Clinical Setting Research Articles

Fabrication of a graphite-paraffin carbon paste electrode and demonstration of its use in electrochemical detection strategies.

Electrochemical detection methods hold many advantages over their optical counterparts, such as operation in complex sample matrices, low-cost and high volume manufacture and possible equipment miniaturisation. Despite these advantages, the use of electrochemical detection is currently limited in the clinical setting. There is a wide range of potential electrode materials, selected for optimal signal-to-noise ratios and reproducibility when detecting target analytes. The use of carbon paste electrodes (CPEs) for electrochemical detection can be limited by their analytical performance, however they remain very attractive due to their low cost and biocompatibility. This paper presents the fabrication of an easy-to-make and use graphite powder/paraffin wax paste combined with a substrate produced via additive manufacturing and confirms its functionality for both direct and indirect electrochemical measurements. The produced CPEs enable the direct voltammetric detection of hexaammineruthenium(III) chloride and dopamine at an experimental limit of detection (ELoD) of 62.5 μM. The key inflammatory biomarker Interleukin-6 through an enzyme-linked immunosorbant assay (ELISA) was also quantified, yielding a clinically-relevant ELoD of 150 pg ml-1 in 10% human serum. The performance of low-cost and easy-to-use CPEs obtained in 0.5 hours is showcased in this study, demonstrating the platform's potential uses for point-of-need electroanalytical applications.

The protective effect of benfotiamine on gastric ulcers in male rats: an experimental study.

Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.The results demonstrated that 100 and 200mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine's gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings.

Activities-specific balance confidence scale: a Rasch evaluation of the Arabic version in lower-limb prosthetic users.

To evaluate the psychometric properties of the Arabic version of the Activities-Specific Balance Confidence Scale using the 5-option response categories for individuals with lower limb amputation (ABC-5/Ar). This was a methodological study on a convenience sample of individuals with unilateral lower-limb amputation attending outpatient rehabilitation centres in Saudi Arabia and Turkey (N = 155). Rasch analysis (WINSTEPS version 4.6.5) was used to examine the 5-categories rating scale structure, item fit, item difficulty hierarchy, person separation index, unidimensionality, local item dependency, and differential item functioning. The ABC-5/Ar 5-response option demonstrated an appropriate model fit. Most items fit the Rasch model, except for item #12 "walk in a crowded mall," which showed an overfitting value of 0.63. The person separation indices 2.95 (Cronbach's α = 0.96). Principal component analysis of residuals confirmed the unidimensionality of the scale; however, local dependency was detected between item #14 "Ride in escalator holding rail," and item #15 "Ride in escalator not holding rail." The findings suggest that the ABC-5/Ar shows promise in assessing balance confidence in Arabic-speaking lower-limb prosthesis users. However, further studies with larger sample sizes and in diverse clinical contexts are needed to confirm its effectiveness in various clinical settings.

Artificial intelligence methods available for cancer research.

Cancer is a heterogeneous and multifaceted disease with a significant global footprint. Despite substantial technological advancements for battling cancer, early diagnosis and selection of effective treatment remains a challenge. With the convenience of large-scale datasets including multiple levels of data, new bioinformatic tools are needed to transform this wealth of information into clinically useful decision-support tools. In this field, artificial intelligence (AI) technologies with their highly diverse applications are rapidly gaining ground. Machine learning methods, such as Bayesian networks, support vector machines, decision trees, random forests, gradient boosting, and K-nearest neighbors, including neural network models like deep learning, have proven valuable in predictive, prognostic, and diagnostic studies. Researchers have recently employed large language models to tackle new dimensions of problems. However, leveraging the opportunity to utilize AI in clinical settings will require surpassing significant obstacles-a major issue is the lack of use of the available reporting guidelines obstructing the reproducibility of published studies. In this review, we discuss the applications of AI methods and explore their benefits and limitations. We summarize the available guidelines for AI in healthcare and highlight the potential role and impact of AI models on future directions in cancer research.

Cervical Auscultation for Detecting Oropharyngeal Aspiration in Paediatric and Adult Populations: A Systematic Review and Meta-Analysis.

