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Abstract Background Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies. Methods We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes. Results Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032). Conclusion This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development. Understanding molecular alterations is essential for evaluating possible targets for more effective systemic therapies for the rare malignancy penile squamous cell carcinoma.

3D printing using fused deposition modeling (FDM) includes a multitude of control parameters. It is difficult to predict a priori what surface finish will be achieved when certain values are set for these parameters. The objective of this work is to compare the models generated by decision tree algorithms (C4.5, random forest, and random tree) and to analyze which makes the best prediction of the surface roughness in polyethylene terephthalate glycol (PETG) parts printed in 3D using the FDM technique. The models have been created using a dataset of 27 instances with the following attributes: layer height, extrusion temperature, print speed, print acceleration, and flow rate. In addition, a dataset has been created to evaluate the models, consisting of 15 additional instances. The models generated by the random tree algorithm achieve the best results for predicting the surface roughness in FDM parts.

The fused deposition modeling (FDM) technique is used today by companies engaged in the fabrication of traffic signs for the manufacture of light-emitting diode LED spotlights. In this sector, the surface properties of the elements used (surface finish, hydrophobic features) are decisive because surfaces that retain little dirt and favor self–cleaning behavior are needed. A design of experiments (L27) with five factors and three levels has been carried out. The factors studied were: Layer height (LH), print temperature (T), print speed (PS), print acceleration (PA), and flow rate (F). Polyethylene terephthalate glycol (PETG) specimens of 25.0 × 25.0 × 2.4 mm have been printed and, in each of them, the surface roughness (Ra,0, Ra,90), sliding angle (SA0, SA90), and contact angle (CA0, CA90) in both perpendicular directions have been measured. Taguchi and ANOVA analysis shows that the most influential variables in this case are printing acceleration for Ra, 0 (p–value = 0.052) and for SA0 (p–value = 0.051) and flow rate for Ra, 90 (p–value = 0.001) and for SA90 (p–value = 0.012). Although the ANOVA results for the contact angle are not significant, specimen 8 (PA = 1500 mm/s2 and flow rate F = 110%) and specimen 10 (PA =1500 mm/s2 and F = 100%) have reached contact angle values above or near the limit value for hydrophobia, respectively.

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg−1·day−1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Rhythmic abilities are linked to performance across a range of cognitive tasks, yet the mechanisms underlying this relationship remain unclear. We evaluated 98 Mexican participants using the Speech-to-Speech Synchronization Test (SSS-Test), a self-report measure of musical training, and an extensive cognitive battery. Analyses revealed that phonological language processing and temporal attention are the core cognitive skills associated with auditory-motor rhythmic proficiency (as assessed by the SSS-Test). Importantly, this relationship appears thresholded: cognitive benefits emerge only when rhythmic abilities exceed a specific level, with further refinements conferring no additional advantage. Moreover, we show that the link between musical training and cognition is fully mediated by this rhythmic performance threshold. These findings provide a unifying framework for understanding how rhythmic skills impact cognition and clarify the mechanisms through which musical training may confer cognitive benefits. Rhythmic ability enhances attention and phonological processing only after surpassing a specific threshold; beyond this point, additional improvements confer no further benefit. This thresholded relationship may explain the positive impact of musical training on cognition.

BackgroundIntervertebral disc nucleus degeneration initiates a degenerative cascade and can induce chronic low back pain. Nucleus replacement aims to replace the nucleus while the annulus is still intact. Over time, several designs have been introduced, but the definitive solution continues to be elusive. Therefore, we aimed to create a new nucleus replacement that replicates intact intervertebral disc biomechanics, and thus has the potential for clinical applications. Materials and methodsTwo implants with an outer ring and one (D2) with an additional midline strut were compared. Static and fatigue tests were performed with an INSTRON 8874 following the American Society for Testing and Materials F2267-04, F2346-05, 2077-03, D2990-01, and WK4863. Implant stiffness was analyzed at 0–300 N, 500–2000 N, and 2000–6000 N and implant compression at 300 N, 1000 N, 2000 N, and 6000 N. Wear tests were performed following ISO 18192-1:2008 and 18192-2:2010. GNU Octave software was used to calculate movement angles and parameters. The statistical analysis package R was used with the Deducer user interface. Statistically significant differences between the two designs were analyzed with ANOVA, followed by a post hoc analysis.ResultsD1 had better behavior in unconfined compression tests, while D2 showed a “jump.” D2 deformed 1 mm more than D1. Sterilized implants were more rigid and deformed less. Both designs showed similar behavior under confined compression and when adding shear. A silicone annulus minimized differences between the designs. Wear under compression fatigue was negligible for D1 but permanent for D2. D1 suffered permanent height deformation but kept its width. D2 suffered less height loss than D1 but underwent a permanent width deformation. Both designs showed excellent responses to compression fatigue with no breaks, cracks, or delamination. At 10 million cycles, D2 showed 3-times higher wear than D1. D1 had better and more homogeneous behavior, and its wear was relatively low. It showed good mechanical endurance under dynamic loading conditions, with excellent response to axial compression fatigue loading without functional failure after long-term testing.ConclusionD1 performed better than D2. Further studies in cadaveric specimens, and eventually in a clinical setting, are recommended.Level of evidence 2c.

