Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational processes impact the evolution of anti-EGFR antibody resistance in colorectal cancer

Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRC) but acquired resistance invariably evolves. Which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis, a transient cetuximab-induced increase in mutagenesis, contributes in patients is unknown. We investigated this in exome sequencing data of 42 baseline and progression biopsies from cetuximab treated CRCs. Mutation loads did not increase from baseline to progression. Evidence for a contribution of cetuximab-induced mutagenesis was limited. However, the mutational Signature 17 was a key contributer of specific KRAS/NRAS and EGFR driver mutations that are common at acquired resistance. Signature 17 activity before treatment predicted shorter progression free survival. This demonstrates the utility of mutational signatures to predict cancer drug resistance evolution. SIGNIFICANCE Drug resistance evolution occurs ubiquitously in solid tumours during treatment with targeted drugs. Biomarkers that can be assessed prior to treatment to predict the time to resistance evolution and the genetic resistance mechanisms that will evolve have not been described. We identified the mutational Signature 17 as the first candidate biomarker that predicts shorter time to progression and several specific KRAS/NRAS and EGFR mutations that will likely evolve in CRCs during cetuximab treatment. Understanding the mutational mechanism underlying Signature 17 may open opportunities to delay resistance acquisition. The potential of mutational signatures to predict resistance to a broader range of drugs in other tumor types should be assessed.
Depression and anxiety during 2019 coronavirus disease pandemic in Saudi Arabia: a cross-sectional study

Background: COVID 19 outbreak in 2020 was associated with a high rate of depression and anxiety among individuals in the affected countries. The aim of this study is to explore the influence of the COVID 19 epidemic on the psychological distress of residents of the Kingdom of Saudi Arabia. Methods: A cross sectional study using an online survey was conducted in Saudi Arabia between 27th of March and 27th of April 2020. The Patient Health Questionnaire (PHQ 9) and Generalized Anxiety Disorder-7 (GAD 7) were used to assess depression and anxiety. Logistic regression analysis was used to identify predictors of depression and anxiety. Results: The prevalence of depression and anxiety among the entire study participants was 9.4% and 7.3%, respectively. Non-Saudi residents, aged 50 years and above, divorced, retired, university students, and those with income (2000 to 10,000 RS) were at higher risk of developing depression. Saudi individuals, married, unemployed, and those with high income (> 10,000 RS) were at higher risk of developing anxiety. Conclusions: There is a wide range of the Saudi residents who are at higher risk of mental illness during COVID 19 pandemic. Policymakers and mental healthcare providers are advised to provide continuous monitoring of the psychological consequences during this pandemic, and provide mental support.
The antimicrobial peptide DGL13K is active against drug-resistant gram-negative bacteria and sub-inhibitory concentrations stimulate bacterial growth without causing resistance

Antimicrobial peptides may be alternatives to traditional antibiotics with reduced bacterial resistance. The antimicrobial peptide GL13K was derived from the salivary protein BPIFA2. This study determined the relative activity of the L-and D-enantiomers of GL13K to wild-type and drug-resistant strains of three gram-negative species and against Pseudomonas aeruginosa biofilms. DGL13K displayed in vitro activity against ESBL and KPC-producing Klebsiella pneumoniae (MICs 16-32 μg/ml), MDR and XDR P. aeruginosa, and XDR Acinetobacter baumannii carrying metallo-beta-lactamases (MICs 8-32 μg/ml). P. aeruginosa showed low inherent resistance to DGL13K and the increased metabolic activity and growth caused by sub-MIC concentrations of GL13K peptides did not result in acquired bacterial resistance. Daily dosing for approximately two weeks did not increase the MIC of DGL13K or cause cross-resistance between LGL13K and DGL13K. These data suggest that DGL13K is a promising candidate antimicrobial peptide for further development.
Behaviors and attitudes in response to the COVID-19 pandemic: Insights from a cross-national Facebook survey

