Clinical Research Research Articles

Building large-scale registries from unstructured clinical notes using a low-resource natural language processing pipeline

Building clinical registries is an important step in clinical research and improvement of patient care quality. Natural Language Processing (NLP) methods have shown promising results in extracting valuable information from unstructured clinical notes. However, the structure and nature of clinical notes are very different from regular text that state-of-the-art NLP models are trained and tested on, and they have their own set of challenges. In this study, we propose Sentence Extractor with Keywords (SE-K), an efficient and interpretable classification approach for extracting information from clinical notes and show that it outperforms more computationally expensive methods in text classification. Following the Institutional Review Board (IRB) approval, we used SE-K and two embedding based NLP approaches (Sentence Extractor with Embeddings (SE-E) and Bidirectional Encoder Representations from Transformers (BERT)) to develop comprehensive registry of anterior cruciate ligament surgeries from 20 years of unstructured clinical data at a multi-site tertiary-care regional children's hospital. The low-resource approach (SE-K) had better performance (average AUROC of 0.94 ± 0.04) than the embedding-based approaches (SE-E: 0.93 ± 0.04 and BERT: 0.87 ± 0.09) for out of sample validation, in addition to minimum performance drop between test and out-of-sample validation. Moreover, the SE-K approach was at least six times faster (on CPU) than SE-E (on CPU) and BERT (on GPU) and provides interpretability. Our proposed approach, SE-K, can be effectively used to extract relevant variables from clinic notes to build large-scale registries, with consistently better performance compared to the more resource-intensive approaches (e.g., BERT). Such approaches can facilitate information extraction from unstructured notes for registry building, quality improvement and adverse event monitoring.

Current Vaccination Practice in Diabetic (Diabetes I) Patients.

The worldwide prevalence of diabetes, an endocrine condition, is rising quickly. The alarming rise of diabetes in recent years has emerged as a major contributor to premature death and illness among persons of working age. The potential use of immunomodulatory drugs to prevent diabetes has been a source of worry in light of recent advances in our understanding of the role of autoimmune responses in the development of diabetes. Vaccines can work in a variety of ways, including by eliminating autoreactive T-cells or by blocking the connections between immune cells. Most diabetes vaccines that have been created so far have only been evaluated in animal models, with just a small number having undergone successful human trials. In this article, the authors also look at the clinical trial research that are currently being conducted to create a prototype diabetes vaccine.

Carob (Ceratonia siliqua L.), Pharmacological and Phytochemical Activities of Neglected Legume of the Mediterranean Basin, as Functional Food.

Carob (Ceratonia siliqua L.) has been widely cultivated in different parts of the world, particularly in the Mediterranean region, and the tree belongs to the family Leguminosae. Several studies have indicated that carobs and their products can improve human health and help prevent different specific chronic diseases. Carob can considered as functional food due to its high content in dietary fibers, low-fat content, and high content of minerals. Its fruit is a pod containing 10%-20% seeds, and the pods consist of sugars, proteins, crude fibers, minerals, vitamins, polyphenols, vitamins, and lipids. In many countries in the Middle east, carob is mainly used to prepare as a traditional drink and some kinds of confectioneries. The powders can be utilized to prepare carob juice concentrate. The systematic review of documents from clinical trials and scientific societies dedicated to traditional medicine in China has been carried out. The goal of this review article is a survey of chemical compounds, and pharmaceutical benefits of carob, especially by considering traditional medicinal sciences. Moreover, clinical trials research promotes studies to highlight and focus on the scope of application of traditional medicinal science in the growing system of medicine.

Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma

The widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, B cell heterogeneity in PDAC remains unexplored. Studying TIL-Bs in PDAC aims to identify new treatment strategies. We performed single-cell RNA sequencing to study the heterogeneity of B cells in PDAC. The prognostic and immunologic value of the identified CD38+ B cells was explored in FUSCC (n=147) and TCGA (n=176) cohorts. Flow cytometry was conducted to characterize the relationship between CD38+ B cells and other immune cells, as well as their phenotypic features. Invitro and in vivo experiments were performed to assess the putative effect of CD38+ B cells on antitumor immunity. The presence of CD38+ B cells in PDAC was associated with unfavorable clinicopathological features and poorer overall survival (p<0.001). Increased infiltration of CD38+ B cells was accompanied by reduced natural killer (NK) cells (p=0.021) and increased regulatory T cells (p=0.016). Molecular profiling revealed high expression of IL-10, IL-35, TGF-β, GZMB, TIM-1, CD5 and CD21, confirming their putative regulatory B cell-like features. Co-culture experiments demonstrated suppression of NK cell cytotoxicity by CD38+ B cell-derived IL-10 (p<0.001). Finally, invivo experiments suggested adoptive transfer of CD38+ B cells reduced antitumor immunity and administration of a CD38 inhibitor hampered tumor growth (p<0.001). We discovered regulatory B cell-like CD38+ B cell infiltration as an independent prognostic factor in PDAC. The use of CD38 inhibitor may provide new possibilities for PDAC immunotherapy. This study was supported by the National Natural Science Foundation of China (U21A20374), Shanghai Municipal Science and Technology Major Project (21JC1401500), Scientific Innovation Project of Shanghai Education Committee (2019-01-07-00-07-E00057), Special Project for Clinical Research in the Health Industry of the Shanghai Health Commission (No. 20204Y0265) and Natural Science Foundation of Shanghai (23ZR1479300).

MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study

Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40-94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4-569.6] vs 441 [IQR 223.4-731.5] ng/ml, p<0.0001) but not MMP-2 concentrations were increased within collateral blood vessels. The median MMP-9 expression level of invading neutrophils was elevated (fluorescence intensity, arbitrary unit: 2276 [IQR 1007-5086] vs 3078 [IQR 1108-7963], p=0.0018). Gelatine zymography experiments indicated the locally confined proteolytic activity of MMP-9 but not of MMP-2. Pretherapeutic MMP-9 release into stroke-affected brain regions predicted the degree of intracerebral haemorrhages and clinical stroke severity after recanalisation, and independently increased the odds of space-occupying parenchymal haematomas (HBC1c-3a) by 1.54 times, and the odds of severe disability or death (mRS ≥5at hospital discharge) by 2.33 times per 1000ng/ml increase. Excessive concentrations of MMP-9 indicated impending parenchymal haematomas and severe disability or death with high specificity. Measurement of MMP-9 within collateral blood vessels is feasible and identifies patients with stroke at risk of major intracerebral haemorrhages and poor outcome before therapeutic recanalisation by EVT, thereby providing evidence of the concept validity of ultra-early local stroke biomarkers. This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Würzburg.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study

The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P=0.023; 0.879 [0.767-0.950], P=0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P>0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P=0.041) to the level of senior pathologists (both P>0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P<0.0001;-34%, P<0.0001;-29%, P<0.0001; and-27%, P=0.00031). ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

The burden and management competency of cardiomyopathies in China: a nationwide survey study

The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Ultrasonication assisted percolation extraction, isolation, identification and in silico studies of secondary metabolites from Caesalpinia bonduc (L.) Roxb. seeds with special reference to the target proteins involved in Benign Prostatic Hyperplasia

