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Therapeutic drug monitoring of paracetamol (acetaminophen, N-acetyl-p-aminophenol, APAP) metabolites in plasma and serum samples was conducted using two-dimensional liquid chromatography (2D-LC) by means of online heart-cutting passive modulation. The selective and efficient 2D-LC approach here developed was applied for the simultaneous determination of six paracetamol metabolites: its major metabolite, the glucuronide conjugate (APAP-GLUC), and its main transformation product p-aminophenol (PAP), along with the bioactive N-arachidonoylphenolamine (AM404), the reactive hepatotoxic N-Acetyl-p-benzoquinone imine (NAPQI), in addition to glutathione (APAP-GLUT) and protein-derived cysteine (APAP-CYS) conjugates. Online heart-cutting mode allowed the combination of C18 reversed-phase column in the first dimension and a Primesep SB analytical column (C18-anion exchange) in the second dimension promoting the effective separation of such different paracetamol metabolites, ranging from highly polar to extremely hydrophobic. The results suggest the promising potential of the proposed 2D-LC methodology for therapeutic drug analysis and pharmacokinetic studies., 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., (Copyright © 2025. Published by Elsevier B.V.)

Objectives: To: 1) analyze possible differences in the CIEDE2000 lightness, chroma and hue of the gingiva at the free gingival margin (FGM) and the middle zone of keratinized gingiva (MZ) between participants with an ISFP in the maxillary anterior region and participants with natural dentition and healthy gums; and 2) examine the perceptibility/acceptability of the differences in CIEDE2000 lightness, chroma and hue and in overall color, using the Euclidean and CIEDE2000 formulae., Methods: The L*, a* and b* color coordinates were measured in 60 adult participants (30 with an ISFP and 30 with healthy teeth and gums) using a Spectroshade™ Micro spectrophotometer. From these coordinates, the changes in lightness (ΔL'), chroma (ΔC') and hue (ΔH') CIEDE2000 between the participants with and without an ISFP were quantified. The one sample t-tests were used to test whether there were significant changes in lightness, chroma and hue between the participants with and without an ISFP, and effect size was assessed with Cohen's d. The authors examined the differences in CIEDE2000 lightness, chroma and hue, and the overall color differences between the participants in pairs (with ISFP-without ISFP), comparing results with the published perceptibility and acceptability thresholds., Results: Statistically significant differences were found (p < 0.05) between participants with and without an ISFP in all color attributes at both zones, with all color attributes observed to be lower in the gingiva of participants with an ISFP. In both gingival zones, the ISFP had a large effect on lightness (Cohen's d > 0.8) and a medium effect on hue (Cohen's d between 0.5 to 0.8). The mean gingival color difference of participants with and without an ISFP was 8.72 units in the MZ and 9.60 units at the FGM, using CIEDE2000., Conclusions: CIEDE2000 lightness, chroma and hue are significantly lower in participants with an ISFP, both at the FGM and the MZ, with particularly marked differences in lightness. The average color difference between healthy gingiva next to natural teeth and the gingiva adjacent to an ISFP is clinically unacceptable., Clinical Relevance: Gingival color needs to be considered an indicator of success, given the potential unesthetic gray show-through of transmucosal abutments with ISFPs. Unacceptable color changes caused by poorly planned ISFPs can lead patients to demand treatment be repeated with more esthetic materials or mucogingival surgery to "camouflage" the discoloration., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Aim: While the importance of gingival aesthetics is increasingly recognized, a questionnaire quantifying its psychosocial impact is still lacking. We have adapted the validated Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) for the gingival context. This study's aim was to develop a new Psychosocial Impact of Gingival Aesthetics Questionnaire (PIGAQ) and test its validity for the general population in Spain, exploring the underlying dimensions of the construct assessed., Materials and Methods: The PIDAQ was adapted to address gingival aesthetics. PIGAQ (23 items) was completed by 200 patients aged from 18 to 85 years, and socio-demographic variables were recorded. The four-dimensional structure of the PIDAQ was respected, adapting the subscales to focus on the gingiva. Descriptive analysis, assessments of reliability and validity and an exploratory factor analysis were performed., Results: The revised PIGAQ (now containing 20 items) has a Cronbach's alpha coefficient of 0.88 with four underlying factors explaining 61.5% of the total variance. Three items (SI-1, PI-2 and PI-5) were eliminated because of unacceptable fit indices. The Cronbach's alpha coefficients for the subscales are as follows: Gingival Self-Confidence, 0.85; Social Impact, 0.84; Psychological Impact, 0.79; and Aesthetic Concern, 0.76., Conclusion: PIGAQ is a reliable and potentially valid instrument for assessing psychosocial perceptions of gingival aesthetics. The scale was shown to have a satisfactory factor structure and level of internal consistency., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objective: Demonstrate the effectiveness of complex decongestive therapy (CDT) in patients with chronic venous insufficiency (CVI)., Methods: A single-blind randomized controlled trial was conducted, where the participants were patients with CVI (n = 21/42) were assigned randomly to an experimental group (n = 11/22) or a control group (n = 9/18). A treatment of CDT (manual lymphatic drainage, intermittent pneumatic presotherapy, bilayer bandage) was applied to the experimental group for 4 weeks 2 days per week and no treatment was applied to the control group. The patients were evaluated at baseline (t0), 1 week after finishing the intervention (t1), and 6 weeks after the intervention (t2). The effectiveness of the treatment on symptoms and quality of life (QoL) (heaviness, pain and Chronic Venous Insufficiency Quality of Life [CIVIQ-20] questionary), edema, venous flow, and impedanciometry measurements was evaluated., Results: An improvement in the patient's QoL was observed: there was a decrease in symptoms such as heaviness and pain, an increase in the average velocity of the left femoral vein and left internal saphenous vein (ISV), a decrease in the ISV diameter in both extremities and a decrease in body mass index and fat mass in both extremities. These results were maintained when following up at 6 weeks, except for the improvement of QoL., Conclusions: CDT treatment improves the CIVIQ-20 and Venous Clinical Severity Scores. It also improves symptoms (pain and heaviness), venous flow velocity (superficial veins and deep veins [common femoral vein, femoral vein, popliteal vein]) and decreases body mass index, fat mass, and ISV diameter., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare no competing interests.

