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Department of Pharmacology

 

Comparison of conventional and novel rotational FNA needles using conventional microscopy and image analysis to quantitatively assess yield

Recent Publications - Wed, 09/04/2025 - 11:00

Cancer Cytopathol. 2025 May;133(5):e70014. doi: 10.1002/cncy.70014.

ABSTRACT

BACKGROUND: There is increasing interest in designing new fine-needle aspiration (FNA) needles to maximize tissue acquisition. This study compares cytological preparations from a new rotating FNA needle (CytoCore) with conventional FNA (ConvFNA) using semiquantitative evaluation and quantitative image analysis (IA).

METHODS: FNA were performed on ex vivo tissue in quadruplicate for each needle type (ConvFNA and CytoCore), including different sizes (22 G and 25 G) and variable procedure time (5 and 20 s). The Nikon Elements (v5.41.02) was used to quantify the cellularity and size of the largest tissue fragment on cell blocks.

RESULTS: A total of 96 cytology specimens were evaluated were evaluated from benign and malignant specimens. For both ConvFNA and CytoCore, a longer procedure time (20 s) tended to produce greater cellularity and larger tissue fragments in the cell block specimens for both needles when analyzed with image analysis and was statistically significant for the CytoCore needle (p < .01). The ConvFNA tended to perform better with short procedure time. There was no statistically significant difference using different needle gauges.

CONCLUSION: This study shows that IA can help to quantitatively evaluate sample cellularity in the cell blocks from specimens acquired with different needles. A longer procedure time tended to produce more cellular samples and larger tissue fragments in the cell block for both ConvFNA and CytoCore needles and was statistically significant for CytoCore. Additional larger studies, including those with true clinical cases, should be considered to evaluate the different needle types further.

PMID:40202788 | DOI:10.1002/cncy.70014

Unveiling Coverage-Dependent Interactions of <em>N</em>-Methylaniline with the Pt(111) Surface

Recent Publications - Wed, 09/04/2025 - 11:00

J Phys Chem C Nanomater Interfaces. 2025 Mar 21;129(13):6196-6210. doi: 10.1021/acs.jpcc.4c08116. eCollection 2025 Apr 3.

ABSTRACT

This study aims to elucidate the adsorption and surface chemistry of N-methylaniline (NMA) on Pt(111), using it as a model molecule to probe the activation mechanisms of aromatic amines on catalytic surfaces. Through a combination of density functional theory (DFT) calculations and experimental techniques such as temperature-programmed X-ray photoelectron spectroscopy (TP-XPS), temperature-programmed desorption (TPD), and Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), we explored the coverage-dependent behavior of NMA on Pt(111) to identify key steps in the activation process. The population of certain reaction paths is driven by a coverage-dependent balance between molecule surface charge transfer and intermolecular interactions, dictating the selective activation of specific bonds. Our findings reveal how coverage influences the orientation and bonding of NMA on the Pt(111) surface. At lower coverages, the molecule binds to the surface through the phenyl ring and activation, facilitating C-N bond cleavage to the ring under HCN formation. In comparison, at higher coverages, the molecule binds only through the nitrogen atom and desorbs intact. These insights into variable bond activation lay the groundwork for understanding the fundamental processes involved in potential heterogeneously catalyzed reactions of aromatic amines, contributing to the development of new catalytic strategies.

PMID:40201732 | PMC:PMC11973917 | DOI:10.1021/acs.jpcc.4c08116

Fundamental Trade-Offs in the Robustness of Biological Systems with Feedback Regulation

Recent Publications - Tue, 08/04/2025 - 11:00

ACS Synth Biol. 2025 Apr 8. doi: 10.1021/acssynbio.4c00704. Online ahead of print.

