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Background: Patients with a penicillin allergy label are at risk of an associated increase in adverse antibiotic events and hospitalization costs. Aim: We aimed to study the economic savings derived from the correct diagnosis and delabeling inpatients with suspected beta-lactam allergy, considering the acquisition cost of antimicrobials prescribed during a patient's hospital stay. Method: We prospectively evaluated patients admitted to the University Hospital of Salamanca who had been labeled as allergic to beta-lactams and performed a delabeling study. Subsequently, cost differences between antibiotics administered before and after the allergy study and those derived from those patients who received alternative antibiotics during admission and those who switched to beta-lactams after the allergy study were calculated. Results: One hundred seventy-seven inpatients labeled as allergic to beta-lactams underwent a delabeling study; 34 (19.2%) were confirmed to have allergy to beta-lactams. Of the total number of patients, 136 (76.8%) received antibiotics during their hospitalization, involving a mean (SD) cost of €203.07 (318.42) and a median (IQR) cost of €88.97 (48.86–233.56). After delabeling in 85 (62.5%) patients, the antibiotic treatment was changed to beta-lactams. In this group of patients, the mean cost (SD) decreased from €188.91 (351.09) before the change to 91.31 (136.07) afterward, and the median cost (IQR) decreased from €72.92 (45.82–211.99) to €19.24 (11.66–168). The reduction was significant compared to the median cost of patients whose treatment was not changed to beta-lactams (p<0.001). Conclusion: Delabeling hospitalized patients represents a cost-saving measure for treating patients labeled as allergic to beta-lactams. [ABSTRACT FROM AUTHOR]

Abstract We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.

One of the main important features of the noisy intermediate-scale quantum (NISQ) era is the correct evaluation and consideration of errors. In this paper, we analyse the main sources of errors in current (IBM) quantum computers and we present a useful tool (TED-qc) designed to facilitate the total error probability expected for any quantum circuit. We propose this total error probability as the best way to estimate a lower bound for the fidelity in the NISQ era, avoiding the necessity of comparing the quantum calculations with any classical one. In order to contrast the robustness of our tool we compute the total error probability that may occur in three different quantum models: 1) the Ising model, 2) the Quantum-Phase Estimation (QPE), and 3) the Grover's algorithm. For each model, the main quantities of interest are computed and benchmarked against the reference simulator's results as a function of the error probability for a representative and statistically significant sample size. The analysis is satisfactory in more than the 99 % of the cases. In addition, we study how error mitigation techniques are able to eliminate the noise induced during the measurement. These results have been calculated for the IBM quantum computers, but both the tool and the analysis can be easily extended to any other quantum computer. [ABSTRACT FROM AUTHOR]

Background: In a case study in Spain, the unequal proportion of men and women in a research organization in the energy sector is severe, and long-established dynamics that might determine differences in access to leadership positions and inequalities in research careers are evident. The gender gap in historically masculinized fields, such as energy engineering reflects more than simply the differences in male and female values and personalities. This study seeks to explore the gender gap in energy research centres and to identify barriers that potentially hinder the research careers of women. It proposes the development of a diagnostic tool, based upon indicators, to monitor and evaluate gender roles and inequalities in the management of research centres for identifying and addressing the dynamics and obstacles that hinder women's progress in the energy sector and their potential contribution to the field. This participatory multicriteria-based tool prioritizes the proposed indicators by their influence and importance in the context of energy research and applies it to the monitoring of a specific Spanish energy research centre. Results: The results are threefold: (i) the methodology is adaptable to different research centres; (ii) the analysis of indicators' prioritization could lead to recommendations that should be addressed first; (iii) the diagnostic tool used in this in-depth case study of an energy research centre in Spain allowed results to be achieved in terms of gender dynamics. Two indicators stand out as the most relevant in our analysis: gender diversity in leadership positions and uncomplicated application of work–life balance measures. In this case study, the measurement of the first indicator has drawn unsatisfactory results, and the research of the latter is considered still insufficient. In conclusion, this difference becomes a vicious or negative circle for attracting and retaining more women to the research centre. Despite these results, no gender gap seems to be recognized and thus, no measures are being taken to improve the situation. Conclusions: Comprehensive data and contextualized monitoring are necessary to effectively study and enhance the presence and participation of women in the energy science sector. This approach, combining quantitative and qualitative techniques, is suitable for any research centre that would like to monitor its gender gap, identify potential sources of inequity and address them. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. Methods: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. Results: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. Conclusion: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications. [ABSTRACT FROM AUTHOR]

