Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of ProGlide vs. Prostar in patients undergoing transcatheter aortic valve implantation.

BACKGROUND Expanding indications to transcatheter aortic valve implantation (TAVI) warrant meticolous vascular management and minimization of access site complications. Two leading vascular closure devices (VCD) are currently used for TAVI, Proglide vs Prostar, but their comparative effectiveness and safety are debated. We aimed at comparing acute and 1-month outcomes of patients undergoing TAVI using as VCD either ProGlide (Perclose) or Prostar (XL). METHODS The prospective RISPEVA database was queried for baseline, procedural, and outcome details of patients undergoing TAVI and in whom either ProGlide or Prostar had been used as VCD. Outcomes of interest were death, vascular complication, and bleeding, distinguishing specific subtypes. Outcomes were adjudicated according to current Valve Academic Research Consortium definitions. RESULTS A total of 1987 subjects were included, 913 (46.0%) receiving ProGlide, and 1074 receiving Prostar (54.0%). Several baseline and procedural differences were evident, including surgical risk, concomitant coronary artery disease, sheath size, use of predilation, and chosen TAVI device (all p<0.05). Peri-procedurally, despite similar rates of device success (p=0.262), Prostar was associated with a lower risk of vascular stenosis (p=0.005), but a higher rate of device malfunction (p=0.028). Unadjusted analysis for 1-month outcomes suggested higher rates of major adverse events, any bleeding, major bleeding, and renal failure in patients receiving Prostar (all p<0.05). However, propensity score-adjusted analysis did not confirm any significant differences, suggesting that confounding factors mostly drove unadjusted differences. CONCLUSIONS Use of ProGlide and Prostar as VCD of choice for TAVI appears similarly safe and effective, despite some potential benefits associated with Proglide. Further randomized trials are warranted to confirm or disprove these findings.
A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord injury (SCI), an animal model used in rehabilitation medicine research, in order to improve the quality of experiments, avoiding unnecessary suffering. The aims of this investigation were 1- to assess acute surgical pain in mice subjected to SCI, 2- to compare the efficacy of commonly used analgesia (three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) with a combination of opioid and NSAID (one subcutaneous injection of 5 mg/kg carprofen before surgery followed by three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) and 3- to test if Infrared Thermography (IRT) could be a potential new Refinement method to easily assess thermoregulation, an important metabolic parameter. Finally, we aimed to achieve these goals without recruiting animals on purpose, but using mice already scheduled for studies on SCI. By using behaviours analysis, we found that, despite being commonly used, buprenorphine does not completely relieve acute surgical pain, whereas the combination of buprenorphine and carprofen significantly decreases pain signs by 80%. IRT technology turned out to be a very useful Refinement tool being a non invasive methods to measure animal temperature, particularly useful when rectal probe cannot be used, as in the case of SCI. We could find that temperatures constantly and significantly increased until 7 days after surgery and then slowly decreased and, finally, we could observe that in the buprenorphine and carprofen treated group, temperatures were statistically lower than in the buprenorphine-alone treated mice. To our knowledge this is the first work providing an analgesic Refinement and a description of thermoregulatory response using the IRT technology, in mice subjected to SCI.
Association between personal, medical and positive psychological variables with somatization in university health sciences students

ABSTRACT Objective To measure personal, medical and psychological positive and negative variables and to determine their relation with somatization in a sample of health sciences students. Subjects and methods: A total of 594 (34.43%) of the 1725 health science students of a public university answered an online survey with personal and medical information as well as the following psychological variables: phsychological well-being, five facets mindfulness questionnaire (FFMQ), life satisfaction, depression, and academic stress. Additionally, the presence of 11 somatic symptoms and 11 diseases during the last year was measured. Results: Most students were women (74.06%) who were 19.96 ± 4.28 years old. The global frequency of somatization in the previous year was 66.59%, and the presence of any measured disease 14.75%. With the multivariate analysis, self-acceptance was the most related variable (negatively) with somatization, followed by the sum of diseases, female gender, academic stress, smoking, and depression, in a model with an R-value of 0.634, self-acceptance was also the most related variable (negatively) with depression, being this last the most related variable with academic stress. Conclusions: After analyzing all variables considered in this study, self-acceptance was the most related variable with somatization and depression; this highlights the importance of strengthening the acceptance of the self in the student population in order to prevent these conditions and their consequences.
Ascorbate Deficiency Does Not Limit Nonphotochemical Quenching in Chlamydomonas reinhardtii1[OPEN]

In C. reinhardtii, in contrast to seed plants, ascorbate is not required for violaxanthin de-epoxidation and energy-dependent nonphotochemical quenching, but it mitigates photoinhibitory quenching. Ascorbate (Asc; vitamin C) plays essential roles in development, signaling, hormone biosynthesis, regulation of gene expression, stress resistance, and photoprotection. In vascular plants, violaxanthin de-epoxidase requires Asc as a reductant; thereby, Asc is required for the energy-dependent component of nonphotochemical quenching (NPQ). To assess the role of Asc in NPQ in green algae, which are known to contain low amounts of Asc, we searched for an insertional Chlamydomonas reinhardtii mutant affected in theVTC2 gene encoding GDP-l-Gal phosphorylase, which catalyzes the first committed step in the biosynthesis of Asc. The Crvtc2-1 knockout mutant was viable and, depending on the growth conditions, contained 10% to 20% Asc relative to its wild type. When C. reinhardtii was grown photomixotrophically at moderate light, the zeaxanthin-dependent component of NPQ emerged upon strong red illumination both in the Crvtc2-1 mutant and in its wild type. Deepoxidation was unaffected by Asc deficiency, demonstrating that the Chlorophycean violaxanthin de-epoxidase found in C. reinhardtii does not require Asc as a reductant. The rapidly induced, energy-dependent NPQ component characteristic of photoautotrophic C. reinhardtii cultures grown at high light was not limited by Asc deficiency either. On the other hand, a reactive oxygen species-induced photoinhibitory NPQ component was greatly enhanced upon Asc deficiency, both under photomixotrophic and photoautotrophic conditions. These results demonstrate that Asc has distinct roles in NPQ formation in C. reinhardtii as compared to vascular plants.
Bacterial Pathogens Hijack the Innate Immune Response by Activation of the Reverse Transsulfuration Pathway

Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages. ABSTRACT The reverse transsulfuration pathway is the major route for the metabolism of sulfur-containing amino acids. The role of this metabolic pathway in macrophage response and function is unknown. We show that the enzyme cystathionine γ-lyase (CTH) is induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase (PI3K)/MTOR and the transcription factor SP1. This results in the synthesis of cystathionine, which facilitates the survival of pathogens within myeloid cells. Our data demonstrate that the expression of CTH leads to defective macrophage activation by (i) dysregulation of polyamine metabolism by depletion of S-adenosylmethionine, resulting in immunosuppressive putrescine accumulation and inhibition of spermidine and spermine synthesis, and (ii) increased histone H3K9, H3K27, and H3K36 di/trimethylation, which is associated with gene expression silencing. Thus, CTH is a pivotal enzyme of the innate immune response that disrupts host defense. The induction of the reverse transsulfuration pathway by bacterial pathogens can be considered an unrecognized mechanism for immune escape. IMPORTANCE Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages.
Safety and effectiveness of bevacizumab in Japanese patients with malignant glioma: a post-marketing surveillance study

Abstract Objective This surveillance study was conducted to verify the post-market safety and effectiveness of bevacizumab, which was approved in Japan in 2013 for the treatment of patients with newly diagnosed and or recurrent malignant glioma. Methods This was a prospective, observational, multicenter post-marketing surveillance study. Patients with newly diagnosed or recurrent malignant glioma scheduled for bevacizumab treatment were enrolled. The incidence and severity of adverse drug reactions were calculated. The effectiveness of bevacizumab was assessed by the 1-year survival rate and the overall survival rate. Results The safety analysis set and the effectiveness analysis set each comprised 258 of the 268 enrolled patients: tumours were newly diagnosed in 80 patients (31%) and recurrent in 178 patients (68.9%). The incidence of grade ≥ 3 adverse drug reactions was 15.1%. Adverse drug reactions of special interest included 14 cerebral bleeding events and 11 infections. Of the 80 patients with newly diagnosed malignant glioma, 44 (55%) were alive throughout the 18-month observation period. The 1-year survival rate for patients with newly diagnosed glioblastoma was 78%. Median overall survival was not calculated, but 51.2% of patients were alive at the last date of observation of the last observed patient. In patients with recurrent glioblastoma, the 1-year survival rate was 38.9%, and the median overall survival was 10.2 months. Conclusions The results suggest no new safety concerns, and the effectiveness might be similar to previously reported data in clinical trials. Therefore, bevacizumab is considered as one of the treatment options for patients with malignant glioma in real-world clinical practice.
Finding confidence and inner trust as a parent: experiences of group-based compassion-focused therapy for the parents of adolescents with mental health problems

ABSTRACT Purpose: Compassion-focused therapy (CFT) can alleviate the stress and challenges faced by the parents of adolescents with mental health (MH) problems. Although CFT interventions have shown promising results, few studies have examined its effectiveness in adolescent psychiatric settings. Therefore, this study examined the participant experiences of group-based CFT for the parents of adolescents with MH problems. Methods: The reflective lifeworld research (RLR) approach was used to conduct in-depth interviews with eleven parents, focusing on participant experiences of group-based CFT. Meaning-oriented data analysis was undertaken. Results: The essential meaning of the phenomenon of participating in group-based CFT was understood as finding confidence and inner trust as a parent, characterized by an understanding of one’s own needs, which provided parents with the confidence to support their children. The phenomenon is further explicated with its three constituents: (a) taking care of oneself and one’s child; (b) being open and sharing experiences; and (c) acceptance and hope for the future. Conclusions: The CFT intervention enabled parents to find their agency and strengthened their relationships with their children. The findings underscore the need to acknowledge the supportive role parents play in the recovery of children who receive psychiatric care.
Predictable real-time constraints reveal anticipatory strategies of coupled planning in a sequential pick and place task

Planning a sequence of two motor elements is much more than concatenating two independent movements. However, very little is known about the cognitive strategies that are used to perform fluent sequences for intentional object manipulation. In this series of studies, the participants’ task was to reach for and pick to place a wooden cylinder to set it on a place pad of three different diameters, which served to modify terminal accuracy constraints. Participants were required to perform the sequences (1) at their preferred speed or (2) as fast as possible. Action kinematics were recorded with the Qualisys motion-capture system in order to implement a real-time protocol to get participants to engage in a true interactive relation. Results revealed that with low internal constraints (at preferred speed), low coupling between the two elements of the motor sequence was observed, suggesting a step-by-step planning strategy. Under high constraints (at fastest speed), an important terminal accuracy effect back propagated to modify early kinematic parameters of the first element, suggesting strong coupling of the parameters in an encapsulated planning strategy. In Studies 2 and 3, we further manipulated instructions and timing constraints to confirm the importance of time and predictability of external information for coupled planning. These findings overall sustain the hypothesis that coupled planning can take place in a pick and place task when anticipatory strategies are possible. This mode of action planning may be the key reason why motor intention can be read through the observation of micro variations in body kinematics.
Obesity in kidney transplantation

The prevalence of obesity among patients with chronic kidney disease continues to increase as a reflection of the trend observed in the general population. Factors affecting the access to the waiting list and the transplantability of this specific population will be analysed. From observational studies, kidney transplantation in obese patients carries an increased risk of surgical complications compared to the nonobese population; therefore, many centres have been reluctant to proceed with transplantation, despite this treatment modality confers a survival advantage over dialysis. As a consequence, obese patients continue to face decreased access to the waiting list, with a lower likelihood of being transplanted and higher waiting times when compared to the nonobese candidates. In this review will be described the current strategies for treatment of obesity in different settings (pretransplant, at transplant and post‐transplant). Obesity represents a risk factor for surgical complications but not a contraindication for kidney transplantation; outcomes could be greatly improved with its multidisciplinary and multimodal treatment. The modern technology with minimally invasive techniques, mainly using robotic platform, allows a reduction in the surgical complications rate, with graft and patient survival rates comparable to the nonobese counterpart.
Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell‐derived retinal organoids

Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age‐related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has shown that a simple three‐dimensional culture system enables differentiation of human pluripotent stem cells to retinal organoids containing large numbers of photoreceptors developing alongside retinal neurons and Müller glia cells in a laminated structure that resembles the native retina. Despite these promising developments, current protocols show different efficiencies across pluripotent stem cells and result in retinal organoids with a mixture of photoreceptor cells at varying maturation states, along with nonphotoreceptor cell types. In this study, we investigated the impact of stage‐specific addition of retinoic acid (RA), 9‐cis‐retinal, 11‐cis‐retinal, levodopa (l‐DOPA), triiodothyronine (T3), and γ‐secretase inhibitor ((2S)‐N‐[(3,5‐Difluorophenyl)acetyl]‐l‐alanyl‐2‐phenyl]glycine1,1‐dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 120 of differentiation enhanced the generation of rod and S‐cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 of differentiation led to enhanced generation of L/M‐cones at the expense of rods. l‐DOPA when added together with RA during days 90 to 120 of differentiation also promoted the emergence of S‐cones at the expense of rod photoreceptors. Collectively, these data represent an advance in our ability to direct generation of rod and cone photoreceptors in vitro.
CRISPR/Cas13a powered electrochemical microfluidic biosensor for nucleic acid amplification-free miRNA diagnostics

Non-coding small RNAs, such as microRNAs, are becoming the biomarkers of choice for multiple diseases in clinical diagnostics. A dysregulation of these microRNAs can be associated to many different diseases, such as cancer, dementia or cardiovascular conditions. The key for an effective treatment is an accurate initial diagnosis at an early stage, improving the patient’s survival chances. Here, we introduce a CRISPR/Cas13a powered microfluidic, integrated electrochemical biosensor for the on-site detection of microRNAs. Through this unique combination, the quantification of the potential tumor markers microRNA miR-19b and miR-20a has been realized without any nucleic acid amplification. With a readout time of 9 minutes and an overall process time of less than 4 hours, a limit of detection of 10 pM was achieved, using a measuring volume of less than 0.6 µl. Furthermore, we demonstrate the feasibility of our versatile sensor platform to detect miR-19b in serum samples of children, suffering from brain cancer. The validation of our results with a standard qRT-PCR method shows the ability of our system to be a low-cost and target amplification-free tool for nucleic acid based diagnostics.
Early outcome of aortic balloon occlusion during total aortic arch replacement with the frozen elephant trunk technique for aortic dissection.

OBJECTIVES The aim of this study was to propose and evaluate the new operative technique of aortic balloon occlusion in total aortic arch replacement (TAR) with the frozen elephant trunk that can significantly decrease the time of circulatory arrest and increase the hypothermic cardiopulmonary bypass (CPB) temperature. METHODS Between 2010 and 2018, 1335 patients with aortic dissection who underwent TAR with the frozen elephant trunk were included in the study. The newest 80 cases were treated with aortic balloon occlusion. To illustrate the difference with the new procedure, 1255 conventional TAR cases served as the historical control. Femoral and right axillary artery cannulations were used for CPB and antegrade selective cerebral perfusion. Circulatory arrest was implemented at the nasopharyngeal temperature of 28°C with continuous antegrade selective cerebral perfusion. After the stent graft was inserted into the true lumen of the descending aorta, the aortic balloon in a sheath was deployed into the stent graft and positioned at the metal part of the stent graft. When the balloon was inflated with enough saline to compress the stent graft, the sheath was simultaneously pressed by hand to properly fix the balloon and avoid displacement. Then femoral perfusion could be resumed. RESULTS The aortic balloon occlusion technique was successful in all patients, with the median duration of circulatory arrest being 5 (interquartile range 3-7) min. The 30-day mortality rate was 6.25% (5/80), whereas with the conventional method it was 9.40% (118/1255). The postoperative conscious revival (8.67 vs 11.40 h, P < 0.001) and mechanical ventilation times (19.70 vs 24.45 h, P = 0.02) were significantly shorter. Decreases in postoperative acute kidney injuries (13.75% vs 32.11%, P = 0.001) and liver injuries (8.75% vs 37.61%, P < 0.001) were also observed. The patients were transfused with lesser quantities of red blood cells, plasma and platelets. CONCLUSIONS The aortic balloon occlusion technique is a feasible way to shorten circulatory arrest significantly, to obviate the need for deep hypothermia in TAR with the frozen elephant trunk and to provide favourable protective effects on the central nervous, haematological and visceral systems. With these satisfactory results, this technique deserves further investigation.
Predicting Depression and Emotions in the Cross-roads of Cultures, Para-linguistics, and Non-linguistics

Cross-language, cross-cultural emotion recognition and accurate prediction of affective disorders are two of the major challenges in affective computing today. In this work, we compare several systems for Detecting Depression with AI Sub-challenge (DDS) and Cross-cultural Emotion Sub-challenge (CES) that are published as part of the Audio-Visual Emotion Challenge (AVEC) 2019. For both sub-challenges, we benefit from the baselines, while introducing our own features and regression models. For the DDS challenge, where ASR transcripts are provided by the organizers, we propose simple linguistic and word-duration features. These ASR transcript-based features are shown to outperform the state of the art audio visual features for this task, reaching a test set Concordance Correlation Coefficient (CCC) performance of 0.344 in comparison to a challenge baseline of 0.120. Our results show that non-verbal parts of the signal are important for detection of depression, and combining this with linguistic information produces the best results. For CES, the proposed systems using unsupervised feature adaptation outperform the challenge baselines on emotional primitives, reaching test set CCC performances of 0.466 and 0.499 for arousal and valence, respectively.