ABSTRACT

Natural biological systems use feedback regulation to effectively respond and adapt to their changing environment. Even though in engineered systems we understand how accurate feedback can be depending on the electronic or mechanical parts that it is implemented with, we largely lack a similar theoretical framework to study feedback regulation in biological systems. Specifically, it is not fully understood or quantified how accurate or robust the implementation of biological feedback actually is. In this paper, we study the sensitivity of biological feedback to variations in biochemical parameters using five example circuits: positive autoregulation, negative autoregulation, double-positive feedback, positive-negative feedback, and double-negative feedback (the toggle switch). We find that some of these examples of biological feedback are subjected to fundamental performance trade-offs, and we propose multi-objective optimization as a framework to study their properties. The impact of this work is to improve robust circuit design for synthetic biology and to improve our understanding of feedback for systems biology.

PMID:40198741 | DOI:10.1021/acssynbio.4c00704

Geographic Disparities in Oral Cancer Survival From 10 Population-Based Cancer Registries in India

Recent Publications - Tue, 08/04/2025 - 11:00

JAMA Netw Open. 2025 Apr 1;8(4):e253910. doi: 10.1001/jamanetworkopen.2025.3910.

ABSTRACT

IMPORTANCE: India accounts for more than one-third of oral cancer (OC) cases globally. Cancer survival measures the effectiveness of the health care system's cancer control efforts and the proportion of people who survive during a specified time.

OBJECTIVE: To estimate the 5-year survival rates among patients with OC diagnosed in India and assess the association of survival with age, place of residence, histologic type, and clinical extent of OC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated survival of patients diagnosed with primary OC (International Classification of Diseases for Oncology, Third Revision, codes C01-C06) between January 1, 2012, and December 31, 2015, and followed up until June 30, 2021. Patients were included from 10 population-based cancer registries (PBCRs). Data were analyzed between March 15 and August 20, 2024.

EXPOSURES: Demographic factors (patient age, sex, and place of residence) and disease factors (clinical extent of disease and histologic type).

MAIN OUTCOMES AND MEASURES: The main outcome was 5-year age-standardized relative survival (ASRS) for OC among male and female patients. A multivariable Cox proportional hazards model estimated hazard ratio (HR) and 95% CI, adjusting for covariates.

RESULTS: Data from the 10 PBCRs encompassed 14 059 patients of all ages (median age, 55 [IQR, 45-65] years; 10 380 male [73.8%]) diagnosed with OC. The overall 5-year ASRS rate for OC was 37.2% (range, 20.9%-58.4%). The estimated ASRS rates at 5 years were 36.0% (range, 20.7%-59.3%) for male and 39.6% (range, 21.4%-54.8%) for female patients. Ahmedabad urban had the highest 5-year ASRS at 58.4% (95% CI, 56.3%-60.4%) for both sexes, while Manipur had the lowest rates at 20.9% (95% CI, 14.9%-27.6%). Survival rates differed significantly between rural areas (34.1%; 95% CI, 31.4%-36.9%) and urban areas (48.5%; 95% CI, 47.4%-49.7%). Pooled data from Kollam and Thiruvananthapuram revealed that individuals 65 years or older (HR, 1.76; 95% CI, 1.44-2.14) and those with distant metastasis (HR, 3.95; 95% CI, 2.78-5.60) had a significantly higher risk of death.

CONCLUSIONS AND RELEVANCE: In this cohort study from India, significant survival disparities were observed among patients with OC based on demographic factors and clinical characteristics. Survival rates were lower in rural areas compared with urban regions, underscoring the inequalities in quality of care and services and emphasizing the need to improve OC survival rates in India.

PMID:40198071 | DOI:10.1001/jamanetworkopen.2025.3910

Recent Advances in Immune Checkpoint Inhibitors for Triple-Negative Breast Cancer

Recent Publications - Tue, 08/04/2025 - 11:00

Immunotargets Ther. 2025 Apr 3;14:339-357. doi: 10.2147/ITT.S495751. eCollection 2025.