In the absence of medical treatment and vaccination, the mitigation and containment of the ongoing COVID-19 pandemic relies on behavioral changes. Timely data on attitudes and behaviors are thus necessary to develop optimal intervention strategies and to assess the consequences of the pandemic for different demographic groups. We developed a rapid response monitoring system via a continuously run online survey (the "COVID-19 Health Behavior Survey") across eight countries (Belgium, France, Germany, Italy, the Netherlands, Spain, the United Kingdom, the United States). The survey was specifically designed to collect key information on people's health status, behaviors, close social contacts, and attitudes in response to the COVID-19 pandemic. We developed an innovative approach to recruit participants via targeted Facebook advertisement campaigns in order to generate balanced samples for post-stratification. In this paper, we present results for the period from March 13-April 19, 2020. We estimate important differences by sex: women show a substantially higher perception of threat along with a lower level of confidence in the health system. This is paralleled by sex-specific behaviors, with women more likely to adopt a wide range of preventive behaviors. We thus expect behavior to serve as a protective factor for women. Our findings also show a higher level of awareness and concern among older respondents, in line with the evidence that the elderly are at highest risk of severe complications following infection from COVID-19. While across all the samples respondents were less concerned for themselves than for their country or for the world, we also observed substantial temporal and spatial heterogeneity in terms of confidence in institutions and responses to non-pharmaceutical interventions.
Relevance of Aβ 1-42 Intrahippocampal Injection as An Animal Model of Inflamed Alzheimers Disease Brain

Injection of amyloid-beta peptide (Abeta1-42) into hippocampal and cortical regions of brain may have utility as an animal model of Alzheimer's disease (AD) emphasizing the inflammatory component of disease pathology. This review summarizes recent evidence supporting the relevance of the peptide injection model to describe inflammatory conditions in AD brain. A wide spectrum of responses are considered from effects of Abeta1-42 on animal behavior and cognitive performance to peptide actions at the cellular and molecular levels. In the latter case a particular focus is placed on inflammatory responses mediated by activated microglia. Specific pharmacological modulations of microglial signaling pathways and factors and how they shape patterns of inflammatory reactivity in peptide-injected brain are included. Overall, the considerations for the validity and limitations of Abeta1-42 injection as an animal model for AD pathology are also discussed.
Larvicidal and Adulticidal Effects of Extracts from Some Indigenous Plants against the Malaria Vector, Anopheles arabiensis (Diptera: Culicidae) in Ethiopia

The mosquito Anopheles not only cause nuisance by their bites but also transmit deadly diseases like malaria in Sub-Saharan Africa, where most of the malaria deaths occur in the world. In Ethiopia, despite the use of native plants in traditional combat against mosquitoes, use in a modern way has remained scanty. The present study, being based on an initial ethno botanical survey, carried out screening experiments on five indigenous ethno botanical species (Aloe pirottae Berger, Aloaceae; Acokanthera schimperi (A.DC) Schweinf, Appocynaceae; Brassica nigra L. Koch, Brassicaceae; Oreosyce africana Hook.f. , Cucurbitaceae and Piper capense L.f. , Piperaceae). The larvicidal activity of 80% methanol extracts of the first two plant species against the fourth instars of Anopheles arabiensis Patton, and adulticidal activity with the same solvent extracts of the latter four species against Anopheles arabiensis adults, gave positive results upon evaluation under laboratory condition. The 80% methanol extract of the gel of A. pirottae had more activity within 24 hours on the larvae than the leaf extract of Acokanthera schimperi. The highest (100%) mortality in the fourth instars occurred on treatment with 160 ppm extract of Aloe pirottae and 480 ppm extract of Acokanthera schimperi. The maximum adult mortality was detected in the leaf extract of Oreosyce africana (LC50 18.74 and LC90 39.66 ppm) followed by fruit extract of Piper capense (LC50 24.30 and LC90 46.32 ppm), while no mortality was noticed in the control groups. Phytochemical screening of the methanol extracts of the leaves of Oreosyce africana and the fruits of Piper capense had key secondary metabolites (alkaloids, saponins, flavonoids, cardiac glycosides), further corroborating their adulticidal properties. These findings announce the first evidence that Aloe pirottae is a promising mosquito larvicide while Oreosyce africana and Piper capense carry huge potentials as mosquito adulticides contributing to integrated malaria control through proper mosquito management.
Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

The Infinium Human Methylation450 and Methylation EPIC BeadChips are useful tools for the study of the methylation state of hundreds of thousands of CpG across the human genome at affordable cost. However, in a wide range of experimental settings in particular for studies in infectious or brain-related diseases, human samples cannot be easily obtained. Hence, due to their close developmental, immunological and neurological proximity with humans, non-human primates are used in many research fields of human diseases and for preclinical research. Few studies have used DNA methylation microarrays in simian models. Microarrays designed for the analysis of DNA methylation patterns in the human genome could be useful given the genomic proximity between human and nonhuman primates. However, there is currently information lacking about the specificity and usability of each probe for many nonhuman primate species, including rhesus macaques (Macaca mulatta), originating from Asia, and African green monkeys originating from West-Africa (Chlorocebus sabaeus). Rhesus macaques and African green monkeys are among the major nonhuman primate models utilized in biomedical research. Here, we provide a precise evaluation and re-annotation of the probes of the two microarrays for the analysis of genome-wide DNA methylation patterns in these two Cercopithecidae species. We demonstrate that up to 162,000 of the 450K and 255,000 probes of the EPIC BeadChip can be reliably used in Macaca mulatta or Chlorocebus sabaeus. The annotation files are provided in a format compatible with a variety of preprocessing, normalization and analytical pipelines designed for data analysis from 450K/EPIC arrays, facilitating high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus. They provide the opportunity to the research community to focus their analysis only on those probes identified as reliable. The described analytical workflow leaves the choice to the user to balance coverage versus specificity and can also be applied to other Cercopithecidae species.
Estimating and forecasting COVID-19 attack rates and mortality

