4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway.

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

Different fates of Sb(III) and Sb(V) during the formation of jarosite mediated by Acidithiobacillus ferrooxidans.

Secondary iron-sulfate minerals such as jarosite, which are easily formed in acid mine drainage, play an important role in controlling metal mobility. In this work, the typical iron-oxidizing bacterium Acidithiobacillus ferrooxidans ATCC 23270 was selected to synthesize jarosite in the presence of antimony ions, during which the solution behavior, synthetic product composition, and bacterial metabolism were studied. The results show that in the presence of Sb(V), Fe2+ was rapidly oxidized to Fe3+ by A. ferrooxidans and Sb(V) had no obvious effect on the biooxidation of Fe2+ under the current experimental conditions. The presence of Sb(III) inhibited bacterial growth and Fe2+ oxidation. For the group with Sb(III), products with amorphous phases were formed 72 hr later, which were mainly ferrous sulfate and pentavalent antimony oxide, and the amorphous precursor was finally transformed into a more stable crystal phase. For the group with Sb(V), the morphology and structure of jarosite were changed in comparison with those without Sb. The biomineralization process was accompanied by the removal of 94% Sb(V) to form jarosite containing the Fe-Sb-O complex. Comparative transcriptome analysis shows differential effects of Sb(III) and Sb(V) on bacterial metabolism. The expression levels of functional genes related to cell components were much more downregulated for the group with Sb(III) but much more regulated for that with Sb(V). Notably, cytochrome c and nitrogen fixation-relevant genes for the A.f_Fe2+_Sb(III) group were enhanced significantly, indicating their role in Sb(III) resistance. This study is of great value for the development of antimony pollution control and remediation technology.

Rapid detection of colored and colorless macro- and micro-plastics in complex environment via near-infrared spectroscopy and machine learning.

To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.

Diagnostic accuracy of endoscopic ultrasonographic shear wave elastography for assessing early chronic pancreatitis using the Japanese diagnostic criteria 2019.

Background and Aim: Endoscopic ultrasound shear wave elastography (EUS-SWE) can facilitate an objective evaluation of pancreatic fibrosis. Although it is primarily applied in evaluating chronic pancreatitis, its efficacy in assessing early chronic pancreatitis (ECP) remains underinvestigated. This study evaluated the diagnostic accuracy of EUS-SWE for assessing ECP diagnosed using the Japanese diagnostic criteria 2019. Methods: In total, 657 patients underwent EUS-SWE. Propensity score matching was used, and the participants were classified into the ECP and normal groups. ECP was diagnosed using the Japanese diagnostic criteria 2019. Pancreatic stiffness was assessed based on velocity (Vs) on EUS-SWE, and the optimal Vs cutoff value for ECP diagnosis was determined. A practical shear wave Vs value of ≥50% was considered significant. Results: Each group included 22 patients. The ECP group had higher pancreatic stiffness than the normal group (2.31 ± 0.67 m/s vs. 1.59 ± 0.40 m/s, p < 0.001). The Vs cutoff value for the diagnostic accuracy of ECP, as determined using the receiver operating characteristic curve, was 2.24m/s, with an area under the curve of 0.82 (95% confidence interval: 0.69-0.94). A high Vs was strongly correlated with the number of EUS findings (rs = 0.626, p < 0.001). Multiple regression analysis revealed that a history of acute pancreatitis and ≥2 EUS findings were independent predictors of a high Vs. Conclusions: There is a strong correlation between EUS-SWE findings and the Japanese diagnostic criteria 2019 for ECP. Hence, EUS-SWE can be an objective and invaluable diagnostic tool for ECP diagnosis.

Efficacy and safety of different polymyxin-containing regimens for the treatment of pneumonia caused by multidrug-resistant gram-negative bacteria: a systematic review and network meta-analysis.

BACKGROUND: The optimal administration of polymyxins for treating multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia remains unclear. This study aimed to systematically assess the efficacy and safety of three polymyxin-containing regimens by conducting a comprehensive network meta-analysis. METHODS: We comprehensively searched nine databases. Overall mortality was the primary outcome, whereas the secondary outcomes encompassed microbial eradication rate, clinical success, acute kidney injury, and incidence of bronchospasm. Extracted study data were analyzed by pairwise and network meta-analyses. Version 2 of the Cochrane risk-of-bias tool and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool were used to assess the risk of bias in randomized trials and cohort studies, respectively. RESULTS: This study included 19 observational studies and 3 randomized controlled trials (RCTs), encompassing 3318 patients. Six studies with high risk of bias were excluded from the primary analysis. In the pairwise meta-analysis, compared to the intravenous (IV) polymyxin-containing regimen, the intravenous plus inhaled (IV + IH) polymyxin-containing regimen showed a significant decrease in overall mortality, while no statistically significant difference was found in the inhaled (IH) polymyxin-containing regimen. The network meta-analysis indicated that the IV + IH polymyxin-containing regimen had significantly lower overall mortality (OR 0.67; 95% confidence interval [CI] 0.50-0.88), higher clinical success rate (OR 1.90; 95% CI 1.20-3.00), better microbial eradication rate (OR 2.70; 95% CI 1.90-3.90) than the IV polymyxin-containing regimen, and significantly better microbial eradication rate when compared with the IH polymyxin-containing regimen (OR 2.30; 95% CI 1.30-4.20). Furthermore, compared with IV + IH and IV polymyxin-containing regimens, the IH polymyxin-containing regimen showed a significant reduction in acute kidney injury. CONCLUSIONS: Our study indicates that among the three administration regimens, the IV + IH polymyxin-containing regimen may be the most effective for treating MDR-GNB pneumonia, with a significantly lower overall mortality compared to the IV regimen and a considerably higher microbial eradication rate compared to the IH regimen. The IH regimen may be considered superior to the IV regimen due to its substantially lower incidence of acute kidney injury, even though the reduction in overall mortality was not significant.

Comparing different postoperative sedation strategies for patients in the intensive care unit after cardiac surgery: A systematic review of randomized controlled trials and network meta-analysis.

BACKGROUND: Various postoperative sedation protocols with different anaesthetics lead to profound effects on the outcomes for post-cardiac surgery patients. However, a comprehensive analysis of optimal postoperative sedation strategies for patients in the intensive care unit (ICU) after cardiac surgery is lacking. METHODS: We systematically searched for randomized controlled trials (RCTs) in databases including PubMed and Embase. The primary outcome measured the duration of mechanical ventilation (MV) in the ICU, and the secondary outcome encompassed the length of stay (LOS) in the ICU and hospital and the monitoring adverse events. RESULTS: The literature included 18 RCTs (1652 patients) with 13 sedation regimens. Dexmedetomidine plus ketamine and sevoflurane were associated with a significantly reduced duration of MV when compared with propofol. Our results also suggested that dexmedetomidine plus ketamine may associated with a shorter LOS in ICU, and sevoflurane associated with a shorter LOS in the hospital, respectively. CONCLUSIONS: The combination of dexmedetomidine and ketamine seems to be a better option for adult patients needing sedation after cardiac surgery, and the incidence of side effects is lower with dexmedetomidine. These findings have potential implications for medication management in the perioperative pharmacotherapy of cardiac surgery patients.

The impact of hyperandrogenemia on pregnancy complications and outcomes in patients with PCOS: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder. Current research findings present conflicting views on the effects of different PCOS phenotypes on outcomes in pregnancy and for newborns. METHODS: This research study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A thorough search of literature was carried out using the Cochrane Menstrual Disorders and Subfertility Group trials register, Web of Science, and EMBASE databases from their start to December 2023. The search focused on studies examining the links between hyperandrogenic and non-hyperandrogenic PCOS phenotypes and risks in pregnancy and neonatology. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using either a fixed-effects or random-effects model. RESULTS: Our analysis incorporated 10 research studies. Expectant mothers with a hyperandrogenic PCOS subtype had increased ORs for gestational diabetes mellitus (GDM) and preeclampsia (PE) compared to those with a non-hyperandrogenic PCOS subtype, with respective values of 2.14 (95% CI, 1.18-3.88, I2 = 0%) and 2.04 (95% CI, 1.02-4.08, I2 = 53%). Nevertheless, no notable differences were detected in ORs for outcomes like preterm birth, live birth, miscarriage, cesarean delivery, pregnancy-induced hypertension, small for gestational age babies, large for gestational age newborns, and neonatal intensive care unit admissions between pregnant women with hyperandrogenic PCOS phenotype and those without. CONCLUSIONS: This meta-analysis highlights that the presence of hyperandrogenism heightens the risks of GDM and PE within the PCOS population. Healthcare providers ought to be aware of this connection for improved patient management.

