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Importance: Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). Objective: To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. Design, Setting, and Participants: This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Exposure: Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. Main Outcomes and Measures: The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. Results: The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). Conclusions and Relevance: In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

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Newts are excellent vertebrate models for investigating tissue regeneration due to their remarkable regenerative capabilities. To investigate the mRNA and microRNAs (miRNAs) profiles within the blastema niche of regenerating newt limbs, we amputated the limbs of Chinese fire belly newts (Cynops orientalis) and conducted comprehensive analyses of the transcriptome and microRNA profiles at five distinct time points post-amputation (0 hours, 1 day, 5 days 10 days and 20 days). We identified 24 significantly differentially expressed (DE) genes and 20 significantly DE miRNAs. Utilizing weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment analysis, we identified four genes likely to playing crucial roles in the early stages of limb regeneration: Cemip, Rhou, Gpd2 and Pcna. Moreover, mRNA-miRNA integration analysis uncovered seven human miRNAs (miR-19b-1, miR-19b-2, miR-21-5p, miR-127-5p, miR-150-5p, miR-194-5p, and miR-210-5p) may regulate the expression of these four key genes. The temporal expression patterns of these key genes and miRNAs further validated the robustness of the identified mRNA-miRNA landscape. Our study successfully identified candidate key genes and elucidated a portion of the genetic regulatory mechanisms involved in newt limb regeneration. These findings offer valuable insights for further exploration of the intricate processes of tissue regeneration.

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Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as Pax3, Gab1, Pxn, Tln2 and Arpc, were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.

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Modifications to highly conserved developmental gene regulatory networks are thought to underlie morphological diversification in evolution and contribute to human congenital malformations. Relationships between gene expression and morphology have been extensively investigated in the limb, where most of the evidence for alterations to gene regulation in development consists of pre-transcriptional mechanisms that affect expression levels, such as epigenetic alterations to regulatory sequences and changes to cis-regulatory elements. Here we report evidence that alternative splicing (AS), a post-transcriptional process that modifies and diversifies mRNA transcripts, is dynamic during limb development in two mammalian species. We evaluated AS patterns in mouse (Mus musculus) and opossum (Monodelphis domestica) across the three key limb developmental stages: the ridge, bud, and paddle. Our data show that splicing patterns are dynamic over developmental time and suggest differences between the two mammalian taxa. Additionally, multiple key limb development genes, including Fgf8, are differentially spliced across the three stages in both species, with expression levels of the conserved splice variants, Fgf8a and Fgf8b, changing across developmental time. Our data demonstrates that AS is a critical mediator of mRNA diversity in limb development and provides an additional mechanism for evolutionary tweaking of gene dosage.

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Background Current terms used to describe the MRI findings for musculoskeletal infections are nonspecific and inconsistent. Purpose To develop and validate an MRI-based musculoskeletal infection classification and scoring system. Materials and Methods In this retrospective cross-sectional internal validation study, a Musculoskeletal Infection Reporting and Data System (MSKI-RADS) was designed. Adult patients with radiographs and MRI scans of suspected extremity infections with a known reference standard obtained between June 2015 and May 2019 were included. The scoring categories were as follows: 0, incomplete imaging; I, negative for infection; II, superficial soft-tissue infection; III, deeper soft-tissue infection; IV, possible osteomyelitis (OM); V, highly suggestive of OM and/or septic arthritis; VI, known OM; and NOS (not otherwise specified), nonspecific bone lesions. Interreader agreement for 20 radiologists from 13 institutions (intraclass correlation coefficient [ICC]) and true-positive rates of MSKI-RADS were calculated and the accuracy of final diagnoses rendered by the readers was compared using generalized estimating equations for clustered data. Results Among paired radiographs and MRI scans from 208 patients (133 male, 75 female; mean age, 55 years ± 13 [SD]), 20 were category I; 34, II; 35, III; 30, IV; 35, V; 18, VI; and 36, NOS. Moderate interreader agreement was observed among the 20 readers (ICC, 0.70; 95% CI: 0.66, 0.75). There was no evidence of correlation between reader experience and overall accuracy (P = .94). The highest true-positive rate was for MSKI-RADS I and NOS at 88.7% (95% CI: 84.6, 91.7). The true-positive rate was 73% (95% CI: 63, 80) for MSKI-RADS V. Overall reader accuracy using MSKI-RADS across all patients was 65% ± 5, higher than final reader diagnoses at 55% ± 7 (P < .001). Conclusion MSKI-RADS is a valid system for standardized terminology and recommended management of imaging findings of peripheral extremity infections across various musculoskeletal-fellowship-trained reader experience levels. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Schweitzer in this issue.

