-A machine learning model to predict surgical site infection after surgery of lower extremity fractures.

PURPOSE: This study aimed to develop machine learning algorithms for identifying predictive factors associated with the risk of postoperative surgical site infection in patients with lower extremity fractures. METHODS: A machine learning analysis was conducted on a dataset comprising 1,579 patients who underwent surgical fixation for lower extremity fractures to create a predictive model for risk stratification of postoperative surgical site infection. We evaluated different clinical and demographic variables to train four machine learning models (neural networks, boosted generalised linear model, naïve bayes, and penalised discriminant analysis). Performance was measured by the area under the curve score, Youdon's index and Brier score. A multivariate adaptive regression splines (MARS) was used to optimise predictor selection. RESULTS: The final model consisted of five predictors. (1) Operating room time, (2) ankle region, (3) open injury, (4) body mass index, and (5) age. The best-performing machine learning algorithm demonstrated a promising predictive performance, with an area under the ROC curve, Youdon's index, and Brier score of 77.8%, 62.5%, and 5.1%-5.6%, respectively. CONCLUSION: The proposed predictive model not only assists surgeons in determining high-risk factors for surgical site infections but also empowers patients to closely monitor these factors and take proactive measures to prevent complications. Furthermore, by considering the identified predictors, this model can serve as a reference for implementing preventive measures and reducing postoperative complications, ultimately enhancing patient outcomes. However, further investigations involving larger datasets and external validations are required to confirm the reliability and applicability of our model.

Enhancing Prostate Tumor Biobanking Reliability with Improved Sampling Technique and Histological Characterization.

Acquiring fresh and well-characterized tumor tissue samples is critical for conducting high-quality "omics" studies. However, it can be particularly challenging in the context of prostate cancer (PC) due to the unique nature of this organ and the high heterogeneity associated with this tumor. On the other hand, histopathologically characterizing samples before their storage without causing significant tissue alterations is also an intriguing challenge. In this context, we present a new method for acquiring, mapping, characterizing, and micro-dissecting resected prostate tissue based on anatomopathological criteria. Unlike previously published protocols, this method reduces the time required for histopathological analysis of the prostate specimen without compromising its structure, which is crucial for assessing surgical margins. Furthermore, it enables the delineation and micro-macro dissection of fresh prostate tissue samples, with a focus on histological tumor areas defined by pathological criteria such as Gleason score, precursor lesions (high-grade prostatic intraepithelial neoplasia - PIN), and inflammatory lesions (prostatitis). These samples are then stored in a Biobank for subsequent research analyses.

Peripheral arterial disease in hemodialysis patients 10 years later.

BACKGROUND AND OBJECTIVE: Patients with chronic kidney disease (CKD) on hemodialysis present high cardiovascular comorbidity. Peripheral arterial disease (PAD) is associated with higher mortality and the interest in its early detection and treatment is increasing. The objective of this study is to determine the frequency and severity of symptomatic PAD, and to establish its relationship with mortality in HD patients that have received treated early and compare them with a cohort of our center already reported. MATERIAL AND METHODS: Retrospective study on a cohort of incident patients since 2014 and followed up until December 2019. Demographic data, cardiovascular risk, the presence of symptomatic PAD at baseline and during follow-up were collected. Trophic lesions were graded using the Rutherford scale. RESULTS: Initially, there were 91 patients and 7 cases that were not included in the study were lost to follow-up. Age 64 ±â€¯16 years, men 51.6% (47/91). The percentage of baseline PAD was 10.7% (9/84). During a median follow-up of 35 months (20-57), the diagnosis of PAD increased to 25% (21/84). Half of the patients with PAD 52.38% (11/21) obtained a score greater than 3 in the Rutherford Clinical Classification, which corresponds to severe disease. 13/21 patients required reoperation due to recurrence of symptoms (61.9% of cases with PAD). The development of PAD was significantly associated with: an elevated index of Charlson (3.9±2.1 vs. 7.7 ±â€¯3.5; P = 0.001),being male (19 vs. 2; P = 0.001), diabetic (no: 7; yes: 15; P = 0.001) and with a history of chronic ischemic heart disease (no: 13; yes: 8; P = 0.001), 38.1% (8/21) had ischemic heart disease in patients who developed PAD, while in the absence of PAD the presence of ischemic heart disease was 9.5% (6/63). Furthermore, more than half (66.7% [14/21]) of those who developed PAD were diabetic. Univariate analysis showed that age, C reactive protein, albumin, and number of surgical interventions, but not PAD, were associated with mortality. In the multivariate analysis adjusted for other factors, only C reactive protein was related to overall survival Exp ß: 2.17; P = 0.011; CI (1.19-3.97). Regarding cardiovascular mortality, in the multivariate Cox analysis, only PAD was related to mortality of cardiovascular origin Exp ß: 1.73; P = 0.006; CI (1.17-2.56). CONCLUSIONS: A significant number of patients on hemodialysis develop PAD requiring peripheral vascular surgery. PAD was not associated with overall mortality in our cohort, but it did show an association with cardiovascular mortality. Prospective studies with a larger sample size are necessary. New surgical treatments and Follow-up by vascular surgeons could improve the severity of PAD and the long-term prognosis.

Review of bone deficiency in total elbow arthroplasty revision.

Total elbow arthroplasty revision rates have been increasing over time due to the increasing use of the procedure with the accompanying increase in complications. The most common complications that typically require revision surgery include aseptic loosening, periprosthetic fractures, infection, and component failure. The associated instability has an overall revision rate reported to be as high as 13%. One important factor when performing a revision surgery is bone quality and bone loss; this represents a challenge during the clinical decision-making process. Currently, there are several strategies used to address bone loss such as arthrodesis, resection arthroplasty, impaction grafting, allograft-prosthetic composite reconstruction, and custom prostheses. The aim of this review article is to provide a comprehensive review of the current strategies to improve diagnosis of failed total elbow arthroplasty and improve management and outcomes of this patient population.

Biocrusts Modulate Climate Change Effects on Soil Organic Carbon Pools: Insights From a 9-Year Experiment.

Accumulating evidence suggests that warming associated with climate change is decreasing the total amount of soil organic carbon (SOC) in drylands, although scientific research has not given enough emphasis to particulate (POC) and mineral-associated organic carbon (MAOC) pools. Biocrusts are a major biotic feature of drylands and have large impacts on the C cycle, yet it is largely unknown whether they modulate the responses of POC and MAOC to climate change. Here, we assessed the effects of simulated climate change (control, reduced rainfall (RE), warming (WA), and RE + WA) and initial biocrust cover (low (< 20%) versus high (> 50%)) on the mineral protection of soil C and soil organic matter quality in a dryland ecosystem in central Spain for 9 years. At low initial biocrust cover levels, both WA and RE + WA increased SOC, especially POC but also MAOC, and promoted a higher contribution of carbohydrates, relative to aromatic compounds, to the POC fraction. These results suggest that the accumulation of soil C under warming treatments may be transitory in soils with low initial biocrust cover. In soils with high initial biocrust cover, climate change treatments did not affect SOC, neither POC nor MAOC fraction. Overall, our results indicate that biocrust communities modulate the negative effect of climate change on SOC, because no losses of soil C were observed with the climate manipulations under biocrusts. Future work should focus on determining the long-term persistence of the observed buffering effect by biocrust-forming lichens, as they are known to be negatively affected by warming. Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-022-00779-0.

Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development.

Development of multicellular organisms is orchestrated by persistent cell-cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell-cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell-cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.

B-Lines Lung Ultrasonography Simulation Using Finite Element Method.

INTRODUCTION: Lung Ultrasonography (LUS) is a fast technique for the diagnosis of patients with respiratory syndromes. B-lines are seen in response to signal reverberations and amplifications into sites with peripheral lung fluid concentration or septal thickening. Mathematical models are commonly applied in biomedicine to predict biological responses to specific signal parameters. OBJECTIVE: This study proposes a Finite-Element numerical model to simulate radio frequency ultrasonic lines propagated from normal and infiltrated lung structures. For tissue medium, a randomized inhomogeneous data method was used. The simulation implemented in COMSOL® used Acoustic Pressure and Time-Explicit models, which are based on the discontinuous Galerkin method (dG). RESULTS: The RF signals, processed in MATLAB®, resulted in images of horizontal A-lines and vertical B-lines, which were reasonably similar to real images. DISCUSSION: The use of inhomogeneous materials in the model was good enough to simulate the scattering response, similar to others in the literature. The model is useful to study the impact of the lung infiltration characteristics on the appearance of LUS images.

Spontaneous transitions between amoeboid and keratocyte-like modes of migration.

