Search Results (1,304)

Background/Objectives: The recently proposed revised Dynamic International Prognostic Scoring System (DIPSS-R) excludes age and constitutional symptoms and relies exclusively on disease-related variables. We aimed to externally validate the DIPSS-R and to characterize how it reclassifies patients relative to the DIPSS. Methods: We retrospectively studied 285 patients with primary or secondary myelofibrosis from seven centers. Both scores were calculable in 270 patients (148 deaths). The two systems were compared for discrimination, reclassification, calibration, and robustness across pre-specified subgroups and landmarks. Results: During a median follow-up of 90.3 months, median overall survival (OS) was 66.1 months (5-year OS 52.7%). The two systems showed similar discrimination (C-index 0.691 vs. 0.697; difference −0.006, 95% CI −0.046 to +0.030; p = 0.77) with no significant difference across any subgroup, fibrosis grade, driver mutation, age or sex. The DIPSS-R assigned more patients to higher-risk categories (59.3% vs. 46.3%; p < 0.001). Reclassification was discordant in 57 patients (21.1%); the DIPSS-R up-stratified 46 patients (17.0%) classified as lower-risk by the DIPSS, and these patients had significantly worse survival than concordantly lower-risk patients (5-year OS 57.7% vs. 81.7%; p < 0.001). Among transplant-eligible patients aged ≤65 years, the DIPSS-R up-stratified 26 (22.6%). The reclassification was driven by the DIPSS-R-specific variables (monocytosis, leukocytosis and thrombocytopenia). In multivariable analysis the DIPSS-R remained independently prognostic of the Charlson comorbidity index (CCI), with both retaining independent value (DIPSS-R: HR 1.96 per category, 95% CI 1.58–2.44, p < 0.001; CCI: HR 1.18 per point, 95% CI 1.06–1.32, p = 0.003). In secondary myelofibrosis the DIPSS-R discriminated comparably to the disease-specific MYSEC-PM (C-index 0.659 vs. 0.698; p = 0.44). Conclusions: The DIPSS-R matches the DIPSS in discrimination while identifying additional adverse-risk patients, most relevantly transplant-eligible younger patients, who would otherwise be considered lower-risk by the age-containing DIPSS; in secondary myelofibrosis it performs comparably to the disease-specific MYSEC-PM. Full article

Pediatric Monteggia fracture-dislocations may be overlooked when ulnar injury is incomplete or plastically deformed and radiocapitellar malalignment is subtle. Radiographic interpretation is further complicated by incomplete ossification, non-standard projection, and the limitations of applying a single alignment line across all ages and imaging scenarios. This narrative review synthesizes clinically relevant evidence on radiocapitellar alignment assessment in suspected pediatric Monteggia lesions and proposes an imaging interpretation framework for radiographs and problem-solving imaging. The review integrates developmental anatomy, radiographic adequacy, radiocapitellar line behavior, forearm-based P-line assessment, lateral humeral line assessment, ulnar bow sign, and targeted second-line imaging with ultrasound, MRI, and arthrography. The framework emphasizes three practical steps: first determining whether the available images are adequate for line-based assessment; then selecting the line or sign according to age, ossification stage, projection, and available landmarks; and finally reporting discordant or limited studies as equivocal rather than forcing a binary normal/abnormal interpretation. We also summarize diagnostic error considerations, structured reporting elements, and future directions for AI-assisted measurement and uncertainty-aware interpretation. The proposed framework is intended to support consistent radiologic reasoning and communication among emergency physicians, radiologists, and pediatric orthopedic surgeons. It is not a validated diagnostic rule, and prospective observer-performance studies are needed before implementation as a clinical pathway. Full article