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BACKGROUND: The standard treatment for localized osteosarcoma is neoadjuvant chemotherapy before surgery, followed by adjuvant chemotherapy. Our aim was to report the rate of histopathological response to neoadjuvant chemotherapy for the treatment of extremity osteosarcoma in Vietnam. METHODS: We performed a retrospective study of stage II conventional osteosarcoma patients under 40 years-old who received MAP regimen as neoadjuvant chemotherapy at the Vietnam National Cancer Hospital between June 2019 and June 2022. Histopathological response was evaluated using the Huvos grading system, in which a good histopathological response was defined as a necrotic rate of 90% or more. RESULTS: Thirty-five eligible patients were included in the study. Male patients accounted for 65.7%, with a median age of 16 years (range, 8-38 years). Of the 35 cases, 31 were reported as stage IIB (88.6%). The femur and tibia were the most common sites in our study, accounting for 51.4% and 34.3%, respectively. The most common pathologic subtype was osteoblastic osteosarcoma (68.6%), followed by chondroblastic subtype (20%). After two cycles of MAP-regimen neoadjuvant chemotherapy, 28 of 35 patients (80%) underwent limb-sparing surgery. A good histopathological response was observed in 18 of 35 patients (51.4%). There were significant correlations between the duration of symptoms (P = 0.016), LDH (P = 0.001) serum levels at initial presentation, and ALP (P = 0.043) serum levels at initial presentation with histopathological response. CONCLUSION: This retrospective study suggests a possible association between symptom duration, pre-treatment LDH levels, and pre-treatment ALP levels with histopathological response rates. Additional clinical investigations with long-term follow-up are needed to investigate survival outcomes in the Asian population.

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INTRODUCTION: Radiotherapy improves local tumour control in patients with soft tissue sarcoma of the extremities (STSE) but it also increases the probability of long-term toxicities such as tissue fibrosis, joint stiffness and lymphoedema. The use of radiation dose and volume thresholds, called dose constraints, may potentially reduce the development of toxicities in STSE. The aim of this study is to determine predictors of radiotherapy-related side effects for STSE. METHODS AND ANALYSIS: Predicting radiotherapy response, Toxicities and quality-of-life related functional outcomes in soft tissue sarcoma of the extremities (PredicT) is a multicentre observational study comprising two cohorts (PredicT A and B). PredicT A, a retrospective analysis of the UK VorteX (NCT00423618) and IMRiS clinical trials (NCT02520128), is aimed at deriving a statistical model for development of dose-volume constraints. This model will use receiving operator characteristics and multivariate analysis to predict radiotherapy side effects and patient-reported outcomes. PredicT B, a prospective cohort study of 150 patients with STSE, is aimed at testing the validity of those dose-volume constraints. PredicT B is open and planned to complete recruitment by September 2024. ETHICS AND DISSEMINATION: PredicT B has received ethical approval from North West - Liverpool Central Research Ethics Committee (20/NW/0267). Participants gave informed consent to participate in the study before taking part. We will disseminate our findings via publications, presentations, national and international conference meetings and engage with local charities. TRIAL REGISTRATION NUMBER: NCT05978024.

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BACKGROUND AND OBJECTIVES: Ataxia is primarily considered to originate from the cerebellum. However, it can manifest without obvious cerebellar damage, such as in anterior circulation stroke, leaving the mechanisms of ataxia unclear. The aim of this study was to investigate whether stroke lesions causing limb ataxia localize to a common brain network. METHODS: In this prospective cohort study, adult patients with new-onset stroke with visible lesions on CT or MRI from Turku University Hospital, Finland, were clinically examined (1) after their stroke while still admitted to the hospital (baseline) and (2) 4 months later (follow-up) to assess limb ataxia. Lesion locations and their functional connectivity, computed using openly available data from 1,000 healthy volunteers from the Brain Genome Superstruct Project, were compared voxel-by-voxel across the whole brain between patients with and without ataxia, using voxel-based lesion-symptom mapping and lesion network mapping. The findings were confirmed in an independent stroke patient cohort with identical clinical assessments. RESULTS: One hundred ninety-seven patients (mean age 67.2 years, 39%female) were included in this study. At baseline, 35 patients (68.3 years, 34%female) had and 162 (67.0 years, 40%female) did not have new-onset acute limb ataxia. At follow-up, additional 4 patients had developed late-onset limb ataxia, totalling to 39 patients (68.6 years, 36%female) with limb ataxia at any point. One hundred eighteen patients (66.2 years, 40%female) did not have ataxia at any point (n = 40 with missing follow-up data). Lesions in 54% of the patients with acute limb ataxia were located outside the cerebellum and cerebellar peduncles, and we did not find an association between specific lesion locations and ataxia. Lesions causing acute limb ataxia, however, were connected to a common network centered on the intermediate zone cerebellum and cerebellar peduncles (lesion connectivity in patients with vs without acute limb ataxia, pFWE < 0.05). The results were similar when comparing patients with and without ataxia at any point, and when excluding lesions in the cerebellum and cerebellar peduncles (pFWE < 0.05). The findings were confirmed in the independent stroke dataset (n = 96), demonstrating an OR of 2.27 (95% CI 1.32-3.91) for limb ataxia per standard deviation increase in limb ataxia network damage score. DISCUSSION: Lesions causing limb ataxia occur in heterogeneous locations but localize to a common brain network.

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BACKGROUND: Excessive intraoperative bleeding remains a challenge in limb surgeries. The exsanguination tourniquet ring has emerged as a potential solution for effective exsanguination and hemostasis. This study aims to evaluate its efficacy and safety compared to the conventional exsanguination and hemostasis approach (pneumatic tourniquet combined with Esmarch bandage). METHODS: This randomized controlled trial evaluates the exsanguination tourniquet ring's effectiveness and safety versus the conventional approach in 220 participants undergoing various limb surgeries. Allocation included experimental and control groups, assesses through efficacy (including intraoperative and total blood loss, hemoglobin levels, and exsanguination and hemostasis effectiveness) and safety (adverse event occurrence) indicators. RESULTS: The experimental group (n = 110) utilizes the exsanguination tourniquet ring, while the control group (n = 110) employs the conventional approach. As for intraoperative blood loss, the experimental group is non-inferior to the control group (p-value < 0.001). While no significant difference is found in total blood loss (for the full analysis set, p-value = 0.442; for the per protocol set, p-value = 0.976) and differences in postoperative and preoperative hemoglobin levels (for the full analysis set, p-value = 0.502; for the per protocol set, p-value = 0.928). Regarding exsanguination and hemostasis effectiveness, the full analysis set reveals significantly superior ratings in the experimental group compared to the control group (p-value = 0.002 < 0.05), while the per protocol set analysis indicates no significant difference between the groups (p-value = 0.504). As for safety indicators, adverse events related to the device are minimal in two groups, with only one severe event unrelated to the device. CONCLUSIONS: The exsanguination tourniquet ring is an effective and safe device for intraoperative blood loss control in various limb surgeries. TRIAL REGISTRATION: Comparison of Exsanguination and Hemostasis Devices for Limb Surgery A Prospective Multicenter Randomized Controlled Study, ChiCTR2300077998, 11/27/2023.

