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Cervical cancer is a significant public health issue in Mexico and many developing countries. Early detection is crucial for combating this disease. The official screening test for cervical cancer is cytology, but this technique faces several barriers, including methodological, educational, and sociocultural challenges. Liquid-based cytology is an improved version of this test, however it does not address the aforementioned complications. Biomarkers for cervical precursor lesions and cervical cancer can improve timely detection of the disease. A previous study from our group identified four circulating human proteins as potential biomarkers for these conditions. For molecular screening, we selected GAPDH as the biomarker for cervical precursor lesions and HNRNPA1 as the biomarker for cervical cancer -chosen from the three previously identified options based on antibody availability- to be detected in sera. Participants underwent a comprehensive panel of tests, including liquid-based cytology, PCR detection of Human papillomavirus (HPV), colposcopy, and histopathology -when applicable-. The last two tests were used as references for determining sensitivity and specificity, with histopathology being the gold standard for cervical cancer diagnosis. All the participants successfully received colposcopies (n = 99) and only those women with visible or suspected cervical lesions/malignancies were biopsied (n = 62). A subset of randomly selected biopsies underwent p16INK4a immunohistochemistry (n = 36). This study compares the performance of liquid-based cytology with the molecular screening. With colposcopy as reference, liquid-based cytology showed 30% sensitivity and 96% specificity, while the molecular screening showed 90% sensitivity and 43% specificity. With histopathology as reference, liquid-based cytology showed 21% sensitivity and 93% specificity, while the molecular screening showed 85% sensitivity and 61% specificity. The molecular screening outperformed the liquid-based cytology in several areas, including detecting true-positive cases, reducing false-negative cases by 34.62%, application time, simplicity of result´s categories, and acceptance among participants. An ideal screening test requires high sensitivity, maintains moderate specificity, and minimizes false negatives. Our proposed screening test meets these criteria, making it an ideal complement -or alternative- for cervical cancer screening.

ABSTRACT Limiting the availability of transition metals at infection sites serves as a critical defense mechanism employed by the innate immune system to combat microbial infections. Pseudomonas aeruginosa exhibits a remarkable ability to thrive in zinc-deficient environments, facilitated by intricate cellular responses governed by numerous genes regulated by the zinc-responsive transcription factor Zur. Many of these genes have unknown functions, including those within the predicted PA2911-PA2914 and PA4063-PA4066 operons. A structural bioinformatics investigation revealed that PA2911-PA2914 comprises a TonB-dependent outer membrane receptor and inner membrane ABC-permeases responsible for importing metal-chelating molecules, whereas PA4063-PA4066 contains genes encoding a MacB transporter, likely involved in the export of large molecules. Molecular genetics and biochemical experiments, feeding assays, and intracellular metal content measurements support the hypothesis that PA2911-PA2914 and PA4063-PA4066 are engaged in the import and export of the pyochelin-cobalt complex, respectively. Notably, cobalt can reduce zinc demand and promote the growth of P. aeruginosa strains unable to import zinc, highlighting pyochelin-mediated cobalt import as a novel bacterial strategy to counteract zinc deficiency. These results unveil an unexpected role for pyochelin in zinc homeostasis and challenge the traditional view of this metallophore exclusively as an iron transporter.IMPORTANCEThe mechanisms underlying the remarkable ability of Pseudomonas aeruginosa to resist the zinc sequestration mechanisms implemented by the vertebrate innate immune system to control bacterial infections are still far from being fully understood. This study reveals that the Zur-regulated gene clusters PA2911-2914 and PA4063-PA4066 encode systems for the import and export of cobalt-bound pyochelin, respectively. This proves to be a useful strategy to counteract conditions of severe zinc deficiency since cobalt can replace zinc in many proteins. The discovery that pyochelin may contribute to cellular responses to zinc deficiency leads to a reevaluation of the paradigm that pyochelin is a siderophore involved exclusively in iron acquisition and suggests that this molecule has a broader role in modulating the homeostasis of multiple metals.

