New hybrid EC-PROMETHEE method with multiple iterations of random weight ranges: Step-by-step application in Python.

The decision-making process consists of finding the best solution to an analyzed problem. This search is carried out in the face of countless interactions when analyzing an alternative criterion by criterion, under which weights are assigned that distinguish the degree of importance they have for the decision-makers. The definition of weight for each criterion gives rise to three lines of thought on the subject. There are objective, subjective, and hybrid methods. This discussion concerns the degree to which experts define the criteria weights. Based on this discussion, we developed a hybrid method to integrate the Entropy and CRITIC methods with the PROMETHEE method, called EC-PROMETHEE. The innovation of this method is that the combination of the Entropy and CRITIC methods does not result in a single set of weights. In reality, the weights generated by each method are used to define each criterion's upper and lower limits. The range of weights generated for each criterion is emulated "n" times and builds a set of weights that are applied to the ranking definition process. The model generates "n" rankings, defining a single ranking. In this article, we demonstrate a step-by-step application of a tool developed in Python called EC-PROMETHEE and use it as an example of the problem of choosing rotary-wing airplanes for application in the military police service.➢The method reduces discretion in determining the weights of the criteria;➢The innovation lies in the use of a range of weights for criteria;➢Consistency in defining the final ranking.

Cellular calcium handling and electrophysiology are modulated by chronic physiological pacing in human induced pluripotent stem cell-derived cardiomyocytes.

Electric pacing of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) has been increasingly used to simulate cardiac arrhythmias in vitro and to enhance cardiomyocyte maturity. However, the impact of electric pacing on cellular electrophysiology and Ca2+-handling in differentiated hiPSC-CM is less characterized. Here we studied the effects of electric pacing for 24h or 7d at a physiological rate of 60 bpm on cellular electrophysiology and Ca2+-cycling in late-stage, differentiated hiPSC-CM (>90% troponin+, >60d post differentiation). Electric culture pacing for 7d did not influence cardiomyocyte cell size, apoptosis or generation of reactive oxygen species in differentiated hiPSC-CM compared to 24h pacing. However, epifluorescence measurements revealed that electric pacing for 7d improved systolic Ca2+-transient amplitude and Ca2+-transient upstroke, which could be explained by elevated sarcoplasmic reticulum Ca2+-load and SERCA activity. Diastolic Ca2+-leak was not changed in line-scanning confocal microscopy suggesting that the improvement in systolic Ca2+-release was not associated with a higher open probability of RyR2 during diastole. While bulk cytosolic Na+-concentration and NCX activity were not changed, patch-clamp studies revealed that chronic pacing caused a slight abbreviation of the action potential duration (APD) in hiPSC-CM. We found in whole-cell voltage-clamp measurements that chronic pacing for 7d led to a decrease in late Na+-current, which might explain the changes in APD. In conclusion, our results show that chronic pacing improves systolic Ca2+-handling and modulates the electrophysiology of late-stage, differentiated iPSC-CM. This study might help to understand the effects of electric pacing and its numerous applications in stem cell research including arrhythmia simulation.

Sub-lethal effects of metals and pesticides on the freshwater dinoflagellate Palatinus apiculatus and environmental implications.

Microalgae are unicellular, photosynthetic organisms in aquatic environments and are sensitive to water quality and contaminants. While green algae and diatoms are widely used for toxicity assessments, there is a relatively limited amount of toxicity data available for freshwater dinoflagellates. Here, we evaluated the sub-lethal effects of the metals Cu, Cr, Ni, and Zn and the herbicides atrazine and S-metolachlor on the freshwater dinoflagellate Palatinus apiculatus. Based on the 72-h median effective concentration (EC50), P. apiculatus showed sensitive responses to metals in the order of Cu (0.052 mg L-1), Cr (0.085 mg L-1), Zn (0.098 mg L-1), and Ni (0.13 mg L-1). Among the tested herbicides, P. apiculatus was more sensitive to atrazine (0.0048 mg L-1) than S-metolachlor (0.062 mg L-1). In addition, we observed morphological alterations and significant increases in reactive oxygen species (ROS) production in cells exposed to 0.05 mg L-1 of Cu and 0.005 mg L-1 of atrazine. These indicated that metals and pesticides induced oxidative stress in cellular metabolic processes and consequently caused severe physiological damage to the cells. Our results provide baseline data on the toxic effects of typical environmental contaminants on freshwater dinoflagellate, suggesting that P. apiculatus could be used as a bioindicator in freshwater toxicity assessments. PRACTITIONER POINTS: The sub-lethal effects of metals and pesticides on the freshwater dinoflagellate Palatinus apiculatus were evaluated. Palatinus sensitively responded to metals and pesticides; of test chemicals, atrazine (0.0048 mg L-1 of EC50) was the most sensitive. Metals and pesticides induced oxidative stress and consequently caused severe physiological damage to the Palatinus cells. The freshwater dinoflagellate Palatinus can be used as a bioindicator in freshwater toxicity assessments.

