Quantum control of a cat qubit with bit-flip times exceeding ten seconds.

Quantum bits (qubits) are prone to several types of error as the result of uncontrolled interactions with their environment. Common strategies to correct these errors are based on architectures of qubits involving daunting hardware overheads1. One possible solution is to build qubits that are inherently protected against certain types of error, so the overhead required to correct the remaining errors is greatly reduced2-7. However, this strategy relies on one condition: any quantum manipulations of the qubit must not break the protection that has been so carefully engineered5,8. A type of qubit known as a cat qubit is encoded in the manifold of metastable states of a quantum dynamical system, and thereby acquires continuous and autonomous protection against bit-flips. Here, in a superconducting-circuit experiment, we implemented a cat qubit with bit-flip times exceeding 10 s. This is an improvement of four orders of magnitude over previously published cat-qubit implementations. We prepared and imaged quantum superposition states, and measured phase-flip times greater than 490 ns. Most importantly, we controlled the phase of these quantum superpositions without breaking the bit-flip protection. This experiment demonstrates the compatibility of quantum control and inherent bit-flip protection at an unprecedented level, showing the viability of these dynamical qubits for future quantum technologies.

[Case report of a cystic lung disease: From a rarity to the discovery of an unknown genetic variant]. / À propos d'un cas clinique de maladie kystique pulmonaire : d'une rareté à la découverte d'un variant génétique inconnu.

INTRODUCTION: Cystic lung diseases are rare, with numerous differential diagnoses. Iconographic discovery consequently necessitates medical examinations in view of proposing an etiological orientation. CASE REPORT: A 57-year-old woman consulted in pulmonology following fortuitous detection of a cystic lung disease on an abdominal CT scan. Complementary medical examinations did not allow orientation towards a particular diagnosis. During a follow-up consultation, the patient informed her pulmonologist of the recent detection of a monoallelic variant of a FAT4 gene in one of her daughters, who was suffering from edema of the lower limbs secondary to a disease of the lymphatic system. As our patient had a similar history, she likewise received a genetic analysis. A monoallelic variant not described in the genetic databases was observed, and considered as a probable pathogenic variant (class 4/5 on the pathogenicity scale of genetic variants). CONCLUSION: After analyzing the available literature data, we raise questions about a possible link between this variant of the FAT4 gene, chronic lymphedema and our patient's cystic lung disease.

Valley-Polarized Quantum Hall Phase in a Strain-Controlled Dirac System.

In multivalley systems, the valley pseudospin offers rich physics going from encoding of information by its polarization (valleytronics), to exploring novel phases of matter when its degeneracy is changed. Here, by strain engineering, we reveal fully valley-polarized quantum Hall phases in the Pb_{1-x}Sn_{x}Se Dirac system. Remarkably, when the valley energy splitting exceeds the fundamental band gap, we observe a "bipolar quantum Hall phase," heralded by the coexistence of hole and electron chiral edge states at distinct valleys in the same quantum well. This suggests that spatially overlaid counterpropagating chiral edge states emerging at different valleys do not interfere with each other.

Teleconsultations in oral medicine: dentist perception during the COVID-19 pandemic in Brazil.

BACKGROUND: The aim of this study was to describe the perception of dentists from the North macroregion of Minas Gerais, Brazil, users of telediagnosis in Oral Medicine, during the COVID-19 pandemic. MATERIAL AND METHODS: This is a cross-sectional and descriptive study. Data collection was carried out online, between May and October 2022. The information was transferred to the Statistical Package for the Social Sciences for Windows (SPPS)® version 24. RESULTS: The sample consisted of 255 dentists, predominantly female. Regarding perception, a significant percentage (47.8%) of respondents agreed that they would like to use telediagnosis frequently, more than half (60.6%) agreed that the technology is easy to use, only a small percentage (8.8%) needed technical support to use it and almost half (48.2%) mentioned the desire to continue using it after the pandemic. When asked if patients felt confident and comfortable when passing on information, more than half disagreed or remained neutral (58.4%), a similar result was found in relation to confidence in the application of the instrument by professionals. CONCLUSIONS: It is concluded that, during the pandemic, telediagnosis in Oral Medicine was an easy and adequate tool. However, professionals must be trained and prepared to be comfortable and ready for use.

