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With the rapid spread and evolution of SARS-CoV-2, the ability to monitor its transmission and distinguish among viral lineages is critical for pandemic response efforts. The most commonly used software for the lineage assignment of newly isolated SARS-CoV-2 genomes is pangolin, which offers two methods of assignment, pangoLEARN and pUShER. PangoLEARN rapidly assigns lineages using a machine-learning algorithm, while pUShER performs a phylogenetic placement to identify the lineage corresponding to a newly sequenced genome. In a preliminary study, we observed that pangoLEARN (decision tree model), while substantially faster than pUShER, offered less consistency across different versions of pangolin v3. Here, we expand upon this analysis to include v3 and v4 of pangolin, which moved the default algorithm for lineage assignment from pangoLEARN in v3 to pUShER in v4, and perform a thorough analysis confirming that pUShER is not only more stable across versions but also more accurate. Our findings suggest that future lineage assignment algorithms for various pathogens should consider the value of phylogenetic placement.

Summary Postural balance requires the interplay between several physiological signals. Indirect evidence suggests that the perception of signals arising from the autonomic nervous system might play a role (e.g. cardiac awareness). Here, we tested this hypothesis by investigating the relationship between postural control and cardiac awareness (i.e. interoception) in a sample of N = 70 healthy individuals. Postural control was measured using a medical robotic device, while cardiac awareness was evaluated using the heartbeat counting task. A within-subject design included two platform configurations (static, unstable) and two visual feedback conditions (eyes open, eyes closed). For each condition, we measured the sway area and the range of oscillation of the platform, as well as the range of oscillation and the quantity of movement of participants’ trunk. In the “platform unstable, eyes closed” condition, participants with higher cardiac awareness demonstrated a significantly smaller sway area and reduced oscillations of both the platform and their trunk. These findings hint at a potential link between interoception and postural control, suggesting that the perception of internal body signals might sustain balance.

The objective of this study was to present the main factors responsible for falls in older adults, measures for assessing risk, and prevention strategies. This is a qualitative study, developed from the international and national gerontology literature. Two models were created, one including the main fall risk factors and another including common assessment and prevention measures. Five types of intervention procedures were identified: educational, physical, cognitive, exergames and exercise programs. It was concluded that early identification of fall risk is important. The most appropriate intervention methodologies for preventing falls in the elderly include periodic dual and multi-task physical training followed by educational measures. In addition, exercise programs and exergames are effective in preventing falls, especially in congregate housing.

Human Hsp70-escort protein 1 (hHep1) is a cochaperone that assists in the function and stability of mitochondrial HSPA9. Similar to HSPA9, hHep1 is located outside the mitochondria and can interact with liposomes. In this study, we further investigated the structural and thermodynamic behavior of interactions between hHep1 and negatively charged liposomes, as well as interactions with cellular membranes. Our results showed that hHep1 interacts peripherally with liposomes formed by phosphatidylserine and cardiolipin and remains partially structured, exhibiting similar affinities for both. In addition, after being added to the cell membrane, recombinant hHep1 was incorporated by cells in a dose-dependent manner. Interestingly, the association of HSPA9 with hHep1 improved the incorporation of these proteins into the lipid bilayer. These results demonstrated that hHep1 can interact with lipids also present in the plasma membrane, indicating roles for this cochaperone outside of mitochondria.

