Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term events following catheter‐ablation for atrial fibrillation in heart failure with preserved ejection fraction

Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF).
Humoral and Cellular Immunogenicity of Six Different Vaccines against SARS-CoV-2 in Adults: A Comparative Study in Tunisia (North Africa)

Background: The mass vaccination campaign against SARS-CoV-2 was started in Tunisia on 13 March 2021 by using progressively seven different vaccines approved for emergency use. Herein, we aimed to evaluate the humoral and cellular immunity in subjects aged 40 years and over who received one of the following two-dose regimen vaccines against SARS-CoV-2, namely mRNA-1273 or Spikevax (Moderna), BNT162B2 or Comirnaty (Pfizer-BioNTech), Gam-COVID-Vac or Sputnik V (Gamaleya Research Institute), ChAdOx1-S or Vaxzevria (AstraZeneca), BIBP (Sinopharm), and Coronavac (Sinovac). Material and methods: For each type of vaccine, a sample of subjects aged 40 and over was randomly selected from the national platform for monitoring COVID-19 vaccination and contacted to participate to this study. All consenting participants were sampled for peripheral blood at 3–7 weeks after the second vaccine dose to perform anti-S and anti-N serology by the Elecsys® (Lenexa, KS, USA) anti-SARS-CoV-2 assays (Roche® Basel, Switzerland). The CD4 and CD8 T cell responses were evaluated by the QuantiFERON® SARS-CoV-2 (Qiagen® Basel, Switzerland) for a randomly selected sub-group. Results: A total of 501 people consented to the study and, of them, 133 were included for the cellular response investigations. Both humoral and cellular immune responses against SARS-CoV-2 antigens differed significantly between all tested groups. RNA vaccines induced the highest levels of humoral and cellular anti-S responses followed by adenovirus vaccines and then by inactivated vaccines. Vaccines from the same platform induced similar levels of specific anti-S immune responses except in the case of the Sputnik V and the AstraZeneca vaccine, which exhibited contrasting effects on humoral and cellular responses. When analyses were performed in subjects with negative anti-N antibodies, results were similar to those obtained within the total cohort, except for the Moderna vaccine, which gave a better cellular immune response than the Pfizer vaccine and RNA vaccines, which induced similar cellular immune responses to those of adenovirus vaccines. Conclusion: Collectively, our data confirmed the superiority of the RNA-based COVID-19 vaccines, in particular that of Moderna, for both humoral and cellular immunogenicity. Our results comparing between different vaccine platforms in a similar population are of great importance since they may help decision makers to adopt the best strategy for further national vaccination programs.
Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients

Immunosuppressant drugs (ISDs) are routinely used in clinical practice to maintain organ transplant survival. However, these drugs are characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability, and a series of severe adverse effects. In particular, genetic factors have been estimated to play a role in this variability because of polymorphisms regarding genes encoding for enzymes and transporters involved in the ISDs pharmacokinetic. Several studies showed important correlations between genetic polymorphisms and ISDs blood levels in transplanted patients; therefore, this review aims to summarize the pharmacogenetics of approved ISDs. We used PubMed database to search papers on pharmacogenetics of ISDs in adults or pediatric patients of any gender and ethnicity receiving immunosuppressive therapy after kidney transplantation. We utilized as search term: “cyclosporine or tacrolimus or mycophenolic acid or sirolimus or everolimus and polymorphism and transplant”. Our data showed that polymorphisms in CYP3A5, CYP3A4, ABCB1, and UGT1A9 genes could modify the pharmacokinetics of immunosuppressants, suggesting that patient genotyping could be a helpful strategy to select the ideal ISDs dose for each patient.
A Modified Yeast Two-Hybrid Platform Enables Dynamic Control of Expression Intensities to Unmask Properties of Protein–Protein Interactions

The yeast two-hybrid (Y2H) assay is widely used for protein–protein interaction characterization due to its simplicity and accessibility. However, it may mask changes in affinity caused by mutations or ligand activation due to signal saturation. To overcome this drawback, we modified the Y2H system to have tunable protein expression by introducing a fluorescent reporter and a pair of synthetic inducible transcription factors to regulate the expression of interacting components. We found that the application of inducers allowed us to adjust the concentrations of interacting proteins to avoid saturation and observe interactions otherwise masked in the canonical Y2H assay, such as the abscisic acid-mediated increase in affinity of monomeric abscisic acid receptors to the coreceptor. When applied in future studies, our modified system may provide a more accurate characterization of protein–protein interactions.
A Generalizable Evaluated Approach, Applying Advanced Geospatial Statistical Methods, to Identify High Lead Exposure Locations at Census Tract Scale: Michigan Case Study

