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Introduction: Previous studies link higher degree of negativity in the news to cynicism and indifference of citizens towards politics and politicians (theory of Spiral of Cynicism). Methods: We content-analyzed 563 news pieces of 10 Spanish media (3 newspapers, 2 TV stations and 5 online media). The degree of negativity was measured through a negativity index, conformed by indicators of tonality, conflict, incapability and unfavorability, proposed by Leanguer, Esser and Berganza. (2012). Results and conclusions: Data confirmed that Spanish media depict political news in a negative way, although levels of negativity were lower than those of other European countries. A higher degree of negativity was found in items related to controversial topics, produced in formats of higher implication, and published by private, print or traditional media. [ABSTRACT FROM AUTHOR]

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner., Methods: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples., Results: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients)., Conclusions: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome., (© 2024. The Author(s).)

Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N -oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.

Background: In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed., Results: IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20-40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs., Conclusions: The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA)., (© 2024. The Author(s).)

In vitro maturation (IVM) of oocytes is clinically used in horses to produce blastocysts but current conditions used for horses are suboptimal. We analyzed the composition of equine preovulatory follicular fluid (FF) secretome and tested its effects on meiotic competence and gene expression in oocytes subjected to IVM. Preovulatory FF was obtained, concentrated using ultrafiltration with cut-off of 10 kDa, and stored at -80 °C. The metabolic and proteomic composition was analyzed, and its ultrastructural composition was assessed by cryo-transmission microscopy. Oocytes obtained post-mortem or by ovum pick up (OPU) were subjected to IVM in the absence (control) or presence of 20 or 40 μg/ml (S20 or S40) of secretome. Oocytes were then analyzed for chromatin configuration or snap frozen for gene expression analysis. Proteomic analysis detected 255 proteins in the Equus caballus database, mostly related to the complement cascade and cholesterol metabolism. Metabolomic analysis yielded 14 metabolites and cryo-transmission electron microscopy analysis revealed the presence of extracellular vesicles (EVs). No significant differences were detected in maturation rates among treatments. However, the expression of GDF9 and BMP15 significantly increased in OPU-derived oocytes compared to post-mortem oocytes (fold increase ± SEM: 9.4 ± 0.1 vs. 1 ± 0.5 for BMP15 and 9.9 ± 0.3 vs. 1 ± 0.5 for GDF9, respectively; p < 0.05). Secretome addition increased the expression of TNFAIP6 in S40 regardless of the oocyte source. Further research is necessary to fully understand whether secretome addition influences the developmental competence of equine oocytes., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions and a dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes to therapeutic resistance. However, within the heterogeneous CAF population, fibroblast activation protein (FAP) emerges as a promising target for Gallium-68 FAP inhibitor positron emission tomography (Ga68FAPI-PET) imaging. Notably, 68Ga-FAPI-PET demonstrates promising diagnostic sensitivity and specificity, especially in conjunction with low tracer uptake in non-tumoral tissues. Moreover, it provides valuable insights into tumor-stroma interactions, a critical aspect of PDAC tumorigenesis not adequately visualized through conventional methods. The clinical implications of this innovative imaging modality extend to its potential to reshape treatment strategies by offering a deeper understanding of the dynamic TME. However, while the potential of 68Ga-FAPI-PET is evident, ongoing correlative studies are essential to elucidate the full spectrum of CAF heterogeneity and to validate its impact on PDAC management. This article provides a comprehensive review of CAF heterogeneity in PDAC and explores the potential impact of 68Ga-FAPI-PET on disease management.