Fluoride removal using a rotating anode electro-coagulation reactor: Parametric optimization using response surface methodology, isotherms and kinetic studies, economic analysis and sludge characterization.

The presence of fluoride in drinking water can cause various diseases, such as dental fluorosis and skeletal fluorosis. The present study aims to intensify the fluoride removal using a rotating anode electro-coagulation (EC) reactor with providing the proper hydrodynamics conditions. This fluoride removal is modeled and optimized using Response Surface Methodology (RSM) and central composite design (CCD) with varying operational parameters (rotation speed: 20-80 RPM, current: 0.2-1.0 A, initial fluoride concentration: 8-40 mg/L and time: 15-75 min). The maximum fluoride removal is obtained as 96.87% (predicted) and 95.40% (experimental) for the optimized process parameters, initial concentration of 32 mg/L, 0.8 A current, 60 min, and 60 RPM of rotating speed. Kinetic analysis reveals that the removal process adheres to a second-order kinetic model, suggesting that the rate of fluoride removal is dependent on the concentration of fluoride ions present. Isothermal studies indicate that the effective sorption of fluoride onto the generated flocs follows a sips isotherm. The optimal cost analysis is carried out to determine the operational cost as 0.256 USD/m3 for F removal of 93.49% at initial concentration 24 mg/L, time 50 min, current 0.7 A, and rotation 70 rpm and presenting a cost-effective solution for fluoride mitigation. Further, characterizations of the resultant sludge through X-Ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FTIR), and the Toxicity Characteristic Leaching Procedure (TCLP) confirmed the safe disposal potential of the sludge. The findings show a promising approach for fluoride removal, combining high efficiency, economic viability, and environmental safety.

Non-constant mean relative potency for antibody-dependent cellular cytotoxicity assays.

Bioassays are regulated, analytical methods used to ensure proper activity (potency) of biological products at release and during long-term storage. Potency is commonly reported on a relative basis by comparing and calibrating a concentration-response curve from the test material to that of a reference standard material. The relative potency approach depends on an assumption that the two concentration-response curves exhibit similar (equivalent) shapes, except for a potency shift. In certain circumstances, however, biological factors preclude the similarity assumption, and the traditional approach becomes unworkable. The antibody-mediated cytotoxicity assay is one example where the similarity assumption does not always hold. Other examples also arise in the fields of toxicology and pharmacology. In this work, we present a non-constant mean relative potency approach which averages the relative potency across a common range of the concentration-response curves. The proposed method captures the changing nature of the relative potency into a summary statistic that can be reported for batch calibration and quality control purposes. We provide inferential methods for this statistic and summarize the results of a simulation comparing these methods across a number of non-constant relative potency scenarios and assay conditions.

Tetraspanins in digestive­system cancers: Expression, function and therapeutic potential (Review).

The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system­related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed.

Acute and Chronic Ecotoxicity of Daphnia magna Exposed to Ash Leachate from the Cotopaxi Volcano, Ecuador.

Ecuador's wetlands and aquatic ecosystems are chronically exposed to ash contamination due to the frequent volcanoes' eruptions in the country. Still, the short and long-term effects of ash contamination on the aquatic biota are not well understood. We used ashes released by the Cotopaxi volcano in 2016 to investigate their acute and chronic effects in Daphna magna. We calculated the half maximal effective concentration (EC50) after 2 and 21 days of exposure, the non-observed effect concentration (NOEC), and the lowest observed effect concentration (LOEC) on offspring production. We also analyzed the metal concentration present in the ashes. The EC50 values at 2 and 21 days were found at 80% and 5% ash leachate concentrations, respectively. After 21 days of exposure, high mortality and low neonatal production were observed in all leachate concentrations (NOEC was at 15%, and LOEC was at 20% leachate concentration). Our results suggest that the ashes from the Cotopaxi volcano can cause acute and chronic toxicity to aquatic life and should be classified as hazardous waste, depending on the dose. There is an urgent need for further studies that assess toxicity caused by the intense volcanic activity in Ecuador.

