Magnetic resonance tumor regression grade (MR-TRG) to assess pathological complete response following neoadjuvant radiochemotherapy in locally advanced rectal cancer

This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for quantitative assessment of the percentage of fibrosis developed within locally advanced rectal cancers (LARC) after neoadjuvant radiochemotherapy (RCT). A total of 65 patients were enrolled in the study and MR studies were performed on 3.0 Tesla scanner; patients were followed-up for 30 months. The percentage of fibrosis was quantified on T2-weighted images, using automatic K-Means clustering algorithm. According to the percentage of fibrosis, an optimal cut-off point for separating patients into favorable and unfavorable pathologic response groups was identified by ROC analysis and tumor regression grade (MR-TRG) classes were determined and compared to histopathologic TRG. An optimal cut-off point of 81% of fibrosis was identified to differentiate between favorable and unfavorable pathologic response groups resulting in a sensitivity of 78.26% and a specificity of 97.62% for the identification of complete responders (CRs). Interobserver agreement was good (0.85). The agreement between P-TRG and MR-TRG was excellent (0.923). Significant differences in terms of overall survival (OS) and disease free survival (DFS) were found between favorable and unfavorable pathologic response groups. The automatic quantification of fibrosis determined by MR is feasible and reproducible

Skeletal anomalies in dusky grouper Epinephelus marginatus (Lowe 1834) juveniles reared with different methodologies and larval densities

The first attempts to reproduce dusky grouper (Epinephelus marginatus, Lowe 1834) under controlled conditions started in 1995, but the egg and larvae quality was very low. Mass production is still encountering many difficulties, mainly concentrated in the larval period when very high mortality rates are observed, confirming what has been observed in the rearing of other grouper species. The main bottlenecks have been identified as the difficulty to properly nourish the larvae, stress shock syndrome, and the high deformation rates. We analysed 633 dusky grouper larvae and juveniles (0.2–7.2 cm total length, TL), sampled during two larval rearing cycles carried out in 2001 and 2002 in Italy. The specimens at different development stages were stained in toto for bone and cartilage and examined for skeletal anomalies during dusky grouper ontogenesis. The incidence of anomalies in groupers hatched from the same egg batch but reared using two different methods (green waters and semi-intensive rearing) and three stocking densities (8, 16 and 28 larvae/l) was compared, with a view to providing tools for identifying the most appropriate larval rearing method in order to at least limit the onset of skeletal anomalies. Our results suggest that during development no particular skeletal anomaly patterns (or fate) can be clearly identified as a high variability was observed in malformation typologies and the regions affected. No significant differences in the morphological quality between groupers reared using semi-intensive (LV02 lot) and green water (GW02-01 lot) methodologies were observed, whilst groupers reared at the highest stocking density (28 larvae/l) showed the highest frequency of deformed individuals (75.8%), the highest malformation charge (average of 5.5 anomalies per deformed individual), the largest range of anomaly typologies (38), and the highest incidence of individuals with at least one severe anomaly (30.9%). Whilst in green waters no evident effects of larvae density were observed on survival rates, the survival rate in large volume reared individuals (17.5%) was considerably higher with respect to those reared in green waters (0.2%) at 7–8 larvae/l. This indicates that the semi-intensive methodology should be considered more effective in enhancing the survival rate of dusky grouper larvae

Rabbit IgG antibodies against phospholipase A2 from Crotalus durissus terrificus neutralize the lethal activity of the venom

Crotalus durissus terrificus (C.d.t.) (South American rattlesnake) venom possesses myotoxic and neurotoxic activities, both of which are also expressed by crotoxin, the principal toxin of this venom. Crotoxin contains a basic phospholipase A2 (PLA2) and a non toxic acidic protein, crotapotin. We have produced and investigated the ability of IgG antibodies raised in rabbits against PLA2 to neutralize the lethality of the whole venom. PLA2 was isolated by gel filtration chromatography (Sephadex G-75). Specific antibodies were obtained by subcutaneous and intramuscular inoculation of PLA2 (700 μg) with Freund adjuvant. Groups of six mice (20 ± 2 g) were inoculated with 0.5 ml i.p. of C. d. t. venom (4 μg) or a mixture of venom that had been preincubated with the desired volume of IgG antibodies. Mortality, recorded 24 and 48 h after inoculation, showed that IgG anti-PLA2 were more effective than anticrotalic serum in neutralizing the lethal activity. These results demonstrate that it could be possible to obtain an anti-venom made by specific antibodies with a high level of protection against the lethal component of C.d.t. venom, and/or the inclusion of these antibodies as a supplement in heterologous anti-venoms

