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Abstract Magnetic resonance imaging (MRI) has changed veterinary diagnosis but its long-sequence time can be problematic, especially because animals need to be sedated during the exam. Unfortunately, shorter scan times implies a fall in overall image quality and diagnosis reliability. Therefore, we developed a Generative Adversarial Net-based denoising algorithm called HawkAI. In this study, a Standard-Of-Care (SOC) MRI-sequence and then a faster sequence were acquired and HawkAI was applied to the latter. Radiologists were then asked to qualitatively evaluate the two proposed images based on different factors using a Likert scale (from 1 being strong preference for HawkAI to 5 being strong preference for SOC). The aim was to prove that they had at least no preference between the two sequences in terms of Signal-to-Noise Ratio (SNR) and diagnosis. They slightly preferred HawkAI in terms of SNR (confidence interval (CI) being [1.924–2.176]), had no preference in terms of Artifacts Presence, Diagnosis Pertinence and Lesion Conspicuity (respective CIs of [2.933–3.113], [2.808–3.132] and [2.941–3.119]), and a very slight preference for SOC in terms of Spatial Resolution and Image Contrast (respective CIs of [3.153–3.453] and [3.072–3.348]). This shows the possibility to acquire images twice as fast without any major drawback compared to a longer acquisition.

Abstract Background Postnatal care, crucial for preventing and assessing complications after birth, remains low in India. An interactive mHealth community-based postnatal intervention was implemented to promote healthy maternal behaviors through knowledge and social support in rural Northern India. However, there is limited information on how virtual health interventions in resource-constrained settings are perceived by the users and which elements influence their engagement and sustained participation. Objective We explored the user perceptions of acceptability and impact of a virtual interactive maternal and child health intervention pilot tested in Punjab State, India, including their perspectives on barriers and facilitators to engage with this intervention. Methods This qualitative study was embedded within extensive mixed-method research, and oriented by the Realist Evaluation approach. Sixteen participants were recruited from the parent study. They were identified by purposive sampling to cover diverse levels of attendance and engagement with the intervention. In-depth interviews were conducted by phone. Following translation, a framework analysis was completed to search for the main themes. Feedback was requested from intervention moderators during the process to prioritize local interpretation. Results Study participants reported overall satisfaction with the intervention. The mothers appreciated the educational material provided and the communication with other participants and health professionals. Across context, intervention, and actor domains, the barriers most commented on were network and connectivity challenges, lack of time due to household responsibilities, and feeling uncomfortable sharing personal experiences. Family buy-in and support were fundamental for overcoming the high domestic workload and baby care. Another facilitator mentioned was moderators’ guidance on using the different intervention modalities. Regarding perceived impact, participants shared that MeSSSSage increased their capability and motivation to breastfeed, seek care as needed, and use contraception according to their preferences. Finally, participants suggested adding more topics to the educational content and adjusting the dynamics within the group calls to improve the intervention. Conclusions This study identifies the high acceptability and perceived impact of a novel postnatal care program in a rural setting, including the users’ perceived barriers to engaging with the intervention and possible solutions to overcome them. These findings enable refinement of the ongoing intervention, providing a more robust framing for its scalability and long-term sustainability. On a larger scale, conclusions from this research provide new insights and encouragement to global stakeholders who aspire to improve maternal and neonatal outcomes in low-income and middle-income countries through mHealth. Trial Registration ClinicalTrials.gov NCT04693585 (Registration date: 05/01/21).

