Glass-like Relaxation Dynamics during the Disorder-to-Order Transition of Viral Nucleocapsids.

Nucleocapsid self-assembly is an essential yet elusive step in virus replication. Using time-resolved small-angle X-ray scattering on a model icosahedral ssRNA virus, we reveal a previously unreported kinetic pathway. Initially, RNA-bound capsid subunits rapidly accumulate beyond the stoichiometry of native virions. This is followed by a disorder-to-order transition characterized by glass-like relaxation dynamics and the release of excess subunits. Our molecular dynamics simulations, employing a coarse-grained elastic model, confirm the physical feasibility of self-ordering accompanied by subunit release. The relaxation can be modeled by an exponential integral decay on the mean squared radius of gyration, with relaxation times varying within the second range depending on RNA type and subunit concentration. A nanogel model suggests that the initially disordered nucleoprotein complexes quickly reach an equilibrium size, while their mass fractal dimension continues to evolve. Understanding virus self-assembly is not only crucial for combating viral infections, but also for designing synthetic virus-inspired nanocages for drug delivery applications.

Nonsurgical Rhinoplasty after Rhinoplasty: A Systematic Review of the Technique, Results, and Complications.

Introduction: Surgical rhinoplasty is a complex procedure with a high revision rate. Nonsurgical rhinoplasty (NSR) could avoid secondary rhinoplasty allowing the correction of postsurgical defects. A systematic review has been performed among adult patients who had previously undergone surgical rhinoplasty and now presenting for NSR with filler, demonstrated most common indications, fillers, and complications in this technique. Materials and Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) system guidelines. Primary outcomes included indications for NSR in patients with prior rhinoplasty and complication rate. Secondary outcomes included filler material and degree of patient satisfaction. Results: Twenty articles met the inclusion criteria, obtaining 2,048 patients analyzed in the review. Hyaluronic acid was the most used filler, found in 67% of patients. Indications were highly variable, considering deformities of the middle third of the nose the most remarkable. A high degree of satisfaction was found in the analyzed studies and the rate of major complications was low. Discussion and Conclusions: NSR in patients with prior rhinoplasty is a useful option for correcting a range from subtle aesthetic defects to severe nasal deformities. However, this technique is not exempt from complications, since an increased risk of skin necrosis has been observed.

In vivo measurements of change in tissue oxygen level during irradiation reveal novel dose rate dependence.

BACKGROUND AND PURPOSE: This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates. MATERIALS AND METHODS: Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s. RESULTS: Radiation-induced change in tissue oxygenation (ΔpO2) increased linearly with dose and correlated with baseline tissue oxygenation levels in the range of 0 - 30 mmHg. At higher baseline tissue oxygenation levels, such as those observed in muscle and brain, there was no corresponding increase in ΔpO2. When we modulated dose rate, ΔpO2 increased steeply up to âˆ¼ 20 Gy/s and plateaued thereafter. The relationship between ΔpO2 and dose rate showcases the interplay between ROD and reoxygenation. CONCLUSION: While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants.

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Angle-Resolved Linear Dichroism to Probe the Organization of Highly Ordered Collagen Biomaterials.

Controlling the assembly of high-order structures is central to soft-matter and biomaterial engineering. Angle-resolved linear dichroism can probe the ordering of chiral collagen molecules in the dense state. Collagen triple helices were aligned by solvent evaporation. Their ordering gives a strong linear dichroism (LD) that changes sign and intensity with varying sample orientations with respect to the beam linear polarization. Being complementary to circular dichroism, which probes the structure of chiral (bio)molecules, LD can shift from the molecular to the supramolecular scale and from the investigation of the conformation to interactions. Supported by multiphoton microscopy and X-ray scattering, we show that LD provides a straightforward route to probe collagen alignment, determine the packing density, and monitor denaturation. This approach could be adapted to any assembly of chiral (bio)macromolecules, with key advantages in detecting large-scale assemblies with high specificity to aligned and chiral molecules and improved sensitivity compared to conventional techniques.