Increased effective connectivity from the hypothalamus to the left superior frontal gyrus and its association with visual analogue scale in persons with migraines.

Background: In recent years, several functional imaging studies have shown that the hypothalamus is closely associated with migraine and have suggested that the hypothalamus may be a potential site of migraine generation. Studying the characteristics of the functional network of the hypothalamus in persons with migraines may help to understand the neural mechanisms of migraine. We thus used resting-state functional magnetic resonance imaging (rsfMRI) and Granger causal analysis to investigate the effective connectivity (EC) of the hypothalamus in persons with migraines. Methods: The study included 17 healthy volunteers and 39 persons with migraines. The EC calculation was based on rsfMRI data from a 3-T magnetic resonance imaging scanner. The brain networks of the hypothalamus were compared using a general linear model to determine if there were any differences between the two groups. We used Pearson correlation analysis to examine the correlation between EC values in abnormal brain regions and clinical variables. Results: Compared with healthy controls, those with migraines showed decreased EC from the hypothalamus to the left fusiform and increased EC from the hypothalamus to the medial frontal gyrus/orbital part, right lingual gyrus, left superior frontal gyrus, and right middle frontal gyrus (P<0.05). Meanwhile, persons with migraines also showed decreased EC from the left middle frontal gyrus and right medial frontal gyrus/orbital part to the hypothalamus (P<0.05). EC from the hypothalamus to the left superior frontal gyrus correlated significantly and positively with the visual analogue scale in those with migraines (r=-0.3820; P=0.0164). Conclusions: Disturbances in the EC between the hypothalamus and the prefrontal gyrus and visual cortex may play a key role in the neuropathological features of persons with migraines. The current study adds to our understanding of the complexity of migraine mechanisms.

New screen-printed electrodes for Raman spectroelectrochemistry. Determination of p-aminosalicylic acid.

BACKGROUND: The availability of new surface enhanced Raman scattering (SERS) substrates is essential to develop quantitative analytical methods. Electrochemistry is an easy, fast and reproducible methodology to prepare SERS substrates on screen-printed electrodes (SPEs). RESULTS: This work proposes new SPEs based on a three-electrode system all made of silver. Using the same ink for the whole electrode system facilitates the fabrication process, reduces production costs, and leads to excellent analytical performance. The results showed that Raman enhancement depends strongly on the type of silver ink. To demonstrate the capabilities of the new electrodes developed, 4-aminosalicylic acid was determined in complex matrices and in the presence of strong interfering compounds such as salicylic acid and acetylsalicylic acid. The proposed analytical method is based on the electrochemical surface oxidation enhanced Raman scattering (EC-SOERS) strategy. AgCl nanocrystals are generated on the working electrode surface, which amplify the Raman signal of 4-aminosalicylic acid. Good figures of merit were obtained both in the absence and in the presence of the interfering compounds, achieving a correct estimation of a 4-aminosalicylic test sample in complex matrices. SIGNIFICANCE: The new SPEs have been demonstrated to be very sensitive and reproducible which, together to the high specificity of the Raman signal, makes this methodology very attractive for chemical analysis.

Successful Surveillance Using Endometrial Cytology in a Woman With Lynch Syndrome.