Colonization and diversification processes are responsible for the distinctiveness of island biotas, with Madagascar standing out as abiodiversity hotspot exceptionally rich in species and endemism. Regardless of its significance, the evolutionary history and diversification drivers of Madagascar's flora remain understudied. Here we focus on Helichrysum (Compositae, Gnaphalieae) to investigate the evolutionary and biogeographic origins of the Malagasy flora. We inferred a highly resolved phylogeny based on target-enrichment data from 327 species (including 51 % of Malagasy endemics) and conducted ancestral range estimation analyses. Our results revealed at least six trans-oceanic dispersal events from different African regions to Madagascar during the Pliocene. In this process, biome conservatism prevailed, as evidenced by similarities between Malagasy lineages and their African relatives. The southern African grasslands, known to be the center of diversification and the main source of African Helichrysum lineages, played a key role in the colonization of Madagascar as the ancestral source area of at least three clades. The Tropical Afromontane region was revealed as the source of at least two montane Malagasy lineages that substantially radiated in-situ. Finally, a dispersal event from southwestern Africa led to a lineage represented by a single species adapted to the island's southwestern arid conditions. The main radiations of Helichrysum in Madagascar's mountains occurred within the last 2 My, coinciding with a transition towards cooler and drier conditions and the expansion of open habitats, likely driven by a combination of geographic and ecological speciation. Overall, our findings highlight the affinities between the montane floras of continental Africa and Madagascar., 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., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: to evaluate the efficacy and chromatic stability after 4weeks, in all three thirds of the central incisor of two whitening treatments: in-office 37.5 % hydrogen peroxide (HP) treatment alone, and 37.5 % in-office HP followed by use of 6 % HP whitening strips (WS)., Methods: 60 participants were randomly divided into two groups of 30. Group 1 was treated solely with in-office 37.5 % HP. Group 2 followed the same in-office 37.5 % HP protocol, followed by WS over 2 weeks. The CIELAB colour were measured before and after every treatment stage. Colour differences were quantified and compared to the perceptibility thresholds., Results: In-office 37.5 % HP treatment created a statistically significant increase in the L* coordinate and a statistically significant decrease in the a* and b* coordinates, resulting in perceptible colour changes in over 80 % of participants in all thirds of the tooth. In the group that used WS, the increase in L* and the decrease in a* and b* were maintained in the cervical and middle thirds after 4 weeks, whereas only the decrease in b* was maintained in the incisal third. In the group that did not use WS, the decrease in a* and b* was maintained in all thirds of the tooth after 4 weeks, but the increase in lightness was lost., Conclusions: The use of WS helped maintain that increase in lightness over 4 weeks. The decrease in the a* and b* coordinates caused by the 37.5 % HP treatment persisted after 4 weeks, whether WS were used or not. All the colour changes evaluated were perceptible in over 70 % of participants., Clinical Significance: In-office treatment with 37.5 % HP increases lightness and decreases the quantity of yellow and red immediately but, if WS are not used, the impact on lightness is lost after 4 weeks. WS are a valid and effective treatment option in combination with in-office treatments to temporally extend the clinical treatment's whitening effect., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Listeria (L.) monocytogenes can survive for extended periods in the food producing environment. Here, biofilms possibly provide a niche for long-term survival due to their protective nature against environmental fluctuations and disinfectants. This study examined the behaviour of a L. monocytogenes ST121 isolate in a multispecies biofilm composed of Pseudomonas (P.) fragi, Brochothrix (B.) thermosphacta, and Carnobacterium (C.) maltaromaticum, previously isolated from a meat processing facility. The composition of the biofilm community and matrix, and transcriptional activity were analysed. L. monocytogenes colonised the multispecies biofilm, accounting for 6.4 % of all total biofilm cells after six hours. Transcriptomic analysis revealed 127 significantly up-regulated L. monocytogenes genes compared to the inoculum, including motility, chemotaxis, iron, and protein transport related genes. When comparing the differentially expressed transcripts within the multispecies biofilm with and without L. monocytogenes, only a cadmium/zinc exporting ATPase gene in C. maltaromaticum was significantly upregulated, while the other 9313 genes in the biofilm community showed no significant differential expression. We further monitored biofilm development over time (6, 24 hours and 7 days). P. fragi remained the dominant species, while L. monocytogenes was able to survive in the multispecies biofilm accounting for 2.4 % of total biofilm cells after 7 days, without any significant changes in its abundance. The presence of L. monocytogenes did neither alter the biofilm community nor its matrix composition (amount of extracellular DNA, carbohydrates, and protein). Our data indicate that L. monocytogenes resides in multispecies biofilms, potentially increasing survival against cleaning and disinfection in food processing environments, supporting persistence., Competing Interests: Declaration of Competing