Medical sciences (Basel, Switzerland)最新文献

{"title":"From Sentiment to Signal: Narrative-Physiology Discordance as a Testable Target for Artificial Intelligence in Critical Care.","authors":"Ignacio Martin-Loeches, Hongliu Cai","doi":"10.3390/medsci14050595","DOIUrl":"10.3390/medsci14050595","url":null,"abstract":"<p><p>Intensive care units generate dense physiological, laboratory, imaging, microbiological and treatment data, yet much of the clinical reasoning that drives decisions is recorded only in free text. Over the past decade, clinical sentiment analysis has repeatedly shown that the affective tone of nursing and medical notes is associated with mortality. The incremental discrimination over established severity scores has nevertheless been small, of the order of 0.01 in the area under the receiver operating characteristic curve in the largest published intensive care cohort, and general-purpose sentiment tools transfer poorly to critical care text. We argue that this plateau reflects a misspecified prediction target rather than a limitation of natural language processing. Mortality at 28 days is not the question the clinician asks at the bedside. We propose that the clinically useful quantity is the narrative-physiology discordance score: the signed difference, expressed on a common calibrated scale, between the short-horizon deterioration risk implied by the documented assessment and the risk implied by time-aligned multimodal data. We specify this quantity formally, fix index time and forecast horizon, and set out the leakage, copy-forward and provenance controls without which retrospective performance is uninterpretable. We then treat alert burden as a design constraint rather than a post hoc observation, deriving the operating threshold from an explicit and context-dependent alert budget, and we outline a staged evaluation pathway aligned with TRIPOD + AI and DECIDE-AI in which discordant cases are adjudicated by clinicians. Until that adjudication has been performed, discordance is a record-level inconsistency that prompts reassessment, not evidence of missed deterioration. Clinical sentiment analysis becomes useful when it stops predicting death and starts flagging disagreement.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges of Effective Clinical Teaching Organization at Public Medical Universities in Poland: A Delphi Method Study.","authors":"Pawel Zawieja, Anna Lipert, Remigiusz Kozlowski","doi":"10.3390/medsci14050594","DOIUrl":"10.3390/medsci14050594","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Clinical teaching as a form of interpersonal education organized in a real clinical setting is very dynamic and sensitive to many factors that may influence its effectiveness. To strengthen clinical education organization, responsible bodies should meet emerging challenges, which are best understood from the perspective of the direct recipients and providers of clinical teaching. Therefore, the aim of this study was to explore and analyze the existing challenges of clinical teaching organization in public medical universities in Poland from students' and academics' perspectives. <b>Methods</b>: A modified two-round Delphi study was conducted in six Polish medical universities. Round 1 included 218 experts (131 students and 87 academics), while 124 experts completed Round 2 (attrition rate: 43.1%). Consensus was predefined as a median score ≥ 4.0 and IQR ≤ 1.0. <b>Results</b>: Items with the highest mean values (approximately 4.4 on a five-point Likert scale) indicated a clear perception of space shortages and demand for updated teaching methods. The exploratory correlation revealed two broad thematic patterns: (1) space and overcrowding; (2) teaching methods. <b>Conclusions</b>: The findings suggest that stakeholders perceive educational space, overcrowding and modernization of teaching methods as important areas for improvement in clinical teaching.