Lynch syndrome (LS) results from pathogenic variants in mismatch repair genes and is the most common hereditary cancer syndrome. Some guidelines or studies recommend restricting screening according to endometrial cancer (EC) using endometrial biopsy. The pooled sensitivity and specificity of endometrial cytology for detecting endometrial atypical hyperplasia or cancer have been reported to be as high as the pooled sensitivity and specificity of endometrial biopsy. We conduct transvaginal ultrasound and endometrial cytology in women with LS every six months as surveillance for gynecological malignancy. Through this surveillance program, we can detect early-stage EC in women with LS. Here, we report the case of a patient with stage IA EC detected by endometrial cytology and treated completely. The patient was a 47-year-old woman under surveillance for gynecological malignancy. She was diagnosed as having LS with a germline pathogenic variant in MSH6 after surgery for rectal cancer. Thereafter, gynecological surveillance was started. She had regular menstruation and never experienced atypical genital bleeding. However, her cytopathological findings indicated grade 1 endometrial carcinoma. Endometrial biopsy was performed and endometrial carcinoma was confirmed pathologically. A laparoscopic modified radical hysterectomy with bilateral salpingo-oophorectomy was performed. The resected specimen was reviewed pathologically, and the tumor was finally diagnosed as grade 1 endometrioid carcinoma confined to the endometrium without lymphovascular space invasion. She has remained asymptomatic and free of cancer for five years without any adjuvant therapy. We achieved successful surveillance using endometrial cytology. Endometrial cytology could replace endometrial biopsy as a screening tool for EC.

Age-related wall shear stress changes assessed by vascular vector flow mapping in the carotid arteries of healthy adults: a cross-sectional study.

Background: Wall shear stress (WSS) is related to the pathogenesis of atherosclerosis. WSS is affected by a variety of hemodynamic factors, and there is still a lack of accurate and objective methods for measuring it. This study sought to evaluate hemodynamic changes in WSSmaximum (max), WSSmean, WSSminimum (min) in the common carotid artery of healthy adults of different ages using vascular vector flow mapping (VFM). Methods: A retrospective analysis was conducted on 70 healthy volunteers aged 20-89 years who were recruited from our Ultrasound Department between February 2021 and June 2021. An ultrasound system with a 3-15 MHz probe was used to determine regions of interest (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting ROIs with optimal image quality from three full cardiac cycles. The participants were divided into the following seven age groups: the 20s group, the 30s group, the 40s group, the 50s group, the 60s group, the 70s group, and the 80s group. The WSS parameters were compared among the age groups. An analysis of variance or a Kruskal-Wallis test was used to evaluate the difference among the groups, and a Pearson analysis and linear regression were used for the correlation and trend analysis. Results: The WSS parameters were quantified using vascular VFM software. The WSSmax, WSSmean, WSSmin differed among the age groups and gradually decreased with age, the elderly were significantly lower than the young. The Pearson correlation coefficient of the WSSmax and age was -0.556 (P<0.001), that of the WSSmean and age was -0.461 (P<0.001), and that of the WSSmin and age was -0.308 (P<0.001). The WSS parameters with age are negatively correlated the carotid intima-media thickness differed between the groups. Conclusions: The carotid WSSmax, WSSmean, WSSmin can be quantitatively and visually analyzed using the vascular VFM technique. In healthy adults of different ages, the carotid WSSmax, WSSmean, WSSmin decreased with age. Our findings about the normal values of carotid WSS maybe have clinical reference value for future studies.

The causal effect of hot beverage temperature preference on esophageal cancer risk: a Mendelian randomization study.

Background: Previous research has found a link between the temperature of food and beverages and the risk of esophageal cancer (EC). A causal relationship between the two has not been well established. Herein, we used Mendelian randomization (MR) analysis to assess the causal effect of temperature preference for hot beverages on EC risk. Methods: Genome-wide association studies (GWAS) data for hot beverage temperature preference were obtained from the UK biobank. There were 457,873 European and 2,617 East Asian participants included. GWAS data for EC were obtained from the Integrative Epidemiology Unit (IEU) project database. Two datasets from the European population and two datasets from the East Asian population were included. Totally, 4,426 EC cases and 1,202,270 control subjects were included. The "TwoSampleMR" R package was used to conduct a two-sample MR analysis. A random-effect inverse variance weighted (IVW) was used as the main analytical method to estimate the causal effect, and various sensitivity analyses, including MR Egger, weighted median, simple mode, and weighted mode, were used to examine the potential violation of the second and third MR assumptions. Meta-analyses were performed to further confirm the results. Results: Sixty-eight single nucleotide polymorphisms (SNPs) from the European population and 11 SNPs from the East Asian population were used for MR analysis. No significant causal effect was found between hot beverage temperature preference and EC risk in the European population {for the ieu-b-4960 dataset, inverse variance weighted odds ratio (ORIVW) =1.00 [95% confidence interval (CI): 0.99-1.00], P=0.54; for the ebi-a-GCST90018841 dataset, ORIVW =0.35 (95% CI: 0.10-1.29), P=0.12} or in the East Asian population [for the bbj-a-117 dataset, ORIVW =1.09 (95% CI: 0.80-1.48), P=0.59; for the ebi-a-GCST90018621 dataset, ORIVW =0.11 (95% CI: 0.82-1.50), P=0.49]. Meta-analyses of the European population datasets and the Asian population datasets showed consistent results. Conclusions: The current MR analysis provides new genetic evidence for a null causal relationship between hot beverage temperature preference and EC, both in the European population and the East Asian population. Evidence to prevent EC by reducing the intake of hot beverages is insufficient.

