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This study aimed to determine what information is used during observational learning and how this depends on task constraints using a mixed-design (between- and within-subjects) experimental approach. Specifically, the study aimed to examine whether full-body information or limited-body information enhances observational learning, and whether the influence of information is mediated by task constraints. For this purpose, participants (N = 48, mean age = 24 ± 5.3, male) were assigned to one of three demonstration conditions, each observing a point-light display (PLD) of a throwing action with varying kinematic information: full-body motion (BODY, 17 markers across major joints), right-arm motion (ARM, 4 markers on the throwing arm), or wrist-only motion (WRIST, 1 marker on the wrist). Each condition was divided into two sub-groups: one replicating the throwing action with a ball to a target (BODY-ball, ARM-ball, WRIST-ball) and one replicating the action without a ball, focusing on movement form (BODY-no ball, ARM-no ball, WRIST-no ball). These conditions manipulated the scope of visual kinematic cues and the presence of object-related task constraints to investigate their effects on motor learning outcomes. During the acquisition phase, participants performed 20 acquisition trials where a demonstration was shown five times on the first trial and then once again before each of the remaining trials. Twenty-four hours later, a retention test (5 trials with no demonstration) was performed. After retention, participants performed 10 further trials as re-acquisition. All participants observed a full-body PLD model in this period. Movement outcome, the similarity of intra-limb coordination, and wrist peak velocity in relation to the model were calculated. Results showed that in shoulder-elbow coordination, the BODY-ball group performed less like the model than the other groups in the retention test, all P < 0.05. In wrist-elbow coordination, a significant difference was observed in the ball condition, and the BODY group performed less like the model than the ARM and WRIST groups, all P < 0.05. Additionally, the no ball groups performed more like the model than the ball groups, all P < 0.05. In wrist peak velocity, the WRIST group performed less like the model than the BODY and ARM groups, all P < 0.05, and also, the ball groups performed more like the model than the no ball groups, all P < 0.05. These findings highlight that learning coordination patterns benefits from focused visual cues and minimal task demands, whereas learning velocity-related parameters depends on object interaction and more comprehensive kinematic information. This suggests that effective observational learning requires matching the type of visual information to the specific motor control demands of the task, offering insights for designing motor skill training protocols.

Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established. The application of neoadjuvant therapy in locally advanced disease may be indicated, the routine use of systemic therapy prior to surgery for cholangiocarcinoma patients with an upfront resectable disease is less well established, but discussed and performed in selected cases. In advanced disease, only combination chemotherapy regimens have been demonstrated to achieve disease control in untreated patients. Molecular profiling of the tumor has demonstrated that many BTC might bear actionable targets, which might be addressed by biological treatments, thus improving the prognosis of the patients. Furthermore, the addition of the immunotherapy to standard chemotherapy might improve the prognosis in a subset of patients. This review seeks to give a comprehensive overview about the role of neoadjuvant as well as palliative systemic treatment approaches and an outlook about novel systemic treatment concept in BTC.

Background Assessing liver health and its determinants in the elderly is crucial. Lifestyle factors, including nutrition and exercise, may influence liver function. This study aimed to investigate the association between macronutrients and energy intake with serum levels of aminotransferases in elderly Iranian athletes and non-athletes. Methods A cross-sectional study involving 811 elderly participants (369 athletes, 442 non-athletes) from the Neyshabur Longitudinal Study on Aging (NeLSA) was conducted. Dietary intake was assessed using a food frequency questionnaire. Serum Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Regression analyses were employed to evaluate the associations between macronutrient intake and liver enzymes, adjusting for potential confounding variables. Results In elderly athletes, higher calorie, protein, and carbohydrate intake were significantly associated with elevated ALT levels ( p  < 0.01 for all). Additionally, higher carbohydrate and calorie intake were linked to increased AST levels in athletes ( p  < 0.05 for both). For elderly non-athletes, only higher protein intake was significantly associated with increased ALT levels ( p  < 0.05), while no nutritional factors were associated with changes in AST levels. Conclusions This study revealed that higher calorie, protein, and carbohydrate intake were associated with elevated ALT and AST levels in elderly individuals, particularly athletes. For athletes, all three nutrients were linked to elevated ALT, while only carbohydrates and calories impacted AST. For non-athletes, only protein affected ALT. These findings suggest that tailored nutritional strategies may be necessary to preserve liver health in active aging populations.

