Recent Publications

Protein Sci. 2025 Jun;34(6):e70150. doi: 10.1002/pro.70150.

ABSTRACT

Amyloid fibrils are ordered aggregates that are a pathological hallmark of many neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The process of amyloid formation involves a complex cascade by which soluble monomeric protein converts to insoluble, ordered aggregates (amyloid fibrils). Although inhibiting the aggregation pathway is a key target for therapeutic development, the heterogeneous collection of aggregation-prone species formed in this process, including oligomers, protofibrils, and fibrils, represents other targets for modifying disease pathology. Developing molecules that can bind to amyloid fibrils and potentially disrupt the harmful interactions between the fibrils and the cellular components would be advantageous. Designing peptide modulators for α-synuclein aggregation is of great interest; however, effective inhibitory peptides are often hydrophobic and hence difficult to handle. Therefore, developing strategies to display these peptides in a soluble scaffold would be very beneficial. Here we demonstrate that the ultra-stable consensus-designed tetratricopeptide repeat (CTPR) protein scaffold can be grafted with "KLVFF" derived peptides previously identified to inhibit protein aggregation and interact with amyloid fibrils to produce proteins that bind along the surface of α-synuclein fibrils with micromolar affinity. Given the ability to insert hydrophobic peptides to produce soluble, CTPR-based binders, this method may prove beneficial in screening for peptide modulators of protein aggregation.

PMID:40371781 | DOI:10.1002/pro.70150

J Am Chem Soc. 2025 May 12. doi: 10.1021/jacs.5c00567. Online ahead of print.

ABSTRACT

This study investigates the roles of ethylene and ethylidyne in the surface chemistry of N-methylaniline (NMA) on Pt(111). Using X-ray photoelectron spectroscopy, temperature-programmed desorption, and density functional theory calculations, we demonstrate that ethylidyne is not merely a passive spectator species but actively contributes to hydroamination. It facilitates C-N bond formation by transferring a methyl group to NMA, leading to the formation of N,N-dimethylaniline. Additionally, it stabilizes reaction intermediates and suppresses the decomposition of NMA. This works demonstrates, in contrast to the widely accepted notion, that ethylidyne is not just an inert spectator species; rather, it plays a dual role as both an active reaction partner and a stabilizer. In addition, the coadsorption of ethylene on an NMA-precovered surface shows a side reaction of ethylene with the decomposition products of NMA.

PMID:40353685 | DOI:10.1021/jacs.5c00567

Spec Care Dentist. 2025 May-Jun;45(3):e70041. doi: 10.1111/scd.70041.

ABSTRACT

INTRODUCTION: Poor oral health (OH) can led to severe general health issues, including respiratory infections and malnutrition, impacting the quality of life. In Malaysia, high prevalence of oral diseases including dental caries among individuals with disabilities (IWDs) has been reported, indicating a possible gap in the current system. This study aimed to analyze caries experience using DMFT index of IWDs in community-based rehabilitation (CBR) centers across Selangor, Malaysia.

METHODS: A CBR centers-based cross-sectional study was conducted on IWDs or CBR trainees in the period between August 2022 and December 2023. Recruitments of the study participants were done via census sampling method, involving all the trainees within the specific centers. Data collection was done using the World Health Organization oral health survey tool (WHO, 2013) and analyzed using SPSS 24.

RESULTS: Two hundred and twenty-six students with the age range of 2-47 years old were included in the study. Clinical examination of CBR trainees revealed (1) the mean DMFT scores were low for primary dentition (2.02), moderate for both mixed (3.86), and permanent dentitions (4.17); (2) prevalence of caries among those with primary, mixed, and permanent dentitions as 44.44%, 74.4%, and 74.80%, respectively.

CONCLUSIONS: Trainees with primary dentition had a low prevalence of dental caries and mean DMFT score, while those with mixed and permanent dentition exhibited moderate levels. A statistically significant association was observed between the total DMFT scores for participants with primary dentition with both gender and disability types.