Cervical auscultation (CA) involves listening to swallowing and respiratory sounds and/or vibrations to detect oropharyngeal aspiration (OPA). CA has shown promising diagnostic test accuracy when used with the clinical swallowing examination and is gaining popularity in clinical practise. There has not been a review to date analysing the accuracy of CA in paediatric and adult populations with meta-analyses. To determine the accuracy of CA in detecting OPA in paediatric and adult populations, when compared to instrumental assessments. Databases searched included MEDLINE, PubMed, Embase, CINAHL, AustHealth, Cochrane and Web of Science. The search was restricted between 01 October 2012 and 01 October 2022. Inclusion criteria included (a) all clinical populations of all ages, (b) who have had an instrumental assessment and (c) CA. All study types were included. Studies were reviewed independently by two authors. The methodological quality of the studies was analysed using the QUADAS-2. Ten studies met the inclusion criteria for this review and meta-analyses. The pooled diagnostic performance of CA in detecting OPA was 0.91 for sensitivity and 0.79 for specificity. The area under the curve summary receiver operating curve (sROC) was estimated to be 0.86, thereby indicating good discrimination of OPA. Most studies scored high for risk of bias in at least one domain in the QUADAS-2, likely attributed to a lack of high-quality prospectively designed studies. There are promising diagnostic test accuracies for the use of CA in detection of OPA. Future research could include using CA in specific clinical populations and settings, and identifying standardised criteria for CA.

Basophil FceRI expression-A management tool in anti-IgE treatment of allergic asthma.

Immune-based therapy targeting immunoglobulin E (IgE), anti-IgE treatment, has emerged as an adjunct treatment for children with severe allergic asthma. After start of anti-IgE treatment, an effect of the treatment cannot be monitored by Total-IgE, because current methods measure both bound and free IgE molecules. Basophil activation test may be very useful for monitoring anti-IgE treatment efficacy. The objective of this paper is to evaluate if basophil activation test is applicable in regulating the anti-IgE treatment. A case series of 20 children with IgE-mediated severe allergic asthma were treated according to guidelines with anti-IgE (Omalizumab). Blood samples were drawn for total IgE, specific IgE, number of IgE receptors (FcεRI) and basophil sensitivity were measured at baseline before anti-IgE treatment and 4 months after initiation of anti-IgE treatment. A total of 19 out of 20 children had statistically significant and clinically relevant effects of anti-IgE treatment on symptom score, lung function and medication. All 20 children had a significant reduction in basophil allergen sensitivity and the number of IgE receptors (FcεRI) on blood basophils. Anti-IgE treatment was found to be well controlled by measuring basophil allergen sensitivity and FceRI density on blood basophils. This cohort study demonstrates a promising method, measuring basophil allergen sensitivity and in particular blood basophil FceRI density, concerning the monitoring of anti-IgE treatment in different clinical situations. There are no randomized controlled trials evaluating this method in clinical settings.

Assessment during clinical education among nursing students using two different assessment instruments

BackgroundAssessment of undergraduate students using assessment instruments in the clinical setting is known to be complex. The aim of this study was therefore to examine whether two different assessment instruments, containing learning objectives (LO`s) with similar content, results in similar assessments by the clinical supervisors and to explore clinical supervisors’ experiences of assessment regarding the two different assessment instruments.MethodA mixed-methods approach was used. Four simulated care encounter scenarios were evaluated by 50 supervisors using two different assessment instruments. 28 follow-up interviews were conducted. Descriptive statistics and logistic binary regression were used for quantitative data analysis, along with qualitative thematic analysis of interview data.ResultWhile significant differences were observed within the assessment instruments, the differences were consistent between the two instruments, indicating that the quality of the assessment instruments were considered equivalent. Supervisors noted that the relationship between the students and supervisors could introduce subjectivity in the assessments and that working in groups of supervisors could be advantageous. In terms of formative assessments, the Likert scale was considered a useful tool for evaluating learning objectives. However, supervisors had different views on grading scales and the need for clear definitions. The supervisors concluded that a complicated assessment instrument led to limited very-day usage and did not facilitate formative feedback. Furthermore, supervisors discussed how their experiences influenced the use of the assessment instruments, which resulted in different descriptions of the experience. These differences led to a discussion of the need of supervisor teams to enhance the validity of assessments.ConclusionThe findings showed that there were no significant differences in pass/fail gradings using the two different assessment instruments. The quantitative data suggests that supervisors struggled with subjectivity, phrasing, and definitions of the LO´s and the scales used in both instruments. This resulted in arbitrary assessments that were time-consuming and resulted in limited usage in the day-to-day assessment. To mitigate the subjectivity, supervisors suggested working in teams and conducting multiple assessments over time to increase assessment validity.

Understanding the Evolution and Transmission Dynamics of Antibiotic Resistance Genes: A Comprehensive Review.

Antibiotic resistance poses a formidable challenge to global public health, necessitating comprehensive understanding and strategic interventions. This review explores the evolution and transmission dynamics of antibiotic resistance genes, with a focus on Bangladesh. The indiscriminate use of antibiotics, compounded by substandard formulations and clinical misdiagnosis, fuels the emergence and spread of resistance in the country. Studies reveal high resistance rates among common pathogens, emphasizing the urgent need for targeted interventions and rational antibiotic use. Molecular assessments uncover a diverse array of antibiotic resistance genes in environmental reservoirs, highlighting the complex interplay between human activities and resistance dissemination. Horizontal gene transfer mechanisms, particularly plasmid-mediated conjugation, facilitate the exchange of resistance determinants among bacterial populations, driving the evolution of multidrug-resistant strains. The review discusses clinical implications, emphasizing the interconnectedness of environmental and clinical settings in resistance dynamics. Furthermore, bioinformatic and experimental evidence elucidates novel mechanisms of resistance gene transfer, underscoring the dynamic nature of resistance evolution. In conclusion, combating antibiotic resistance requires a multifaceted approach, integrating surveillance, stewardship, and innovative research to preserve the efficacy of antimicrobial agents and safeguard public health.

Implicit learning provides advantage over explicit learning for gait-cognitive dual-task interference

Dual-task performance holds significant relevance in real-world scenarios. Implicit learning is a possible approach for improving dual-task performance. Analogy learning, utilizing a single metaphor to convey essential information about motor skills, has emerged as a practical method for fostering implicit learning. However, evidence supporting the effect of implicit learning on gait-cognitive dual-task performance is insufficient. This exploratory study aimed to examine the effects of implicit and explicit learning on dual-task performance in both gait and cognitive tasks. Tandem gait was employed on a treadmill to assess motor function, whereas serial seven subtraction tasks were used to gauge cognitive performance. Thirty healthy community-dwelling older individuals were randomly assigned to implicit or explicit learning groups. Each group learned the tandem gait task according to their individual learning styles. The implicit learning group showed a significant improvement in gait performance under the dual-task condition compared with the explicit learning group. Furthermore, the implicit learning group exhibited improved dual-task interference for both tasks. Our findings suggest that implicit learning may offer greater advantages than explicit learning in acquiring autonomous motor skills. Future research is needed to uncover the mechanisms underlying implicit learning and to harness its potential for gait-cognitive dual-task performance in clinical settings.

Midwifery Students' Experiences of Bias in the Clinical Setting: Prevalence, Types, and Impact.

Exposure to bias in clinical learning environments may undermine students' confidence, cause emotional harm, impede learning, and potentially delay graduation. However, little is known about the prevalence of bias experienced by midwifery students in the United States. This cross-sectional, descriptive study aimed to quantify clinical midwifery students' experiences of bias based on 7 self-identified characteristics (gender identity, race or ethnicity, body size, age, sexual orientation, religion, and occupational background). Additionally, this research explored the impact of bias on student well-being, learning, and professional commitment. The survey consisted of 39 items addressing (1) prevalence and types of bias, (2) emotional impact and influence on clinical learning, (3) ways students coped, (4) whether anyone spoke up at the time bias occurred, (5) whether students reported bias to faculty, and (6) impact of bias on commitment to midwifery. The survey was distributed to midwifery students and recent graduates in 2022 via American College of Nurse-Midwives email discussion lists and social media. Participants were eligible if they were in a clinical rotation in an Accreditation Commission for Midwifery Education-accredited midwifery program between 2019 and 2022. Surveys were returned by 383 participants, with 301 meeting inclusion criteria. Most participants (66.5%) reported personally experiencing or witnessing bias against at least 1 of 7 personal characteristics. The most commonly reported biases were related to gender, occupational background, age, and race or ethnicity. Only half of the participants reported these occurrences to someone with academic authority, and nearly a third considered withdrawing from their educational programs. In this study bias was common and significantly impacted students. These results underscore the need for creative and bold interventions at personal, educational, and institutional levels to prevent and mitigate bias. Safeguarding clinical learning environments will enable students to thrive, graduate with confidence and competence, and thereby contribute to the diversification and strengthening of the midwifery profession.

The link between patient safety competence and adverse event among master of nursing students: a cross-sectional mixed-methods study

BackgroundPatient safety (PS) is a core competency for registered nurses. However, there is a gap between the PS competence of nursing students and their clinical experience in PS. This study explored the effect of PS competence levels on the occurrence of adverse events (AEs) among nursing master’s students in China.MethodsA sequential mixed methods design was used, with a purposive sample across seven colleges. A total of 327 graduate nursing students, aged 22 to 38, participated in the survey, and 15 participated in qualitative interviews. The Health Professional Education in Patient Safety Survey (H-PEPSS) assessed the students’ competence levels in PS. The respondents also reported any AEs that they had been involved in over the past year.ResultsA total of 78 AEs occurred in the past year, with 17.7% of the participants involved 1 to 3 AEs. The most common AEs were medication administration errors (30.77%) and improper use of medical equipment/supplies (28.20%). Students acquired more competencies from the clinical setting than from the classroom setting. Three competencies learned from classroom settings were associated with clinical AEs: low clinical safety skills [OR = 0.61], inappropriate identify, response to and disclosing AE and close calls [OR = 0.454], and low confidence in working in teams with other health professionals [OR = 2.168]. Qualitative data analysis revealed five themes: recognizing AEs, reducing harm by addressing immediate risks to patients and others involved, promoting safe medication and clinical practice, managing members’ authority and team dynamics, and dealing with inter-professional conflict.ConclusionsThe quantitative and qualitative data align, supporting the enhancement of students’ PS competence.

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

Immune-related gene signature improves prognosis prediction in patients with breast cancer and associates it with tumor immunity and inflammatory response

BackgroundThe prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients.MethodsWe analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes.ResultsPatients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration.ConclusionsThe immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses

BackgroundHigh-grade gliomas including glioblastoma (GBM) and diffuse midline gliomas (DMG) represent the most lethal and aggressive brain cancers where current treatment modalities offer limited efficacy. Chimeric antigen receptor (CAR) T...

Homeostasis and self-regulation

ABSTRACT Homeostasis, a self-regulating process that aims for stability, is presented to be the most fundamental regulatory principle of the psyche. Stability, or avoiding the extremes, is crucial for survival. The mind operates on different layers of homeostasis. Freud’s three phylogenetic layers and regulating principles, namely nirvana, constancy, and psychic structure, are reviewed here. The self-image and its identity of perception form the core of the structure. In a clinical context, a cure that deviates too much from the self-image is perceived as threatening stability. The therapeutic relationship is an ideal setting for fostering the ego’s mentalization capacity and the development of psychic structure. This paper demonstrates how mentalization and autonomous self-regulation challenge pathologic homeostatic regulation through clinical examples. The defensive resistance to cure, with its intriguing deep unconscious phylogenetic roots in homeostatic regulation, underscores the practical implications of these theoretical viewpoints in a clinical setting.

Exploring the association between patient-drawn pain diagrams and psychological and physical health variables: A large-scale study of patients with low back pain.

Despite the use of Patient-Drawn Pain Drawings (PDPDs) in clinical settings, their validity as indicators of psychological distress remains debated. We aimed to assess the association between PDPD areas and physical health and psychological variables. This study analysed digitally-drawn PDPDs from 15,345 chronic low back pain (LBP) patients at a Danish outpatient hospital unit. We employed a novel quantitative approach to calculate four log-transformed geometric pain areas for each PDPD. We assessed six psychological constructs and seven physical health variables. Associations were modelled using multivariable linear regression. Increasing leg pain intensity (estimates from 0.12 to 0.25), disability (estimates from 0.3 to 0.14), and pain duration (estimates from 0.10 to 0.33) had the strongest associations with increasing pain areas. Conversely, increasing fear of movement (estimates from -0.02 to -0.05) and catastrophizing (estimates from -0.02 to -0.03) were associated with slight reductions in pain areas. Anxiety and depression had the weakest and most uncertain relationships to pain area size. Increasing levels of leg pain intensity, pain duration, and pain-related disability were consistently associated with larger geometric pain areas in PDPDs. Conversely, the associations between the psychological constructs and the geometric pain areas exhibited varying directions and were notably weaker. Clinicians are encouraged to focus on the association of PDPDs with physical symptoms rather than psychological conditions during clinical assessments. This large-scale study demonstrates that extensive pain areas in pain drawings drawn by LBP patients do not signify psychological distress. Our findings reveal that these pain representations are more closely linked to increased pain intensity, pain duration, and disability rather than being independently associated with psychological factors. Clinicians are encouraged to focus on the association of extensive pain areas with physical symptoms rather than psychological distress during clinical assessments.

Human Leukocyte Antigen-DR and Cluster Designation 34: Double-negative Acute Myeloid Leukemias – Our Experience in Clinical Setting

Abstract Introduction: Dual negativity for cluster designation (CD) 34 and human leukocyte antigen (HLA)-DR antigen in leukemia panel is an important finding in clinical practice. The combination of this finding though seen classically in acute promyelocytic leukemia (APL) is not specific to it but can be seen in many other myeloid leukemias like the ones associated with nucleophosmin 1 (NPM1) or FMS-related tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) abnormalities. It is important to identify APL from non-APL leukemia as treatment and prognosis vary. Aims and Objectives: We analyzed CD 34 and HLA-DR dual-negative acute myeloid leukemia (AML) cases presented to us over 2.5 years (26 cases) and segregated them into APL and non-APL groups to study their morphological/flow cytometric and cytogenetic profile and correlation with treatment response. Materials and Methods: It was a prospective study including all newly diagnosed AMLs showing CD 34 and HLA-DR dual negativity in flow cytometry profile. Cases in which complete information/cytogenetics/molecular profile were not available, were excluded from the study. The patients were followed up till the end of induction to look for morphological response to induction therapy. The clinical and treatment records were pulled out from the patient database after ethical committee clearance. Results: A total of 139 new AML cases were encountered during the study period out of which 28 (20%) were found to be dual negative for CD34 and HLA-DR. The non-APL group showed higher mean age, TLC at baseline, variable morphology, and more number of aberrant expression on flow cytometry profile. No significant difference was noted in terms of gender, presence of hepatosplenomegaly, DIC as complication, or percentage of blasts/blasts equivalent at baseline. Our study found that while all APL patients had PML-RARA, the associated molecular abnormalities were much lesser as compared to the non-APL group which showed a variety of abnormalities such as NPM1, FLT3, RAS mutation, and mutations involving epigenetic modifiers. The response rate to induction therapy was significantly lower in the non-APL group as compared to the APL group. Conclusion: The non-APL myeloid leukemia which is dual negative is commonly found to be associated with cup-shaped morphology, NPM, or FLT3-ITD mutation along with other abnormalities. These patients were older in age, showed higher TLC and higher blast counts, associated with poorer response to induction therapy as compared to the APL group.

Assessing the use of the novel tool Claude 3 in comparison to ChatGPT 4.0 as an artificial intelligence tool in the diagnosis and therapy of primary head and neck cancer cases.