ABSTRACT

While immunotherapy has transformed treatment across various cancers, its impact on breast cancer is relatively limited. Recent advances have established immunotherapy as an effective approach for triple-negative breast cancer (TNBC), an aggressive subtype with limited therapeutic targets and poor prognosis. Specifically, pembrolizumab, an immune checkpoint inhibitor (ICI), is now approved for both first-line metastatic and early-stage TNBC. In metastatic TNBC, combining ICIs with chemotherapy, particularly pembrolizumab, has demonstrated survival benefits in patients with PD-L1-positive disease. However, extending these benefits to broader populations has proven challenging, highlighting the need for better patient selection and novel strategies. Emerging approaches include combining ICIs with antibody-drug conjugates, PARP inhibitors, dual ICIs, and bispecific antibodies targeting angiogenesis and immune checkpoints. These strategies aim to overcome resistance and expand immunotherapy's efficacy beyond the PD-1/PD-L1 pathway. In early-stage disease, pembrolizumab combined with chemotherapy in the neoadjuvant setting has significantly improved pathologic complete response, event-free survival, and overall survival, establishing a new standard of care. Ongoing research aims to determine the optimal timing for ICI administration, explore less toxic chemotherapy backbones, utilize biomarkers for personalized treatment, and assess whether adding complementary treatments, such as radiation therapy for high-risk cases, can improve outcomes. This review examines the successes and setbacks of ICI use in TNBC, offering a comprehensive overview of current practices and future directions. It emphasizes optimizing ICI timing, leveraging biomarkers, and integrating novel agents to refine treatment approaches for both metastatic and early-stage TNBC. As immunotherapy continues to evolve, future research must address the unmet needs of this challenging breast cancer subtype, offering hope for improved outcomes.

PMID:40196378 | PMC:PMC11974553 | DOI:10.2147/ITT.S495751

Recent advances in 3D printing applications for CNS tumours

Recent Publications - Sun, 06/04/2025 - 11:00

Eur J Med Res. 2025 Apr 7;30(1):251. doi: 10.1186/s40001-025-02483-w.

ABSTRACT

Three-dimensional printing (3DP) has emerged as a transformative technology in the field of central nervous system (CNS) tumours, offering innovative advancements in various aspects of diagnosis, treatment and education. By precisely replicating the microenvironment of CNS tumours, modelling tumour vascularisation, and capturing genetic heterogeneity, 3DP enables the development of targeted therapies and personalised treatment strategies. The technology has markedly enhanced preoperative planning and intraoperative guidance, providing highly accurate, patient-specific models that improve tumour localisation, facilitate tailored surgical planning, and offer superior visualisation of complex anatomical structures. Furthermore, 3DP has revolutionised education and training for neurosurgeons, trainees, and patients by delivering realistic simulations that enhance surgical skills and decision-making. Despite its transformative potential, the widespread adoption of 3DP faces challenges, including material biocompatibility issues, high costs, and technical limitations. Furthermore, the ethical and regulatory landscape for 3DP in clinical practice requires further development. This review concludes that while 3DP offers significant promise for advancing CNS tumour treatment, ongoing research is essential to address these challenges and optimising its clinical impact.

PMID:40189551 | DOI:10.1186/s40001-025-02483-w

Targeting Bacterial Cells with DNA Nanostructures

Pharmacology Cambridge RSS Paper feed - Wed, 02/04/2025 - 11:00

Methods Mol Biol. 2025;2901:103-115. doi: 10.1007/978-1-0716-4394-5_8.

ABSTRACT

DNA origami nanostructures offer wide potential for controlled functionalization with molecules of interest, such as peptides, enzymes, small-molecule drugs, and fluorophores. Here, we describe a protocol for the synthesis and characterization of aptamer-modified DNA origami nanostructures that can act as a vehicle for delivering antimicrobials to Gram-positive and Gram-negative bacterial targets in a specific and efficient manner.

