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461 papers

Radiolabeled Angiopep-2 Peptide Vector as a Preclinical Platform for Blood-Brain Barrier Targeting: Synthesis, Radiolabeling, and Preliminary In Vivo Biodistribution in Mice.

Fotou E et al. · Jul 1, 2026

Brain tumor therapy remains limited by the blood-brain barrier (BBB), which restricts drug access. BBB-penetrating peptides offer a promising strategy for delivering therapeutic and diagnostic payloads. Angiopep-2 is a well-established vector, yet novel radioconjugates based on this vector remain of interest. We report the synthesis and evaluation of DOTA-Angiopep-2 for radiolabeling with Lutetium-177 ( 177 Lu) and Terbium-161 ( 161 Tb). Notably, 177 Lu serves as a β- and γ-emitter, whereas 161 Tb is an Auger and β-emitter; both are utilized in therapy and SPECT imaging. Peptides were synthesized via solid-phase peptide synthesis. Cytotoxicity assays in T98 glioblastoma cells showed that Angiopep-2 is well-tolerated, maintaining ~100% viability at 20 μM and a moderate decline up to 100 μM. Radiolabeling achieved yields > 95% with excellent radiochemical stability at room temperature for up to 10 days and moderate stability in the presence of human serum. Biodistribution in healthy CFW mice showed a brain-associated radioactivity of 0.24% ± 0.05% IA/g at 5 min p.i. and a 12-fold increase in the brain-to-blood ratio (0.028-0.339) by 60 min p.i. These results support DOTA-Angiopep-2 as a versatile platform for radionuclide delivery and a potential candidate for future glioma-targeted studies. Further studies in tumor-bearing models are ongoing to evaluate therapeutic efficacy and translational potential.

Materials Science

Diffusion-weighted Imaging Distortion in Prostate MRI: A Cross-sectional Study Comparing Supine and Prone Positioning.

Lee KL et al. · Jul 1, 2026

Objectives Diffusion weighted imaging (DWI) is a key component of multiparametric (mp) prostate MRI. DWI using echo-planar techniques is susceptible to distortion at the recto-prostatic air-tissue interface. This study was to determine whether prone patient positioning reduces adjacent rectal air and DW image distortion when compared with standard-of-care supine positioning. Materials and methods This prospective study included consecutive patients undergoing mpMRI for suspected PCa between 2023 and 2024. Prostate segmentation was performed on DW and contrast-enhanced images. DWI distortion was measured quantitatively. Qualitative image quality of DWI and T2-weighted imaging (T2WI) was evaluated using PI-QUAL version 2; a separate 5-point clinically based Likert scale was employed to evaluate the volume of rectal air adjacent to the prostate. Results Fifty-two patients were enrolled. In total, 58% of patients expressed a preference for supine imaging versus 20% for prone imaging. Qualitative DWI image quality improved significantly in the prone position [median: 4 (3 to 4)] versus supine [3 (1 to 4)]; P 4 cm 3 of supine rectal air (n = 19), distortion was significantly reduced by prone imaging [3.49 mm (2.84 to 4.03)] compared with supine [4.60 mm (3.17 to 5.95)]; P = 0.02. The mean additional scanning time for the necessary prone imaging was 8 minutes 18 seconds. Conclusions Prone positioning significantly reduces DWI distortion artefact when rectal air is present, but consistently results in degraded T2WI quality.

Medicine

Mental Health Outcome Trends in a Nationally Representative Sample of Canadian Migrant Adolescents From 2014 to 2022.

Ji D et al. · Jul 1, 2026

Background Migrant youth are at disproportionate risk of mental health challenges. Overcoming barriers to accessing services requires large-scale data to inform policies and interventions. This study maps mental health outcome trends of migrant youth over 8 years. Methods Canadian Health Behavior in School-aged Children study data from 2014, 2018, and 2022 were analyzed for mental health outcome trends. Age-adjusted logistic regressions examined health across years stratified by migrant status, separately by sex. Using nonmigrants as the referent group and 2014 as the referent year, contrasts for disparities were examined across migrant status to test widening, narrowing, or stability in differences of outcome prevalences between migrant and nonmigrant youth. Results Health worsened from 2014 to 2022 among migrants, especially migrant girls. Compared to 2014, life satisfaction, health, and self-confidence for migrant youth dropped in 2022. Health complaints and feeling sad/hopeless increased in 2022 among girls. Migrant youth reported fewer health complaints than nonmigrants in 2018 and 2022. Implications Investment in free/affordable, culturally safe/relevant, confidential school-based mental health supports with avenues for community collaboration are recommended. Conclusions Mental health outcomes worsened from 2014 to 2022, especially among migrants and girls; however, migrant youth exhibit resilience to adversity.