Background: Despite great progress in reducing environmental lead (Pb) levels, many children in the United States are still being exposed. Objective: Our aim was to develop a generalizable approach for systematically identifying, verifying, and analyzing locations with high prevalence of children’s elevated blood Pb levels (EBLLs) and to assess available Pb models/indices as surrogates, using a Michigan case study. Methods: We obtained ∼1.9 million BLL test results of children <6 years of age in Michigan from 2006–2016; we then evaluated them for data representativeness by comparing two percentage EBLL (%EBLL) rates (number of children tested with EBLL divided by both number of children tested and total population). We analyzed %EBLLs across census tracts over three time periods and between two EBLL reference values (≥5 vs. ≥10μg/dL) to evaluate consistency. Locations with high %EBLLs were identified by a top 20 percentile method and a Getis-Ord Gi* geospatial cluster “hotspot” analysis. For the locations identified, we analyzed convergences with three available Pb exposure models/indices based on old housing and sociodemographics. Results: Analyses of 2014–2016 %EBLL data identified 11 Michigan locations via cluster analysis and 80 additional locations via the top 20 percentile method and their associated census tracts. Data representativeness and consistency were supported by a 0.93 correlation coefficient between the two EBLL rates over 11 y, and a Kappa score of ∼0.8 of %EBLL hotspots across the time periods (2014–2016) and reference values. Many EBLL hotspot locations converge with current Pb exposure models/indices; others diverge, suggesting additional Pb sources for targeted interventions. Discussion: This analysis confirmed known Pb hotspot locations and revealed new ones at a finer geographic resolution than previously available, using advanced geospatial statistical methods and mapping/visualization. It also assessed the utility of surrogates in the absence of blood Pb data. This approach could be applied to other states to inform Pb mitigation and prevention efforts. https://doi.org/10.1289/EHP9705
Gene-Based Therapeutics for Parkinson’s Disease

Parkinson’s disease (PD) is a complex multifactorial disorder that is not yet fully surmised, and it is only when such a disease is tackled on multiple levels simultaneously that we should expect to see fruitful results. Gene therapy is a modern medical practice that theoretically and, so far, practically, has demonstrated its capability in joining the battle against PD and other complex disorders on most if not all fronts. This review discusses how gene therapy can efficiently replace current forms of therapy such as drugs, personalized medicine or invasive surgery. Furthermore, we discuss the importance of enhancing delivery techniques to increase the level of transduction and control of gene expression or tissue specificity. Importantly, the results of current trials establish the safety, efficacy and applicability of gene therapy for PD. Gene therapy’s variety of potential in interfering with PD’s pathology by improving basal ganglial circuitry, enhancing dopamine synthesis, delivering neuroprotection or preventing neurodegeneration may one day achieve symptomatic benefit, disease modification and eradication.
Nanoscopic Spatial Association between Ras and Phosphatidylserine on the Cell Membrane Studied with Multicolor Super Resolution Microscopy

Recent work suggests that Ras small GTPases interact with the anionic lipid phosphatidylserine (PS) in an isoform-specific manner, with direct implications for their biological functions. Studies on PS-Ras associations in cells, however, have relied on immuno-EM imaging of membrane sheets. To study their spatial relationships in intact cells, we have combined the use of Lact-C2-GFP, a biosensor for PS, with multicolor super resolution imaging based on DNA-PAINT. At ~20 nm spatial resolution, the resulting super resolution images clearly show the nonuniform molecular distribution of PS on the cell membrane and its co-enrichment with caveolae, as well as with unidentified membrane structures. Two-color imaging followed by spatial analysis shows that KRas-G12D and HRas-G12V both co-enrich with PS in model U2OS cells, confirming previous observations, yet exhibit clear differences in their association patterns. Whereas HRas-G12V is almost always co-enriched with PS, KRas-G12D is strongly co-enriched with PS in about half of the cells, with the other half exhibiting a more moderate association. In addition, perturbations to the actin cytoskeleton differentially impact PS association with the two Ras isoforms. These results suggest that PS-Ras association is context-dependent and demonstrate the utility of multiplexed super resolution imaging in defining the complex interplay between Ras and the membrane.
Is It First the Egg or the Shrimp? – Diversity and Variation in Microbial Communities Colonizing Broods of the Vent Shrimp Rimicaris exoculata During Embryonic Development