PMID:40175870 | DOI:10.1007/978-1-0716-4394-5_8

Targeting Bacterial Cells with DNA Nanostructures

Recent Publications - Wed, 02/04/2025 - 11:00

Methods Mol Biol. 2025;2901:103-115. doi: 10.1007/978-1-0716-4394-5_8.

ABSTRACT

DNA origami nanostructures offer wide potential for controlled functionalization with molecules of interest, such as peptides, enzymes, small-molecule drugs, and fluorophores. Here, we describe a protocol for the synthesis and characterization of aptamer-modified DNA origami nanostructures that can act as a vehicle for delivering antimicrobials to Gram-positive and Gram-negative bacterial targets in a specific and efficient manner.

PMID:40175870 | DOI:10.1007/978-1-0716-4394-5_8

Police Officers' Attitudes, Intentions, and Stereotyping Towards Mental Health Help Seeking Behaviors

Recent Publications - Tue, 01/04/2025 - 11:00

Res Sq [Preprint]. 2025 Mar 20:rs.3.rs-6181234. doi: 10.21203/rs.3.rs-6181234/v2.

ABSTRACT

Police officers have been known to have decreased willingness to seek mental health help. Increasing focus has been placed on enhancing the officer's mental wellbeing but has this improved the officer's help-seeking behavior? Methods . This cross-sectional quantitative study evaluated officers' mental health help-seeking attitudes, intentions, and stereotyping of others seeking help using mental distress levels. Data was collected from 337 officers across 22 states. Results . Statistical significance was found in 1) age and mental distress, 2) gender on help-seeking attitudes, intentions, and stereotyping, and 3) experience and mental distress. Officers reported more positive help-seeking attitudes, intentions, and stereotyping. Discussion . This study supported and contradicted past studies regarding these variables. Officers within this study reported increased officer help-seeking behaviors and less mental distress. Is increased mental health education helping to improve officer help-seeking behaviors, or are officers with lower mental distress willing to participate in mental health research versus those with high mental distress resulting in skewed overall results?

PMID:40166002 | PMC:PMC11952654 | DOI:10.21203/rs.3.rs-6181234/v2

Police Officers' Attitudes, Intentions, and Stereotyping Towards Mental Health Help Seeking Behaviors

Recent Publications - Mon, 31/03/2025 - 11:00

Res Sq [Preprint]. 2025 Mar 11:rs.3.rs-6181234. doi: 10.21203/rs.3.rs-6181234/v1.

ABSTRACT

Police officers have been known to have decreased willingness to seek mental health help. Increasing focus has been placed on enhancing the officer's mental wellbeing but has this improved the officer's help-seeking behavior? Methods . This cross-sectional quantitative study evaluated officers' mental health help-seeking attitudes, intentions, and stereotyping of others seeking help using mental distress levels. Data was collected from 337 officers across 22 states. Results . Statistical significance was found in 1) age and mental distress, 2) gender on help-seeking attitudes, intentions, and stereotyping, and 3) experience and mental distress. Officers reported more positive help-seeking attitudes, intentions, and stereotyping. Discussion . This study supported and contradicted past studies regarding these variables. Officers within this study reported increased officer help-seeking behaviors and less mental distress. Is increased mental health education helping to improve officer help-seeking behaviors, or are officers with lower mental distress willing to participate in mental health research versus those with high mental distress resulting in skewed overall results?

PMID:40162219 | PMC:PMC11952654 | DOI:10.21203/rs.3.rs-6181234/v1

Differential neuropilin isoform expressions highlight plasticity in macrophages in the heterogenous TME through <em>in-silico</em> profiling

Pharmacology Cambridge RSS Paper feed - Wed, 26/03/2025 - 10:00

Front Immunol. 2025 Mar 11;16:1547330. doi: 10.3389/fimmu.2025.1547330. eCollection 2025.