Research Letter: Characterizing spin in psychiatric clinical research literature using large language models.

Importance: Spin is a common form of biased reporting that misrepresents study results in publications as more positive than an objective assessment would indicate, but its prevalence in psychiatric journals is unknown. Objective: To apply a large language model to characterize the extent to which original reports of pharmacologic and non-pharmacologic interventions in psychiatric journals reflect spin. Design: We identified abstracts from studies published between 2013 and 2023 in 3 high-impact psychiatric journals describing randomized trials or meta-analyses of interventions. Main Outcome and Measure: Presence or absence of spin estimated by a large language model (GPT4-turbo, turbo-2024-04-09), validated using gold standard abstracts with and without spin. Results: Among a total of 663 abstracts, 296 (44.6%) exhibited possible or probable spin - 230/529 (43.5%) randomized trials, 66/134 (49.3%) meta-analyses; 148/310 (47.7%) for medication, 107/238 (45.0%) for psychotherapy, and 41/115 (35.7%) for other interventions. In a multivariable logistic regression model, reports of randomized trials, and non-pharmacologic/non-psychotherapy interventions, were less likely to exhibit spin, as were more recent publications. Conclusions and Relevance: A substantial subset of psychiatric intervention abstracts in high-impact journals may contain results presented in a potentially misleading way, with the potential to impact clinical practice. The success in automating spin detection via large language models may facilitate identification and revision to minimize spin in future publications.

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

Chronic illness experience in the context of resource-limited settings: a concept analysis.

AIM: This review describes the ways in which individuals experience chronic illnesses in resource-limited settings; to define the concept and understand its attributes, antecedents and consequences. METHODS: A comprehensive analysis of the databases CINAHL, PubMed and Google Scholar was conducted. During literature search the following limits were applied: articles published in English with available full-text; articles that focused on living with chronic illness in adults from the patient's perspective. RESULTS: The following three attributes of chronic illness experience were identified: transformational experience, acceptance and self-management. Prominent predisposing factors (antecedents) were: genetic inheritance, malnutrition and poverty, high levels of stress and unhealthy lifestyle. The most dominant consequences were as follows: impact on quality of life; self-management burden; burden to others and economic stressors. CONCLUSIONS: The findings underscore the need for health-care professionals to understand the chronic illness experience in the context of resource-limited settings and its consequences. The greater insights into the concept of chronic illness experience in resource-limited settings will guide nurses to support people in the realities of chronic illness experience in resource-limited settings in developing countries. This knowledge can guide nurses in providing competent care to chronically ill individuals, including meeting their individual needs with such illnesses.

Therapeutic potential of Buddleja Polystachya Fresen (stem and leaves) extracts: antimicrobial and cytotoxic properties for ocular disease management.

This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant's potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Geochemical characterization of changes in the chemical composition of river sediments under the continuous anthropogenic influence of Yerevan, Armenia.

The long-term study of the chemical composition of river sediments within urban areas and the establishment of baseline values of major and trace elements is an important task. Therefore, this study aims to provide a geochemical characterization of the sediments, establish a local geochemical baseline, unveil geochemical associations of elements, study the trend of changes in element pollution levels and the associated ecological risks. The results indicate that the change of the local physical characteristics across the river flow (canyon-flat relief surrounded by buildings-reservoir-flat relief under the influence of contamination sources) and locations of contamination sources conditioned the formation of positive extreme values detected for the majority of the studied elements. An analogous variation pattern of major and trace elements median values (2019-2023) was observed for Cr, V, Cu, Fe, Co, Zr Mn, Zn, K, Ba over 5 years representing the geochemical signature of the local geological composition (basalt, andesibasalts, andesite, tuff, K-feldspar). The pollution level and the ecological risk assessment showed that during the study period moderately and highly hazardous levels of multi-element pollution were detected in the southwestern part of the river located near the industrial enterprises. In the meantime, moderate (in 2020) and considerable (in 2021) ecological risk levels were observed at the site near the artificial reservoir. A hierarchical clustering combined with the geochemical ratio analysis reveals three groups of geochemical associations that have a natural (Fe, Mn, Co, V, Ti, Zr, K, Rb, Ba); anthropogenic (Cu, Zn, Pb, Mo) and mixed (Ca, Sr, Cr) origin. Moreover, the anthropogenic association shows affinity to Ca hence denominating the dominant role of carbonates in the fixation and coprecipitation of Cu2+, Pb2+, Mo2+, Zn2+ ions. The comparison of the baseline values of the studied elements with the upper continental crust values confirmed their applicability for differentiation of their origin.

Microbial DNA sample preservation and possible artifacts for field-based research in remote tropical peatlands.

Surveying bacterial and archaeal microbial communities in host and environmental studies requires the collection and storage of samples. Many studies are conducted in distant locations challenging these prerequisites. The use of preserving buffers is an important alternative when lacking access to cryopreservation, however, its effectivity for samples with challenging chemistry or samples that provide opportunities for fast bacterial or archaeal growth upon exposure to an aerobic environment, like peat samples, requires methodological assessment. Here, in combination with an identified optimal DNA extraction kit for peat soil samples, we test the application of several commercial and a homemade preservation buffer and make recommendations on the method that can most effectively preserve a microbiome reflective of the original state. In treatments with a non-optimal buffer or in the absence, we observed notable community shifts beginning as early as three days post-preservation lowering diversity and community evenness, with growth-driven artifacts from a few specific phyla. However other buffers retain a very close composition relative to the original state, and we described several metrics to understand some variation across them. Due to the chemical effects of preservation buffers, it is critical to test their compatibility and reliability to preserve the original bacterial and archaeal community in different environments.

The impact of national savings on economic development: a focused study on the ten poorest countries in Sub-Saharan Africa.

The purpose of this study is to examine the impact of national savings on economic development, as measured by the Human Development Index (HDI), Inequality-adjusted HDI (iHDI), and Multidimensional Poverty Index (MPI), in ten of the poorest countries in Sub-Saharan Africa. The study employs a sequential Generalized Method of Moments (GMM) analysis to address potential endogeneity issues and account for the dynamic nature of the relationships, covering the period from 2009 to 2019. The findings reveal a complex relationship between national savings and the selected development indicators. While national savings exhibit positive impacts on HDI and iHDI, the results are not consistently statistically significant across all the sequential models. However, the analysis suggests that national savings have a positive influence on reducing multidimensional poverty, as measured by MPI, particularly when effectively channeled into productive investments. The study also highlights the significant positive impact of government expenditure and foreign direct investment (FDI) on human development, underscoring the importance of strategic public investments and foreign capital. The results suggest that while national savings are crucial, their effective utilization is essential for enhancing human development indices. Strategic investments in public goods and foreign capital are also important. The mixed effects of inflation and official development assistance (ODA) emphasize the need for stable economic policies and effective utilization of foreign aid. The modest positive impact of institutional quality suggests that improvements in governance and institutional frameworks can contribute to human development. The findings underscore the need for policies promoting financial inclusion, efficient public expenditure, foreign direct investment, and stable macroeconomic conditions to leverage national savings for economic development. The study's findings provide valuable insights for policymakers in Sub-Saharan Africa, highlighting the need for comprehensive strategies that leverage national savings, public expenditure, and foreign investment to drive sustainable economic development and poverty reduction.

Fractional order cancer model infection in human with CD8+ T cells and anti-PD-L1 therapy: simulations and control strategy.

In order to comprehend the dynamics of disease propagation within a society, mathematical formulations are essential. The purpose of this work is to investigate the diagnosis and treatment of lung cancer in persons with weakened immune systems by introducing cytokines ( I L 2 & I L 12 ) and anti-PD-L1 inhibitors. To find the stable position of a recently built system TCD I L 2 I L 12 Z, a qualitative and quantitative analysis are taken under sensitive parameters. Reliable bounded findings are ensured by examining the generated system's boundedness, positivity, uniqueness, and local stability analysis, which are the crucial characteristics of epidemic models. The positive solutions with linear growth are shown to be verified by the global derivative, and the rate of impact across every sub-compartment is determined using Lipschitz criteria. Using Lyapunov functions with first derivative, the system's global stability is examined in order to evaluate the combined effects of cytokines and anti-PD-L1 inhibitors on people with weakened immune systems. Reliability is achieved by employing the Mittag-Leffler kernel in conjunction with a fractal-fractional operator because FFO provide continuous monitoring of lung cancer in multidimensional way. The symptomatic and asymptomatic effects of lung cancer sickness are investigated using simulations in order to validate the relationship between anti-PD-L1 inhibitors, cytokines, and the immune system. Also, identify the actual state of lung cancer control with early diagnosis and therapy by introducing cytokines and anti-PD-L1 inhibitors, which aid in the patients' production of anti-cancer cells. Investigating the transmission of illness and creating control methods based on our validated results will both benefit from this kind of research.

Assessment of heat stress contributing factors in the indoor environment among vulnerable populations in Klang Valley using principal component analysis (PCA).

Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations.

The neural representation of stereotype content.

Judgments about social groups are characterized by their position in a representational space defined by two axes, warmth and competence. We examined serial dependence (SD) in evaluations of warmth and competence while measuring participants' electroencephalographic (EEG) activity, as a means to address the independence between these two psychological axes. SD is the attraction of perceptual reports towards things seen in the recent past and has recently been intensely investigated in vision. SD occurs at multiple levels of visual processing, from basic features to meaningful objects. The current study aims to (1) measure whether SD occurs between non-visual objects, in particular social groups and (2) uncover the neural correlates of social group evaluation and SD using EEG. Participants' judgments about social groups such as "nurses" or "accountants" were serially dependent, but only when the two successive groups were close in representational space. The pattern of results argues in favor of a non-separability between the two axes, because groups nearby on one dimension but far on the other were not subject to SD, even though that other dimension was irrelevant to the task at hand. Using representational similarity analysis, we found a brain signature that differentiated social groups as a function of their position in the representational space. Our results thus argue that SD may be a ubiquitous cognitive phenomenon, that social evaluations are serially dependent, and that reproducible neural signatures of social evaluations can be uncovered.

Mapping of the network connection between sleep quality symptoms, depression, generalized anxiety, and burnout in the general population of Peru and El Salvador.

BACKGROUND: A meta-analysis of randomized controlled trials has suggested a bidirectional relationship between sleep problems and mental health issues. Despite these findings, there is limited conclusive evidence on the relationship between sleep quality, depression, anxiety, and burnout. OBJECTIVE: The current study aimed to evaluate the relationships between sleep quality symptoms, anxiety, depression, and burnout in samples of adult individuals from two Latin American countries, Peru and El Salvador, through network analysis and to identify key symptoms that reinforce the correlation and intensify the syndromes. METHODS: A total of 1012 individuals from El Salvador and Peru participated, with an average age of 26.5 years (SD = 9.1). Symptom networks were constructed for both countries based on data from the Jenkins Sleep Scale, Patient Health Questionnaire-2, General Anxiety Disorder-2, and a single burnout item. RESULTS: The results indicated that Depressed Mood, Difficulty Falling Asleep, and Nervousness were the most central symptoms in a network in the participating countries. The strongest conditional associations were found between symptoms belonging to the same construct, which were similar in both countries. Thus, there is a relationship between Nervousness and Uncontrollable Worry, Anhedonia and Depressed Mood, and Nighttime Awakenings and Difficulty in Staying Asleep. It was observed that burnout is a bridge symptom between both countries and presents stronger conditional associations with Tiredness on Awakening, Depressed Mood, and Uncontrollable Worry. Other bridge symptoms include a Depressed Mood and Nervousness. The network structure did not differ between the participants from Peru and El Salvador. CONCLUSION: The networks formed by sleep quality, anxiety, depression, and burnout symptoms play a prominent role in the comorbidity of mental health problems among the general populations of Peru and El Salvador. The symptom-based analytical approach highlights the different diagnostic weights of these symptoms. Treatments or interventions should focus on identifying central and bridge symptoms.

Transcriptomic changes in the posterior pallium of male zebra finches associated with social niche conformance.

Animals plastically adjust their physiological and behavioural phenotypes to conform to their social environment-social niche conformance. The degree of sexual competition is a critical part of the social environment to which animals adjust their phenotypes, but the underlying genetic mechanisms are poorly understood. We conducted a study to investigate how differences in sperm competition risk affect the gene expression profiles of the testes and two brain areas (posterior pallium and optic tectum) in breeding male zebra finches (Taeniopygia castanotis). In this pre-registered study, we investigated a large sample of 59 individual transcriptomes. We compared two experimental groups: males held in single breeding pairs (low sexual competition) versus those held in two pairs (elevated sexual competition) per breeding cage. Using weighted gene co-expression network analysis (WGCNA), we observed significant effects of the social treatment in all three tissues. However, only the treatment effects found in the pallium were confirmed by an additional randomisation test for statistical robustness. Likewise, the differential gene expression analysis revealed treatment effects only in the posterior pallium (ten genes) and optic tectum (six genes). No treatment effects were found in the testis at the single gene level. Thus, our experiments do not provide strong evidence for transcriptomic adjustment specific to manipulated sperm competition risk. However, we did observe transcriptomic adjustments to the manipulated social environment in the posterior pallium. These effects were polygenic rather than based on few individual genes with strong effects. Our findings are discussed in relation to an accompanying paper using the same animals, which reports behavioural results consistent with the results presented here.

Efficacy and toxicity of KRASG12C inhibitors in advanced solid tumors: a meta-analysis.

BACKGROUND: The efficacy and toxicity of KRASG12C inhibitors were evaluated for advanced solid tumors in several studies; however, the results were not fully consistent. METHODS: Clinical trials evaluating KRASG12C inhibitors for advanced solid tumors were searched from PubMed, Embase, and Cochrane Library online databases up to 31st December 2023. The characteristics of the studies and the results of objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate, and treatment-related adverse events (trAEs) were extracted. RESULTS: Ten studies with 925 heavily pretreated advanced patients harboring KRASG12C mutation were included. For total population, the pooled analysis of ORR was 28.6% (95%CI, 21.2-36.6%), DCR was 85.5% (95%CI, 82.2-88.6%), PFS rate at 6 months (PFS6) was 49.6% (95%CI, 41.4-57.9%), PFS rate at 12 months (PFS12) was 26.7% (95%CI, 19.8-34.1%), OS rates at 6 months (OS6) was 76.2% (95%CI, 68.8-82.9%), OS rates at 12 months (OS12) was 47.8% (95%CI, 38.6-57.0%). The pooled analysis of any grade trAEs was 79.3% (95%CI, 66.2-90.0%) and grade three or more trAEs was 24.4% (95%CI, 16.7-32.9%). The median time to response and DoR results from individual data were 1.39 months (95%CI, 1.37-1.41 months) and 10.54 months (95%CI, 7.72-13.36 months). Sotorasib had significantly lower pooled incidences of any trAEs (OR, 0.07, 95%CI, 0.03-0.14) and grade three or more trAES (OR, 0.34, 95%CI, 0.24-0.49) compared with adagrasib. CONCLUSIONS: KRASG12C inhibitors have good ORR, DCR, PFS rate, OS rate, tolerable trAEs, and early response with long duration in advanced solid tumors; however, most of the pooled results were heterogeneous. Sotorasib has shown better safety results.