Tractostorm 2: Optimizing tractography dissection reproducibility with segmentation protocol dissemination

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White‐matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time‐consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in‐depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel‐based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.     

Aβ induces its own prion protein N-terminal fragment (PrPN1)–mediated neutralization in amorphous aggregates

Plasma membrane cellular prion protein (PrP^C) is a high-affinity receptor for toxic soluble amyloid-β (Aβ) oligomers that mediates synaptic dysfunction. Secreted forms of PrP^C resulting from PrP^C α-cleavage (PrPN1) or shedding (shed PrP^C) display neuroprotective activity in neuronal cultures and in mouse models of Aβ-induced neuronal dysfunction. In vitro, recombinant PrPN1 and PrP inhibit Aβ fibrillization. However, the mechanism by which PrPN1 and shed PrP^C neutralize Aβ oligomers is unclear, and evidence of such neuroprotective activity in Alzheimer's disease (AD) patients is lacking. Here, we show that PrPN1 association with Aβ causes a conformational change resulting in the formation of amorphous and insoluble aggregates that are not compatible with the assembly of Aβs. Using postmortem brain tissues of AD patients, we were able to coimmunoprecipitate Aβ with PrP^C molecules and observed a coaggregation of Aβ and PrPN1 in the guanidine-extractable fraction presumably representing insoluble amyloid plaques. Furthermore, PrP^C α-cleavage is increased in AD brains, and we noticed a significant positive correlation between the levels of α-cleavage and of guanidine-extractable Aβ. These data strongly support the hypothesis that PrP^C α-cleavage is an endogenous neuroprotective mechanism in AD and support the development of PrP^C-derived peptides as therapeutic molecules for AD.     

Analysis of the skin of mice humanized for the immune system

Development of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen‐presenting cells at the vaccination site allowed the induction of an immune response.     

Intra-rater Reliability of a Qualitative Landing Scale for the Single-Hop Test: A Pilot Study

BackgroundThe test battery classically used for return-to-sport (RTS) decision-making after anterior cruciate ligament (ACL) reconstruction (ACLR) may not be sufficient, as it does not include a qualitative analysis of movement. Therefore, the Landing Error Scoring System (LESS) scale was adapted to a primary functional test in the typical RTS test battery: the single leg hop for distance (SHD).Hypothesis/ PurposeThe aim of this study was to determine the intra-rater reliability of the LESS scale adapted to the SHD (SHD-LESS scale) in healthy young athletes.Study DesignReliability analysisMethodsNineteen healthy individuals (14 men, 5 women; mean age: 22.4 years) participated in the study. Participants performed the SHD tasks on both limbs (dominant and non-dominant) using a standardized protocol in two sessions that were one week apart (single reviewer; 2-dimensional video). Intra-class correlation coefficients (ICC2,1) were used to measure the reproducibility of the scale in the dominant (dom) and non-dominant (nondom) limbs. Additionally, limb data (dom and nondom) were pooled and evaluated collectively with intra-class correlation coefficients. The Kappa coefficient was used to assess the reproducibility of each individual item of SHD-LESS scale.ResultsThe intra-rater reliability was good (ICCdom = 0.77; ICCnondom = 0.87; ICCpooled = 0.87) for the overall SHD-LESS scale scores. Agreement of SHD-LESS individual items ranged from 62% to 100%. Dorsiflexion at initial contact (97% agreement; kappa value=0.79) and knee valgus after landing (88% agreement; kappa value=0.65) had excellent agreement and kappa values.ConclusionThe newly-adapted SHD-LESS scale showed good intra-rater reliability overall. Further studies should evaluate the impact of using the SHD-LESS scale within the RTS test battery on outcomes in patients after ACLR.Level of Evidence3     

Œsophagite à éosinophiles : une cause rare de dysphagie

Eosinophilic esophagitis is an unrecognized and emerging entity. Its incidence increases with allergic disorders. A 29-year-old man presented with a 4-year history of intermittent and paroxysmal dysphagia. The triad including allergy, young age, and impaction of foreign bodies, combined with a chronic dysphagia is almost pathognomonic of eosinophilic esophagitis. Endoscopic esophageal features can be diverse, so systematic esophageal biopsies are required. Diagnosis is established with the demonstration of an eosinophilic infiltrate with a cell count exceeding 15 eosinophils per high power field (×400). First line therapy includes swallowed topical corticosteroids and removal of an allergic cause, when it could be identified.     