Fractal dimension of cerebral white matter : A consistent feature for prediction of the cognitive performance in patients with small vessel disease and mild cognitive impairment

Patients with cerebral small vessel disease (SVD) frequently show decline in cognitive performance. However, neuroimaging in SVD patients discloses a wide range of brain lesions and alterations so that it is often difficult to understand which of these changes are the most relevant for cognitive decline. It has also become evident that visually-rated alterations do not fully explain the neuroimaging correlates of cognitive decline in SVD. Fractal dimension (FD), a unitless feature of structural complexity that can be computed from high-resolution T1-weighted images, has been recently applied to the neuroimaging evaluation of the human brain. Indeed, white matter (WM) and cortical gray matter (GM) exhibit an inherent structural complexity that can be measured through the FD. In our study, we included 64 patients (mean age \ub1 standard deviation, 74.6 \ub1 6.9, education 7.9 \ub1 4.2 years, 53% males) with SVD and mild cognitive impairment (MCI), and a control group of 24 healthy subjects (mean age \ub1 standard deviation, 72.3 \ub1 4.4 years, 50% males). With the aim of assessing whether the FD values of cerebral WM (WM FD) and cortical GM (GM FD) could be valuable structural predictors of cognitive performance in patients with SVD and MCI, we employed a machine learning strategy based on LASSO (least absolute shrinkage and selection operator) regression applied on a set of standard and advanced neuroimaging features in a nested cross-validation (CV) loop. This approach was aimed at 1) choosing the best predictive models, able to reliably predict the individual neuropsychological scores sensitive to attention and executive dysfunctions (prominent features of subcortical vascular cognitive impairment) and 2) identifying a features ranking according to their importance in the model through the assessment of the out-of-sample error. For each neuropsychological test, using 1000 repetitions of LASSO regression and 5000 random permutations, we found that the statistically significant models were those for the Montreal Cognitive Assessment scores (p-value =.039), Symbol Digit Modalities Test scores (p-value =.039), and Trail Making Test Part A scores (p-value =.025). Significant prediction of these scores was obtained using different sets of neuroimaging features in which the WM FD was the most frequently selected feature. In conclusion, we showed that a machine learning approach could be useful in SVD research field using standard and advanced neuroimaging features. Our study results raise the possibility that FD may represent a consistent feature in predicting cognitive decline in SVD that can complement standard imaging

Infrared absorption from Charge Density Waves in magnetic manganites

The infrared absorption of charge density waves coupled to a magnetic background is first observed in two manganites La{1-x}Ca{x}MnO{3} with x = 0.5 and x = 0.67. In both cases a BCS-like gap 2 Delta (T), which for x=0.5 follows the hysteretic ferro-antiferromagnetic transition, fully opens at a finite T{0} < T{Neel}, with 2 Delta(T{0})/kT{c} close to 5. These results may also explain the unusual coexistence of charge ordering and ferromagnetism in La{0.5}Ca{0.5}MnO{3}.Comment: File revtex + 3 figs. in epsf. To appear on Phys. Rev. Let

Robotic Versus Open Kidney Transplantation from Deceased Donors : A Prospective Observational Study

