Search Results (5,295)

Fibromyalgia is a chronic pain condition associated with reduced quality of life, psychological symptoms, cognitive impairment, and low adherence to exercise-based interventions. Immersive virtual reality (IVR) has gained attention as a rehabilitation approach; however, the relationship between user experience, adherence, and clinical outcomes remains unclear. This post hoc exploratory secondary analysis was derived from a randomized controlled clinical trial (NCT07605143) and included 16 women with fibromyalgia who completed a six-week IVR-based rehabilitation program. Associations between user experience, adherence, and clinical outcomes were explored among participants exposed to IVR. Quality of life was assessed using the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), psychological symptoms using the Depression Anxiety Stress Scales (DASS-21), and user experience using the Player Experience of Need Satisfaction (PENS) questionnaire. Within-group changes were observed in FIQ-R scores (p = 0.001; d = 1.08) and DASS-21 stress levels (p = 0.025). Participants demonstrated favorable adherence and positive user experience. A significant correlation was identified between intuitive control and changes in depression scores (ρ = 0.63, p = 0.008). This exploratory analysis identified favorable user experience and adherence among women participating in an IVR-based rehabilitation program. However, due to the absence of a concurrent control group, no conclusions regarding treatment efficacy can be drawn. These findings should be considered hypothesis-generating. Full article

Background: Managing neuropathic pain (NP) is particularly challenging in the context of opioid use, and the mechanisms behind chronic pain remain unclear. Objective: This study evaluated the impact of turmeric bioactive compounds on brain regions including frontal cortex (FC), hippocampus (HPC), and hypothalamus (HPT) in the spinal nerve ligation (SNL) in a rat model of NP. Methods: Twenty-four SD rats were assigned to four groups (N = 6 per group), namely sham+vehicle (Sham-V), SNL+vehicle (SNL-V), SNL + 100 mg/kg curcumin (SNL+100CUR), and SNL + 50 mg/kg bisdemethoxycurcumin (SNL+50BDMC), treated daily for four weeks via oral gavage. Gene expression levels related to neuroinflammation, oxidative stress, and mitochondrial homeostasis were measured using qRT-PCR. Protein-level or functional mitochondrial assays were not performed due to limited sample availability. Results: In the FC, SNL decreased the expression level of NRF1 and OPA1, but only OPA1 was increased by BDMC. In the HPC, SNL increased CD11b, NRF2, and MFN1; BDMC decreased CD11b and increased IBA1, NRF1, TFAM, PGC1α and Complex I; and CUR increased NRF1, TFAM, DRP1 and Complex I levels. In the HPT, SNL decreased GFAP and MFN1, with CUR and BDMC further decreasing GFAP but not affecting MFN1. Additionally, CUR and BDMC decreased the expression of several key markers of neuroimmune signaling and mitochondrial homeostasis, including IBA1, CD11b, NFkB, NRF1/2, DRP1, OPA1, PGC1α, TFAM, and PINK1. Conclusions: CUR and BDMC induced region-specific transcriptional remodeling of mitochondrial homeostasis across FC, HPC, and HPT in SNL rats, with somewhat limited effects in the FC, mixed effects in the HPC, and broader downregulation in the HPT. Full article

Coronary artery vasospasm (CAV) is a transient, reversible constriction of the epicardial coronary arteries that reduces coronary blood flow and may cause myocardial ischemia. Despite its clinical significance, CAV remains underdiagnosed and can present as chest pain, acute coronary syndrome, malignant arrhythmias or sudden cardiac death. Vasospasm may occur in both angiographically normal coronary arteries and at sites of pre-existing atherosclerotic stenosis. The pathophysiology of CAV is multifactorial and involves vascular smooth muscle cells (VSMCs) hyperreactivity, endothelial dysfunction, chronic inflammation and autonomic dysregulation. VSMCs contraction is mediated by phosphorylation of the myosin light chain (MLC) through calcium (Ca²⁺)/calmodulin-dependent myosin light chain kinase (MLCK), while relaxation is regulated by myosin light chain phosphatase (MLCP). Increased intracellular Ca²⁺ levels and enhanced Ca²⁺ sensitivity contribute to excessive vasoconstriction. Rho-kinase (ROCK) plays a pivotal role in sustained vasospasm by inhibiting MLCP, thereby promoting prolonged smooth muscle contraction. Endothelial dysfunction contributes to CAV by disrupting normal vascular tone regulation, largely as a result of decreased nitric oxide (NO) mediated vasodilation. Chronic low-grade inflammation and oxidative stress exacerbate both endothelial dysfunction and VSMCs contraction. Understanding these molecular mechanisms is essential for identifying novel therapeutic targets. Emerging treatment strategies, including ROCK inhibitors, endothelin receptor antagonists and anti-inflammatory agents, may improve outcomes in patients with refractory CAV. Full article