Introduction: One Anastomosis Duodenal Switch (OADS/SADI-S) is used both as a one stage and a second-step procedure, either planned or revisional after a failed sleeve gastrectomy. However, there is lack of adjusted comparative evidence validating its use. Material and Methods: Propensity-score matched comparison between patients submitted to one-stage vs. two-step OADS, adjusted by age, gender, and initial body mass index (BMI). Results: One hundred ninety-five patients (130 one-stage and 65 two-step OADS) were included, with mean initial BMI 52.4 kg/m2. Overall complication rate was 6.6% in the short-term (3.3% Clavien-Dindo ≥ III), and 7.3% in the long-term, with no differences between groups. Follow-up at 1 and 3 years was 83.6% and 61.5%. After one-stage OADS, total weight loss was 36.6 ± 8.2% at 1 year and 30.4 ± 10.3% at 3 years, vs. 30.2 ± 9.4% and 25.6 ± 10.2% after two-steps OADS (p = 0.021). Resolution rates of diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea were 86.4%, 80.4%, 78.0%, and 73.3%, with no differences between groups. Conclusion: One-stage OADS is a safe and effective bariatric technique for patients with grade III and IV obesity. The two-step strategy does not reduce postoperative risks and may compromise weight loss results at mid-term. [ABSTRACT FROM AUTHOR]

The integration of technology in healthcare has revolutionized physical rehabilitation of patients affected by neurological conditions, such as spinal cord injuries and strokes. However, a significant gap remains in addressing the needs of the visually impaired, as most current solutions are visually-centric. This paper presents a novel haptic-based system tailored for the visually impaired that aims to bridge this gap in upper limb rehabilitation. The system is underpinned by a multi-layer architecture that allows both patient guidance during rehabilitation and the definition and analysis of exercises by the therapist. The architecture design includes functionality to track the user's body by means of natural user interfaces, to register the user's movement, and to guide them through the vibrations of the haptic glove or through voice commands. Thus, the proposed solution empowers visually impaired individuals to perform therapist-defined hand exercises autonomously, fostering independence and optimizing therapeutic resources. The system captures detailed kinematic data, offering therapists a comprehensive insight into the patient's exercise execution. To assess the system's functionality, a pilot trial was conducted. This study also allowed us to compare the similarity of exercise performance under vibration-based guidance to the exercises defined by the therapist with that of verbal guidance. The results highlighted a significant increase in similarity to therapist-defined exercises when using the vibration-based guidance facilitated by the designed haptic glove. [ABSTRACT FROM AUTHOR]

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas. Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly. [ABSTRACT FROM AUTHOR]

Key message: Modification of silent latent endosperm-enabled promoters (SLEEPERs) allows the ectopic activation of non-expressed metabolic genes in rice callus Metabolic engineering in plants typically involves transgene expression or the mutation of endogenous genes. An alternative is promoter modification, where small changes in the promoter sequence allow genes to be switched on or off in particular tissues. To activate silent genes in rice endosperm, we screened native promoters for near-miss cis-acting elements that can be converted to endosperm-active regulatory motifs. We chose rice PHYTOENE SYNTHASE 1 (PSY1), encoding the enzyme responsible for the first committed step in the carotenoid biosynthesis pathway, because it is not expressed in rice endosperm. We identified six motifs within a 120-bp region, upstream of the transcriptional start site, which differed from endosperm-active elements by up to four nucleotides. We mutated four motifs to match functional elements in the endosperm-active BCH2 promoter, and this promoter was able to drive GFP expression in callus and in seeds of regenerated plants. The 4 M promoter was not sufficient to drive PSY1 expression, so we mutated the remaining two elements and used the resulting 6 M promoter to drive PSY1 expression in combination with a PDS transgene. This resulted in deep orange callus tissue indicating the accumulation of carotenoids, which was subsequently confirmed by targeted metabolomics analysis. PSY1 expression driven by the uncorrected or 4 M variants of the promoter plus a PDS transgene produced callus that lacked carotenoids. These results confirm that the adjustment of promoter elements can facilitate the ectopic activation of endogenous plant promoters in rice callus and endosperm and most likely in other tissues and plant species. [ABSTRACT FROM AUTHOR]

Background: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). Methods and results: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. Conclusions: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations. [ABSTRACT FROM AUTHOR]

Objective(s): To confirm that hilar transoral submandibular sialolitectomy (TOSL) is the first treatment option for submandibular hilar lithiasis (SHL) in terms of glandular parenchyma recovery, salivary system restoration, and patient quality of life (QoL) improvement. Methods: Depending on whether the stone was easily palpable, TOSL was carried out with or without sialendoscopy. For the first time in the literature, Magnetic Resonance Sialography (MR-Si) was performed before and after TOSL, to evaluate stone characteristics, glandular parenchyma status, hilum dilation and main duct recanalization. Radiological data was examined independently by two radiologists. COSQ, a recently validated and specific questionnaire, was used to assess associated QoL. Results: Between 2017 and 2022, 29 TOSL patients were examined. With a high interobserver correlation, MR-Si was confirmed as a very useful radiological test in the pre- and post-surgical evaluation of SHL. The salivary main duct was completely recanalized in all cases. The presence of lithiasis was found in 4 patients (13.8%). After surgery, the majority of patients (79.31%) had hilum dilation. There was a statistically significant improvement in parenchyma status, but no significant progression to glandular atrophy. After surgery, COSQ mean values always improved (22.5 to 4.5). Conclusions: TOSL is the ideal surgical technique for the management of SHL, resulting in improved parenchymal inflammatory changes, recanalization of Wharton's duct, and enhancement patients' QoL. As a result, before removing the submandibular gland, TOSL should be considered as the first treatment option for SHL. [ABSTRACT FROM AUTHOR]