Background: While robot-assisted kidney transplantation (RAKT) from living donors has been shown to achieve favourable outcomes, there is a lack of evidence on the safety and efficacy of RAKT as compared with the gold standard open kidney transplantation (OKT) in the setting of deceased donors, who represent the source of most grafts worldwide. Objective: To compare the intraoperative, perioperative, and midterm outcomes of RAKT versus OKT from donors after brain death (DBDs). Design, setting, and participants: Data from consecutive patients undergoing RAKT or OKT from DBDs at a single academic centre between October 2017 and December 2020 were prospectively collected. Intervention: RAKT or OKT. Outcome measurements and statistical analysis: The primary outcomes were intraoperative adverse events, postoperative surgical complications, delayed graft function (DGF), and midterm functional outcomes. A multivariable logistic regression analysis assessed the independent predictors of DGF, trifecta, and suboptimal graft function (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m) at the last follow-up. Results and limitations: Overall, 138 patients were included (117 [84.7%] OKTs and 21 [15.3%] RAKTs). The yearly proportion of RAKT ranged between 10% and 18% during the study period. The OKT and RAKT cohorts were comparable regarding all graft-related characteristics, while they differed regarding a few donor- and recipient-related factors. The median second warm ischaemic time, ureterovesical anastomosis time, postoperative complication rate, and eGFR trajectories did not differ significantly between the groups. A higher proportion of patients undergoing OKT experienced DGF; yet, at a median follow-up of 31 mo (interquartile range 19-44), there was no difference between the groups regarding the dialysis-free and overall survival. At the multivariable analysis, donor- and/or recipient-related factors, but not the surgical approach, were independent predictors of DGF, trifecta, and suboptimal graft function at the last follow-up. The study is limited by its nonrandomised nature and the small sample size. Conclusions: Our study provides preliminary evidence supporting the noninferiority of RAKT from DBDs as compared with the gold standard OKT in carefully selected recipients. Patient summary: Kidney transplantation using kidneys from deceased donors is still being performed with an open surgical approach in most transplant centres worldwide. In fact, no study has compared the outcomes of open and minimally invasive (robotic) kidney transplantation from deceased donors. In this study, we evaluated whether robotic kidney transplantation using grafts from deceased donors was not inferior to open kidney transplantation regarding the intraoperative, postoperative, and midterm functional outcomes. We found that, in experienced hands and provided that there was a time-efficient organisation of the transplantation pathway, robotic kidney transplantation from deceased donors was feasible and achieved noninferior outcomes as compared with open kidney transplantation

Optical conductivity of CuO_2 infinite-layer films

The infrared conductivity of CaCuO_2, SrCuO_{2-y}, and Sr_{0.85}Nd_{0.15}CuO_2 infinite-layer films is obtained from reflectivity measurements by taking into account the substrate contribution. SrCuO_{2-y} and Sr_{0.85}Nd_{0.15}CuO_2 exhibit extra-phonon modes and structured bands in the midinfrared, not found in stoichiometric CaCuO_2. These features mirror those observed in the perovskitic cuprates, thus showing that the polaronic properties of high-T_c superconductors are intrinsic to the CuO_2 planes.Comment: File latex, 5 p. incl. 4 fig. in epsf. Submitted to Solid State Com

Prediction of the information processing speed performance in multiple sclerosis using a machine learning approach in a large multicenter magnetic resonance imaging data set

Many patients with multiple sclerosis (MS) experience information processing speed (IPS) deficits, and the Symbol Digit Modalities Test (SDMT) has been recommended as a valid screening test. Magnetic resonance imaging (MRI) has markedly improved the understanding of the mechanisms associated with cognitive deficits in MS. However, which structural MRI markers are the most closely related to cognitive performance is still unclear. We used the multicenter 3T-MRI data set of the Italian Neuroimaging Network Initiative to extract multimodal data (i.e., demographic, clinical, neuropsychological, and structural MRIs) of 540 MS patients. We aimed to assess, through machine learning techniques, the contribution of brain MRI structural volumes in the prediction of IPS deficits when combined with demographic and clinical features. We trained and tested the eXtreme Gradient Boosting (XGBoost) model following a rigorous validation scheme to obtain reliable generalization performance. We carried out a classification and a regression task based on SDMT scores feeding each model with different combinations of features. For the classification task, the model trained with thalamus, cortical gray matter, hippocampus, and lesions volumes achieved an area under the receiver operating characteristic curve of 0.74. For the regression task, the model trained with cortical gray matter and thalamus volumes, EDSS, nucleus accumbens, lesions, and putamen volumes, and age reached a mean absolute error of 0.95. In conclusion, our results confirmed that damage to cortical gray matter and relevant deep and archaic gray matter structures, such as the thalamus and hippocampus, is among the most relevant predictors of cognitive performance in MS