Abstract Background The invasive and metastatic spread of serous ovarian cancer (SOC) results from the cooperative interactions between cancer and stroma, which include extracellular matrix (ECM) and cellular components, including cancer-associated fibroblasts (CAFs). Soluble factors secreted by cancer and stromal cells contribute to stroma remodeling through the secretion of ECM proteins, providing a favorable environment for cancer cell dissemination. The peptide endothelin-1 (ET-1), through two G protein-coupled receptors (GPCR), endothelin receptor type A (ETAR) and B (ETBR), acts on both cancer and stromal cells, engaging the protein β-arrestin1 (β-arr1), to bolster SOC progression. However, its role in the regulation of the ECM proteins by ovarian fibroblasts is not understood. This study delves into the role of ET-1 as a regulator of type I collagen (Col1) and fibronectin (FN). Methods We used human primary ovarian fibroblasts (HOFs) and CAFs. The expression of Col1 (COL1A1) and FN (FN1) were detected by western blotting (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and confocal laser scanning microscopy (CLSM) in cells and tumor tissue sections from mice xenografts, while the transcription of COL1A1 was detected by luciferase reporter gene assay. The nuclear function of β-arr1 was evaluated by silencing and rescue expression with wild-type (WT) and nuclear mutant plasmid constructs, RNA seq and differential gene expression and gene sets enrichment analyses. The prognostic role of COL1A1, FN1, EDN1 (ET-1) and ARRB1 (β-arr1) gene expression was evaluated using the Kaplan–Meier plotter database and clinical ovarian cancer tissue samples. Results We demonstrated that ET-1 boosts Col1 and FN expression in HOFs, akin to ovarian CAF levels. Both receptors are implicated, evident from inhibitory effects after ETAR or ETBR antagonist treatments and notably with bosentan, a dual antagonist, in vitro and in vivo. At the molecular level, ET-1 triggers the activation of COL1A1 promoter activity and its enhanced expression via β-arr1 nuclear function. Transcriptome analysis of β-arr1-silenced HOFs confirms the nuclear role of β-arr1 in collagen and ECM remodeling-related protein transcriptional regulation. Accordingly, a high level of EDN1/ARRB1 expression in combination with either COL1A1 or FN1 is associated with the poor prognosis of SOC patients. Conclusions These findings hint at ET-1 involvement in ECM remodeling and early SOC stages by modulating the expression of Col1 and FN. Targeting ET-1 signaling with ETAR/ETBR antagonists might interfere with the ability of CAFs to produce key ECM proteins in this tumor.

Abstract The common bottlenose dolphin is a cosmopolitan species that can be found worldwide in all oceans except polar and sub-polar waters. This wide distribution is associated with a certain level of morphological variation, which seems consistent with the presence of a globally distributed pelagic/offshore ecotype and several coastal/inshore ecotypes distributed along the continental shelf. In the Mediterranean Sea, the common bottlenose dolphin is a regularly occurring species and the second most sighted cetacean after the striped dolphin. According to some studies, the Mediterranean bottlenose dolphin is more closely related to the Atlantic coastal ecotype, while others suggest a closer link with the pelagic ecotype. This apparent contradiction could stem from the coexistence of two ecotypes also within the Mediterranean Sea, as suggested by genetic analyses. We analysed data collected from 2004 to 2019 by 43 different research groups, distributed in different areas of the basin, and shared on the web-based GIS platform Intercet. We analysed the distribution and movements of 4919 bottlenose dolphins, individually identified through their natural dorsal fin markings, in relation to bathymetry and in particular to the 200-meter isobath that marks the edge of the continental shelf. In addition, we reconstructed the associations between individuals within connectivity networks, to identify possible segregations between ecotypes. Our results show that most bottlenose dolphin geographical units find their habitat over the continental shelf, while the analysed data do not support the coexistence of different ecotypes (pelagic vs. coastal) living in parapatry, as described in the adjacent waters of the eastern Atlantic Ocean.