ABSTRACT

INTRODUCTION: The nuanced roles of neuropilin (NRP) isoforms, NRP1 and NRP2, have attracted considerable scientific interest regarding cancer progression. Their differential expressions across various cancer types are specific to NRP isoforms which are shown in a cancer type-dependent manner. It accounts for the different mechanisms involved, driven by a co-expression of gene-sets associated with overexpressed NRP1 or NRP2. Their different expressions on tumour-associated macrophages (TAMs) with disparate markers are associated with the heterogenous tumour microenvironment (TME) through their plasticity and pro-tumorigenic activities.

METHODS: Single-cell RNA sequencing (scRNA-seq) analyses were performed on tumours from clear cell Renal Cell Carcinoma (ccRCC) and skin cutaneous melanoma (SKCM) which exhibit the highest expressions of NRP1 and NRP2, respectively. Datasets were processed using established bioinformatics pipelines, including clustering algorithms, to determine cellular heterogeneity and quantify NRP isoform expression within distinct macrophage populations. Using differential gene expression analysis (DEGA) alongside co-enrichment studies, we explored gene-sets associated with NRP1 or NRP2 overexpression in TAMs.

RESULTS: Our analysis revealed a marked upregulation of NRP1 in TAMs isolated from ccRCC and elevated NRP2 expression in SKCM-derived TAMs. Both NRP1+ and NRP2+ macrophages showed an M2-like polarisation characterised by immune suppression and extracellular matrix degradation. Coupled with the previously uncharacterised NRP isoform specific- subpopulations within these cancers identified by DEGA, co-enrichment analyses demonstrated that the upregulation of gene-sets associated with NRP1 is associated with angiogenesis and tumour progression through VEGF signalling, while gene-sets with NRP2 showed dual functionality in the TME-dependent manner. Their distinct roles in regulating macrophage plasticity, tumour invasion, and metastasis were highlighted.

DISCUSSION: These findings underscore distinct isoform-specific mechanisms by which NRP1 and NRP2 contribute to TAM-mediated cancer progression. This study aims to establish a foundation for future research, leading to biological experiments with focused gene-sets derived from our findings. This approach can contribute to the development of immunomodulatory strategies targeting specific NRP isoforms in macrophages, tailored to individual cancer types and abnormal expressions of those gene markers, potentially offering a more effective therapeutic approach compared to broad-spectrum NRP inhibition strategies.

PMID:40134439 | PMC:PMC11933088 | DOI:10.3389/fimmu.2025.1547330

Differential neuropilin isoform expressions highlight plasticity in macrophages in the heterogenous TME through <em>in-silico</em> profiling

Recent Publications - Wed, 26/03/2025 - 10:00

Front Immunol. 2025 Mar 11;16:1547330. doi: 10.3389/fimmu.2025.1547330. eCollection 2025.

ABSTRACT

INTRODUCTION: The nuanced roles of neuropilin (NRP) isoforms, NRP1 and NRP2, have attracted considerable scientific interest regarding cancer progression. Their differential expressions across various cancer types are specific to NRP isoforms which are shown in a cancer type-dependent manner. It accounts for the different mechanisms involved, driven by a co-expression of gene-sets associated with overexpressed NRP1 or NRP2. Their different expressions on tumour-associated macrophages (TAMs) with disparate markers are associated with the heterogenous tumour microenvironment (TME) through their plasticity and pro-tumorigenic activities.

METHODS: Single-cell RNA sequencing (scRNA-seq) analyses were performed on tumours from clear cell Renal Cell Carcinoma (ccRCC) and skin cutaneous melanoma (SKCM) which exhibit the highest expressions of NRP1 and NRP2, respectively. Datasets were processed using established bioinformatics pipelines, including clustering algorithms, to determine cellular heterogeneity and quantify NRP isoform expression within distinct macrophage populations. Using differential gene expression analysis (DEGA) alongside co-enrichment studies, we explored gene-sets associated with NRP1 or NRP2 overexpression in TAMs.