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Audiometric Monitoring and Its Determinants in Patients Undergoing Chemoradiotherapy for Head and Neck Cancer.","authors":"Anda-Ioana Morgovan, Nicolae Constantin Balica, Cristina Mihaela Negru, Kristine Guran, Alexandru Orasan, Mihaela Andreea Banta, Crina Oana Pintea, Mihaela Iuliana Ciortan Sirbu, Horatiu Eugen Stefanescu","doi":"10.3390/medsci14050593","DOIUrl":"10.3390/medsci14050593","url":null,"abstract":"<p><strong>Background and objectives: </strong>Audiometric monitoring is recommended for patients receiving ototoxic (chemo)radiotherapy for head and neck cancer (HNC), yet real-world uptake is poorly characterized and potentially inequitable. We quantified the uptake and timing of audiometric testing and examined rural-urban residence and age as candidate determinants.</p><p><strong>Materials and methods: </strong>We conducted a single-center retrospective cohort study of 70 consecutive patients with HNC treated with radiotherapy between November 2024 and September 2025, comparing rural (<i>n</i> = 32) and urban (<i>n</i> = 38) residents. Outcomes were audiometric testing at treatment initiation, repeat audiometry during follow-up, and post-treatment hearing change. Analyses included Fisher's exact and Mann-Whitney U tests, Spearman correlations, Firth-penalized logistic regression, inverse probability of treatment weighting (IPTW), restricted cubic splines, and sensitivity analyses.</p><p><strong>Results: </strong>Audiometry at treatment initiation was performed in 31/70 patients (44.3%) and repeat audiometry in only 10/70 (14.3%); among tested patients with documented dates, just 19.4% underwent audiometry before the first radiotherapy fraction, so that a true pre-exposure baseline existed for only 6/70 patients (8.6%). Uptake at initiation was 53.7% with concurrent cisplatin, 14.3% with carboplatin, and 36.4% with radiotherapy alone (<i>p</i> = 0.114). Uptake did not differ by residence (rural 40.6% vs. urban 47.4%; odds ratio (OR) 0.76, 95% confidence interval (CI) 0.30-1.96, <i>p</i> = 0.634), with an IPTW-weighted risk difference of -9.9% (95% CI -30.9 to +11.8). Age was the dominant determinant: uptake fell from 90.5% below 65 years to 24.5% at ≥65 years (adjusted OR per decade 0.32, 95% CI 0.15-0.71, <i>p</i> = 0.005), with significant non-linearity (<i>p</i> = 0.015). Pre-existing hearing loss was associated with lower testing (OR 0.29, 95% CI 0.10-0.91, <i>p</i> = 0.032). Post-treatment hearing change occurred in 54.3% overall (rural 46.9% vs. urban 60.5%, <i>p</i> = 0.336), comprising a subjective hearing complaint in 51.4% and audiometric deterioration in six of the nine patients with paired audiograms.</p><p><strong>Conclusions: </strong>Audiometric monitoring was incomplete, rarely obtained before irradiation, and steeply age-patterned, whereas rural residence was not associated with lower uptake; structured, exposure-based referral pathways, triggered by planned cisplatin and clinically relevant cochlear dose and applied irrespective of age, are warranted.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, Regional, and Country Incidence of Peritoneal Dialysis-Associated Peritonitis in the Contemporary Peritoneal Dialysis Practice: A Systematic Review and Meta-Analysis.","authors":"Surapon Nochaiwong, Chidchanok Ruengorn, Kajohnsak Noppakun, Kiatkriangkrai Koyratkoson, Mati Chuamanochan, Panjit Chieosilapatham, Pajaree Mongkhon, Nuttaya Wachiraphansakul, Thanawat Vongchaiudomchoke, Tanun Ngamvichchukorn, Kednapa Thavorn, Manish M Sood, Greg A Knoll, Apichat Tantraworasin","doi":"10.3390/medsci14050592","DOIUrl":"10.3390/medsci14050592","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Since peritoneal dialysis (PD) has been used in nephrology practice for several decades, contemporary evidence on global, regional, and country incidence rates of PD-associated peritonitis has not been comprehensively synthesized. We performed a systematic review and meta-analysis to estimate the incidence rates of PD-associated peritonitis worldwide in contemporary PD practice. &lt;b&gt;Methods&lt;/b&gt;: We systematically searched 6 electronic databases to identify all relevant English-language articles that reported rates of PD-associated peritonitis according to International Society for Peritoneal Dialysis (ISPD) criteria, regardless of age, sex, or PD modality, from 2011 to 2026. We used a random-effects meta-analysis to estimate the pooled incidence rate (episodes per