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Department of Pharmacology

 

Discharge after coronary artery bypass grafting: A qualitative study highlighting the need for individualised, person-centred care

Recent Publications - Wed, 17/06/2026 - 11:00

PLoS One. 2026 Jun 17;21(6):e0349948. doi: 10.1371/journal.pone.0349948. eCollection 2026.

ABSTRACT

BACKGROUND: This study explores patient preparedness and support during discharge following coronary artery bypass graft (CABG) surgery. Despite the importance of effective discharge planning, many patients feel unprepared and unsupported, which can hinder recovery and increase readmission risk.

AIM: To examine patient experiences of the discharge process post-CABG, focusing on education received and perceptions of person-centred discharge planning.

METHODS: A qualitative study using constructivist grounded theory was conducted with eleven participants, interviewed 4-6 weeks post-surgery at a UK Northern NHS hospital. Semi-structured interviews were digitally recorded, transcribed, and analysed using a constant comparative method. Recruitment, data collection, and analysis occurred concurrently. Despite the modest sample size, the study achieved strong information power as the research aim was narrow and clearly focused on exploring the lived experiences of patients who had had a coronary artery bypass graft. This allowed for in-depth engagement with each participant, with relevant experience, enhancing the relevance and the richness of the data. Thematic saturation was observed early in the analysis, indicating that the data sufficiently addressed the research questions. The use of a rigorous analytical approach further ensured that the insights drawn were both meaningful and robust, supporting the adequacy of the sample size. The COREQ checklist guided reporting.

RESULTS: Four key themes emerged: Patients avoided seeking support or "making a fuss." Many felt unprepared for discharge. The information booklet was a valuable resource. Lack of post-discharge contact and continuity caused concern. Some participants reported insufficient pre-discharge information and unclear pathways for post-discharge support. The booklet was often the primary source of guidance. The participants' reluctance to seek support could reflect a pattern of self-management shaped by uncertainty, low confidence, a desire not to burden healthcare professionals or a belief that doctors know best. Yet many felt unprepared for discharge perhaps highlighting gaps in communication and discharge planning. There also seems a reliance on written materials, such as the information booklet. Limited post- discharge contact, created further anxiety, where patients were unsure where to turn for advice. These findings point to the need for clearer, more person‑centred discharge processes. Better communication, improved pre‑discharge education, and clear pathways for follow‑up support could strengthen patient confidence and safety. Although booklets are helpful, they should supplement and not replace ongoing contact and personalised guidance. Ensuring continuity of care and enabling patients to seek help without hesitation is essential for effective person‑centred discharge practice.

CONCLUSION: Findings highlight the importance of person-centred approaches in discharge planning. Tailored education and support could improve patient confidence and symptom management during recovery, potentially reducing readmission rates.

PMID:42308236 | DOI:10.1371/journal.pone.0349948

Surgical Versus Nonoperative Treatment for Adult Spinal Deformity: A Multicenter Propensity Score-Matched Study of 2-Year Patient-Reported Outcomes

Recent Publications - Tue, 16/06/2026 - 11:00

Spine (Phila Pa 1976). 2026 Jun 9. doi: 10.1097/BRS.0000000000005770. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective comparative study using prospectively collected data from a multicenter adult spinal deformity (ASD) registry across six centers, with propensity score (PS) matching to compare surgical versus nonoperative management.

OBJECTIVE: To compare 2-year patient-reported outcomes and serious adverse events after surgical versus nonoperative management of adult spinal deformity (ASD).

SUMMARY OF BACKGROUND DATA: Randomized trials comparing operative and nonoperative treatment for ASD are rarely feasible, and ASD presents heterogeneous clinical and radiographic features, complicating treatment decisions. Propensity score methods can reduce measured confounding and strengthen comparative effectiveness estimates from observational cohorts.

METHODS: Consecutive adults meeting radiographic criteria for ASD were identified from six participating centers. The primary endpoint was change in Oswestry Disability Index (ODI) at 2 years; secondary endpoints included SRS-22 outcomes. Propensity scores for surgery were estimated using logistic regression including age, sex, body mass index, major Cobb angle, pelvic incidence-lumbar lordosis mismatch, global tilt, pelvic tilt, baseline ODI, and SRS-22 total score. One-to-one nearest-neighbor matching (caliper 0.25) generated balanced pairs. Outcomes were compared within the matched cohort.

RESULTS: Among 764 screened patients, 580 were eligible (338 surgical; 242 nonoperative). Propensity score matching produced 160 well-balanced pairs (n=320). In the matched cohort, mean age was ~45 years in both groups. At 2 years, ODI improvement was greater after surgery than after nonoperative care (-19.4±14.2 vs. -4.2±12.3; P<0.001); 72% of surgical patients versus 29% of nonoperative patients achieved a clinically meaningful ODI improvement (≥15 points; P<0.001). SRS-22 outcomes favored surgery, including higher 2-year SRS-22 total score (3.95±0.67 vs. 3.46±0.75; P<0.0001) and a higher proportion achieving MCID for SRS-22 total score (81.3% vs. 36.9%; P<0.001).

CONCLUSION: In a multicenter PS-matched ASD cohort largely representing younger patients with mild-to-moderate baseline impairment, surgery was associated with superior 2-year disability and HRQoL outcomes compared with nonoperative care.

PMID:42302161 | DOI:10.1097/BRS.0000000000005770

Determinants of happiness among pregnant women in Bangladesh

Recent Publications - Fri, 12/06/2026 - 11:00

Acta Psychol (Amst). 2026 Jun 12;268:107235. doi: 10.1016/j.actpsy.2026.107235. Online ahead of print.

ABSTRACT

Maternal happiness, an important indicator of well-being, has also been linked to child stunting, child survival and other health outcomes. This study examined factors associated with happiness among 2,722 pregnant women in Bangladesh, using nationally representative data from the 2019 Multiple Indicator Cluster Survey. Chi-square tests were used to assess associations between happiness status and selected covariates, and survey-weighted ordinal logistic regression models were applied to identify potential predictors of happiness. Women's age, education level, functional difficulties, mobile phone ownership, and total number of children born were significantly associated with happiness among pregnant women. For instance, younger pregnant women aged 15-19 years were 2.54 times more likely to report being happy than those aged 35-49 years. Women with no education and those with only primary education were 55 and 50% less likely, respectively, to report happiness compared to those with secondary or higher education. Women without functional difficulties and those with no previous children also had significantly higher odds of reporting greater happiness than their counterparts. This study identified key factors influencing maternal happiness in Bangladesh. Addressing disparities in education, physical functioning, and access to resources such as mobile technology may enhance emotional well-being during pregnancy. Promoting maternal happiness is essential not only for improving individual quality of life, but also for advancing child health outcomes.

PMID:42284720 | DOI:10.1016/j.actpsy.2026.107235

DnaK unmasked: Potential contributions of intrinsic disorder to the hijacking of human proteostasis by a bacterial chaperone

Recent Publications - Thu, 11/06/2026 - 11:00

Int J Biol Macromol. 2026 Jun 11:153019. doi: 10.1016/j.ijbiomac.2026.153019. Online ahead of print.

ABSTRACT

Bacteria are abundantly present through the body, and the proteins they secrete into the cellular microenvironment both interact with surface receptors and are internalized and interact with internal proteins responsible for important pathways and functions. One of these proteins is DnaK, a moonlighting bacterial chaperone interacting with many human proteins. Intrinsically disordered regions (IDRs) enable structural flexibility essential for multifunctionality, yet their role in DnaK and its interactors remains unclear. Analyzing data from our previous studies of Mycoplasma DnaK and human protein interactions, this study is the first to employ computational analysis to assess disorder in bacterial DnaK, bacterial proteomes, and human interactors, aiming to elucidate novel disorder-mediated mechanisms of bacterial pathogenesis. Results indicate that bacterial chaperones, including DnaK, are expected to be significantly more disordered than the proteome averages (~27-42% chaperones are highly disordered vs. ~7-10% proteome-wide highly disordered proteins). Human proteins interacting with bacterial DnaK cluster in chromatin organization and RNA processing networks. DnaK interactors are significantly more disordered than human HSP70/HSC70 interactors, as well as average human proteins, nuclear proteins, and proteins involved in RNA processing and DNA repair. Confirmed interactors, such as XRCC1 and USP10, feature long IDRs with many PTMs, have multiple disorder-based binding regions, and show high LLPS propensity, suggesting that disorder facilitates cellular pathways subversion. These findings are consistent with a model, in which DnaK, by virtue of its structural flexibility, may preferentially engage disordered host proteins, potentially influencing cellular pathways, paving the way for a hypothesis that warrants direct experimental validation.

PMID:42276495 | DOI:10.1016/j.ijbiomac.2026.153019

Dual-beam differential optical imaging for atmospheric turbulence mitigation in free-space propagation

Recent Publications - Thu, 11/06/2026 - 11:00

Opt Express. 2026 May 18;34(10):17770-17793. doi: 10.1364/OE.584795.

ABSTRACT

Atmospheric turbulence imposes a fundamental barrier to reliable object detection in consumer-grade free-space optical (FSO) systems, degrading performance in applications such as drone navigation, smart surveillance, and portable satellite terminals. Current approaches, exemplified by the hybrid adversarial contrastive framework (HACF), operate in the post-acquisition domain, treating turbulence as irrecoverable stochastic noise and relying on statistical pseudo-label refinement to mitigate its effects. We introduce differential beam imaging (DBI), a physics-driven, acquisition-layer paradigm that transcends this limitation by physically isolating object reflectance at the moment of signal capture. DBI exploits the spatial correlation of atmospheric turbulence through simultaneous dual-beam probing; one beam illuminates the object, while an adjacent reference beam captures only the turbulence field. By differencing these measurements, DBI cancels turbulence at its source, preserving the object's structural integrity before any information loss occurs. We formalize and solve four non-incremental scientific problems: (P1) establishing the wave-optics-based spatial correlation regime for valid cancellation, (P2) optimizing beam separation under turbulence crosstalk trade-offs, (P3) designing a Siamese-cross attention network (SCAN) that learns turbulence-invariant features from differential image pairs, and (P4) co-designing a real-time, low-power (<1 W, <100 cm3) hardware-software stack for consumer deployment. Simulation-based validation demonstrates that DBI achieves a Turbulence Cancellation Efficiency (TCE) exceeding 2.3 and maintains a mean average precision (mAP) of 64.1 under moderate turbulence (Cn2=10-14 m-2/3), outperforming HACF by 35% in detection accuracy while operating at 30 FPS. This work establishes a new class of differential optical systems, shifting the paradigm from algorithmic robustness to physical-layer intelligence for robust perception in dynamic optical environments.

PMID:42271921 | DOI:10.1364/OE.584795

Solitons, bifurcation, chaos, and stability of the fractional Schrödinger-Hirota equation with beta derivative

Recent Publications - Wed, 10/06/2026 - 11:00

Sci Rep. 2026 Jun 10. doi: 10.1038/s41598-026-57123-y. Online ahead of print.

ABSTRACT

The fractional nonlinear Schrödinger-Hirota equation is a dynamic model for describing optical soliton propagation in dispersive fibers, capturing complex higher-order dispersion and fractional scaling effects. In this study, we investigate the underlying dynamics of this framework by incorporating the β-fractional derivative. By employing the extended Riccati scheme, we derive a broad spectrum of novel exact analytical solutions, including kink, dark, periodic, and mixed bright-dark soliton profiles. Beyond exact solutions, this work provides a qualitative assessment of the system's dynamics using planar dynamical system theory and bifurcation analysis to classify equilibrium states. Furthermore, the introduction of external periodic perturbations reveals a distinct transition from stable oscillatory motion to chaotic behavior. This chaotic transition is precisely quantified through Poincaré sections and the Lyapunov exponent, demonstrating the system's sensitivity to fractional scaling and perturbation parameters. Finally, linear stability analysis confirms the robustness and physical viability of the derived solitons under disruptive conditions. The results enrich the mathematical understanding of fractional nonlinear dynamics and provide valuable physical insights for optimizing stable, high-capacity optical fiber communication systems and next-generation photonic devices.

PMID:42270832 | DOI:10.1038/s41598-026-57123-y

Using a NanoBRET-Based Ligand-Binding Assay at the β<sub>2</sub>-Adrenoceptor for Undergraduate Pharmacology Education

Pharmacology Cambridge RSS Paper feed - Tue, 09/06/2026 - 11:00

Pharmacol Res Perspect. 2026 Jun;14(3):e70275. doi: 10.1002/prp2.70275.

ABSTRACT

The teaching of pharmacology includes a fundamental understanding of ligand binding; how it is measured and how it is calculated. We sought to modernize the techniques by which ligand affinity is determined by undergraduate students and introduce them to parameter estimation through curve fitting. We taught a NanoBRET ligand binding assay to student cohorts completing their second year of undergraduate study in Natural Sciences (71 and 61 students in 2024 and 2025 respectively). The aim was to measure the affinity of fluorescent and unlabeled ligands for the β2-adrenoceptor in live cells. Affinities were then calculated from their data using a custom Microsoft Excel spreadsheet. This series of practical classes was well received by students, with most students able to follow the protocol and successfully determine ligand affinities. Furthermore, students recognized the benefit of the practical class for their education, confirming they felt it improved their understanding of how ligand affinity is calculated. We also demonstrated that this protocol could be scaled up to accommodate larger class sizes (class of 367 students studying medicine and veterinary sciences).

PMID:42262233 | DOI:10.1002/prp2.70275

Using a NanoBRET-Based Ligand-Binding Assay at the β<sub>2</sub>-Adrenoceptor for Undergraduate Pharmacology Education

Recent Publications - Tue, 09/06/2026 - 11:00

Pharmacol Res Perspect. 2026 Jun;14(3):e70275. doi: 10.1002/prp2.70275.

ABSTRACT

The teaching of pharmacology includes a fundamental understanding of ligand binding; how it is measured and how it is calculated. We sought to modernize the techniques by which ligand affinity is determined by undergraduate students and introduce them to parameter estimation through curve fitting. We taught a NanoBRET ligand binding assay to student cohorts completing their second year of undergraduate study in Natural Sciences (71 and 61 students in 2024 and 2025 respectively). The aim was to measure the affinity of fluorescent and unlabeled ligands for the β2-adrenoceptor in live cells. Affinities were then calculated from their data using a custom Microsoft Excel spreadsheet. This series of practical classes was well received by students, with most students able to follow the protocol and successfully determine ligand affinities. Furthermore, students recognized the benefit of the practical class for their education, confirming they felt it improved their understanding of how ligand affinity is calculated. We also demonstrated that this protocol could be scaled up to accommodate larger class sizes (class of 367 students studying medicine and veterinary sciences).

PMID:42262233 | DOI:10.1002/prp2.70275

Potential Lactic Acid Bacteria Characterized From the Gastrointestinal Tract of Butter Catfish, <em>Ompok pabda</em> for Implying as Probiotics in Aquaculture

Recent Publications - Mon, 08/06/2026 - 11:00

Int J Microbiol. 2026 Jun 1;2026:8825568. doi: 10.1155/ijm/8825568. eCollection 2026.

ABSTRACT

Probiotics derived from an identical host's gastrointestinal (GI) system confer superior colonization and provide greater benefits than other commercial sources. This study reports on the probiotic potentials of lactic acid bacteria (LAB) identified from the gut content of Ompok pabda through morphological, physiological, and molecular sequencing for their usefulness in aquaculture. Molecular sequencing confirmed two LAB strains affiliated with the genus Weissella; namely Weissella confusa OPL2 and Weissella cibaria OPL3. Each strain was evaluated for its capability to withstand conditions relevant to feed application and gastrointestinal survival, including fluctuations in temperature, NaCl concentration, pH, and gut bile. Both strains consistently tolerated acidic pH (pH 2-5), bile concentration up to 7.5%, elevated temperature (4°C-45°C), and salt concentration (3%-6%). In addition, the strains demonstrated strong cell-surface properties, including higher hydrophobicity with time (68.77 ± 0.17% to 69.36 ± 0.41% in xylene, 65.62 ± 0.48% to 67.73 ± 0.36% in toluene), pronounced autoaggregation capacity (64.15 ± 0.35% and 64.12 ± 0.53%), notable coaggregation rates of 52.79 ± 2.15% and 53.05 ± 0.35% with Bacillus aerius, and 50.11 ± 0.16% and 49.51 ± 0.81% with Staphylococcus epidermidis, for W. cibaria OPL3 and W. confusa OPL2, respectively. Furthermore, the strains showed marked in vitro antagonism against Aeromonas veronii OPP8 and Plesiomonas shigelloides OPP9. Safety assessment further supported their suitability as probiotics, as they were found nonhemolytic in nature, as well as susceptible to several commonly used antibiotics. Therefore, the findings indicate W. cibaria OPL3 and W. confusa OPL2 as a safe and promising probiotic candidate from O. pabda with clear probiotic potentials in the aquaculture industry.

PMID:42256051 | PMC:PMC13238506 | DOI:10.1155/ijm/8825568

Pediatric Risk Mapping From Co-Exposure to Extreme Temperatures and Air Pollutants

Recent Publications - Mon, 08/06/2026 - 11:00

Geohealth. 2026 May 30;10(6):e2025GH001743. doi: 10.1029/2025GH001743. eCollection 2026 Jun.

ABSTRACT

Exposure to extreme temperatures and fine particulate matter is hazardous to human health, especially among children. With growing evidence on the impact of these environmental hazards on child health-including increased risks of respiratory illnesses, heat-related illnesses, and developmental challenges-there is a substantial need to identify high-risk areas for potential adverse pediatric health outcomes. In this study, we developed pediatric vulnerability indices at the census tract scale across the contiguous United States (CONUS) using five dimensionality reduction methods, including unsupervised machine learning and deep learning approaches. We integrated these indices with data on extreme temperature (2012-2024), PM2.5, and black carbon exposures from 2010 to 2020, enabling spatial analysis of environmental hazards and pediatric vulnerability. Among the five methods tested, principal component analysis (PCA) was selected for its balanced representation of 12 vulnerability factors, which explained 23% of the variance in the data. We observed that co-exposure to extreme temperature and air pollutant exposures were highest in the West, Southwest, and certain parts of the South and Northeast. Approximately 36% of the CONUS showed statistically significant hotspots of co-exposures to higher temperatures and air pollutants, concentrated in the West, Northwest, and Southwest. High-risk areas for pediatric vulnerability and co-exposure to environmental hazards were identified in both urban and rural communities, including indigenous lands and agricultural regions. These findings can aid policymakers and public health officials as a preliminary resource in developing heat action plans and allocating cooling centers to protect children living in the most affected communities.

PMID:42255323 | PMC:PMC13239795 | DOI:10.1029/2025GH001743

Safety of Transcranial Direct Current Stimulation With a Programmable Ventriculoperitoneal Shunt: A Case Report

Recent Publications - Wed, 03/06/2026 - 11:00

J ECT. 2026 Jun 3. doi: 10.1097/YCT.0000000000001294. Online ahead of print.

ABSTRACT

Disorders of consciousness (DoC) following severe brain injury have limited therapeutic options. Noninvasive brain stimulation (NIBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has shown promise in improving consciousness. However, the use of NIBS in patients with programmable ventriculoperitoneal (VP) shunt valves poses unique challenges, as these devices are susceptible to electromagnetic interference. While TMS may alter valve settings or induce heating, the safety of tDCS in such patients remains largely unexplored. We report the feasibility and safety of high-definition tDCS (HD-tDCS) in a 9-year-old girl with a minimally conscious state following severe traumatic brain injury and an implanted programmable VP shunt. Stimulation targeting the left dorsolateral prefrontal cortex was delivered using a neuronavigation-guided montage optimized through computational modeling. Sessions were conducted with continuous clinical monitoring and serial imaging to assess valve pressure. The patient completed 15 sessions with gradual titration of current intensity up to 1 mA. No major adverse events were observed. Serial imaging confirmed stable VP shunt position and pressure settings throughout the intervention. Although no significant change was noted in Coma Recovery Scale-Revised scores, subtle clinical improvements were observed, including increased spontaneous movements, improved muscle tone, enhanced eye movements, and intermittent responsiveness to environmental stimuli. This case highlights the potential safety and feasibility of HD-tDCS in patients with programmable VP shunts. tDCS may represent a viable neuromodulatory alternative when TMS is contraindicated, warranting further systematic investigation.

PMID:42233486 | DOI:10.1097/YCT.0000000000001294

Explosive nucleation and growth of Pb islands on Ge(111) below room temperature via collective diffusion

Recent Publications - Tue, 02/06/2026 - 11:00

J Phys Condens Matter. 2026 Jun 2. doi: 10.1088/1361-648X/ae76a9. Online ahead of print.

ABSTRACT

Nucleation is a fundamental process in nature controlling phase transitions and pattern formation. Classical nucleation is based on the gradual aggregation of diffusing atoms after a critical cluster size is reached. Contrary to these expectations, we have observed in real time the formation of perfect Pb(111) islands with more than 105atoms emerging out of the compressed wetting layer within a few seconds during growth of Pb on Ge(111) below room temperature. Pb deposited on Ge(111) in a temperature range between -30°C and 10°C exhibited explosive nucleation of height-selected islands upon reaching a critical coverage of 1.33±0.07ML with respect to Ge(111). Island nucleation was fueled by the 2% compression of the Pb wetting layer at the critical coverage. The island areas grew linearly with time, exhibiting collective diffusion, where thousands of atoms follow correlated, non-random walk diffusion. The total growth rate was higher with increasing temperature. Density functional theory simulations of the chemical potential and binding sites of the Pb/Ge(111) system give insight into the role of the compression of the wetting layer and the strain within the growing Pb layers, which explain this nonclassical behavior of the system.

PMID:42229502 | DOI:10.1088/1361-648X/ae76a9

Evaluating 7‑Aminopyrazolo[4,3‑<em>d</em>]pyrimidines as Human A<sub>1</sub> and A<sub>3</sub> Adenosine Receptor Antagonists

Pharmacology Cambridge RSS Paper feed - Mon, 01/06/2026 - 11:00

ACS Omega. 2026 May 14;11(20):29623-29637. doi: 10.1021/acsomega.5c13024. eCollection 2026 May 26.

ABSTRACT

This study aimed to improve the adenosine receptor (AR) subtype selectivity of the previously reported 7-benzylamino-1-methyl-3-phenyl-pyrazolo-[3,4-d]-pyridazine analogue PPZ I, a nanomolar dual nonselective adenosine hA1/hA3 receptor antagonist (Ki = 11 nM hA1R/13 nM hA3R). To this end, 31 novel derivatives bearing the pyrazolo-[4,3-d]-pyrimidine scaffold were designed and synthesized, incorporating either 7-benzylamino or 7-phenylamino substituents. Binding affinities were determined using a bioluminescence resonance energy transfer assay against hA1R and hA3R, alongside functional characterization of antagonistic activity and selectivity across all four AR subtypes. These studies identified compounds 9 and 40 as the most promising derivatives in the series. Compound 9 exhibited approximately 4-fold selectivity for hA1R over hA3R, whereas compound 40 showed a 10-fold preference for hA3R over hA1R. Both compounds displayed low-affinity binding to the two hA2R subtypes, which was more significant against hA2AR. Overall, compounds 9 and 40 exhibited up to 3- and 6-fold selectivity for hA1R and hA3R, respectively, over the other hAR subtypes. Studies of the binding profile of 9 and 40 inside the orthosteric binding site of hA1R and hA3R showed that the pyrazole ring forming hydrogen bonding interactions with N6.55 was complemented using molecular dynamics simulations and relative binding free energy calculations and validated through site-directed mutagenesis. The findings of this study will lead to the design and synthesis of more effective compounds against hARs that may have a therapeutic effect against human diseases, such as glaucoma and asthma.

PMID:42222808 | PMC:PMC13216935 | DOI:10.1021/acsomega.5c13024

Evaluating 7‑Aminopyrazolo[4,3‑<em>d</em>]pyrimidines as Human A<sub>1</sub> and A<sub>3</sub> Adenosine Receptor Antagonists

Recent Publications - Mon, 01/06/2026 - 11:00

ACS Omega. 2026 May 14;11(20):29623-29637. doi: 10.1021/acsomega.5c13024. eCollection 2026 May 26.