PMID:40353331 | DOI:10.1111/scd.70041

Lancet Oncol. 2025 May 7:S1470-2045(25)00156-1. doi: 10.1016/S1470-2045(25)00156-1. Online ahead of print.

ABSTRACT

BACKGROUND: Carriers of BRCA1 and BRCA2 pathogenic variants are at elevated risk of developing breast and ovarian cancers. To mitigate ovarian cancer risk, bilateral salpingo-oophorectomy (BSO) is commonly recommended for unaffected carriers and those with personal breast cancer history. Assessing BSO's long-term health outcomes in carriers with previous breast cancer history is essential. This study aims to examine the association between BSO and long-term health outcomes in individuals carrying pathogenic variants in BRCA1 and BRCA2 and with personal history of breast cancer.

METHODS: Data from the National Cancer Registration Dataset (NCRD) were linked with data from genetic testing laboratories to identify carriers of BRCA1 and BRCA2 pathogenic variants affected by breast cancer using pseudonymised patient identifiers. Further linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) dataset identified patients who had undergone BSO. Women aged 20-75 years, with a diagnosis of breast cancer as their first primary malignancy in 1995-2019 were eligible. Long-term health outcomes were identified from HES-APC and NCRD. Missing data were imputed using multivariate imputations by chained equations. Multivariable Cox regression was used to examine the associations with mortality (all-cause mortality, breast cancer-specific mortality, and non-breast cancer-specific mortality), second non-breast cancer, cardiovascular diseases, ischaemic heart disease, cerebrovascular diseases, contralateral breast cancer, and depression. Analyses were adjusted for age at diagnosis, diagnosis year, ethnicity, deprivation index, tumour characteristics, Charlson comorbidity index, cancer treatment, and second cancer diagnosis before the start of follow-up.

FINDINGS: We included 1674 BRCA1, 1740 BRCA2, and nine BRCA1 and BRCA2 carriers who were diagnosed with breast cancer between 1995 and 2019, with median follow-up time of 5·5 years (IQR 3·4-8·2). The study population (n=3423) consisted of 3002 (88·7%) White, 170 (5·0%) Asian, 59 (1·7%) Black, 26 (0·8%) mixed, and 74 (2·2%) other ethnic groups, and 92 (2·7%) had missing ethnicity. The uptake of BSO was significantly lower among Black women (odds ratio [OR] vs White women 0·48, 95% CI 0·34-0·67), and Asian women (0·47, 0·27-0·82). BSO uptake was higher in women living in the least socioeconomically deprived areas (OR vs most deprived 1·38, 95% CI [1·10-1·72]). BSO was associated with a reduced risk of all-cause mortality for both BRCA1 and BRCA2 pathogenic variant carriers (HR 0·52, 95% CI 0·41-0·64) and reduced breast cancer-specific mortality (BRCA1: HR 0·62, 95% CI 0·42-0·92 and BRCA2: 0·48, 0·34-0·68). It was also associated with a reduced risk of second non-breast cancer in the combined BRCA1 and BRCA2 sample (HR 0·59, 95% CI 0·37-0·94). There BSO was not associated with increased risk of cardiovascular diseases (HR 0·73, 95% CI 0·53-1·01), ischaemic heart disease (1·04, 0·48-2·26), cerebrovascular disease (0·32, 0·11-0·90), non-breast cancer specific mortality (0·72, 0·45-1·16), contralateral breast cancer (1·18, 0·64-2·16), or depression (0·94, 0·62-1·42).

INTERPRETATION: The evidence supports offering BSO to BRCA1 and BRCA2 pathogenic variant carrriers with a personal history of breast cancer, as they appear to benefit from having the procedure, without evidence of an increased risk of adverse long-term health outcomes.

FUNDING: Cancer Research UK.

PMID:40347974 | DOI:10.1016/S1470-2045(25)00156-1

J Vasc Surg Venous Lymphat Disord. 2025 May 5:102255. doi: 10.1016/j.jvsv.2025.102255. Online ahead of print.

