Search

The preparation of bridged bicyclooctadienes through the dearomatization of simple arenes is an interesting synthetic tool to access a vast chemical space of elegant molecular architectures from a wide range of simple and cheap building blocks. However, the energetic toll due to the loss of the aromatic stabilization has greatly limited the development of para-cycloadditions, especially with respect to intermolecular processes. We report herein the first general approach for the selective dearomatization of simple naphthalene. The visible-light-promoted reaction occurs under mild conditions over an ample range of substrates and it involves the initial sensitization of an acylallenamide. Moreover, complete control on the difunctionalization of either the internal or the terminal C–C double bond is observed depending on the substrate functionalization.

Abstract Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.

Abstract Background The introduction of technology-assisted rehabilitation (TAR) uncovers promising challenges for the treatment of motor disorders, particularly if combined with exergaming. Patients with neurological diseases have proved to benefit from TAR, improving their performance in several activities. However, the subjective perception of the device has never been fully addressed, being a conditioning factor for its use. The aims of the study were: (a) to develop a questionnaire on patients’ personal experience with TAR and exergames in a real-world clinical setting; (b) to administer the questionnaire to a pilot group of neurologic patients to assess its feasibility and statistical properties. Methods A self-administrable and close-ended questionnaire, Technology Assisted Rehabilitation Patient Perception Questionnaire (TARPP-Q), designed by a multidisciplinary team, was developed in Italian through a Delphi procedure. An English translation has been developed with consensus, for understandability purposes. The ultimate version of the questionnaire was constituted of 10 questions (5 with multiple answers), totalling 29 items, exploring the patient’s performance and personal experience with TAR with Augmented Performance Feedback. TARPP-Q was then administered pre-post training in an observational, feasible, multi-centric study. The study involved in-patients aged between 18 and 85 with neurological diseases, admitted for rehabilitation with TAR (upper limb or gait). FIM scale was run to control functional performance. Results Forty-four patients were included in the study. All patients answered the TARPP-Q autonomously. There were no unaccounted answers. Exploratory factor analyses identified 4 factors: Positive attitude, Usability, Hindrance perception, and Distress. Internal consistency was measured at T0. The values of Cronbach’s alpha ranged from 0.72 (Distress) to 0.92 (Positive attitude). Functional Independence Measure (FIM®) scores and all TARPP-Q factors (Positive attitude, Usability, Hindrance perception, except for Distress (p = 0.11), significantly improved at the end of the treatment. A significant positive correlation between Positive attitude and Usability was also recorded. Conclusions The TARPP-Q highlights the importance of patients’ personal experience with TAR and exergaming. Large-scale applications of this questionnaire may clarify the role of patients’ perception of training effectiveness, helping to customize devices and interventions.

Abstract Background Less invasive alternatives than early cholecystectomy (EC) for acute calculous cholecystitis (ACC) treatment have been spreading in recent years. We still lack a reliable tool to select high-risk patients who could benefit from these alternatives. Our study aimed to prospectively validate the Chole-risk score in predicting postoperative complications in patients undergoing EC for ACC compared with other preoperative risk prediction models. Method The S.P.Ri.M.A.C.C. study is a World Society of Emergency Surgery prospective multicenter observational study. From 1st September 2021 to 1st September 2022, 1253 consecutive patients admitted in 79 centers were included. The inclusion criteria were a diagnosis of ACC and to be a candidate for EC. A Cochran-Armitage test of the trend was run to determine whether a linear correlation existed between the Chole-risk score and a complicated postoperative course. To assess the accuracy of the analyzed prediction models—POSSUM Physiological Score (PS), modified Frailty Index, Charlson Comorbidity Index, American Society of Anesthesiologist score (ASA), APACHE II score, and ACC severity grade—receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUC) was used to compare the diagnostic abilities. Results A 30-day major morbidity of 6.6% and 30-day mortality of 1.1% were found. Chole-risk was validated, but POSSUM PS was the best risk prediction model for a complicated course after EC for ACC (in-hospital mortality: AUC 0.94, p

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP’s prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child–Pugh class B–C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child–Pugh class B–C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

El presente artículo expone los resultados preliminares del relevamiento realizado en el marco del proyecto "Movimentos socioterritoriais em perspectiva comparativa" (UNESP, Brasil, 2019-2022), implementado en distintas universidades de América Latina, cuyo objetivo es el estudio y la comparación de los movimientos socioespaciales y socioterritoriales a partir del análisis de sus acciones colectivas. Lxs autorxs de este trabajo pertenecemos a la Universidad Nacional de La Plata, y la información a presentar se encuadra en contextos urbanos de la Argentina durante el año 2021. A partir de su relevamiento se construye una matriz de información, en la que se organizan y clasifican bajo distintos criterios de agregación los datos obtenidos. Con los resultados preliminares de dicha base, realizamos un recorte teórico que permitió enfocarnos en aquellas acciones colectivas vinculadas a la lucha por la vivienda y el hábitat en diferentes regiones del país, a partir de las cuales se realizaron mapas y gráficos que dan cuenta de la distribución de dicha conflictividad. A su vez, nos propusimos identificar dentro de este entramado aquellas estrategias que responden a formas mercantilizadas y desmercantilizadas de producción del hábitat, formas que creemos que conviven y entran en tensión al interior del repertorio de acción al que nos referimos. Presentaremos el análisis de dos casos que, creemos, pueden ayudarnos a echar luz sobre estas tensiones, para finalizar con algunas conclusiones en torno a los resultados obtenidos del análisis de las acciones relevadas, en combinación con reflexiones teóricas del cuerpo de autores elegido.

Abstract The relationship between chromosomal and morphological variation in mammals is poorly understood. We analyzed the cranial size and shape variation in Ctenomys lami concerning to the geographic variation in their chromosome numbers. This subterranean rodent occurs in a narrow range of sand-dunes in the Coastal Plain of southern Brazil. This species presents a high karyotypic variation with diploid numbers varying from 2n = 54 to 2n = 58, involving the fission and fusion of chromosome pairs 1 and 2. Due to different chromosome rearrangement frequencies along their geographic distribution, four karyotypic blocks were proposed. This study, explored cranium shape and size variation in geographical, chromosomal polymorphism, and chromosome rearrangements contexts to test whether the four karyotypic blocks reflect morphologically distinct units. For this, we measured 89 craniums using geometric morphometrics and used uni and multivariate statistics to discriminate the predicted groups and test for an association among chromosomal and morphological variation. Our results show the size and shape of sexual dimorphism, with males larger than females, and support the existence of four karyotypic blocks for Ctenomys lami based on morphological variation. However, our results do not support a direct relationship between chromosomal and cranial morphological variation in C. lami.

Abstract The current study focuses on the investigation of AVPR2 (VTR2C) protein-coupled receptor variants specific to different primate taxa. AVPR2 is activated by the neurohormone AVP, which modulates physiological processes, including water homeostasis. Our findings reveal positive selection at three AVPR2 sites at positions 190, 250, and 346. Variation at position 250 is associated with human Congenital Nephrogenic Diabetes Insipidus (cNDI), a condition characterized by excessive water loss. Other 13 functional sites with potential adaptive relevance include positions 185, 202, 204, and 252 associated with cNDI. We identified SH3-binding motifs in AVPR2’s ICL3 and N-terminus domains, with some losses observed in clades of Cercopithecidae, Callitrichinae, and Atelidae. SH3-binding motifs are crucial in regulating cellular physiology, indicating that the differences may be adaptive. Co-evolution was found between AVPR2 residues and those in the AVP signal peptide/Neurophysin-2 and AQP2, other molecules in the same signaling cascade. No significant correlation was found between these Primates’ taxon-specific variants and the bioclimatic variables of the areas where they live. Distinct co-evolving amino acid sequences in functional sites were found in Platyrrhini and Catarrhini, which may have adaptive implications involving glucocorticoid hormones, suggesting varied selective pressures. Further studies are required to confirm these results.

The upgrade of the Large Hadron Collider (LHC) at CERN towards the High Luminosity-LHC (HL-LHC) presents different challenges, among them, the upgrade of the power converters associated to the inner triplet magnets to reach the required rated current of 18kA. In order to reach this current and to accomplish the stringent requirements associated to this kind of application, even under a fault scenario, redundancy and modularity are foreseen in the converter design. Consequently, the development of a 18kA/±10V power converter built from 10 parallel-connected sub-converters, each consisting of M modules, is carried out. Additionally, due to the converter being installed in an underground gallery, most of the heat must be extracted by using a water cooling system. Therefore, the reduction of power losses and an appropriate thermal design become key factors. These requirements, together with the large number of devices associated with the parallelization-based modular system, determine the choice of switching semiconductor devices as an important aspect in the design of the converter. This paper presents the process carried out for the choice of semiconductor devices based on analysis of power losses, thermal behavior and integration complexity. In this process, multiple variants in terms of semiconductor, number of modules, parallelization of devices, and switching frequency are considered. The proper operation of the selected device was verified on a 2kA sub-converter prototype based on the interconnection of 9 MOSFET based modules.