A New Bacillus velezensis Strain CML532 Improves Chicken Growth Performance and Reduces Intestinal Clostridium perfringens Colonization.

Bacillus velezensis has gained increasing recognition as a probiotic for improving animal growth performance and gut health. We identified six B. velezensis strains from sixty Bacillus isolates that were isolated from the cecal samples of fifteen different chicken breeds. We characterized the probiotic properties of these six B. velezensis strains. The effect of a selected strain (B. velezensis CML532) on chicken growth performance under normal feeding and Clostridium perfringens challenge conditions was also evaluated. The results revealed that the six B. velezensis strains differed in their probiotic properties, with strain CML532 exhibiting the highest bile salt and acid tolerance and high-yield enzyme and antibacterial activities. Genomic analyses showed that genes related to amino acid and carbohydrate metabolism, as well as genes related to starch and cellulose hydrolysis, were abundant in strain CML532. Dietary supplementation with strain CML532 promoted chicken growth, improved the gut barrier and absorption function, and modulated the gut microbiota. Under the C. perfringens challenge condition, strain CML532 alleviated intestinal damage, reduced ileal colonization of C. perfringens, and also improved chicken growth performance. Collectively, this study demonstrated that the newly isolated B. velezensis strain is a promising probiotic with beneficial effects on chicken growth performance and gut health.

Enzymatically prepared neoagarooligosaccharides improve gut health and function through promoting the production of spermidine by Faecalibacterium in chickens.

Maintaining animal gut health through modulating the gut microbiota is a constant need when antibiotics are not used in animal feed during the food animal production process. Prebiotics is regarded as one of the most promising antibiotic alternatives for such purpose. As an attractive prebiotic, the role and mechanisms of neoagarooligosaccharides (NAOS) in promoting animal growth and gut health have not been elucidated. In this study, we first cloned and expressed marine bacterial ß-agarase in yeast to optimize the NAOS preparation and then investigated the role and the underlying mechanisms of the prepared NAOS in improving chicken gut health and function. The marine bacterial ß-agarase PDE13B was expressed in Pichia pastoris GS115 and generated even-numbered NAOS. Dietary the prepared NAOS promoted chicken growth and improved intestinal morphology, its barrier, and digestion capabilities, and absorption function. Metagenomic analysis indicated that NAOS modulated the chicken gut microbiota structure and function, and microbial interactions, and promoted the growth of spermidine-producing bacteria especially Faecalibacterium. Through integration of gut metagenome, gut content metabolome, and gut tissue transcriptome, we established connections among NAOS, gut microbes, spermidine, and chicken gut gene expression. The spermidine regulation of genes related to autophagy, immunity, and inflammation was further confirmed in chicken embryo intestinal epithelium cells. We also verified that NAOS can be utilized by Faecalibacterium prausnitzii to grow and produce spermidine in in vitro experiments. Collectively, we provide a systematic investigation of the role of NAOS in regulating gut health and demonstrate the microbial spermidine-mediated mechanism involved in prebiotic effects of NAOS, which lays foundation for future use of NAOS as a new antibiotic alternative in animal production.

Metabotropic Glutamate Receptor 2 Expression Is Chronically Elevated in Male Rats With Post-Traumatic Stress Disorder Related Behavioral Traits Following Repetitive Low-Level Blast Exposure.

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. In this report, we explored mGluR2/3 expression following blast exposure in male rats. Western blotting revealed that mGluR2 protein (but not mGluR3) was increased in all brain regions studied (anterior cortex, hippocampus, and amygdala) at 43 or 52 weeks after blast exposure but not at 2 weeks or 6 weeks. mGluR2 RNA was elevated at 52 weeks while mGluR3 was not. Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury.

Schizochytrium sp. and lactoferrin supplementation alleviates Escherichia coli K99-induced diarrhea in preweaning dairy calves.