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFS targeted /PFS pre-chemotherapy ) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

BackgroundTherapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer.MethodsIn this multicenter retrospective cohort analysis, we identified patients with metastatic biliary tract adenocarcinoma who were treated with Nal-IRI in combination with 5-fluorouracil and folinic acid following tumor progression under standard therapy at one of the study centers between May 2016 and January 2019. We assessed disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).ResultsThere were 14 patients; the median age at the time of diagnosis and the median age at the initiation of Nal-IRI were 59.3 and 60.0 years, respectively. Nal-IRI in combination with 5-fluorouracil and folinic acid was administered as second-, third-, fourth-, and fifth-line treatment in 6 (43%), 5 (36%), 2 (14%), and 1 (7%) patient with metastatic disease, respectively. The objective DCR with Nal-IRI was 50% (7/14 patients). Six patients (43%) had partial response, and one patient (7%) had stable disease. Progressive disease was observed in seven patients. The median PFS and median OS following Nal-IRI initiation were 10.6 and 24.1 months, respectively.ConclusionsThis retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer.

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) bears a dismal prognosis due to the limited activity of systemic chemotherapy. In our platform for precision medicine, we aim to offer molecular-guided treatments to patients without further standard therapy options. Methods: In this single center, real-world retrospective analysis of our platform, we describe the molecular-based therapy approaches used in all 50 patients diagnosed with therapy-refractory mPDAC. A molecular portrait of the tumor specimens was created by next-generation sequencing, immunohistochemistry (IHC), microsatellite instability (MSI) testing, and fluorescence in situ hybridization. Results: In total, we detected 123 mutations in 50 patients. The five most frequent mutations were KRAS (n = 40; 80%), TP53 (n = 29; 58%), CDKN2A (n = 8; 16%), SMAD4 (n = 4; 8%), and NOTCH1 (n = 4; 8%), which together accounted for 40.2% of all mutations. Two patients had gene fusions, namely, TBL1XR1–PIK3CA and EIF3E–RSPO2. IHC detected expression of EGFR, phosphorylated mTOR, and PTEN in 36 (72%), 33 (66%), and 17 patients (34%), respectively. For 14 (28%) of the 50 patients, a targeted therapy was suggested based on the identified molecular targets. The recommended treatments included the mTOR inhibitor everolimus (n = 3), pembrolizumab (n = 3), palbociclib (n = 2), nintedanib (n = 2), and cetuximab, crizotinib, tamoxifen, and the combination of lapatinib and trastuzumab, in one patient each. Finally, five patients received the recommended therapy. Four patients died due to disease progression before radiological assessment. One patient was treated with nintedanib and achieved stable disease for 6 months. Conclusion: Based on our observations, precision medicine approaches are feasible and implementable in clinical routine and may provide molecular-based therapy recommendations for mPDAC.

The water entry problem of three-dimensional pounders with different geometric shapes of cube, cylinder, sphere, pyramid, and cone was numerically simulated by the commercial software Abaqus, and the effects of pounder shape and drop height from the free surface of water on deepwater displacement and velocity as well as pinch-off time and depth were investigated. An explicit dynamic analysis method was employed to model fluid-structure interactions using a Coupled Eulerian-Lagrangian (CEL) formulation. The simulation results are verified by showing the computed shape of the air cavity, displacement of sphere, pinch-off time, and depth which all agreed with the experimental results. The results reveal that the drag force of water has the highest and lowest effect on cubical and conical pounders, respectively. Increasing the pounder drop height up to the critical height leads to increased pounder velocity while impacting the model bed and more than the critical drop height has a reverse effect on pounder impact velocity. Pinch-off time is a very weak function of pounder impact velocity; but pinch-off depth increases linearly with increased impact velocity.

Growth-promoting bacteria (GPB) have shown promising effects on serving plants against environmental constraints such as drought. Nevertheless, simultaneous effects of different GPB have less been considered for arid land plants and under field conditions. We investigated the effects of single and combined application of GPB, including free-living nitrogen-fixing bacteria (NFB), phosphate solubilizing bacteria (PSB), potassium solubilizing bacteria (KSB), a combination of NFB, PSB, and KSB (NPK), and control, at three drought stress treatments. In order to better understand the interactions between drought and GPB, we measured the morphological, biochemical, and physiological plant traits. The target plant was salt tree ( Halimodendron Halodendron (Pall.) Voss), a legume shrub native to arid lands of Central and West Asia. All biofertilizer treatments enhanced the growth, physiology, and biochemistry of salt tree seedlings, and there were significant differences among the treatments. KSB and PSB treatments increased photosynthetic pigments, but KSB treatment was more efficient in transpiration rate and stomatal regulation and increased the soluble carbohydrates. PSB treatment had the highest effect on root traits, such as taproot length, root volume, cumulative root length, and the ratio of root to shoot. NFB treatment enhanced root diameter and induced biomass translocation between root systems. However, only the application of mixed biofertilizer (i.e., NPK treatment) was the most significant treatment to improve all plant morphological and physiological characteristics of salt tree under drought stress. Therefore, our results provided improvement of some specific plant traits simultaneous with application of three biofertilizers to increase growth and establishment of salt tree seedlings in the degraded arid lands.

Penile cancer, though a rare malignancy, presents a significant challenge in the domain of male genitourinary oncology, particularly due to its limited treatment options and due to the profound physical and psychological impact on patients [...]