Robot assisted laparoscopic transperitoneal para-aortic lymphadenectomy in the management of advanced cervical carcinoma

ObjectivesAdequate staging of advanced cervical cancer is essential in order to optimally treat the patient. FIGO clinical staging, imaging techniques such as CT scan, MRI and PET sometimes underestimate the extension of tumors. The presence of para-aortic lymph node metastases in advanced cervical cancer identifies patients with poor prognosis who need to be treated aggressively. Laparoscopic para-aortic lymph node dissection is now proposed as a diagnostic tool in many guidelines. We evaluated the feasibility and safety of a robot assisted laparoscopic transperitoneal approach to para-aortic lymph node dissection.Study designEight patients with advanced cervical carcinoma who were eligible for primary pelvic radiotherapy combined with concurrent cisplatin chemotherapy or pelvic exenteration underwent a pre-treatment robot assisted transperitoneal laparoscopic para-aortic lymphadenectomy.ResultsWe isolated from 1 to 38 para-aortic nodes per patient and had one para-aortic node positive patient who was treated with extended doses of pelvic radiotherapy. We did not encounter any major complications and post-operative morbidity was low.ConclusionsRobot assisted transperitoneal laparoscopic para-aortic lymphadenectomy is feasible and provides the surgeon with greater precision than classical laparoscopy. Larger prospective multicentric trials are needed to validate the generalised usefulness of this technique.     

The Effects of Word Completion and Word Prediction on Typing Rates Using On-Screen Keyboards

Word prediction is often recommended by therapists as a means to improve typing speed for clients with physical limitations. Although literature suggests that word prediction does have an effect on writing proficiency, increased speed is not one of its benefits when used with a standard keyboard. One reason given for the failure of word prediction to accelerate typing is that the user must look away from any source document to scan the prediction list during typing. Looking away from the source document may slow the typist more than any acceleration offered by word prediction. For input methods that already require the typist to look away from the copy, this effect might be irrelevant. The focus of this research was to determine whether word completion or word prediction programs would increase typing speed when used with an input method (an on-screen keyboard) that also requires looking away from the source document. Ten people, five men and five women, aged 20 to 38 years, participated in this study. The study used a single-subject, successive intervention design to test typing speed and accuracy using an on-screen keyboard with integrated word prediction software. Seven participants had their fastest typing speed with word prediction. Two participants had their fastest typing speed with word completion. Only one participant demonstrated no improvement in speed when using these two programs. Overall, these results show that the use of word prediction and word completion may assist on-screen keyboard users to improve typing speed.     

MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression and which have been implicated in cancer. We evaluated whether five candidate predictive miRNAs, derived from a pilot study in which 249 miRNAs were assayed, were associated with clinical benefit of tamoxifen therapy in advanced breast cancer. These five miRNAs were measured in an independent series of 246 estrogen receptor (ER)-positive primary breast tumors of patients who received tamoxifen for advanced disease by quantitative Real Time PCR. Univariate analysis showed that higher expression levels of hsa-miR-30a-3p, hsa-miR-30c, and hsa-miR-182 were significantly associated with benefit of tamoxifen treatment and with longer PFS (all P-values <0.01). In multivariate analysis, corrected for the traditional predictive factors, only hsa-miRNA-30c was an independent predictor (P-value <0.01). Finally, in an attempt to understand the biology connected to this miRNA, Global testing pathway analysis showed an association of hsa-miRNA-30c expression with HER and RAC1 signaling pathways. We identified hsa-miRNA-30c as an independent predictor for clinical benefit of tamoxifen therapy in patients with advanced breast cancer. Assessment of tumor levels and connected pathways could be helpful to improve treatment strategies.