Unraveling the Deposition and Dissolution Behavior of the Ag-Modified Li Surface Based on Electrochemical Atomic Force Microscopy.

Lithium is a promising anode material for advanced batteries because of its high capacity and low redox potential. However, its practical use is hindered by nonuniform Li deposition and dendrite formation, leading to safety concerns in Li metal batteries. Our study shows that Ag-based materials enhance the uniformity of Li deposition on Ag-modified Li (AgLi) surfaces, thereby addressing these key challenges. This improvement is due to the strong affinity of Ag for Li, which promotes uniform deposition and dissolution. Additionally, the AgLi surface demonstrated an improved cycling stability, which is crucial for long-term battery reliability. Emphasizing our analytical approach, we utilized comprehensive techniques such as Kelvin probe force microscopy (KPFM) and electrochemical atomic force microscopy (EC-AFM) to locally analyze the electrical properties and unravel the Li deposition/dissolution mechanisms. KPFM analysis provided crucial insights into surface potential variations, while EC-AFM highlighted topographical changes during the Li deposition and dissolution processes, contributing significantly to the development of safer and more efficient Li metal batteries.

The ratio of concentration of organic carbon and elemental carbon bound to particulate matter in ambient air: a global systematic review and meta-analysis.

Four hundred and sixty-six references with 625 data reports were included in our study. The high frequency of ratio OC/EC for PM0.1 was observed in 3.92-5.93; PM1 in 1.08-3.08; PM2.5, 2.08-4.08; PM10 in 2.70-4.70 and TSP in 2.66-4.66. The rank order of areas based on the pooled concentration of OC bound to PM2.5 was traffic (17.893 µg/m3) > industrial (10.58 µg/m3) > urban (7.696 µg/m3) > rural (4.08 µg/m3). The rank order of areas based on the pooled (mean) concentration of EC in PM2.5 was traffic (17.893 µg/m3) > industrial (2.65 µg/m3) > Urban (1.48 µg/m3) > rural (1.06 µg/m3). The pooled concentrations of OC and EC bound to PM2.5 in traffic areas were higher than in other areas. Therefore, it is recommended that monitoring and effectively reducing concentration plans are carried out, especially in traffic areas.

Assessing fecal contamination from human and environmental sources using Escherichia coli as an indicator in rural eastern Ethiopian households - a study from the EXCAM project.

Enteric pathogens are a leading causes of diarrheal deaths in low- and middle-income countries. The Exposure Assessment of Campylobacter Infections in Rural Ethiopia (EXCAM) project, aims to identify potential sources of bacteria in the genus Campylobacter and, more generally, fecal contamination of infants during the first 1.5 years of life using Escherichia coli as indicator. A total of 1,310 samples (i.e., hand rinses from the infant, sibling and mother, drinking and bathing water, food and fomite provided to or touched by the infants, areola swabs, breast milk and soil) were collected from 76 households between May 2021 and June 2022. Samples were assigned to two groups by infant age: TP1 (time point 1), infants between 4 and 8 months of age, and TP2, infants between 11 and 15 months of age. Fluorometric and semi-selective colorimetric approaches were used to quantify E. coli in the field samples. Overall, E. coli was ubiquitous within selected households (56.8% across the study). E. coli was more frequently detected than average (>53%) with high concentration (>2-log CFU) in soil (g) and per pair of hand, while the opposite trend (<33%; <1.5-log CFU) was observed in food provided to the infants (g or ml), per areola, and breast milk (ml; P<0.01). E. coli was frequently detected in fomites touched by the infants, drinking and bathing water (>51%), but at low concentration (<1.5-log CFU). Correlation analysis between E. coli concentration in different sample types suggested that the mother's hands might play a key role in the transmission of E. coli between the environment (i.e., soil, bathing water and fomites) and other family members (i.e., infant and sibling; P<0.04; r2>0.3). Using E. coli as surrogate, our study identified mother (hands and areola) as reservoirs likely to be involved in frequent transmission of fecal contaminants to infants within rural Ethiopian households.

