Miracle-dz/UniFAR-FTUs huggingface dataset:
Seaweeds influence oyster microbiota and disease susceptibility.

A growing awareness of role that microbiota can play in mediating the effects of pathogens on hosts has given rise to the concept of the pathobiome. Recently, we demonstrated that the Pacific oyster mortality syndrome affecting Crassostrea gigas oysters is caused by infection with the Ostreid herpesvirus type 1 (OsHV-1) followed by infection with multiple bacterial taxa. Here we extend the concept of this pathobiome beyond the host species and its bacterial microbiota by investigating how seaweed living in association with oysters influences their response to the disease. We hypothesized that by their mere presence in the environment, different species of seaweeds can positively or negatively influence the risk of disease in oysters by shaping their bacterial microbiota and their immune response. Although seaweed and oysters do not have direct ecological interactions, they are connected by seawater and likely share microbes. To test our hypothesis, oysters were acclimated with green, brown or red algae for 2 weeks and then challenged with OsHV-1. We monitored host survival and pathogen proliferation and performed bacterial microbiota and transcriptome analyses. We found that seaweeds can alter the bacterial microbiota of the host and its response to the disease. More particularly, green algae belonging to the genus Ulva spp. induced bacterial microbiota dysbiosis in oyster and modification of its transcriptional immune response leading to increased susceptibility to the disease. This work provides a better understanding of a marine disease and highlights the importance of considering both macrobiotic and microbiotic interactions for conservation, management and exploitation of marine ecosystems and resources.
The a’ velocity by tissue-Doppler echocardiography correlates to invasive mean left atrial pressure in patients with normal ejection fraction

Abstract Objectives To evaluate the correlation of a’ velocity by tissue-Doppler measurements with invasively measured mean left atrial pressure in patients with normal ejection fraction. Design In this retrospective study, we evaluated the septal a’, lateral a’ and average a’ velocity by tissue-Doppler echocardiography, in 125 in-hospital patients, 1–12 h before an elective pulmonary vein isolation due to intermittent atrial fibrillation, and compared to invasively measured mean left atrial pressure (LAP) during the invasive procedure. The patients, aged 35–81 years, had to be in sinus rhythm at both examinations, no atrial fibrillation during two procedures, no or mild valve disease and normal ejection fraction (>50%). Results Invasively measured mean LAP correlated well to septal a’ (r = −0.435), lateral a’ (r = −0.473) and average a’ velocity (r = −0.491). Normal mean LAP (≤12 mmHg) was found in 95 patients and elevated mean LAP (>12 mmHg) in 30 patients. The patients with elevated mean LAP had a lower septal a’ velocity (6.5 ± 2.7 vs 8.6 ± 2.3 cm/s; p < .01), lateral a’ velocity (5.9 ± 2.3 vs 8.6 ± 2.1 cm/s; p < .01) and average a’ velocity (6.2 ± 2.4 vs 8.8 ± 2.1 cm/s; p < .01) compared to patients with normal mean LAP. Septal a’, lateral a’ and average a’ velocity were good predictors of elevated mean LAP with AUC of 0.78, 0.83 and 0.82. Average a’ velocity with cut-off < 7.25 cm/s had a sensitivity of 83% and a specificity of 77% to predict elevated mean LAP. Conclusion The a’ velocity is a good indicator of mean LAP and might be considered in the evaluation of left ventricle filling pressure in patients with normal ejection fraction.
Selecting a multiplex PCR panel for accurate molecular diagnosis of intestinal protists: a comparative study of Allplex® (Seegene®), G-DiaParaTrio (Diagenode®), and RIDA®GENE (R-Biopharm®) assays and microscopic examination

