Search Results (164)

Pancreatic cancer is frequently accompanied by cancer-associated cachexia, a debilitating metabolic syndrome marked by progressive skeletal muscle wasting and systemic metabolic dysfunction. This study presents a systems biology framework to simultaneously identify therapeutic targets for both pancreatic ductal adenocarcinoma (PDAC) and its associated cachexia (PDAC-CX), using cell-specific genome-scale metabolic models (GSMMs). The human metabolic network Recon3D was extended to include protein synthesis, degradation, and recycling pathways for key inflammatory and structural proteins. These enhancements enabled the reconstruction of cell-specific GSMMs for PDAC and PDAC-CX, and their respective healthy counterparts, based on transcriptomic datasets. Medium-independent metabolic biomarkers were identified through Parsimonious Metabolite Flow Variability Analysis and differential expression analysis across five nutritional conditions. A fuzzy multi-objective optimization framework was employed within the anticancer target discovery platform to evaluate cell viability and metabolic deviation as dual criteria for assessing therapeutic efficacy and potential side effects. While single-enzyme targets were found to be context-specific and medium-dependent, eight combinatorial targets demonstrated robust, medium-independent effects in both PDAC and PDAC-CX cells. These include the knockout of SLC29A2, SGMS1, CRLS1, and the RNF20–RNF40 complex, alongside upregulation of CERK and PIKFYVE. The proposed integrative strategy offers novel therapeutic avenues that address both tumor progression and cancer-associated cachexia, with improved specificity and reduced off-target effects, thereby contributing to translational oncology. Full article

Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and additive manufacturing to assess a chronic, infected gunshot injury in the knee joint of a red deer. This unique approach serves as a translational model for complex skeletal trauma. Methods: Multimodal imaging—including clinical CT, MRI, and HR-pQCT—was used to characterise the extent of osseous and soft tissue damage. Histopathological and molecular analyses were performed to confirm the infectious agent. HR-pQCT datasets were segmented and processed for 3D printing using PolyJet, stereolithography (SLA), and fused deposition modelling (FDM). Printed models were quantitatively benchmarked through 3D surface deviation analysis. Results: Imaging revealed comminuted fractures, cortical and trabecular degradation, and soft tissue involvement, consistent with chronic osteomyelitis. Sphingomonas sp., a bacterium that forms biofilms, was identified as the pathogen. Among the printing methods, PolyJet and SLA demonstrated the highest anatomical accuracy, whereas FDM exhibited greater geometric deviation. Conclusions: HR-pQCT-guided 3D printing provides a powerful tool for the anatomical visualisation and quantitative assessment of complex bone pathology. This approach not only enhances diagnostic precision but also supports applications in surgical rehearsal and forensic analysis. It illustrates the potential of digital imaging and additive manufacturing to advance orthopaedic and trauma care, inspiring future research and applications in the field. Full article

The longstanding debate over early hominin subsistence strategies, particularly the hunting-versus-scavenging hypothesis, as well as discussions regarding the functionality of Oldowan sites, has been primarily centered on the archeological and paleoanthropological record of Olduvai Gorge. Historically, FLK Zinj has been at the core of these debates, serving as a principal empirical reference due to the prevailing assumption that most other Bed I sites at Olduvai represented non-anthropogenic accumulations However, recent discoveries have significantly reshaped this perspective. Newly identified early sites, including PTK, DS, and AGS, situated within the paleolandscape and thin stratigraphic context of FLK Zinj, provide crucial new anthropogenic datasets. These sites offer additional dimensions to the study of early hominin behavior, facilitating a more nuanced reconstruction of their adaptive strategies in this paleoenvironment. Furthermore, methodological advancements in recent years—including controlled experimental and actualistic studies, sophisticated statistical modeling, and the integration of machine learning algorithms—have greatly enhanced the analytical frameworks available for investigating early hominin behavior. These innovations have refined the ability to formulate and test hypotheses within a rigorous scientific paradigm, significantly improving the resolution of archeological and taphonomic interpretations. This study presents an in-depth taphonomic analysis of the faunal assemblage from level 22A at DS, a Bed I site at Olduvai Gorge dated to approximately 1.84 Ma. The assemblage exhibits exceptional preservation, enabling detailed assessments of skeletal part representation, fragmentation patterns, and surface modifications. By combining traditional taphonomic methodologies with state-of-the-art AI-driven bone surface modification (BSM) analyses, this research contributes novel insights into the interactions between early hominins and carnivores, elucidating the complex ecological dynamics of an Early Pleistocene African paleolandscape. Full article