Psychology

Audience Interpretation of Risks in Health Promotion Campaigns About Underage Drinking: Qualitative Interviews With Parents of Adolescents.

Nguyen HV. · Jul 1, 2026

Issue addressed Underage alcohol use has been linked to risks of physical, mental, and social harms to young people. Despite the known risks, research shows that parents may choose to supply alcohol to their children on occasions for various reasons. This has prompted several health promotional campaigns aimed at parents to discourage the practice of parental supply of alcohol, but there has been little evidence of how the messages are received by the target audiences, i.e., parents of adolescents. Methods Grounded in the existing literature on alcohol-related harms, social dimensions and communication of risks, the current paper conducted a qualitative analysis of interviews with parents of adolescents to understand their interpretation of risks in a series of Australian health promotion campaigns that addressed underage drinking. Result The study demonstrated how target audiences brought in their own lived experiences and social worldviews to interpret and internalise messaging about risks in ways that are nuanced and situational. Conclusions The findings demonstrated how parents' lived experiences and worldviews influenced their interpretation and alignment with the health promotion messages about parental supply of alcohol. While the ways the parents negotiated with the health promotion messages may not be scientifically-grounded, it was not always due to unawareness of risks but based upon strategies and assessment of risks in situational contexts. SO WHAT?: Understanding of how lived experiences inform interpretation of health promotion campaigns has implications for more effective alcohol-related risk communication aimed at behaviour change to reduce alcohol-related harms among young people.

Medicine

Cardiac output measurement in Malawian children ages 2 months-12 years hospitalised with severe anaemia (COM-TRACT).

Chintolo E et al. · Jul 1, 2026

Background Little is known about myocardial perturbations in African children hospitalised with severe anaemia. Methods An observational study nested within a clinical trial of blood transfusion was conducted on the paediatric ward in Blantyre, Malawi. Children were ages 2 months-12 years hospitalized with uncomplicated severe anaemia (haemoglobin 4-6 g/dl). By randomisation, 13 children received 30 ml/kg whole blood, 13 received 20 ml/kg whole blood and 26 had no immediate transfusion (usual care). We measured standard parameters of cardiac function using ultrasonic cardiac output monitoring (USCOM) at enrolment, 8 and 24 hours and discharge. Results Fifty-two children, median age 39 months (interquartile range [IQR] 25-58) and median haemoglobin 5.1 g/dl (IQR 4.8-5.6) were studied. Severe tachycardia and tachypnoea over time corrected faster in the transfused arms than the controls. At enrolment, the stroke volume index was within the normal range and 26/52 (50%) had a cardiac output index (COI) >97.5% the standard centile. The COI decreased in all arms by discharge but was greatest in the transfusion arms (p=0.05 for 20 ml/kg and p=0.009 for 30 ml/kg). A higher volume or receipt of whole blood did not worsen cardiac function. No child required diuretics. Conclusions The data generated by this small but granular study of haemodynamic and cardiac function provide reassuring physiological evidence showing the safety of higher doses of blood transfusion than currently recommended. It also supports the findings of a secondary analysis of the Transfusion and Treatment of Severe Anaemia in African Children trial indicating that whole blood transfusions are safe. These data support the new evidence-based paediatric transfusion algorithm for anaemic African children and its recommendation for safe use.

Medicine

Accuracy and Documentation of Richmond Agitation-Sedation Scale Assessments in a Cardiothoracic Critical Care Unit: A Prospective, Cross-Sectional Audit.

