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Abstract Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn’s Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.

Abstract Background Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. Methods Data from two decades (2000–2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. Results This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. Discussion (Conclusion) The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

A partir do estado da arte da crítica contemporânea e seus atores, trata-se de avaliar sua noção de ensaio filosófico para caracterizar a crítica de Danto. A redução desse à análise filosófica se mostra insuficiente para qualificar a função e linguagem peculiar da crítica, e estimula a investigação das considerações de Adorno sobre a forma do ensaio, errática e inquisitiva, que o caracteriza entre a especulação e a estética. Essa comparação é substanciada em Danto com suas teses sobre a relação entre filosofia e literatura, que embora distintas compartilham estilos pondo em relevo a forma, e finalmente, reporta-se a distinção entre filosofia e critica que reintroduz a diferença de linguagens.

Abstract Background Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients. Methods We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively. Results We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain. Conclusions Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

A series of ordinary concrete is casted in order to examine the influence of the manganiferous siltstone rocks on the physical, mechanical, and gamma-ray shielding properties. Thus, a partial replacement for the coarse aggregates by siltstone rocks was performed during the fabrication of the currently ordinary concrete. The test revealed that raising the siltstone concentration improved the mechanical characteristics and density of the developed concretes. The addition of siltstone rocks at concentrations ranging from 0 to 40 wt% of the coarse aggregate concentration raises the density of the concrete from 2.05 g/cm3 to 2.3 g/cm3. Furthermore, partial substitution of basalt with siltstone rocks improves gamma-ray shielding properties. The experimental results for the linear attenuation coefficient show an increase in its value from 0.146 cm1 to 0.160 cm−1 when the siltstone concentration is increased between 0 and 40 wt% at 0.662 MeV. Furthermore, increasing the concentrations of siltstone affected the half-value thickness, which varied between 4.759 and 4.319 cm at 0.662 MeV. Therefore, the replacement presents a new alternative coarse aggregate that can enhance the mechanical and radiation shielding properties of ordinary concretes.

Abstract Background Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. Methods Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. Results Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. Conclusion The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide.

Online teaching became an alternative approach for the teacher to run the teachinglearning activities during the COVID-19 pandemic. In this context, this study aimed to identify the issues of mathematics teachers in teaching mathematics through online mode during the pandemic where issues represented the problems and challenges. Altogether 415 mathematics teachers from different levels participated in this crosssectional survey. A self-constructed tool consisting of six categories of problems as Skills and training related problems (STP), learner related problems (LRP), course management and evaluation related problems (CMERP), resource using skills and infrastructure related problems (RUSIP), teaching related problem (TRP), and support and collaboration related problem (SCP) was employed in the study. T-test, ANOVA, correlation, and multiple linear regression were the major statistical techniques used to analyze the data. The findings indicate that the technical skills and digital resources with the learners and teaching figures and curves were major challenges of mathematics teachers in online mode of instruction. Additionally, gender, number of available devices, institute types, teaching levels, ICT training, and types of job were explanatory factors to determine the challenges of mathematics teachers in online teaching during the pandemic.

Heterotopic ossification (HO) refers to abnormal bone formation in soft tissues, which is a common complication of traumatic spinal cord injury (SCI). Current therapeutic approaches are non-specific, have limited efficacy and pose serious off-target effects due to insufficient knowledge of HO mechanisms. In the absence of clinically relevant models of traumatic SCI-associated HO, a novel mouse model of polytrauma with concomitant SCI and musculotendinous injury (MTI) was developed. SCI was induced by T9-T10 spinal cord transection, and muscle crush/tenotomy was performed on left quadricepses (SCI+MTI), leaving right limbs intact as internal controls. Age and sex-matched control mice underwent left hindlimb MTI alone or SCI with left quadriceps crush only (SCI+MI). High-resolution micro-computed tomography revealed variable amounts of ectopic mineral deposits only in injured hindlimbs of SCI+MI and SCI+MTI mice. Median ectopic mineral volumes in SCI+MTI mice were higher than SCI+MI mice at 1 and 4 weeks postoperative. Histology of serial sections confirmed von Kossa-positive mineral colocalizing with ALP-positive osteoblast activity and TRAP-positive osteoclast activity, with a significant increase in ALP between both timepoints. Immunofluorescence indicated F4/80-positive macrophages infiltrating ectopic mineral in SCI+MTI mice at 1 week postoperative, and Osterix-positive osteoblasts lining trabecular bone in HO at 4 weeks postoperative. Orthotopic bone loss manifested as cortical thinning and trabecular bone loss in femurs of SCI mice at 4 weeks postoperative. This study thus identifies SCI+MTI mice as a clinically relevant small animal model of polytrauma with SCI in which to study pathogenic mechanisms and assess novel therapeutic approaches to SCI-associated HO.