patient-year), with corresponding 95% confidence intervals. We reported summary incidence rates of PD-associated peritonitis for the global estimation (overall rate), World Health Organization (WHO) region, and each country. We also estimated meta-syntheses by causative microorganism of PD-associated peritonitis. &lt;b&gt;Results&lt;/b&gt;: We identified 12,364 records, of which 153 unique study populations of PD patients fulfilled the study selection criteria. These included over 132,000 PD patients from 37 countries worldwide. Despite substantial heterogeneity, the global incidence rate estimate of PD-associated peritonitis was 0.31 (0.28-0.34) episodes per patient-year (total peritonitis episodes, 88,769; total patient-years at risk, 264,296.30). According to WHO region (&lt;i&gt;p&lt;/i&gt; for difference between regions &lt;0.001), the regional incidence rates of PD-associated peritonitis were 0.99 (0.68-1.45) for the African Region; 0.38 (0.31-0.45) for the Region of the Americas; 0.41 (0.35-0.48) for the South-East Asia Region; 0.37 (0.30-0.46) for the European Region; 0.39 (0.31-0.49) for the Eastern Mediterranean Region; and 0.21 (0.19-0.24) for the Western Pacific Region. Across 37 different countries, the top three highest incidence rates of PD-associated peritonitis were observed in South Africa, followed by Portugal and Sri Lanka. Meanwhile, the top three lowest incidence rates of PD-associated peritonitis were observed in South Korea, followed by mainland China and Japan. According to the ISPD benchmark, 10 of the 37 included countries had an overall PD-associated peritonitis rate &gt; 0.40 episodes per patient-year. Regarding the causative microorganisms of PD-associated peritonitis, Gram-positive bacteria had the highest pooled incidence rate of PD-associated peritonitis (0.127 [0.113-0.142]), followed by culture-negative (0.073 [0.065-0.083]), Gram-negative bacteria (0.065 [0.058-0.073]), polymicrobial (0.017 [0.014-0.021]), fungus (0.009 [0.008-0.011]), and Mycobacterium (0.004 [0.003-0.006]). &lt;b&gt;Conclusions&lt;/b&gt;: These global estimates of PD-associated peritonitis incidence rates demonstrated variation across regions and countries. Given differences in healthcare ","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome.","authors":"Marko P Ravić, Ivan M Srejović, Marijana M Andjić, Maja D Murić, Jasmina Z Sretenović, Nevena S Jeremić, Isidora M Milosavljević, Miona Lj Vuletić, Nemanja N Murić, Katarina R Ravić, Sergey B Bolevich, Svetlana P Sergeeva, Alexander A Gorbunov, Stefani S Bolevich, Vladimir Lj Jakovljević, Jovana N Novaković","doi":"10.3390/medsci14050590","DOIUrl":"10.3390/medsci14050590","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metabolic syndrome (MetS) increases susceptibility to myocardial ischemia/reperfusion (I/R) injury through metabolic disturbance, hypertension, and oxidative stress. This study aimed to compare the effects of liraglutide and semaglutide on post-ischemic cardiac function, oxidative stress, and histomorphological changes in rats with MetS.</p><p><strong>Methods: </strong>MetS was induced in male Wistar rats by a high-fat diet followed by low-dose streptozotocin. After confirmation of MetS, animals were treated with saline, liraglutide, or semaglutide for 6 weeks. Blood pressure, glycemia, oral glucose tolerance, and lipid profile were assessed during the protocol. In vivo cardiac function was evaluated by echocardiography, whereas ex vivo I/R injury was induced using the Langendorff technique. Cardiodynamic parameters, coronary flow, oxidative stress markers, and histological changes in the heart, liver, and pancreas were analyzed.</p><p><strong>Results: </strong>Both liraglutide and semaglutide improved the cardiometabolic profile of MetS rats, with semaglutide showing a more evident effect on body weight control. In the Langendorff model, both treatments improved post-ischemic recovery of myocardial contractility and relaxation during reperfusion. Treated animals also showed a more favorable oxidative stress profile, particularly lower superoxide anion levels and enhanced antioxidant defense. Histologically, both agents attenuated myocardial hypertrophy and collagen deposition, improved hepatic architecture by reducing inflammatory changes, and preserved pancreatic structure with less lipid accumulation and tissue injury.