The different energy transition efforts in the EU-27 countries are analysed, paying special attention to the achievement of set energy targets and the real influence on energy dependence and GHG reduction. Various methodologies were used, ranging from construction of timelines to geo-statistical analysis using Geographic Information Systems (GIS) and the implementation of machine learning techniques and models, using R. The results show how different modifications of the energy saving and efficiency targets, along with lower power consumption due to the COVID pandemic, resulted in that although most of the EU-27 countries have achieved their saving and efficiency targets, this has not been reflected in a real reduction in consumption (compared to 1990 levels). In addition, the fulfilment of the objectives has not resulted in a reduction in energy dependence, generating a false sense of security and satisfaction in the fulfilment of the targets. Concerning GHGs, almost all EU-27 countries decrease their GHG emissions per capita compared to 2000 (with the exception of Lithuania, Bulgaria, Croatia and Latvia), with this decrease being mainly related to the fulfilment of renewable energy targets in transport. The conclusion highlights the need to make greater efforts to achieve saving and efficiency in the near future; otherwise, higher power consumption via renewable energy sources, while helping meet future increases in energy demand, will not impact the reduction in energy dependence compared to current levels. Achievement of energy transition targets. Contribution to the reduction in greenhouse gases and energy dependence. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. Material and methods: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. Results: Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14–32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61–10.48, p = 0.003). Conclusions: Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. Clinical relevance: The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the future. [ABSTRACT FROM AUTHOR]

Long-term persistent symptoms of COVID-19 affect 30–80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium–high effect size (g = −.68, p =.02) with a 95% CI (−1.05 to −.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p <.001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear. [ABSTRACT FROM AUTHOR]

Digital technologies have brought changes to the nature and scope of education and led education systems worldwide to adopt strategies and policies for ICT integration. The latter brought about issues regarding the quality of teaching and learning with ICTs, especially concerning the understanding, adaptation, and design of the education systems in accordance with current technological trends. These issues were emphasized during the recent COVID-19 pandemic that accelerated the use of digital technologies in education, generating questions regarding digitalization in schools. Specifically, many schools demonstrated a lack of experience and low digital capacity, which resulted in widening gaps, inequalities, and learning losses. Such results have engendered the need for schools to learn and build upon the experience to enhance their digital capacity and preparedness, increase their digitalization levels, and achieve a successful digital transformation. Given that the integration of digital technologies is a complex and continuous process that impacts different actors within the school ecosystem, there is a need to show how these impacts are interconnected and identify the factors that can encourage an effective and efficient change in the school environments. For this purpose, we conducted a non-systematic literature review. The results of the literature review were organized thematically based on the evidence presented about the impact of digital technology on education and the factors that affect the schools' digital capacity and digital transformation. The findings suggest that ICT integration in schools impacts more than just students' performance; it affects several other school-related aspects and stakeholders, too. Furthermore, various factors affect the impact of digital technologies on education. These factors are interconnected and play a vital role in the digital transformation process. The study results shed light on how ICTs can positively contribute to the digital transformation of schools and which factors should be considered for schools to achieve effective and efficient change. [ABSTRACT FROM AUTHOR]