Sickle cell disease (SCD) is one of the most common inherited blood disorders worldwide. Clinical manifestations are variable, but include hyposplenism, renal impairment, cardiovascular disease, respiratory complications, and cerebrovascular disease. Frequent painful vaso-occlusive crises, hospitalisations, and other physical and psychological ramifications can have profound effects, including children missing school time resulting in impaired academic performance and adults missing work leading to employment loss. This narrative review examines the possible risks and benefits of exercise in the SCD population. Regular exercise plays an important role in improving physical and mental health, but fears around the potential consequences of exercise for the SCD population are present in children, their families, schools, and other organisations. This can result in children not taking part in as much regular exercise as their peers and being excluded from group activities. Studies have suggested that healthcare professionals often do not discuss the possible benefits of physical exercise with patients, likely because there are no guidelines regarding a safe level of activity. An acute increase in inflammation secondary to exercise could increase the risk of vaso-occlusive crises, but regular physical activity is known to play an important role in disrupting chronic inflammation across a wide range of pro-inflammatory diseases. Indeed, studies have demonstrated positive responses to exercise in the SCD population, from improvements in skeletal muscle microvasculature to performance in cardiovascular tests. It is important that recommendations are developed regarding types of exercise and the ideal amount of exercise for maximum benefit with minimum risk in SCD individuals. Full article

Endometriosis is a long-term gynecological condition marked by the growth of endometrial-like tissue outside the uterus, which undergoes proliferation, bleeding, and regeneration. This disease is associated with disrupted steroid hormone signaling, notably progesterone (P4) resistance and estradiol (E2) dominance. P4 resistance has been associated with impaired activation of the progesterone receptor (PR) and reduced transcription of P4 target genes, while elevated E2 levels induce estrogen receptor (ER)-mediated signaling, enhancing estrogen-dependent lesion growth. This hormonal imbalance contributes to a pro-inflammatory microenvironment, chronic pelvic pain, infertility, and enhanced neuroangiogenesis. Emerging evidence indicates that the coordinated regulation of neurotrophins and sex hormones promotes nerve fibers and blood vessel growth and invasion within endometriotic lesions. P4 and E2 have been shown to modulate the expression of key neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This review presents current evidence on the interplay between neurotrophins and ovarian steroids in endometriosis, with a specific focus on their contribution to neuroangiogenesis and pain pathophysiology. The review includes articles in English containing the Medical Subject Headings (MeSH) terms: “endometriosis”, “neurotrophins”, “nerve growth factor”, “brain-derived neurotrophic factor”, “neuroangiogenesis”, “progesterone”, and “estradiol”, found in the PubMed database published between 2000 and 24 May 2026. This review included a range of original research articles, systematic reviews, meta-analyses, prospective observational studies, case–control studies, and review papers, for a total of 122 articles. Full article