Phylogenetics has been foundational to SARS-CoV-2 research and public health policy, assisting in genomic surveillance, contact tracing, and assessing emergence and spread of new variants. However, phylogenetic analyses of SARS-CoV-2 have often relied on tools designed for de novo phylogenetic inference, in which all data are collected before any analysis is performed and the phylogeny is inferred once from scratch. SARS-CoV-2 data sets do not fit this mold. There are currently over 14 million sequenced SARS-CoV-2 genomes in online databases, with tens of thousands of new genomes added every day. Continuous data collection, combined with the public health relevance of SARS-CoV-2, invites an "online" approach to phylogenetics, in which new samples are added to existing phylogenetic trees every day. The extremely dense sampling of SARS-CoV-2 genomes also invites a comparison between likelihood and parsimony approaches to phylogenetic inference. Maximum likelihood (ML) and pseudo-ML methods may be more accurate when there are multiple changes at a single site on a single branch, but this accuracy comes at a large computational cost, and the dense sampling of SARS-CoV-2 genomes means that these instances will be extremely rare because each internal branch is expected to be extremely short. Therefore, it may be that approaches based on maximum parsimony (MP) are sufficiently accurate for reconstructing phylogenies of SARS-CoV-2, and their simplicity means that they can be applied to much larger data sets. Here, we evaluate the performance of de novo and online phylogenetic approaches, as well as ML, pseudo-ML, and MP frameworks for inferring large and dense SARS-CoV-2 phylogenies. Overall, we find that online phylogenetics produces similar phylogenetic trees to de novo analyses for SARS-CoV-2, and that MP optimization with UShER and matOptimize produces equivalent SARS-CoV-2 phylogenies to some of the most popular ML and pseudo-ML inference tools. MP optimization with UShER and matOptimize is thousands of times faster than presently available implementations of ML and online phylogenetics is faster than de novo inference. Our results therefore suggest that parsimony-based methods like UShER and matOptimize represent an accurate and more practical alternative to established ML implementations for large SARS-CoV-2 phylogenies and could be successfully applied to other similar data sets with particularly dense sampling and short branch lengths.

Abstract Background Muscle strength and balance abilities have been related to game performance injury prevention. This study aimed to (1) assess knee muscle strength performance based on intra- and inter-limb asymmetries, (2) investigate the relationships between knee muscle strength, body composition, and balance, and (3) analyze the variance in the overall stability index (OSI) explained by knee muscle strength indicators after controlling for age and body composition. Methods The sample included 104 young male soccer players (16.0 ± 1.6 years). Body composition, knee muscle strength, and balance ability were assessed. A paired samples t-test was used to examine differences between the preferred leg (PL) and the non-preferred leg (NPL). Pearson correlations and hierarchical multiple regression were conducted to explore the relationships between strength, body composition, and balance. Results No significant inter-limb asymmetries were detected for the knee flexors (KF) and knee extensors (KE) performance. The hamstrings-to-quadriceps ratio does not suggest the existence of intra-limb asymmetries (p = 0.06). Significant and negative correlations were found between KF (r = -0.38, p ≤ 0.01) and KE (r = -0.58, p ≤ 0.01) for the PL. Concerning the NPL, KE also revealed a significant and negative relationship with balance (r = -0.30, p ≤ 0.01). Significant and positive relationships were found between bodyweight, fat-free mass, and balance. After controlling for age and body composition, knee muscle strength could explain between 13% and 30% of the variance observed in the OSI (NPL and PL, respectively). Conclusions The results underline knee muscle strength as an important predictor of balance. Thus, training programs targeting knee muscle strength development should be considered during the season periodization by coaches and their staff throughout the players’ developmental stages.

Abstract Background Brazil is one of the countries with the highest rates of caesarean sections (CS), reaching almost 90% of births in the private sector. A quality improvement project called “Adequate Childbirth Project (PPA)” was conceived to reduce CS in the private sector. This project consisted of four primary components: “Governance”, “Participation of Women”, “Reorganization of Care” and “Monitoring”. This paper aims to evaluate: (1) which specific activities of the PPA had the largest effect on the probability of a woman having a vaginal delivery; (2) which primary component of the PPA had the largest effect on the probability of vaginal delivery and (3) which scenarios combining the implementation of different activities planned in the PPA had a higher effect on the probability of vaginal delivery. Methods A sample of 12 private hospitals participating in the PPA was evaluated. We used a Bayesian Network (BN) to capture both non-linearities and complex cause-effect relations. The BN integrated knowledge from experts and data from women to estimate 26 model parameters. The PPA was evaluated in 2473 women belonging to groups 1–4 of the Robson classification, who were divided into two groups: those participating or not participating in the PPA. Results The probability of a woman having a vaginal delivery was 37.7% higher in women participating in the PPA. The most important component of the project that led to an increase in the probability of vaginal delivery was “Reorganization of Care”, leading to a 73% probability of vaginal delivery among women in labor. The activity that had the greatest effect on the type of delivery was access to best practices during labor, with a 72% probability of vaginal delivery. Considering the 12 scenarios combining the different activities of the PPA, the best scenarios included: a non-scheduled delivery, access to information about best practices, access to at least 4 best practices during labor and respect of the birth plan, with an 80% probability of vaginal delivery in the best combinations. Conclusion PPA has been shown to be an effective quality improvement program, increasing the likelihood of vaginal delivery in private Brazilian hospitals.