ABSTRACT

OBJECTIVE: Mechanochemical ablation is a feasible endovenous nonthermal, nontumescent treatment method for saphenous vein insufficiency.1,2,3 Nevertheless, the ideal approach to managing varicose veins following intervention of the saphenous trunk remains ambiguous.1 Treatment of varicose veins can be administered either simultaneously or in a staged manner.1 The aim of this three-year follow-up study was to present the midterm outcomes of a randomized controlled trial, comparing concomitant and staged treatment of tributaries.

METHODS: Venous outpatient clinic patients with unilateral CEAP (clinical, etiological, anatomical, pathophysiological) C2-4 venous disease were enrolled in a randomized controlled trial during 2016-2017 at Helsinki University Hospital. After eligibility assessment of 1149 patients, 85 met the inclusion criteria: age of 20-70 years, ultrasound-verified refluxing above-knee great saphenous vein with a diameter of 5-10 millimeters, written consent from patients and not having deep venous reflux, peripheral artery disease, pregnancy, lymphoedema, body mass index > 40 kg/m2, allergy to the sclerosant, a history of deep vein thrombosis or any form of coagulopathy.

PARTICIPANTS: Were randomized, in a 1:1 ratio, to receive either staged tributary treatment with foam sclerotherapy at three months, if required (Group 1), or concomitant phlebectomies (Group 2), adjunct to mechanochemical ablation of the great saphenous trunk. All patients were invited to attend a three-year follow-up, during which the initially treated leg was assessed with duplex ultrasound. The primary outcome was reintervention rate during follow-up. Secondary outcomes comprised presence of above-knee great saphenous vein reflux, patient satisfaction, status of the great saphenous vein, number of varicose veins, and symptoms at follow-up.

RESULTS: During follow-up, 11.4 % (n=5/44) [95% CI, 0.02-0.21] in Group 1 and 4.9 % (n=2/41) [95% CI, -0.02-0.11] in Group 2 was in need of additional treatment (Group 1 vs Group 2 OR=2.5 [95% CI 0.46-13.67], P=0.435). The treatment groups did not elicit statistically significant variances in above-knee great saphenous vein reflux (P=0.603), disease-specific and health-related quality of life (P=0.238 and P=0.255 respectively), status of the great saphenous vein (P=0.112), or symptoms. However, noninferiority analysis suggests the staged approach to be inferior to the concomitant approach. Furthermore, Group 1 exhibited more varicosities at three years compared to Group 2, but this did not cause differences in the extent of symptoms or overall patient satisfaction.

CONCLUSION: Staged treatment of tributaries in C2-4 venous disease provides acceptable midterm outcomes compared to simultaneous treatment. However, its potential inferiority should be taken into consideration when prioritizing durable treatment outcomes in the long term.

PMID:40335021 | DOI:10.1016/j.jvsv.2025.102255

EMBO J. 2025 May 6. doi: 10.1038/s44318-025-00447-8. Online ahead of print.

ABSTRACT

The identification of tumour-specific protein-protein interactions remains a challenge for the development of targeted cancer therapies. In this study we describe our approach for the identification of triple negative breast cancer (TNBC)-specific protein-protein interactions focusing on the oncogene BCL11A. We used a proteomic approach to identify the BCL11A protein networks in TNBC and compared it to its network in B-cells, a cell type in which BCL11A plays crucial roles. This approach identified the chromatin remodeller CHD8 as a TNBC-specific interaction partner of BCL11A. We show that CHD8 also plays a key role in TNBC pathogenesis, with detailed multi-omics analysis revealing that BCL11A and CHD8 co-regulate several targets and synergise to drive tumour development and progression. Using a battery of biophysical assays, we confirm that the BCL11A-CHD8 interaction is direct and identify chemical fragments that disrupt this interaction and affect downstream targets, decreasing proliferation in 3D colony assays. Our study provides a proof-of-principle approach for investigating tumour-specific protein-protein interactions and identifies lead chemical compounds that could be developed into novel therapeutics for TNBC.

PMID:40328966 | DOI:10.1038/s44318-025-00447-8

Angew Chem Int Ed Engl. 2025 May 5:e202503958. doi: 10.1002/anie.202503958. Online ahead of print.