</p><p><strong>Conclusions: </strong>Liraglutide and semaglutide exerted significant cardioprotective and tissue-protective effects in experimental MetS complicated by myocardial I/R injury. These findings support their potential in limiting post-ischemic cardiac dysfunction and multiorgan damage in metabolically compromised conditions.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Direct 3D Scans and Plaster Casts in Digital Ankle-Foot Orthosis Workflows.","authors":"Chenxi Peng, Simon Lalor, Nasim Shokoohi, Ling Chen, Erich Rutz","doi":"10.3390/medsci14050589","DOIUrl":"10.3390/medsci14050589","url":null,"abstract":"<p><p><b>Background:</b> Digital ankle-foot orthosis (AFO) workflows depend on accurate lower limb geometry acquisition. Direct 3D scanning on the lower limb may reduce plaster use, but its geometrical agreement with orthotist plaster casting remains insufficiently investigated. <b>Objective:</b> This study compared posterior lower limb surfaces captured by direct 3D scanning with surfaces obtained from orthotist plaster casts digitised using the same scanner. <b>Methods:</b> Seven healthy paediatric participants underwent bilateral direct scanning and bilateral plaster casting, giving 14 limb comparisons. Cast meshes were digitised, trimmed to reduce boundary effect, globally registered to the direct scans, and segmented into posterior foot, ankle, calf and knee proxy regions. Cast-to-scan distances were then calculated. <b>Results:</b> The ankle region showed the greatest residual mismatch, with a weighted mean distance of 3.49 mm (95% CI 3.16-3.81 mm). It also had the highest proportions of vertices exceeding 2 mm (74.8%) and 5 mm (21.2%), and was the highest-error region in 13 of 14 limbs. The knee region had the lowest weighted mean distance (2.28 mm, 95% CI 1.92-2.60 mm) but showed the largest upper-tail spread. <b>Conclusions:</b> These preliminary findings indicate direct scanning and plaster casting did not produce completely interchangeable posterior limb surfaces in this cohort. The ankle was the most consistently discrepant AFO-relevant region, indicating that digital AFO workflows should include local geometric quality control rather than relying only on whole-limb agreement.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between Flow and Absolute Humidity During Active Humidification for High-Flow Therapy: A Bench Study.","authors":"Riccardo Re, Sergio Lassola, Eleonora Balzani, Marco Parisi, Michele Zeni, Giacomo Bellani","doi":"10.3390/medsci14050588","DOIUrl":"10.3390/medsci14050588","url":null,"abstract":"<p><p>Active humidification of medical gases is a fundamental component of high-flow oxygen therapy (HFOT). Given the high gas flow rates employed, it remains unclear whether the theoretically expected relationship between flow rate, temperature, and absolute humidity is maintained under clinical conditions. This bench-top study aimed to characterize the relationship between absolute humidity (AH) and gas flow rate and to identify optimal AH targets across different HFOT settings. This relationship was assessed by measuring water consumption by the heated humidifier at different temperatures and across a range of high-flow settings. Statistical analysis showed that AH increased by approximately 3.7 mg/L for each 1 °C increase in temperature and decreased by approximately 0.4 mg/L for each additional 1 L/min of delivered flow. Utilizing the alveolar absolute humidity value of 44 mg/L at 37 °C as the reference, the derived slope was used to estimate the corresponding AH targets for each high-flow therapy setting: 10.4 mg/L for Continuous Positive Airway Pressure via Helmet (H-CPAP), 25.3 mg/L for High Flow Nasal Cannula (HFNC), and 36.5 mg/L for HFOT-tracheostomy. Given the decrease in absolute humidity with increasing gas flow rate, the study also proposes a temperature-compensation model that may be used to achieve target absolute humidity values across different high-flow therapy settings.