Interest The author(s) declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignant tumors that originate from the biliary tract. They are usually diagnosed in advanced stages, leading to a poor prognosis for affected patients. As CCA often arises as a sporadic cancer in individuals lacking specific risk factors or with heterogeneous backgrounds, and there are no defined high-risk groups, the implementation of effective surveillance programs for CCA is problematic. The identification and validation of new biomarkers useful for risk stratification, diagnosis, prognosis, and prediction of treatment response remains an unmet need for patients with CCA, even though numerous studies have been conducted lately to try to discover and validate CCA biomarkers. In this review, we overview the available information about the different types of biomarkers that have been investigated in recent years using minimally invasive biospecimens (blood, serum/plasma, bile, and urine) and their potential usefulness in diagnosis, prognosis, and risk stratification. It is widely accepted that early detection of CCA will impact patients' outcomes, by improving survival rates, quality of life, and the possibility of less invasive and/or curative treatments; however, challenges to its translation and clinical application for patients with CCA need to be resolved., Competing Interests: Disclosure Statement The authors declare the following competing financial interests: Y.H. served as a consultant on advisory boards from Helio Genomics, Espertiva Therapeutics, Roche Diagnostics, and Elevar Therapeutics; and is a shareholder of Alentis Therapeutics and Espervita Therapeutics. H.K. served as a consultant on advisory boards from Takeda and Bayer., (Copyright © 2025 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Polyploidisation is a significant reproductive barrier, yet genetic evidence indicates that interploidy admixture is more common than previously thought. Theoretical models and controlled crosses support the 'triploid bridge' hypothesis, proposing that hybrids of intermediate ploidy facilitate gene flow. However, comprehensive evidence combining experimental and genetic data from natural mixed-ploidy species is missing. Here, we investigated the rates and directionality of gene flow within a diploid-autotetraploid contact zone of Cardamine amara, a species with abundant natural triploids. We cytotyped over 400 individuals in the field, conducted reciprocal interploidy crosses, and inferred gene flow based on genome-wide sequencing of 84 individuals. Triploids represent a conspicuous entity in mixed-ploidy populations (5%), yet only part of them arose through interploidy hybridisation. Despite being rarely formed, triploid hybrids can backcross with their parental cytotypes, producing viable offspring that are often euploid (in 42% of cases). In correspondence, D-statistics and coalescent simulations documented a significant genome-wide signal of bidirectional gene flow in sympatric but not allopatric populations. Triploids, though rare, thus seem to play a key role in overcoming polyploidy-related reproductive barriers in C. amara. In sum, we present integrative evidence for interploidy gene flow mediated by a triploid bridge in natural populations., (© 2025 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Background: The aim of this pilot study was to analyze the influence of a nickel-titanium archwire (NiTi) and a copper-nickel-titanium archwire (Cu-NiTi) on pain levels in adult patients during the first two months of orthodontic treatment with self-ligating brackets., Methods: This prospective observational pilot study was carried out at the Dental Clinic of the University of Salamanca between 2023 and 2024. This study analyzed 30 adult orthodontic patients who began treatment with self-ligating brackets. The participants were distributed into two study groups (n = 15) for treatment with initial NiTi and Cu-NiTi archwires. At the beginning, a 0.014-inch archwire was used, and a 0.016-inch archwire was used after a month. The level of pain was measured using a visual analog scale (VAS) at the beginning of treatment (T0), at one month (T1), and at two months (T2). At each time point (T0, T1, and T2), pain was measured at baseline and at 4, 24, and 48 h after archwire placement or replacement. The data were analyzed using Spearman's correlation coefficient and the Mann-Whitney test (p < 0.05)., Results: The mean age of the participants (n = 30) was 31.34 (± 6.05) years. The maximum pain peak was in the first 48 h after placing the initial archwire (5.57 ± 1.72). The age and sex of the participants did not influence the pain levels in the sample studied. The composition of the orthodontic archwire only influenced the pain levels at the beginning of treatment (T0) (p < 0.05); in this case, the NiTi group (1.73 ± 1.53) described a higher level of pain than that of the Cu-NiTi group (1.07 ± 1.36); in the rest of the follow-up period, no significant differences were observed., Conclusions: Within the limitations of this study, we observed that the orthodontic archwire material (nickel-titanium versus copper-nickel-titanium) only influenced pain levels at the beginning of orthodontic treatment., Competing Interests: Declarations. Ethics approval and consent to participate: The approval of the Research Ethics Committee of the University of Salamanca was obtained (protocol number 1073; date: 25/10/2023). Written informed consent was obtained from parents or caregiver of patients after full explanation of the study, in according to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Epidemiological studies suggest that exposure to greenness may protect children attention-deficit/hyperactivity disorder (ADHD) diagnosis. However, evidence to date is limited while no previous research has independently investigated exposure to prenatal greenness., Objective: We conducted a nested case-control study with data from Born in Bradford (BiB) and INfancia y Medio Ambiente (INMA) birth cohorts to investigate the association between exposure to various types of residential greenness and ADHD diagnosis, considering both pregnancy and early childhood exposure periods independently. PM 2.5 was tested as a potential mediator of the association., Methods: Children with ADHD were identified based on a confirmed medical diagnosis. Pregnancy and early childhood exposure to residential greenness were estimated through Normalized Difference Vegetation Index (NDVI) within 300-m, urban green space and natural green space percentages within 300-m, and the linear distance to the closest green space in meters. We performed a conditional logistic regression to analyze the association between the included greenness metrics and ADHD., Results: We found no statistically significant associations between any of the pregnancy and early childhood greenness metrics and ADHD diagnosis in the BiB cohort. Further analysis on the INMA cohort found that higher urban green space percentage slightly increased the risk of ADHD diagnosis during both pregnancy (total effects: OR 1.04, 95 % CI 1.01 to 1.07, p = 0.012; direct effects: OR 1.06, 95 % CI 1.03 to 1.10, p < 0.001) and early childhood (total effects: OR 1.03, 95 % CI 1.00 to 1.07, p = 0.042; direct effects: OR 1.04, 95 % CI 1.00 to 1.07, p = 0.033). However, these associations were not supported by the sensitivity analyses., Conclusions: This study found both null and inconsistent associations between the included greenness metrics and ADHD. Further research is warranted to elucidate the potential role of exposure to different types of greenness in ADHD diagnosis., 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., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Therapy-induced senescence (TIS) alters calcium (Ca²⁺) flux and Mitochondria-ER Contact Sites (MERCS), revealing critical vulnerabilities in senescent cells. In this study, TIS was induced using Doxorubicin and Etoposide, resulting in an increased MERCS contact surface but a significant reduction in ER-mitochondria Ca²⁺ flux. Mechanistically, TIS cells exhibit decreased expression of IP3R isoforms and reduced interaction between type 1 IP3R and VDAC1, impairing Ca²⁺ transfer. This flux is crucial for maintaining the viability of senescent cells, highlighting its potential as a therapeutic target. Inhibition of ER-mitochondria Ca²⁺ flux demonstrates senolytic effects both in vitro and in vivo, offering a novel strategy for targeting senescent cells., Competing Interests: Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Armen Zakarian and J. Cesar Cardenas hold a patent on the synthesis of dmXeB., (© 2025. The Author(s).)

This study systematically maps the network structure of the editors-in-chief in social sciences journals, focusing on their gender representation, geographical distribution, and institutional composition. Drawing upon large-scale data from 3,320 JCR-ranked journals of 57 different fields in the social sciences (4,868 editors-in-chief from 1,485 affiliations of 71 countries), the study aims to illustrate the current connections of editorial leadership in social sciences. Findings reveal that two countries-the U.S. and the U.K.-and their institutions shape almost all fields of the social sciences, with institutions from other geographies, particularly non-English-speaking countries, being substantially underrepresented. However, there is no central institution that dominates across all fields, but within dominant geographies, a reduced number of different affiliations prevail in the most important intellectual terrains. In terms of gender representation, there is a significant imbalance across all dimensions under study. Male editors-in-chief outnumber females across most fields (66.67%), countries (76.60%), and affiliations (63.16%). All in all, by critically mapping the connections of editors-in-chief in social sciences journals, this study seeks to advance our understanding of the current structure of editorial governance and, in turn, stimulate initiatives aimed at fostering a more representative leadership in social science, keeping levels of scientific excellence constant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Goyanes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Psychosocial Rehabilitation Project (PRP) is a tool designed to structure and organize mental health care, guided by the theoretical and practical principles of Psychosocial Rehabilitation (PR). This article aims to identify the initial requirements for the prototyping of a "Psychosocial Rehabilitation Project App". To achieve this, an integrative review was conducted with the research question: what initial requirements are important to compose the prototype of the "Psychosocial Rehabilitation Project App" in mental health? In the search process, 834 articles were identified and exported to the online systematic review application Rayyan QCRI, resulting in 36 eligible articles for this study, along with one app. The reading of this material allowed the elicitation of three themes: privacy and data protection policy; design; and software and programming. The prototyping of the "Psychosocial Rehabilitation Project App" should prioritize data security and protection, simplicity in design, and the integration of technological resources that facilitate the management, construction, monitoring, and evaluation of psychosocial rehabilitation projects by mental health professionals., Competing Interests: The authors declare no conflicts of interest.