Jung, the Rebirth Motif and Psychedelics I: Documenting Jung's Contact with the British Pioneers.

C. G. Jung wrote very little about psychedelic drugs and he took a sceptical view of them. However, he was sufficiently impressed by Aldous Huxley's 1954 account of taking mescaline, The Doors of Perception, to invite Huxley to visit him in Switzerland. Huxley declined Jung's invitation but Huxley's collaborator Humphry Osmond met Jung instead. This paper documents Jung's contact with the British pioneers of psychedelics research and presents the scant material illuminating his views about these drugs. It also determines the efforts of British psychiatrist Ronald Sandison, who was the first to develop an "explicitly Jungian approach" to psychedelic-assisted psychotherapy (Hill, 2013), and it highlights a connection between Sandison's initiative and the Society of Analytical Psychology (SAP) through the involvement of two SAP members: Margot Cutner, Sandison's colleague, and Michael Fordham, who supervised a trainee working with one of Sandison's former patients. Despite Jung's objections to the use of psychedelics, Sandison and Cutner developed ground-breaking protocols during the 1950s and they were among the first to document the phenomenon of "spiritual rebirth symbolized in the birth experience known to many LSD therapists" (Sandison, 2001). In two companion papers, I consider Jung's treatment of the rebirth motif in his commentary on The Tibetan Book of the Dead, which later became a central text in the psychedelic movement, and I chart the evolution in psychedelics research from an association with schizophrenia during the 1950s to the mystical paradigms of the 1960s and beyond.

C.G. Jung a très peu écrit sur les drogues psychédéliques et il avait à leur égard une attitude sceptique. Cependant il fut suffisamment impressionné par le récit d'Aldous Huxley de son expérience avec la mescaline en 1954, Les Portes de la Perception, pour inviter Huxley à lui rendre visite en Suisse. Huxley déclina l'invitation de Jung mais son collaborateur Humphry Osmond rencontra Jung à sa place. Cet article rend compte des contacts de Jung avec les recherches des pionniers britanniques en matière de drogues psychédéliques. Il présente aussi le peu de matériel qui illustre ses opinions concernant ces drogues. L'article explore les efforts du psychiatre britannique Ronald Sandison ­ qui fut le premier à développer une « approche spécifiquement jungienne ¼ à la psychothérapie assistée par des drogues psychédéliques ­ et il souligne un lien entre l'initiative de Sandison et The Society of Analytical Psychology (SAP) par l'implication de deux de ses membres : Margot Cutner, collègue de Sandison, et Michael Fordham, qui supervisa un candidat sur son travail avec un des anciens patients de Sandison. Malgré les objections de Jung sur l'utilisation des drogues psychédéliques, Sandison et Cutner ont développé des protocoles très innovants durant les années 1950 et furent parmi les premiers à documenter le phénomène de la « renaissance spirituelle symbolisée par l'expérience de naissance, bien connue par la plupart des thérapeutes utilisant le L.S.D. ¼ (Sandison, 2001). Dans deux articles apparentés j'examine la manière dont Jung a traité le motif de la renaissance dans son commentaire sur Le Livre des Morts Tibétain, qui devint par la suite un texte central dans le mouvement psychédélique, et je retrace l'évolution dans la recherche sur les drogues psychédéliques à partir d'une association avec la schizophrénie dans les années 1950 et jusqu'aux paradigmes mystiques des années 1960 et au­delà.