The motility of adherent eukaryotic cells is driven by the dynamics of the actin cytoskeleton. Despite the common force-generating actin machinery, different cell types often show diverse modes of locomotion that differ in their shape dynamics, speed, and persistence of motion. Recently, experiments in Dictyostelium discoideum have revealed that different motility modes can be induced in this model organism, depending on genetic modifications, developmental conditions, and synthetic changes of intracellular signaling. Here, we report experimental evidence that in a mutated D. discoideum cell line with increased Ras activity, switches between two distinct migratory modes, the amoeboid and fan-shaped type of locomotion, can even spontaneously occur within the same cell. We observed and characterized repeated and reversible switchings between the two modes of locomotion, suggesting that they are distinct behavioral traits that coexist within the same cell. We adapted an established phenomenological motility model that combines a reaction-diffusion system for the intracellular dynamics with a dynamic phase field to account for our experimental findings.

Adaptation to environmental temperature in divergent clades of the nematode Pristionchus pacificus.

Because of ongoing climate change, populations of organisms are being subjected to stressful temperatures more often. This is especially problematic for ectothermic organisms, which are likely to be more sensitive to changes in temperature. Therefore, we need to know if ectotherms have adapted to environmental temperature and, if so, what are the evolutionary mechanisms behind such adaptation. Here, we use the nematode Pristionchus pacificus as a case study to investigate thermal adaptation on the Indian Ocean island of La Réunion, which experiences a range of temperatures from coast to summit. We study the evolution of high-temperature tolerance by constructing a phylogenetic tree of strains collected from many different thermal niches. We show that populations of P. pacificus at low altitudes have higher fertility at warmer temperatures. Most likely, this phenotype has arisen recently and at least twice independently, consistent with parallel evolution. We also studied low-temperature tolerance and showed that populations from high altitudes have increased their fertility at cooler temperatures. Together, these data indicate that P. pacificus strains on La Réunion are subject to divergent selection, adapting to hot and cold niches at the coast and summit of the volcano. Precisely defining these thermal niches provides essential information for models that predict the impact of future climate change on these populations.

Awake Percutaneous Fixation for Unstable Fractures of the Spine in High-risk Patients: A Retrospective Study.

INTRODUCTION: Unstable fractures in sick or elderly patients are on the rise. These patients who are at high risk for surgery present a challenge for surgeons and anesthesiologists. In patients with American Society of Anesthesiologists (ASA) scores 3 to 4, the risk is even higher because of the high rate of intraoperative complications. METHODS: All patients with ASA scores 3 to 4 who presented with unstable fractures of the spine to a level-one trauma center were assessed, and they underwent awake spinal percutaneous fixation, with mild sedation and local anesthesia. Demographics, radiology, and the outcome were collected. RESULTS: Nineteen patients were operated between the years 2019 and 2021. Average follow-up was 12 months (range 8 to 24 months); six patients were female and 13 males. The average age was 77.7 years; the ASA score was 3 to 4 in all patients. There were 10 extension-type injuries, six unstable burst injuries, two chance fractures, and one teardrop fracture. All patients underwent unilateral fixation, and just one patient underwent bilateral fixation; cement augmentation was done in 16 of the patients. No neurologic complication was observed. One case of infection presented 4 months after surgery. All patients were discharged ambulating. CONCLUSIONS: Awake fixation in extreme cases is safe and feasible; a dedicated team including an anesthesiologist and radiologist is needed to treat these cases safely and quickly.

Pulmonary hypertension in adults with congenital heart disease. Clinical phenotypes and outcomes in the advanced pulmonary vasodilator era.

BACKGROUND: Mortality of pulmonary hypertension associated with congenital heart disease (PAH-CHD) in adults remains high. OBJECTIVES: To identify predictors of death and to assess the impact of treatment on outcome. METHODS: Retrospective, multicenter cohort study of 103 adults with PAH-CHD followed-up for 8.6 ± 4.6 years. Patients were grouped according to underlying shunt type into pre-tricuspid, post-tricuspid and complex. Survival rates were analyzed and predictors of death were investigated with Cox regression models. RESULTS: In the post-tricuspid and complex groups (38 and 37 patients, respectively), the most common clinical PAH-CHD subgroup was Eisenmenger syndrome (76.3% and 59.5%, respectively) whereas, in the pre-tricuspid group (28 patients), 46.5% of patients had small or corrected defects. Overall, 88 patients received vasodilators; 39% required combination-therapy. Overall survival at 10 years was 65%. Mortality was highest in the pre-tricuspid group, FC-III-IV and amongst patients receiving monotherapy (p < 0.050). On multivariate analysis, predictors of poor outcome were pericardial effusion (HR: 4,520 [1,470-13,890]; p = 0,008), oxygen saturation(HR: 0.940 [0,900 - 0,990]; p = 0,018) and genetic syndromes(HR: 3,280 [1,098-9,780]; p = 0,033). CONCLUSIONS: Patients in advanced stages at initiation of treatment were at high risk of death and strong consideration should be given for more aggressive therapy.