Background: Blood biomarkers can improve the ability to diagnose dementia, providing new information to better understand the pathophysiology and causes of the disease. Some studies with patients have already shown changes in metabolic profiles among patients with pathological cognitive decline or Alzheimer's disease, when compared to individuals with normal cognition., Methods: To search for new metabolic biomarkers of dementia, we analyzed serum levels of several metabolites, measured by nuclear magnetic resonance spectroscopy, in elderly individuals, a group with normal cognitive decline (control), and three other groups with cognitive decline. pathological (low, moderate, and severe)., Results: Decreased plasma levels of tyrosine, glutamate, valine, leucine, and isoleucine are associated with worsening of pathological cognitive decline. However, the area under analysis of receptor operating characteristics suggests that tyrosine and glutamate have low specificity and sensitivity. Valine, leucine, and isoleucine are influenced by blood glucose or diabetes, but these conditions do not seem to be of great influence in the differences observed. Isobutyrate, histidine, acetone and unknown-1 metabolite also decrease their plasma levels with increasing CD. Isobutyrate ad histidine could have neuroprotective and antioxidant actions, respectively. To elucidate the role of decreased unknown metabolite-1 as a CD biomarker, it will be necessary to previously investigate its identity. To define and elucidate the role of acetone in pathological CD, additional laboratory and clinical studies must be performed. All these metabolites together may constitute a set of biomarkers with capability to identify pathological CD or dementia., Significance and Novelty: Decrease of glutamate, tyrosine, valine, leucine, isoleucine, histidine, isobutyrate, acetone and unknown-1 metabolite together are a set of biomarkers able to identify pathological CD or dementia. Histidine, isobutyrate, acetone and unknown-1 metabolite are more specific biomarkers of CD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Hidradenitis suppurativa is a chronic inflammatory disease which affects apocrine glands and hair follicles of the skin, primarily in the axillary and groin regions. This condition can be highly debilitating, causing painful lesions and a negative psychological impact on patients. While medical and minimally invasive treatments are available, surgical intervention may be necessary for severe cases. In cases involving axillary defects, the use of local flaps such as the parascapular flap is a viable option. In this case report, we present a 34-year-old woman who presented to our clinic with a history of recurrent abscesses and cutaneous infections in the axillary region. After thorough evaluation, we chose to use the parascapular flap for reconstruction. The parascapular flap is a one-stage procedure that allows for extensive resection of the axillary area without resulting in contractions or retractions over the long term. Additionally, this technique allows for preservation of the axilla's original shape with minimal donor site morbidity., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Circulating cytokines could be optimal biomarkers for prognostication and management decisions in colorectal cancer (CRC). Chemorefractory CRC patients with available plasma samples were included in this study. In the discovery cohort ( n = 85), 182 circulating cytokines were tested with a semi-quantitative multiplex assay, and prognostic cytokines were analyzed in the validation cohort ( n = 111) by ELISA. Overall survival (OS) was the primary outcome measure, with the false discovery rate (FDR) method (significance level of <0.01) being used to correct for multiple comparisons. Four cytokines were associated with OS in the discovery cohort: insulin-like growth factor-binding protein 1 (IGFBP-1) (HR 2.1 [95%CI: 1.58-2.79], FDR < 0.001), insulin-like growth factor-binding protein 2 (IGFBP-2) (HR 1.65 [95%CI: 1.28-2.13], FDR = 0.006), serum amyloid A (SAA) (HR 1.84 [95%CI: 1.39-2.43], FDR < 0.001), and angiotensin II (HR 1.65 [95%CI: 1.29-2.1], FDR = 0.006). Of these, IGFBP-1 (HR 2.70 [95%CI: 1.56-4.76], FDR = 0.007) and IGFBP-2 (HR 3.33 [95%CI: 1.64-6.67], FDR = 0.008) were confirmed to be independently associated with OS in the validation cohort. Patients with high concentrations of IGFBP-1 and/or IGFBP-2 had a median OS of 3.0 months as compared with 6.9 months for those with low concentrations of both cytokines (HR 2.44 [95%CI: 1.52-4.0], FDR = 0.002) Validation of circulating IGFBP-1 and IGFBP-2 as independent prognostic biomarkers for chemorefractory CRC in larger, independent series is warranted.