Abstract Background Chemsex, characterized by the intentional use of specific drugs to enhance sexual experiences during group sessions, represents a challenge for the health of some sexually active communities, such as men who have sex with men (MSM). MSM may experience mental health issues associated with chemsex participation. This survey aims to investigate the characteristics, prevalence, and correlates of sexualized drug use (SDU) and chemsex with a focus on the emotional vulnerability associated with chemsex and SDU engagement among MSM at high risk of sexually transmitted infections (STI). Methods A self-administered anonymous questionnaire to investigate demographical data, attitudes toward substance dependence, sexual behaviors and vulnerability for common mental disorders (CMD), was offered to consecutive MSM attending the STI/HIV Unit of San Gallicano Dermatological Institute of Rome, Italy, from 1 to 30 November 2023. The Mann-Whitney and Fisher’s test were used to assess differences in terms of sexual behavior, SDU, STI risk and vulnerability for CMD between MSM who don’t engage in SDU, who engage only in SDU (no chemsex) and chemsex. Results One hundred and twenty-two MSM agreed to participate. Overall, 47.3% (57/119) were people living with HIV (PLWH) on antiretroviral therapy (ART); fifty (40.9%, 95% CI: 32.7–49.9) participants reported SDU, 24 (19.7%, 95% CI: 13.6–27.6) of which reported chemsex. Participants reporting SDU or chemsex were in unstable relationships (p =

Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.

Segmentation of running data into gait cycles and stance/swing phases is crucial for evaluating running biomechanics. The benefit of magneto-inertial sensors is their ability to capture data in outdoor conditions. However, state-of-the-art inertial-based methods for estimating running temporal parameters are limited to a restricted range of running speeds and, thus, not able to analyze running at variable speeds. This limitation prevents their use for real-world analysis for a wide range of runners and for sports disciplines where athletes vary their running speed. This study evaluated the speed-dependance of eight relevant foot-mounted inertial-based methods from previous research and proposed a novel method that could be robust to speed changes. The proposed method applied, for the first time, a template-matching algorithm based on dynamic time warping to running analysis and compared it to existing methods. All the implemented methods were tested on 30 runners at different speeds ranging from jogging to sprinting (8 km/h, 10 km/h, 14 km/h, 19-30 km/h) on both treadmill and overground. The most speed-robust performance was achieved by the proposed template-based method, providing estimation errors below 0.1% in stride, between 7%-19% in stance, and between 3%-6% in swing across running speeds. Conversely, all the tested methods from the literature were significantly speed-dependent. Thus, this study suggested that template-based approach is a valid solution for the inertial-based estimation of temporal parameters during running from slow jogging to fast sprinting. MATLAB codes and templates have been made available online.

Abstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I2). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus.

Abstract Background Poor quality of life in adults with anorexia nervosa (AN) and persistent high rates of readmission highlight the necessity of developing interventions to optimize treatment outcomes. ECHOMANTRA is a novel online intervention based on interventions for carers (Experienced Carers Helping Others, ECHO) and patients (Maudsley Model of Anorexia Nervosa Treatment for Adults, MANTRA) with anorexia nervosa. The objective of this paper is to describe the study protocol of a randomized control trial (RCT) aimed at evaluating the efficacy of an adaptation of the ECHOMANTRA for adults AN inpatients and outpatients, and their carers, to be implemented as an add-on to treatment-as-usual (TAU). Methods In a multi − center pilot randomized controlled trial (RCT), 148 adult AN patients, and their carers, will be randomized to receive treatment as usual (TAU) or TAU plus ECHOMANTRA. Assessments will take place at baseline (T0), post-intervention (2-month) (T1), 6-month follow-up (T2), and 12-month follow-up (T3). Primary outcomes will be eating disorder psychopathology and psychological well-being. For carers, outcome variables will include psychological well-being, accommodation and enabling behaviors, expressed emotion, illness burden, quality of life and care skills. Discussion This study will provide evidence of the efficacy of this novel, online and protocolized intervention in facilitating the recovery of these patients. Trial registration ISRCTN registry (Identifier: 80253157 https://doi.org/10.1186/ISRCTN80253157 ).