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INTRODUCTION: With similar prevalence to injuries from fires, stings, and natural disasters, soft tissue injuries may occur from fireworks, industrial accidents, or other explosives. Surgeons are less familiar with treating high-velocity penetration from small debris, which may increase the chance of infection and subsequent fatality. Penetration risk curves have been developed to predict V50, the velocity with 50% probability of penetration, for various sized projectiles. However, there has been limited research using nonmetallic materials to achieve lower density projectiles less than 1 g cm-2, such as sand or rocks. MATERIAL AND METHODS: To emulate the size and density of these energized particles, 14 ball bearings of stainless steel, silicon nitride, or Delrin acetal plastic ranging from 1.59 mm (1/16") to 9.53 mm (3/8") with sectional densities between 0.3 g cm-2 and 5 g cm-2 were launched toward porcine legs at a range of velocities to determine the penetration thresholds. High-speed videography was captured laterally at 40 kHz and impact velocity was captured using a physics-based tracking software. A generalized linear model with repeated measures and a logit link function was used to predict probability of penetration for each projectile. A total of 600 impacts were conducted to achieve at least 15 penetrating impacts for each projectile over a range of velocities. RESULTS: Higher impact velocities were required to penetrate the skin as sectional density of the projectile decreased, and the relationship between velocity and sectional density exhibited an exponential relationship (V50, $ = 184.6*S{D^{ - 0.385}}$, R2 = 0.95) with substantial change for nonlinearity in sectional densities ranging from 0.3 g cm-2 to 1 g cm-2. Compared to previous studies, the empirical relationship was consistent in the linear region (2-5 g cm-2), and novel experimentation filled in the gaps for sectional densities less than 1 g cm-2, which expressed more nonlinearity than previously estimated. For low-density projectiles with diameters of 1.59 (1/16") or 3.18 (1/8"), 32 impacts were lodged into the epidermis but did not penetrate through the dermis; however, penetration was defined as displacement into or through the dermis. CONCLUSIONS: These experimental results may be used to develop and validate finite element simulations of low-density projectile impacts to address complex, multivariate loading conditions for the development of protective clothing to reduce wounding and subsequent infection rates.

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Minor traumatology is a common reason for consultation in the emergency room and requires a radiographic assessment in most cases. To improve patient comfort, reduce the feeling of waiting and decrease the length of stay, actions entrusted to the triage nurse (TN) have been developed, such as the anticipated prescription of X-ray (APXray). In Switzerland, this practice seems to be heterogeneous and lacks any established legal framework, prescribing being an exclusively medical act. In this article, we review the impact and performance of the APXray by TN in minor limb trauma.

La traumatologie mineure est un motif fréquent de consultation aux urgences et nécessite un bilan radiographique dans la plupart des cas. Pour améliorer le confort, diminuer le sentiment d'attente et la durée de séjour, des actions peuvent être médico-déléguées à l'infirmière d'accueil et de tri, comme la prescription de radiographie anticipée au tri (PRAT). En Suisse, cette pratique reste hétérogène et sans cadre légal clairement établi, la prescription étant un acte exclusivement médical. Dans cet article, nous proposons un état des lieux de l'impact et de la performance de la PRAT dans les traumatismes mineurs des membres.

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PURPOSE: Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long-term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis. PATIENTS AND METHODS: The COSS database 1980-04/2019 was searched for 5-year survivors of primary high-grade central osteosarcoma of the extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5 years of follow-up. RESULTS: Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5-63.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%); extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries <1/3 vs. ≥1/3 of the involved bone 997 (67.8%) vs. 474 (32.2%) (456 unknown); localized vs. primary metastatic 1881 (93.6%) vs. 128 (6.4%); osteosarcoma as a secondary malignancy 41/2009 (2.0%)). Therapy starting by chemotherapy versus primary surgery 1860 (92.6%) versus 149 (7.4%); definitive tumor surgery by limb salvage versus ablative 1347 (67.0%) versus 659 (1 no surgery, 2 unknown); tumor response to preoperative chemotherapy documented for 1765 (94.9%) patients receiving neoadjuvant chemotherapy, good (<10% viable tumor) versus poor 1130 (64.0%) versus 635 (36.0%), local radiotherapy documented for 19 (0.9%) tumors. Recurrence during preceding 5 years no versus yes 1681 (83.7%) versus 328 (16.3%). Median follow-up starting 5 years after initial diagnosis 6.1 (0.002-32.2) years; 1815 survivors and 194 deaths. Overall survival after another 5/10/15/20 years 91.7%/88.9%/85.8%/83.4% for all patients; 97.5%/95.2%/92.4%/89.9% if in remission years 1-5 versus 62.7%/57.3%/53.0%/51.2% if recurrence year 1-5 (p < 0.001). Significant predictors of survival for all patients age at diagnosis (p = 0.038), tumor site (p = 0.030), having experienced the osteosarcoma as secondary malignancy (p < 0.001), tumor response to preoperative chemotherapy (p = 0.002). Multivariate Cox regression testing possible for 1759 (87.6%) patients with complete dataset: Having had a recurrence in years 1-5 (p < 0.001), older age at diagnosis (p = 0.009), and osteosarcoma as secondary malignancy (p = 0.013) retained significance. DISCUSSION: Highly important predictors of death such as the extent of tumor response to chemotherapy no longer remain valid after 5-year survival. The individual history of malignancies and their outcomes seems to gain pivotal importance. CONCLUSION: This benchmark analysis clearly defined risk factors for the further course of 5-year survivors from osteosarcoma. It argues for large disease-oriented databases as well as for very long follow-up periods. Novel findings will most likely require innovative statistical models to analyze such cohorts.