Introduction: The New Zealand (NZ) Central Region Stroke Network, serving 1.17 million catchment population, changed to tenecteplase for stroke thrombolysis in 2020 but was forced to revert to Alteplase in 2021 due to a sudden cessation of drug supply. We used this unique opportunity to assess for potential before and after temporal trend confounding., Patients and Methods: In NZ all reperfused patients are entered prospectively into a national database for safety monitoring. We assessed Central Region patient outcomes and treatment metrics over three time periods: alteplase use (January 2018-January 2020); during switch to tenecteplase (February 2020-February 2021) and after reverting to alteplase (February 2021-December 2022) adjusting regression analyses for hospital, age, onset-to-needle, NIHSS, pre-morbid mRS and thrombectomy., Results: Between January 2018 and December 2022, we treated 1121 patients with Alteplase and 286 with tenecteplase. Overall, patients treated with tenecteplase had greater odds of favorable outcome ordinal mRS [aOR = 1.43 (95% CI = 1.11-1.85)]; shorter door-to-needle (DTN) time [median 52 (IQR 47-83) vs 61 (45-84) minutes, p  < 0.0001] and needle to groin (NTG) times [118 (74.5-218.5) vs 185 (118-255); p  = 0.02)]. Symptomatic intracerebral hemorrhage (sICH) rate was lower in tenecteplase group [aOR 0.29 (0.09-0.95)]. Findings similarly favored tenecteplase when comparing tenecteplase to only the second alteplase phase. There was no inter-group difference when comparing the two alteplase phases., Conclusions: Our results suggest that previously reported benefits from tenecteplase in a real-world setting were not likely attributable to a temporal confounding., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors., Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05., Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival ( p = 0.043), but not with respect to overall survival ( p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes ( p = 0.012), perineural invasion ( p = 0.004) and tumour differentiation grade ( p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion., Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Introduction: In 2017, the Spanish National Polytrauma Registry (SNPR) was initiated in Spain with the goal to improve the quality of severe trauma management and evaluate the use of resources and treatment strategies. The objective of this study is to present the data obtained with the SNPR since its inception., Methods: We conducted an observational study with prospective data collection from the SNPR. The trauma patients included were over 14 years of age, with ISS ≥ 15 or penetrating mechanism of injury, from a total of 17 tertiary hospitals in Spain., Results: From 1/1/17 to 1/1/22, 2069 trauma patients were registered. The majority were men (76.4%), with a mean age of 45 years, mean ISS 22.8, and mortality 10.2%. The most common mechanism of injury was blunt trauma (80%), the most frequent being motorcycle accident (23%). Penetrating trauma was presented in 12% of patients, stab wounds being the most common (84%). On hospital arrival, 16% of patients were hemodynamically unstable. The massive transfusion protocol was activated in 14% of patients, and 53% underwent surgery. Median hospital stay was 11 days, while 73.4% of patients required intensive care unit (ICU) admission, with a median ICU stay of 5 days., Conclusions: Trauma patients registered in the SNPR are predominantly middle-aged males who experience blunt trauma with a high incidence of thoracic injuries. Early addressed detection and treatment of these kind of injuries would probably improve the quality of trauma care in our environment., (Copyright © 2023 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Different populations of plant species can adapt to their local pollinators and diverge in floral traits accordingly. Floral traits are subject to pollinator-driven natural selection to enhance plant reproductive success. Studies on temperate plant systems have shown pollinator-driven selection results in floral trait variation along elevational gradients, but studies in tropical systems are lacking. We analyzed floral traits and pollinator assemblages in the Neotropical bee-pollinated taxon Costus guanaiensis var. tarmicus across four sites along a steep elevational gradient in Peru. We found variations in floral traits of size, color, and reward, and in the pollinator assemblage along the elevational gradient. We examined our results considering two hypotheses, (1) local adaptation to different bee assemblages, and (2) the early stages of an evolutionary shift to a new pollinator functional group (hummingbirds). We found some evidence consistent with the adaptation of C. guanaiensis var. tarmicus to the local bee fauna along the studied elevational gradient. Corolla width across sites was associated with bee thorax width of the local most frequent pollinator. However, we could not rule out the possibility of the beginning of a bee-to-hummingbird pollination shift in the highest-studied site. Our study is one of the few geographic-scale analyses of floral trait and pollinator assemblage variation in tropical plant species. Our results broaden our understanding of plant-pollinator interactions beyond temperate systems by showing substantial intraspecific divergence in both floral traits and pollinator assemblages across geographic space in a tropical plant species., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Purpose: Over the last decade, immune checkpoint inhibitors (ICI) have emerged as cornerstone in the treatment of many metastatic tumour types, including gastrointestinal cancers. In many solid tumours, the effective therapies in the metastatic field are progressively brought into the curative setting. Consequently, earlier tumoural settings have become a field of experiment for immunotherapies. In melanoma, lung, and bladder cancers, excellent results were recorded, possibly explained by differences in the tumour microenvironment between metastatic and non-metastatic settings. In gastrointestinal (GI) Oncology, nivolumab is the first immune checkpoint inhibitor to become a standard-of-care adjuvant treatment after curative surgery for oesophagal or gastroesophageal junction cancer., Recent Findings: We herein discuss the results of a selection of the most relevant studies presented/published over the last 18 months testing immunotherapies in non-metastatic GI cancers. Among immunotherapies, ICI have been investigated in pre-, peri- and postoperative setting across tumour types, alone or in combination with chemo- and/or radiotherapy. Vaccines are also a new field of investigation., Summary: Promising results from two studies (NCT04165772 and NICHE-2 study) demonstrating never-seen-before responses to neoadjuvant immunotherapy in MMR deficient (dMMR) colorectal cancers raise hope for improving the patients' outcome and developing organ-sparing strategies in this situation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

(1) Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the first two decades of life. One third of cases appear in the head and neck, with 60% of these being embryonal type. RMS is extremely rare in adults, comprising only 1% of adult malignancies, and of those, only 3.3% are rhabdomyosarcomas. (2) Case report: A 46 y.o. male presented with a 1 cm exophytic pediculated painless lesion on the dorsum of his tongue, with progressive growth for 3 months. An excisional biopsy revealed an "embryonal rhabdomyosarcoma with fusocellular areas, with negative rearrangement for gen FOXO1A, negative MDM2 (only focal positivity), and positive INI-1". Subsequent contrast-enhanced MRI concluded the presence of a lesion with imprecise margins in the right half-tongue, 15 × 8 × 7 mm (longitudinal × transverse × craniocaudal), compatible with a sarcoma. The patient underwent a partial centrolingual glossectomy followed by reconstruction with a buccinator muscle local flap. After surgery, he received chemotherapy with eight cycles of VAC (vincristine, actinomycin, and cyclophosphamide) protocol. The patient is now disease free after 42 months, with good tongue function. (3) Discussion and conclusions: Embryonal RMS is an extremely rare sarcoma in adults, and the location in the tongue is even more exceptional (only two more similar cases are reported in the literature). The prognosis in adults is significantly poorer than in children. A complete margin-free resection with an adequate chemotherapy protocol is the treatment of choice in cases such as these.