La finalidad de este artículo se encuentra orientada a realizar una evaluación integral del índice de (in)cumplimiento de las medidas de reparación ordenadas por la Corte IDH al Estado partiendo de la revisión individualizada de las resoluciones de supervisión de cumplimiento tanto de los casos archivados como de los casos abiertos; así como de las medidas identificadas por la jurisprudencia de la Corte: i) compensación; ii) rehabilitación; iii) restitución; iv) satisfacción y garantías de no repetición, logrando identificar de manera cuantitativa el nivel de cumplimiento que varía según el tipo de reparación ordenada, analizando criterios referentes a la responsabilidad internacional desde la esfera de los Derechos Humanos

Abstract Ribonucleotides represent the most common non-canonical nucleotides found in eukaryotic genomes. The sources of chromosome-embedded ribonucleotides and the mechanisms by which unrepaired rNMPs trigger genome instability and human pathologies are not fully understood. The available sequencing technologies only allow to indirectly deduce the genomic location of rNMPs. Oxford Nanopore Technologies (ONT) may overcome such limitation, revealing the sites of rNMPs incorporation in genomic DNA directly from raw sequencing signals. We synthesized two types of DNA molecules containing rNMPs at known or random positions and we developed data analysis pipelines for DNA-embedded ribonucleotides detection by ONT. We report that ONT can identify all four ribonucleotides incorporated in DNA by capturing rNMPs-specific alterations in nucleotide alignment features, current intensity, and dwell time. We propose that ONT may be successfully employed to directly map rNMPs in genomic DNA and we suggest a strategy to build an ad hoc basecaller to analyse native genomes.

Shallow landslides pose a widely growing hazard and risk, globally and particularly in Mediterranean areas. The implementation of adequate adaptation and mitigation measures necessarily requires the development of practical and affordable methodologies and technologies for assessing the shallow landslides hazard and its territorial impact. The assessment of shallow landslide hazard maps involves two different and sequential steps: the susceptibility and the runout analysis, respectively, aimed at the identification of the initiation and the propagation areas. This paper describes the application in the Giampilieri and Briga Villages area (Sicily, Italy) of a shallow landslide risk process at a basin scale with an innovative approach in the runout assessment segment. The runout analysis was conducted using specific GIS tools employing an empirical–geometric approach at a basin scale. The exposure and vulnerability values of the elements at risk were assigned using a qualitative and semi-quantitative approach, respectively. The results highlight the effectiveness of the procedure in producing consistent runout hazard and risk assessments in the valley areas where the more important and vulnerable exposed elements are located. This study contributes to addressing the public administration demand for valuable and user-friendly tools to manage and drive regional planning.

Plastic contamination is commonly reported in urban and rural soils, as well as in fresh and ocean waters. Canada’s government has attempted to limit the contamination of single-use plastic by banning the manufacturing and selling of specific types of plastic. In British Columbia, current regulations governing commercial composting state that when compost has less than 1% of its dry weight representing foreign materials (including plastic), it can be sold and used in soils. However, due to the low density of plastic and its potential to break down into microparticles, this amount may be enough to become toxic when used in agricultural soils. This paper studies contamination of plastic in garden soils and summarizes how this can affect the environment with a preliminary examination of a garden soil sample. The examination showed that the garden soil sample contained mainly low-density polyethylene, polyethylene and polypropylene plastics (identified through ATR-FTIR) in oxidized and unoxidized forms that can come from commercial composting and hypothesizes that this plastic could break down into microplastic particles. In order to limit the amount of plastic contamination in agricultural soils, it is necessary to modify current compost regulations in order to treat plastic differently than other foreign materials (glass, metal, wood).

Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons' perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with ≥70% agreement considered consensus and ≥80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS's benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS's use during PDAC surgery.

Ecuador has become a benchmark when it comes to sustainable electricity generation in recent years. This research is based on advances in the energy sector, with the aim of knowing the impact of the consumption of renewable electrical energy on economic growth. To carry out the study, annual time series data were used for the period 1990-2021, as well as the unit root tests proposed by Dickey and Fuller in 1981 and Clemente, Montañez and Reyes in 1998. In addition, the proposed by Bayer and Hanck which is the combined cointegration test and the autoregressive distributed lag model (ARDL) to know the impact in the short and long term. Finally, to determine causality, the VECM Granger causality framework was used. The findings demonstrated a positive impact, for every 1% increase in per capita consumption of renewable electrical energy, economic growth will increase by 5.32% in the short term. However, in the long term, for every 1% increase in per capita consumption of renewable electrical energy, economic growth will contract by 0.85%.

Background and purpose: To assess feasibility, toxicity and outcome of moderately hypofractionated radiotherapy concomitant to capecitabine after induction chemotherapy for advanced pancreatic cancer. Materials and methods: Patients with advanced pancreatic cancer without distant progression after induction chemotherapy (CHT) were considered. Radiochemotherapy (RCT) consisted of 44.25 Gy in 15 fractions to the tumor and involved lymph-nodes concomitant to capecitabine 1250 mg/m2/day. Feasibility and toxicity were evaluated in all pts. Overall survival (OS), progression free survival (PFS), distant PFS (DPFS) and local PFS (LPFS) were assessed only in stage III patients. Results: 254 patients, 220 stage III, 34 stage IV, were treated. Median follow up was 19 months. Induction CHT consisted of Gemcitabine (35 patients), or drug combination (219 patients); median duration was 6 months.Four patients (1.6 %) did not complete RT (1 early progression, 3 toxicity), median duration of RT was 20 days, 209 patients (82 %) received ≥ 75 % of capecitabine dose.During RCT G3 gastrointestinal toxicity occurred in 3.2% of patients, G3-G4 hematologic toxicity in 5.4% of patients. Subsequently, G3, G4, G5 gastric or duodenal lesions occurred in 10 (4%), 2 (0.8%) and 1 patients (0.4%), respectively.Median PFS, LPFS, and DPFS were 11.9 months (95 % CI:11.4–13), 16 months (95 % CI:14.2–17.3) and 14.0 months (95 % CI:12.6–146.5), respectively.Median OS was 19.5 months (95 % CL:18.1–21.3). One- and two-year survival were 85.2 % and 36 %, respectively. Conclusions: The present schedule of hypofractionated RT after induction CHT is feasible with acceptable toxicity rate and provides an outcome comparable with that achievable with standard doses and fractionation.

Abstract We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception.

This study examines high school student dropout and proposes a support tool that utilizes a neuro-fuzzy system to mitigate this issue. The system analyzes a student’s economic and social information through a human-machine interface, registering data to evaluate dropout risk levels. It is proposed as an innovative alternative and considered a development project that seeks to perform diagnostics without compromising current support mechanisms. The successful implementation of this proposal will result in tangible benefits, particularly when considering the student community in various regions of the State of Chiapas, specifically in vulnerable areas. The system yielded positive results, manifesting its stability and robustness in both design and implementation. This endeavor not only tackles the identified issue, but also functions as an efficacious and dependable mechanism for assessing and averting student attrition, thereby fortifying the education system in these locales.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Pancreatic neuroendocrine neoplasms (panNENs) have been historically regarded as rare, but their incidence has raised more than 6-fold over the last 3 decades, mostly owing to improvement in the detection of small asymptomatic tumours with imaging. Early detection and proper classification and staging are essential for the prognosis and management of panNENs. Histological evaluation is mandatory in all patients for the diagnosis of panNEN. Regarding localization and staging, multiphasic contrast-enhanced computer tomography is considered the imaging study of choice. Nevertheless, several other diagnostic modalities might present complementary information that can help in diagnosis and staging optimization: magnetic resonance imaging, somatostatin receptor imaging using positron emission tomography in combination with computed tomography (PET/CT), PET/CT with fluorodeoxyglucose (18F-FDG), and endoscopic ultrasound. Approximately 10% of panNENs are due to an inherited syndrome, which includes multiple endocrine neoplasia type 1, von Hippel-Lindau disease, neurofibromatosis type 1 (NF-1), tuberous sclerosis complex, and Mahvash disease. In this review, the Portuguese Pancreatic Club summarizes the classification, diagnosis, and staging of panNENs, with a focus on imaging studies. It also summarizes the characteristics and particularities of panNENs associated with inherited syndromes.