Advancements in load-bearing tissue repair increasingly demand biomaterials that not only support structural integrity but also interact dynamically with the physiological environment. This review examines the latest progress in smart biomaterials designed for skeletal reconstruction, with emphasis on mechanoresponsive scaffolds, bioactive composites, and integrated microsensors for real-time monitoring. We explore material formulations that enhance osseointegration, resist micromotion-induced loosening, and modulate inflammatory responses at the bone–implant interface. Additionally, we assess novel fabrication methods—such as additive manufacturing and gradient-based material deposition—for tailoring stiffness, porosity, and degradation profiles to match host biomechanics. Special attention is given to sensor-augmented platforms capable of detecting mechanical strain, biofilm formation, and early-stage implant failure. Together, these technologies promise a new class of bioresponsive, diagnostic-capable constructs that extend beyond static support to become active agents in regenerative healing and post-operative monitoring. This multidisciplinary review integrates insights from materials science, mechanobiology, and device engineering to inform the future of implantable systems in skeletal tissue repair. Full article

The following work is based on the historical–anthropological analysis of 93 skeletal remains belonging to post-war casualties who died in 1946 and remained missing for years. In 2019, 93 metal boxes containing skeletal remains of Slavic origin, belonging to civilians and soldiers who perished in the immediate postwar period following World War II, were found inside the ossuary of the Monumental Cemetery in Bari (Italy). At the beginning of the search, these people were thought to have died in prison camps in Apulia, such as Torre Tresca and Grumo Appula, in the province of Bari. Later, thanks to the discovery of war badges and years of extensive historical research, it was discovered that these remains had been missing for 75 years and belonged to soldiers of the Royal Yugoslav Army and civilians, probably their relatives, who died in 1946 in the refugee camp of Eboli, in the province of Salerno, Campania (Italy). To unveil this truth that remained hidden for over 75 years, a multidisciplinary study divided into two phases was applied. The first phase, grounded in historical research study, aimed to determine the historical and temporal context in which they lived and confirm the life they actually lived in the Eboli refugee camp. The second phase, grounded in anthropological research, aimed to reconstruct the biological profile of each individual, identify the presence of antemortem, perimortem, and postmortem lesions, assess potential pathological conditions, and determine, where possible, the cause of death. Finally, a correlation of the collected data was conducted to ascertain and corroborate, with reasonable certainty, the living conditions to which they were subjected in the refugee camp where they resided. Italy after 1943 became the scene of intense fighting and a dramatic situation for prisoners of war, including many Yugoslav soldiers. This work brought to light a history that had been lost for as many as 75 years, highlighted the importance, specifically, of the role of the Eboli refugee camp, a context little known and forgotten by many, and above all made it possible to remember and restore dignity to the victims of the Great War. Full article

Background: The optimal treatment for proximal tibial osteosarcoma (OS) in skeletally immature patients remains controversial. A custom hinged endoprosthesis has been used to preserve the growth potential of the distal femur. This study aims to report (1) the 2-year follow-up outcomes after surgery for pediatric proximal tibial OS; (2) the complications associated with this endoprosthesis; and (3) the extent to which the growth potential of the adjacent open physis can be preserved. Methods: Seven skeletally immature patients (mean age, 11.1 years; range, 9–13 years) with proximal tibial OS were included between November 2020 and December 2022. All underwent tumor resection and reconstruction by this custom endoprosthesis. Postoperative limb function was evaluated by the Musculoskeletal Tumor Society (MSTS) score system and complications were recorded. Overall leg length and femoral length were measured radiographically to determine the growth rate. Results: The mean follow-up time was 34.7 months (standard deviation (SD), 8.9 months). One patient presented with local recurrence 12 months after surgery, and another patient had pulmonary metastasis 3 months postoperatively. The range of flexion of the knee after rehabilitation was between 90° and 125°, with an average of 103.6° (SD, 12.5°). The average MSTS score of the patients after surgery was 27.4 (SD, 1.5). Wound dehiscence took place in three patients after chemotherapy. At the last follow-up, the overall limb length discrepancy was 2.1 cm (SD, 2.4 cm). Growth at the distal femoral physis after surgery was observed in all patients during follow-up, with an average of 81.4% (range, 57.78–100%) of growth of the contralateral distal femoral physis. Conclusions: This custom hinged endoprosthesis can preserve the growth potential of the adjacent distal femur and provide satisfying functional outcomes with lower postoperative complication rate. It could serve as an alternative for proximal tibial OS in skeletally immature children. Full article