ABSTRACT

Targeted protein degradation (TPD) has emerged as a transformative therapeutic strategy for eliminating disease-associated proteins, with relevance across disorders ranging from cancer to neurodegeneration. Since its inception nearly two decades ago, TPD has attracted strong academic and commercial interest, with multiple candidates advancing into clinical trials. Despite this progress, the field faces persistent challenges, including limited solubility, poor cellular uptake, and unpredictable structure-activity relationship of small-molecule degraders, which complicate rational design. To address these limitations, alternative platforms such as nanoparticle-mediated protein degraders (NanoPDs) have gained attention. First reported 17 years ago, NanoPDs harness a diverse array of materials, degradation mechanisms, and linker chemistries to achieve protein clearance through novel pathways. While promising, their clinical translation remains constrained by barriers such as lysosomal entrapment, protein corona formation, and biocompatibility concerns. In this review, we present a comprehensive overview of the current landscape of nanoparticle-mediated TPD. We emphasize the design principles underlying nano-bio interfaces and explore the role of proximity-induced biology as a mechanism for orchestrating protein interactions. Finally, we highlight critical challenges and key questions that must be addressed to fully realise the therapeutic potential of NanoPDs.

PMID:40324952 | DOI:10.1002/anie.202503958

Cureus. 2025 Apr 3;17(4):e81670. doi: 10.7759/cureus.81670. eCollection 2025 Apr.

ABSTRACT

INTRODUCTION: Women and racial minorities remain underrepresented in orthopaedic surgery. While there is extensive research into the recruitment of these groups into the field, as well as more recent research regarding their representation in academic medicine and research, there is limited data on their experiences during residency. The purpose of this study is to assess the perceptions of orthopaedic surgery residents regarding their experiences during residency.

METHODS: In mid-2022, a voluntary survey was sent to 2,122 orthopaedic surgery residents addressing mentorship, access to opportunities, and "fit" within their residency programs. Responses were compared by race and gender, with 345 responses received, yielding a response rate of 16.3%.

RESULTS: Compared to male and Caucasian residents, female and underrepresented in medicine (URM) residents reported feeling less satisfied with the training they received, felt less supported, and perceived greater difficulty for women and minorities in being promoted within orthopaedics. Female residents also reported having less mentorship, receiving less recognition for their accomplishments, and being less satisfied with their career choice than male residents.

CONCLUSIONS: The results of this study highlight the need to improve equity and inclusion within orthopaedic surgery residencies in order to continue advancing diversity in the field.

PMID:40322420 | PMC:PMC12049239 | DOI:10.7759/cureus.81670

Biochem Pharmacol. 2025 May 2:116970. doi: 10.1016/j.bcp.2025.116970. Online ahead of print.

ABSTRACT

All commonly prescribed statins have been reported to cause reversible memory loss within weeks of therapy, though the exact molecular mechanism remains unknown. However, whether therapeutic concentrations of statins can directly regulate the contractility of resistance cerebral arteries that control cerebrovascular perfusion remains unexplored. Here, we examined the acute vascular effects of statins on rat cerebral arteries and the underlying molecular mechanisms. Our pressure myography data demonstrate that, at therapeutically-relevant nanomolar concentrations, statins produced a robust and rapid vasoconstriction, appearing within 2-3 min of drug application. Interestingly, such vasoconstriction was largely absent in female rat cerebral arteries. Endothelial denudation or mevalonate supplementation did not alter statin-induced vasoconstriction, suggesting an endothelium- and cholesterol-independent mechanism. In contrast, such vasoconstriction was abolished upon removal of extracellular Ca2+, pharmacological blockade of the smooth muscle cell voltage-gated Ca2+ channel, CaV1.2, or siRNA knockdown of CaV1.2 - all of which reduced [Ca2+]i, indicating that Ca2+ entry through CaV1.2 plays a critical role in cerebral artery vasoconstriction. Arterial biotinylation revealed that acute statin exposure did not alter the surface expression, distribution, or function of CaV1.2 channels. Altogether, our data unveil an unexpected role of statins in rapidly inducing constriction of resistance cerebral arteries by directly stimulating CaV1.2 in smooth muscle cells. These findings offer a plausible explanation for statin-associated reversible memory impairment, its mitigation by calcium channel blockers, and why such effects may not be observed in all subjects, particularly those concurrently taking antihypertensive agents.