Background: Pain is a prominent and disabling manifestation of inflammatory bowel disease (IBD), including abdominal, pelvic, musculoskeletal, axial, and neuropathic pain phenotypes. Patients referred to pain clinics represent a selected subgroup with clinically meaningful, persistent, refractory, or diagnostically complex pain. Objective: To characterize pain phenotypes, treatment patterns, interventional pain-care exposure, and utilization burden among patients with IBD evaluated in tertiary pain-clinic settings and to explore differences between Crohn’s disease and ulcerative colitis patients. Methods: We performed a retrospective electronic medical-record cohort study of patients with documented IBD who were evaluated in pain-clinic settings between 24 October 2010 and 14 May 2026. Repeated clinical entries were aggregated into unique visit dates and patient-level variables. IBD diagnosis, pain phenotypes, treatment documentation, interventional procedures, and pain-clinic utilization were summarized descriptively using counts, percentages, means, medians, interquartile ranges, and ranges as appropriate. Crohn’s disease and ulcerative colitis subgroups were compared using univariable odds ratios with 95% confidence intervals and two-sided p-values. Because repeated clinical entries could belong to the same patient, the primary analytic unit was the patient rather than the individual note. Results: The source dataset included 19,615 clinical entries representing 7053 unique pain-clinic visits among 596 unique patients with IBD. The cohort included 314 patients with Crohn’s disease (52.7%), 247 with ulcerative colitis (41.4%), and 35 with IBD-unclassified (5.9%). The mean number of pain-clinic visits per patient was 11.8, with a median of four visits (interquartile range, 1–11). The dominant patient-level pain phenotypes were limb or peripheral joint pain (395/596, 66.3%), back or axial spine pain (358/596, 60.1%), and abdominal or pelvic pain (246/596, 41.3%). Overall, 437 patients (73.3%) had documentation of at least one interventional pain procedure. Compared with ulcerative colitis, Crohn’s disease was associated with higher documentation of abdominal or pelvic pain (148/314, 47.1% vs. 82/247, 33.2%; odds ratio, 1.79; 95% confidence interval, 1.27–2.53; p = 0.001) and fibromyalgia-like or widespread pain (83/314, 26.4% vs. 39/247, 15.8%; odds ratio, 1.92; 95% confidence interval, 1.25–2.93; p = 0.0027). In contrast, radiofrequency procedures (59/314, 18.8% vs. 78/247, 31.6%; odds ratio, 0.50; 95% confidence interval, 0.34–0.74; p = 0.0005) and facet or medial branch procedures (79/314, 25.2% vs. 87/247, 35.2%; odds ratio, 0.62; 95% confidence interval, 0.43–0.89; p = 0.012) were less frequently documented in Crohn’s disease than in ulcerative colitis. Conclusions: Among patients with IBD referred to tertiary pain-clinic evaluation, pain was heterogeneous and predominantly musculoskeletal, axial, neuropathic, and procedurally targetable rather than exclusively visceral. These findings support structured, mechanism-based pain assessment integrated with gastroenterology, rheumatology, and pain-medicine care. Full article

Background/Objectives: Labor pain is a multidimensional experience associated with physiological, cultural, psychological, and contextual factors. This study aimed to examine the association of personality-related characteristics, cultural beliefs, obstetric characteristics, and proxy indicators of post-disaster context with labor pain perception among women giving birth in Hatay after the 2023 Türkiye earthquakes. Methods: This prospective observational study was conducted with 314 women admitted to Hatay Training and Research Hospital between February and June 2025. Participants were between 38 and 42 gestational weeks, had a singleton healthy fetus, were admitted in active labor, and were expected to give birth vaginally. Data were collected using a researcher-developed questionnaire, the Ten-Item Personality Inventory, and the Visual Analog Scale. Labor pain was assessed at 6 cm, 8 cm, and full cervical dilatation (10 cm). Results: VAS scores increased significantly across cervical dilatation points, from 5.04 ± 0.81 at 6 cm to 7.01 ± 0.82 at 8 cm and 8.06 ± 0.93 at full cervical dilatation (10 cm). Repeated-measures ANOVA showed a significant within-person increase in pain intensity across the three assessment points, F(2, 626) = 996.444, p < 0.001, partial η² = 0.761. Age was not significantly correlated with VAS pain score at full cervical dilatation. In exploratory unadjusted comparisons, VAS scores at full cervical dilatation differed according to education level, official marriage status, previous birth history and mode, attendance at antenatal education, and praying to relieve labor pain. In the multivariable regression model, higher Extraversion and higher education level were associated with lower VAS scores, whereas attendance at antenatal education, greater importance given to traditional rules, previous assisted vaginal/cesarean birth, and current place of residence were independently associated with VAS scores. Conscientiousness was not significantly associated with VAS scores in the adjusted model. Earthquake experience was not significantly associated with VAS scores. Conclusions: Labor pain perception was associated with selected sociodemographic, obstetric, and cultural characteristics. The findings support the importance of individualized, culturally sensitive, and trauma-informed midwifery care in disaster-affected regions. Personality-related findings should be interpreted cautiously because the corrected reliability analysis showed low internal consistency for Agreeableness, Emotional Stability, and Openness to Experience, although Extraversion showed high internal consistency and Conscientiousness showed relatively better but still limited internal consistency. Disaster-related findings should also be interpreted cautiously because post-disaster context was assessed using only limited proxy indicators; current place of residence was independently associated with VAS scores in the adjusted model, whereas earthquake experience was not. Because of the observational design, causal interpretations cannot be made. Full article