Medicinal plant-derived phytochemicals provide a vast pool of diverse bioactive compounds for novel drug development. Caesalpinia bonduc L. Roxb. is a traditional medicinal plant that is reported for diverse pharmacological properties. This study aims to compare conventional (maceration) and novel extraction techniques (ultrasonication assisted maceration extraction) to evaluate their efficiency, yield and bioactive potential of hydroalcoholic extracts from C. bonduc seeds. Furthermore, the study also aimed to isolate the bioactive compounds from the hydroalcoholic seed extract obtained from ultrasonication assisted maceration and in-silico studies of isolated compounds against the protein targets involved in Benign Prostatic Hyperplasia (BPH). For comparing the influence of extraction methods, the seeds were extracted using a novel and conventional techniques. Chemical profiling, antioxidant activities, cytotoxic and apoptotic studies were conducted using obtained extracts. The extract yielded from the novel technique recorded the highest yield, significant antioxidant activity, cytotoxicity and chemical content when compared to the conventional technique. From the hydroalcoholic extract, three major bioactive compounds, namely ethyl glucoside, methyl lineolate and linoleic acid, were isolated using column chromatography. The structures of the compounds were elucidated on the basis of extensive NMR (1H, 13C, DEPT, 2D NMR- HMBC and HSQC) and HR-ESI-MS analysis. In-silico anti-BPH activity of isolated compounds clearly reveals that the compounds were targeting 5α‒Reductase and α1-Adrenoceptor linked to the BPH progressions. Based on this investigation, it is demonstrated that isolated molecules or active molecule-enriched fractions of C. bonduc should be further researched to confirm the anti-BPH activity through in-depth preclinical and clinical research for the development of products. Ethyl glucoside and methyl lineolate were isolated for the first time from C. bonduc.

A process-based approach to transtheoretical clinical research and training

Background The science and practice of psychopathology and psychological intervention of today is more like an island archipelago than it is a single land mass, and connections between different traditions are both limited and fraught with misunderstanding. Method Our analysis and solution to the problem is process-based therapy (PBT). PBT defines psychopathology as failed adaptation processes to a given context. Therapy involves adaptation through context-dependent or context-altering applications of biopsychosocial strategies that allows a goal to be met. Results This coherent approach to more transtheoretical and integrative concepts of clinical training and practice provides a firm foundation by targeting biopsychosocial processes of change, analyzing these processes using an idiographic complex network analytic approach, and organizing findings on the intellectual agora of multi-dimensional and multi-level evolutionary science. Conclusion PBT is a new empirical form of functional analysis, resulting in interventions and trainings that are built on elements or kernels of direct relevance to client’s specific needs. In PBT, case formulation continues as long as treatment persists.

Opinion & Special Article: Community Approach Toward Inclusion of Sex and Gender Diversity in Graduate Neurology Education.

Sex and gender diverse (SGD) neurology trainees include transgender, nonbinary, and intersex people. There has been historical exclusion of SGD trainees from participating in clinical care, medical research, and academic training programs. Therefore, neurology educators have unique opportunities to support SGD trainees and colleagues, but may lack the education to appropriately do so. Training programs and professional organizations can collaborate to create safe pathways for SGD trainees to disclose their identities in professional settings. Referral to community support and resources is important for SGD trainees considering professional disclosure. Educators should address the challenges and discrimination unique to SGD graduate trainees in neurology, such as lack of inclusion, affirming environments, supportive policies, and medical accommodations. Faculty training on sensitivity, bias, and bystander effects should be ongoing among institutions. Topics regarding sex and gender diversity are lacking in graduate medical education. Educational curricula often use outdated terminology or binary paradigms to teach about sex and gender. Health care training inequities may cause downstream harm to SGD patients; therefore, training curricula that are reflective of an accurate and affirming understanding of sex and gender may mitigate the potential for inequities. This article provides recommendations to support SGD neurology trainees and to incorporate specific training on sex and gender diversity in academic neurology curricula. Such support is critical to the career success and development of SGD neurology trainees.