Szentgyorgyi L et al. · Jul 1, 2026

Background Sedation is a fundamental component of critical care and requires regular, accurate assessment to support its safe titration and minimise harm. International guidelines and local policy at the Wythenshawe Hospital's Cardiothoracic Critical Care Unit mandate hourly documentation of the Richmond Agitation-Sedation Scale (RASS). Aims This audit evaluated adherence to these standards and explored factors associated with documentation completeness and assessment accuracy. Study design A prospective, cross-sectional audit of bedside RASS assessment was conducted without prior notification. Nursing RASS scores were compared with expert auditor ratings. Data were collected using an anonymous, secure, auditor-completed online survey. Statistical analysis examined the relationship between documentation completion and RASS accuracy. Results Seventy-six nursing assessments were included. Most nurses were Band 5, with a median of 3.5 years of experience. Patients were predominantly male, mechanically ventilated and receiving sedation. Overall, 75% of nurse RASS assessments (n = 57) were accurate; however, only 33% (n = 25) were documented hourly as required by policy. Greater nursing experience was associated with improved accuracy in RASS. Deeper sedation was associated with lower agreement between nurse and expert assessments. Higher self-reported confidence was associated with poorer completion of documentation. Most discrepancies were small, with nurse and expert ratings differing by one RASS point. Conclusions This audit identified important gaps in the accuracy and documentation of nurse-led RASS assessment in a cardiothoracic critical care setting. The findings suggest that perceived familiarity and confidence may not be sufficient to ensure accurate and consistently documented sedation assessment. Relevance to clinical practice Suboptimal RASS documentation and scoring accuracy may limit reliable titration of sedation in critically ill patients and reduce the effectiveness of protocolised sedation strategies. These findings support targeted staff education, reinforcement of standardised assessment processes and improvements in documentation systems to strengthen sedation monitoring and patient safety.

Medicine

Crossing Borders of Care: The Professionalization of Women in Nursing and China-US Collaboration at Xiangya, 1909-1926.

Tang Y et al. · Jul 1, 2026

This article examines the development of modern nursing education in China through a case study of the Xiangya School of Nursing in Changsha between 1909 and 1926. Founded in 1911 by the Yale-in-China Association, a non-denominational mission, Xiangya was among the earliest nursing schools in China to promote undergraduate nursing education and public health nursing. Drawing on archival materials, published primary sources, and Chinese and English historiography, we analyze the cultural, political, and gendered challenges that shaped the school's development under the leadership of American nurse Nina Gage. While Gage initially sought to implement an Americanized model of nursing education, she and her colleagues adapted admission policies, educational goals, and curricula to local social and cultural conditions. Recognizing the need for Chinese nursing leadership, they prioritized the establishment of a Bachelor of Science degree to prepare nurses for teaching, administration, and public health roles. By 1926, Xiangya had trained approximately 16% of China's qualified nurses and had become one of only two schools in China offering university-level nursing education. This history highlights the interplay of transnational influence, cultural adaptation, and gendered reform in the professionalization of nursing in early 20th-century China.

Nursing

Clinicopathological and molecular characterization of HPV-associated cervical poorly cohesive carcinoma: a rare aggressive entity.

Liu W et al. · Jul 1, 2026

Primary signet-ring cell carcinoma and poorly differentiated adenocarcinoma with poorly cohesive morphology in the cervix are rare conditions, and their clinicopathological features remain poorly described. This study defines primary cervical poorly differentiated adenocarcinomas meeting the diagnostic criteria for poorly cohesive carcinoma as outlined in the 2019 WHO Classification of Digestive System Tumors as 'HPV-associated cervical poorly cohesive carcinomas' (HPV-associated CPCC) and describe their clinicopathological and molecular features. Sixteen HPV-associated CPCC cases were analyzed and classified into three histological subtypes: signet-ring cell carcinoma (n = 4), not otherwise specified (n = 6), and mixed types (n = 6). All patients were Chinese (median age: 46 years; range: 30-66). Vaginal bleeding was the primary presenting symptom (100.0%). High-risk human papillomavirus (HPV) was identified in all tumors, with HPV-18 as the predominant genotype (n = 13), HPV-16 in two cases, and a single case exhibiting concurrent infection with HPV-16, -18, and -58. Overall, 56.3% presented with advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] IIIB-IVB), frequently involving regional lymph nodes (56.3%) and distant sites (18.8%). Histopathological examination revealed diffuse stromal infiltration (100%), lymphovascular invasion (75.0%), necrosis (75.0%), and desmoplasia. Immunohistochemically, all cases showed p16 block positivity. Variable expression of antibody-drug conjugate targets was observed, with HER2-low expression (33.3%), and positive staining for Trop-2 (85.7%), nectin-4 (42.9%), and tissue factor (92.3%). During follow-up, disease-specific mortality was 50.0%. The 3-year overall survival rate was 56.3%, which was significantly lower in advanced-stage disease (45.0%) than in early-stage disease (75.0%). Whole-exome sequencing revealed low tumor mutational burden (median 1.28 Muts/Mb), recurrent mutations in AK1, ARHGAP39, KRT24, MICAL3, SLC6A9 (27.3%), KRAS, and KMT2C (18.2%), alongside MUC2 copy gain (63.6%) and bidirectional Y_RNA alterations (gain 54.5%/loss 45.5%). Collectively, HPV-associated CPCC represents a distinct and aggressive subtype characterized by distinctive histopathological features, a predominant association with HPV18, frequent presentation at advanced stages, and marked molecular and biomarker heterogeneity.