Background/Objectives: Automated cephalometric landmark detection using deep learning has the potential to streamline routine orthodontic diagnosis. However, the clinical relevance of artificial intelligence (AI) localisation accuracy depends on how detection errors propagate into derived angular measurements and skeletal classifications. We retrospectively evaluated 14 YOLO-based model configurations and quantified the agreement between AI-derived and expert-derived ANB-based skeletal classifications. Methods: Twelve working YOLO-based models (YOLOv5xu, YOLOv11 nano/small/medium/large variants) were trained on a single-centre dataset of 120 lateral cephalograms and evaluated on an independent test set of 11 cephalograms (stratified across skeletal Classes I, II, III). The four ANB-defining landmarks (Sella, Nasion, A-point, B-point) were the focus of the analysis. Each test cephalogram had been annotated by four orthodontists (44 measurements per image), yielding the expert reference. We assessed the effects of architecture, bounding-box size (40/100/150 px), training dataset scale (235–4255 images) and training epochs on localisation accuracy (mean radial error, MRE; Successful Detection Rate, SDR) and on the downstream ANB-based skeletal classification. Diagnostic concordance was quantified by classification agreement, Cohen’s $\kappa$ with bootstrap 95% confidence intervals (10,000 iterations), an exact one-sided binomial test for discordance, and Wilson exact CIs per class. Results: The best-performing model (Model 2; YOLOv11l, 40 × 40 px bounding box, 1175 training images) achieved an MRE of $3.10\pm 1.00$ mm and a SDR@4 mm of 87.2% for S, N, A, and B. ANB-based skeletal classification demonstrated 96.9% concordance with expert assessments (95% bootstrap CI: 93.8–99.2%; Cohen’s $\kappa$ = 0.946 [95% CI 0.89–0.99]; exact binomial test against a 90% concordance threshold $p=0.003$). Per-class concordance was Class I 95.8% (23/24), Class II 94.9% (56/59), and Class III 100% (47/47). Three of four discordant cases clustered near the Class I/II diagnostic threshold (expert ANB $\approx 4.5°$). Bounding-box size dominated localisation accuracy, with a 3.5-fold increase in MRE from 40 × 40 to 150 × 150 px configurations and SDR@4 mm collapsing from 82.8% to 0%. Conclusions: Within the constraints of a retrospective single-centre design with a small (n = 11) independent test set, YOLO-based AI landmark detection demonstrated promising diagnostic concordance with expert consensus for ANB-based skeletal classification. These findings warrant prospective, multi-centre external validation before clinical deployment and support a confidence-aware workflow in which AI predictions for borderline ANB values undergo mandatory clinician verification. Bounding-box calibration emerged as the single most impactful preprocessing decision. Full article

Background/Objectives: Fertility preservation is a key component of cancer care in women of reproductive age, and controlled ovarian stimulation (COS) followed by oocyte/embryo cryopreservation is considered the standard strategy. Although COS protocols are generally standardized, systemic effects related to different malignancies may interfere with ovarian reserve assessment and influence stimulation planning and counselling. This study aimed to evaluate COS outcomes across different malignancy types in women undergoing fertility preservation. Methods: This retrospective study included 331 oncological patients who underwent COS for fertility preservation at a single referral center between May 2008 and May 2025. Patients were stratified into three groups according to malignancy type: breast cancer, hematological malignancies, and other cancers. Ovarian reserve was assessed using serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). COS outcomes, including stimulation duration, total gonadotropin dose, number of retrieved and mature oocytes, follicular output rate (FORT), and follicle-to-oocyte index (FOI), were compared among groups. Results: Patients with hematological malignancies were significantly younger and showed higher AFC values compared with the other groups, whereas AMH levels did not differ significantly. After adjustment for age and AFC, patients with hematological malignancies showed significantly lower AMH levels compared with breast cancer patients (β = −0.94 ng/mL, 95% CI −1.40 to −0.48, p < 0.001), supporting the presence of a relative AMH–AFC discordance. In unadjusted analyses, gonadotropin requirements were higher in breast cancer patients, whereas the number of retrieved and mature oocytes was higher in patients with hematological malignancies. However, after adjustment for age and AFC, malignancy type was not independently associated with retrieved oocytes, mature oocytes, total gonadotropin dose, or stimulation duration. FORT and FOI were comparable among groups. Conclusions: Malignancy type did not appear to independently impair ovarian responsiveness to stimulation. Patients with hematological malignancies showed preserved stimulation outcomes despite AMH values not being proportionally higher than expected based on their younger age and higher AFC. These findings suggest that AMH should be interpreted with caution in systemic malignancies and that AFC may be particularly useful for tailoring fertility preservation counselling and stimulation strategies when AMH and AFC are discordant. Full article