Calf diarrhea, a common disease mainly induced by Escherichia coli infection, is one of the main reasons for nonpredator losses. Hence, an effective nonantibacterial approach to prevent calf diarrhea has become an emerging requirement. This study evaluated the microalgae Schizochytrium sp. (SZ) and lactoferrin (LF) as a nutrient intervention approach against E. coli O101:K99-induced preweaning calve diarrhea. Fifty 1-d-old male Holstein calves were randomly divided into 5 groups (n = 10): (1) control, (2) blank (no supplement or challenge), (3) 1 g/d LF, (4) 20 g/d SZ, or (5) 1 g/d LF plus 20 g/d SZ (LFSZ). The experimental period lasted 14 d. On the morning of d 7, calves were challenged with 1 × 1011 cfu of E. coli O101:K99, and rectum feces were collected on 3, 12, 24, and 168 h postchallenge for the control, LF, SZ, and LFSZ groups. The rectal feces of the blank group were collected on d 14. Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). The E. coli K99 challenge decreased the average daily gain (ADG) and increased feed-to-gain ratio (F:G) and diarrhea frequency (control vs. blank). Compared with the control group, the LFSZ group had a higher ADG and lower F:G, and the LFSZ and SZ groups had lower diarrhea frequency compared with the control group. In addition, the LFSZ and SZ groups have no differences in diarrhea frequency compared with the blank group. Compared with the control group, the blank group had lower serum nitric oxide (NO), endothelin-1, d-lactic acid (D-LA), and lipopolysaccharide (LPS) concentrations, as well as serum IgG, IL-1ß, IL-6, IL-10, and TNF-α levels on d 7 and 14. On d 7, compared with the control group, all treatment groups had lower serum NO level, the SZ group had a lower serum D-LA concentration, and the LF and LFSZ groups had lower serum LPS concentration. On d 14, compared with the control group, the fecal microbiota of the blank group had lower Shannon, Simpson, Chao1, and ACE indexes, the LFSZ group had lower Shannon and Simpson indexes, the SZ and LFSZ groups had a higher Chao1 index, and all treatment groups had a higher ACE index. In fecal microbiota, Bifidobacterium and Actinobacteria were negatively associated with IL-10 and d-lactate, while Akkermansia was negatively associated with endothelin-1 and positively correlated with LPS, fecal scores, and d-lactate levels. Our results indicated that LF and SZ supplements could alleviate E. coli O101:K99-induced calf diarrhea individually or in combination. Supplementing 1 g/d LF and 20 g/d SZ could be a potential nutrient intervention approach to prevent bacterial diarrhea in calves.

The underwater soundscape of the North Sea.

As awareness on the impact of anthropogenic underwater noise on marine life grows, underwater noise measurement programs are needed to determine the current status of marine areas and monitor long-term trends. The Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) collaborative project was funded by the EU Interreg to collect a unique dataset of underwater noise levels at 19 sites across the North Sea, spanning many different countries and covering the period from 2019 to 2020. The ambient noise from this dataset has been characterised and compared - setting a benchmark for future measurements in the North Sea area. By identifying clusters with similar sound characteristics in three broadband frequency bands (25-160 Hz, 0.2-1.6 kHz, and 2-10 kHz), geographical areas that are similarly affected by sound have been identified. The measured underwater sound levels show a persistent and spatially uniform correlation with wind speed at high frequencies (above 1 kHz) and a correlation with the distance from ships at mid and high frequencies (between 40 Hz and 4 kHz). Correlation with ocean current velocity at low frequencies (up to 200 Hz), which are susceptible to nonacoustic contamination by flow noise, was also evaluated. These correlations were evaluated and simplified linear scaling laws for wind and current speeds were derived. The presented dataset provides a baseline for underwater noise measurements in the North Sea and shows that spatial variability of the dominant sound sources must be considered to predict the impact of noise reduction measures.

Quercetin-enriched Lactobacillus aviarius alleviates hyperuricemia by hydrolase-mediated degradation of purine nucleosides.