PMID:40320051 | DOI:10.1016/j.bcp.2025.116970

Curr Opin Chem Biol. 2025 May 3;87:102600. doi: 10.1016/j.cbpa.2025.102600. Online ahead of print.

ABSTRACT

Electrochemical gradients exist not only across the plasma membrane (PM) but also across membranes of organelles. Various endomembrane-localised ion channels and transporters have been identified, the activity of which is critical for organellar (and also cellular) ionic homeostasis that underpins diverse cellular processes. Aberrant organellar ion flux underlies several diseases, identifying organellar channels and transporters as potential drug targets. Therefore, the need for probing the functions of these proteins in situ cannot be overemphasised. The acidic interior of a few organelles as well as the dynamic nature of most organelles historically presented challenges for reliable estimation of luminal ionic concentrations. But there have been significant methodological and technical advancements by now, allowing measurement of levels of specific ions within these organelles as well as their flux across endomembranes with increasing precision. Evidence also continues to amass reporting mechanosensitivity of the endomembranes and its physiological significance. Here we highlight some recent developments in tools and techniques for measuring the levels and movement of some selected organellar cations as well as organellar mechanosensitivity.

PMID:40319567 | DOI:10.1016/j.cbpa.2025.102600

Cardiooncology. 2025 May 2;11(1):43. doi: 10.1186/s40959-025-00341-6.

ABSTRACT

The emerging discipline of cardio-oncology addresses the cardiovascular complications associated with cancer therapies. In sub-Saharan Africa (SSA), where both cardiovascular disease (CVD) and cancer-related mortality are increasing, the development of cardio-oncology services remains limited. This correspondence assesses the current state of cardio-oncology in Africa, highlighting significant gaps in infrastructure, workforce, and policy. Despite the establishment of a single accredited cardio-oncology unit in South Africa, formalized services are lacking in the majority of African countries, leading to fragmented care and increased incidence of treatment-related cardiotoxicity. Key barriers include inadequate specialist training, limited diagnostic resources and a lack of standardized care protocols. The paper outlines strategic interventions, including multidisciplinary training, integration of cardiovascular screening into oncology, research funding, and policy reform. Strengthening cardio-oncology services is essential to reduce the dual burden of cancer and CVD and improve clinical outcomes for affected populations in SSA.

PMID:40317026 | DOI:10.1186/s40959-025-00341-6

Commun Biol. 2025 May 2;8(1):691. doi: 10.1038/s42003-025-08104-w.

ABSTRACT

In recent years the development of proteolysis-targeting chimeras (PROTACs) has enhanced the field of ubiquitin signalling through advancing therapeutic targeted protein degradation (TPD) strategies and generating tools to explore the ubiquitin landscape. However, the interplay between PROTACs and their substrates, and other components of the ubiquitin proteasome system (UPS), raises fundamental questions about cellular parameters that might influence the action of PROTACs and the amenability of a given target to PROTAC-mediated degradation. In this perspective we discuss examples of cellular parameters that have been shown to influence PROTAC sensitivity and consider others likely to be important for PROTAC-mediated target degradation but not yet routinely considered in design of novel TPD strategies: Target localisation and accessibility on the one hand, and expression patterns, localisation and activity of E3 ligases, deubiquitinases (DUBs) and wider ubiquitin machinery on the other, are critical parameters in the exploitation of PROTACs, and establishing a better understanding of these parameters will facilitate the rational design of PROTACs.

PMID:40316744 | DOI:10.1038/s42003-025-08104-w

J Anal Methods Chem. 2025 Apr 22;2025:5522915. doi: 10.1155/jamc/5522915. eCollection 2025.

ABSTRACT

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of triclabendazole (TCB) and ivermectin (IVM) in pharmaceutical dosage form. A mobile phase consisting of acetonitrile/water (50:50 v/v) with a flow rate of 1.5 mL/min was used for chromatographic separation of the mixture of TCB and IVM. The developed method was found to be linear with the correlation coefficient (r = 0.999) for TCB and IVM in the presence of suspension. The limit of quantitation (LOQ), robustness, specificity, accuracy, and precision were validated for the developed method. The peak areas of five replicates of the samples were recorded, and the acceptance rate of suspension recovery was 98%. The intraday accuracies for TCB and IVM were 98.71% and 100.79%, respectively, with a relative standard deviation (RSD) of 0.87%. The limits of detection (LOD) of TCB and IVM were 0.058 mg/mL and 0.112 μg/mL, respectively, while the LOQ of TCB and IVM were 0.178 μg/mL and 0.340 μg/mL, respectively. The method's % RSD for intra- and interday precision was deemed satisfactory. The developed method could be utilized for the determination and measurement of TCB and IVM in other samples.

PMID:40308629 | PMC:PMC12041623 | DOI:10.1155/jamc/5522915

J Public Health Res. 2025 Apr 26;14(2):22799036251330711. doi: 10.1177/22799036251330711. eCollection 2025 Apr.

ABSTRACT

BACKGROUND: Retention in care is a critical indicator of the quality of HIV care and a cornerstone for achieving epidemic control. Interruption in treatment (IIT) poses a significant threat to achieving the global 95-95-95 targets and leads to adverse health outcomes. This study assessed the effect of the national clinical mentorship program on retention in care and IIT among HIV clients in Nasarawa State, Nigeria.

METHODOLOGY: In the 47 facilities where mentors worked, every client who missed an appointment was tracked immediately. A list of potential IIT clients was generated and followed through by linking those clients to trackers who ensured they were returned to care. Mentors ensured that the process of tracking in the facilities was strengthened as part of their routine mentoring activities including facilitating the release of tracking funds. Data from the Retention and Audit Determination Tool (RADET) for patients reported between November 2021 and August 2022 were extracted and imported into an Excel template. Demographic and clinical program parameters were analyzed using descriptive statistics, bi-variate, and multivariate analysis, including Chi-square and logistic regression. The parameters in the facilities where mentorship was deployed were then compared to pre-deployment parameters.

RESULTS: This study found that a clinical mentorship program reduced the Interruption in treatment (IIT) rate from 7% to 0.5% between 2021 and 2022. Although the 25-34 age group had the highest IIT rate, it decreased from 41.6% to 33.3% after the mentorship program. Tertiary facilities still have the highest IIT rates. Non-pregnant women were more likely to continue with treatment than pregnant women. The mentorship program successfully reduced IIT rates in Nasarawa State.

CONCLUSION: Clinical mentoring can reduce IIT among HIV patients. The study found a decrease from 7% to 0.5%. Tailored mentorship programs can improve retention in HIV care and reduce IIT rates. Gender-specific barriers should be addressed, and interventions should be customized for pregnant women for better program effectiveness and health outcomes.

PMID:40296886 | PMC:PMC12035571 | DOI:10.1177/22799036251330711

Nanoscale. 2025 Apr 28. doi: 10.1039/d5nr00229j. Online ahead of print.

ABSTRACT

The experimental realization of kagome lattices that exhibit the predicted coexistence of topological states with high electron kinetics and non-dispersing quantum states remains challenging. Additionally, the robustness of these states against structural perturbations has rarely been explored. Here, we report on the formation of an analogue kagome structure via the electrostatic self-assembly of 4,7-dibromobenzo[c]-1,2,5-thiadiazole (2Br-BTD) molecules on Au(111). Local spectroscopic measurements, supported by theoretical calculations, reveal that the weak molecular coupling reshapes the topological-induced Shockley surface state of Au(111) by imposing a (7 × 7) periodicity, resulting in new band crossings. The molecular overlayer favours the opening of electron gaps at these positions manifested as sharp peaks in dI/dV spectra and electron localization in either the hexagonal or triangular sublattices of the kagome structure. To explore the robustness of these topological states, we monitored their stability under varied conditions, including different temperatures, the unaltered herringbone reconstruction of the Au(111) surface and local structural relaxation of the molecular assembly. These results demonstrate the degree of topological protection of these states, which holds potential for fundamental and applied research.