Background/Objectives: Angiographic stenosis severity and functional significance are discordant in up to 65% of intermediate coronary lesions. Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has shown better clinical outcomes than standard angiography-guided PCI, therefore functional significance defines revascularization. This review evaluates the contemporary evidence for intracoronary physiology assessment tools, such as FFR, non-hyperemic pressure ratios (NHPRs), angiography-derived wire-free indices, and microvascular function testing, and proposes a framework for their implementation into clinical practice. Methods: We conducted a narrative review, synthesizing data from landmark randomized controlled trials (DEFER, FAME I–III, DANAMI-3-PRIMULTI, COMPARE-ACUTE, DEFINE-FLAIR, iFR-SWEDEHEART, iMODERN, FAVOR III China and Europe, FAST III, ALL-RISE, CorMicA), along with pooled analyses, meta-analyses, position papers, and relevant guidelines. Results: FFR-guided revascularization resulted in a 28% reduction in cardiac death or myocardial infarction in pooled analyses (HR 0.72, 95% CI 0.54–0.96). leading to a Class I, Level A indication. NHPRs, including iFR, achieved non-inferiority to the FFR at 1 year; however, a 5-year pooled meta-analysis raised concerns of increased all-cause mortality with iFR guidance compared to the FFR (HR 1.34, 95% CI 1.08–1.67). Approximately 20% of lesions show FFR–iFR discordance, driven by vessel-specific physiology and microvascular factors. Wire-free technologies yielded conflicting results: the FAVOR III China trial favored the QFR over angiography, yet FAVOR III Europe failed non-inferiority versus the FFR, while the recent FAST III and ALL-RISE trials demonstrated the non-inferiority of angiography-derived physiology at 1 year. Up to 40% of patients with angina have non-obstructed coronary arteries, and coronary vasomotor function testing can identify treatable microvascular endotypes improving symptoms and quality of life. Conclusions: Functional invasive coronary angiography is advocated to decipher vessel hemodynamics and to guide treatment. The FFR remains the gold standard for invasive physiological assessments, while NHPRs and wire-free technologies are valuable adjuncts with specific indications and limitations. A thorough microvascular evaluation is essential for differentiating between various INOCA endotypes and is gradually being adopted by the interventional community. While NHPRs and virtual technologies struggle to dethrone the king FFR, a comprehensive intracoronary physiology assessment is essential to guide treatment. Full article

Background/Objectives: Anaplastic lymphoma kinase (ALK) fusion is a driver gene translocation detected in 3–5% of patients with non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS)-based tests are the standard of care for detecting actionable gene alterations; however, false negatives remain a concern. Immunohistochemical staining is another reliable, rapid, and low-cost method for detecting ALK fusions. Previous studies have reported high concordance with NGS, although further studies are needed to draw definitive conclusions. Methods: A retrospective analysis was conducted on consecutive patients with NSCLC who were tested using the Oncomine Dx Target Test (ODxTT), an amplicon-based DNA and RNA NGS test for NSCLC, and ALK-immunohistochemistry (IHC) at our institution between 8 August 2019 and 11 April 2025. Results: Of 919 eligible patients included in this study, ALK fusion was detected in 30 (3.26%) patients, whereas ALK-IHC was positive in 35 (3.80%) patients. The concordance and κ coefficient of the two tests were 99.4% and 0.920, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ALK-IHC for ODxTT were 100%, 99.4%, 85.7%, and 100%, respectively. Five discordant patients were NGS negative and IHC positive. Among the five discordant cases, one had a false-negative NGS result, whereas the remaining four had false-positive ALK-IHC results, including three patients with neuroendocrine carcinomas. Conclusions: ALK-IHC shows diagnostic accuracy comparable to ODxTT, although prudent interpretation is needed for patients without adenocarcinoma. Our findings suggest the complementary role of ALK-IHC alongside NGS-based testing, particularly in patients with a high pre-test probability of harbouring ALK fusions. Full article