The development of hyperuricemia (HUA) and gout is associated with dysbiosis of the gut microbiota. Quercetin can reduce serum uric acid levels and thus alleviate HUA by modulating the gut microbiota. However, the detailed mechanisms involved in this process are not fully understood. Here, we showed that quercetin significantly reduced the serum uric acid level in a chicken HUA model by altering the chicken cecal microbiota structure and function and increasing the abundance of Lactobacillus aviarius. An L. aviarius strain, CML180, was isolated from the quercetin-treated chicken gut microbiota. Strain characterization indicated that quercetin promoted the growth of L. aviarius CML180 and increased its adhesion, hydrophobicity, and co-aggregation abilities. Gavage of live L. aviarius CML180 to a mouse model of HUA-established by adenosine and potassium oxonate-reduced the serum uric acid level and alleviated HUA. The ability of L. aviarius CML180 to decrease the level of uric acid was due to its degradation of purine nucleosides, which are the precursors for uric acid production. A nucleoside hydrolase gene, nhy69, was identified from the genome of L. aviarius CML180, and the resulting protein, Nhy69, exhibited strong purine nucleoside-hydrolyzing activity at mesophilic temperature and neutral pH conditions. These findings provide mechanistic insights into the potential of quercetin to treat HUA or gout diseases via a specific gut microbe.

Estimating pregnancy rate from blubber progesterone levels of a blindly biopsied beluga population poses methodological, analytical and statistical challenges.

Beluga (Delphinapterus leucas) from the St. Lawrence Estuary, Canada, have been declining since the early 2000s, suggesting recruitment issues as a result of low fecundity, abnormal abortion rates or poor calf or juvenile survival. Pregnancy is difficult to observe in cetaceans, making the ground truthing of pregnancy estimates in wild individuals challenging. Blubber progesterone concentrations were contrasted among 62 SLE beluga with a known reproductive state (i.e. pregnant, resting, parturient and lactating females), that were found dead in 1997 to 2019. The suitability of a threshold obtained from decaying carcasses to assess reproductive state and pregnancy rate of freshly-dead or free-ranging and blindly-sampled beluga was examined using three statistical approaches and two data sets (135 freshly harvested carcasses in Nunavik, and 65 biopsy-sampled SLE beluga). Progesterone concentrations in decaying carcasses were considerably higher in known-pregnant (mean ± sd: 365 ± 244 ng g-1 of tissue) than resting (3.1 ± 4.5 ng g-1 of tissue) or lactating (38.4 ± 100 ng g-1 of tissue) females. An approach based on statistical mixtures of distributions and a logistic regression were compared to the commonly-used, fixed threshold approach (here, 100 ng g-1) for discriminating pregnant from non-pregnant females. The error rate for classifying individuals of known reproductive status was the lowest for the fixed threshold and logistic regression approaches, but the mixture approach required limited a priori knowledge for clustering individuals of unknown pregnancy status. Mismatches in assignations occurred at lipid content < 10% of sample weight. Our results emphasize the importance of reporting lipid contents and progesterone concentrations in both units (ng g-1 of tissue and ng g-1 of lipid) when sample mass is low. By highlighting ways to circumvent potential biases in field sampling associated with capturability of different segments of a population, this study also enhances the usefulness of the technique for estimating pregnancy rate of free-ranging population.

Effect of social class on personal control beliefs.

OBJECTIVE: This research investigated the effect of social class on personal control beliefs. BACKGROUND: Differences in personal control beliefs serve as a central theoretical explanation for social class differences in cognition, emotion, and behavior. However, prior empirical research has not yet conclusively demonstrated that personal control beliefs differ between social classes. METHOD: Across four studies (total N = 138,417), we investigated the link between social class and personal control beliefs with well-established measures of social class (e.g., ISEI, McArthur Scale),representative samples, and data that allow for causal conclusions (e.g., experimental, and longitudinal data). RESULTS: We found that (a) higher social class was associated with higher personal control beliefs across 60 countries. Furthermore, we observed that (b) higher social class of parents was associated with higher personal control beliefs in their children, and that (c) experimentally induced higher (vs. lower) social class led to increases (vs. decreases) of personal control beliefs. CONCLUSIONS: Individuals from lower social classes consistently have weaker personal control beliefs than individuals from upper social classes. Social class differences in this fundamental personality characteristic are bound to have important consequences in various life domains (e.g., psychological and physical well-being, and academic success).

Evaluation of remote teaching in master programs in the Oral Pathology and Oral Medicine during the COVID-19 pandemic. Brazilian multicentric study.

BACKGROUND: With the COVID-19 pandemic, there was a need to adopt online teaching methods in a generalized and sudden way, a situation that led to unprecedented changes in the routine of post-graduate students and research development. This study aimed to analyze the evaluation of remote teaching by graduates of master's degrees and advisors in master's programs in the Oral Pathology and Oral Medicine who needed to adapt to a remote teaching methodology in the pandemic. MATERIAL AND METHODS: This quantitative study evaluated the remote teaching in the perception of master's graduates and advisors from postgraduate programs in Oral Pathology and Oral Medicine. Data were collected through an online Google forms® questionnaire. RESULTS: Participated in the study 14 master graduates and 14 master's advisors. Master graduates evaluated that the professors had a good performance (p=0.001), that the duration of the classes was adequate (p=0.015), that the interaction with professors was satisfactory (p=0.007), that they had good interaction with the advisor (p=0.001), that they were satisfied with the remote guidance process (p=0.038) and that face-to-face practical activities were missed (p=0.002). Master's advisors reported satisfaction with remote teaching, good adaptation (p=0.018) and motivation for remote teaching (p=0.016), they evaluated that students were cooperative in activities (p=0.019) and that face-to-face practical activities were missed (p=0.002). CONCLUSIONS: Despite the difficulties, remote teaching proved to be an effective alternative to face-to-face teaching.

Suicidal ideation and suicide attempt in patients with psychiatric disorders in a Mexico City hospital.

BACKGROUND: One of the population groups at higher risk of suicide is that of people who attend mental health institutions. OBJECTIVE: To know the demographic and clinical characteristics of people admitted for suicidal ideation and suicide attempt to the observation area of a psychiatric hospital in a period of 10 non-consecutive months. MATERIAL AND METHODS: Retrospective, descriptive, correlational study. A total of 439 medical records were collected, out of which 62.9% (n = 276) corresponded to women, 36.7% (n = 161) to men and 0.5% (n = 2) to transgender people; age ranged from 17 to 74 years. RESULTS: The highest incidence of cases was observed between 18 and 25 years of age; the most frequent diagnosis was depressive disorder, and 45.5% (n = 200) of the cases had a suicide attempt. The main method for committing a suicidal act was poisoning by taking various medications, followed by self-inflicted injuries with sharp objects. A positive correlation was found between suicide attempt and self-harm (c² = 1.965, p < 0.05). CONCLUSIONS: The findings highlight the importance of early identification of risk factors that may contribute to an increase in suicidal behaviors.

ANTECEDENTES: Uno de los grupos poblacionales en mayor riesgo de suicidio lo constituyen las personas que asisten a instituciones de salud mental. OBJETIVO: Conocer las características demográficas y clínicas de las personas ingresadas por ideación e intento suicida al área de observación de un hospital psiquiátrico en un periodo de 10 meses no consecutivos. MATERIAL Y MÉTODOS: Estudio retrospectivo, descriptivo y correlacional. Se recabaron 439 expedientes, de los cuales las mujeres representaron 62.9 % (n = 276), los hombres 36.7 % (n = 161) y las personas transgénero 0.5 % (n = 2); el rango de edad varió de 17 a 74 años. RESULTADOS: La mayor incidencia de casos se observó entre los 18 y 25 años, el diagnóstico más frecuente fue el trastorno depresivo y 45.5 % (n = 200) de los casos presentó una tentativa suicida. El principal método para cometer un acto suicida fue el envenenamiento por diversos medicamentos seguido por las lesiones autoinflingidas con objeto punzocortante. Se encontró correlación positiva entre intento suicida y autolesiones (c² = 1.965, p < 0.05). CONCLUSIONES: Los hallazgos resaltan la importancia de la identificación temprana de los factores de riesgo que pueden contribuir al incremento del comportamiento suicida.

Enzymatically prepared alginate oligosaccharides improve broiler chicken growth performance by modulating the gut microbiota and growth hormone signals.

BACKGROUND: Alginate oligosaccharide (AOS) holds great potential as a novel feed supplement in farm animals. However, the effects of AOS on chicken health and the underlying mechanisms are not fully understood. This study aimed to optimize the enzymatic preparation of AOS by using bacterial alginate lyases expressed in yeast, investigate the effects of the prepared AOS on the growth performance and gut health of broiler chickens, and reveal the underlying mechanisms. RESULTS: Five alginate lyases from bacteria were cloned into Pichia pastoris GS115 and the alginate lyase PDE9 was expressed at relatively high yield, activity and stability in P. pastoris. Animal trials were carried out using 320 1-day-old male Arbor Acres broilers (four groups; 8 replicates/group × 10 chicks/replicate) receiving either a basal diet or the same diet supplemented with 100, 200 and 400 mg/kg PDE9-prepared AOS for 42 d. The results showed that dietary supplementation of 200 mg/kg AOS displayed the highest activity in promoting the birds' ADG and ADFI (P < 0.05). AOS ameliorated the intestinal morphology, absorption function and barrier function, as indicated by the enhanced (P < 0.05) intestinal villus height, maltase activity, and the expression of PEPT, SGLT1, ZNT1, and occludin. AOS also increased serum insulin-like growth factor-1, ghrelin (P < 0.05), and growth hormone (P < 0.1). Moreover, the concentrations of acetate, isobutyrate, isovalerate, valerate, and total SCFAs in cecum of birds fed AOS were significantly higher than the control birds (P < 0.05). Metagenomic analysis indicated that AOS modulated the chicken gut microbiota structure, function, and microbial interactions and promoted the growth of SCFAs-producing bacteria, for example, Dorea sp. 002160985; SCFAs, especially acetate, were found positively correlated with the chicken growth performance and growth-related hormone signals (P < 0.05). We further verified that AOS can be utilized by Dorea sp. to grow and to produce acetate in vitro. CONCLUSIONS: We demonstrated that the enzymatically produced AOS effectively promoted broiler chicken growth performance by modulating the chicken gut microbiota structure and function. For the first time, we established the connections among AOS, chicken gut microbiota/SCFAs, growth hormone signals and chicken growth performance.

Ideación e intento suicida en pacientes con padecimientos psiquiátricos en un hospital de la Ciudad de México / Suicidal ideation and suicide attempt in patients with psychiatric disorders in a Mexico City hospital

Resumen Antecedentes: Uno de los grupos poblacionales en mayor riesgo de suicidio lo constituyen las personas que asisten a instituciones de salud mental. Objetivo: Conocer las características demográficas y clínicas de las personas ingresadas por ideación e intento suicida al área de observación de un hospital psiquiátrico en un periodo de 10 meses no consecutivos. Material y métodos: Estudio retrospectivo, descriptivo y correlacional. Se recabaron 439 expedientes, de los cuales las mujeres representaron 62.9 % (n = 276), los hombres 36.7 % (n = 161) y las personas transgénero 0.5 % (n = 2); el rango de edad varió de 17 a 74 años. Resultados: La mayor incidencia de casos se observó entre los 18 y 25 años, el diagnóstico más frecuente fue el trastorno depresivo y 45.5 % (n = 200) de los casos presentó una tentativa suicida. El principal método para cometer un acto suicida fue el envenenamiento por diversos medicamentos seguido por las lesiones autoinflingidas con objeto punzocortante. Se encontró correlación positiva entre intento suicida y autolesiones (χ2 = 1.965, p < 0.05). Conclusiones: Los hallazgos resaltan la importancia de la identificación temprana de los factores de riesgo que pueden contribuir al incremento del comportamiento suicida.

Abstract Background: One of the population groups at higher risk of suicide is that of people who attend mental health institutions. Objective: To know the demographic and clinical characteristics of people admitted for suicidal ideation and suicide attempt to the observation area of a psychiatric hospital in a period of 10 non-consecutive months. Material and methods: Retrospective, descriptive, correlational study. A total of 439 medical records were collected, out of which 62.9% (n = 276) corresponded to women, 36.7% (n = 161) to men and 0.5% (n = 2) to transgender people; age ranged from 17 to 74 years. Results: The highest incidence of cases was observed between 18 and 25 years of age; the most frequent diagnosis was depressive disorder, and 45.5% (n = 200) of the cases had a suicide attempt. The main method for committing a suicidal act was poisoning by taking various medications, followed by self-inflicted injuries with sharp objects. A positive correlation was found between suicide attempt and self-harm (χ2 = 1.965, p < 0.05). Conclusions: The findings highlight the importance of early identification of risk factors that may contribute to an increase in suicidal behaviors.

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial).

BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use. PATIENTS AND METHODS: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors. RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids. CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.

Effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on NRF2, KEAP1, SOD1, and GPX2 expression in human colorectal cancer cell lines

We investigated the effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on the expression of cytoprotective genes nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2), kelch-like ECH-associated protein 1 (KEAP1), superoxide dismutase (SOD1), and glutathione peroxidase (GPX2) in human colorectal cancer cell lines (HT-29 and Caco-2). Cells were cultured for 24 h in Dulbecco's Modified Eagle's Medium containing juçara fruit pulp (5, 10, or 50 mg/mL) or lyophilized extract (0.05, 0.1, or 0.5 mg/mL), and gene expression was quantified using real-time quantitative reverse transcription polymerase chain reaction. All studied genes showed significant variation in gene expression among different concentrations of pulp or lyophilized extract. Overall, the expression of the selected genes decreased in both cell lines following exposure to the pulp or lyophilized extract in a dose-dependent manner for most of the concentrations studied. In summary, our study showed that the compounds in juçara fruit inhibited the expression of cytoprotective genes associated with the antioxidant response and that, although not cytotoxic at the concentrations studied, they could potentially block the activation of the NRF2/KEAP1 pathway.

Identification of antibodies cross-reactive with woodchuck immune cells and activation of virus-specific and global cytotoxic T cell responses by anti-PD-1 and anti-PD-L1 in experimental chronic hepatitis B and persistent occult hepadnaviral infection.

Woodchuck (Marmota monax) infected with woodchuck hepatitis virus (WHV) is the most pathogenically compatible naturally occurring model of human hepatitis B virus (HBV) infection, chronic hepatitis B, and HBV-induced hepatocellular carcinoma. This system plays a crucial role in discovery and preclinical evaluation of anti-HBV therapies. Its utilization remains tempered by the relatively narrow range of validated immunologic and molecular tools. We evaluated commercial antibodies against immune cell phenotypic markers and T cell molecules for cross-reactivity with woodchuck antigenic equivalents. The confirmed antibodies against programed cell death protein-1 (PD-1) and its ligand (PD-L1) were examined for ex vivo ability to activate WHV-specific, global and bystander cytotoxic T cells (CTLs) in chronic hepatitis and asymptomatic infection persisting after self-resolved acute hepatitis. Examination of 65 antibodies led to identification or confirmation of 23 recognizing woodchuck T, regulatory T, B and natural killer cells, T cell-associated PD-1, PD-L1, CTLA-4 and TIM-3 molecules, CD25 and CD69 markers of T cell activation, and interferon gamma (IFNγ). Antibodies against woodchuck PD-1 and PD-L1 triggered in vitro highly individualized WHV-specific and global activation of CTLs in both chronic hepatitis and persistent occult infection. WHV-specific CTLs were more robustly augmented by anti-PD-1 than by anti-PD-L1 in chronic hepatitis, while global IFNγ-positive CTL response was significantly suppressed in chronic hepatitis compared to persistent occult infection. Anti-PD-1 and anti-PD-L1 also occasionally activated CTLs to specificities other than those tested suggesting their potency to trigger side effects. This was particularly apparent when T cells from chronic hepatitis were treated with anti-PD-L1. The current findings indicate that inhibition of the PD-1/PD-L1 pathway could reactivate virus-specific and global T cell responses in both chronic hepatitis and asymptomatic persistent infection. They suggest a mechanism of potential reactivation of clinically silent infection during anti-PD-1/PD-L1 treatment and indicate that this therapy may also subdue occult HBV infection.