Introduction: Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a safe and effective technique with good short- and mid-term weight control and associated medical problems remission for patients with a body mass index (BMI) > 45 kg/m2. The aim of this study was to analyze patient-reported symptoms, specifically symptomatic gastroesophageal reflux disease symptoms (GERD), depositional habit, and quality of life (QOL) following SADI-S, using telemedicine and validated tests. Methods: A prospective unicentric cross-sectional study was conducted including all patients submitted to SADI-S in the University Hospital of Bellvitge from May 2014 to September 2019. A baseline control group was composed of 67 patients who were planning to undergo SADI-S in the following 4 months. Patients were divided into four groups: pre-SADIS, < 2 years, 2–3 years, and > 3 years after surgery. The information gathered via a telematic questionnaire was analyzed and compared with its presence in patients' clinical history derived from the last presential visit. Results: The response rate to telematic tests was 86.9%. The mean BMI exhibited significant differences depending on the moment of evaluation: 50.8 kg/m2, 30.0 kg/m2, 31.1 kg/m2, and 32.7 kg/m2 at pre-SADIS, < 2, 2–3, and > 3 years follow-up, respectively (p < 0.001). The proportion of GERD symptoms increased over time (17.9%, 18.8%, 26.9%, and 30.2%, p = 0.320). After SADIS, the percentage of patients with loose stools was progressively higher (17.4% vs 25.4% vs 30.2%, p = 0.04). Patients with < 2-year follow-up presented an improvement in both physical component (PCS) and mental component (MCS) summaries compared to the baseline group (PCS = 51.3, and MCS = 49.4). The mean BMI of patients with PCS ≥ 50 was 31.9 kg/m2, compared with 41.7 kg/m2 in the PCS < 50 group (p < 0.001). In the MCS ≥ 50 group, there were more patients with a BMI < 35 kg/m2 than the MCS < 50 group (66.7% vs 48.7%, p = 0.004). Telematic follow-up offered a more systemic and detailed information: in the last presential visit only, 13.9% of patients had complete data regarding weight evolution, remission of associated medical problems, GERD symptoms, and depositional habit in comparison with the 82.9% of patients with telematic follow-up (p < 0.001). Conclusion: Weight control is the main factor related to long-term QOL after SADI-S. The incidence of GERD symptoms and diarrhea was up to 30% in patients with > 3-year follow-up. Monitoring postoperative patient-related symptoms with validated objective tests seems a feasible and useful resource for the long-term follow-up of patients submitted to SADI-S. [ABSTRACT FROM AUTHOR]

Despite being landed in commercial cephalopod fisheries, species of Alloteuthis are not yet well defined, with A. subulata and A. media often confused. DNA barcoding combined with morphometric analyses has begun to clarify the distinction between these two morphologically similar species but has been limited in its geographic coverage to date. Herein, we provide DNA barcodes for 228 specimens collected from Guinea Bissau in the south, up the Atlantic coast, to the Irish shelf and North Sea. Employing species delimitation analyses, and with comparison to the literature, we identified 24 individuals of A. africana, 66 individuals of A. subulata and 138 individuals of A. media. We confirm that A. media has the northernmost distribution and is the only species identified by DNA sequencing from the Irish shelf and North Sea. We analysed morphometric measures and indices from 388 individuals from the North Sea, a subset of which (n = 58) were barcoded. The most useful traits for identification were tail length as a percentage of dorsal mantle length, and largest club sucker width as a percentage of head width. By comparison to other published data, we determined that A. media phenotypes vary substantially across the geographic range of this species. This partly explains the difficulties in morphological identification and suggests regional identification guides may be required in support of fisheries management. Interregional analyses suggest character displacement may occur where species co-exist. [ABSTRACT FROM AUTHOR]

Cribriform morular thyroid carcinoma (CMTC) is a rare malignant thyroid tumor with a peculiar growth pattern secondary to permanent activation of the WNT/β-catenin pathway. CMTC may be associated with familial adenomatous polyposis or sporadic; it shares morphological features with papillary thyroid carcinoma (PTC) and was considered a variant of PTC in the 2017 WHO classification of tumors of endocrine organs. The new 5th edition of the WHO classification of endocrine and neuroendocrine tumors considered CMTC an independent thyroid neoplasm of uncertain histogenesis. A thymic/ultimobranchial pouch-related differentiation in CMTC has been recently postulated. We, however, have used the pathological and immunohistochemical features of this case of CMTC with 2 novel oncogenic somatic variants (c.3428_3429insA, p.(Tyr1143Ter) and c.3565del, p. (Ser1189Hisfs*76) of the APC gene to propose an origin from follicular cells (or their endodermal precursors). As usual in CMTC, the morular component of this tumor was positive for CDX2. Given the fact that WNT/β-catenin signaling, through CDX2, activates large intestine and small intestine gene expression, we postulate that in CMTC, the tumor cells have their terminal differentiation blocked, thus showing a peculiar primitive endodermal (intestinal-like) phenotype negative for sodium-iodide symporter, thyroperoxidase, and thyroglobulin. Establishing the histogenesis of CMTC is very relevant for the development of appropriate therapies of redifferentiation, particularly in patients where the tumor cannot be controlled by surgery. [ABSTRACT FROM AUTHOR]