Resonance frequency analysis (RFA) has been used as a diagnostic method to measure implant stability at all stages of healing. In addition to evaluating the status of the peri-implant marginal bone, it can also indicate the most appropriate time to load the implant. This in vitro study aimed to evaluate the efficacy of RFA as a diagnostic method for the detection of peri-implant marginal bone loss (MBL). Forty bone-level Klockner Vega implants were placed in a polyurethane block with elastic properties similar to those of the maxillary bone. The insertion torque and primary implant stability at the time of placement were measured using an RFA device. A circumferential peri-implant defect was created by removing the cortical bone portion in each implant using a trephine. The stability values were measured again using RFA. The stability values measured using RFA were lower after the creation of the circumferential peri-implant defect, indicating a statistically significant decrease in implant stability. The results of the study tend to show a relationship between peri-implant marginal bone loss and modifications in implant stability measured by RFA.

Purpose: Survival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities., Methods: A systematic review of randomized controlled trials of MM that reported testing for HRCA between January 1, 2000, and December 9, 2021, was performed. Groups were contacted and asked to locally perform a novel, federated analysis of their data for single hit (one HRCA) and double hit (≥two HRCAs), using a centrally provided algorithm. Analysis results were centrally collated and meta-analyzed to assess the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) for one/≥two HRCAs across patient subgroups using random-effects models., Results: Twenty-four trials including 13,926 patients were included. The median age of participants was 66.5 years (IQR, 59-72) and 56.5% were male (IQR, 52-60). The HR for PFS was 2.28 (95% CI, 2.05 to 2.54) for patients with ≥two HRCAs and 1.51 (95% CI, 1.38 to 1.65) for patients with one HRCA. The HR for OS was 2.94 (95% CI, 2.49 to 3.47) and 1.69 (95% CI, 1.52 to 1.88) for the two subgroups, respectively. In studies initiated since 2015, the effect abides (≥two HRCA PFS, HR, 2.39 [95% CI, 1.96 to 2.91]; OS, 3.10 [95% CI, 2.10 to 4.60]) both for NDMM and RRMM. Heterogeneity related to transplant eligibility and relapsed/refractory status was as expected., Conclusion: The association of ≥two HRCAs with the poorest outcome in NDMM and RRMM, and across treatment modalities, as demonstrated here for the first time to our knowledge, allows for more focused development of novel approaches to these patients with high unmet need.

Background and Objectives: Given the stigma of dementia, individuals with the condition may be wary to disclose their diagnosis to other people, both in face-to-face and digital settings. While sharing one's dementia diagnosis with others is essential for accessing valuable support for social, cognitive, and physical well-being, this area of research has largely been neglected. In this meta-synthesis, we aimed to systematically review qualitative research on the factors associated with online and offline self-disclosure in people with dementia., Research Design and Methods: We conducted a systematic search in 6 electronic databases. Inclusion criteria comprised qualitative and mixed-methods studies describing experiences with self-disclosure in people with any type of dementia. Quality of the included studies was assessed using the Mixed Methods Appraisal Tool. The meta-synthesis was conducted in NVivo using a thematic synthesis approach., Results: 28 studies were included. 3 analytical themes were generated: "Concealment," "Stigma and fear," and "Taking control," the latter 2 with subthemes. Findings from this review were corroborated with people with dementia and family carers as part of Patient and Public Involvement meetings. Our findings reveal that while stigma plays a pivotal role, people with dementia can take control of the meaning of their diagnosis through self-disclosure., Discussion and Implications: Self-disclosure is complex and multifaceted. People with dementia, particularly those experiencing stigma, can benefit from post-diagnostic support that encompasses resources and interventions for self-disclosure. Further research is required to investigate people with dementia's disclosure decision-making process., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Gerontological Society of America.)