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal Outcomes Associated with Maternal-Factor-Related Diagnoses: Real-World Evidence from a National Inpatient Database (2010-2025).","authors":"Tímea Csákvári, Zsuzsanna Kívés, Réka Vajda, Krisztina Palkovics, Ilona Karácsony, Annamária Pakai, Diána Elmer","doi":"10.3390/medsci14050591","DOIUrl":"10.3390/medsci14050591","url":null,"abstract":"<p><strong>Background/objectives: </strong>Maternal conditions and lifestyle exposures strongly influence neonatal morbidity, but population-level longitudinal data from Central and Eastern Europe remain limited. This nationwide study evaluated 16-year trends (2010-2025) in neonatal hospital episodes with maternal-factor-related diagnostic codes (ICD-10 P00, P04, and P70.0-P70.1) in Hungary and quantified associations with severe clinical attributes.</p><p><strong>Methods: </strong>In a retrospective study of 1,546,439 hospital birth episodes, administrative registry data were analysed. Cases with ICD-10 codes P00.0-P00.9 (maternal conditions), P04.0-P04.9 (noxious influences/lifestyle), and P70.0-P70.1 (carbohydrate disorders) were identified. Severity levels, birth weight, surgical interventions, and mechanical ventilation were derived from the Hungarian Diagnosis-Related Group (h-DRG) labels. Temporal trends were evaluated using Joinpoint regression, and episode-level prevalence ratios (PR) with 95% confidence intervals were estimated compared with neonates without recorded maternal factor-related ICD-10 diagnoses.</p><p><strong>Results: </strong>Maternal-factor codes were present in 145,571 episodes (9.41%; P70: 49.96%, P00: 31.33%, P04: 18.71%). Case rates per 1000 live births increased for P04 (7.08-fold), P00 (6.88-fold), and P70 (2.59-fold; overall AAPC: 9.98%, 95% CI: 9.12-10.85). Maternal-factor episodes had a higher prevalence of severe morbidity (PR = 2.18, 95% CI: 2.13-2.23), birth weight 1500-1999 g (PR = 2.27, 95% CI: 2.20-2.34), major surgery (PR = 2.18, 95% CI: 1.86-2.56), and mechanical ventilation > 5 days (PR = 5.04, 95% CI: 4.62-5.51). Mean length of stay increased by 11.05% in P04 episodes (from 4.14 to 4.60 days) and decreased by 15.59% and 23.60% in P00 and P70.0-P70.1 episodes, respectively.</p><p><strong>Conclusions: </strong>Maternal-factor conditions were recorded in nearly one in ten neonatal hospital delivery episodes in Hungary, showing an increase in recorded episode rates and resource use. These coded episodes are associated with a higher prevalence of low birth weight, major surgery, and prolonged mechanical ventilation.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Characterization of RTK-RAS Pathway Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.","authors":"Harsh Goel, Ravi Kumar Majhi, Jagdish Prasad Meena, Anita Chopra, Sameer Bakhshi, Lata Singh, Rachna Seth, Bibekananda Kar, Pranay Tanwar, Aditya Kumar Gupta","doi":"10.3390/medsci14050583","DOIUrl":"10.3390/medsci14050583","url":null,"abstract":"<p><strong>Background/objectives: </strong>Juvenile myelomonocytic leukemia (JMML) is a rare and very aggressive pediatric myelodysplastic/myeloproliferative neoplasm with molecular heterogeneity and constitutive activation of the RAS signaling pathway. The aim of this study was to identify the mutational landscape, driver genes, mutational signatures, functional pathways, and therapeutic targets of mutations that affect receptor tyrosine kinases (RTKs) and RAS pathways in JMML.</p><p><strong>Methods: </strong>We collected tumor and matched buccal swab samples from 35 patients with JMML and performed whole-exome sequencing. Variants were called using GATK-Mutect2 and annotated with ANNOVAR. Mutational profiling, co-occurrence analysis, protein domain mapping, and driver gene identification were performed using maftools and OncodriveCLUST. DGIdb was used to explore drug-gene interactions, MutationalPatterns was used for the characterization of mutational signatures, and the clusterProfiler package was used for the functional enrichment analyses.