PSGL-1, ADAM8, and selectins as potential biomarkers in the diagnostic process of systemic lupus erythematosus and systemic sclerosis: an observational study.

Background: Early diagnosis and treatment of Systemic lupus erythematosus (SLE) and Systemic sclerosis (SSc) present significant challenges for clinicians. Although various studies have observed changes in serum levels of selectins between healthy donors and patients with autoimmune diseases, including SLE and SSc, their potential as biomarkers has not been thoroughly explored. We aimed to investigate serum profiles of PSGL-1 (sPSGL-1), ADAM8 (sADAM8) and P-, E- and L-selectins (sP-, sE- and sL-selectins) in defined SLE and SSc patient cohorts to identify disease-associated molecular patterns. Methods: We collected blood samples from 64 SLE patients, 58 SSc patients, and 81 healthy donors (HD). Levels of sPSGL-1, sADAM8 and selectins were analyzed by ELISA and leukocyte membrane expression of L-selectin and ADAM8 by flow cytometry. Results: Compared to HD, SLE and SSc patients exhibited elevated sE-selectin and reduced sL-selectin levels. Additionally, SLE patients exhibited elevated sPSGL-1 and sADAM8 levels. Compared to SSc, SLE patients had decreased sL-selectin and increased sADAM8 levels. Furthermore, L-selectin membrane expression was lower in SLE and SSc leukocytes than in HD leukocytes, and ADAM8 membrane expression was lower in SLE neutrophils compared to SSc neutrophils. These alterations associated with some clinical characteristics of each disease. Using logistic regression analysis, the sL-selectin/sADAM8 ratio in SLE, and a combination of sL-selectin/sE-selectin and sE-selectin/sPSGL-1 ratios in SSc were identified and cross-validated as potential serum markers to discriminate these patients from HD. Compared to available diagnostic biomarkers for each disease, both sL-selectin/sADAM8 ratio for SLE and combined ratios for SSc provided higher sensitivity (98% SLE and and 67% SSc correctly classified patients). Importantly, the sADAM8/% ADAM8(+) neutrophils ratio discriminated between SSc and SLE patients with the same sensitivity and specificity than current disease-specific biomarkers. Conclusion: SLE and SSc present specific profiles of sPSGL-1, sE-, sL-selectins, sADAM8 and neutrophil membrane expression which are potentially relevant to their pathogenesis and might aid in their early diagnosis.

Complete Blood Count Values Over Time in Young Children During the Dengue Virus Epidemic in the Dominican Republic From 2018 to 2020.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings.

Retinochoroidal Vascular Changes in Long-Term Type 1 Diabetic Patients Assessed by Optic Coherence Tomography Angiography.

To study retinal and choriocapillaris (CC) alterations using optical coherence tomography angiography (OCTA) in long-term type 1 diabetic (DM1) patients without diabetic retinopathy (DR). Seventy-eight eyes from 78 well-controlled DM1 patients diagnosed at least 15 years prior and 130 eyes of 130 healthy subjects were included in a cross-sectional descriptive study. Six eyes were excluded from the DM1 group. OCTA with Deep Range Imaging (DRI)-Triton swept source (SS)-OCT was performed. Statistically significant differences were found in all areas of the superficial capillary plexus (SCP), with lower values in DM1 patients. Differences were noted in all quadrants of the deep capillary plexus (DCP) except for the central area. Significant changes in CC blood flow were only found in the center. The foveal avascular zone (FAZ) area and diameters in the SCP were significantly different, while the DCP FAZ area was similar in both groups. Disease duration and microalbuminuria correlated negatively with some SCP areas and positively with FAZ values. Anatomical evaluation revealed microaneurysms in both plexuses, FAZ modifications, and areas lacking blood perfusion. Long-term type 1 diabetic patients without DR display microvascular abnormalities affecting retinal and CC blood perfusion, along with anatomical changes in retinal blood vessels.