Background: The relationship between alcohol consumption and vascular structure and arterial stiffness is not clear, especially in people diagnosed with persistent COVID. The aim of this study was to evaluate how alcohol use is related to vascular structure and arterial stiffness in adults with persistent COVID., Methods: A descriptive cross-sectional study was conducted involving 305 individuals (97 men and 208 women) diagnosed with persistent COVID according to the WHO criteria. Arterial stiffness was assessed by measuring the cardio-ankle vascular index (CAVI) and the brachial-ankle pulse wave velocity (ba-PWV) with a VaSera VS-1500 device, and the carotid-femoral pulse wave velocity (cf-PWV) with a Sphygmocor device. Vascular structure was assessed by measuring carotid intima-media thickness (c-IMT) with a Sonosite Micromax ultrasound unit. Alcohol intake was calculated using a standardized questionnaire and quantified in g/week., Results: Mean alcohol intake was 29 ± 53 g/week (men 60 ± 76 g/w and women 15 ± 27 g/w; p < 0.001). Heavy drinkers showed higher levels of c-IMT, cf-PWV, ba-PWV and CAVI than non-drinkers ( p < 0.05). The multinomial regression analysis adjusted for sex and lifestyles showed a positive association between heavy drinking and c-IMT and cf-PWV values (β = 1.08 (95% CI 1.01-1.17); β = 1.37 (95% CI 1.04-1.80); ba-PWV and CAVI figures showed a similar trend, without reaching statistical significance., Conclusions: The results of this study indicate that high alcohol use in patients with persistent COVID is linked to higher c-IMT and cf-PWV figures than in non-drinkers.

Background: Long COVID has been associated with increased cardiovascular risk and chronic low-grade inflammation, raising concerns about its long-term metabolic consequences. Given that the Mediterranean diet (MD) has shown beneficial effects on cardiovascular risk factors and inflammation in various populations, it is important to explore its potential impact on individuals with Long COVID. Therefore, the aim is to determine the association of the MD with cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in Caucasian subjects diagnosed with Long COVID., Methods: Cross-sectional study, 305 subjects diagnosed with Long COVID were included following the WHO criteria. Adherence to MD was evaluated with the MEDAS (Mediterranean Diet Adherence Screener) with 14 items used in Prevention with Mediterranean Diet study (PREDIMED study). The criteria considered to diagnose MetS were blood pressure, glycemia, triglycerides, HDL cholesterol, and waist circumference. Other CVRFs considered were tobacco consumption, total cholesterol, LDL cholesterol, body mass index, and baseline uric acid levels. The association between MD with CVRF and the number and components of MetS was analyzed using multiple regression models and multinomial regression., Results: The mean age was 52.75 ± 11.94 years (men 55.74 ± 12.22 and women 51.33 ± 11.57; p = 0.002), (68% women). The mean of the MEDAS questionnaire was 7.76 ± 2.37. The presented MetS were 23.6% (39.8% men and 15.9% women p < 0.001). In the multiple regression analysis, after adjusting for age and average time from acute COVID-19 infection to the date of inclusion in this study, the mean MD score showed a negative association with uric acid (β = -0.295; 95% CI: -0.496 to -0.093), BMI (β = -0.049; 95% CI: -0.096 to -0.002), the number of MetS components (β = -0.210; 95% CI: -0.410 to -0.010), and waist circumference (WC) (β = -0.021; 95% CI: -0.037 to -0.003) and a positive association with HDL cholesterol (β = -0.018; 95% CI: 0.001 to -0.037)., Conclusions: The findings of this study suggest that higher Mediterranean diet scores are associated with lower levels of uric acid, fewer MetS components, smaller waist circumference, and higher HDL cholesterol levels in individuals with Long COVID.

Purpose: Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients' survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease-negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed/refractory (RR) MM., Patients and Methods: Individual patient data from 20 randomized multicenter trials were collected. Eleven studies (4,773 patients) with sufficient data were analyzed to evaluate whether 9- or 12-month MRD-CR classified at a 10 -5 threshold could be reasonably likely to predict the clinical benefit of new agents regarding PFS and OS. Global odds ratio (OR) was estimated using the bivariate Plackett Copula model. Supportive evaluation included correlations of the treatment effects on MRD-CR end points and PFS/OS, evaluated by both linear regression ( R 2 weighted least squared ) and Copula ( R 2 Copula ) models., Results: The analysis demonstrated that both 9- and 12-month MRD-CR strongly correlated with PFS at patient level in NDTE patients, NDTinE patients, and patients with RRMM. Global ORs ranged from 3.06 to 16.24, all with 95% CIs excluding 1.0. Encouraging trial-level correlations ( R 2 , 0.61-0.70) were observed by pooling three populations and were stronger ( R 2 , 0.67-0.78) in the ND population. Similar results were observed for OS., Conclusion: Our findings provided the support for use of MRD-CR classified at a 10 -5 threshold at either 9 or 12 months after starting of the treatment, as an intermediate end point to support accelerated approvals, in future trials in NDTE patients, NDTinE patients, and patients with RRMM.