{We describe a model for estimating past and current infections as well as future deaths due to the ongoing COVID-19 pandemic. The model does not use confirmed case numbers and is based instead on recorded numbers of deaths and on the age-specific population distribution. A regularized deconvolution technique is used to infer past infections from recorded deaths. Forecasting is based on a compartmental SIR-type model, combined with a probability distribution for the time from infection to death. The effect of non-pharmaceutical interventions (NPIs) is modelled empirically, based on recent trends in the death rate. The model can also be used to study counterfactual scenarios based on hypothetical NPI policies.
Biomarkers in Psychiatry: Concept, Definition, Types and Relevance to the Clinical Reality

During the last years, an extraordinary effort has been made to identify biomarkers as potential tools for improving prevention, diagnosis, drug response and drug development in psychiatric disorders. Contrary to other diseases, mental illnesses are classified by diagnostic categories with a broad variety list of symptoms. Consequently, patients diagnosed from the same psychiatric illness present a great heterogeneity in their clinical presentation. This fact together with the incomplete knowledge of the neurochemical alterations underlying mental disorders, contribute to the limited efficacy of current pharmacological options. In this respect, the identification of biomarkers in psychiatry is becoming essential to facilitate diagnosis through the developing of markers that allow to stratify groups within the syndrome, which in turn may lead to more focused treatment options. In order to shed light on this issue, this review summarizes the concept and types of biomarkers including an operational definition for therapeutic development. Besides, the advances in this field were summarized and sorted into five categories, which include genetics, transcriptomics, proteomics, metabolomics, and epigenetics. While promising results were achieved, there is a lack of biomarker investigations especially related to treatment response to psychiatric conditions. This review includes a final conclusion remarking the future challenges required to reach the goal of developing valid, reliable and broadly-usable biomarkers for psychiatric disorders and their treatment. The identification of factors predicting treatment response will reduce trial-and-error switches of medications facilitating the discovery of new effective treatments, being a crucial step towards the establishment of greater personalized medicine.
LUM Expression and Its Prognostic Significance in Gastric Cancer