Rimicaris exoculata is one of the most well-known and emblematic species of endemic vent fauna. Like many other species from these ecosystems, Rimicaris shrimps host important communities of chemosynthetic bacteria living in symbiosis with their host inside the cephalothorax and gut. For many of these symbiotic partners, the mode of transmission remains to be elucidated and the starting point of the symbiotic relationship is not yet defined, but could begin with the egg. In this study, we explored the proliferation of microbial communities on R. exoculata broods through embryonic development using a combination of NGS sequencing and microscopy approaches. Variations in abundance and diversity of egg microbial communities were analyzed in broods at different developmental stages and collected from mothers at two distinct vent fields on the Mid-Atlantic Ridge (TAG and Snake Pit). We also assessed the specificity of the egg microbiome by comparing communities developing on egg surfaces with those developing on the cuticle of pleopods, which are thought to be exposed to similar environmental conditions because the brood is held under the female’s abdomen. In terms of abundance, bacterial colonization clearly increases with both egg developmental stage and the position of the egg within the brood: those closest to the exterior having a higher bacterial coverage. Bacterial biomass increase also accompanies an increase of mineral precipitations and thus clearly relates to the degree of exposure to vent fluids. In terms of diversity, most bacterial lineages were found in all samples and were also those found in the cephalothorax of adults. However, significant variation occurs in the relative abundance of these lineages, most of this variation being explained by body surface (egg vs. pleopod), vent field, and developmental stage. The occurrence of symbiont-related lineages of Epsilonbacteraeota, Gammaproteobacteria, Zetaproteobacteria, and Mollicutes provide a basis for discussion on both the acquisition of symbionts and the potential roles of these bacterial communities during egg development.
Osteotomies and Total Knee Arthroplasty: Systematic Review and Meta-Analysis

Total knee replacement (TKA) is a frequent modality performed in patients with osteoarthritis. Specific circumstances can make it much more difficult to execute successfully, and additional procedures such as osteotomy may be required. The aim of this study was to perform a meta-analysis and systematic review of osteotomies combined with TKA. Methods: In June 2022, a search PubMed, Embase, Cochrane, and Clinicaltrials was undertaken, adhering to PRISMA guidelines. The search included the terms “osteotomy” and “total knee arthroplasty”. Results: Two subgroups (tibial tubercle osteotomy and medial femoral condyle osteotomy) were included in the meta-analysis. Further subgroups were described as a narrative review. The primary outcome showed no significant difference in favor to TTO. Secondary outcomes showed improved results in all presented subgroups compared to preoperative status. Conclusion: This study showed a significant deficit of randomized control trials treated with osteotomies, in addition to TKA, and a lack of evidence-based surgical guidelines for the treatment of patients with OA in special conditions: posttraumatic deformities, stiff knee, severe varus, and valgus axis or patella disorders.
Ultrasound Cyclo Plasty in Glaucoma: 2-Year Outcomes

Précis: UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden. Purpose: The purpose of this study is to evaluate the 2-year outcomes of Ultrasound Cyclo Plasty (UCP) in uncontrolled glaucoma. Materials and Methods: A retrospective cohort study included patients with uncontrolled primary or secondary glaucoma who underwent UCP at King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, between 2016 and 2021. The main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, and presence of vision-threatening complications. The surgical outcome of each eye was classified as complete success, qualified success, or failure based on the main outcome measures. Results: One hundred and eighty-two eyes of 158 patients were included in the study. The mean follow-up period was 29.71 months (±18.1). The IOP and the number of antiglaucoma medications decreased significantly from a mean of 23.46 mm Hg (±6.3) and 3.33 (±0.9) to 17.33 (±7.1) and 2.14 (±1.4), and 16.24 (±6.3) and 1.90 (±1.5) on the 12th and 24 months, respectively. The overall success rates were 78.0% (143/182) and 85.6% (95/111), and the failure rates were 21.4% (39/182) and 14.4% (16/111) on the 12th and 24th months, respectively. The most common complications were cataract development/progression and anterior chamber reaction. Conclusions: UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.
Changes in the Care Activity in Addiction Centers with Dual Pathology Patients during the COVID-19 Pandemic

Background: Health care provision during the COVID-19 pandemic and confinement has led to significant changes in the activity of addiction centers. These changes in healthcare activity may have had a greater impact on patients with dual pathology. The aim of this study is to compare the treatment indicators of patients with dual pathology in addiction centers during the pre-confinement, confinement, and post-confinement periods. Methods: A retrospective observational study was conducted for the period between 1 February 2019 and 30 June 2021. A total of 2785 patients treated in specialized addiction services were divided into three periods according to their time of admission: pre-confinement, confinement, and post-confinement. Results: During the pre-pandemic period, the addiction centers attended to an average of 121.3 (SD = 23.58) patients, decreasing to 53 patients during confinement (SD = 19.47), and 80.69 during the post-confinement period (SD = 15.33). The number of appointments scheduled monthly for each patient decreased during the confinement period, although this number increased after confinement. There was a reduction in the number of toxicological tests carried out both during and after confinement (except for alcohol). Conclusions: The results show a reduction in the number of patients seen and the care activity delivered to dual diagnosis patients. These results, which were caused by the COVID-preventive measures, may affect the progress and recovery of dual patients. A greater investment is needed to bring the care activity up to the standards of the years prior to confinement.
Incidental physical pain reduces brain activities associated with affective social feedback and increases aggression