Background: Adult-onset recessive cerebellar ataxias remain frequently unresolved after next-generation sequencing, partly because phenotype-driven filtering can deprioritize biallelic variants in genes historically associated with severe pediatric multisystem disease. This review examines how attenuated, hypomorphic, or residual-function genotypes may present as late-onset, cerebellar-predominant disease and aims to support clinical interpretation of apparently discordant recessive findings. Methods: We performed a narrative, pathway-based synthesis of autosomal recessive adult- or late-onset ataxia involving genes classically linked to lysosomal/neuronal ceroid lipofuscinosis and peroxisomal disorders. Reports were assessed for age at onset, cerebellar and extracerebellar chronology, variant class, zygosity, segregation/in-trans confirmation, biochemical or functional evidence, and implications for clinician–laboratory interpretation. Results: Published reports indicate that selected NCL-related and peroxisomal genes may be clinically relevant in adult-onset cerebellar ataxia, especially when accompanied by retinal disease, hearing loss, neuropathy, cognitive or psychiatric features, epilepsy/myoclonus, movement-disorder signs, or subtle biochemical abnormalities. Apparent phenotype–gene discordance may be compatible with residual function, allelic-series effects, and cerebellar selective vulnerability, although evidence is often limited to case reports or small series with variable segregation, biochemical, and functional support. We propose a workflow based on structured phenotype transfer, in-trans confirmation, targeted re-phenotyping, ACMG/AMP-informed evidence weighting, and avoidance of label-based exclusion from “ataxia gene” lists. Conclusions: Adult-onset recessive ataxia should not be interpreted only through canonical pediatric disease labels. A pathway-aware, phenotype-complete approach may reduce avoidable VUS retention and improve recognition of attenuated genetic presentations. Full article

Background/Objectives: Aphids are among the most economically damaging agricultural pests globally. However, the internal phylogeny of their largest subfamily, Aphidinae, remains contentious, particularly regarding intergeneric relationships, tribal boundaries, and monophyletic status. Here, we coupled refined taxon sampling with rigorous data-filtering strategies to resolve these persistent phylogenetic discordances. Methods: We sequenced the genomes of four aphid species: Lipaphis pseudobrassicae, Rhopalosiphum maidis, Hyalopterus arundiniformis, and Uroleucon helianthicola. Integrating these new data with public genomic and transcriptomic resources, we established a comprehensive phylogenomic framework for Aphidinae. To address conflicting topologies, we compared a taxonomically broad 157-taxa dataset against a high-completeness 47-taxa core dataset. Furthermore, we evaluated the impact of intrinsic sequence properties, such as compositional heterogeneity and substitution rates, on phylogenetic conflict. Results: Our analyses demonstrate that filtering phylogenetically inconsistent loci and accounting for site heterogeneity significantly improve the topological stability of previously recalcitrant taxa. Conclusions: This study provides a refined evolutionary framework for the Aphidinae and underscores the critical importance of rigorous data curation when resolving rapid evolutionary radiations. Full article