RESULTS: Our analysis revealed a marked upregulation of NRP1 in TAMs isolated from ccRCC and elevated NRP2 expression in SKCM-derived TAMs. Both NRP1+ and NRP2+ macrophages showed an M2-like polarisation characterised by immune suppression and extracellular matrix degradation. Coupled with the previously uncharacterised NRP isoform specific- subpopulations within these cancers identified by DEGA, co-enrichment analyses demonstrated that the upregulation of gene-sets associated with NRP1 is associated with angiogenesis and tumour progression through VEGF signalling, while gene-sets with NRP2 showed dual functionality in the TME-dependent manner. Their distinct roles in regulating macrophage plasticity, tumour invasion, and metastasis were highlighted.

DISCUSSION: These findings underscore distinct isoform-specific mechanisms by which NRP1 and NRP2 contribute to TAM-mediated cancer progression. This study aims to establish a foundation for future research, leading to biological experiments with focused gene-sets derived from our findings. This approach can contribute to the development of immunomodulatory strategies targeting specific NRP isoforms in macrophages, tailored to individual cancer types and abnormal expressions of those gene markers, potentially offering a more effective therapeutic approach compared to broad-spectrum NRP inhibition strategies.

PMID:40134439 | PMC:PMC11933088 | DOI:10.3389/fimmu.2025.1547330

Autism spectrum disorder (ASD) - An analysis of the ASD interventions utilized in Bangladesh

Recent Publications - Sat, 22/03/2025 - 10:00

Res Dev Disabil. 2025 Mar 21;160:104971. doi: 10.1016/j.ridd.2025.104971. Online ahead of print.

ABSTRACT

OBJECTIVES: This study focused on analysing treatment applicability and effectiveness for ASD in Bangladesh based on the perspectives of parents/guardians, and educational or healthcare professionals.

METHODS AND PROCEDURES: We utilized a cross-sectional survey and a mixed methods approach was employed, integrating quantitative and qualitative data about interventions used, effectiveness, and satisfaction levels. Data were analysed via descriptive and inferential statistics, including independent sample t-tests.

RESULTS: The results revealed that developmental approaches were the most commonly used and participants expressed a high level of satisfaction with the interventions. Educational and healthcare professionals emphasized the importance of a multidisciplinary approach. The study also found no statistically significant difference in the effectiveness of interventions between the two cities.

CONCLUSIONS: The research highlights the need for a comprehensive and tailored approach to support individuals with ASD and provides valuable insights for organizations, policymakers, and professionals to improve the provision of effective interventions, It also focuses on the significance of involving caregivers in the treatment process. Further research is recommended to explore other regions' interventions and evaluate the long-term outcomes of different treatment approaches.

PMID:40120153 | DOI:10.1016/j.ridd.2025.104971

Current status of neurotrauma management in resource-limited settings

Recent Publications - Thu, 20/03/2025 - 10:00

Ann Med Surg (Lond). 2025 Jan 7;87(2):673-683. doi: 10.1097/MS9.0000000000002901. eCollection 2025 Feb.

ABSTRACT

Over the last several decades neurotrauma has become recognized as a significant contributor to poor health outcomes, with growing physical, cognitive, social, and economic burdens. Although it serves as a significant contributor globally, it disproportionately affects low- and middle-income countries (LMIC). In this manuscript, we will be comparing how neurotrauma is managed across the globe with special consideration on how variations in environment, resources, infrastructure, and access can influence patient care and outcomes. Moreover, we will be examining the challenges faced by health care systems in LMIC and exploring strategies for quality improvement.

PMID:40110290 | PMC:PMC11918690 | DOI:10.1097/MS9.0000000000002901

Multi-channel MRI reconstruction using cascaded Swinμ transformers with overlapped attention

Recent Publications - Wed, 19/03/2025 - 10:00

Phys Med Biol. 2025 Mar 19;70(7). doi: 10.1088/1361-6560/adb933.