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Pattern recognition (PR)-based myoelectric control systems can naturally provide multifunctional and intuitive control of upper limb prostheses and restore lost limb function, but understanding their robustness remains an open scientific question. This study investigates how limb positions and electrode shifts-two factors that have been suggested to cause classification deterioration-affect classifiers' performance by quantifying changes in the class distribution using each factor as a class and computing the repeatability and modified separability indices. Ten intact-limb participants took part in the study. Linear discriminant analysis (LDA) was used as the classifier. The results confirmed previous studies that limb positions and electrode shifts deteriorate classification performance (14-21% decrease) with no difference between factors (p > 0.05). When considering limb positions and electrode shifts as classes, we could classify them with an accuracy of 96.13 ± 1.44% and 65.40 ± 8.23% for single and all motions, respectively. Testing on five amputees corroborated the above findings. We have demonstrated that each factor introduces changes in the feature space that are statistically new class instances. Thus, the feature space contains two statistically classifiable clusters when the same motion is collected in two different limb positions or electrode shifts. Our results are a step forward in understanding PR schemes' challenges for myoelectric control of prostheses and further validation needs be conducted on more amputee-related datasets.

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The Forkhead box transcription factors FOXC1 and FOXC2 are expressed in condensing mesenchyme cells at the onset of endochondral ossification. We used the Prx1-cre mouse to ablate Foxc1 and Foxc2 in limb skeletal progenitor cells. Prx1-cre;Foxc1Δ/Δ;Foxc2Δ/Δ limbs were shorter than controls, with worsening phenotypes in distal structures. Cartilage formation and mineralization was severely disrupted in the paws. The radius and tibia were malformed, whereas the fibula and ulna remained unmineralized. Chondrocyte maturation was delayed, with fewer Indian hedgehog-expressing, prehypertrophic chondrocytes forming and a smaller hypertrophic chondrocyte zone. Later, progression out of chondrocyte hypertrophy was slowed, leading to an accumulation of COLX-expressing hypertrophic chondrocytes and formation of a smaller primary ossification center with fewer osteoblast progenitor cells populating this region. Targeting Foxc1 and Foxc2 in hypertrophic chondrocytes with Col10a1-cre also resulted in an expanded hypertrophic chondrocyte zone and smaller primary ossification center. Our findings suggest that FOXC1 and FOXC2 direct chondrocyte maturation towards hypertrophic chondrocyte formation. At later stages, FOXC1 and FOXC2 regulate function in hypertrophic chondrocyte remodeling to allow primary ossification center formation and osteoblast recruitment.

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Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star genome is the most rearranged among echinoderms sequenced so far, featuring a reorganized Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasize the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems.

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Hominoids exhibit a strikingly diverse set of locomotor adaptations-including knuckle-walking, brachiation, quadrumanuous suspension, and striding bipedalism-while also possessing morphologies associated with forelimb suspension. It has been suggested that changes in limb element integration facilitated the evolution of diverse locomotor modes by reducing covariation between serial homologs and allowing the evolution of a greater diversity of limb lengths. Here, I compare limb element integration in hominoids with that of other primate taxa, including two that have converged with them in forelimb morphology, Ateles and Pygathrix. Ateles is part of a clade that, such as hominoids, exhibits diverse locomotor adaptations, whereas Pygathrix is an anomaly in a much more homogeneous (in terms of locomotor adaptations) clade. I find that all atelines (and possibly all atelids), not just Ateles, share reduced limb element integration with hominoids. Pygathrix does not, however, instead resembling other members of its own family. Indriids also seem to have higher limb integration than apes, despite using their forelimbs and hindlimbs in divergent ways, although there is more uncertainty in this group due to poor sample size. These results suggest that reduced limb integration is characteristic of certain taxonomic groups with high locomotor diversity rather than taxa with specific, specialized locomotor adaptations. This is consistent with the hypothesis that reduced integration serves to open new areas of morphospace to those clades while suggesting that derived locomotion with divergent demands on limbs is not necessarily associated with reduced limb integration.