As queimaduras são traumas de importante relevância, não somente pela frequência com que ocorrem, mas, sobretudo pela capacidade de provocar sequelas, prolongar o tempo de internação e impactar negativamente na qualidade de vida. A terapia de fotobiomodulação é um tratamento promissor para auxiliar na cicatrização de feridas agudas ou crônicas, estimulando a microcirculação, reduzindo a inflamação, edema, dor e a carga bacteriana, com consequente redução dos custos relacionados às coberturas, antibióticos e tempo de internação. Mapear as evidências disponíveis a respeito da fotobiomodulação no processo de cicatrização de queimaduras: uma revisão integrativa. Revisão integrativa de literatura, descrita por Whittemore e Knafl. Após acesso às bases de dados e aplicação dos critérios de inclusão e exclusão, foram selecionados 07 artigos, publicados entre 2013 e 2023. A partir da análise dos artigos, emergiram três categorias: Aumento da proliferação celular, organização das fibras de colágeno, neoangiogênese e diminuição da inflamação mediadas pela fotobiomodulação; fotobiomodulação na redução da carga bacteriana em feridas por queimaduras infectadas; e associação de terapias na cicatrização de queimaduras. Conclui-se que a fotobiomodulação oferece uma abordagem não invasiva e promissora no tratamento de queimaduras, acelerando a cicatrização, reduzindo a inflamação e melhorando a aparência estética. Com mais pesquisas e avanços tecnológicos, espera-se que essa terapia se torne cada vez mais eficaz e amplamente utilizada no cuidado de pacientes com queimaduras.

ABSTRACT Epstein-Barr virus (EBV) is associated with 10% of human gastric carcinomas, which are distinguished by a CpG island methylator phenotype. In gastric carcinoma tumors and cell lines, the EBV genome also exhibits a high degree of 5-methyl cytosine (5mC) marks, which are propagated by host DNA methyltransferases (DNMT) with each cell cycle. Therefore, we sought to determine the effect of DNMT inhibition by the small molecule Decitabine (DCB) on EBV genomic 5mC and chromatin structure in two tumor-derived gastric cancer cell lines, YCCEL1 and SNU719. Decitabine effects on EBV genomic 5mC, chromatin structure, and viral gene expression were profiled by reduced representation bisulfite sequencing, ATAC-seq, and RNA-seq, respectively. Decitabine treatment resulted in global viral genome hypomethylation and a global increase in open chromatin. The most striking finding resulted from analyzing the methylation pattern from single RRBS sequencing reads, showing that the EBV genome contains a heterogeneous pool of epigenetic states, each of which is eroded upon Decitabine treatment. We observed heterogeneous 5mC epiallele patterns around EBV genomic CTCF binding sites and lytic gene transcriptional start sites. These results highlight the importance of 5mC in maintaining EBV genomic chromatin structure and latency. Furthermore, the presence of 5mC epialleles suggests EBV+ gastric cancers harbor transcriptionally distinct EBV episomes, which may exert distinct functional roles in maintaining latency and driving tumorigenesis. IMPORTANCE Epstein-Barr virus (EBV) latency is controlled by epigenetic silencing by DNA methylation [5-methyl cytosine (5mC)], histone modifications, and chromatin looping. However, how they dictate the transcriptional program in EBV-associated gastric cancers remains incompletely understood. EBV-associated gastric cancer displays a 5mC hypermethylated phenotype. A potential treatment for this cancer subtype is the DNA hypomethylating agent, which induces EBV lytic reactivation and targets hypermethylation of the cellular DNA. In this study, we identified a heterogeneous pool of EBV epialleles within two tumor-derived gastric cancer cell lines that are disrupted with a hypomethylating agent. Stochastic DNA methylation patterning at critical regulatory regions may be an underlying mechanism for spontaneous reactivation. Our results highlight the critical role of epigenetic modulation on EBV latency and life cycle, which is maintained through the interaction between 5mC and the host protein CCCTC-binding factor.