Firmiana colorata (Roxb.) R.Br. is a medicinal tree used in traditional systems of the Indian subcontinent, but its pharmacognostic profile remains insufficiently consolidated. This PRISMA-guided review integrates the available evidence on its taxonomy, distribution, botanical characteristics, genetic background, phytochemistry, and biological activity, with explicit consideration of nomenclatural synonyms during database searching. The reviewed literature indicates that F. colorata contains diverse phenolic, flavonoid, coumarin, lipid, and other specialized metabolites, while pharmacological studies suggest activity mainly in inflammation-, pain-, oxidative stress-, microbial-, and cancer-related experimental models. However, the current evidence remains fragmented and is still dominated by crude extracts, preliminary assays, limited mechanistic validation, and insufficient safety data. Plastome-level information supports taxonomic authentication and evolutionary placement, but the relationship between genetic background and phytochemical variability remains unresolved. The available data therefore justify further investigation of F. colorata, provided that future studies emphasize phytochemical standardization, validated mechanisms, dose justification, toxicity assessment, and translational relevance. Full article

Background: The management of diabetic foot disease and knee osteoarthritis (OA) with smart orthotics holds significant importance during the early stages of these conditions, given their potential consequences, including functional impairment, chronic pain, and economic burden. Real-time monitoring of plantar foot pressure enables early detection of abnormal force distribution and gait biomechanics, allowing for the redirection of forces away from affected ulcers or arthritic joints. This is the first systematic review to synthesise clinical evidence for smart orthotics technology with real-time plantar pressure sensor biofeedback across both diabetic foot ulcer prevention and knee osteoarthritis management simultaneously. A search of the PROSPERO register confirmed no existing registration covers this specific combination. Objectives: To examine the clinical evidence for the use of standard and smart orthotics in the prevention and management of diabetic foot ulcers (DFUs) and knee OA, and to evaluate their impact on plantar pressure redistribution, ulcer recurrence, pain, biomechanics, and economic burden. Eligibility criteria: Studies published in English involving human adult participants (≥18 years) with a clinical diagnosis of diabetes mellitus (at risk of DFU or with peripheral neuropathy) or knee OA, where the intervention involved any orthotic device or smart/intelligent insole with clinical outcomes reported, were included. Studies on healthy individuals only, those not reporting participant age, and non-weight-bearing protocols not differentiated from weight-bearing were excluded. Information sources: Five databases were searched: CINAHL (EBSCO Information Services, Ipswich, MA, USA), PubMed Advanced (National Library of Medicine, Bethesda, MD, USA), Wiley Online Library (John Wiley & Sons, Hoboken, NJ, USA), Cochrane Library (Cochrane Collaboration, London, UK), and Google Scholar (Google LLC, Mountain View, CA, USA). Searches were completed in May 2026. Methods: We conducted a comprehensive literature review. This review was structured and reported with reference to the PRISMA 2020 statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; University of Ottawa, Ottawa, ON, Canada) to guide transparency of reporting. It does not constitute a full Cochrane-style systematic review; risk of bias assessment was applied to key included studies and GRADE (Grading of Recommendations Assessment, Development and Evaluation; McMaster University, Hamilton, ON, Canada) certainty ratings were applied informally and narratively rather than as formal per-outcome evidence profiles. Five databases were searched yielding 92,637 records. After removal of 398 duplicates by Rayyan, 92,239 records remained. A subsequent automated keyword-based relevance filter applied within Rayyan (Rayyan AI, Doha, Qatar), prior to human screening, excluded 84,572 records that did not contain any terms related to orthotics, diabetic foot, or knee osteoarthritis, yielding 7667 records for human title/abstract screening. A narrative synthesis approach was adopted owing to the heterogeneity of study designs and outcome measures across included studies, which precluded meta-analysis. This review was not prospectively registered. A complete list of all 78 included