This study aims to determine whether the application of cattle manure and associated bioturbation by dung beetles and other invertebrates can increase oak seedling establishment in the high biodiversity Mediterranean silvopastoral systems known as "dehesas", which are comprised of scattered oaks and a grassland layer and are used for livestock rearing. A two-year study was conducted in a representative dehesa in southern Spain. Firstly, the effect of cattle dung pads on acorn consumption by livestock and wild predators was monitored, along with dung beetle abundance and plot bioturbation. Secondly, the indirect effects of bioturbation on acorn burial, acorn predation by rodents and oak seedling establishment were assessed under the condition of livestock exclusion. The results consistently demonstrate a high positive indirect effect of the presence of cattle manure on the persistence of acorns, as well as on seedling establishment, as a result of reduced predation by rodents and improved microhabitat conditions for the acorns and seedlings. These processes were mediated by bioturbation. Tunneler dung beetles, which move a great amount of soil material, were dominant in our records, which suggest their importance for passive acorn burial, without disregarding the influence of other edaphic invertebrates present. We conclude that the presence of cattle manure significantly improves oak seedling establishment in Mediterranean dehesas through the passive burial of acorns by bioturbation, which acts to protect them from predation by rodents, desiccation and other damage. Passive acorn burial by dung beetles and other invertebrates thus emerges as an important ecosystem service that has been little-studied to date. Appropriate rotational management of livestock could therefore contribute to addressing the bottleneck of oak regeneration in Mediterranean dehesas. [ABSTRACT FROM AUTHOR]

Background: The use of therapeutic algorithms for the reconstruction of defects in different anatomical locations is common in plastic surgery. Nevertheless, axillary reconstruction has been unnoticed in this regard. The aim of this article is to review the surgical techniques employed in the reconstruction of axillary defects focusing on the indication for each one, with the aim of creating a therapeutic algorithm that serves as a guide for decision-making in axillary defect reconstruction. Methods: A systematic review was performed using the MEDLINE, EMBASE and Cochrane library databases and including articles published between 2000 and 2020. Results: After excluding case reports, duplicates and non-relevant articles, we selected a total of 11 relevant articles. Relevant information was extracted and employed to create a therapeutic algorithm. We suggest a reconstructive algorithm that classifies the defects according to their size in three categories. Conclusions: We propose the use of local flaps for smaller defects (less than 30 cm2), regional flaps for medium-sized defects (30 to 200 cm2) and microsurgical fasciocutaneous flaps for large defects (more than 200 cm2). Regarding regional flaps, we consider the TDAP flap as the first choice for axillary reconstruction. Level of evidence: Not ratable [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the influence of continuous chelation on apical transportation and centrality in shaped curved canals prepared with a martensitic file system and evaluated by micro-CT. Twenty-four lower molar canals with a curvature of 25º–40º were scanned pre-operatively with micro-CT and divided into 2 groups according to two different irrigation regimens (n = 12). Group 1 was irrigated with NaOCl, group 2 with Dual Rinse. All canals were prepared with VDW.ROTATE system. The samples were scanned post-operatively and evaluated at 1, 3 and 5 mm from the apex to determine apical transportation and canal centrality using VG Studio software. Statistical analysis was performed with SPSS software using the non-parametric Mann–Whitney test. No statistically significant differences were found between the two groups for both apical transportation and canal centrality at any of the levels studied (p < 05). The use of continuous chelation during the instrumentation of the canals with martensitic alloy files does not produce greater transportation and does not generate changes in centralization compared to NaOCl-only irrigation. Combined chelation and disinfection while shaping with martensitic NiTi can simplify the irrigation regimen without inducing iatrogenic aberrations. [ABSTRACT FROM AUTHOR]

Introduction: The implication of copy number variations in familial heart disease is known, although in-depth knowledge is lacking; hence, more studies are needed to further our understanding. Massively parallel sequencing, thanks to its recent surge in use, is emerging as a valid tool for the detection of this type of variant, through the use of appropriate software. Methods: We conducted a study with 182 patients diagnosed with mendelian cardiovascular diseases who underwent sequencing using a cardiac gene panel and then a specific calling process for copy number variations (CNVs) with ExomeDepth software, which provides us with a Bayes factor (BF), a score of the probability that a CNV detected is true. Results: After a rigorous CNV prioritization process, we confirmed the variants obtained by MLPA or SNP-based array, finding three real CNVs in five individuals in the MYH11, FBN1 and PDMI7 genes. Conclusion: The confirmed CNVs present in all cases BF values > 60, thus establishing a threshold to consider real CNVs in the calling process carried out by ExomeDepth on our gene panel. [ABSTRACT FROM AUTHOR]

The paradigm proposed by Responsible Research and Innovation in the European Commission policy discourse identifies Public Engagement as a key area for exchange and dialogue among multiple actors following an inclusive and participatory process. Two definite set of indicators have already arisen at European level to monitor Public Engagement activities in the Science and Innovation realm. Our study aims to propose a deliberative participatory process, which involves selected stakeholders, for the adaptation of the European indicators to the specific Spanish scientific and innovation context. The methodological procedure is of exploratory nature and will be based in a combination of, on the one hand, qualitative content analysis techniques for the in-depth study of the deliberative process and the generation of indicators; and, on the other hand, a multi-criteria decision analysis technique such as the Analytic Hierarchy Process for the prioritization of the indicators. The discussion will focus on the procedure to articulate stakeholders' values and use them as the basis for creating a context-based improved list of indicators. Two types of research questions arise: (i) Is the proposed methodology adequate for the adaptation of the European indicators to the Spanish context? (ii) What are the main indicators to monitor and to expand reflection on the public engagement in the Spanish science and innovation? [ABSTRACT FROM AUTHOR]