Primary hepatic masses in dogs represent a heterogeneous group of lesions with variable biological behavior and challenging preoperative characterization. The objective of this retrospective study was to describe the clinical presentation, diagnostic findings, surgical management, and outcome of dogs with primary hepatic lesions treated surgically. Ten dogs with resectable hepatic lesions and no evidence of extrahepatic metastasis were included. Clinical records, imaging findings, histopathological diagnoses, treatment, and follow-up data were reviewed. Histopathological diagnoses included hepatocellular carcinoma (n = 3), nodular hyperplasia (n = 2), lobular hyperplasia (n = 1), hepatocellular adenoma (n = 1), undifferentiated sarcoma (n = 1), osteosarcoma (n = 1), and one case without a definitive histological diagnosis. Tumor size ranged from 3.3 to 18 cm. Both benign and malignant lesions were represented across this size range. Cytological findings were discordant with the final histopathological diagnosis in three dogs, whereas one sample was non-diagnostic due to blood contamination. Abdominal ultrasound identified solitary lesions in all evaluated dogs, although surgery revealed previously undetected multifocal disease in two cases. Six of the ten lesions involved the right medial hepatic lobe, although the small sample size precludes conclusions regarding lesion distribution. All dogs underwent surgical resection. Two perioperative deaths occurred secondary to postoperative renal failure. Among the surviving dogs, clinical status during follow-up was generally reported as improved compared with preoperative presentation, and survival times ranged from 4 to more than 730 days, including dogs with malignant neoplasms. Four dogs remained alive and disease-free at the end of the follow-up period (>730 days). This retrospective case series illustrates the clinical and pathological heterogeneity of primary hepatic masses in dogs. Discrepancies between preoperative assessment and intraoperative or histopathological findings were observed in some cases. Given the small sample size, heterogeneous diagnoses and non-standardized diagnostic workup, these observations should be interpreted cautiously and considered hypothesis-generating. Full article

Background/Objectives: Ultrasound-guided fascial hydrorelease (FHR) occasionally elicits a brief localized contraction (“local twitch”) at the moment the needle tip contacts a fascial layer; the anatomical basis of this reaction has not yet been systematically characterized. To examine local twitch occurrence relative to stacking fascia (yes/no) at the needle tip (primary outcome), as well as the anatomical distribution and per-video capture rate (secondary outcomes). Methods: We retrospectively analyzed 11,205 ultrasound videos from a single pain clinic (October 2015–March 2026). Twitches were identified by prospective clinical observation and computational screening (frame-difference-based Profile Match classifier; 417 candidates over 30 review rounds). The stacking fascia status was independently determined by two FHR-experienced clinicians, with discordant cases jointly adjudicated. Results: Inter-rater agreement was 86/90 (95.6%; 95% CI 89.0–98.8%); one case was reassessed, deemed to not be a twitch, and excluded. In the final cohort (n = 89), local twitches occurred at stacking fascia in 89/89 (100%; 95% CI 95.9–100%). Events were concentrated in gluteal/pelvic (51%) and lumbar paraspinal (29%) regions, with a per-video capture rate of 0.98% (110/11,205; 95% CI 0.81–1.18%). Conclusions: Local twitches during ultrasound-guided FHR essentially always coincide with the needle tip lying within stacking fascia, identifying this as the structural locus within this cohort. This figure represents inclusion-criterion-bound selectivity within the twitch-positive subset, not the positive predictive value of stacking fascia for twitch occurrence. Full article