The present study aims at investigating the potential impacts of agricultural policies on GHG emissions from agriculture across the European Union. The study begins by providing evidence on how the key CAP reforms contributed to the structural changes the European agriculture faced in the past. Based on these facts, we introduce the context of implementation of the 2014–2022 Common Agricultural Policy (CAP), within which many interventions were designed to improve sustainability and increase competitiveness, and we formulate hypotheses on how CAP instruments can contribute differently to influencing GHG emissions from agriculture. The hypotheses formulated concern the following: (1) the influence of the income support payment on land prices and, consequently, on land distribution between small and large landowners; (2) the influence of the coupled payment on agricultural specialization; (3) the influence of agri-environmental-climate measures on the sustainable management of agricultural lands. These causalities can have direct and indirect effects on GHG emissions from agriculture. The method of qualitative comparative analysis (QCA) is used to investigate the above-mentioned causalities and to cluster observations based on similar combinations of conditions (i.e., drivers) and outcomes (i.e., positive or negative variations in GHG emissions from agriculture between the end and the beginning of the CAP programming period). The results reveal that the increase in GHG emissions from agriculture over the study period is mainly attributable to the low share of agricultural land under management contracts targeting climate change mitigation and carbon sequestration through the CAP. CAP payments coupled with production were found to contribute to further increasing GHG emissions from agriculture in some eastern and northern EU countries. Livestock concentrations, income support payments and the high price of agricultural land drive the increase in GHG emissions for other central and eastern EU countries. The paper concludes by addressing existing shortcomings due to conflicting interventions in the current CAP strategic plans.

Abundancia de la población reproductiva más septentrional de jaguar Panthera onca El jaguar es el depredador apical de los ecosistemas tropicales y subtropicales en las Américas, pero su conservación está comprometida debido a la pérdida de hábitat, la cacería furtiva y los conflictos por depredación. La Reserva Jaguar del Norte (RJN) fue creada por Naturalia A.C. con la finalidad de proteger la población más norteña de jaguar en una propiedad privada de 24,4 ha, que acoge a otras especies protegidas. Con el propósito de verificar el estado de su población y con ello evaluar el grado de efectividad de la RJN y contribuir al conocimiento de su ecología poblacional, se estimó la densidad mediante modelos tradicionales de marcaje y modelos de captura-recaptura espacialmente explícitos (SERC) y áreas de actividad, mediante un muestreo en 56 estaciones de cámaras-trampa durante 12 periodos bimestrales. En total, se obtuvo un esfuerzo de muestreo de 40.880 días-cámaras y 2,32 reg./1.000 días-cámara para todo el estudio. La densidad de jaguares, calculada con los modelos de captura-recaptura, varió entre 0,30 y 1,44 indiv./100 km2, mientras que en los modelos SERC se obtuvo una densidad de entre 0,21 y 3,04 indiv./100 km2. El área de actividad fue de 78,9 y 45,1 km2 para machos y hembras, respectivamente. El seguimiento de la población a largo plazo y la creación de nuevas Áreas Destinadas Voluntariamente a la Conservación (ADVC), una figura creada recientemente por el Gobierno mexicano, como la RJN, podrían ser una estrategia válida para fortalecer la conservación del jaguar y, con ello, mantener procesos ecológicos clave para otras especies y su hábitat en el noroeste de México.

BackgroundPeripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan (Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise.ObjectivesThis study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant’s risk of drug exposure.MethodsThe InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal–infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions.ResultsValsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants.ConclusionThe transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of

Summary: Obesity is characterized by the accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys), without a concomitant increase in apoptosis. These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRβ repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest a potential role for partially dysfunctional PD-1+CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.