Purpose: Chronic obstructive sialadenitis (COS) is a recurring inflammation of the salivary gland. To date, there are no known predisposing factors for COS. Given the advances seen in radiology and sialendoscopy, we must update our knowledge of COS, analyzing factors that can favor its development. Methods: We prospectively analyzed 333 patients who underwent sialendoscopy between 2012 and 2021. Epidemiologic, radiologic, and sialendoscopy-related factors were correlated. Suspected diagnosis was established based on the clinical and radiologic data. The final diagnosis was determined on the basis of sialendoscopic findings. Results: The most common etiology of COS was stricture (40.8%). Lack of papilla distensibility (LPD) was also described as an etiology. COS was related to patient gender and age. Submandibular gland involvement was significantly more associated with lithiasis and LPD, while COS of the parotid gland was most frequently caused by stricture. Radioiodine sialadenitis and Sjögren's syndrome were significantly associated with stricture. MR sialography (MR-Si) showed the best overall sensitivity and specificity. Conclusion: In our series, stricture was the most common cause of COS. We describe LPD as a frequent cause of COS in this series; ours is the first study to report this finding. There was a significant association between the salivary gland involved, patient sex and age, and the cause of COS. MR-Si showed the greatest diagnostic yield. [ABSTRACT FROM AUTHOR]

Purpose: The aims were to compare the 5-year outcomes of duodenal switch (DS) and single-anastomosis duodenal switch (SADI-S) in terms of weight loss; remission of comorbidities; nutritional status short- and long-term complications; postoperative mortality; and need for revisional surgery. Materials and Methods: Multicenter prospective observational study of all consecutive patients undergoing DS or SADI-S in three high-volume hospitals. Results: A total of 87 patients were included in the study, 43 submitted to DS and 44 to SADI-S, with similar basal characteristics, nutritional parameters, and BMI (52.9 kg/m2 DS vs. 52.5 kg/m2 SADI-S). Operative time was 152 min (± 32.6) in DS vs. 116 min (± 21.9) in SADI-S (p = 0.043). Short-term complications were similar for DS and SADI-S, both overall (11.8% vs. 11.6%), and ranged as Clavien-Dindo > II (4.5% vs. 4.7%), with no mortality. At 5 years, DS and SADI-S results were as follows: BMI 30.6 vs. 33.3 kg/m2 (p = 0.023); %EWL 80.5% vs. 68.6% (p = 0.006); and %TWL 42.1 vs. 36.0 (p = 0.006). Comorbidity remission rates for DS and SADI-S were as follows: for diabetes, 92.8% vs. 85.7% (n.s.); for hypertension, 95.2% vs. 85.1% (n.s.); for sleep apnea, 75% vs. 73.3% (n.s.); and for dyslipidemia, 76.4% vs. 73.3% (n.s.). DS showed lower levels of vitamin B12, iron, vitamin E, and zinc than SADI-S (p = < 0.005). In the long term, there were 4 surgical reinterventions (due to 1 internal hernia in the DS group and 1 internal hernia and 2 biliary refluxes in the SADI-S group) with no cases of persistent diarrhea or malnutrition. Conclusion: Both DS and SADI-S allowed good weight control and resolution of comorbidities. DS achieved a greater weight loss compared to SADI-S, at the expense of longer operative time and lower vitamin and mineral levels. [ABSTRACT FROM AUTHOR]

Purpose: Describe and analyze the safety and weight loss performance of biliopancreatic diversion and duodenal switch (BPD-DS) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S), verifying any possible superiority according to preoperative BMI. Methods : Retrospective review of patients who underwent primary SADI-S or BPD-DS in three bariatric centers. Study groups were further stratified according to preoperative BMI (subgroup 1: BMI < 50; subgroup 2: 50 ≤ BMI < 55; subgroup 3: BMI ≥ 55). Results : Four hundred and sixty patients underwent BPD-DS (n = 220) or SADI-S (n = 240). The mean LOS was 3.48 ± 3.7 and 3.13 ± 2.3 days for BPD-DS and SADI-S respectively (p = 0.235). The mean operative time was shorter in the SADI-S group (167.25 ± 33.6 vs 140.85 ± 56.7 min) (p < 0.00). The mean %EWL was 44.2, 62.4, and 69.4 for the BPD-DS group and 48.4, 64.5, and 67.1 for the SADI-S group at 6, 12, and 24 months respectively. The mean %TBWL was 25, 35.9, and 40.3 for the BPD-DS group, and 26.2, 35, and 36.9 for the SADI-S group at 6, 12, and 24 months respectively. Overall complication rates were comparable between BPD-DS and SADI-S groups (14% vs 18%) (p = 0.219). SADI-S showed greater emergency department visits (17% vs 7%) (p = 0.005); similar readmission rates (6% vs 7%) (p = 0.80); similar reoperation rates (3% vs 7%) (p = 0.102); and similar mortality rate (0.9% vs 0.4%), after BPD-DS and SADI-S respectively. Conclusion: BPD-DS achieved greater %TBWL at 2 years, but no superiority was perceived among study subgroups. SADI-S and BPD-DS showed similar overall complication rates. [ABSTRACT FROM AUTHOR]