Background/Objectives: Medication adherence is a critical determinant of therapeutic outcomes in type 2 diabetes mellitus (T2DM); however, its relationship with glycemic control remains inconsistent, particularly in real-world and socially vulnerable settings. This study aimed to evaluate medication adherence using multiple validated instruments, assess disease-related knowledge, and examine their relationship with glycemic control, with a focus on potential discordance between self-reported adherence and objective metabolic outcomes. Methods: A cross-sectional analytical study was conducted with 237 adults with T2DM receiving care in a primary health care (PHC) unit in the Brazilian Amazon. Medication adherence was assessed using the Almeida Adherence Scale, ARMS-12, and the Haynes–Sackett test, while disease-related knowledge was evaluated using the Batalla–Martínez questionnaire. Glycemic control was determined based on glycated hemoglobin (HbA1c) values obtained from clinical records within the previous three months. Descriptive and comparative analyses were performed. Results: The study population was predominantly female (64.1%) and aged 40–59 years (55.7%), with a high prevalence of socioeconomic vulnerability. Non-adherence was identified in 55.7% of participants using the Almeida Adherence Scale, whereas higher adherence rates were observed with ARMS-12 (91.1%) and the Haynes–Sackett test (72.2%). Inadequate disease-related knowledge was found in 77.2% of participants. Among individuals with available HbA1c data (n = 116), the mean HbA1c was 8.63% (SD = 1.65), and 81.9% presented inadequate glycemic control (HbA1c ≥ 7%). Notably, among participants classified as adherent by the ARMS-12 scale (91.1%), inadequate glycemic control was nonetheless present in 81.9% of those with available HbA1c data, illustrating the magnitude of the observed discordance between self-reported adherence and objective metabolic outcomes. Cross-tabulation of each adherence instrument against glycemic control showed no statistically significant associations (chi-square with Yates correction; ARMS-12: p = 0.631, φ = 0.045; Almeida Adherence Scale: p = 0.301, φ = 0.096; Haynes–Sackett: p = 0.800, φ = 0.024). Multivariable logistic regression (Nagelkerke R² = 0.321; AUC = 0.834) identified older age (aOR = 0.92; 95% CI: 0.87–0.96; p < 0.001) and higher income (aOR = 9.96; 95% CI: 2.05–48.32; p = 0.004) as independent predictors of glycemic outcome, while no adherence measure was independently associated with HbA1c ≥ 7%. A sensitivity analysis using HbA1c ≥ 8.0% revealed poor control in 59.5% of participants (n = 69/116). Conclusions: Despite varying levels of self-reported medication adherence, inadequate glycemic control was highly prevalent. The absence of statistically significant associations between self-reported adherence and HbA1c, combined with the high prevalence of poor glycemic control regardless of adherence status, is consistent with the hypothesis that adherence alone does not fully explain metabolic outcomes in T2DM. Given the cross-sectional design, no causal inferences can be drawn. These findings highlight the need for integrated care strategies in primary health care, including improved health literacy, structured pharmacotherapeutic follow-up, and the use of multiple adherence assessment tools to better inform clinical decision-making. Full article

Telomere length (TL) measurement is increasingly used in the evaluation of pulmonary fibrosis and suspected telomere biology disorders, with flow cytometry–fluorescence in situ hybridisation (Flow-FISH) representing the current clinical reference standard. However, Flow-FISH provides a population-averaged relative TL, has a high analytical variability and is largely restricted to PBMC-based measurements. We evaluated a long-read sequencing–based assay, Telo-Seq, for clinical TL assessment in an Australian cohort. In this observational study, TL was measured by both Flow-FISH and Telo-Seq in PBMC from 156 healthy controls and a small cohort of 24 patients undergoing clinical evaluation for interstitial lung disease, using the same blood processing and assay workflows. In an exploratory subset of samples, TL was also assessed in whole lung lavage fluid and explanted lung tissue. In the assessment of PBMC, Telo-Seq correlated with Flow-FISH (R² ≈ 0.77) and showed lower inter-assay variability (CV ~1.4% vs. ~4.6%). Classification relative to assay-specific age-adjusted 10th-percentile thresholds was largely concordant between Flow-FISH and Telo-Seq, although discordant cases occurred in both directions near clinically relevant thresholds. Long-read sequencing provides a reproducible approach to TL assessment and supports further evaluation in disease-relevant tissues. Full article

Amyloid positron emission tomography (PET) has become a critical tool in the diagnosis and treatment of Alzheimer’s disease (AD). The Centiloid (CL) scale, a tracer/scanner-independent, standardized quantification unit introduced in 2015, transforms tracer- and scanner-specific standardized uptake value ratios (SUVRs) into a common metric anchored at 0 CL in young cognitively unimpaired individuals and 100 CL in patients with mild-to-moderate AD. This review synthesizes current evidence on the clinical role of the CL scale across three domains: (1) diagnostic classification, with established thresholds of <10 CL for amyloid negativity and >30 CL for high-certainty amyloid positivity; (2) treatment eligibility, where a 2024 Alzheimer’s Association Research Roundtable consensus of global experts recommended a 24–30 CL threshold for initiating lecanemab or donanemab therapy in patients with mild cognitive impairment (MCI) or mild AD dementia; and (3) longitudinal therapy monitoring, in which serial CL measurements provide objective evidence of amyloid clearance. We also review the emerging ‘gray zone’ (10–30 CL) as a distinct clinical entity with elevated progression risk, the critical role of CL quantification in complementing visual reads in borderline cases, technical limitations, and the future integration of CL in clinical practice. This review also critically addresses the ongoing debate on whether amyloid clearance represents a reliable surrogate for clinical benefit, strategies for managing discordant biomarker findings, and the practical feasibility of serial amyloid PET in routine care. With FDA approval of both lecanemab and donanemab, familiarity with the CL scale as a functional treatment biomarker is increasingly relevant for neuroradiologists and nuclear medicine physicians in the modern AD care pathway. As with all imaging modalities, the CL has physiologic and technical limitations. Although the CL scale was designed to reduce heterogeneity across tracers and scanner platforms, the impact of different commercial quantification software packages on CL output remains incompletely characterized. Consistent use of a single software platform for longitudinal monitoring in individual patients is therefore recommended. Full article