Regulation of monocyte apoptosis and DNA extrusion in monocyte extracellular traps by PSGL-1: Relevance in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by severe organ damage and lacking curative treatment. While various immune cell types, especially dysfunctional B and T cells and neutrophils, have been related with disease pathogenesis, limited research has focused on the role of monocytes in SLE. Increased DNA extracellular traps, apoptosis and necrosis have been related to lupus pathogenesis. Our goal is to analyze the contribution of P-selectin glycoprotein ligand 1 (PSGL-1) in SLE monocytes to disease pathogenesis by investigating the control exerted by PSGL-1 on monocyte apoptosis and DNA extrusion in extracellular traps (METs). Monocytes from active disease patients (aSLE) exhibited reduced levels of PSGL-1. Importantly, lower PSGL-1 levels in SLE monocytes associated with several clinical characteristics, including anti-dsDNA autoantibodies, lupus anticoagulant, clinical lung involvement, and anemia. Monocytes from SLE patients showed higher susceptibility to apoptosis than healthy donors (HD) monocytes and PSGL-1/P-selectin interaction decreased secondary necrosis in HD but not in aSLE monocytes. Regarding METs, aSLE monocytes exhibited higher susceptibility to generate METs than HD monocytes. The interaction of HD monocytes with P-selectin induced Syk activation and reduced the levels of DNA extruded in METs. However, in aSLE monocytes, PSGL-1/P-selectin interaction did not activate Syk or reduce the amount of extruded DNA. Our data suggest a dysfunctional PSGL-1/P-selectin axis in aSLE monocytes, unable to reduce secondary necrosis or the amount of DNA released into the extracellular medium in METs, potentially contributing to lupus pathogenesis.

A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

Reproducible protocol for the extraction and semi-automated quantification of macroscopic charcoal from soil.

Charcoal fragments preserved in soils or sediments are used by scientists to reconstruct fire histories and thereby improve our understanding of past vegetation dynamics and human-plant relationships. Unfortunately, most published methods for charcoal extraction and analysis are incompletely described and are therefore difficult to reproduce. To improve the standardization and replicability of soil charcoal analysis, as well as to facilitate accessibility for non-experts, we developed a detailed, step-by-step protocol to isolate charcoal from soil and to efficiently count and measure charcoal fragments. The extraction phase involves the chemical soaking and wet sieving of soils followed by the collection of macrocharcoal (≥500 µm). The analysis phase is performed semi-automatically using the open-source software ImageJ to count and measure the area, length, and width of fragments from light stereo microscope images by means of threshold segmentation. The protocol yields clean charcoal fragments, a set of charcoal images, and datasets containing total charcoal mass, number of fragments, and morphological measurements (area, length, and width) for each sample. We tested and validated the protocol on 339 soil samples from tropical savannas and forests in eastern lowland Bolivia. We hope that this protocol will be a valuable resource for scientists in a variety of fields who currently study, or wish to study, macroscopic charcoal in soils as a proxy for past fires.

Association between widespread pain and psychosocial factors in people with knee osteoarthritis: a cross-sectional study of patients from primary care in Denmark.

INTRODUCTION: The relationship between psychosocial factors and bodily pain in people with knee osteoarthritis (KOA) is unclear. PURPOSE: To examine whether widespread pain was associated with poorer self-efficacy, more anxiety, depression, and kinesiophobia in people with KOA. METHODS: This was a cross-sectional study based on data from Good Life with osteoArthritis in Denmark (GLA:D®). The association between widespread pain (multiple pain sites) and self-efficacy (Arthritis Self-Efficacy Scale), anxiety and depression (item from the EQ-5D-5 L), and kinesiophobia (yes/no) was examined using multiple linear tobit or logistic regression models. RESULTS: Among 19,323 participants, 10% had no widespread pain, 37% had 2 pain sites, 26% had 3-4 pain sites, and 27% had ≥5 pain sites. Widespread pain was associated with poorer self-efficacy (-0.9 to -8.3 points), and the association was stronger with increasing number of pain sites (p-value <.001). Significant increasing odds ratios (ORs) were observed for having anxiety or depression with 3-4 pain sites (OR 1.29, 95% CI 1.12; 1.49) and ≥5 pain sites (OR 1.80, 95% CI 1.56; 2.07). Having 2 and 3-4 pain sites were associated with lower odds of kinesiophobia compared to having no widespread pain. CONCLUSION: Widespread pain was associated with lower self-efficacy and more anxiety and depression but also lower kinesiophobia in people with KOA.

Destructuration of Canola Protein Gels during In Situ Gastrointestinal Digestion Studied by X-ray Scattering.

We are studying the destructuration of canola protein gels, as a solid food model, during in situ gastrointestinal digestion using synchrotron small-angle X-ray scattering (SAXS). Digestion of two gels, prepared by heating pH 8 and pH 11 solutions, was carried out by diffusion of enzymatic juices into the gel from the top of the capillary and monitored for several tens of hours. Very similar time evolutions of SAXS curves occur at different positions of the gel in the capillary, with a delay determined by the distance from the surface initially in contact with the digestive juice. The main phenomena observed are (i) at the scale of the protein conformation (1-5 nm). The scattering curve is a power law, the exponent of which measures the compactness (related to the degree of unfolding). It can be plotted as a function of the characteristic size of proteins/and interprotein distances and as a function of the scattering intensity. Such diagrams clearly show successive digestion processes. For the pH 11 gel, in which proteins are initially hardly unfolded, the digestive processes are unfolding (1st step), recompaction-aggregation phenomena (2nd step) due to gastrointestinal pH conditions and enzymatic cleavage, further unfolding-disaggregation (3rd step), and final protein cleavage (4th step) down to small peptides. For the pH 8 gel, proteins are initially unfolded, and only the last three steps are observed, showing the influence of easier access for the enzymes. (ii) At the scale of large aggregates (10-50 nm), we observe for both gels a decrease in the size and/or number of these aggregates during digestion and alteration of their interfaces. (iii) At the scale of the secondary protein structure, wide-angle X-ray scattering is very useful for detecting the degradation of the secondary protein structure at different steps of digestion.

Transfer Learning with Active Sampling for Rapid Training and Calibration in BCI-P300 Across Health States and Multi-centre Data.

Machine learning and deep learning advancements have boosted Brain-Computer Interface (BCI) performance, but their wide-scale applicability is limited due to factors like individual health, hardware variations, and cultural differences affecting neural data. Studies often focus on uniform single-site experiments in uniform settings, leading to high performance that may not translate well to real-world diversity. Deep learning models aim to enhance BCI classification accuracy, and transfer learning has been suggested to adapt models to individual neural patterns using a base model trained on others' data. This approach promises better generalizability and reduced overfitting, yet challenges remain in handling diverse and imbalanced datasets from different equipment, subjects, multiple centres in different countries, and both healthy and patient populations for effective model transfer and tuning. In a setting characterized by maximal heterogeneity, we proposed P300 wave detection in BCIs employing a convolutional neural network fitted with adaptive transfer learning based on Poison Sampling Disk (PDS) called Active Sampling (AS), which flexibly adjusts the transition from source data to the target domain. Our results reported for subject adaptive with 40% of adaptive fine-tuning that the averaged classification accuracy improved by 5.36% and standard deviation reduced by 12.22% using two distinct, internationally replicated datasets. These results outperformed in classification accuracy, computational time, and training efficiency, mainly due to the proposed Active Sampling (AS) method for transfer learning.

Inter- and intra-observer variation in phytolith morphometry.

BACKGROUND: Archaeobotanists and palaeoecologists extensively use geometric morphometrics to identify plant opal phytoliths. Particularly when applied to assemblages of phytoliths from concentrations retrieved from closed contexts, morphometric data from archaeological phytoliths compared with similar data from reference material may allow taxonomic attribution. Observer variation is one aspect of phytolith morphometry that has received little attention but may be an important source of error, and hence cause of potential misidentification of plant remains. SCOPE: To investigate inter- and intra-observer variation in phytolith morphometry, eight researchers (observers) from different laboratories measured 50 samples each from three phytolith morphotypes, Bilobate, Bulliform flabellate and Elongate dendritic, three times, under the auspices of the International Committee for Phytolith Morphometrics (ICPM). METHODS: Data for 17 size and shape variables were collected for each phytolith by manually digitising a phytolith outline (mask) from a photograph, followed by measurement of the mask with open-source morphometric software. KEY RESULTS: Inter-observer variation ranged from 0 to 23% difference from the mean of all observers. Intra-observer variation ranged from 0 to 9% difference from the mean of individual observers per week. Inter- and intra-observer variation was generally higher among inexperienced researchers. CONCLUSIONS: Scaling errors were a major cause of variation and occurred more with less experienced researchers, which is likely related to familiarity with data collection. The results indicate that inter- and intra-observer variation can be substantially reduced by providing clear instructions for and training with the equipment, photo capturing, software, data collection and data cleaning. In this paper, the ICPM provides recommendations to minimise variation.Advances in automatic data collection may eventually reduce inter- and intra-observer variation, but until this is common practice, the ICPM recommends that phytolith morphometric analyses adhere to standardised guidelines to assure that measured phytolith variables are accurate, consistent and comparable between different researchers and laboratories.

Interrogating a Compound Library in Search of an Inhibitor for TREM-like Transcript-1 to Fibrinogen Binding.

Cardiovascular disease (CVD) remains one of leading causes of death worldwide. Aberrant platelet function mediate fibrin(ogen) rich thrombi that lead to occlusive thrombi associated with mortality. The receptor, TREM-like transcript-1 (TLT-1), stored in the platelet a-granules and released upon platelet activation, binds fibrinogen and von Willebrand factor. Once it is released from platelets TLT-1 is a potential therapeutic target to prevent the thrombosis associated with CVD. Here we design an assay to screen a compound library of small molecules inhibitors. HEK-293 cells stably transfected with a full length human treml-1 construct were used to screen library of 800 compounds, for inhibition of TLT-1 to fibrinogen binding in an attachment assay using crystal violet staining. The possible cytotoxicity of the best compounds was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide MTT and calcein AM staining assays. Here we demonstrate that the addition of TLT-1 to HEK-293 cells increases cell adhesion by more than 2-fold. We identified ~80 compounds that inhibit binding by more than 80%. We further tested the top compounds and confirmed that reduction of hTLT-1 to fibrinogen bound in the top compounds was not caused by cytotoxicity, as per colorimetric and fluorescent viability assays. Four compounds were identified as potential small molecule inhibitors one of which, BM-8372, demonstrated significant effect in platelet aggregation assays. Significance Statement TLT-1 is a key platelet receptor that binds fibrinogen and mediates clot formation The developed assay successfully screens 800 small molecules, pinpointing ~80 potent inhibitors that reduce TLT-1 binding by over 80%. Importantly, the study rigorously rules out cytotoxicity concerns, affirming the therapeutic potential of the identified compounds. By elucidating TLT-1's role and presenting promising inhibitors, this research offers a significant stride toward developing novel strategies to combat CVD-related thrombosis.

Risk of prostate cancer in the proximity of industrial installations: A multicase-control study in Spain (MCC-Spain).

BACKGROUND: Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified. OBJECTIVE: To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain). METHODS: This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables. RESULTS: No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air. CONCLUSIONS: The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.

Marginal changes at bone-level implants supporting dental prostheses with or without intermediate standardised abutments after 36 months: Randomised controlled clinical trial.

OBJECTIVE: The objective of this study is to evaluate the changes at marginal bone level at implants restored with screw-retained prosthesis connected directly to the implants or with an intermediate abutment, after 3-year follow-up. MATERIAL AND METHODS: Thirty-six partially edentulous patients received 72 implants. Each patient received 2 implants and a 2-4-unit screw-retained implant-prosthesis. The test group implants received a screw-retained prosthesis connected directly to the implant shoulder, the control group prosthesis were connected through a 3-mm standardised intermediate abutment. Clinical and radiological data were recorded at baseline and at 6-, 12-, and 36-month follow-up. RESULTS: At 36 months, the mean marginal bone loss was 0.13 ± 0.18 mm for the control group and 0.20 ± 0.24 for the test group, with no significant differences between groups (p > .05). Clinical variables (Probing Pocket Depth, Bleeding on Probing and Plaque Index) at 36 months also showed no significant difference between groups. Minor complications frequency was 6.7% in the control group and 5.3% in test group. None of the groups suffered from mayor complications. Patient Reported Outcomes (PROs) showed a General Satisfaction mean score in the control group of 9.40 (SD 0.82) and 9.37 (SD 1.06) in the test group with no significant differences between groups. CONCLUSIONS: Bone-level implants restored with screw-retained partial prostheses with or without intermediate abutments showed similar radiographic and clinical outcomes after 3 years.

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer with PD-L1 ≥ 1 %: A subgroup analysis from the EMPOWER-Lung 3 part 2 trial.

OBJECTIVES: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, assessed cemiplimab (anti-programmed cell death protein 1) plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 aberrations, regardless of histology or PD-L1 expression levels. We report results from subgroup analysis of patients with PD-L1 expression ≥ 1 %. MATERIALS AND METHODS: Patients were randomized to receive cemiplimab 350 mg or placebo with chemotherapy every 3 weeks for up to 108 weeks. Overall survival (OS), progression-free survival (PFS), overall response rates (ORRs), patient-reported outcomes (PROs), and safety were assessed. RESULTS: Of the 327 patients with PD-L1 ≥ 1 % (466 in the overall study), 217 received cemiplimab plus chemotherapy and 110 received chemotherapy alone. After median follow-up of 28.0 months, median OS for cemiplimab plus chemotherapy was 23.5 months (95 % confidence interval [CI]: 20.9-27.2) vs. 12.1 months (95 % CI: 10.1-15.7) for chemotherapy alone (hazard ratio [HR] = 0.51, 95 % CI: 0.38-0.69, P < 0.0001); median PFS was 8.3 months (95 % CI: 6.7-10.8) versus 5.5 months (95 % CI: 4.3-6.2; HR = 0.48; 95 % CI: 0.37-0.62, P < 0.0001), and ORR was 47.9 % versus 22.7 %, respectively. PRO results favored cemiplimab plus chemotherapy over chemotherapy alone. Improved efficacy over chemotherapy alone was observed in both squamous and non-squamous histology. Safety was consistent with previous reports. CONCLUSION: In this subgroup analysis from EMPOWER-Lung 3 part 2, cemiplimab plus chemotherapy demonstrated clinical benefit over chemotherapy alone in patients with advanced squamous or non-squamous NSCLC with PD-L1 ≥ 1 %.

Shared Decision-making in Breast Cancer Reconstructive Surgery: Experience in a Leading Hospital.

Background: The paradigm of healthcare has evolved toward patient-centered approaches, where shared decision-making (SDM) plays a pivotal role. This study aimed to explore the implementation of SDM during breast cancer reconstruction consultations and assess its impact on patient satisfaction and the decision-making process as a whole. Methods: A total of 102 female patients undergoing breast reconstruction were included in a multidisciplinary breast pathology unit. A streamlined SDM model involving choice introduction, option description, and preference exploration was implemented. A validated Spanish version of the nine-item Shared Decision Making Questionnaire was used alongside a complementary questionnaire. Data analysis was carried out using electronic data capture software. Results: The nine-item Shared Decision Making Questionnaire results indicate strong agreement in presenting various options and explaining their advantages and disadvantages. Patients were less confident about their participation in decision-making. The Complementary Shared Decision Making Questionnaire highlighted high satisfaction with interview times and language clarity but areas for improvement in consultation space and therapeutic choice participation. Conclusions: Integrating SDM into breast reconstruction consultations empowers patients in the decision-making process and enhances satisfaction. Decision aids prove effective in this context, facilitating patients' comprehension and reducing decisional conflict. There are areas for improvement within the SDM strategy, and they are detectable through scales. Although challenges in information transmission and patient involvement persist, adopting an SDM model has potential benefits that warrant further investigation.