studies, including those not individually discussed in the results and discussion. Results: The available clinical studies report promising findings for orthotics and smart orthotics in pain reduction, ulcer prevention, and potential reduction in economic burden, though conclusions are limited by small sample sizes, heterogeneity, and predominantly open-label designs. Recent research found that orthotics can be used to alter the gait pattern that influences knee OA by reducing excessive force on the affected joint. A randomised controlled trial demonstrated an 80% relative risk reduction in DFU recurrence (RR = 0.20; 95% CI: 0.06–0.79; p = 0.022), with absolute event rates of 6.3% in the intervention group versus 30.8% in controls (ARR = 24.5%); a second trial reported a 71% reduction in ulcer incidence over 18 months; and a third randomised controlled trial demonstrated statistically significant plantar pressure reduction (p < 0.01) in patients with diabetic neuropathy. Conclusions: The available evidence suggests that orthotics may be associated with improved pressure redistribution, reduced ulcer incidence, and benefit in the management of knee OA. Although the number of studies directly comparing smart orthotics with standard orthotics remains limited, the limited comparative studies suggested that smart orthotics showed promising results in reducing ulcer incidence, providing the patient with real-time feedback to offload via their electronic devices. These findings, while preliminary, highlight the potential of smart orthotic technology as an adjunct to standard orthotic care in reducing the overall burden of diabetic foot disease and knee osteoarthritis. Limitations: The primary methodological limitation of this review is the open-label design of all included smart orthotic trials, which precludes participant blinding and introduces performance bias. However, this limitation is structural and inherent to the wearable technology field—analogous to surgical trials—and is substantially mitigated by the use of objective primary outcome measures (plantar pressure and ulcer recurrence) across the three included RCTs, the consistency of effect direction across independent RCTs conducted in different countries, and a narrative sensitivity analysis confirming robustness of findings (Risk of Bias Across Studies Section). Formal per-outcome GRADE evidence profiles were not produced; overall certainty of evidence was assessed narratively with reference to GRADE domains and is judged to be low to moderate for smart orthotics in DFU prevention and low for knee OA management, consistent with the Level 2–3 evidence base and open-label study designs. Future adequately powered, multi-site RCTs with standardised outcome reporting, minimum 24-month follow-up, and integrated health economic modelling are the highest priority to extend these preliminary findings. Registration: This review was not prospectively registered. Full article

Background/Objectives: Chronic non-specific low back pain (CNLBP) is a leading cause of disability worldwide. Although several randomized trials have evaluated treatment effectiveness, less attention has been given to the responsiveness of outcome measures used to assess clinical change. This study aimed to evaluate the internal and external responsiveness of commonly used outcome measures in individuals with CNLBP. Methods: This study is a secondary analysis of a randomized controlled trial. Participants were analyzed as active and placebo groups and assessed at baseline, post-intervention, and follow-up. Internal responsiveness was evaluated using standardized mean differences (SMD) and standardized response means (SRM). External responsiveness was assessed using anchor-based approaches, including correlations with the Global Rating of Change Scale (GRCS) and receiver operating characteristic (ROC) curve analysis. Results: Outcome measures demonstrated moderate to high internal responsiveness, with large effect sizes observed for pain intensity (NRS) and quality of life (EQ-5D-3L). However, external responsiveness was limited, with all instruments presenting area under the curve (AUC) values below 0.70. The Bournemouth Questionnaire showed the highest discriminative performance among the instruments. Conclusions: The evaluated instruments were sensitive to detecting change at the group level but showed limited ability to discriminate clinically meaningful improvement at the individual level. These findings support the use of combined outcome measures to improve clinical interpretation and decision-making in CNLBP. Full article

Background: Research on nursing interventions for breast cancer patients undergoing radiotherapy is increasing. However, comprehensive mapping and synthesis regarding the field’s overall knowledge structure and development remain limited. This study aims to utilize bibliometric methods to analyze the current status, research hotspots, and emerging trends in this field. Methods: We conducted a bibliometric analysis of 256 publications from the Web of Science Core Collection and PubMed. Results: Publication volume showed a notable increase after 2020 (16–25 articles per year). The United States leads in output (82 articles, 32.0%), followed by China (25 articles). At the institutional level, the University of California, San Francisco (10 articles) is the most productive, while George Washington University leads in total citations (1759). Oncology Nursing Forum is the leading journal both in publication volume (20 articles) and h-index (13). Twelve major research clusters were identified, primarily focusing on symptom management (specifically pain) and psychosocial support. Keyword burst analysis suggests that current frontiers have shifted from acute symptom control toward systematic management approaches and psychological symptom interventions. Conclusions: Based on the analysis of 256 publications and 12 research clusters, this study indicates that the focus of nursing research appears to be expanding from acute symptom control toward comprehensive case management and targeted psychological research. These findings may provide useful directions for future research and clinical practice, particularly regarding the integration of psychosocial care into nursing management. Full article

Background: Needle-related procedures such as venipuncture can be distressing for children and may trigger severe fear and behavioral dysregulation, particularly in those with previous traumatic experiences. Trauma-informed care (TIC) is a framework that recognizes the widespread impact of trauma and integrates this knowledge into clinical practice to prevent re-traumatization and support emotional regulation during medical procedures. Methods: This before-and-after study included 135 children aged 4–8 years who had previously shown severe distress during venipuncture, including escape attempts, shouting, or self/other-directed aggressive behaviors. Before venipuncture, children and their families received a TIC-based intervention delivered by a psychological counselor in a dedicated preparation room. Fear, behavioral responses during venipuncture, procedural pain, and heart rate were evaluated before and after the intervention using parent reports, the Children’s Fear Scale, the Wong–Baker FACES Pain Rating Scale, and pulse oximetry. Results: Following the TIC intervention, significant pre–post reduction were observed in distress-related behaviors during venipuncture, including escape attempts, shouting/crying, and self-/other-directed harmful behaviors. The proportion of children rated as experiencing high levels of fear decreased from 96.2% before the intervention to 15.5% after. Among the 85 children with complete heart-rate measurements available, mean heart rate decreased from 113.6 ± 10.1 beats/min to 87.3 ± 8.43 beats/min. Many families reported a more positive venipuncture experience compared with previous procedures. Conclusions: A trauma-informed care intervention delivered before venipuncture is associated with meaningful reductions in behavioral distress, fear, and physiological arousal in children with prior needle-related traumatic experiences. These pre–post associations support the feasibility and potential value of the TIC model, though controlled studies are needed to confirm these findings without confounding clinical effects. Full article

Background/Objectives: First-generation CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) target the conserved ATP-binding pocket of CDK4 and, despite clinical success, are limited by acquired resistance and insufficient exploration of alternative regulatory sites. This study aimed to identify a putative allosteric small-molecule candidate at the CDK4 αE-helix–Cyclin D1 α1-helix protein–protein interaction (PPI) interface within the CDK4/Cyclin D1/p21 ternary complex using RapidFunnel-AI, a decision-interpretable virtual-screening pipeline. Methods: Starting from 50,000 ChEMBL 33 molecules, the pipeline sequentially applied a Q-Fold/RapidFunnel topological Tanimoto scan based on clinical CDK4/6 inhibitor motifs, fragment-level electronic-property enrichment, ADMET/PAINS filtering, dry Vina-GPU docking, hydration-mediated AutoDock-GPU (Version 1.6) docking, explicit-solvent molecular dynamics, contact-retention analysis, and MM-GBSA energy decomposition. The Q-Fold Thermo-Core surrogate model provided fragment-level enrichment, predicting the HOMO–LUMO gap (R² = 0.93) and isotropic polarizability (R² = 0.98) on QM9. Candidate selection did not rely on the lowest docking or MM-GBSA score alone, but on pose persistence, contact continuity, and energy-component consistency. Results: The workflow reduced the initial library to 43 topologically prioritized candidates, 25 ADMET/PAINS-filtered ligands, and 9 docking-derived complexes for MD validation. Ligand_020 emerged as the only candidate that preserved a persistent binding mode at Site 2 during a 500 ns simulation—an interface engagement reproduced across three independent 500 ns replicates with no full dissociation in any replicate—with a protein Cα RMSD of 2.88 ± 0.32 Å, a ligand heavy-atom RMSD of 3.56 ± 0.28 Å, and a van der Waals-dominated MM-GBSA profile (ΔGbind = −28.23 ± 3.57 kcal/mol). In contrast, palbociclib and ribociclib, forcibly placed at Site 2 as negative controls, lost most initial contacts within 5 ns and tended to detach despite more favorable MM-GBSA values. Conclusions: These results suggest that single-score docking or MM-GBSA ranking can generate false positives at shallow PPI interfaces. By integrating AI-assisted prioritization, multipocket docking, explicit-solvent MD, contact-retention analysis, and energy-component consistency, RapidFunnel-AI nominated Ligand_020 as an experimentally testable putative allosteric hit targeting the CDK4/Cyclin D1 interface, offering a reusable platform for PPI-focused oncological drug discovery. Full article

Background: Radiation dermatitis (ARD), particularly its most severe form, moist desquamation (MD), is a frequent and distressing complication of external beam radiotherapy (RT) in head and neck (H&N) cancer patients. Standard management often provides limited benefit for healing and symptom control. Silicone-based foam dressings, including Mepilex Lite and Mepilex Ag, may offer atraumatic adherence, moisture balance, and pain reduction. This study evaluated their real-world effectiveness for MD after conventional RT. Methods: Ten H&N cancer patients with clinically confirmed MD post-radiotherapy were prospectively followed until healing. Patients received Mepilex Lite or Mepilex Ag based on exudate level and infection risk, with dressings changed every three days. Patient- and healthcare provider-reported measures were collected throughout follow-up. The primary endpoint was time to MD resolution, defined as healing to grade 1 skin status. Secondary endpoints included changes in symptom burden, dressing tolerability and satisfaction, and adverse events. Results: Median age was 69 years (range 44–78). All wounds healed to grade 1, with a mean time of 8.6 days (SD 3.9). No infections or adverse events occurred. Pain, burning, and interference with daily activity decreased, and most patients reported improved comfort. Conclusions: In this small prospective cohort study, use of Mepilex dressings was associated with rapid healing, good tolerability, and improvement in patient-reported symptoms of acute radiation dermatitis. These findings suggest that Mepilex dressings may be a promising management option and warrant evaluation in larger comparative studies. Full article

Objectives: The diagnosis of pediatric acute appendicitis remains challenging due to clinical findings that overlap with nonspecific abdominal pain (NSAP). In this study, the value of fibrinogen in the diagnosis of pediatric acute appendicitis and in the classification of disease severity was investigated. Methods: In a single-center, retrospective cohort study, 145 patients aged 1 month to 18 years who underwent contrast-enhanced abdominal computed tomography were divided into three groups: NSAP (n = 62), uncomplicated appendicitis (n = 44), and complicated appendicitis (n = 39). Hemogram parameters, CRP, procalcitonin, albumin, and fibrinogen levels were compared. Diagnostic performance was assessed using ROC analysis, and independent predictors were evaluated via multivariate logistic regression. Results: Fibrinogen levels showed a gradual and statistically significant increase from NSAP to uncomplicated appendicitis and then to complicated appendicitis (p < 0.001 for all pairwise comparisons). In distinguishing appendicitis from NSAP, fibrinogen achieved the highest diagnostic accuracy among the biomarkers examined (AUC = 0.95); CRP, WBC, ANC, and NLR demonstrated lower discriminatory performance. In multivariate logistic regression analysis, fibrinogen was validated as an independent predictor of appendicitis (p < 0.001). Conclusions: Fibrinogen demonstrates high discriminatory performance in the diagnosis of pediatric acute appendicitis and shows a graded relationship with disease severity. These findings suggest that fibrinogen may be a promising biomarker for the evaluation of pediatric acute appendicitis. However, larger prospective multicenter studies are required before its routine integration into diagnostic algorithms can be recommended. Full article