C. G. Jung escribió muy poco sobre las drogas psicodélicas y adoptó una postura escéptica hacia ellas. Sin embargo, quedó lo suficientemente impresionado por el relato, Las Puertas de la Percepción, que Aldous Huxley hizo en 1954 en referencia a su consumo de mescalina, como para invitar a Huxley a visitarle en Suiza. Huxley declinó la invitación, pero en su lugar Jung se reunió con Humphry Osmond, colaborador de Huxley. Este artículo documenta el contacto de Jung con los pioneros británicos en investigación psicodélica y presenta el escaso material que da cuenta de las opiniones de estos, sobre dichas drogas. También determina los esfuerzos del psiquiatra británico Ronald Sandison, que fue el primero en desarrollar un "enfoque explícitamente Junguiano" de la psicoterapia asistida por psicodélicos (Hill, 2013), y destaca una conexión entre la iniciativa de Sandison y la Sociedad de Psicología Analítica (SAP) a través de la participación de dos miembros de la SAP: Margot Cutner, colega de Sandison, y Michael Fordham, quien supervisaba a un candidato a analista que trabajaba con uno de los antiguos pacientes de Sandison. A pesar de las objeciones de Jung al uso de psicodélicos, Sandison y Cutner desarrollaron innovadores protocolos durante la década de 1950 y fueron los primeros en documentar el fenómeno del "renacimiento espiritual simbolizado en la experiencia del nacimiento conocida por muchos terapeutas del LSD" (Sandison, 2001). En dos artículos complementarios, considero el tratamiento que Jung da al motivo del renacimiento en su comentario sobre El Libro Tibetano de los Muertos, que más tarde se convirtió en un texto central del movimiento psicodélico, y trazo la evolución de la investigación sobre psicodélicos desde su asociación con la esquizofrenia durante la década de 1950 hasta los paradigmas místicos de la década de 1960 y posteriores.

Short-term outcomes of three- and two-field lymphadenectomy with minimally invasive esophagectomy for esophageal cancer: a propensity score-matching analysis.

Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL. Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay. Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group. Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.

Novel Aminocoumarin-Based Schiff Bases: High Antifungal Activity in Agriculture.

Structural modification is an effective way to improve the antifungal activity of natural products and has been widely used in the development of novel fungicides. In this work, a series of aminocoumarin-based Schiff bases were synthesized and characterized by 1H NMR, 13C NMR and HR-MS spectra. The in vitro inhibition activity of all compounds was tested against four phytopathogenic fungi (Alternaria solani, Fusarium oxysporum, Botrytis cinerea, and Alternaria alternata) using the mycelial growth rate method. The results showed that most of the target compounds exhibited significant antifungal activities. In particular, compounds 5b, 5c, 5d, 5h, 5n, 7c, 7n, and 7p exhibited more effective antifungal activity than commercially available fungicides, chlorothalonil and azoxystrobin. The structure-activity relationship revealed that the electron-withdrawing groups with more electronegativity introduced at the C-3 position were effective in improving the inhibitory activity and that halogenated benzaldehydes would be necessary in the preparation of Schiff bases. The compound 5n against Fusarium oxysporum (EC50=8.73 µg/mL) and the compound 7p against Alternaria alternata (EC50=26.25 µg/mL) were much better than the positive controls. Therefore, compounds 5n and 7p could serve as promising lead compounds for the development of novel broad-spectrum fungicides, which could be useful for applications in the agriculture industry.

Safety evaluation of the food enzyme ß-galactosidase from the genetically modified Bacillus licheniformis strain DSM 34099.

The food enzyme ß-galactosidase (ß-d-galactoside galactohydrolase; EC 3.2.1.23) is produced with the genetically modified Bacillus licheniformis strain DSM 34099 by Kerry Group Services International, Ltd. (KGSI). The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. The production strain met the requirements for the qualified presumption of safety (QPS) approach. The food enzyme is intended to be used in two food manufacturing processes. Dietary exposure was estimated to be up to 7.263 mg total organic solids/kg body weight per day in European populations. Given the QPS status of the production strain and the absence of concerns resulting from the food enzyme manufacturing process, toxicity tests, other than an assessment of allergenicity, were considered unnecessary by the Panel. A search for the identity of the amino acid sequence of the food enzyme to known allergens was made and one match with a food allergen from kiwi fruit was found. The Panel considered that a risk of allergic reactions upon dietary exposure to this food enzyme, particularly in individuals sensitised to kiwi fruit, cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.

Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206+) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206+ macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8+ T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC.