be useful to educational leaders and policymakers.
Large Polarization Change Induced by Spin Crossover-Driven Fe(II) Ion Shuttling within a Tripodal Ligand
An anonymized, de-identified registry study protocol to determine the effectiveness and safety of weight loss with enavogliflozin in patients with type 2 diabetes mellitus
Sodium-glucose co-transporter 2 inhibitors, such as enavogliflozin, offer promising metabolic benefits for patients with type 2 diabetes (T2D), including glycemic control and improved cardiac function. Despite the clinical evidence, real-world evidence is needed to validate their safety and effectiveness. This study aims to evaluate the effects of weight loss and safety of enavogliflozin administration in patients with T2D in a real-world clinical setting over 24 weeks. This is a large-scale, prospective, multicenter, non-interventional observational study and will be conducted in 12 primary care centers nationwide between 2024 and 2026. Data will be collected at baseline, 12 weeks, and 24 weeks in a real-world clinical setting, including demographic details, clinical history, lifestyle habits, medication use, and various health indicators. Eligible participants are adults aged 19 to 80 with T2D and a body mass index (BMI) of ≥23 kg/m2 who are currently receiving treatment with Envlo (enavogliflozin) or Envlomet (enavogliflozin/metformin) tablets or planning to start treatment. The primary outcome is the change in BMI and body weight at 24 weeks from baseline. Secondary outcomes evaluated are changes in BMI and weight at 12 weeks, the proportion of participants achieving significant reductions in BMI and weight at 12 and 24 weeks, and body composition and glycemic improvements at 12 and 24 weeks. The study will analyze shifts in lipid profiles, liver and kidney functions, and body composition at 12 and 24 weeks as exploratory outcomes. For safety outcomes, the trial will prioritize the monitoring of adverse drug reactions and specific events of interest such as hypoglycemia, urinary tract infections, genital infections, polyuria, and polydipsia. This study design enables us to evaluate the effectiveness and safety of enavogliflozin for weight loss in a real-world setting while exploring its potential positive effects on cardiac function and metabolic risk factors in overweight or obese patients with T2D.
Advancing the Mechanosensitivity of Atropisomeric Diarylethene Mechanophores through a Lever-Arm Effect
Creatine kinase and neuromuscular fatigue responses following differing spells of simulated cricket fast bowling
The fast-bowling action demands repetitive high-intensity whole body movements, imposing complex physical and perceptual demands on players that vary significantly throughout the season. This study aimed to assess and establish practical methods and metrics for quantifying fatigue after four simulated fast bowling spells. Eleven senior club male fast bowlers (age 27.3 ± 7.0 y; body mass 83.7 ± 11.6 kg; height 1.80 ± 0.06 m) completed four different bouts of the modified Cricket Australia-Australian Institute of Sport bowling skills test over consecutive weeks. Neuromuscular function (countermovement jump [CMJ]) and creatine kinase (CK) levels were assessed at baseline, immediately post- (+0 h), and +24 h post-simulation. Perceptual measures (session rating of perceived exertion [sRPE]) and well-being were recorded pre and post fast-bowling simulations, with physical demands (PlayerLoad™) recorded throughout each simulation. Significant reductions in CMJ height were observed at +0 hours (t = 9.789, P < 0.01, d = 0.50) and +24 hours post-simulation (t = 4.051, P < 0.01, d = 0.21) compared to baseline. Moderate correlations were found between deliveries bowled (r = 0.48, P < 0.01), simulation duration (r = 0.49, P < 0.01), PlayerLoad™ (r = 0.41, P < 0.01), sRPE (r = 0.48, P < 0.01), and the change in CK concentration at +24 hours post-simulation. These findings suggest that lower-body neuromuscular function may be compromised following spells of fast bowing for up to 24 hours. Moreover, a ‘dose-response’ relationship was observed between the change in CK concentrations and PlayerLoad™, sRPE and number of deliveries bowled at +24 hours post-bowling spell. Coaches and support staff could use a combination of tools to monitor training and playing to enhance their ability to make informed decisions about a player’s readiness to perform.
Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Triflates with Alkyl Halides: Mechanism-Informed Design of More General Conditions
The climate impact and land use of cultivated meat: Evaluating agricultural feedstock production
As global demand for meat continues to rise, alternative and sustainable methods of production are being explored. Cultivated meat (CM) is one such alternative that holds potential for sustainable production with less environmental impact. This study develops an approach to evaluate CM production based on agricultural feedstock. The specific objectives are to determine the minimum land area required to produce a certain amount of cell medium–feedstock for CM production–on agricultural land and to identify potential future land use scenarios assuming that the macro components of the cell medium are solely produced from common agricultural crops in southern Germany. A linear programming model was developed to analyze four different scenarios of CM production, considering factors such as crop rotation, nutrient sourcing, and solar energy use. The results indicate that CM production using plants as raw material for the cell medium cannot improve land use efficiency substantially compared to conventional pork production. Extraction methods, crop choice, and energy sources will strongly influence future pathways for CM. We also find that there is no substantial benefit from CM in terms of climate change mitigation when feedstock is sourced solely from plants. This study provides valuable insights into the limitations of using agricultural feedstock for sustainable CM production. The findings suggest that future research should focus on optimizing the land use efficiency of CM. This includes exploring alternatives such as sourcing cell media from precision fermentation instead of relying solely on crops, and utilizing upcycling possibilities.
Molecular Design of Hole-Collecting Materials for Co-Deposition Processed Perovskite Solar Cells: A Tripodal Triazatruxene Derivative with Carboxylic Acid Groups
Self-acupressure for patients with breast cancer experiencing aromatase inhibitor-associated musculoskeletal symptoms: Protocol for the AcuAIM randomized pilot trial
Background Aromatase inhibitors (AI) reduce hormone receptor-positive breast cancer recurrence risk by about 50%. However, half of AI-treated postmenopausal women report new or worsened musculoskeletal symptoms (AIMSS), and 20% discontinue therapy prematurely. Acupuncture is effective for reducing symptoms, but many women are not able to access acupuncture therapy. We hypothesize that self-administered acupressure will reduce AIMSS. Materials and methods Postmenopausal women who have been receiving treatment with an AI for more than 3 weeks but less than 2 years, and who report new or worsened joint pain or myalgias since starting AI therapy with worst pain of at least 4 out of 10 on a numerical rating scale, are eligible. Fifty participants will be enrolled and randomized 1:1 to treatment with true or sham acupressure for 12 weeks. Participants will self-apply pressure for 3 minutes to each of the 9 acupoints daily. All participants will complete a pain assessment weekly, and a battery of symptom questionnaires every 6 weeks. Optional stool samples will be collected after 0 and 12 weeks of acupressure to examine changes in the gut microbiome. The primary endpoint is change in worst pain on the Brief Pain Inventory-Short Form with 12 weeks of the acupressure intervention, evaluated with generalized estimating equations. Conclusion Determination that self-administered acupressure reduces AIMSS in this randomized phase 2 pilot trial will lead to a larger randomized phase 3 clinical trial to confirm the efficacy of self-acupressure. Reduction of AI-related arthralgias may improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for AI-treated patients. Trial registration Clinicaltrials.gov NCT06228768.
Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters
Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed. Chimeric antigen receptor (CAR)-modified natural killer (NK) cells have demonstrated potent anti-tumor effects, making them as a promising immunotherapy strategy for cancer treatment. Glypican-3 (GPC3), a cell surface oncofetal glycoprotein, is highly expressed in most HCC tissues, but not in normal tissues, and functions as a key driver of carcinogenesis. Given its high expression level on the cell surface, GPC3 is considered as an attractive immunotherapy target for HCC. In this study, two GPC3-specific CAR-NK cells, NK92MI/HN3 and NK92MI/HS20, were established using NK92MI cells, a modified IL-2-independent NK cell line. These cell lines were engineered with third generation GPC3-specific CARs, and their activities were subsequently evaluated in the treatment of HCC. We found that NK92MI/HN3 cells, rather than NK92MI/HS20 cells, exhibited a significant cytotoxicity effect against GPC3+ HepG2 cells in vitro and efficiently suppressed tumor growth in a xenograft model using NSG mice. In addition, irradiated NK92MI/HN3 cells displayed similar anti-tumor efficacy to unirradiated NK92MI/HN3 cells. Furthermore, we observed that NK92MI/HN3 cells showed higher killing activity against the GPC3 isoform 2 overexpression cell line (Sk-Hep1-v2) than those with GPC3 isoform 1 overexpression cell line (Sk-Hep1-v1). This suggest that the presence of different GPC3 isoforms in HCC may impact the cytotoxicity activity of NK92MI/HN3 cells and potentially influence therapeutic outcomes. These findings highlight the effective anti-HCC effects of NK92MI/HN3 cells and reveal the role of GPC3 isoforms in influencing therapy outcomes, suggesting that isoform analysis should be considered to optimize CAR-NK therapies to improve patient outcomes.