Background The presence of chondral lesions in patients with chronic ankle instability is common and has been suggested as a possible cause of persistent pain in some cases, even after successful ligament reconstruction. For this reason, some authors have proposed combining ankle stabilization with cartilage microfracture; however, the results reported in literature are contradictory. Materials and methods The study was designed as a prospective randomized clinical study with two parallel arms. Patients with an anterior talofibular ligament tear causing pain and instability, associated with a Berndt–Harty stage I–IIb talar osteochondral lesion of < 150 mm 2 that had not responded to conservative treatment, were blindly assigned to either isolated ligament reconstruction (REC) or reconstruction plus microfracture (REC + MIC). Evaluators were also blinded. Results A total of 71 patients were included in the study, with 36 in the REC group and 35 in the REC + MIC group. The groups were comparable in terms of anthropometry and pathology. The operating time was significantly longer in the REC + MIC group (48.0 ± 4.5 min) compared with the REC group (24.9 ± 3.9 min; p  < 0.001). At the end of follow-up, both patient groups showed similar results on the American Orthopaedic Foot and Ankle Society (AOFAS) score ( p  = 0.755), Self-Reported Foot and Ankle Score (SEFAS) ( p  = 0.862), Karlsson score ( p  = 0.993), and visual analog scale (VAS) ( p  = 0.870). However, the time to recovery differed between the groups, with patients in the REC group recovering faster from before the operation (pre-op) through the third month after the operation (post-op). The difference in recovery at 3 months post-op was statistically significant on the AOFAS ( p  < 0.001), SEFAS ( p  < 0.001), and Karlsson ( p  < 0.001) scores. No statistically significant difference was observed in terms of pain ( p  = 0.342). The failure rate was also comparable between the groups, with four (11.1%) reoperations in the REC group and five (14.3%) in the REC + MIC group ( p  = 0.735). Conclusions At 2 years post surgery, no differences were observed in function (according to the AOFAS, SEFAS, and Karlsson scores), pain, or complications in patients with ankle instability and associated chondral damage treated with or without microfractures. However, patients who underwent microfractures experienced a significantly slower recovery of function. Level of evidence: Level 1. Trial registration: ClinicalTrials.gov Identifier NCT06947317 (retrospectively registered). Date: 1 May 2025. ( https://clinicaltrials.gov/study/NCT06947317 ).

Background: Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer. New Adjuvant Trial with Ribociclib [LEE011] (NATALEE) is a trial evaluating the efficacy and safety of adjuvant ribociclib plus endocrine therapy (ET) versus ET alone in patients with HR+/HER2− early nonmetastatic breast cancer (EBC). Methods/design: NATALEE is a multicenter, randomized, open-label, Phase III trial in patients with HR+/HER2− EBC. Eligible patients include women, regardless of menopausal status, and men aged ⩾18 years. Select patients with stage IIA, stage IIB, or stage III disease (per the anatomic classification in the AJCC Cancer Staging Manual, 8th edition) with an initial diagnosis ⩽18 months prior to randomization are eligible. Patients receiving standard (neo)adjuvant ET are eligible if treatment was initiated ⩽12 months before randomization. Patients undergo 1:1 randomization to ribociclib 400 mg/day (3 weeks on/1 week off) +ET (letrozole 2.5 mg/day or anastrozole 1 mg/day [investigator’s discretion] plus goserelin [men or premenopausal women]) or ET alone. Ribociclib treatment duration is 36 months; ET treatment duration is ⩾60 months. The primary end point is invasive disease-free survival. Discussion: The 36-month treatment duration of ribociclib in NATALEE is extended compared with that in other adjuvant cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor trials and is intended to maximize efficacy due to longer duration of CDK4/6 inhibition. Compared with the 600-mg/day dose used in advanced breast cancer, the reduced ribociclib dose used in NATALEE may improve tolerability while maintaining efficacy. NATALEE includes the broadest population of patients with HR+/HER2− EBC of any Phase III trial currently evaluating adjuvant CDK4/6 inhibitor treatment. Trial registration: ClinicalTrials.gov identifier: NCT03701334 (https://clinicaltrials.gov/ct2/show/NCT03701334)

The aim of this study was to analyze the impact of surgical correction of the thoracic deformity on the cardiorespiratory function of patients with moderate-severe Scheuermann’s hyperkyphosis (SK). A series of 23 adolescents with SK who underwent surgery through an only posterior approach using all pedicle screw constructs were included in the study. Cardiorespiratory parameters were measured during a maximal exercise tolerance test before and 2 years after surgery. Heart rate, oxygen saturation (SatO2), maximum oxygen uptake (VO2 max), ventilatory capacity at maximal exercise (VEmax), and energy costs were recorded. There were statistically significant differences in the forced vital capacity (FVC) ( P  < 0.05), total VO 2 max (ml/min) ( P  < 0.01), maximum expired volume (VEmax) per minute ( P  < 0.01) and cardiovascular efficiency (HR/VO2 ratio) ( P  < 0.05). None of these changes were clinically relevant. There were no changes in the VO 2 max per kg of body mass. The magnitude of the kyphosis correction did not correlate with the change in normalized VO2max or VEmax. In conclusion, patients with moderate-severe SK improve their baseline respiratory limitations and the tolerance to maximum exercise 2 years after surgery. However, the slight cardiorespiratory functional improvements should not necessarily be attributed to the surgery, and could also be caused solely by the residual growth of the lungs and thorax. Furthermore, respiratory functional changes are under thresholds considered as clinically relevant.

Premise of the study: Field methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes. Methods and Results: Living trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness. Conclusions: Sonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees.