A guide to facilitate the creation of a femoral tunnel for arthroscopic ligamentum teres reconstruction: a three-dimensional computed tomography study.

The ideal femoral tunnel passing through the centre of the femoral neck targeted to the footprint of the ligamentum teres (LT) is established during the LT reconstruction surgery with the free-hand technique. We aimed to quantitatively determine the entry site and define the angular orientation of the ideal femoral tunnel with its relevance to the femoral valgus angle (FVA) and the femoral anteversion angle (FAA) to facilitate the creation of an ideal femoral tunnel during the LT reconstruction surgery. A total of 60 randomly selected CT images were obtained to reconstruct three-dimensional femur models. A virtual reamer representing the ideal femoral tunnel was placed in the femur models. The femur length, FVA, FAA, the femoral tunnel anterior angle, the femoral tunnel superior angle and the skin- and bony-entry sites were measured. The femoral tunnel angular orientation was strongly correlated with the FVA and the FAA. Mathematical formulas were defined by which entry site of the reamer and the anterior and superior angulation of the femoral tunnel could be estimated before the surgery. The mean skin-entry site was 67.3 mm distal and 0.1 mm anterior to the centre of the greater trochanter's superior border. The angular orientation of the femoral tunnel using FVA and FAA can be easily estimated using mathematical formulas before LT reconstruction surgery. The entry site and angular orientation of the femoral tunnel described in this study can be used to reduce dependency on the usage of fluoroscopy and the workload on the surgeon during the LT reconstruction surgery.

Phenotype screens of murine pancreatic cancer identify a Tgf-α-Ccl2-paxillin axis driving human-like neural invasion.

Solid cancers like pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer, frequently exploit nerves for rapid dissemination. This neural invasion (NI) is an independent prognostic factor in PDAC, but insufficiently modeled in genetically engineered mouse models (GEMM) of PDAC. Here, we systematically screened for human-like NI in Europe's largest repository of GEMM of PDAC, comprising 295 different genotypes. This phenotype screen uncovered 2 GEMMs of PDAC with human-like NI, which are both characterized by pancreas-specific overexpression of transforming growth factor α (TGF-α) and conditional depletion of p53. Mechanistically, cancer-cell-derived TGF-α upregulated CCL2 secretion from sensory neurons, which induced hyperphosphorylation of the cytoskeletal protein paxillin via CCR4 on cancer cells. This activated the cancer migration machinery and filopodia formation toward neurons. Disrupting CCR4 or paxillin activity limited NI and dampened tumor size and tumor innervation. In human PDAC, phospho-paxillin and TGF-α-expression constituted strong prognostic factors. Therefore, we believe that the TGF-α-CCL2-CCR4-p-paxillin axis is a clinically actionable target for constraining NI and tumor progression in PDAC.

The Perception of Spontaneous and Volitional Laughter Across 21 Societies.

Laughter is a nonverbal vocalization occurring in every known culture, ubiquitous across all forms of human social interaction. Here, we examined whether listeners around the world, irrespective of their own native language and culture, can distinguish between spontaneous laughter and volitional laughter-laugh types likely generated by different vocal-production systems. Using a set of 36 recorded laughs produced by female English speakers in tests involving 884 participants from 21 societies across six regions of the world, we asked listeners to determine whether each laugh was real or fake, and listeners differentiated between the two laugh types with an accuracy of 56% to 69%. Acoustic analysis revealed that sound features associated with arousal in vocal production predicted listeners' judgments fairly uniformly across societies. These results demonstrate high consistency across cultures in laughter judgments, underscoring the potential importance of nonverbal vocal communicative phenomena in human affiliation and cooperation.

Detecting affiliation in colaughter across 24 societies.

Laughter is a nonverbal vocal expression that often communicates positive affect and cooperative intent in humans. Temporally coincident laughter occurring within groups is a potentially rich cue of affiliation to overhearers. We examined listeners' judgments of affiliation based on brief, decontextualized instances of colaughter between either established friends or recently acquainted strangers. In a sample of 966 participants from 24 societies, people reliably distinguished friends from strangers with an accuracy of 53-67%. Acoustic analyses of the individual laughter segments revealed that, across cultures, listeners' judgments were consistently predicted by voicing dynamics, suggesting perceptual sensitivity to emotionally triggered spontaneous production. Colaughter affords rapid and accurate appraisals of affiliation that transcend cultural and linguistic boundaries, and may constitute a universal means of signaling cooperative relationships.