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INTRODUCTION: The objective of this study was to compare limb circumference measurements between a three-dimensional scanner and a measuring tape. METHODS: Patients older than 18 years, who were bitten by a green pit viper and visited the emergency department between 1 October and 20 December, 2019 were included. Two physicians measured the circumference of a bitten limb and a contralateral unaffected limb twice using both a measuring tape and a three-dimensional scanner. Each patient was measured at the first emergency department visit and again at 24 h, 48 h, and 72 h post-snakebite. There were three points of measurement on both limbs. RESULTS: There were 408 anatomical locations from 17 patients for measurement. The three-dimensional scanner and the measuring tape demonstrated a very high correlation (r-squared >0.940, P value <0.001) in measuring limb circumferences. Bland Altman plots also demonstrated the two methods measured limb circumferences with similar results with mean differences <1 cm. Intraclass correlation coefficient between the two methods was greater than 0.8 in every site for the lower limbs, but for the upper limbs, most sites had a poor agreement (ranges: 0.073-0.633). For limb volume measurement, the three-dimensional scanner provided excellent and moderate inter and intrarater reliabilities for the lower and upper limbs, respectively. DISCUSSION: The three-dimensional scanner could be reliably used to assess limb circumference with a strong correlation and with a relatively small error compared with the conventional method. Pictures from the scan can also be constructed to calculate limb volume that could have potential for other clinical purposes such as in evaluating antivenom response for limb swelling. CONCLUSIONS: Circumferences from the three-dimensional scanner were comparable to those from the measuring tape, especially for the lower limbs, and the three-dimensional scanner demonstrated an added value for calculating limb volume.

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INTRODUCTION: Postmortem evaluation of the human vascular system has a long history, with advancements ranging from dissections to modern imaging techniques like computed tomography (CT scan). This study designs a novel combination of Angiofil, a liquid radiopaque polymer, and latex, a flexible cast material, for cadaveric vascular analysis. MATERIAL & METHODS: The aim was to synergize the advantages of both components, providing accurate radiological images and optimal dissection conditions. Three arterial territories (lateral circumflex femoral artery, profunda brachii artery, and radial artery) were injected and assessed through CT scans and dissections. RESULTS: The Angiofil-latex mixture allowed successful visualization of the vascular networks, offering a simple, reproducible, and non-toxic approach. Quantitative assessments of the three territories, including diameters and lengths, showed comparable results between CT scan and dissection. DISCUSSION: The technique precision and versatility make it an accessible and valuable tool for anatomical studies, potentially extending its application to MRI analyses. Overall, the Angiofil-latex combination presents a cost-effective solution for researchers, offering enhanced visibility and detailed anatomical insights for various applications, including anatomical variation studies.

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Many salamanders can completely regenerate a fully functional limb. Limb regeneration is a carefully coordinated process involving several defined stages. One key event during the regeneration process is the patterning of the blastema to inform cells of what they must differentiate into. Although it is known that many genes involved in the initial development of the limb are re-used during regeneration, the exact molecular circuitry involved in this process is not fully understood. Several large-scale transcriptional profiling studies of axolotl limb regeneration have identified many transcription factors that are up-regulated after limb amputation. Sall4 is a transcription factor that has been identified to play essential roles in maintaining cells in an undifferentiated state during development and also plays a unique role in limb development. Inactivation of Sall4 during limb bud development results in defects in anterior-posterior patterning of the limb. Sall4 has been found to be up-regulated during limb regeneration in both Xenopus and salamanders, but to date it function has been untested. We confirmed that Sall4 is up-regulated during limb regeneration in the axolotl using qRT-PCR and identified that it is present in the skin cells and also in cells within the blastema. Using CRISPR technology we microinjected gRNAs specific for Sall4 complexed with cas9 protein into the blastema to specifically knockout Sall4 in blastema cells only. This resulted in limb regenerate defects, including missing digits, fusion of digit elements, and defects in the radius and ulna. This suggests that during regeneration Sall4 may play a similar role in regulating the specification of anterior-proximal skeletal elements.

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