ABSTRACT

Objective.Deep neural networks have been shown to be very effective at artifact reduction tasks such as magnetic resonance imaging (MRI) reconstruction from undersampled k-space data. In recent years, attention-based vision transformer models have been shown to outperform purely convolutional models at a wide variety of tasks, including MRI reconstruction. Our objective is to investigate the use of different transformer architectures for multi-channel cascaded MRI reconstruction.Approach.In this work, we explore the effective use of cascades of small transformers in multi-channel undersampled MRI reconstruction. We introduce overlapped attention and compare it to hybrid attention in shifted-window (Swin) transformers. We also investigate the impact of the number of Swin transformer layers in each architecture. The proposed methods are compared to state-of-the-art MRI reconstruction methods for undersampled reconstruction on standard 3T and low-field (0.3T) T1-weighted MRI images at multiple acceleration rates.Main results.The models with overlapped attention achieve significantly higher or equivalent quantitative test metrics compared to state-of-the-art convolutional approaches. They also show more consistent reconstruction performance across different acceleration rates compared to their hybrid attention counterparts. We have also shown that transformer architectures with fewer layers can be as effective as those with more layers when used in cascaded MRI reconstruction problems.Significance.The feasibility and effectiveness of cascades of small transformers with overlapped attention for MRI reconstruction is demonstrated without incorporating pre-training of the transformer on ImageNet or other large-scale datasets.

PMID:40105018 | DOI:10.1088/1361-6560/adb933

A comprehensive review of the clinical presentation, diagnosis, and treatment of calcineurin inhibitor-induced pain syndrome

Recent Publications - Mon, 17/03/2025 - 10:00

Eur J Med Res. 2025 Mar 17;30(1):177. doi: 10.1186/s40001-025-02357-1.

ABSTRACT

Calcineurin inhibitor-induced pain syndrome (CIPS), a rare but recognized complication of calcineurin inhibitor (CNI) therapy in transplant recipients, presents as severe bilateral lower extremity pain. This syndrome, first described in 1989, primarily affects patients receiving tacrolimus or cyclosporine. Proposed mechanisms include intraosseous vasoconstriction, bone marrow edema, and altered bone metabolism, possibly involving TRSK channels and NFAT signaling. The diagnosis relies on clinical history, characteristic pain patterns, and imaging findings such as bone marrow edema on MRI. The management of CIPS revolves around reducing or discontinuing the offending CNI while maintaining immunosuppression. Alternative immunosuppressants like mammalian target rapamycin (mTOR) inhibitors or mycophenolate mofetil are considered to mitigate symptoms. Symptomatic relief includes calcium channel blockers, bisphosphonates, and analgesics like NSAIDs or opioids. Physical therapy and close monitoring are also integral to improving outcomes and managing chronic pain effectively in affected transplant recipients. This review synthesizes current knowledge on CIPS, highlighting diagnostic challenges, treatment options, and areas for future research to optimize clinical management and enhance patient outcomes.

PMID:40091077 | DOI:10.1186/s40001-025-02357-1

Molybdenum-Catalyzed Asymmetric Amination of α-Hydroxy Esters: Synthesis of α-Amino Acids

Recent Publications - Mon, 10/03/2025 - 10:00

Adv Sci (Weinh). 2025 Mar 10:e2403437. doi: 10.1002/advs.202403437. Online ahead of print.

ABSTRACT

Unnatural α-amino acids are found in a wide variety of bioactive compounds ranging from proteins to pharmaceutical agents to materials science. As a result, the investigation of efficient and simple methods for their synthesis is a major purpose in reaction development. In this study, it is found that a catalyst based on molybdenum, an earth-abundant transition metal, can facilitate the amination of readily accessible α-hydroxy esters to afford N-protected unnatural α-amino acid esters in high yield. This simple process also enables enantioselective amination, which proceeds through cooperative catalysis of chiral molybdenum complex with chiral phosphoric acid (CPA), and complements earlier procedures to the catalytic synthesis of this important class of compounds. The obtained protected α-amino acid ester products are directly useful or further utilized for the synthesis of commercially available drugs and analogs.