Practitioner, patient and public views on the acceptability of mobile stroke units in England and Wales: A mixed methods study
Background Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation. Methods This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024. Survey data were collected from clinicians involved in emergency stroke care. Qualitative data involved clinical and non-clinical professionals involved in stroke care alongside patient and public representatives with experience of stroke. Survey data were descriptively analysed while content analysis was used on open-ended questions. Qualitative data were thematically analysed, prior to triangulation using a convergent coding matrix. Results The study results, drawn from 25 respondents to the survey and 21 participants in qualitative workshops, found that almost all participants had positive affective attitudes to the concept of MSUs. However, several key areas of concern were identified that need to be addressed prior to implementing MSUs. These concerns included how MSUs would be staffed; whether and how telemedicine could contribute; the types of economic impacts; extent to which triage systems could accurately identify stroke patients for MSUs to attend; where the base location and geographic coverage of MSUs should be, the impact of MSUs on equitable access to stroke care, and how to improve public awareness of MSUs. Conclusion Whilst MSUs are mostly acceptable to key stakeholders, numerous areas of concern need to be addressed prior to MSU implementation. We recommend further research to address these issues prior to implementation in the NHS.
Covalent Plant Natural Product that Potentiates Antitumor Immunity
In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study
Objective Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. 23Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain 23Na MRI. Methods 1H and 23Na brain MRI were collected prospectively from 28 ALS patients. Individual map of abnormal total sodium concentration (TSC) was computed using voxel-based statistical mapping for each patient compared to a local database of 62 healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), ALSFRS-R slope, ALSFRS-R at 6-month and survival time. Results Individual maps quantifying voxels with TSC increase evidenced a high heterogeneity between patients consistent with clinical presentation. The main areas involved were the corticospinal tracts. Half of patients showed abnormal TSC increase within more than 1% of whole brain voxels. Patients with TSC increase had worse clinical severity: higher ALSFRS-R slope (p = 0.02), lower ALSFRS-R at 6-month (p = 0.04), and shorter survival (p = 0.04). ALS patients with limited TSC increase had slower progression of disability or predominant lower motor neuron phenotype or shorter disease duration. Discussion This study mapping sodium homeostasis disturbances at the individual level in ALS patients through 23Na MRI evidenced heterogeneity of TSC increase among patients associated with clinical presentation and disease severity. These findings suggest that TSC increase detected at the individual level by 23Na MRI may be a useful marker of the clinical heterogeneity of ALS patients, a factor that is likely to greatly influence the results of therapeutic trials.
Light-Enabled Reversible Hydrogen Storage of Borohydrides Activated by Photogenerated Vacancies
AI enabled, mobile soil pH classification with colorimetric paper sensors for sustainable agriculture
For optimizing production yield while limiting negative environmental impact, sustainable agriculture benefits from real-time, on-the-spot chemical analysis of soil at low cost. Colorimetric paper sensors are ideal candidates, however, their automated readout and analysis in the field is needed. Using mobile technology for paper sensor readout could, in principle, enable the application of machine-learning models for transforming colorimetric data into threshold-based classes that represent chemical concentration. Such a classification method could provide a basis for soil management decisions where high-resolution lab analysis is not required or available. In tropical regions, where reliable soil data is difficult to acquire, this approach would be particularly useful. Here, we report a mobile chemical analysis system based on colorimetric paper sensors that operates under tropical field conditions. A standard smartphone equipped with a dedicated software application automatically classifies the paper sensor results into three classes—low, medium, or high soil pH—which provides a basis for soil correction. The classification task is performed by a machine-learning model which was trained on the colorimetric pH indicators deployed on the paper sensor. By mapping topsoil pH on a test site with an area of 9 hectares, the mobile system was benchmarked in the field against standard soil lab analysis. The mobile system has correctly classified soil pH in 97% of test cases, while reducing the analysis turnaround time from days (soil lab) to minutes (mobile). By performing on-the-spot analyses using the mobile system in the field, a 9-fold increase of spatial resolution reveals pH-variations not detectable in the standard compound mapping mode of lab analysis. We discuss how the mobile analysis can support smallholder farmers and enable sustainable agriculture practices by avoiding excessive soil correction. The system can be extended to perform multi-parameter chemical tests of soil nutrients for applications in environmental monitoring at marginal manufacturing cost.