Search Results (2,325)

DIALOGUE (DIagnostic AI Learning through Objective Guided User Experience) is a generative artificial intelligence (GenAI)-based training program designed to enhance diagnostic communication skills in medical students. In this single-arm pre–post study, we evaluated whether DIALOGUE could improve students’ ability to disclose a type 2 diabetes mellitus (T2DM) diagnosis with clarity, structure, and empathy. Thirty clinical-phase students completed two pre-test virtual encounters with an AI-simulated patient (ChatGPT, GPT-4o), scored by blinded raters using an eight-domain rubric. Participants then engaged in ten asynchronous GenAI scenarios with automated natural-language feedback. Seven days later, they completed two post-test consultations with human standardized patients, again evaluated with the same rubric. Mean total performance increased by 36.7 points (95% CI: 31.4–42.1; p < 0.001), and the proportion of high-performing students rose from 0% to 70%. Gains were significant across all domains, most notably in opening the encounter, closure, and diabetes specific explanation. Multiple regression showed that lower baseline empathy (β = −0.41, p = 0.005) and higher digital self-efficacy (β = 0.35, p = 0.016) independently predicted greater improvement; gender had only a marginal effect. Cluster analysis revealed three learner profiles, with the highest-gain group characterized by low empathy and high digital self-efficacy. Inter-rater reliability was excellent (ICC ≈ 0.90). These findings provide empirical evidence that GenAI-mediated training can meaningfully enhance diagnostic communication and may serve as a scalable, individualized adjunct to conventional medical education. Full article

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

Background: Cognitive behavioral therapy (CBT) has shown consistent efficacy in individuals with psychosis, as supported by many trials. One classical distinction is that between affective and non-affective psychosis. Few studies have specifically examined the possible moderating role of substantial affective elements. In this systematic review and meta-regression analysis, we assess how CBT response differs across the affective spectrum in psychosis. Methods: We included studies assessing various CBT modalities, including third-wave therapies, administered in people with psychosis. The study protocol is published in the Open Science Framework. Meta-regression was conducted to assess whether the proportion of participants with affective psychosis (AP), as proxied by a documented diagnosis of schizoaffective (SZA) disorder, moderated CBT efficacy across positive, negative, and depressive symptom domains. Results: The literature search identified 4457 records, of which 39 studies were included. The median proportion of SZA disorder participants was 17%, with a total of 422 AP participants represented. Meta-regression showed a trend toward lower CBT efficacy for positive symptoms with a higher SZA disorder proportion (β = +0.10 SMD per 10% increase in AP; p = 0.12), though it was not statistically significant. No significant associations were found for negative (β = +0.05; p = 0.73) or depressive symptoms (β = −0.02; p = 0.78). Heterogeneity was substantial across all models (I² ranging from 54% to 80%), and funnel plot asymmetry was observed in negative and depressive symptoms, indicating possible publication bias. Risk of bias assessment showed the anticipated inherent difficulty of psychotherapies in blinding and possibly dropout rates affecting some studies. Conclusions: Affective symptoms may reduce the effectiveness of CBT for positive symptoms in psychotic disorders, although the findings did not reach statistical significance. Other patient-level characteristics in psychosis could indicate which patients can benefit most from CBT modalities. Full article