Abstract Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.

Abstract Background Following WHO guidelines, microscopy is the gold standard for malaria diagnosis in endemic countries. The Parasitology-Mycology laboratory (LPM) is the National Reference Laboratory and is currently undergoing ISO 15189 accreditation. In this context, we assessed the performance of the laboratory by confirming the reliability and the accuracy of results obtained in accordance with the requirements of the ISO 15189 standards. This study aimed to verify the method of microscopic diagnosis of malaria at the LPM, in the Aristide Le Dantec hospital (HALD) in Dakar, Senegal. Methods This is a validation/verification study conducted from June to August 2020. Twenty (20) microscopic slides of thick/thin blood smear with known parasite densities (PD) selected from the Cheick Anta Diop University malaria slide bank in Dakar were used for this assessment. Six (6) were used to assess microscopists’ ability to determine PD and fourteen (14) slides were used for detection (positive vs negative) and identification of parasites. Four (4) LPM-HALD microscopists read and recorded their results on prepared sheets. Data analysis was done with Microsoft Excel 2010 software. Results A minimum threshold of 50% concordance was used for comparison. Of the twenty (20) slides read, 100% concordance was obtained on eight (8) detection (positive vs negative) slides. Four (4) out of the six (6) parasite density evaluation slides obtained a concordance of less than 50%. Thirteen (13) out of the fourteen (14) identification slides obtained a concordance greater than 50%. Only one (1) identification slide obtained zero agreement from the microscopists. For species identification a concordance greater than 80% was noted and the microscopists obtained scores between 0.20 and 0.4 on a scale of 0 to 1 for parasite density reading. The microscopists obtained 100% precision, sensitivity, specificity and both negative and positive predictive values. Conclusion This work demonstrated that the microscopic method of malaria diagnosis used in the LPM/HALD is in accordance with the requirements of WHO and ISO 15189. Further training of microscopists may be needed to maintain competency.

Abstract Background Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. Methods This study examined parasites from 3147 clinical infections sampled between the years 2012–2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. Results Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence ( 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was

ABSTRACTBackground: PTSD is a significant mental health problem worldwide. Current evidence-based interventions suffer various limitations. Ketamine is a novel agent that is hoped to be incrementally better than extant interventions.Objective: Several randomized control trials (RCTs) of ketamine interventions for PTSD have now been published. We sought to systematically review and meta-analyse results from these trials to evaluate preliminary evidence for ketamine’s incremental benefit above-and-beyond control interventions in PTSD treatment.Results: Omnibus findings from 52 effect sizes extracted across six studies (n = 221) yielded a small advantage for ketamine over control conditions at reducing PTSD symptoms (g = 0.27, 95% CI = 0.03, 0.51). However, bias-correction estimates attenuated this effect (adjusted g = 0.20, 95%, CI = −0.08, 0.48). Bias estimates indicated smaller studies reported larger effect sizes favouring ketamine. The only consistent timepoint assessed across RCTs was 24-hours post-initial infusion. Effects at 24-hours post-initial infusion suggest ketamine has a small relative advantage over controls (g = 0.35, 95% CI = 0.06, 0.64). Post-hoc analyses at 24-hours post-initial infusion indicated that ketamine was significantly better than passive controls (g = 0.44, 95% CI = 0.03, 0.85), but not active controls (g = 0.24, 95% CI = −0.30, 0.78). Comparisons one-week into intervention suggested no meaningful group differences (g = 0.24, 95% CI = 0.00, 0.48). No significant differences were evident for RCTs that examined effects two-weeks post initial infusion (g = 0.17, 95% CI = −0.10, 0.44).Conclusions: Altogether, ketamine-for-PTSD RCTs reveal a nominal initial therapeutic advantage relative to controls. However, bias and heterogeneity appear problematic. While rapid acting effects were observed, all control agents (including saline) also evidenced rapid acting effects. We argue blind penetration to be a serious concern, and that placebo is the likely mechanism behind reported therapeutic effects.