Focus group interviews as part of a clinical research immersion experience

Background Research is an essential component of the dental profession and should be integrated into dental education and training curricula. Opportunities to participate in clinical research studies can enrich the learning experience of those involved. Methods This paper reports a new educational method utilized to enhance the experiences of novice members of a research study team in conducting Focus Group Interviews (FGIs) as part of a double-blind clinical trial exploring an oral probiotic intervention. Study team members participated in a series of in-person FGIs conducted at the beginning and toward the end of a University-based clinical trial, which took place from October 2021 to October 2022. Results Study team members consisting of faculty, staff, and pre-doctoral dental students help plan and conduct interviews, curate, and qualitatively analyze the data. Study team members acquired experience with regard to interpersonal communication skills, organization, research subject communication, the application of human subject protection, FGI methodology, data analysis, developing presentations, and preparing scientific data presentation and publications. Conclusion Exposing dental faculty and students to clinical research studies in university settings can offer opportunities for experiential, multidimensional learning and the development of new research knowledge and skills.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometrystrategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.

Integrating Diversity, Equity, and Inclusion into Preclinical, Clinical, and Public Health Mathematical Models.

Mathematical modelling applied to preclinical, clinical, and public health research is critical for our understanding of a multitude of biological principles. Biology is fundamentally heterogeneous, and mathematical modelling must meet the challenge of variability head on to ensure the principles of diversity, equity, and inclusion (DEI) are integrated into quantitative analyses. Here we provide a follow-up perspective on the DEI plenary session held at the 2023 Society for Mathematical Biology Annual Meeting to discuss key issues for the increased integration of DEI in mathematical modelling in biology.

The Rights of Physicians and Future Physicians Who Are Lactating, Breastfeeding, or Chestfeeding: An American Medical Women's Association Position Article.

Breastfeeding is a fundamental and biologically normal function with well-established benefits for both lactating parents and infants. Despite these benefits, physicians, particularly those in training, often face significant obstacles when attempting to meet their breastfeeding and pumping goals. In response to these challenges, the American Medical Women's Association (AMWA) and a diverse group of health care professionals have come together to advocate for comprehensive lactation support policies in medical learning environments and workplaces. This position article highlights the ethical necessity of comprehensive lactation support in medical educational and workplace settings, emphasizing the importance of not only providing physical accommodations but also fostering a cultural shift, educational initiatives, and policy reforms to empower lactating parents. It offers an examination of the difficulties encountered by lactating parents within medical environments and proposes guidelines for the formulation and enhancement of supportive policies. The position article envisions a future where medical professionals can thrive in both their careers and parenthood through collaborative efforts and a commitment to the key elements of Effective Lactation Support Programs in medical workplaces based on the following: (1) well-equipped lactation facilities, (2) customized work schedules, (3) mentorship and support networks, (4) lactation support in clinical settings, and (5) research and advocacy.

Prevalence and factors associated with uptake of pre-exposure prophylaxis amongst women vulnerable to HIV who received HIV antibodies in Antibody Mediated Prevention HVTN703/HPTN081 trial in Harare, Zimbabwe: a cross-sectional study

IntroductionThere is limited evidence on pre-exposure prophylaxis (PrEP) uptake post-trial participation for women vulnerable to HIV. This study investigates the prevalence and factors associated with PrEP uptake post-participation in an...

International Collaborative Clinical Research (ICCR) Conference Abstracts

International Collaborative Clinical Research (ICCR) Conference Abstracts

Cultural Adaptation of the Functional External Memory Aid Tool for Use in the United Kingdom and Australia