</p><p><strong>Results: </strong>Alteration of the RTK-RAS pathway was found in 77.1% of patients. <i>PTPN11</i> (23%), <i>NRAS</i> (20%), and <i>KRAS</i> (14%) were the most frequently altered genes, followed by <i>PTEN</i> (11%) and <i>FLT3</i>, <i>ROS1</i>, <i>FGFR4</i>, <i>ERBB2</i>, and <i>EGFR</i> (9% each). Domain mapping of protein sequences identified the grouping of mutations within the conserved functional domains of the proteins. The alterations in receptor tyrosine kinase genes demonstrated a significant degree of co-occurrence, while the alterations in canonical JMML genes showed mutual exclusivity. <i>PTPN11</i>, <i>NRAS</i>, <i>ROS1,</i> and <i>FGFR4</i> were top driver genes based on driver gene analysis. Functional enrichment analysis revealed significant enrichment of receptor tyrosine kinase signaling, Ras/MAPK and PI3K-AKT pathways. The mutational signatures were mostly SBS5-like, with enrichment of C>T transitions, indicative of endogenous mutational processes. Drug-gene interaction analysis identified <i>EGFR</i>, <i>ALK</i>, <i>ROS1</i>, <i>ERBB2</i>, <i>FLT3</i>, <i>FGFR4</i>, and <i>PDGFRA</i> as highly interconnected and potentially actionable therapeutic targets.</p><p><strong>Conclusions: </strong>These findings expand the molecular landscape of JMML and underscore the importance of aberrant RTK-RAS signaling in disease pathogenesis. The identification of recurrent and potentially druggable RTK alterations provides a rationale for future precision medicine approaches in JMML.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Hemorrhagic Shock in Male SD Rats by Fixed Volume Blood Withdrawal Followed by Partial Resuscitation and Long-Term Outcome Assessment.","authors":"Alina M Ismailova, Victor A Palikov, Maria S Severyukhina, Elena A Tukhovskaya, Arina V Kholina, Svetlana G Semushina, Gulsara A Slashcheva, Elvira R Shaykhutdiniva, Irina N Kravchenko, Vitaly A Kazakov, Ekaterina N Kazakova, Marina S Kazakova, Alena B Timakina, Maksim V Shinelev, Vladimir A Rykov, Olga I Patsap, Igor A Dyachenko, Arkady N Murashev","doi":"10.3390/medsci14050587","DOIUrl":"10.3390/medsci14050587","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hemorrhagic shock (HS) is one of the leading causes of disability and mortality in intensive care units. Animal modeling of HS is important for preclinical research to elucidate mechanisms and develop treatments. <b>Methods</b>: Adult male SD rats were divided into three groups, half of which were euthanized on day 8 and the other half on day 29 after HS. HS was simulated in awake animals by withdrawing blood from the carotid artery at a volume of 40% of circulating blood volume (CBV). One hour after HS, volume resuscitation therapy (VRT) was made by administering albumin-containing saline (AS) or autologous blood (AB) at 20% of CBV. Arterial pressure (AP), heart rate (HR), body temperature, blood gases, and blood metabolites, body weight gain, hemostasis, and blood cellular composition were analyzed. On days 8 and 29, bone marrow composition, organ weight, and histology were analyzed. <b>Results</b>: During blood withdrawal, AP dropped, HR increased, and hypothermia developed. After HS and subsequent VRT, 30% of animals receiving SA died, while all animals receiving AB survived. Following HS, a negative weight gain trend, anemia, pronounced inflammatory reaction, and coagulopathy developed. After HS, animals experienced an increase in partial oxygen pressure, a decrease in partial carbon dioxide pressure, total arterial oxygen content in arterial blood, stress-induced glycemia, and metabolic lactatemia. In bone marrow, the number of erythroid cells increased, while leukocyte and lymphocyte numbers decreased. HS resulted in increased spleen weight with increased extramedullary hematopoiesis. Ischemic kidney tissue damage with a decrease in kidney weight was observed, as well as post-ischemic accidental thymus involution with a catastrophic decrease in its weight. In addition, ischemic brain damage was observed in some animals. Animals showed a compensatory increase in hematopoiesis. All changes were less pronounced in AB-treated animals. <b>Conclusions</b>: We have developed a suitable model of HS, comparable to a similar condition in humans. This model can be easily reproduced and applied in most laboratories conducting preclinical studies.</p>","PeriodicalId":74152,"journal":{"name":"Medical sciences (Basel, Switzerland)","volume":"14 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}