PMID:40293340 | DOI:10.1039/d5nr00229j

AJPM Focus. 2025 Mar 18;4(3):100333. doi: 10.1016/j.focus.2025.100333. eCollection 2025 Jun.

ABSTRACT

INTRODUCTION: The study of severe mental conditions has primarily remained under the purview of basic and clinical research. Although global epidemiological data indicate that immigrant groups are at higher risk of these conditions, U.S. data are lacking. Qualitative studies can be an important first step to bring attention to understudied phenomena.

METHODS: This manuscript describes strategies used to conduct semi-structured, in-depth individual interviews on experiences and perceptions of severe mental conditions among South Asian individuals with psychiatric diagnoses (n=21), family members (n=11), and clinicians (n=4) in New York City. These strategies were synthesized from the team's internal notes of adaptations during the study design and data collection, weekly debrief meetings during data analysis, and brainstorm sessions for this manuscript.

RESULTS: The main results of the study are reported elsewhere. This section focuses on lessons learned to improve immigrant participant interest and engagement, including the strengths and limitations of the healthcare setting; recruitment by a multilingual South Asian psychiatrist; interviews by non-clinical South Asian researchers selected for a variety of ages, genders, and languages; and the interview process and content.

DISCUSSION: Overall, these strategies show the feasibility of non-clinical researchers to collect high-quality data about severe mental conditions among immigrant communities, noting that the details of specific strategies and results will be particular to each immigrant community. Public health research on severe mental conditions is essential to understand and address the experiences of severe mental conditions among immigrant communities in the U.S.

PMID:40290863 | PMC:PMC12032897 | DOI:10.1016/j.focus.2025.100333

Cancer Cell Int. 2025 Apr 26;25(1):163. doi: 10.1186/s12935-025-03780-4.

ABSTRACT

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs involved in transposon silencing and linked to cancer progression. However, their role in Wilms tumors (WT) remains unexplored. We conducted a thorough analysis and characterization of piRNAs in serum liquid biopsies of WT patients. Our study examined their expression patterns and functional annotations related to WT pathogenesis, as well as their clinical potential for diagnosis and monitoring. We identified 307 piRNAs expressed in WT serum samples, with 4% classified as repeat-related and 96% as non-repeat-related. The most abundant repeat-related piRNAs originated from LINEs retrotransposon, while tRNA-derived piRNAs were the most prevalent among non-repeat-related piRNAs. Furthermore, a distinct profile of 34 piRNAs showed significant differential expression in WT patients compared to healthy controls-22 downregulated and 12 upregulated. The target genes of differentially expressed piRNAs exhibited significant enrichment in biological pathways related to cytokine activity, inflammatory responses, TGF-beta signaling, p38 MAPK, and ErbB signaling. These genes are also involved in DNA damage response, DNA methylation, cell cycle regulation, as well as kidney development and function. Low expression levels of several piRNAs, especially piR-hsa-1,913,711, piR-hsa-28,190, piR-hsa-28,849, piR-hsa-28,848, and piR-hsa-28,318, showed significant diagnostic potential as non-invasive biomarkers for WT (AUC > 0.8, p < 0.05). Their expression levels also significantly correlated with adverse pathological features, including metastasis, anaplasia, and bilateral WT development. In conclusion, non-transposon-related piRNAs may serve as reliable biomarkers for WT and possess potential non-germline functions, particularly in regulating DNA methylation, cell growth, immune responses, and immune responses. Further studies are warranted to elucidate their functional significance.

PMID:40287690 | DOI:10.1186/s12935-025-03780-4

Eur Child Adolesc Psychiatry. 2025 Apr 25. doi: 10.1007/s00787-025-02722-9. Online ahead of print.