Background: Lumican (LUM) is a member of the small leucine-rich proteoglycan family and plays dual roles as an oncogene and a tumor suppressor gene. The effect of LUM on tumors is still controversial. Methods: Gene expression profiles and clinical data of gastric cancer (GC) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of LUM in GC tissues and adjacent nontumor tissues was analyzed by R software and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and comprehensive meta-analysis. The relationship between LUM expression and clinicopathological parameters was assessed by chi-square test and logistic regression. Kaplan–Meier survival analysis and Cox proportional hazards regression model were chosen to assess the effect of LUM expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in GC between the low and the high LUM expression datasets. Results: The expression of LUM in GC tissues was significantly higher than that in adjacent nontumor tissues (P < 0.001) from the TCGA database. qRT-PCR (P = 0.022) and comprehensive meta-analysis (standard mean difference = 0.90, 95% CI: 0.34–1.46) demonstrated that LUM was upregulated in GC. The chi-square test showed that the high expression of LUM was correlated with tumor differentiation (P = 0.024) and T stage (P = 0.004). Logistic regression analysis showed that high LUM expression was significantly correlated with tumor differentiation (OR = 1.543 for poor vs. well or moderate, P = 0.043), pathological stage (OR = 3.149 for stage II vs. stage I, P = 0.001; OR = 2.505 for stage III vs. stage I, P = 0.007), and T classification (OR = 13.304 for T2 vs. T1, P = 0.014; OR = 18.434 for T3 vs. T1, P = 0.005; OR = 30.649 for T4 vs. T1, P = 0.001). The Kaplan–Meier curves suggested that patients with high LUM expression had a poor prognosis. Multivariate analysis showed that a high expression of LUM was an important independent predictor of poor overall survival (HR, 1.189; 95% CI, 1.011–1.400; P = 0.037). GSEA indicated that 14 signaling pathways were evidently enriched in samples with the high-LUM expression phenotype. Conclusions: LUM might act as an oncogene in the progression of GC and could be regarded as a potential prognostic indicator and therapeutic target for GC.
Immunoglobulin G Subclass-Specific Glycosylation Changes in Primary Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) was previously shown to be associated with glycosylation changes of total serum and total IgG proteins. However, as a majority of previous studies analyzed released glycan profiles, still little is known about IgG subclass-specific alterations in ovarian cancer. Hence, in this study, we investigated EOC-related glycosylation changes of the three most abundant IgG subclasses, namely, IgG1, IgG2 and IgG3 isolated from sera of 87 EOC patients and 74 age-matched healthy controls. In order to separate IgG2 and IgG3, we performed a two-step affinity purification employing Protein A and Protein G Sepharose. After tryptic digestion, IgG glycopeptides were enriched and measured by MALDI-TOF-MS. Finally, EOC-related glycosylation changes were monitored at the level of total agalactosylation, monogalactosylation, digalactosylation, sialylation, bisection and fucosylation, which were calculated separately for each IgG subclass. Interestingly, aside from an EOC-related increase in agalactosylation/decrease in monogalactosylation and digalactosylation observed in all IgG subclasses, some subclass-specific trends were detected. Glycosylation of IgG1 was found to be most strongly affected in EOC, as it exhibited the highest number of significant differences between healthy controls and EOC patients. Specifically, IgG1 was the only subclass that showed a significant decrease in sialylation and a significant increase in fucosylation in EOC patients. Interestingly, IgG2 and IgG3 that were often investigated collectively in previous studies, were found to have distinct glycosylation patterns. IgG3 displayed stronger EOC-related increase in agalactosylation/decrease in digalactosylation and was characterized by notably higher sialylation, which consequently decreased in EOC patients. In conclusion, our study indicates that IgG subclasses exhibit subtly distinct glycosylation patterns of EOC-related alterations and that IgG1 and IgG3 agalactosylation show the strongest association with CA125, the routine diagnostic marker. Additionally, our results show that simultaneous analyses of IgG2 and IgG3 might lead to wrong conclusions as these two subclasses exhibit noticeably different glycosylation phenotypes.
Atração do predador Doru luteipes (Scudder) (Dermaptera: Forficulidae) por estímulos olfativos de dietas alternativas em laboratório

Doru luteipes consumes larvae of Spodoptera frugiperda, which is at this moment the main pest of maize crop in Brazil. In general, if 70% of the plants had this predator the pest would be kept under the threshold of economic damage. However, the predator occurs after the pest damages the plants. Thus, the availability of materials that would attract and anticipate the presence of predator in the field,could reduce pest populations. In such a way, it was studied in the laboratory the attractiveness of artificial diets for males and females of the D. luteipes. The treatments were: ground dehydrated pupa of the silk worm and pollen mixture in the amounts of 0.05, 0.1, 0.2, 0.5 e 1.0g, for both the diets The diet stimulus were compared to control using a olfactometer. In general, attraction increased with rising amounts of the diets. Further investigations were proposed to test the viability of the usage of the materials to manage the pest in the field.
Are All Four-Day School Weeks Created Equal? A National Assessment of Four-Day School Week Policy Adoption and Implementation

Abstract Four-day school weeks are used in over 1,600 schools across twenty-four states but little is known about adoption and implementation of these types of school calendars. Through examinations of school calendars and correspondence with school districts, we have compiled the most complete four-day school week dataset to date. We use this unique database to conduct a comprehensive analysis of four-day school week policy adoption and implementation. We find adoption of four-day school weeks is often financially motivated and has generally remained a small, rural district phenomenon. These schedules feature a day off once a week—often Friday—with increased time in school on each of the remaining four school days that, on average, is nearly an hour longer than the national average among five-day schools. Four-day school week schedules average only 148 school days per year, resulting in less time in school than the national average for five-day schools (180 days per year) despite the longer school days. Substantial heterogeneity exists in the structure of these schedules across states, which may help explain differential four-day school week effects on student outcomes across institutional settings in the previous literature.
The actin-modulating protein synaptopodin mediates long-term survival of dendritic spines

Large spines are stable and important for memory trace formation. The majority of large spines also contains Synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using time-lapse 2-photon-imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP-positive (SP+) spines followed conditional two-phase decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single exponential decays. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines and the presence of SP indicates spines of high stability.