In mountain areas, the phenology and productivity of grassland are closely related to snow dynamics. However, the influence that snow melt timing has on grassland growing still needs further attention for a full understanding, particularly at high spatial resolution. Aiming to reduce this knowledge gap, this work exploits 1 m resolution snow depth and Normalized Difference Vegetation Index observations acquired with an Unmanned Aerial Vehicle at a sub-alpine site in the Pyrenees. During two snow seasons (2019–2020 and 2020–2021), 14 NDVI and 17 snow depth distributions were acquired over 48 ha. Despite the snow dynamics being different in the two seasons, the response of grasslands greening to snow melt-out exhibited a very similar pattern in both. The NDVI temporal evolution in areas with distinct melt-out dates reveals that sectors where the melt-out date occurs in late April or early May (optimum melt-out) reach the maximum vegetation productivity. Zones with an earlier or a later melt-out rarely reach peak NDVI values. The results obtained in this study area, suggest that knowledge about snow depth distribution is not needed to understand NDVI grassland dynamics. The analysis did not reveal a clear link between the spatial variability in snow duration and the diversity and richness of grassland communities within the study area. [ABSTRACT FROM AUTHOR]

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function. Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection can cause an inflammatory syndrome (COVID-19) leading, in many cases, to bilateral pneumonia, severe dyspnea, and in ~5% of these, death. DNA methylation is known to play an important role in the regulation of the immune processes behind COVID-19 progression, however it has not been studied in depth. In this study, we aim to evaluate the implication of DNA methylation in COVID-19 progression by means of a genome-wide DNA methylation analysis combined with DNA genotyping. The results reveal the existence of epigenomic regulation of functional pathways associated with COVID-19 progression and mediated by genetic loci. We find an environmental trait-related signature that discriminates mild from severe cases and regulates, among other cytokines, IL-6 expression via the transcription factor CEBP. The analyses suggest that an interaction between environmental contribution, genetics, and epigenetics might be playing a role in triggering the cytokine storm described in the most severe cases. Genetic associations with severe COVID-19 have been discovered, but epigenetic associations are not as well described. Here, the authors perform a genome-wide epigenetic analysis of COVID-19 patients, discovering an interaction between environmental exposure, genetics, and epigenetics which might play a role in severe disease. [ABSTRACT FROM AUTHOR]

The research compares teachers' and their pupils' performance on plant nutrition. The misconceptions of 89 primary school children from one state school have been compared with those of their four teachers. A questionnaire and a drawing task were used for data collection. The results evidence that children and teachers have serious shortcomings regarding plant nutrition, although they do not always coincide, diverging from common assumptions held by scientific literature. Results have implications for teacher training program design, suggesting that it is important to provide pre-service teachers with a deeper content knowledge and strategies that allow them to detect misconceptions and deal with them successfully in the classroom. [ABSTRACT FROM AUTHOR]

Carbon nanodots modified with Neutral Red covalently inserted in the nanostructure (NR-CDs) have been prepared by a simple synthesis method based on microwave irradiation under controlled temperature and pressure. The synthetized NR-CDs have been characterized by different techniques, demonstrating the covalent bonding of Neutral Red molecules to the carbon dots nanostructure. Fluorescence activity of the prepare NR-CDs has been explored showing different interaction pathways with singled and doubled stranded DNA. These studies have been successfully applied to develop a new fluorescence DNA hybridization assay to the detection of a specific DNA sequence of Escherichia coli bacteria. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe" published in Nature Communications. The correction addresses an error in the Supplementary Information, specifically in Supplementary Movie 1, where the heading "ATC cell line B-CPAP" was incorrectly labeled instead of "PDTC cell line B-CPAP." The corrected version of Supplementary Movie 1 has been included in the updated HTML, while the original incorrect version can be found in the Supplementary Information associated with this correction. The document also provides a link to the online version, which contains additional supplementary material. The authors of the article are Joana S. Rodrigues, Miguel Chenlo, Susana B. Bravo, Sihara Perez-Romero, Maria Suarez-Fariña, Tomas Sobrino, Rebeca Sanz-Pamplona, Román González-Prieto, Manuel Narciso Blanco Freire, Ruben Nogueiras, Miguel López, Laura Fugazzola, José Manuel Cameselle-Teijeiro, and Clara V. Alvarez. [Extracted from the article]