O objetivo do estudo foi validar a metodologia da imunoquimioluminescência (CLIA) através da imunoabsorção enzimática (ELISA), determinando a concentração sérica de progesterona em vacas de leite e de corte, durante o ciclo estral. Foram empregadas 30 vacas multíparas não-prenhes (12 da raça Holandesa Preta e Branca e 18 Nelore). Vacas com corpo luteo foram escolhidas com vistas à sincronização do estro e da ovulação, mediante aplicação de 500 mcg de cloprostenol (im). Após a aplicação do luteolitico, os animais foram diariamente submetidos a exames de ultrasssonagrafia (US) ovariana para verificação da ovulação (=dia 01 do ciclo), bem como eram colhidas 02 amostras de sangue para a determinação da P4 pela CLIA e ELISA. As amostras eram centrifugadas para a obtenção do soro, e congeladas a -20 graus para posterior dosagem. Os valores de ELISA e CLIA foram comparados entre si mediante teste t pareado, regressão, ANOVA e coeficiente de determinação (R2), visando a verificação da sensibilidade e correspondência linear. A concentração de P4 originou perfis similares entre as duas metodologias; os perfis de P4 foram mais elevados em bovinos de corte, que nos de leite. A correspondência entre as metodologias resultou em elevado quociente de R2 nos perfis de P4. Concluiu-se que a CLIA pode ser empregada nas determinações hormonais da P4 serica bovina; a CLIA mostrou elevada correspondência linear com os valores da ELISA; a CLIA pode auxiliar as biotecnicas da reprodução nas determinações hormonais.

Abstract The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.

Este estudo tem como objetivo compreender as repercussões dos indicadores de qualidade que emergem do Sistema de Avaliação da Educação Básica (SAEB) no plano de ações docente do 5º ano do Ensino Fundamental das escolas da Rede Municipal de Ensino de Santa Maria - RS. Para tanto, em movimento de pesquisa qualitativa, analisaram-se dados de duas escolas municipais, que participaram e tiveram seus resultados divulgados, nas últimas cinco edições do SAEB, correspondente aos anos iniciais do Ensino Fundamental. Em cada escola, realizou-se entrevista semiestruturada com uma professora do quinto ano. A partir de seus discursos, emergiram a seguinte grande categoria e suas subcategorias: Repercussões do Sistema de Avaliação da Educação Básica do 5º ano do Ensino Fundamental no trabalho docente; com as subcategorias: marcos da pandemia, performatividade, estreitamento curricular, reducionismo curricular, SAEB, gestão escolar e diálogo da gestão educacional. Como aporte teórico foram utilizados autores como Willmott (1992), Lück (2009), Ball (2005 e 2010), entre outros. Assim, a partir da análise dos dados em interlocução com a base teórica, pode-se compreender que as tecnologias de controle e performáticas fazem parte da realidade vivenciada por docentes e perpassam as práticas pedagógicas, que são modificadas e influenciadas para alcançar índices de avaliações externas.

Abstract Artificial intelligence (AI) systems for detection of COVID-19 using chest X-Ray (CXR) imaging and point-of-care blood tests were applied to data from four low resource African settings. The performance of these systems to detect COVID-19 using various input data was analysed and compared with antigen-based rapid diagnostic tests. Participants were tested using the gold standard of RT-PCR test (nasopharyngeal swab) to determine whether they were infected with SARS-CoV-2. A total of 3737 (260 RT-PCR positive) participants were included. In our cohort, AI for CXR images was a poor predictor of COVID-19 (AUC = 0.60), since the majority of positive cases had mild symptoms and no visible pneumonia in the lungs. AI systems using differential white blood cell counts (WBC), or a combination of WBC and C-Reactive Protein (CRP) both achieved an AUC of 0.74 with a suggested optimal cut-off point at 83% sensitivity and 63% specificity. The antigen-RDT tests in this trial obtained 65% sensitivity at 98% specificity. This study is the first to validate AI tools for COVID-19 detection in an African setting. It demonstrates that screening for COVID-19 using AI with point-of-care blood tests is feasible and can operate at a higher sensitivity level than antigen testing.

Abstract We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study’s goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.