Purpose: The Functional External Memory Aid Tool (FEMAT) is a performance-based measure of applied cognitive-linguistic abilities and attempted use of compensatory aids and strategies (e.g., using a calendar to recall an appointment) through completion of simulated everyday living tasks. The FEMAT was originally developed in the United States (US), and a need arose from clinicians to adapt the FEMAT for use in other countries. The aim of this study is to describe the cultural adaptation process that resulted in the United Kingdom (UK) and Australian (AU) versions of the FEMAT via international clinical research partnerships. Method: The FEMAT was adapted into UK and AU cultures using established guidelines for cultural and linguistic adaptation. The adaptation was completed by researchers and clinicians from the US, UK, and AU, and we followed a six-step process: (a) preparation, (b) forward translation, (c) back translation, (d) committee review, (e) field testing, and (f) finalization. Results: The FEMAT items and materials were successfully adapted from the source culture (i.e., English-US) to the target cultures (i.e., English-UK, English-AU). Through the adaptation process, the FEMAT items were determined to be conceptually appropriate for each culture and minimal modifications were made to the FEMAT materials (e.g., voicemail recordings recorded in target dialect). The finalized FEMAT-English-UK and the FEMAT-English-AU versions are available for free on the FEMAT website. Conclusions: Through successful international clinical research collaborations, the FEMAT was successfully adapted for use in other English-speaking cultures. This work provides guidance to streamline future FEMAT cultural adaptations. Supplemental Material: https://doi.org/10.23641/asha.25564461

Objective Evaluation of Gaze Location Patterns Using Eye Tracking During Cystoscopy and Artificial Intelligence-Assisted Lesion Detection.

Background: The diagnostic accuracy of cystoscopy varies according to the knowledge and experience of the performing physician. In this study, we evaluated the difference in cystoscopic gaze location patterns between medical students and urologists and assessed the differences in their eye movements when simultaneously observing conventional cystoscopic images and images with lesions detected by artificial intelligence (AI). Methodology: Eye-tracking measurements were performed, and observation patterns of participants (24 medical students and 10 urologists) viewing images from routine cystoscopic videos were analyzed. The cystoscopic video was captured preoperatively in a case of initial-onset noninvasive bladder cancer with three low-lying papillary tumors in the posterior, anterior, and neck areas (urothelial carcinoma, high grade, and pTa). The viewpoint coordinates and stop times during observation were obtained using a noncontact type of gaze tracking and gaze measurement system for screen-based gaze tracking. In addition, observation patterns of medical students and urologists during parallel observation of conventional cystoscopic videos and AI-assisted lesion detection videos were compared. Results: Compared with medical students, urologists exhibited a significantly higher degree of stationary gaze entropy when viewing cystoscopic images (p < 0.05), suggesting that urologists with expertise in identifying lesions efficiently observed a broader range of bladder mucosal surfaces on the screen, presumably with the conscious intent of identifying pathologic changes. When the participants observed conventional and AI-assisted lesion detection images side by side, contrary to urologists, medical students showed a higher proportion of attention directed toward AI-detected lesion images. Conclusion: Eye-tracking measurements during cystoscopic image assessment revealed that experienced specialists efficiently observed a wide range of video screens during cystoscopy. In addition, this study revealed how lesion images detected by AI are viewed. Observation patterns of observers' gaze may have implications for assessing and improving proficiency and serving educational purposes. To the best of our knowledge, this is the first study to utilize eye tracking in cystoscopy. University of Tsukuba Hospital, clinical research reference number R02-122.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency (E) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow (Ki/F). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E. Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity (I), which does not affect F', amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

The gut-liver axis in fatty liver disease: role played by natural products

Fatty liver disease, a condition characterized by fatty degeneration of the liver, mainly classified as non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), has become a leading cause of cirrhosis, liver cancer and death. The gut-liver axis is the bidirectional relationship between the gut and its microbiota and its liver. The liver can communicate with the gut through the bile ducts, while the portal vein transports the products of the gut flora to the liver. The intestinal flora and its metabolites directly and indirectly regulate hepatic gene expression, leading to an imbalance in the gut-liver axis and thus contributing to the development of liver disease. Utilizing natural products for the prevention and treatment of various metabolic diseases is a prevalent practice, and it is anticipated to represent the forthcoming trend in the development of drugs for combating NAFLD/ALD. This paper discusses the mechanism of the enterohepatic axis in fatty liver, summarizes the important role of plant metabolites in natural products in fatty liver treatment by regulating the enterohepatic axis, and provides a theoretical basis for the subsequent development of new drugs and clinical research.