ABSTRACT

Digital mental health interventions (DMHIs) are increasingly recommended for children and young people (CYP) as a promising way to prevent and treat mental health problems. Here, we summarised and consolidated findings from existing systematic reviews to provide an overview of what is known, and which areas need further investigation. Systematic searches were conducted until January 2024 using PubMed, PsycINFO, MEDLINE, CINAHL, Scopus and Google Scholar. Records were screened against predefined criteria and quality assessed using A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews. A study protocol was co-developed with key stakeholders and registered on the Open Science Framework. From 941 records, 51 systematic reviews published between 2000 and 2023 of generally moderate quality, targeting CYP 0 to 25 years, were included in our narrative summary. DMHIs were delivered in a variety of ways, including online video calls, apps and various combinations, underpinned mostly by cognitive behaviour therapy. DMHIs supported different mental health problems, but mostly symptoms of anxiety and/or depression. Although generally effective, some studies reported mixed results with limited evidence when focusing on longer-term outcomes. Other benefits of DMHIs included reduced costs and time investments for families, and increased accessibility and acceptability of support. Practitioner preparedness and unclear ethics/safety measures were identified as factors impacting engagement and potential effectiveness. The findings suggest that DMHIs can be a valuable tool for supporting CYP. However, realising the full potential of DMHIs for all CYP may require more high-quality research utilising DMHIs that are diverse in theoretical underpinnings and target audiences.

PMID:40278894 | DOI:10.1007/s00787-025-02722-9

Indian J Gastroenterol. 2025 Apr 24. doi: 10.1007/s12664-025-01780-w. Online ahead of print.

NO ABSTRACT

PMID:40272751 | DOI:10.1007/s12664-025-01780-w

J Arthroplasty. 2025 Apr 20:S0883-5403(25)00372-9. doi: 10.1016/j.arth.2025.04.035. Online ahead of print.

ABSTRACT

BACKGROUND: A better understanding of patient's a preoperative symptom state may assist in a more holistic evaluation of patients pursuing total joint arthroplasty (TJA). This study aimed to determine factors associated with preoperative Patient Acceptable Symptom State (PASS) scores in TJA patients and to determine the predictive ability of patient-reported outcome measures (PROMs) for achieving PASS preoperatively.

METHODS: All patients undergoing primary, elective TJA between January and October 2021 at a single institution and who had completed a preoperative PASS, preoperative Patient-Reported Outcome Measurement Information System (PROMIS) questionnaires, and joint-specific PROMs were eligible for inclusion. Descriptive statistics and independent samples t-tests were utilized. Receiver operating characteristic curves and area under the curve analyses were created to determine threshold values for PROMs representing PASS achievement.

RESULTS: A total of 287 total hip arthroplasty (THA) patients and 378 total knee arthroplasty (TKA) patients completed PASS preoperatively, with 12.9% of THA patients and 29.6% of TKA patients reporting acceptable symptom states. The PASS responses were associated with PROMIS Physical Function (PROMIS-PF) (P < 0.001) but not Hip Dysfunction and Osteoarthritis Score, Joint Replacement (HOOS, JR) (P = 0.073) scores in THA. The PASS responses were similarly associated with PROMIS-PF (P < 0.010) as well as Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR) (P = 0.030) scores in TKA. The HOOS, JR and PROMIS-PF threshold values of 55.6 and 40, respectively, only weakly predicted preoperative PASS achievement in THA. The KOOS, JR and PROMIS-PF threshold values of 52.5 and 39, respectively, only weakly predicted preoperative PASS achievement in TKA.

CONCLUSION: In patients undergoing THA or TKA, 12.9 and 29.6% of patients were satisfied with their symptoms before surgery, respectively. None of the threshold values for the assessed PROMs strongly predict PASS achievement. Given that not all patients indicated for TJA reported unacceptable health states, these findings question the validity of the PASS questionnaire preoperatively.

PMID:40262680 | DOI:10.1016/j.arth.2025.04.035