Compositionally unique mitochondria in filopodia support cellular migration.

Local metabolic demand within cells varies widely and the extent to which individual mitochondria can be specialized to meet these functional needs is unclear. We examined the subcellular distribution of MICOS, a spatial and functional organizer of mitochondria, and discovered that it dynamically enriches at the tip of a minor population of mitochondria in the cell periphery that we term "METEORs". METEORs have a unique composition; MICOS enrichment sites are depleted of mtDNA and matrix proteins and contain high levels of the Ca2+ uniporter MCU, suggesting a functional specialization. METEORs are also enriched for the myosin MYO19, which promotes their trafficking to a small subset of filopodia. We identify a positive correlation between the length of filopodia and the presence of METEORs and show that elimination of mitochondria from filopodia impairs cellular motility. Our data reveal a novel type of mitochondrial heterogeneity and suggest compositionally specialized mitochondria support cell migration.

A supervised multiclass framework for mineral classification of Iberian beads.

Research on personal adornments depends on the reliable characterisation of materials to trace provenance and model complex social networks. However, many analytical techniques require the transfer of materials from the museum to the laboratory, involving high insurance costs and limiting the number of items that can be analysed, making the process of empirical data collection a complicated, expensive and time-consuming routine. In this study, we compiled the largest geochemical dataset of Iberian personal adornments (n = 1243 samples) by coupling X-ray fluorescence compositional data with their respective X-ray diffraction mineral labels. This allowed us to develop a machine learning-based framework for the prediction of bead-forming minerals by training and benchmarking 13 of the most widely used supervised algorithms. As a proof of concept, we developed a multiclass model and evaluated its performance on two assemblages from different Portuguese sites with current mineralogical characterisation: Cova das Lapas (n = 15 samples) and Gruta da Marmota (n = 10 samples). Our results showed that decisión-tres based classifiers outperformed other classification logics given the discriminative importance of some chemical elements in determining the mineral phase, which fits particularly well with the decision-making process of this type of model. The comparison of results between the different validation sets and the proof-of-concept has highlighted the risk of using synthetic data to handle imbalance and the main limitation of the framework: its restrictive class system. We conclude that the presented approach can successfully assist in the mineral classification workflow when specific analyses are not available, saving time and allowing a transparent and straightforward assessment of model predictions. Furthermore, we propose a workflow for the interpretation of predictions using the model outputs as compound responses enabling an uncertainty reduction approach currently used by our team. The Python-based framework is packaged in a public repository and includes all the necessary resources for its reusability without the need for any installation.

Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.

Studying essential genes required for dynamic processes in live mice is challenging as genetic perturbations are irreversible and limited by slow protein depletion kinetics. The first-generation auxin-inducible-degron (AID) system is a powerful tool for analyzing inducible protein loss in cultured cells. However, auxin administration is toxic to mice, preventing its long-term use in animals. Here, we use an optimized second-generation AID system to achieve the conditional and reversible loss of the essential centrosomal protein CEP192 in live mice. We show that the auxin derivative 5-Ph-IAA is well tolerated over two weeks and drives near-complete CEP192-mAID degradation in less than one hour in vivo. Prolonged CEP192 loss led to cell division failure and cell death in proliferative tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice, offering a valuable new tool for interrogating protein function in vivo.

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

Association of intrinsic capacity with functional decline and mortality in older adults: a systematic review and meta-analysis of longitudinal studies.

BACKGROUND: Together with environmental factors, intrinsic capacity (the composite of all the physical and mental capacities of an individual) has been proposed as a marker of healthy ageing. However, whether intrinsic capacity predicts major clinical outcomes is unclear. We aimed to explore the association of intrinsic capacity with functional decline and mortality in older adults. METHODS: In this systematic review and meta-analysis, we conducted a systematic search in MEDLINE (via PubMed), Scopus, and Web of Science from database inception to Feb 14, 2024, of observational longitudinal studies conducted in older adults (age ≥60 years) assessing the association of intrinsic capacity with impairment in basic activities of daily living (BADL) or instrumental activities of daily living (IADL) or risk of mortality. Estimates were extracted by two reviewers (JLS-S and W-HL) and were pooled using three-level meta-analytic models. The quality of each study was independently assessed by two authors (JLS-S and PLV) using the Newcastle-Ottawa Scale for longitudinal studies. Heterogeneity was evaluated using the I2 indicator at two levels: within-study (level 2) and between-study (level 3) variation. For associations between intrinsic capacity and IADL and BADL, we transformed data (standardised ß coefficients and odds ratios [ORs]) into Pearson product moment correlation coefficients (r) using Pearson and Digby formulas to allow comparability across studies. For associations between intrinsic capacity and risk of mortality, hazard ratios (HRs) with 95% CIs were extracted from survival analyses. This study is registered with PROSPERO, CRD42023460482. FINDINGS: We included 37 studies (206 693 participants; average age range 65·3-85·9 years) in the systematic review, of which 31 were included in the meta-analysis on the association between intrinsic capacity and outcomes; three studies (2935 participants) were included in the meta-analysis on the association between intrinsic capacity trajectories and longitudinal changes in BADL or IADL. Intrinsic capacity was inversely associated with longitudinal impairments in BADL (Pearson's r -0·12 [95% CI -0·19 to -0·04]) and IADL (-0·24 [-0·35 to -0·13]), as well as with mortality risk (hazard ratio 0·57 [95% CI 0·51 to 0·63]). An association was also found between intrinsic capacity trajectories and impairment in IADL (but not in BADL), with maintained or improved intrinsic capacity over time associated with a lower impairment in IADL (odds ratio 0·37 [95% CI 0·19 to 0·71]). There was no evidence of publication bias (Egger's test p>0·05) and there was low between-study heterogeneity (I2=18·4%), though within-study (I2=63·2%) heterogeneity was substantial. INTERPRETATION: Intrinsic capacity is inversely associated with functional decline and mortality risk in older adults. These findings could support the use of intrinsic capacity as a marker of healthy ageing, although further research is needed to refine the structure and operationalisation of this construct across settings and populations. FUNDING: None. TRANSLATIONS: For the Spanish and French translations of the abstract see Supplementary Materials section.

Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Patient Safety and Satisfaction With Fully Remote Management of Radiation Oncology Care.

Importance: Patients of Memorial Sloan Kettering Cancer Center in New York, New York, are now offered a choice of either in-person or remote telehealth visits for radiation oncology care. However, safety and satisfaction among patients receiving treatment with fully remote physician management is unclear. Objective: To analyze patient safety and satisfaction, financial implications, and environmental consequences associated with fully remote management among a cohort of patients treated with radiotherapy. Design, Setting, and Participants: This single-institution retrospective cohort study was performed at Memorial Sloan Kettering Cancer Center, with patients treated with radiation who opted for fully remote management between October 1, 2020, and October 31, 2022. Data on patient safety events were prospectively collected with an in-house quality improvement reporting system. Patient satisfaction surveys were distributed electronically before, during, and after treatment. Patient transportation costs and environmental consequences were estimated based on differences in travel distance. Data analysis was performed from March 14 through September 19, 2023. Exposure: Radiotherapy with fully remote physician management. Main Outcomes and Measures: Satisfaction rates among patients opting for fully remote management were analyzed via surveys administered electronically after visits with clinicians. Patient safety events, defined as staff-reported actual events and near misses that had the potential to affect patient care, were reviewed. Rates and types of safety events were analyzed and compared with patients treated by onsite clinicians. Distances between patient home zip codes and treatment site locations were compared with estimated cost savings and decreased emissions. Results: This study included 2817 patients who received radiation oncology care with fully remote physician management. The median age of patients was 65 (range, 9-99) years, and more than half were men (1467 [52.1%]). Of the 764 safety events reported, 763 (99.9%) did not reach patients or caused no harm to patients. Nearly all survey respondents (451 [97.6%]) rated patient satisfaction as good to very good across all domains. For treatment with fully remote physician management, out-of-pocket cost savings totaled $612 912.71 ($466.45 per patient) and decreased carbon dioxide emissions by 174 metric tons. Conclusions and Relevance: In this study, radiation oncology care provided by fully remote clinicians was safe and feasible, with no serious patient events. High patient satisfaction, substantial cost savings, and decreased environmental consequences were observed. These findings support the continuation of a fully remote management option for select patients in the post-COVID-19 era.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center.

Importance: Insurance barriers to cancer care can cause significant patient and clinician burden. Objective: To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants: In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure: Insurance denial for RT. Main Outcomes and Measures: Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. Results: A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance: In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Prognostic Implications of Small Cell Lung Cancer Transcriptional Subtyping for CNS Metastases.

PURPOSE: Small cell lung cancer (SCLC) often metastasizes to the brain and has poor prognosis. SCLC subtypes distinguished by expressing transcriptional factors ASCL1 or NEUROD1 have been identified. This study investigates the impact of transcription factor-defined SCLC subtype on incidence and outcomes of brain metastases (BMs). METHODS: Patients with SCLC with ASCL1 (A) and NEUROD1 (N) immunohistochemical expression status were identified and classified: (1) A+/N-, (2) A+/N+, (3) A-/N+, and (4) A-/N-. Cumulative incidence competing risk analyses were used to assess incidence of CNS progression. Cox proportional hazards models were used for multivariable analyses of overall survival (OS) and CNS progression-free survival (CNS-PFS). RESULTS: Of 164 patients, most were either A+/N- or A+/N+ (n = 62, n = 63, respectively). BMs were present at diagnosis in 24 patients (15%). Among them, the 12-month cumulative incidence of subsequent CNS progression was numerically highest for A+/N- (50% [95% CI, 10.5 to 74.7]; P = .47). Among those BM-free at diagnosis, the 12-month cumulative incidence of CNS progression was numerically the highest for A+/N- (16% [95% CI, 7.5 to 27.9]) and A-/N+ (9.1% [95% CI, 0.0 to 34.8]; P = .20). Both subtypes, A+/N- and A-/N+, had worse OS compared with A+/N+ (A+/N-: hazard ratio [HR], 1.62 [95% CI, 1.01 to 2.51]; P < .05; A-/N+: HR, 3.02 [95% CI, 1.35 to 6.76]; P = .007). Excellent response rates (28, 65% CR/PR) across subtypes were seen in patients who had CNS-directed radiotherapy versus systemic therapy alone (9, 36% CR/PR). CONCLUSION: To our knowledge, this report is the first to investigate CNS-specific outcomes based on transcription factor subtypes in patients with SCLC. BM-free patients at diagnosis with A+/N- or A-/N+ subtypes had worse outcomes compared with those with transcriptional factor coexpression. Further investigation into the mechanisms and implications of SCLC subtyping on CNS-specific outcomes is warranted to ultimately guide personalized care.

Genomic analyses of a new baculovirus isolated from the wheat armyworm, Mythimna sequax (Franclemont) (Lepidoptera: Noctuidae).

We report the genomic analysis of a novel alphabaculovirus, Mythimna sequax nucleopolyhedrovirus isolate CNPSo-98 (MyseNPV-CNPSo-98), obtained from cadavers of the winter crop pest, Mythimna sequax Franclemont (Lepidoptera: Noctuidae). The insects were collected from rice fields in Southern Brazil in the 1980's and belongs to the 'EMBRAPA-Soja' Virus Collection. High-throughput sequencing reads of DNA from MyseNPV occlusion bodies and assembly of the data yielded an AT-rich circular genome contig of 148,403 bp in length with 163 annotated opening reading frames (ORFs) and four homologous regions (hrs). Phylogenetic inference based on baculovirus core protein sequence alignments indicated that MyseNPV-CNPSo-98 is a member of Alphabaculovirus genus that clustered with other group II noctuid-infecting baculoviruses, including viruses isolated from Helicoverpa armigera and Mamestra spp. The genomes of the clade share strict collinearity and high pairwise nucleotide identity, with a common set of 149 genes, evolving under negative selection, except a bro gene. Branch lengths and Kimura-2-parameter pairwise nucleotide distances indicated that MyseNPV-CNPSo-98 represents a distinct lineage that may not be classified in any of the currently listed species in the genus.

Biomarkers associated with pulmonary exacerbations in a randomized trial of nintedanib for radiation pneumonitis.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a common side effect of thoracic radiotherapy and often has a long course characterized by acute exacerbations and progression to permanent lung fibrosis. There are no validated biomarkers of prognosis in patients diagnosed with RP. MATERIALS AND METHODS: We analyzed a time course of serum chemokines, cytokines, and other proteins from patients with grade 2+ RP in a randomized clinical trial of a steroid taper plus nintedanib, a multiple tyrosine kinase inhibitor, versus placebo plus a steroid taper for the treatment of RP. Weighted gene correlation network analysis (WGCNA) and univariable zero inflated Poisson models were used to identify groups of correlated analytes and their associations with clinical outcomes. RESULTS: Thirty enrolled patients had biomarker data available, and 17 patients had enough analytes tested for network analysis. WGNCA identified ten analytes, including transforming growth factor beta-1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), and platelet-derived growth factor (PDGF), that in aggregate were correlated with the occurrence of pulmonary exacerbations (p = 0.008), the total number of acute pulmonary exacerbations (p = 0.002), and treatment arm (p = 0.036). By univariable analysis, an increase in rate of change of two components of the RP module were associated with an increased incidence rate of pulmonary exacerbations: interleukin 5 (IL-5, incidence rate ratio (IRR) 1.02, 95% CI 1.01-1.04, p = 0.002), and tumor necrosis factor superfamily 12 (TNFSF12, IRR 1.06, CI 1-1.11, p = 0.036). An increased slope of epidermal growth factor (EGF) was associated with a decreased incidence rate of exacerbations (IRR 0.94, CI 0.89-1, p = 0.036). CONCLUSION: We identified a panel of serum biomarkers that showed association with nintedanib treatment and acute pulmonary exacerbations in patients with RP. A confirmatory study will be needed to validate this panel for use as a prognostic tool in patients with RP.

Exclusive breastfeeding greater than 50%, success of education in a university hospital in Bogotá: Case-control study.

BACKGROUND: Maintenance rates of exclusive breastfeeding (EBF) worldwide are low, thus, one of the objectives of the summary of policies on breastfeeding (BF) in world nutrition goals for 2025 are that at least 50% of infants under six months of age receive EBF that year. The Objective of this study is to document the rates of EBF in children born in San Ignacio University Hospital (HUSI) and identify factors associated with maintenance. AIM: To document the percentages of EBF in those that were born at HUSI and identify factors associated to their maintenance. METHODS: This is a study of cases and controls in an analytic, retrospective cohort that took children born alive between January 2016 and January 2019 at HUSI located in the city of Bogotá, Colombia. RESULTS: Receiving information about BF at HUSI was able to maintain EBF up until 4 mo (OR = 1.65; 95%CI: 1.02-2.66). The presence of gynecologic and obstetric comorbidities (OR = 0.32; 95%CI: 0.12-0.83), having mastitis (OR = 0.56; 95%CI: 0.33-0.94), and receiving information from mass media (OR = 0.52; 95%CI: 0.31-0.84) are factors associated with not maintaining EBF. CONCLUSION: Receiving education at a Women- and Child-Friendly Institution was the only significant factor to achieve EBF until 4 mo, with a frequency greater than the one reported in the country, which matches multiple studies where counseling and individualized support on BF achieve this purpose. Knowledge about BF and early detection of obstetric/gynecologic complications must be strengthened among the healthcare staff in charge of mothers during post-partum. Additionally, strategies must be promoted to continue BF such as creating milk banks with the objective of increasing BF rates even when mothers return to work.

Valvulitis: a new echocardiographic criterion for the diagnosis of bioprosthetic aortic valve infective endocarditis.

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

An 18F-FDG PET/CT and Mean Lung Dose Model to Predict Early Radiation Pneumonitis in Stage III Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Immunotherapy.

Radiation pneumonitis (RP) that develops early (i.e., within 3 mo) (RPEarly) after completion of concurrent chemoradiation (cCRT) leads to treatment discontinuation and poorer survival for patients with stage III non-small cell lung cancer. Since no RPEarly risk model exists, we explored whether published RP models and pretreatment 18F-FDG PET/CT-derived features predict RPEarly Methods: One hundred sixty patients with stage III non-small cell lung cancer treated with cCRT and consolidative immunotherapy were analyzed for RPEarly Three published RP models that included the mean lung dose (MLD) and patient characteristics were examined. Pretreatment 18F-FDG PET/CT normal-lung SUV featured included the following: 10th percentile of SUV (SUVP10), 90th percentile of SUV (SUVP90), SUVmax, SUVmean, minimum SUV, and SD. Associations between models/features and RPEarly were assessed using area under the receiver-operating characteristic curve (AUC), P values, and the Hosmer-Lemeshow test (pHL). The cohort was randomly split, with similar RPEarly rates, into a 70%/30% derivation/internal validation subset. Results: Twenty (13%) patients developed RPEarly Predictors for RPEarly were MLD alone (AUC, 0.72; P = 0.02; pHL, 0.87), SUVP10, SUVP90, and SUVmean (AUC, 0.70-0.74; P = 0.003-0.006; pHL, 0.67-0.70). The combined MLD and SUVP90 model generalized in the validation subset and was deemed the final RPEarly model (RPEarly risk = 1/[1+e(- x )]; x = -6.08 + [0.17 × MLD] + [1.63 × SUVP90]). The final model refitted in the 160 patients indicated improvement over the published MLD-alone model (AUC, 0.77 vs. 0.72; P = 0.0001 vs. 0.02; pHL, 0.65 vs. 0.87). Conclusion: Patients at risk for RPEarly can be detected with high certainty by combining the normal lung's MLD and pretreatment 18F-FDG PET/CT SUVP90 This refined model can be used to identify patients at an elevated risk for premature immunotherapy discontinuation due to RPEarly and could allow for interventions to improve treatment outcomes.

Clinical Profile and Prognosis of Patients with Left-Sided Infective Endocarditis with Surgical Indication Who Are Not Operated.

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

Genetic diversity of the entomopathogenic fungus Metarhizium rileyi based on de novo microsatellite markers.

Epizootics of the entomopathogenic fungus Metarhizium rileyi regulate lepidopteran populations in soybean, cotton, and peanut agroecosystems to the point that insecticide applications could be unnecessary. However, the contribution and how different strains operate during the epizootic are unknown. Several unanswered questions remain: 1. How many genotypes of M. rileyi are present during an epizootic? 2. Which genotype is the most common among them? 3. Are the genotypes involved in annual epizootics at the same location the same? Therefore, the development of molecular markers to accurately identify these genotypes is very important to answer these questions. SSR primers were designed by prospecting in silico to discriminate genotypes and infer the genetic diversity of M. rileyi isolates from the collection kept at Embrapa Soybean. We tested 13 SSR markers on 136 isolates to identify 43 clones and 12 different genetic clusters, with genetic diversity ranging from Hs = 0.15 (cluster I) to Hs = 0.41 (cluster IV) and an average diversity of 0.24. No clusters were categorically distinguished based on hosts or geographical origin using Bayesian clustering analysis. Nonetheless, some clusters comprised most of the isolates with a common geographic origin; for example, cluster VIII was mainly composed of isolates from Central-western Brazil, cluster II from Southern Brazil, and cluster XII from Quincy, Northern Florida, in the United States. Underrepresented regions (few isolates) from Pacific Island nations of Japan, the Philippines, and Indonesia (specifically from Java) were placed into clusters IX and X. Although the analyzed isolates displayed evidence of clonal structure, the genetic diversity indices suggest a potential for the species to adapt to different environmental conditions.

Association of physical behaviours with sarcopenia in older adults: a systematic review and meta-analysis of observational studies.

BACKGROUND: Physical behaviours (ie, physical activity and sedentary behaviour) might have a role in the development of sarcopenia, although the evidence is unclear. We aimed to explore the association of total and intensity-specific levels of physical activity and sedentary behaviour with sarcopenia and its components (ie, muscle mass, muscle strength, and physical performance) in older adults. METHODS: We conducted a systematic review and meta-analysis and searched MEDLINE (via PubMed), Scopus, and Web of Science from inception to July 26, 2022, for peer-reviewed, observational studies or baseline data from randomised clinical trials conducted in older adults (ie, individual age ≥60 years or mean age ≥65 years) and published in English that reported on the association of physical activity or sedentary behaviour or both with sarcopenia (or its determinants: muscle mass or strength, and physical performance). Physical activity and sedentary behaviour were measured by any method. The main outcome was sarcopenia, which could be diagnosed by any means. Estimates were extracted and pooled using Bayesian meta-analytic models and publication bias was assessed using the Egger's test. This study is registered with PROSPERO, CRD42022315865. FINDINGS: We identified 15 766 records, of which 124 studies (230 174 older adults; 121 301 [52·7%] were female and 108 873 [47·3%] were male) were included in the systematic review. 86 studies were subsequently included in the meta-analysis. Higher levels of total physical activity were inversely associated with sarcopenia both cross-sectionally (21 studies, n=59 572; odds ratio 0·49, 95% credible interval 0·37-0·62) and longitudinally (four studies, n=7545; 0·51, 0·27-0·94). A protective association was also identified for moderate-to-vigorous physical activity in cross-sectional research (five studies, n=6787; 0·85, 0·71-0·99), whereas no association was identified for the remaining physical behaviours (ie, steps, light physical activity, or sedentary behaviour). INTERPRETATION: Total and moderate-to-vigorous physical activity are inversely associated with sarcopenia. These findings might support the importance of moderate-to-vigorous, rather than light, intensity physical activity-based interventions to prevent sarcopenia. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Regional differences in infective endocarditis epidemiology and outcomes in Spain. A contemporary population-based study.

INTRODUCTION AND OBJECTIVES: Our aim was to describe the contemporary epidemiological profile of infective endocarditis (IE) in Spain, and to evaluate variations in IE incidence, characteristics, and outcomes among the different Spanish regions (autonomous communities [AC]). METHODS: We conducted a retrospective, population-based study, using data obtained from national in-patient hospital activity of all patients discharged with a diagnosis of IE from hospitals included in the Spanish National Health System, from January 2016 to December 2019. Differences in the IE profile between the 17 Spanish AC were analyzed. RESULTS: A total of 9008 hospitalization episodes were identified during the study period. Standardized incidence of IE was 5.77 (95%CI, 5.12-6.41) cases per 100 000 population. Regarding predisposing conditions, 26.8% of episodes occurred in prosthetic valve carriers, 36.8% had some kind of valve heart disease, and 10.6% had a cardiac implantable electronic device. Significant differences were found between AC in terms of incidence, predisposing conditions, and microbiological profile. Cardiac surgery was performed in 19.3% of episodes in the total cohort, and in 33.4% of the episodes treated in high-volume referral centers, with wide variations among AC. Overall in-hospital mortality was 27.2%. Risk-adjusted mortality rates also varied significantly among regions. CONCLUSIONS: We found wide heterogeneity among Spanish AC in terms of incidence rates and the clinical and microbiological characteristics of IE episodes. The proportion of patients undergoing surgery was low and in-hospital mortality rates were high, with wide differences among regions. The development of regional networks with referral centers for IE could facilitate early surgery and improve outcomes.

What exercise programme is the most appropriate to mitigate anterior cruciate ligament injury risk in football (soccer) players? A systematic review and network meta-analysis.

OBJECTIVES: To examine the effectiveness of different exercise-based interventions to mitigate the risk of anterior cruciate ligament injury in football players, and to determine which is the most appropriate for them, specifically for female football players. DESIGN: Four databases were accessed in July 2023 using the keywords football, soccer, athletic injuries, anterior cruciate ligament, knee injuries, injury prevention, exercise-based programme, and risk factor. METHODS: Randomised controlled trials that evaluated any exercise-based injury prevention intervention compared with a control group on the prevention of anterior cruciate ligament injury in football players were included. RESULTS: Eleven studies were included. Data were presented as logarithm hazard ratio, credible intervals and standard deviation. FIFA 11+ was the most effective in reducing anterior cruciate ligament injury risk in football players (logarithm hazard ratio = -1.23 [95% credible intervals: -2.20, -0.35]; SD = 0.47), followed by the Knäkontroll programme (logarithm hazard ratio = -0.76 [95% credible intervals: -1.60, -0.03]; standard deviation = 0.42). For females, only Knäkontroll had a significant impact on reducing the risk of anterior cruciate ligament injury (logarithm hazard ratio = -0.62 [95% credible intervals: -1.71, 0.62]; standard deviation = 0.58). CONCLUSIONS: Our results support the use of FIFA 11+ and Knäkontroll to mitigate injury incidence at overall level. However, the effectiveness of these interventions changed when adjusting for females. Knäkontroll is postulated as the programme with the greatest preventive nature, although these results should be interpreted with caution due to the lack of the sample.