Background: The aim of the present study was to assess the accuracy, repeatability and reproducibility of a novel digital technique to analyze the remaining cement after debonding lingual multibracket appliances and after polishing the remaining cement., Methods: Thirteen teeth were embedded in an epoxy resin simulating a dental arch and subsequently a digital impression was taken using an intraoral scanner; obtaining a standard tessellation language (STL1) digital file. Lingual multibracket appliances were bonded and debonded on the lingual surfaces of all teeth and another digital impression was made (STL2). Finally, the polishing procedure of the remaining cement was performed and a digital impression was taken (STL3). The teeth were individually segmented from the digital files and an alignment was performed between STL1 and STL2 and between STL1 and STL3 digital files using specific cephalometric 2D/3D software to assess the remaining cement after debonding and after polishing lingual multibracket appliances. The reproducibility and repeatability capacity of the measurement digital method was assessed using a Gage R&R statistical analysis., Results: The results were assessed by a statistical program and showed a statistically significant ( p < 0.001) decrease in weight, thickness, and height of the cement remaining after polishing, with a mean decrease of 2.09 mm in width (X plane), 0.12 mm in thickness (Y plane), and 1.87 mm in height (Z plane)., Conclusions: The use of novel digital diagnosis software is a repeatable, reproducible, and accurate measurement technique to analyze the remaining cement after debonding lingual multibracket appliances and after polishing the remaining cement., Practical Implications: The diagnosis cephalometric software evaluation of the polishing technique with different materials, burs or polishing sequences brings the research closer to the clinical field. This methodology allows the orthodontist to clinically measure the cement remnants after polishing without the need for teeth extraction and with current clinic objects such as intraoral scanning and orthodontic cephalometric software. This might give orthodontics more clearance in terms of better burs or protocols for polishing.

Background and Objective : Access to high-quality patient-derived brain tumor tissues is instrumental for translational neuro-oncology research. Glioblastoma tumor material resected by ultrasonic aspiration (UA) during surgery offers an abundant source of material; however, it is generally not used for research experiments. We hypothesize that UA-derived tumor tissue represents a source of tissue that accurately reflects the immune infiltrates of glioblastomas. Methods : In this study, we have utilized UA-derived tissue and performed a head-to-head comparison with paired resection tissue from the vital tumor core of the same patient. A combination of 16 fluorochrome-conjugated antibodies was designed to identify tumor-infiltrating T, B, and NK lymphocytes and characterize the TILs by spectral flow cytometry. Furthermore, a 5-plex panel was designed to spatially characterize the T cells, macrophages, and tumor cells on the paired UA and resection tissues. Results : UA-obtained cells exhibited a comparable yield and viability, as well as an abundance of tumor-infiltrating T, B, and NK lymphocytes compared to resection sample-derived cells. Importantly, we observed that there is a high concordance with respect to expression intensities of immune checkpoints by T cells in both types of tissue samples. Conclusions : These findings underscore the feasibility and reliability of utilizing the immune infiltrates from ultrasonic aspiration-acquired glioblastoma tissue.

An inaccurate bonding procedure of the attachments related to clear aligner systems could influence the predictability of tooth movement The aim of this study was to compare the positioning reliability of horizontal and vertical orthodontic clear aligner attachments., Materials and Methods: A total of 70 horizontal and 70 vertical orthodontic clear aligner attachments were bonded to five upper and five lower experimental anatomically based acrylic resin models with 14 clinical crowns each. The experimental anatomically based acrylic resin models were randomly distributed to the following study groups: Group A-horizontal orthodontic clear aligner attachments ( n = 70) (HORIZONTAL) and Group B-vertical orthodontic clear aligner attachments ( n = 70) (VERTICAL). Afterward, the orthodontic clear aligner attachments were digitally planned using orthodontic planning software, and orthodontic templates were manufactured by thermoforming on 3D-printed models in trilayer glycol-modified polyethylene terephthalate. Both horizontal and vertical orthodontic clear aligner attachments were put through an intra-oral scan to obtain a postoperative digital image, and PAPver, PCPver, PMVver, AUver, Alver, PPMhor, PPDhor, PMVhor, AMhor and ADhor cephalometric parameters were analyzed using a t -test or a non-parametric Mann-Whitney-Wilcoxon test., Results: The results showed that all cephalometric parameters showed statistically significant differences ( p < 0.05) between the accuracy of the indirect bonding technique for horizontal and vertical orthodontic clear aligner attachments, except for the PAPver ( p = 0.6079) and PMVhor ( p = 0.5001) cephalometric parameters., Conclusions: The vertical orthodontic clear aligner attachments are more accurate than the horizontal orthodontic clear aligner attachments through the indirect bonding technique.