Abstract Physical pain may lead to aggressive behavior in a social context. However, it is unclear whether this is related to changes of social information processing. Thus, this study aimed to investigate the neural mechanisms underlying pain-induced aggression using functional magnetic resonance imaging. In the experiment, 59 healthy participants were recruited: 31 were treated with topical capsaicin cream (pain group) and 28 with hand cream (control group). Participants completed a social network aggression task, during which they underwent two phases: feedback processing and attack exerting. The results revealed that participants in the pain group exhibited more aggression than those in the control group. During the feedback-processing phase, physical pain reduced brain activation in the right insula, left orbitofrontal cortex and anterior cingulate cortex, which typically exhibited stronger activation in response to negative (and positive) vs neutral social feedback in the control group. However, during the attack-exerting phase, pain did not significantly alter the activation of the dorsolateral prefrontal cortex. These findings suggest that pain increased aggression, while before that, it suppressed brain activities of the salience network involved in the process of salient social information and the value system associated with the value representation of social events.
Flooding and Soil Properties Control Plant Intra- and Interspecific Interactions in Salt Marshes

The stress gradient hypothesis (SGH) states that plant-plant interactions shift from competition to facilitation in increasing stress conditions. In salt marshes, edaphic properties can weaken the application of the SGH by amplifying the intensity of flooding and controlling plant zonation. We identified facilitative and competitive interactions along flooding gradients and tested the role of edaphic properties in exacerbating stress and shaping plant-plant interactions. Morphological traits of two target halophytes (Limonium narbonense and Sarcocornia fruticosa), flooding intensity, soil texture and soil organic C were recorded. The relative plant fitness index was assessed for the two species based on the relative growth in plurispecific rather than monospecific plant communities. Plant fitness increased with increasing stress supporting the SGH. L. narbonense showed larger fitness in plurispecific stands whereas S. fruticosa performed better in conspecific stands. Significant intra- or interspecific interactions were observed along the stress gradient defined by the combination of flooding and clay content in soil. When considering the limited soil organic C as stressor, soil properties were more important than flooding in defining plant-plant interactions. We highlight the need for future improvements of the SGH approach by including edaphic stressors in the model and their possible interactions with the main abiotic drivers of zonation.
Interspecific Contagious Yawning in Humans

Simple Summary Contagious yawning has been observed in humans and a growing number of social vertebrates. While the majority of studies on yawn contagion have documented this phenomenon amongst conspecifics, there is also evidence for interspecific contagious yawning among non-human animals in captivity. This study was the first to formally investigate whether humans also yawn in response to yawns from different species. In particular, participants were exposed to yawning stimuli either from (1) fish, (2) amphibians, (3) reptiles, (4) birds, (5) non-primate mammals, (6) apes, or (7) domesticated cats and dogs. Overall, the results provide strong support for interspecific contagious yawning in humans, with 69% reporting yawn contagion during testing. This response was not altered by phylogenetic proximity or domestication, suggesting that the mechanisms governing yawn contagion are generalized, and can be triggered by varied representations of yawning across diverse taxa. Abstract Contagious yawning, or the reflexive tendency to yawn following the detection of yawning in others, is well-documented among humans and a growing number of social vertebrates. While the most common form of yawn contagion occurs between conspecifics, some non-human animals in captivity have been reported to yawn in response to yawns from human handlers/caregivers. The current research sought to provide the first formal investigation of whether people yawn contagiously in response to yawns from non-human animals. In addition, this study aimed to test whether this response was modulated by phylogenetic relatedness and domestication/social closeness. A total of 296 participants from Amazon Mechanical Turk self-reported on their yawning behavior following exposure to a (1) control (non-yawning) condition or a compilation of yawning stimuli either from (2) fish, (3) amphibians, (4) reptiles, (5) birds, (6) non-primate mammals, (7) apes, or (8) domesticated cats and dogs. The results provide strong support for interspecific yawn contagion. However, neither the propensity to yawn (binary) nor total yawn frequency varied significantly across interspecific conditions. Overall, these findings suggest that the mechanisms governing yawn contagion can be activated by varied forms of yawning stimuli, including those from distantly related and unfamiliar species.