This study examines the application of corpus linguistics in English language teaching (ELT) in Colombia, where its practical adoption remains limited compared to many developed countries. Data were gathered through a survey of English instructors at Colombian universities to assess their familiarity with corpus linguistics. Findings indicate significant challenges, including lack of formal training, low awareness of corpus-based methodologies, and insufficient resources for implementing corpus linguistics applications. The study highlights the potential for enhancing corpus linguistics research and application in Colombia, emphasizing the necessity for improved training and collaborative practices, which could foster greater participation in global corpus linguistics initiatives and enhance the overall effectiveness of ELT.

Abstract RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5). The mechanism of SNAPc cross-polymerase engagement and the role of the SNAPC2 and SNAPC5 subunits remain poorly defined. Here, we present cryo-EM structures of the full-length SNAPc-containing Pol III PIC assembled on the U6 snRNA promoter in the open and melting states at 3.2–4.2 Å resolution. The structural comparison revealed differences with the Saccharomyces cerevisiae Pol III PIC and the basis of selective SNAPc engagement within Pol III and Pol II PICs. Additionally, crosslinking mass spectrometry localizes SNAPC2 and SNAPC5 near the promoter DNA, expanding upon existing descriptions of snRNA Pol III PIC structure.

This study investigates how the relationship between farmers and buyers affects the adoption of sustainable agricultural practices (SAPs) in the vegetable sector in Chile. Specifically, we focus on the dyadic relationships between farmers and different types of buyers, including besides lead firms, intermediaries, and wholesalers, which have received little attention in the scientific literature. Our analysis focuses on formal and informal contracts as governance forms between farmers and buyers, and explores the correlation between contract provisions (e.g., quality, quantity, and the provision of services), relationship attributes (i.e., satisfaction, trust, and opportunism) and adoption of SAPs. We gathered survey data from 352 vegetable farmers in Chile and employed analysis of variance and logit modeling for our analysis. Our findings indicate that small‐scale farmers primarily engage with intermediaries using informal contracts, while medium‐scale farmers trade with wholesalers through spot markets, and large‐scale farmers with lead firms using formal contracts. We also found that farmers who traded through informal contracts, mainly with intermediaries, reported greater satisfaction in the farmer‐buyer relationship than farmers trading through formal contracts. However, farmers engaging in informal contracts were less likely to adopt SAPs than farmers trading through formal contracts. Our results suggest that the governance form (contracts or spot market) adopted for the relationship between farmers and buyers influences the adoption of SAPs, while the impact of relationship attributes on SAP adoption is less clear. A deeper understanding of buyers and their relationship with farmers is essential to enhance policies encouraging SAP adoption in regional and local fresh food supply chains. [EconLit Citations: Q13, Q15, Q56]. [ABSTRACT FROM AUTHOR]

Abstract Porcine Reproductive and Respiratory Syndrome (PRRS) causes huge economic losses to pig farms worldwide. Currently available vaccines do not always offer complete protection, due to the extreme variability of the virus. Therefore, good farming practices must be improved to prevent the disease from spreading across the pig production system. In this study, we inferred the dynamics of PRRSV population in Italy by applying bayesian methods on our ORF7 sequence dataset collected during a 15-years period. Random subsets from the overall dataset were built to reduce analysis runtime. Calculated evolutionary rate was consistent between subsets and with other findings on PRRSV and other RNA viruses (4–7 × 10− 3 substitution/site/year) while Time to the Most Recent Common Ancestor was less consistent (from 1980 to 1990). Despite this, in all population dynamic reconstructions, a massive increase in size calculated in early 2000s lasting until around 2010 was inferred. This spike is followed by very heterogeneous dynamics with some differences between subsets, probably due to the random sampling. Geographical origin was inferred in Emilia-Romagna region despite Lombardy being the region with the highest number of farmed animals and farm size. These findings reflect the choices regarding farm management and biosecurity taken in the last two decades, and not strictly related to PRRS. Phylogeny and phylogeography are powerful tools to better understand microorganisms population dynamics and make appropriate choices for disease control.

Abstract Whole genome sequencing has transformed rare disease research; however, 50–80% of rare disease patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified after reanalysis in 463 (2%) of 24,015 unsolved patients after previous analysis for variants in known disease genes. However, extensive manual interpretation was required. This led us to develop a reanalysis strategy to efficiently reveal candidates from recent disease gene discoveries or newly designated pathogenic/likely pathogenic variants. Optimal settings to highlight new candidates from Exomiser reanalysis were identified with high recall (82%) and precision (88%) when including Exomiser’s automated ACMG/AMP classifier, which correctly converted 92% of variants from unknown significance to pathogenic/likely pathogenic. In conclusion, Exomiser efficiently reinterprets previously unsolved cases.

Abstract Background 1,2-dichloroethane (1,2-DCA) biodegradation can occur through aerobic or anaerobic pathways that can be exploited in bioremediation strategies. Bioremediation interventions are site specific and generally based on anaerobic pathways, nevertheless expanding knowledge on proper conditions favoring the biodegradation and especially on 1,2-DCA degrading microorganisms is crucial. In this work the intrinsic biodegradation potential of an aquifer impacted by Chlorinated Aliphatic Hydrocarbons (mainly 1,2-DCA) was evaluated by characterizing the aquifer microbiome across space and time and by setting up biostimulation treatments in microcosms under different aerobic and anaerobic conditions, in parallel. Results The microbial profiling of the aquifer revealed noticeable alpha and beta diversity across the sampling sites within the aquifer and strong fluctuations over time. Surprisingly both the anaerobic and aerobic biostimulation treatments led to the successful removal of 1,2-DCA in microcosms, the enrichment of known 1,2-DCA degraders and the detection of reductive or hydrolytic dehalogenases. Ancylobacter and Starkeya were enriched in aerobic microcosms. Desulfovibrio and Desulfuromonas, known as perchloroethylene degraders, were enriched in anaerobic microcosms, suggesting they could be yet unknown 1,2-DCA respirers. Conclusions Our results demonstrate the occurrence of both aerobic and anaerobic bioremediation potential in the aquifer despite its negative redox potential. Due to the feasibility of direct oxidation with oxygen insufflation, we propose that an enhanced bioremediation strategy based on direct oxidation of 1,2-DCA could be applied to the contaminated aquifer as an ecofriendly, efficient and cost-effective approach as an alternative to anaerobic biodegradation.

El objetivo de la investigación fue analizar el comportamiento de las exportaciones de café colombiano de la partida 090111190000 durante el periodo 2019-2023, considerando los efectos de la crisis climática en la producción. La metodología adoptó un enfoque cuantitativo y descriptivo, con un diseño no experimental longitudinal, utilizando datos de Trademap organizados en Excel. Este enfoque permitió evaluar las variaciones en el valor FOB y las cantidades exportadas hacia diferentes mercados internacionales, especialmente aquellos con una alta demanda como Estados Unidos, Bélgica, Alemania y China. Los resultados indican que Estados Unidos se mantuvo como el principal destino de exportación en términos de valor FOB, acumulando más de 6 millones de dólares, seguido de Bélgica y Alemania. Sin embargo, la tendencia de exportación hacia Estados Unidos mostró un decrecimiento del 33.82% en 2022-2023, mientras que China experimentó un crecimiento significativo del 75.40% en el mismo periodo, lo que lo posiciona como un mercado emergente relevante para las exportaciones colombianas de café. Las conclusiones destacan la importancia de la diversificación de mercados para la sostenibilidad de las exportaciones de café colombiano, especialmente ante la crisis climática que afecta la productividad en regiones tradicionales. Se sugiere que las estrategias de internacionalización deben centrarse en mercados emergentes como China, aprovechando su tendencia de crecimiento, y reforzar las relaciones con Europa para mantener la competitividad del café colombiano en un contexto global cambiante.

Abstract The scaffold protein AMBRA1, which participates in the autophagy pathway, also promotes CD4+ T cell differentiation to Tregs independent of autophagy through its interactor PP2A. Here we have investigated the role of AMBRA1 in CD8+ T cell differentiation to cytotoxic T cells (CTL). AMBRA1 depletion in CD8+ T cells was associated with impaired expression of the transcription factors RUNX3 and T-BET that drive CTL differentiation and resulted in impaired acquisition of cytotoxic potential. These effects were recapitulated by pharmacological inhibition of the AMBRA1 activator ULK1 or its interactor PP2A. Based on the ability of PP2A to activate TFEB, we hypothesized a role for TFEB in the CTL differentiation program regulated by AMBRA1. We show that TFEB modulates RUNX3 and T-BET expression and the generation of killing-competent CTLs, and that AMBRA1 depletion, or ULK1 or PP2A inhibition, suppresses TFEB activity. These data highlight a role for AMBRA1, ULK1 and PP2A in CTL generation, mediated by TFEB, which we identify as a new pioneering transcription factor in the CTL differentiation program.

Abstract Patients with carotid stenosis can receive indication for either carotid endarterectomy (CEA) or carotid artery stenting (CAS), with both techniques having an impact on the autonomic function and baroreflex control. Seventy carotid stenosis patients randomly assigned to CEA or CAS were enrolled. After exclusion of some recordings, 33 CEA (age 67.79 ± 5.32 yrs, 26 males) and 25 CAS (age 70.32 ± 3.63 yrs, 14 males) were admitted to analysis. Autonomic and baroreflex sensitivity markers were derived from the analysis of heart period and systolic arterial pressure spontaneous variability derived in supine position and during active standing (STAND), before (PRE) the intervention and after a 6 and 12-month follow-up (FU6, FU12). CEA had a preserved response of autonomic and baroreflex control to STAND in PRE and FU6, suggesting an early improvement. CAS had a similar response at PRE but a blunted one at the follow-ups. When directly compared, the two groups had a similar autonomic function, with CAS having a reduced baroreflex control in PRE and lower autonomic function at FU6. All the differences disappeared at the long-term follow-up, showing a similar long term effect of the surgical procedures, suggesting that CEA and CAS induced a similar long-term impairment of autonomic and baroreflex controls.

Abstract Background Solid organ transplant recipients (SOTRs) have an increased risk of developing non melanoma skin cancers (NMSCs). The use of Imiquimod, a toll‐like‐receptor agonist, is still debated in SOTRs. Objectives The aim of this study was to evaluate efficacy and safety of topical Imiquimod in two Dermatology Centres for skin cancers in SOTRs. Methods All SOTRs with age > 18 and a dermoscopic diagnosis of superficial basal cell carcinoma (BCC) and/or actinic keratose (AK), annually followed up between January 2022 and December 2022 were screened. Results 80 NMSCs (41 BCC and 39 AK) in 66 SOTRs were identified and treated. 57 (86.4%) were male. The mean age was 66.2 years (30−85). 60 patients (90.1%) had transplanted kidney, 1 (1.5%) lung, 3 (4.5%) liver, and 1 (1.5%) heart. The average time since first transplant was 17 years (3−40 years). Tacrolimus, steroids, and mycophenolate mofetil were the most frequently used immunosuppressants (71%; 67.7%; 53.2% of cases, respectively). Responses to the first course of treatment were CR in 64.3% of cases (53.6% in AK; 67.7% in BCC); PR in 28.6% of cases (42.9% in AK; 12.9% in BCC); NR in 12.5% of cases (3.6% in AK; 19.4% in BCC). Fourteen patients received a second course of imiquimod for a persistent lesion (1 AK, 4 BCC) or a new lesion (4 AK, 5 BCC). Responses to the second course of treatment were observed in 4 (80%) and 7 (78%) cases in the persistent and new lesion, respectively (p = 0.34). No systemic adverse events were noted. The main side effects were mild: erythema, scales, and crusts, itching, or pain. Conclusions Topical imiquimod represents a viable and safe option in this category of patients. The response to imiquimod in subjects who have had more than one cycle is not related to the response to previous treatments but rather to the intrinsic characteristics of the lesion.

Abstract Background Postoperative intracranial neurosurgical infections (PINI) complicate

Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.

Abstract The restaurant business plays a crucial role in the food economy and, like many industries, faces numerous challenges due to the rapid pace of change, driven by consumer trends and shifting demographics. In response to the pressure on businesses to adapt to these changing circumstances, new restaurant concepts, organizational structures and technologies have emerged in the hope of finding methods that are more agile during unpredictable times. The development of dynamic capabilities is a critical issue for both academics and practitioners, as it can enhance competitive advantages and improve organizational performance. The purpose of this paper is to examine the impact of dynamic capabilities on innovative potential and organizational performance. Through a literature review and the dynamic capability view, a theoretical model is proposed. This model was validated using the PLS-SEM technique, based on responses from 143 restaurants across eight of the largest Russian cities. The results indicate that dynamic capabilities related to the value proposition serve as a complete mediator in the relationship between a company's innovative potential and its performance in a highly volatile context. The proposed theoretical model is both unique and effective, demonstrating high explanatory power. This study enriches the existing literature on dynamic capabilities by addressing empirical research gaps and elucidating the mechanisms through which dynamic capabilities influence organizational performance.

Abstract Background As part of multimodal therapy, spinal manipulation (SM) is a recommended and effective treatment for musculoskeletal pain. However, the underlying physiological mechanisms for pain relief are largely unknown. SM thrusts can be described and quantified using force–time characteristics (e.g. preload force, peak force, thrust speed, thrust duration, and thrust impulse). If these biomechanical parameters of SM are important for clinical outcomes, a large variability in the delivery of SM could lead to inconsistent responses and could thereby potentially mask a significant clinical effect. Our goal was to determine variability, and repeatability of thoracic spinal manipulation (SM) force–time profiles in a sample of Swiss chiropractors. Methods All interventions were performed on a human analogue manikin. Participating chiropractors received three case scenarios with the following scenarios: 50-year-old male patient, 30-year-old male athlete, and a 70-year-old female patient, each presenting with uncomplicated musculoskeletal thoracic pain. Clinicians were asked to perform three consecutive thoracic SM thrusts for each of the scenarios and repeated the same interventions after 24–48 h. Results Eighty-one chiropractors participated in the study, including 32 females (39.5%) with a mean age of 45.22 ± 12.96 years. The variability in SM force–time characteristics between clinicians was substantial, with preload forces ranging from 4.50 to 450.25 N and peak forces ranging from 146.08 to 1285.17 N. Significant differences between case scenarios were observed for peak force (p

Abstract The adipose tissue (AT) surrounding breast cancer (BC) plays a pivotal role in cancer progression and represents an optimal source for new biomarker discovery. The aim of this work was to investigate whether specific AT factors may have prognostic value in estrogen receptor-positive (ER+) BC. Proteoglycan Versican (VCAN), Insulin-like Growth Factor 1 (IGF1), Reticulon 4B (RTN4), chemokines CCL5 (also known as RANTES) and interleukin 8 (IL-8) are expressed in AT and may play important roles in BC progression. Peritumoral AT and tumoral biopsies were obtained from patients with ER+ BC (N = 23). AT specimens were collected also from healthy women (N = 17; CTRL-AT). The analysis of gene expression by qPCR revealed significantly higher mRNA levels of VCAN, IGF1, RTN4, and CCL5 in BC-AT compared to the CTRL-AT, and no difference in IL-8 mRNA levels. VCAN positively correlated with patient Body Mass Index (BMI) in BC-AT, while not in CTRL-AT. Moreover, VCAN and IGF1 positively correlated with RTN4 and negatively with CCL5. Interestingly, VCAN correlated with tumoral Ki67, while IGF1 with tumoral OCT4 that, in turn, correlated with tumoral Ki67 and patient BMI. Thus, peritumoral AT content of VCAN, and IGF1 are related to BC proliferation and aggressiveness.