Medicine

A Single Session of Slackline Training Induces Rapid, Task-Specific Balance Improvements and Elevated Resting-State Beta Band Power.

Kenville R et al. · Jul 1, 2026

Balance training underpins both sports performance and rehabilitation, while its efficacy depends on the amount of training and task difficulty. Here, we characterized neurophysiological changes accompanying the earliest phase of slackline-specific balance acquisition within a closely matched active-control design. For this purpose, 35 healthy, slackline-naïve adults were randomized to a slackline intervention or a time-matched active control. Before and after training, participants completed slackline single-leg stance with eyes open (SL-EO) and eyes closed (SL-EC), resting-state electroencephalography (EEG), and tibial-nerve somatosensory-evoked potentials (SEP). EEG band-specific power was quantified after aperiodic correction and resulting change scores were analyzed with non-parametric mixed models. The intervention group showed larger gains in SL-EO than control, whereas SL-EC showed no between-group difference. Resting-state EEG exhibited a band-specific pattern with a greater post-training increase in beta power in the intervention group, whereas alpha and theta showed no selective group effects. SEP amplitudes did not change pre-post in either group. Finally, within the intervention group, beta power change did not correlate with individual performance gains. Overall, the present study revealed that resting-state beta power was sensitive to the earliest phase of slackline-specific balance acquisition, whereas tibial-nerve SEP amplitudes remained unchanged. These findings suggest that resting beta power may capture acute post-practice sensorimotor network changes after a single session of slackline training. Future work should assess generalizability across tasks and populations, combine task-based EEG with resting measures to link brain state to on-task control, and track if SEP changes arise over practice to refine models of balance learning.

Neuroscience

Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.

Hammoum T et al. · Jul 1, 2026

Peptide-based nanoparticles (PBN) have emerged as a promising alternative to lipid nanoparticles (LNP) for nucleic acid delivery and efficient cellular uptake. In this study, we evaluated the formulation of WRAP5 (W- and R-rich amphipathic peptide 5)-based PBN using a microfluidic device and assessed the impact of key process parameters, flow rate ratio (FRR), total flow rate (TFR), and mixing channel design, on nanoparticle characteristics. Across 72 formulations encapsulating small interfering RNA (siRNA) or plasmid DNA (pDNA), dynamic light scattering revealed consistent mean sizes ranging from 50 to 70 nm, with a low polydispersity index (PdI < 0.22), independent of FRR, TFR, or mixer type. Stability studies demonstrated that siRNA-loaded PBN exhibited moderate size increases during storage at 4°C, whereas pDNA-loaded PBN remained highly stable for up to 70 days. Biological assays confirmed robust activity: WRAP5:siRNA PBN achieved approximately 50% CDK4 silencing in GIST-T1 cells, and WRAP5:pDNA PBN mediated efficient mCHERRY expression in HeLa cells, regardless of formulation method or storage duration. These findings highlight the robustness and scalability of WRAP5-based PBN, contrasting with LNP systems that require stringent control of FRR and TFR, and partially underscore their potential for nucleic acid delivery applications.

Biochemistry, Genetics and Molecular Biology