Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 μm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer

Characterizing large-scale weak interlayer shear zones using conditional random field theory

The shear behavior of large-scale weak intercalation shear zones (WISZs) often governs the stability of foundations, rock slopes, and underground structures. However, due to their wide distribution, undulating morphology, complex fabrics, and varying degrees of contact states, characterizing the shear behavior of natural and complex large-scale WISZs precisely is challenging. This study proposes an analytical method to address this issue, based on geological fieldwork and relevant experimental results. The analytical method utilizes the random field theory and Kriging interpolation technique to simplify the spatial uncertainties of the structural and fabric features for WISZs into the spatial correlation and variability of their mechanical parameters. The Kriging conditional random field of the friction angle of WISZs is embedded in the discrete element software 3DEC, enabling activation analysis of WISZ C2 in the underground caverns of the Baihetan hydropower station. The results indicate that the activation scope of WISZ C2 induced by the excavation of underground caverns is approximately 0.5–1 times the main powerhouse span, showing local activation. Furthermore, the overall safety factor of WISZ C2 follows a normal distribution with an average value of 3.697

Contrasting responses of water use efficiency to drought across global terrestrial ecosystems

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Drought is an intermittent disturbance of the water cycle that profoundly affects the terrestrial carbon cycle. However, the response of the coupled water and carbon cycles to drought and the underlying mechanisms remain unclear. Here we provide the first global synthesis of the drought effect on ecosystem water use efficiency (WUE = gross primary production (GPP)/evapotranspiration (ET)). Using two observational WUE datasets (i.e., eddy-covariance measurements at 95 sites (526 site-years) and global gridded diagnostic modelling based on existing observation and a data-adaptive machine learning approach), we find a contrasting response of WUE to drought between arid (WUE increases with drought) and semi-arid/sub-humid ecosystems (WUE decreases with drought), which is attributed to different sensitivities of ecosystem processes to changes in hydro-climatic conditions. WUE variability in arid ecosystems is primarily controlled by physical processes (i.e., evaporation), whereas WUE variability in semi-arid/sub-humid regions is mostly regulated by biological processes (i.e., assimilation). We also find that shifts in hydro-climatic conditions over years would intensify the drought effect on WUE. Our findings suggest that future drought events, when coupled with an increase in climate variability, will bring further threats to semi-arid/sub-humid ecosystems and potentially result in biome reorganization, starting with low-productivity and high water-sensitivity grassland

CRISPR/Cas9‐mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse

The X‐linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas‐mediated in situ genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies

Carney Complex with PRKAR1A Gene Mutation: A Case Report and Literature Review

Rationale: Carney complex (CNC) is a multiple neoplasia syndrome with autosomal dominant inheritance. CNC is characterized by the presence of myxomas, spotty skin pigmentation, and endocrine overactivity. No direct correlation has been established between disease-causing mutations and phenotype. Patient concerns: A 16-year-old boy was admitted because of excessive weight gain over 3 years and purple striae for 1 year. Physical examination revealed Cushingoid features and spotty skin pigmentation on his face, lip, and sclera. Diagnoses: The patient was diagnosed as Carney complex. Interventions: the patient underwent right adrenalectomy and partial adrenalectomy of the left adrenal gland. Outcome: Results of imaging showed bilateral adrenal nodular hyperplasia, multiple microcalcifications of the bilateral testes, and compression fracture of the thoracolumbar spine. Histopathological results confirmed multiple pigmented nodules in the adrenal glands. DNA sequencing revealed a nonsense mutation in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A; c.205C \u3e T). After the second adrenalectomy, the Cushingoid features disappeared, and cortisol levels returned to normal. Lessons: Carney complex is a rare disease that lacks consistent genotype–phenotype correlations. Our patient, who carried a germline PRKAR1A nonsense mutation (c.205C \u3e T), clinical features included spotty skin pigmentation, osteoporosis, and primary pigmented nodular adrenal disease. Adrenalectomy is the preferred treatment for Cushing syndrome due to primary pigmented nodular adrenal disease

Artificial intelligence in global health equity: an evaluation and discussion on the application of ChatGPT, in the Chinese National Medical Licensing Examination

BackgroundThe demand for healthcare is increasing globally, with notable disparities in access to resources, especially in Asia, Africa, and Latin America. The rapid development of Artificial Intelligence (AI) technologies, such as OpenAI’s ChatGPT, has shown promise in revolutionizing healthcare. However, potential challenges, including the need for specialized medical training, privacy concerns, and language bias, require attention.MethodsTo assess the applicability and limitations of ChatGPT in Chinese and English settings, we designed an experiment evaluating its performance in the 2022 National Medical Licensing Examination (NMLE) in China. For a standardized evaluation, we used the comprehensive written part of the NMLE, translated into English by a bilingual expert. All questions were input into ChatGPT, which provided answers and reasons for choosing them. Responses were evaluated for “information quality” using the Likert scale.ResultsChatGPT demonstrated a correct response rate of 81.25% for Chinese and 86.25% for English questions. Logistic regression analysis showed that neither the difficulty nor the subject matter of the questions was a significant factor in AI errors. The Brier Scores, indicating predictive accuracy, were 0.19 for Chinese and 0.14 for English, indicating good predictive performance. The average quality score for English responses was excellent (4.43 point), slightly higher than for Chinese (4.34 point).ConclusionWhile AI language models like ChatGPT show promise for global healthcare, language bias is a key challenge. Ensuring that such technologies are robustly trained and sensitive to multiple languages and cultures is vital. Further research into AI’s role in healthcare, particularly in areas with limited resources, is warranted

A Novel Germline ARMC5 Mutation in a Patient with Bilateral Macronodular Adrenal Hyperplasia: A Case Report

BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing\u27s syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c. 517C \u3e T, p. Arg173*) alone rather than a two-hit mutation. CASE PRESENTATION: A 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C \u3e T, p. Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related. CONCLUSIONS: A novel germline ARMC5 mutation (c. 517C \u3e T, p. Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease

Novel Genotype-Phenotype Correlations in Five Chinese Families with Von Hippel-Lindau Disease.

CONTEXT: Von Hippel-Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype-phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes. PATIENTS AND DESIGN: A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients\u27 gene sequencing results with their medical records including computed tomography or magnetic resonance imaging scans, eye examinations, and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history. RESULTS: We identified four missense mutations: c. 239G\u3eT (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma (RCC), pheochromocytoma (Pheo), and hemangioma (HB) in the cerebellum; c. 232A\u3eT (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G\u3eA (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum, and spinal cord; c.293A\u3eG (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2. CONCLUSIONS: Characterizing VHL disease genotype-phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance, and treatment of VHL patients