Head and neck squamous cell carcinoma (HNSCC) is a complex malignancy that requires a multidisciplinary tumor board approach for individual treatment planning. In recent years, artificial intelligence tools have emerged to assist healthcare professionals in making informed treatment decisions. This study investigates the application of the newly published LLM Claude 3 Opus compared to the currently most advanced LLM ChatGPT 4.0 for the diagnosis and therapy planning of primary HNSCC. The results were compared to that of a conventional multidisciplinary tumor board; (2) Materials and Methods: We conducted a study in March 2024 on 50 consecutive primary head and neck cancer cases. The diagnostics and MDT recommendations were compared to the Claude 3 Opus and ChatGPT 4.0 recommendations for each patient and rated by two independent reviewers for the following parameters: clinical recommendation, explanation, and summarization in addition to the Artificial Intelligence Performance Instrument (AIPI); (3) Results: In this study, Claude 3 achieved better scores for the diagnostic workup of patients than ChatGPT 4.0 and provided treatment recommendations involving surgery, chemotherapy, and radiation therapy. In terms of clinical recommendations, explanation and summarization Claude 3 scored similar to ChatGPT 4.0, listing treatment recommendations which were congruent with the MDT, but failed to cite the source of the information; (4) Conclusion: This study is the first analysis of Claude 3 for primary head and neck cancer cases and demonstrates a superior performance in the diagnosis of HNSCC than ChatGPT 4.0 and similar results for therapy recommendations. This marks the advent of a newly launched advanced AI model that may be superior to ChatGPT 4.0 for the assessment of primary head and neck cancer cases and may assist in the clinical diagnostic and MDT setting.

Genetic determinants and phenotypic consequences of blood T-cell proportions in 207,000 diverse individuals

T-cells play a critical role in multiple aspects of human health and disease. However, to date the genetic determinants of human T-cell abundance have not been studied at scale because assays quantifying T-cell abundance are not widely used in clinical or research settings. The complete blood count clinical assay quantifies lymphocyte abundance which includes T-cells, B-cells, and NK-cells. To address this gap, we directly estimate T-cell fractions from whole genome sequencing data in over 200,000 individuals from the multi-ethnic TOPMed and All of Us studies. We identified 27 loci associated with T-cell fraction. Interrogating electronic health records identified clinical phenotypes associated with T-cell fraction, including notable changes in T-cell proportions that were highly dynamic over the course of pregnancy. In summary, by estimating T-cell fraction, we obtained new insights into the genetic regulation of T-cells and identified disease consequences of T-cell fractions across the human phenome.

Efficacy and Safety of Escalating the Dose of Oral Semaglutide from 7 to 14mg: A Single-Center, Retrospective Observational Study.

The efficacy and safety of oral semaglutide, the first glucagon-like peptide1 receptor agonist available in tablet form for the treatment of type2 diabetes, were established in the phase3a PIONEER program. However, evidence regarding the titration of oral semaglutide in real-world clinical settings remains insufficient. This study aimed to elucidate the therapeutic advantages of escalating the dose of oral semaglutide from 7 to 14mg through clinical data analysis. This retrospective observational study was conducted at a single center in Japan, focusing on adults with type2 diabetes who were initiated on 14mg oral semaglutide. The primary endpoint was the alteration in HbA1c levels 24weeks after the initial prescription of 14mg oral semaglutide. Secondary endpoints included changes in metabolic parameters and the incidence of adverse events. Data from 66 patients who met the inclusion criteria were analyzed. The mean change in HbA1c levels from baseline to 24weeks following dose escalation was - 0.5 ± 0.8% [from 7.4 ± 1.0% at baseline to 7.0 ± 0.9% at 24weeks (p < 0.01)]. Moreover, a significant reduction in body weight of - 2.0 ± 4.4kg was observed at 24weeks [from 90.0 ± 20.5kg at baseline to 88.2 ± 21.4kg at 24weeks (p < 0.01)], with 41% of patients achieving at least a 3% reduction compared to baseline. Gastrointestinal disorders emerged as the most prevalent adverse event (10.6%), particularly nausea (7.6%), although predominantly of mild or moderate severity, with no instances of serious adverse events necessitating drug discontinuation. Escalating the dose of oral semaglutide to 14mg could be an effective approach for enhancing glycemic control and managing body weight in individuals with type2 diabetes.