To determine the variations in the costs of the prophylaxis of recurrent urinary tract infections (RUTIs) among different prevention protocols, a prospective observational multicenter study on 1614 women receiving RUTI prophylaxis was conducted. The patient groups were as follows: Group A (n = 444): conventional suppressive antibiotic therapy; Group V (n = 732): polyvalent bacterial vaccine; and Group O (n = 438): other adjuvant measures. The variables were age, body mass index, American Society of Anesthesiologists (ASA) physical status classification scale, cost of prophylaxis, duration of the RUTI, number of visits for primary and specialized care, number of UTIs, cost of urinalysis, urine culture, urine cytology, and days of sick leave. The mean age was 57.71 years but was found to be lower in GV. The mean expenditure on UTI prophylaxis and treatment per patient was EUR 4908.07, but this found to be higher in GO. Emergency primary care visits were more frequent in GA. The ordinary scheduled visits to primary care visits were more frequent in GV and GO. The mean successive visits was 2.47 and was shown to be lower in GV. The mean expenditure on successive visits was EUR 341.64 but was found to be lower in GV. The mean number of UTIs was 4.83 at 3 months after finishing prophylaxis and 5.01 at 12 months, and it was observed to be lower in GV. Less frequent VCU usage, older age, more ASA III, more frequent use of urinalyses, urine cultures, ultrasounds, and CT scans were associated with higher costs. In GO, IVU was associated with higher costs. The total expenditure related to RUTIs is associated with older age and the number of RUTIs, a poorer general health status, and the use of urinary tract ultrasounds and CT scans. The use of VCUs instead of ultrasounds and CT scans is cost-effective in the management of RUTIs in older women. Immunoprophylaxis is more cost-effective in reducing the number of visits to the primary care emergency room, the number of successive visits to the Urology Department, the number of intercurrent infections, and the need for urinalyses, urine cultures, CT scans, and ultrasounds in the primary care emergency room.

Background and Rationale: Cholangiocarcinoma (CCA) includes a diverse group of biliary malignancies with poor prognosis. Alterations in post-translational modifications contribute to disrupted protein dynamics, cellular disturbances, and disease. This study investigates the role of protein SUMOylation in cholangiocarcinogenesis and its potential as a therapeutic target., Approach and Results: Analysis of CCA tumors from four patient cohorts and CCA cell lines, revealed increased expression of the SUMOylation machinery genes SAE1 and UBE2I , regardless of the tumor's molecular profile, resulting in elevated levels of SUMO1-conjugated proteins. Higher SAE1 and UBE2I levels were both indicative of unfavorable clinical outcomes. Deregulated SUMOylated proteins in CCA, mostly linked to cell proliferation, survival, and homeostasis, were identified through immunoprecipitation and mass spectrometry. Genetic ( UBE2I -knockdown) and pharmacological (ML792 and SAMe) inhibition of SUMOylation effectively suppressed tumorigenesis in subcutaneous and oncogene-driven CCA models, reducing the presence of cancer-associated fibroblasts (CAFs) and increasing the recruitment of anti-tumor immune cells. In vitro , targeting SUMOylation induced CCA cell death and reduced cell proliferation, colony formation, and spheroid growth. Importantly, ML792 and SAMe did not adversely affect normal human cholangiocytes. Moreover, co-culture of wild-type or UBE2I -knockdown CCA cells with CAFs revealed that depleting SUMOylation in CCA cells impaired CAF cell growth and altered their protein secretome, ultimately disrupting CCA growth through a regulatory feedback loop., Conclusion: Aberrant SUMOylation drives CCA progression by enhancing cell survival, proliferation, and shaping the tumor microenvironment. Targeting SUMOylation shows potential in inhibiting CCA growth, representing a promising therapeutic strategy., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Crohn's disease (CD) negatively impacts quality of life, and a high percentage of patients will need surgery. Ileocecal resection (ICR) is the most common abdominal procedure performed in CD. Postoperative complications are frequent, and recurrence is common. The main objectives of this study were to analyze risk factors (RF) for anastomotic leakage (AL) and recurrence after ICR, as well as quality of life (QoL) in CD in a sample of the Spanish population., Methods: A prospective, multicenter, observational study was designed, including all types of hospitals in Spain from 2018 to 2021. Demographic and medical-surgical characteristics, postoperative complications, hospital types by annual ICR volume, and quality of life (IBDQ-9) up to 1 year follow-up (OYF) were recorded and analyzed., Results: A total of 386 ICRs were recorded. At 60 days, there were 134 (36.4%) complications, 46 (11.91%) of which were major. A total of 23 (5.9%) AL were registered, and RF were Montreal A3 [OR 14.2, 95% CI (2.70-126), p = 0.005], Montreal p [OR 7.29, 95% CI (1.14-44.4), p = 0.029], and intensified adalimumab treatment [3.8, 95% CI (1.2-13.1), p = 0.026]. Recurrences at OYF were 67 (19%), and RF were history of neoplasia [OR 7.14, p = 0.01], Montreal B3 [OR 2.12, p = 0.02], and minimally invasive surgery (MIS) [OR 2.63, p = 0.02]. The mean difference in IBDQ-9 from baseline to 60 days was +1.72 (n = 177, p < 0.001) and to OYF +2.12 (n = 140, p < 0.001)., Conclusions: The AL rate was 5.9%. Montreal A3, perianal disease, and intensified adalimumab were associated with a higher rate of AL. The recurrence rate was 17.6% (OYF). Prior neoplasia, Montreal B3, and MIS were associated with higher risk of recurrence. ICR improves quality of life at 60 days and is maintained 1 year after surgery., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All procedures performed in studies involving human partcipants were in accordance with the ethical standards of the instutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent: The participants have consented to the submission of the paper to the journal., (© 2025. Springer Nature Switzerland AG.)