Abstract The Bcl2-associated athanogene-3 (BAG3) protein, a critical regulator of cellular survival, has been identified as a potential therapeutic target in various malignancies. This study investigates the role of BAG3 within stromal fibroblasts and its interaction with B-cell chronic lymphocytic leukemia (B-CLL) cells. Previous research demonstrated that BAG3 maintains the active state of pancreatic stellate cells (PSCs) and aids pancreatic ductal adenocarcinoma (PDAC) spread via cytokine release. To explore BAG3’s role in bone marrow-derived stromal fibroblasts, BAG3 was silenced in HS-5 cells using siRNA. In co-culture experiments with PBMCs from B-CLL patients, BAG3 silencing in HS-5 cells increased apoptosis and decreased phosphorylation of BTK, AKT, and ERK in B-CLL cells, thus disrupting their pro-survival key signaling pathways. The observation of fibroblast-activated protein (FAP) positive cells in infiltrated bone marrow specimens co-expressing BAG3 further support the involvement of the protein in fibroblast-mediated tumor survival. Additionally, BAG3 appears to support B-CLL survival by modulating cytokine networks, including IL-10 and CXCL12, which are essential for leukemic cell survival and proliferation. A robust correlation between BAG3 expression and the levels of CXCL12 and IL-10 was observed in both co-cultures and patient specimens. These findings point out the need for a more in-depth comprehension of the intricate network of interactions within the tumor microenvironment and provide valuable insights for the selection of new potential therapeutic targets in the medical treatment of CLL.

Abstract The pandemic marked the beginning of an era of dynamic and rapid changes in the diagnosis of respiratory infections. Herein we describe Legionnaires’ disease trend in the years 2016–2023 in a large Italian hospital showing how improvements in diagnostic algorithms impact on its detection.

Abstract Background In the older population, depression, loneliness, and quality of life are closely related, significantly influencing health status. This paper aimed (1) to investigate autoregressive and cross-lagged associations over 2 years between depression, loneliness, and quality of life, and (2) to examine sex-related differences in the 2-year associations between depression, loneliness, and quality of life in a large sample of European citizens aged ≥ 50 years. Methods This is a longitudinal analysis. We included 7.456 individuals (70.89 ± 7.64 years; (4.268 females) who responded to waves 7 (2017) and 8 (2019) of the SHARE project. The variables analyzed in both waves were depression, loneliness, and quality of life. Results Comparatively, females indicated higher depression and loneliness scores than males and a lower perception of quality of life. Autoregressive associations pointed that past depression, loneliness, and quality of life predicted their future episodes 2 years later (p

Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder exacerbated by Staphylococcus aureus colonization. The specific factors that drive S. aureus overgrowth and persistence in AD remain poorly understood. This study analyzed skin barrier functions and microbiome diversity in lesional (LE) and non-lesional (NL) forearm sites of individuals with severe AD compared to healthy control subjects (HS). Notable differences were found in transepidermal water loss, stratum corneum hydration, and microbiome composition. Cutibacterium was more prevalent in HS, while S. aureus and S. lugdunensis were predominantly found in AD LE skin. The results highlighted that microbial balance depends on inter-species competition. Specifically, network analysis at the genus level demonstrated that overall bacterial correlations were higher in HS, indicating a more stable microbial community. Notably, network analysis at the species level revealed that S. aureus engaged in competitive interactions in NL and LE but not in HS. Whole-genome sequencing (WGS) showed considerable genetic diversity among S. aureus strains from AD. Despite this variability, the isolates exhibited convergence in key phenotypic traits such as adhesion and biofilm formation, which are crucial for microbial persistence. These common phenotypes suggest an adaptive evolution, driven by competition in the AD skin microenvironment, of S. aureus and underscoring the interplay between genetic diversity and phenotypic convergence in microbial adaptation.