Background and Objectives: Discrimination between various causes of exudative pleural effusion (PE) remains a major clinical challenge, and to date, definitive biochemical markers for this discrimination remain lacking. An increasing number of studies have reported that serum C-reactive protein (CRPs), pleural fluid CRP (CRPpf), and CRPpf/CRPs ratio (CRPr) are useful for the differential diagnosis of exudative PE; however, their efficacy rate is not similar in these studies. The majority of these studies were conducted on small groups of subjects, and the efficacy of the gradient between CRPs and CRPpf (CRPg—calculated as CRPs—CRPpf) in this differentiation has not been previously investigated. This study aims to evaluate the efficacy rate of CRPs, CRPpf, CRPg, and CRPr in the differential diagnoses of various causes of exudative PE in a relatively large cohort of patients. Materials and Methods: The research group included 282 subjects with exudative PE—146 had parapneumonic effusion (PPE), 126 had malignant pleural effusion (MPE), and 10 had tuberculous pleural effusion (TPE). The values are presented as mean ± SD. Results: The mean CRPs level was significantly higher in the PPE group compared to the MPE group (p < 0.0001) and the TPE group (p < 0.001), and also significantly higher in the TPE group than in the MPE group (p = 0.0009). Similarly, the mean CRPpf level was significantly higher in the PPE group than in the MPE group (p < 0.0001) and the TPE group (p = 0.04), and also significantly higher in the TPE group than in the MPE group (p < 0.0001). The mean CRPg level was significantly higher in the PPE group than in both the MPE group (p < 0.0001) and the TPE group (p < 0.002). The mean CRPr level did not differ significantly among these groups of exudate. Conclusions: CRPs, CRPpf, and CRPg are effective in the differential diagnosis of exudative PE, while CRPr was not effective in this regard. The main limitation of this study is that the sample size of the TPE group is very small. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Fetal tachyarrhythmias, particularly supraventricular tachycardia (SVT) and atrial flutter (AFL), pose significant clinical challenges, especially when complicated by hydrops fetalis. This article provides a comprehensive review of the tachyarrhythmia types, the diagnostic modalities applied, and the therapeutic strategies followed in fetal tachyarrhythmias. Diagnostic techniques such as M-mode echocardiography and fetal magnetocardiography (fMCG) are highlighted for their capacity to provide real-time, high-quality assessments of fetal cardiac rhythms. The review, also, focuses on pharmacologic management via transplacental therapy, discussing the safety and efficacy of the key agents including digoxin, flecainide, and sotalol, under different clinical scenarios, such as hydropic fetus and renal impairment. In addition to transplacental administration, alternative approaches such as direct fetal intramuscular or intravascular injections are examined. These direct methods, while potentially more effective in refractory cases, carry risks that necessitate specialized expertise and careful consideration of maternal and fetal safety. The limitations of current evidence, largely based on small case studies and retrospective analyses, underscore the need for larger, prospective multicenter observational studies and randomized control trials to establish standardized protocols for fetal tachyarrhythmia management. Overall, this review advocates for a personalized, multidisciplinary approach, emphasizing early fetal tachyarrhythmias diagnosis, tailored treatment regimens that balances efficacy with safety, and rigorous monitoring to optimize outcomes for both the fetus and the mother. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

With the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article

Background: Despite significant advancements in diabetes care, many individuals with type 2 diabetes (T2D) do not receive optimal care and treatment. Digital interventions promoting behavioral changes have shown promising long-term results in supporting healthier lifestyles but are not implemented in most healthcare offerings, maybe due to lack of general practice support and collaboration. This study evaluates the efficacy of the Digital, Individualized, and Collaborative Treatment of T2D in General Practice Based on Decision Aid (DICTA), a randomized controlled trial integrating a patient-centered smartphone application for lifestyle support in conjunction with a clinical decision support (CDS) tool to assist general practitioners (GPs) in optimizing antidiabetic treatment. Methods: The present randomized controlled trial aims to recruit 400 individuals with T2D from approximately 70 GP clinics (GPCs) in Denmark. The GPCs will be cluster-randomized in a 2:3 ratio to intervention or control groups. The intervention group will receive one year of individualized eHealth lifestyle coaching via a smartphone application, guided by patient-reported outcomes (PROs). Alongside this, the GPCs will have access to the CDS tool to optimize pharmacological decision-making through electronic health records. The control group will receive usual care for one year, followed by the same intervention in the second year. Results: The primary outcome is the one-year change in estimated ten-year cardiovascular risk, assessed by SCORE2-Diabetes calculated from age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, age at diabetes diagnosis, HbA1c, and eGFR. Conclusions: If effective, DICTA could offer a scalable, digital-first approach for improving T2D management in primary care by combining patient-centered lifestyle coaching with real-time pharmacological clinical decision support. Full article

Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Biomarkers play a pivotal role in disease diagnosis, therapeutic efficacy evaluation, prognostic assessment, and drug screening. However, the trace concentrations of these markers in complex physiological environments pose significant challenges to efficient detection. It is necessary to avoid interference from non-specific signals, which may lead to misjudgment of other substances as biomarkers and affect the accuracy of detection results. With the rapid advancements in electrochemical technologies and artificial intelligence (AI) algorithms, intelligent electrochemical biosensors have emerged as a promising approach for biomedical detection, offering speed, specificity, high sensitivity, and accuracy. This review focuses on elaborating the latest applications of AI-empowered electrochemical biosensors in the biomedical field, including disease diagnosis, treatment monitoring, drug development, and wearable devices. AI algorithms can further improve the accuracy, sensitivity, and repeatability of electrochemical sensors through the screening and performance prediction of sensor materials, as well as the feature extraction and noise reduction suppression of sensing signals. Even in complex physiological microenvironments, they can effectively address common issues such as electrode fouling, poor signal-to-noise ratio, chemical interference, and matrix effects. This work may provide novel insights for the development of next-generation intelligent biosensors for precision medicine. Full article

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management. Full article