ABSTRACT

This study aimed to improve the adenosine receptor (AR) subtype selectivity of the previously reported 7-benzylamino-1-methyl-3-phenyl-pyrazolo-[3,4-d]-pyridazine analogue PPZ I, a nanomolar dual nonselective adenosine hA1/hA3 receptor antagonist (Ki = 11 nM hA1R/13 nM hA3R). To this end, 31 novel derivatives bearing the pyrazolo-[4,3-d]-pyrimidine scaffold were designed and synthesized, incorporating either 7-benzylamino or 7-phenylamino substituents. Binding affinities were determined using a bioluminescence resonance energy transfer assay against hA1R and hA3R, alongside functional characterization of antagonistic activity and selectivity across all four AR subtypes. These studies identified compounds 9 and 40 as the most promising derivatives in the series. Compound 9 exhibited approximately 4-fold selectivity for hA1R over hA3R, whereas compound 40 showed a 10-fold preference for hA3R over hA1R. Both compounds displayed low-affinity binding to the two hA2R subtypes, which was more significant against hA2AR. Overall, compounds 9 and 40 exhibited up to 3- and 6-fold selectivity for hA1R and hA3R, respectively, over the other hAR subtypes. Studies of the binding profile of 9 and 40 inside the orthosteric binding site of hA1R and hA3R showed that the pyrazole ring forming hydrogen bonding interactions with N6.55 was complemented using molecular dynamics simulations and relative binding free energy calculations and validated through site-directed mutagenesis. The findings of this study will lead to the design and synthesis of more effective compounds against hARs that may have a therapeutic effect against human diseases, such as glaucoma and asthma.

PMID:42222808 | PMC:PMC13216935 | DOI:10.1021/acsomega.5c13024

Association between prescribed antidepressant medication and skin cancer (melanoma, basal cell carcinoma and cutaneous squamous cell carcinoma) risk: a systematic review and meta-analysis

Recent Publications - Mon, 01/06/2026 - 11:00

Skin Health Dis. 2026 Apr 17;6(3):232-241. doi: 10.1093/skinhd/vzag028. eCollection 2026 Jun.

ABSTRACT

BACKGROUND: Certain antidepressants act as photosensitizers and may affect skin cancer risk; however, no evidence synthesis has been conducted. With the rising global incidence of skin cancer and widespread antidepressant use, clarifying any potential association is essential for public health.

OBJECTIVES: To assess the association between prescribed antidepressants and skin cancer (basal cell carcinoma, cutaneous squamous cell carcinoma and melanoma) risk.

METHODS: The protocol was registered on PROSPERO. MEDLINE and Embase were searched on 5 October 2025. Titles, abstracts and full texts were screened, and the methodologies appraised by two independent reviewers. The Mantel-Haenszel method (random-effects model) was applied to pool odds ratios (ORs), and the inverse variance method was used for rate ratios (RRs); heterogeneity was assessed using I 2. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework assessed the certainty of evidence. Subgroup analyses included a comparison of skin cancer risk between selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs.

RESULTS: Ten studies were included, five of which contributed to the meta-analysis. The association between antidepressant use and skin cancer risk was not statistically significant [RR 0.83, 95% confidence interval (CI) 0.60-1.16 (P = 0.28, I 2 = 87%); OR 0.93, 95% CI 0.85-1.02 (P = 0.12, I 2 = 69%)]. The subgroup analysis results for those who did and did not use SSRIs were similar and showed no statistically significant associations with skin cancer risk. The certainty of evidence was very low.

CONCLUSIONS: No statistically significant association was found between antidepressant use and skin cancer risk. Further high-quality research considering important confounders such as skin type, skin cancer type, sun exposure-related behaviour and sufficient follow-up is needed to confirm these findings.

PMID:42222680 | PMC:PMC13220031 | DOI:10.1093/skinhd/vzag028

The heart's fibrous web: A bibliometric analysis of cardiac fibrosis in Asia and Oceania

Recent Publications - Sat, 30/05/2026 - 11:00

Medicine (Baltimore). 2026 May 29;105(22):e49017. doi: 10.1097/MD.0000000000049017.

ABSTRACT

BACKGROUND: Cardiac fibrosis is a pathophysiologic condition in heart diseases. It refers to an excess deposition of extracellular matrix, which will cause hardening and stiffness in heart tissues, leading to heart failure. By considering the high prevalence of cardiac fibrosis globally, a bibliometric analysis is conducted to elucidate the research trend involving the unique perspectives in both the Asia and Oceania regions.

METHODS: Data were retrieved from the Scopus database without restrictions on publication year. Documents related to cardiac fibrosis affiliated with countries in Asia and Oceania were identified using the United Nations geoscheme classifications. The dataset was curated using biblioMagika and OpenRefine. Then, bibliometric mapping was conducted using VOSviewer to analyze co-authorship and keyword co-occurrence networks.

RESULTS: A total of 983 publications were identified from 1985 to 2025, with a marked increase in research output from 2010 onwards. China emerged as the leading contributor in terms of productivity and total citations, while Australia showed the highest citation impact per publication. High-impact institutions and authors were identified, and core themes included molecular mechanisms such as transforming growth factor beta signaling, extracellular matrix remodeling, and noncoding RNAs.

CONCLUSION: This study is the first to systematically examine cardiac fibrosis research output across Asia and Oceania using bibliometric methods. It contributes novel insights into the regional dynamics, intellectual structure, and emerging priorities within the field. By identifying key actors, collaboration networks, and knowledge gaps, this research provides valuable guidance for scholars, funding agencies, and policymakers to advance cardiac fibrosis research in regional and global contexts. However, reliance on citation-based metrics may introduce temporal bias, as older publications tend to accumulate more citations over time. Future studies should employ multi-database strategies, altmetric indicators, and machine learning approaches to address these limitations and capture a broader spectrum of research impact.

PMID:42216394 | DOI:10.1097/MD.0000000000049017

From Three to Eight Clusters: A Machine Learning-Based Classification of Operated Adult Spinal Deformity Patients

Recent Publications - Fri, 29/05/2026 - 11:00

Spine J. 2026 May 28:S1529-9430(26)00157-9. doi: 10.1016/j.spinee.2026.05.003. Online ahead of print.

ABSTRACT

BACKGROUND: Adult spinal deformity (ASD) is a heterogeneous condition encompassing diverse etiologies, clinical presentations, and surgical challenges. While previous unsupervised learning models have stratified ASD patients into three broad phenotypes, these often lack clinical granularity for surgical decision-making.

PURPOSE: To refine the classification of operated ASD patients using unsupervised machine learning and assess whether expanding from 3 to 8 clusters improves clinical discrimination and predictive robustness.

STUDY DESIGN: Retrospective multicenter study using machine learning clustering.

PATIENT SAMPLE: 471 adult patients who underwent surgery for ASD across six specialized spine centers.

OUTCOME MEASURES: ODI, SRS-22, spinal alignment metrics, surgical strategy, and postoperative complications.

METHODS: A k-means clustering algorithm was applied to a selected set of 12 demographic, radiographic, and functional variables (C12). Clustering solutions with 3 and 8 groups were compared. Each cluster was analyzed for age, etiology, disability scores (ODI, SRS-22), spinal alignment, surgical strategy, and complication rates. Predictive models using LDA and KNN assessed classification accuracy for new patient assignment.

RESULTS: The 8-cluster model identified clinically distinct phenotypes, including subgroups of young patients with idiopathic scoliosis, structural hyperkyphosis, and early sagittal decompensation. In elderly patients, clusters differentiated pain profiles, alignment, and frailty. The most severe clusters distinguished coronal-dominant versus sagittal collapse deformities, with differing risks and outcomes. LDA maintained robust accuracy (91.4%) in predicting cluster assignment across 50 testing splits, outperforming KNN.

CONCLUSIONS: To our knowledge, this is among the most granular unsupervised ML-based phenotypic classifications of operated ASD patients reported to date. This refined 8-cluster model enhances clinical phenotyping in ASD surgery, offering more precise subgroup stratification than traditional 3-cluster models. It supports the integration of unsupervised learning into personalized surgical planning, risk stratification, and multicenter outcome trials.

PMID:42214688 | DOI:10.1016/j.spinee.2026.05.003

Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65

Pharmacology Cambridge RSS Paper feed - Fri, 29/05/2026 - 11:00

JACS Au. 2026 Apr 20;6(5):2753-2765. doi: 10.1021/jacsau.6c00003. eCollection 2026 May 25.

ABSTRACT

Protein phosphatase 2A (PP2A), an important therapeutic target, comprises scaffold subunit PR65 composed of 15 HEAT (Huntingtin/Elongation/A-subunit/TOR1) repeats, a catalytic subunit, and one of many different regulatory subunits that enable binding to specific substrates. Recently, small molecule activators of PP2A (SMAPs) were identified, although their mechanisms of action have not yet been fully defined. Here, we explore the interaction of PR65 with two SMAPs, ATUX-8385 and the nonfunctional DBK-776, using single-molecule optical tweezers, ensemble methods, and computational analysis. In the absence of SMAP, PR65 shows multiple unfolding and refolding transitions, and the force-extension profiles are very heterogeneous with evidence of misfolding. Similar heterogeneity has been observed for the chemical-induced unfolding of tandem-repeat proteins like PR65, a consequence of the internal symmetry of the repeat architecture. In the presence of ATUX-8385, higher unfolding and refolding forces are observed throughout the structure and there is less misfolding, suggesting that ATUX-8385 acts like a pharmacological chaperone. In contrast, DBK-766-binding induces higher unfolding forces only for a few repeats of PR65, suggestive of a more localized effect; moreover, subsequent stretch-relax cycles show that PR65 is irreversibly locked in the unfolded state. Docking and molecular dynamics simulations provide insights into the distinctive responses of PR65 to mechanical stress in the presence of these two SMAPs: ATUX-8385 stably binds to a key site in the inner face of the PR65 structure, stabilizing a conformation predisposed to associate with the catalytic and regulatory subunits of PP2A. DBK-766, in contrast, exhibits a weaker binding to the outer face of PR65 and elicits relatively large conformational fluctuations in PR65 when bound to the compact form.

PMID:42212067 | PMC:PMC13213488 | DOI:10.1021/jacsau.6c00003

Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65

Recent Publications - Fri, 29/05/2026 - 11:00

JACS Au. 2026 Apr 20;6(5):2753-2765. doi: 10.1021/jacsau.6c00003. eCollection 2026 May 25.

ABSTRACT

Protein phosphatase 2A (PP2A), an important therapeutic target, comprises scaffold subunit PR65 composed of 15 HEAT (Huntingtin/Elongation/A-subunit/TOR1) repeats, a catalytic subunit, and one of many different regulatory subunits that enable binding to specific substrates. Recently, small molecule activators of PP2A (SMAPs) were identified, although their mechanisms of action have not yet been fully defined. Here, we explore the interaction of PR65 with two SMAPs, ATUX-8385 and the nonfunctional DBK-776, using single-molecule optical tweezers, ensemble methods, and computational analysis. In the absence of SMAP, PR65 shows multiple unfolding and refolding transitions, and the force-extension profiles are very heterogeneous with evidence of misfolding. Similar heterogeneity has been observed for the chemical-induced unfolding of tandem-repeat proteins like PR65, a consequence of the internal symmetry of the repeat architecture. In the presence of ATUX-8385, higher unfolding and refolding forces are observed throughout the structure and there is less misfolding, suggesting that ATUX-8385 acts like a pharmacological chaperone. In contrast, DBK-766-binding induces higher unfolding forces only for a few repeats of PR65, suggestive of a more localized effect; moreover, subsequent stretch-relax cycles show that PR65 is irreversibly locked in the unfolded state. Docking and molecular dynamics simulations provide insights into the distinctive responses of PR65 to mechanical stress in the presence of these two SMAPs: ATUX-8385 stably binds to a key site in the inner face of the PR65 structure, stabilizing a conformation predisposed to associate with the catalytic and regulatory subunits of PP2A. DBK-766, in contrast, exhibits a weaker binding to the outer face of PR65 and elicits relatively large conformational fluctuations in PR65 when bound to the compact form.

PMID:42212067 | PMC:PMC13213488 | DOI:10.1021/jacsau.6c00003

Short-term intravenous fluids for prevention of post-ERCP pancreatitis (the STRIPE study): protocol for a five-arm randomised controlled trial

Recent Publications - Wed, 27/05/2026 - 11:00

BMJ Open. 2026 May 27;16(5):e119154. doi: 10.1136/bmjopen-2026-119154.

ABSTRACT

INTRODUCTION: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a significant procedural adverse event (AE), occurring in 5-15% of cases and leading to substantial morbidity and mortality. Aggressive prolonged intravenous (IV) fluid regimens have demonstrated efficacy in reducing PEP in clinical trials. However, these regimens typically involve continuous infusion of IV fluids over 8-24 hours following ERCP, making them impractical for outpatient settings. Data on shorter hydration protocols are lacking. The STRIPE study aims to address this gap by evaluating short-term peri-procedural IV fluid regimens as a practical alternative for mitigating PEP.

METHODS AND ANALYSIS: This proof-of-concept, parallel-arm, randomised controlled trial will evaluate the impact of various short-term IV fluid regimens on post-ERCP serum amylase levels, a surrogate marker for PEP. Participants undergoing ERCP will be randomised into five groups, receiving 500 mL, 1000 mL, 1500 mL, 2000 mL or 2500 mL of IV Ringer's lactate during the peri-procedural period. Patients, endoscopists and outcome assessors will be blinded to treatment allocation during the peri-procedural period. The primary outcome is the serum amylase level 24 hours post-ERCP. Secondary outcomes include PEP, 30-day AEs and unplanned healthcare encounters including those related to volume overload or cardiovascular AEs, duration of hospitalisation (for inpatients), death within 30 days and other relevant laboratory markers at 24 hours. A total of 505 participants (101 in each arm) will be enrolled to ensure adequate power after accounting for attrition and/or sample loss.

ETHICS AND DISSEMINATION: This trial was registered on clinicaltrials.gov on 7 February 2024. The study was approved by the University of Calgary Conjoint Health Research Ethics Board (REB23-0625). On study completion, data will be made available on reasonable request to the corresponding author after completion of the study. Study dissemination and knowledge translation is planned via presentations at scholarly meetings, publications in peer-reviewed journals and, ideally, via adoption of results into clinical practice guidelines.

TRIAL REGISTRATION NUMBER: NCT06260878.

PMID:42203288 | DOI:10.1136/bmjopen-2026-119154