Injuries characterized by significant loss of skeletal muscle tissue volume, known as volumetric muscle loss (VML), lead to substantial impairment in functional capabilities. Natural repair processes and existing medical interventions fall short of fully restoring function post-VML. Despite progress in the VML field, there is an unsatisfactory success rate, donor site morbidity, and inefficient reconstruction of lost muscle tissue. This leads to persistent strength and functional deficits, impacting the quality of life for VML patients. In recent years, studies have explored the potential of bioactive glasses (BGs) as crucial materials in regenerating tissues beyond the skeletal system. BG, used mainly in bone engineering, can aid muscle repair by releasing ions like calcium and phosphate to stimulate cellular response. However, current BG composites struggle to match the mechanical properties of soft tissues, limiting seamless healing. This review summarizes recent advances in various BG structures studied for skeletal muscle tissue regeneration. Full article

Background/Objectives: Local and systemic factors, including nutritional status, influence the prognosis of oral squamous cell carcinoma (OSCC). Skeletal muscle mass (SMM) loss is a poor prognostic factor in older patients and those with cancer. Herein, we examined the SMM index (SMI), rates of surgical site infection (SSI), and prognosis of 92 patients (59 males and 33 females) who underwent resection and free flap reconstructive surgery (FFRS) between 2013 and 2021. Methods: Preoperative computed tomography was performed to measure SMM at L3. The median SMI was 45.94 and 38.03 cm²/m² in males and females, respectively. Patients were classified into low and high SMI groups based on median SMI, and overall survival (OS) was analyzed. Results: Overall, 47 (51.1%) and 45 (48.9%) patients had low and high SMIs, respectively. SSI occurred in 11 (12.0%) patients; wound dehiscence and delayed wound healing were observed in 22 (23.9%). SSI rates were not significantly different between the low and high SMI groups. Conversely, OS was significantly associated with age, pathological N (pN), extranodal extension (ENE), and SMI (high, 81.1%; low, 60.2%). Univariate analyses revealed significant associations between OS and age (≥65 vs. <65 years), SMI (low vs. high), pN (present vs. none), ENE (present vs. none), and albumin (<4.0 vs. ≥4.0 mg/dL). Cox multivariate analysis included SMI (low vs. high; hazard ratio [HR]: 2.339, 95% confidence interval [CI]: 1.008–5.429; p = 0.015) and ENE (present vs. none; HR: 7.727, 95% CI: 3.083–19.368; p < 0.001). Conclusions: SMI and ENE were identified as independent predictive factors of OS in patients with OSCC undergoing FFRS. Full article

Skeleton representation learning offers substantial advantages for action recognition by encoding intricate motion details and spatial–temporal dependencies among joints. However, fully supervised approaches necessitate large amounts of annotated data, which are often labor-intensive and costly to acquire. In this work, we propose the Spatial–Temporal Heatmap Masked Autoencoder (STH-MAE), a novel self-supervised framework tailored for skeleton-based action recognition. Unlike coordinate-based methods, STH-MAE adopts heatmap volumes as its primary representation, mitigating noise inherent in pose estimation while capitalizing on advances in Vision Transformers. The framework constructs a spatial–temporal heatmap (STH) by aggregating 2D joint heatmaps across both spatial and temporal axes. This STH is partitioned into non-overlapping patches to facilitate local feature learning, with a masking strategy applied to randomly conceal portions of the input. During pre-training, a Vision Transformer-based autoencoder equipped with a lightweight prediction head reconstructs the masked regions, fostering the extraction of robust and transferable skeletal representations. Comprehensive experiments on the NTU RGB+D 60 and NTU RGB+D 120 benchmarks demonstrate the superiority of STH-MAE, achieving state-of-the-art performance under multiple evaluation protocols. Full article