The veined squid, Loligo forbesii Steenstrup, 1856, occurs at the European Shelf areas including the Azores and represents a valuable resource for the European commercial fishery in the North East Atlantic. However, very little is known about its population structure and phylogeography. This lack of knowledge also impedes the development of sustainable fishery management for this species. The present study combined the use of two types of markers that retrieve patterns of gene flow in different time spans; the analysis of 16 nuclear microsatellites and sequencing of the mitochondrial cytochrome oxidase subunit I (COI). Whereas the high mutation rate of microsatellites allows the description of recent patterns of connectivity in species, the lower mutation rate of COI provides phylogeographic patterns on a longer timescale. A total of 347 individuals of L. forbesii were investigated from nearly the entire distribution range of the species, including the North East Atlantic Shelf, the Azores and the Mediterranean. Individuals from the Western and Eastern Mediterranean Sea have never been included in a genetic study before. We were able to analyse COI sequences from all 12 sampling areas and define three clades of L. forbesii. Due to our large sampling area, we are presenting 13 COI-haplotypes that were previously unknown. The microsatellite analysis does not include the Azores but three main clades could be identified at the remaining 11 sampling sites. Low FST values indicate gene flow over large geographical distances. However, the genetically significant differences and an additional slight grouping in the microsatellite structure reveal that geographical barriers seem to influence the population structure and reduce gene flow. Furthermore, both markers provide strong evidence that the observed phylogeographic pattern reflects the geographical history of the Azores and the Mediterranean Sea. [ABSTRACT FROM AUTHOR]

The National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient's outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, which could expand or reduce brain injury and its associated neurological sequels. In this work, our aim was to analyze the association of NI with the functional outcome at 3 months and to study clinical biomarkers associated to NI as surrogate biomarkers of ischemic and inflammatory penumbrae in ischemic stroke (IS) patients. We included 663 IS patients in a retrospective observational study. Neutral NI was defined as a variation in the NI scale between − 5 and 5% (37.1%). Positive NI is attributed to patients with an improvement of > 5% NI after 48 h (48.9%), while negative NI is assigned to patients values lower than − 5% (14.0%). Poor outcome was assigned to patients with mRS ≥ 3 at 3 months. We observed an inverse association of poor outcome with positive NI (OR, 0.35; 95%CI, 0.18–0.67; p = 0.002) and a direct association with negative NI (OR, 6.30; 95%CI, 2.12–18.65; p = 0.001). Negative NI showed a higher association with poor outcome than most clinical markers. Regarding good functional outcome, positive NI was the marker with the higher association (19.31; CI 95%, 9.03–41.28; p < 0.0001) and with the highest percentage of identified patients with good functional outcome (17.6%). Patients with negative NI have higher glutamate levels compared with patients with neutral and positive NI (p < 0.0001). IL6 levels are significantly lower in patients with positive NI compared with neutral NI (p < 0.0001), while patients with negative NI showed the highest IL6 values (p < 0.0001). High glutamate levels were associated with negative NI at short latency times, decreasing at higher latency times. An opposite trend was observed for inflammation, and IL6 levels were similar in patients with positive and negative NI in the first 6 h and then higher in patients with negative NI. These results support NI as a prognosis factor in IS and the hypothesis of the existence of a delayed inflammatory penumbra, opening up the possibility of extending the therapeutic window for IS. [ABSTRACT FROM AUTHOR]

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Several laccase-based products have been launched on the market over the years. However, there is little information about their toxicity and/or the toxicity of their residues. We evaluated the toxicity of a simulated denim-laundry wastewater containing Biolite BSN, a laccase-based product used for denim bleaching. The evaluation included a viability test with Saccharomyces cerevisiae, a phytotoxicity test with Sorghum vulgare, and a toxicity test with Daphnia magna. The viability of S. cerevisiae was reduced to 40%. The radicle and plumule growth of S. vulgare was reduced to 62 and 66%, respectively. The CL50 for D. magna was 29.7%, which classified this water as toxic (according to the percent rank method). Biolite BSN was identified as the main cause of the toxic effects; furthermore, the chemical oxygen demand (COD) of the wastewater was significantly high (3346.2 mg/L), and more than 90% of the COD corresponded to Biolite BSN. The anaerobic biodegradability tests showed that the denim-laundry wastewater could be treated anaerobically; therefore, it was treated in an upflow anaerobic sludge blanket (UASB) reactor. The treatment reduced the toxicity and COD in 50 and 77%, respectively, and a methane yield of 311.1 mL CH4/g of CODremoved was obtained. Based on these results, we recommend to analyze the toxicity of all textile chemicals, regardless of whether they are enzyme-based products. A UASB reactor can be used as the first treatment stage for similar effluents in order to reduce the COD and the toxicity and recover methane as an added benefit. [ABSTRACT FROM AUTHOR]