Occurrence records and metadata for sand flies (Diptera, Psychodidae, Phlebotominae) collected in the lands of indigenous people in the Brazilian Amazon.

To contribute to knowledge of the epidemiology of American cutaneous leishmaniasis (ACL) among indigenous people living in sylvatic regions, we studied the sand fly fauna collected in areas of disease transmission in the Brazilian Amazon. Here we report two datasets comprising occurrence data for sand flies from the Suruwaha Indigenous Land in the state of Amazonas collected in 2012-2013, and the Wajãpi Indigenous Land in the state of Amapá collected in 2013-2014. Sand flies were collected using unbaited CDC-like light traps at various sites within each study area and were identified to either genus or species-level by taxonomists with expertise in Amazonian fauna. A total of 4,646 records are reported: 1,428 from the Suruwaha and 3,218 from the Wajãpi. These records will contribute to a better understanding of ACL transmission dynamics, as well as the distribution of insect vectors, in these areas.

Flower lose, a cell fitness marker, predicts COVID-19 prognosis.

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e.g., death and hospitalization) in COVID-19 patients. We performed a post-mortem examination of infected lung tissue in deceased COVID-19 patients to determine hFwe-Lose's biological role in acute lung injury. We then performed an observational study (n = 283) to evaluate whether hFwe-Lose expression (in nasopharyngeal samples) could accurately predict hospitalization or death in COVID-19 patients. In COVID-19 patients with acute lung injury, hFwe-Lose is highly expressed in the lower respiratory tract and is co-localized to areas of cell death. In patients presenting in the early phase of COVID-19 illness, hFwe-Lose expression accurately predicts subsequent hospitalization or death with positive predictive values of 87.8-100% and a negative predictive value of 64.1-93.2%. hFwe-Lose outperforms conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) 0.93-0.97 in predicting hospitalization/death. Specifically, this is significantly higher than the prognostic value of combining biomarkers (serum ferritin, D-dimer, C-reactive protein, and neutrophil-lymphocyte ratio), patient age and comorbidities (AUROC of 0.67-0.92). The cell fitness marker, hFwe-Lose, accurately predicts outcomes in COVID-19 patients. This finding demonstrates how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID-19 pandemic.

Enhanced Performance of Zn/Br Flow Battery Using N-Methyl-N-Propylmorpholinium Bromide as Complexing Agent.

Redox flow batteries (RFB) are one of the most interesting technologies in the field of energy storage, since they allow the decoupling of power and capacity. Zinc-bromine flow batteries (ZBFB) are a type of hybrid RFB, as the capacity depends on the effective area of the negative electrode (anode), on which metallic zinc is deposited during the charging process. Gaseous bromine is generated at the positive electrode (cathode) during the charging process, so the use of bromine complexing agents (BCA) is very important. These BCAs are quaternary amines capable of complexation with bromine and generating an organic phase, immiscible with the aqueous electrolyte. One of the most commonly used BCAs in RFB technology is 4-methylethylmorpholinium bromide (MEM-Br). In this work, an alternative quaternary amine 4-methylpropylmorpholinium bromide (MPM-Br) was studied. MPM-Br was integrated into the electrolyte, and 200 charge-discharge cycles were performed on the resulting ZBFBs. The obtained results were compared with those when MEM-Br was used, and it was observed that the electrolyte with MPM-Br displays a higher resistance in voltage and higher energy efficiency, making it a promising alternative to MEM-Br.

Cell competition in intratumoral and tumor microenvironment interactions.

Tumors are complex cellular and acellular environments within which cancer clones are under continuous selection pressures. Cancer cells are in a permanent mode of interaction and competition with each other as well as with the immediate microenvironment. In the course of these competitive interactions, cells share information regarding their general state of fitness, with less-fit cells being typically eliminated via apoptosis at the hands of those cells with greater cellular fitness. Competitive interactions involving exchange of cell fitness information have implications for tumor growth, metastasis, and therapy outcomes. Recent research has highlighted sophisticated pathways such as Flower, Hippo, Myc, and p53 signaling, which are employed by cancer cells and the surrounding microenvironment cells to achieve their evolutionary goals by means of cell competition mechanisms. In this review, we discuss these recent findings and explain their importance and role in evolution, growth, and treatment of cancer. We further consider potential physiological conditions, such as hypoxia and chemotherapy, that can function as selective pressures under which cell competition mechanisms may evolve differently or synergistically to confer oncogenic advantages to cancer.