Selective androgen receptor modulators (SARMs) are commonly described as tissue-selective anabolic agents, yet the extent to which this selectivity is reflected at the level of receptor-binding energetics remains uncertain. This study evaluated the receptor interaction profiles of the steroidal SARM YK11 and the nonsteroidal SARM ostarine across five steroid hormone nuclear receptors. Flexible molecular docking was performed with AutoDock 4.2 against the androgen (AR), estrogen (ER), progesterone (PR), glucocorticoid (GR), and mineralocorticoid (MR) receptors, using testosterone, estradiol, progesterone, cortisol, and aldosterone as endogenous reference ligands. Binding free energy, docking-derived inhibition constants, intermolecular interaction energies, conformational sampling, and two-dimensional interaction maps were analyzed. Ostarine showed favorable binding across all receptor systems, with binding energies ranging from −10.42 to −12.05 kcal/mol and no pronounced energetic preference for the androgen receptor. YK11 displayed stronger predicted binding, particularly toward the glucocorticoid, progesterone, and androgen receptors, with a docking energy trend of GR > PR > AR > MR > ER. Interaction analysis revealed conserved polar anchoring residues across receptor pockets, together with scaffold-specific contacts that may explain cross-receptor compatibility. These findings indicate that, within the AutoDock 4.2 flexible docking framework applied in this study, docking-derived binding energies primarily describe thermodynamic compatibility with nuclear receptor ligand-binding domains and should not be interpreted as direct predictors of functional SARM tissue selectivity. The observed discordance between predicted receptor affinity and the established tissue-selective pharmacology of ostarine highlights the need for caution when using single-method docking workflows to infer selectivity among closely related steroid hormone receptors. The novelty of this study lies in demonstrating, using a defined AutoDock 4.2-based comparative protocol, that receptor-binding energetics alone do not recapitulate the functional tissue-selective behavior attributed to SARMs. Full article

Background: Early-onset neonatal listeriosis is a rare, life-threatening infection of vertical origin caused by Listeria monocytogenes. First-line therapy is intravenous ampicillin combined with an aminoglycoside; acquired β-lactam resistance is exceptionally uncommon. Case Presentation: A 34-week preterm female neonate (birth weight 1990 g, appropriate for gestational age) was born to a febrile primigravida with fetid greenish amniotic fluid at a regional secondary maternity and transferred at 30 h of life to our tertiary NICU with respiratory failure requiring mechanical ventilation. L. monocytogenes was recovered from blood, gastric aspirate, pharyngeal exudate, ocular secretion, and skin swab. Gradient strip susceptibility testing reported ampicillin and trimethoprim–sulfamethoxazole non-susceptibility, although confirmatory broth microdilution was unavailable. Broad-spectrum empirical therapy was revised on Day 5 to include ampicillin–sulbactam, with piperacillin–tazobactam and gentamicin continued. A follow-up blood culture on Day 9 remained sterile through 7 days. The hospital course was complicated by thrombocytopenia, transiently elevated aminotransferases, and a Grade I subependymal hemorrhage; tertiary NICU length of stay was 25 days. Conclusions: Recovery under a multi-agent regimen precludes attribution of effect to any single component. Discordant gradient strip susceptibility results in L. monocytogenes should be confirmed by broth microdilution before any therapeutic change; survivors of severe early-onset listeriosis require structured multidisciplinary follow-up. Full article