The First Entirely 3D-Printed Training Model for Robot-assisted Kidney Transplantation : The RAKT Box

Robot-assisted kidney transplantation (RAKT) is increasingly performed at selected referral institutions worldwide. However, simulation and proficiency-based progression training frameworks for RAKT are still lacking, making acquisition of the RAKT-specific skill set a critical unmet need for future RAKT surgeons. To develop and test the RAKT Box, the first entirely 3D-printed, perfused, hyperaccuracy simulator for vascular anastomoses during RAKT. The project was developed in a stepwise fashion by a multidisciplinary team including urologists and bioengineers via an iterative process over a 3-yr period (November 2019-November 2022) using an established methodology. The essential and time-sensitive steps of RAKT were selected by a team of RAKT experts and simulated using the RAKT Box according to the principles of the Vattituki-Medanta technique. The RAKT Box was tested in the operating theatre by an expert RAKT surgeon and independently by four trainees with heterogeneous expertise in robotic surgery and kidney transplantation. Surgical procedure: Simulation of RAKT. Video recordings of the trainees' performance of vascular anastomoses using the RAKT Box were evaluated blind by a senior surgeon according to the Global Evaluative Assessment of Robotic Skills (GEARS) and Assessment of Robotic Console Skills (ARCS) tools. All participants successfully completed the training session, confirming the technical reliability of the RAKT Box simulator. Tangible differences were observed among the trainees in both anastomosis time and performance metrics. Key limitations of the RAKT Box include lack of simulation of the ureterovesical anastomosis and the need for a robotic platform, specific training instruments, and disposable 3D-printed vessels. The RAKT Box is a reliable educational tool to train novice surgeons in the key steps of RAKT and may represent the first step toward the definition of a structured surgical curriculum in RAKT. We describe the first entirely 3D-printed simulator that allows surgeons to test the key steps of robot-assisted kidney transplantation (RAKT) in a training environment before performing the procedure in patients. The simulator, called the RAKT Box, has been successfully tested by an expert surgeon and four trainees. The results confirm its reliability and potential as an educational tool for training of future RAKT surgeons

IgG antibodies against phospholipase A2 from Crotalus durissus terrificus: cross-reaction with venoms from Bothrops species from Argentina

We examined the ability of IgG anti-crotalic PLA2 to cross-react with Bothrops spp. venoms, from snakes found in the northeast of Argentina. Immunoblotting and ELISA tests showed that IgG anti-crotalic PLA2 recognize antigens of bothropic venoms. Indirect hemolytic activity tests showed that the quantity of antibodies that neutralized 50% of Crotalus durissus terrificus venom (ED50: 2.1 mg IgG anti-crotalic PLA2/100 µg of venom) were also able to neutralize venom from other snakes in the following proportion: 34% of B. alternatus, 18% of B. diporus and 12% of B. jararacussu. Likewise, direct PLA2 activity neutralization tests showed a similar cross-neutralization pattern including 56% of B. alternatus, 29% of B. diporus and 30% of B. jararacussu. In addition, in a myotoxic activity neutralization test, measured by plasma activity of creatine kinase, 35% of B. alternatus venom and 26% of B. diporus venom were neutralized, while no neutralization was detected with B. jararacussu venom. This study presents original data concerning cross-reactions between bothropic venoms from Argentina and IgG anti-crotalic PLA2. Our results suggest that anti-crotalic PLA2 antibodies should not be used to neutralize PLA2 activity of B. alternatus, B. diporus and especially B. jararacussu venoms; nor to enrich commercial antivenoms against these Bothrops species