PMID:40063505 | DOI:10.1002/advs.202403437

Catalytic Asymmetric Synthesis of β-Amino α-Tertiary Alcohol through Borrowing Hydrogen Amination

Recent Publications - Thu, 06/03/2025 - 11:00

Org Lett. 2025 Mar 6. doi: 10.1021/acs.orglett.5c00283. Online ahead of print.

ABSTRACT

The first enantioconvergent transition-metal-catalyzed amination of racemic α-tertiary 1,2-diols providing access to vicinal β-amino α-tertiary alcohols is disclosed. The iridium-catalyzed amination reaction proceeds through a chiral phosphoric acid-mediated borrowing hydrogen pathway with excellent yields and enantioselectivities for a range of amine nucleophiles and α-tertiary 1,2-diols. An array of β-amino α-tertiary alcohols were obtained with high yields and enantioselectivities (50 examples with up to 91% yield and up to 99% ee). These important chiral amino alcohol products can be easily converted into chiral ligands and bioactive skeletons. Mechanistic investigations proposed a dynamic kinetic resolution pathway involving imine formation and then imine reduction as the enantiodetermining step.

PMID:40048559 | DOI:10.1021/acs.orglett.5c00283

Long-term outcomes of bilateral salpingo-oophorectomy in women with personal history of breast cancer

Recent Publications - Thu, 06/03/2025 - 11:00

BMJ Oncol. 2025 Feb 25;4(1):e000574. doi: 10.1136/bmjonc-2024-000574. eCollection 2025.

ABSTRACT

OBJECTIVES: To investigate the association between bilateral salpingo-oophorectomy (BSO) and long-term health outcomes in women with a personal history of breast cancer.

METHODS AND ANALYSIS: We used data on women diagnosed with invasive breast cancer between 1995 and 2019 from the National Cancer Registration Dataset (NCRD) in England. The data were linked to the Hospital Episode Statistics-Admitted Patient Care dataset to identify BSO delivery. Long-term health outcomes were selected from both datasets. Multivariable Cox regression was used to examine the associations, with BSO modelled as a time-dependent covariate. The associations were investigated separately by age at BSO.

RESULTS: We identified 568 883 women, 23 401 of whom had BSO after the breast cancer diagnosis. There was an increased risk of total cardiovascular diseases with an HR of 1.10 (95% CI 1.04 to 1.16) in women who had BSO<55 years and 1.07 (95% CI 1.01 to 1.13) for women who had BSO≥55 years. There was an increased risk of ischaemic heart diseases, but there was no association with cerebrovascular diseases. BSO at any age was associated with an increased risk of depression (HR 1.20, 95% CI 1.12 to 1.28) and increased risk of second non-breast cancer in older women (HR 1.21, 95%CI 1.08 to 1.35). BSO in older women was associated with reduced risk of all-cause mortality (HR 0.92, 95% CI 0.87 to 096), but not in women who had BSO<55 years.

CONCLUSION: In women with a personal history of breast cancer, BSO before and after the age of 55 years is associated with an increased risk of long-term outcomes. BSO after 55 years is associated with reduced all-cause mortality. Family history or genetic predisposition may confound these associations.

PMID:40046828 | PMC:PMC11880784 | DOI:10.1136/bmjonc-2024-000574

Women in academic nephrology: have we bridged the gender gap?

Recent Publications - Thu, 06/03/2025 - 11:00

Clin Kidney J. 2025 Jan 28;18(3):sfaf019. doi: 10.1093/ckj/sfaf019. eCollection 2025 Mar.

NO ABSTRACT

PMID:40046819 | PMC:PMC11879463 | DOI:10.1093/ckj/sfaf019