(1) Background: Condylar fracture healing pattern classification in children and adolescents is primarily based on the radiological assessment of condylar morphology; however, recent studies showed the presence of a poor correlation between post-treatment radiological findings and clinical temporomandibular joint (TMJ) dysfunction. The present case series aimed to correlate the condylar morphology, shape, and trabecular bone density with the skeletal asymmetry and the clinical recovery of two growing patients with unilateral condylar fractures undergoing orthopedic treatment with the Balters Bionator appliance. (2) Methods: Pre- and post-treatment (12 months) cone-beam computed tomography (CBCT) scans of two growing patients with unilateral condylar fracture were retrieved; both patients were treated with the Balters Bionator appliance for one year. Morphological evaluation of the condylar healing pattern was carried out on CBCT reconstructions of the mandible. Condylar remodeling and skeletal asymmetry were assessed through linear measurements performed on pre- and post-treatment CBCT scans; then, fractal analysis (FA) was employed to assess the condylar trabecular bone density on orthopantomographies (OPTs). Clinical and TMJ functional evaluation were retrieved from patients’ records from before and at the end of the treatment (12 months). (3) Results: Conservative treatment of condylar fractures in growing patients led to an increased bone density of the condylar heads, regardless of the post-treatment size and morphology of the injured condyles. Patient one presented an unchanged condylar morphology on the affected side, while patient two’s condyle was slightly spherical. The qualitative results were confirmed by quantitative measurements on CBCTs. The radiological healing patterns were associated with slightly different functional outcomes. Both patients also exhibited an improvement in skeletal asymmetry and TMJ function. (4) Conclusions: According to the findings in the present study, the condylar remodeling and bone apposition after conservative treatment of condylar fractures in growing patients can exhibit different radiological and functional outcomes. Indeed, an unchanged morphology of the condylar head is more likely to determine a physiological TMJ recovery. Full article

Aim: Class II Division I malocclusion poses significant challenges in orthodontics. The combination of a Herbst appliance and miniscrew anchorage emerged as a practical solution to improve skeletal and dental outcomes. This study employed finite element analysis to evaluate the biomechanical effects of a miniscrew-supported Herbst appliance on mandibular advancement and dentition movement. Methods: High-definition CBCT scans captured the maxilla and mandible’s detailed dental anatomy. The scans were stored in DICOM format for seamless integration with Mimics software (Mimics Innovation Suite research version 21.0, Materialise NV, Leuven, Belgium) for 3D reconstruction and model refinement. The appliance, designed with a maxillary fixed palatal arch and mandibular acrylic splint connected by telescoping rods, incorporated titanium TADs and elastic chains. STL models were optimized in Geomagic x Design for finite element analysis in Abaqus, assigning validated mechanical properties for materials. Tetrahedral meshing and realistic boundary conditions simulated biomechanical interactions. Tetrahedral C3D4 elements were used for meshing, ensuring a balance between computational efficiency and detailed anatomical representation. Tetrahedral meshing and realistic boundary conditions simulated biomechanical interactions. Dynamic simulations in CATIA evaluated mandibular movement. FEA analyzed displacement across dentoalveolar structures along the X, Y, and Z axes to assess treatment efficacy and biomechanical stability. Results: The Z displacement analysis revealed that the incisal edges of the lower central, lateral, and canines shifted lingually by 0.41, 0.4, and 0.47 mm, respectively. Additionally, the apices of the lower central, lateral, and canines displaced backwards by 0.05 mm, 0.05 mm, and 0.07 mm, respectively. Conclusions: The appliance facilitated mandibular advancement, bodily retracted the lower incisors, well-controlled the upper ones, and mesial-tipped the upper posterior teeth. In contrast with traditional functional appliances, it caused the lower anterior teeth to move backwards, while skeletal anchorage overcame some shortcomings of nonsurgical treatments. This method might be a good treatment option for growing skeletal Class II patients. Full article

This study examines four shallow-water, reef-coral-bearing carbonate successions belonging to the Jhill Limestone Unit of the Gaj Formation, exposed in the area near Karachi (southern Pakistan). Sixty-two samples were collected for the quantitative analysis of the skeletal and foraminiferal assemblages. The analysis of large benthic foraminifera suggests a placement within the late Oligocene, characterized by the setup of the Late Oligocene Warming Event. Thanks to quantitative analyses and multivariate statistics, three biofacies were identified: (1) the reef coral biofacies (BFA), indicative of a sheltered, shallow-water environment above fair-weather wave base; (2) the coralline algal biofacies (BFB), deposited within a mesophotic setting and representing the deepest biofacies among the three recognized ones; and (3) the large benthic foraminiferal and coralline algal biofacies (BFC), subdivided into two sub-biofacies, namely (a) the miogypsinid, thin and flat large benthic foraminiferal and coralline algal sub-biofacies (BFC1), indicative of deeper setting, comprised between BFA and BFB, and (b) the miogypsinid and coralline algal sub-biofacies (BFC2), indicative of shallower settings than BFC1, and bearing evidence of paleo-seagrass meadows. All these biofacies were developed within the photic zone, in a relatively flat seafloor punctuated by patch reefs and seagrass meadows and characterized by a notable nutrient influx. Foraminiferal-based experimental paleobathymetric parameters, including the lepidocyclinids/miogypsinids, the flat nummulitids/lepidocyclinids, and the hyaline/porcelaneous foraminifera ratios, were tested and confirmed as reliable tools for paleodepth and paleoenvironmental reconstructions. Full article

Background: The African hedgehog (Atelerix albiventris) exhibits specialized skin differentiation leading to spine formation, yet its regulatory mechanisms remain unclear. Transposable elements (TEs), particularly LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements), are known to influence genome organization and gene regulation. Objectives: Given the high proportion of SINEs in the hedgehog genome, this study aims to characterize the distribution, evolutionary dynamics, and potential regulatory roles of LINEs and SINEs, focusing on their associations with chromatin architecture, DNA methylation, and gene expression. Methods: We analyzed LINE and SINE distribution using HiFi sequencing and classified TE families through phylogenetic reconstruction. Hi-C data were used to explore TE interactions with chromatin architecture, while whole-genome 5mCpG methylation was inferred from PacBio HiFi reads of muscle tissue using a deep-learning-based approach. RNA-seq data from skin tissues were analyzed to assess TE expression and potential associations with genes linked to spine development. Results: SINEs form distinct genomic blocks in GC-rich and highly methylated regions, whereas LINEs are enriched in AT-rich, hypomethylated regions. LINEs and SINEs are associated differently with A/B compartments, with SINEs in euchromatin and LINEs in heterochromatin. Methylation analysis suggests that younger TEs tend to have higher methylation levels, and expression analysis indicates that some differentially expressed TEs may be linked to genes involved in epidermal and skeletal development. Conclusions: This study provides a genome-wide perspective on LINE and SINE distribution, methylation patterns, and potential regulatory roles in A. albiventris. While not establishing a direct causal link, the findings suggest that TEs may influence gene expression associated with spine development, offering a basis for future functional studies. Full article

ACL injury in skeletally immature patients remains a debatable topic in terms of its management, surgical choices and rehabilitation. The treatment preferences vary across the globe. Children are not little adults in terms of their physiology and anatomy. Hence, contemporary treatment inferred from the adult population does not give the same outcomes in pediatric patients. An in-depth study of specific challenges and difficulties is warranted to optimize the treatment strategies to cater to this group of patients. There is a paucity of literature giving long-term follow-up of ACLR in skeletally immature patients and no standardized guidelines are present for managing this group of patients. The authors have tried to summarize the current concepts for managing ACL injuries in skeletally immature patients through this article. Multiple lacunae and controversies exist in the knowledge regarding the optimum treatment of pediatric patients with ACL injuries who are comparatively more prone to ACL tears than their adult counterparts. Identifying the best mode of management of ACL tears in these skeletally immature patients is necessary. Level of evidence: Level IV. Full article

Recognizing human activities from motion data is a complex task in computer vision, involving the recognition of human behaviors from sequences of 3D motion data. These activities encompass successive body part movements, interactions with objects, or group dynamics. Camera-based recognition methods are cost-effective and perform well under controlled conditions but face challenges in real-world scenarios due to factors such as viewpoint changes, illumination variations, and occlusion. The latter is the most significant challenge in real-world recognition; partial occlusion impacts recognition accuracy to varying degrees depending on the activity and the occluded body parts while complete occlusion can render activity recognition impossible. In this paper, we propose a novel approach for human activity recognition in the presence of partial occlusion, which may be applied in cases wherein up to two body parts are occluded. The proposed approach works under the assumptions that (a) human motion is modeled using a set of 3D skeletal joints, and (b) the same body parts remain occluded throughout the whole activity. Contrary to previous research, in this work, we address this problem using a Generative Adversarial Network (GAN). Specifically, we train a Convolutional Recurrent Neural Network (CRNN), whose goal is to serve as the generator of the GAN. Its aim is to complete the missing parts of the skeleton due to occlusion. Specifically, the input to this CRNN consists of raw 3D skeleton joint positions, upon the removal of joints corresponding to occluded parts. The output of the CRNN is a reconstructed skeleton. For the discriminator of the GAN, we use a simple long short-term memory (LSTM) network. We evaluate the proposed approach using publicly available datasets in a series of occlusion scenarios. We demonstrate that in all scenarios, the occlusion of certain body parts causes a significant decline in performance, although in some cases, the reconstruction process leads to almost perfect recognition. Nonetheless, in almost every circumstance, the herein proposed approach exhibits superior performance compared to previous works, which varies between $2.2\%$ and $37.5\%$, depending on the dataset used and the occlusion case. Full article