Cell competition from development to neurodegeneration.

Cell competition is a process by which suboptimal cells are eliminated to the benefit of cells with higher fitness. It is a surveillance mechanism that senses differences in the fitness status by several modes, such as expression of fitness fingerprints, survival factor uptake rate and resistance to mechanical stress. Fitness fingerprints-mediated cell competition recognizes isoforms of the transmembrane protein Flower, and translates the relative fitness of cells into distinct fates through the Flower code. Impairments in cell competition potentiate the development of diseases like cancer and ageing-related pathologies. In cancer, malignant cells acquire a supercompetitor behaviour, killing the neighbouring cells and overtaking the tissue, thus avoiding elimination. Neurodegenerative disorders affect millions of people and are characterized by cognitive decline and locomotor deficits. Alzheimer's disease is the most common form of dementia, and one of the largely studied diseases. However, the cellular processes taking place remain unclear. Drosophila melanogaster is an emerging neurodegeneration model due to its versatility as a tool for genetic studies. Research in a Drosophila Alzheimer's disease model detected fitness markers in the suboptimal and hyperactive neurons, thus establishing a link between cell competition and Alzheimer's disease. In this Review, we overview cell competition and the new insights related to neurodegenerative disorders, and discuss how research in the field might contribute to the development of new therapeutic targets for these diseases.

Evaluation of the Technical Viability of Distributed Mechanical Recycling of PLA 3D Printing Wastes.

3D printing PLA wastes were recovered from a well-known reference grade and from different sources. The recovered wastes were subjected to an energic washing step and then reprocessed into films by melt-extrusion, followed by compression molding to simulate the industrial processing conditions. The obtained materials were characterized and the optical, structural, thermal and crystallization behavior are reported. The mechanical recycling process leads to an increase of the crystallinity and a decrease of the intrinsic viscosity of the formulations, particularly in the sample based on blends of different 3D-PLA wastes. Moreover, the obtained films were disintegrated under composting conditions in less than one month and it was observed that recycled materials degrade somewhat faster than the starting 3D-PLA filament, as a consequence of the presence of shorter polymer chains. Finally, to increase the molecular weight of the recycled materials, the 3D-PLA wastes were submitted to a solid-state polymerization process at 110, 120, and 130 °C, observing that the recycled 3D-wastes materials based on a well-known reference grade experiences an improvement of the intrinsic viscosity, while that coming from different sources showed no significant changes. Thus, the results show that 3D printing PLA products provides an ideal environment for the implementation of distributed recycling program, in which wastes coming from well-known PLA grades can successfully be processed in films with good overall performance.

Role of cell competition in ageing.

Recent advances in rapid medical detection and diagnostic technology have extended both human health and life expectancy. However, ageing remains one of the critical risk factors in contributing to major incapacitating and fatal conditions, including cancer and neurodegeneration. Therefore, it is vital to study how ageing attributes to (or participates in) endangering human health via infliction of age-related diseases and what must be done to tackle this intractable process. This review encompasses the most recent literature elaborating the role of cell competition (CC) during ageing. CC is a process that occurs between two heterogeneous populations, where the cells with higher fitness levels have a competitive advantage over the neighbouring cells that have comparatively lower fitness levels. This interaction results in the selection of the fit cells, within a population, and elimination of the viable yet suboptimal cells. Therefore, it is tempting to speculate that, if this quality control mechanism works efficiently throughout life, can it ultimately lead to a healthier ageing and extended lifespan. Furthermore, the review aims to collate all the important state of the art publications that provides evidence of the relevance of CC in dietary restriction, stem cell dynamics, and cell senescence, thus, prompting us to advocate its contribution and in exploring new avenues and opportunities in fighting age-related conditions.

Cell Competition Boosts Clonal Evolution and Hypoxic Selection in Cancer.

The comparison of fitness between cells leads to the elimination of less competent cells in the presence of more competent neighbors via cell competition (CC). This phenomenon has been linked with several cancer-related genes and thus may play an important role in cancer. Various processes are involved in the regulation of tumor initiation and growth, including tumor hypoxia, clonal stem cell selection, and immune cell response, all of which have been recently shown to have a potential connection with the mechanisms involved in CC. This review aims to unravel the relation between these processes and competitive cell interactions and how this affects disease progression.