Key Clinical Message Concurrent polycystic liver disease and echinococcus infection can hinder diagnosis. Surgery may be needed for accurate diagnosis and treatment. Multidisciplinary collaboration is crucial. Abstract Cystic echinococcosis, caused by Echinococcus granulosus eggs, is a parasitic zoonosis that typically affects humans through accidental ingestion. Polycystic liver disease is a condition characterized by the presence of multiple liver cysts and is often associated with polycystic kidney disease. Here, we present a case of a man in his 70s with a pre‐existing diagnosis of polycystic liver disease. Radiological findings of a suspicious cyst in the S4 segment initially lacked serological evidence of echinococcosis; however, intraoperative confirmation revealed the presence of an echinococcal cyst. This article aims to explore both clinical conditions and highlight the therapeutic considerations for their management. Moreover, we discuss the significance of this unique case, emphasizing the possibility of the coexistence of these two pathologies.

Classical singers train intensively for many years to achieve a high level of vocal control and specific sound characteristics. However, the actual span of singers’ activities often includes venues other than opera halls and requires performing in styles outside their strict training (e.g., singing pop songs at weddings). We examine classical singers’ ability to adjust their vocal productions to other styles, in relation with their formal training. Twenty-two highly trained female classical singers (aged from 22 to 45 years old; vocal training ranging from 4.5 to 27 years) performed six different melody excerpts a cappella in contrasting ways: as an opera aria, as a pop song and as a lullaby. All melodies were sung both with lyrics and with a /lu/ sound. All productions were acoustically analyzed in terms of seven common acoustic descriptors of voice/singing performances and perceptually evaluated by a total of 50 lay listeners (aged from 21 to 73 years old) who were asked to identify the intended singing style in a forced-choice lab experiment. Acoustic analyses of the 792 performances suggest distinct acoustic profiles, implying that singers were able to produce contrasting sounding performances. Furthermore, the high overall style recognition rate (78.5% Correct Responses, hence CR) confirmed singers’ proficiency in performing in operatic style (86% CR) and their versatility when it comes to lullaby (80% CR) and pop performances (69% CR), albeit with occasional confusion between the latter two. Interestingly, different levels of competence among singers appeared, with versatility (as estimated based on correct recognition in pop/lullaby styles) ranging from 62 to 83% depending on the singer. Importantly, this variability was not linked to formal training per se. Our results indicate that classical singers are versatile, and prompt the need for further investigations to clarify the role of singers’ broader professional and personal experiences in the development of this valuable ability.

ObjectivesTo approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.DesignRetrospective cohort study.SettingClinics across North America.ParticipantsThe study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.MethodsPhenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.ResultsAmong 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.DiscussionThe familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

Selected case studies of precipitating ice clouds at Dome C (Antarctic Plateau) were used to test a new approach for the estimation of ice cloud reflectivity at 24 GHz (12.37 mm wavelength) using ground-based far infrared spectral measurements from the REFIR-PAD Fourier transform spectroradiometer and backscattering/depolarization lidar profiles. The resulting reflectivity was evaluated with the direct reflectivity measurements provided by a co-located micro rain radar (MRR) operating at 24 GHz, that was able to detect falling crystals with large particle size, typically above 600 µm. To obtain the 24 GHz reflectivity, we used the particle effective diameter and the cloud optical depth retrieved from the far infrared spectral radiances provided by REFIR-PAD and the tropospheric co-located backscattering lidar to calculate the modal radius and the intercept of the particle size distribution. These parameters spanned in the wide ranges between 570–2400 µm and 10−2–104 cm−5, respectively. The retrieved effective sizes and optical depths mostly varied in the ranges 70–250 µm and 0.1–5, respectively. From these parameters, the theoretical reflectivity at 24 GHz was obtained by integrating the size distribution over different cross sections for various habit crystals provided by Eriksson et al. (2018) databases. From the comparison with the radar reflectivity measurements, we found that the hexagonal column-like habits, the columnar crystal aggregates, and the 5/6 branches bullet rosettes showed the best agreement with the MRR observations. The dispersion coefficient of the crystal particle size distribution was assumed in the range 0–2 according to the temperature dependence found in previous studies. The retrieved values of the intercept and slope were found in good agreement with these studies. The presence of the inferred habits was confirmed by the crystal images taken by the ICE-CAMERA, operating in proximity of REFIR-PAD and the MRR. In particular, the occurrence of hexagonal column-like ice crystals was confirmed by the presence of 22∘ solar halos, detected by the HALO-CAMERA. The average crystal lengths obtained from the retrieved size distribution were also compared to those estimated from the ICE-CAMERA images. The agreement between the two results confirmed that the retrieved parameters of the particle size distributions correctly reproduced the observations.