Commercial multiplex PCR assay panels were developed to overcome the limitations of microscopic examination for parasitological diagnosis on stool samples. However, given the increased supply of this diagnostic approach, these assays must be evaluated to position them in a diagnostic algorithm. Analytical performances of the multiplex PCR assay G-DiaParaTrio, Allplex® GI parasite and RIDA®GENE parasitic stool panel for detecting Blastocystis sp. , Entamoeba histolytica, Giardia duodenalis, Cryptosporidium spp. , Dientamoeba fragilis, and Cyclospora cayetanensis, were assessed through a retrospective comparative study on 184 stool samples initially sent for parasitological investigation. The composite reference method for parasitological diagnosis was microscopic observation and Entamoeba histolytica-specific adhesion detection when necessary. Multiplex PCR assays were performed on extracted DNA from each stool, following the manufacturer’s recommendations. Discrepant results with the composite reference method were investigated with species-specific PCR to approach a final parasitological diagnosis. Overall sensitivity/specificity for the multiplex PCR assays was 93.2%/100% for G-DiaParaTrio, 96.5%/98.3% for Allplex® GI parasite and 89.6%/98.3% for RIDA®GENE, whereas the composite reference method presented an overall sensitivity/specificity of 59.6%/99.8%. These results confirmed the added diagnostic value of the multiplex PCR approach for gastrointestinal protists. Nevertheless, the PCR procedure and the analytical performance for each protist of interest, variable depending on the multiplex PCR assay, must be considered when implementing a PCR-based diagnostic approach.
Real-world evaluation of insulin requirements after GLP1 agonist or SGLT2 inhibitor initiation and titration.

DISCLAIMER In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE To describe insulin adjustments made following initiation of glucagon-like peptide 1 agonist (GLP1a) or sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy in patients within a primary care setting. METHODS This was a multicenter, retrospective cohort study conducted at an academic health system. Adults with type 2 diabetes mellitus initiated on a GLP1a or SGLT2i while on insulin and managed by an ambulatory care pharmacist were included. The primary endpoint was the percent change in total daily insulin dose at specified time points (2 weeks, 4 weeks, 6 weeks, 3 months, and 6 months) after agent initiation. The secondary endpoints included a glycosylated hemoglobin (HbA1c) value of less than 8%, change from baseline HbA1c, and safety profiles of GLP1a therapy and SGLT2i therapy. RESULTS Of the 150 patients included, 123 were initiated on a GLP1a and 27 on an SGLT2i. After 6 months, GLP1a initiation had resulted in a mean 23.5% decrease (P < 0.001) in insulin dosage and SGLT2i resulted in a mean 0.2% increase (P = 0.20). Insulin dosage reduction with GLP1a use was significantly different between baseline and each time point (P < 0.001). About 72% of patients initiated on a GLP1a and 59% of those initiated on an SGLT2i achieved an HbA1c value of less than 8%. The mean absolute change from baseline in HbA1c concentration was -1.7% with GLP1a use and -1.5% with SGLT2i use (P < 0.001 for both comparisons with baseline values). Hypoglycemia occurred in 21% of patients on a GLP1a and 11% of those on an SGLT2i. CONCLUSION After GLP1a initiation, the mean total daily insulin dose decreased by 23.5%; after SGLT2i initiation, insulin requirements increased by a mean of 0.2%. These results will help guide insulin adjustments after initiation of these medications.
A chromosome-level genome assembly and annotation of the desert horned lizard, Phrynosoma platyrhinos, provides insight into chromosomal rearrangements among reptiles

Abstract Background The increasing number of chromosome-level genome assemblies has advanced our knowledge and understanding of macroevolutionary processes. Here, we introduce the genome of the desert horned lizard, Phrynosoma platyrhinos, an iguanid lizard occupying extreme desert conditions of the American southwest. We conduct analysis of the chromosomal structure and composition of this species and compare these features across genomes of 12 other reptiles (5 species of lizards, 3 snakes, 3 turtles, and 1 bird). Findings The desert horned lizard genome was sequenced using Illumina paired-end reads and assembled and scaffolded using Dovetail Genomics Hi-C and Chicago long-range contact data. The resulting genome assembly has a total length of 1,901.85 Mb, scaffold N50 length of 273.213 Mb, and includes 5,294 scaffolds. The chromosome-level assembly is composed of 6 macrochromosomes and 11 microchromosomes. A total of 20,764 genes were annotated in the assembly. GC content and gene density are higher for microchromosomes than macrochromosomes, while repeat element distributions show the opposite trend. Pathway analyses provide preliminary evidence that microchromosome and macrochromosome gene content are functionally distinct. Synteny analysis indicates that large microchromosome blocks are conserved among closely related species, whereas macrochromosomes show evidence of frequent fusion and fission events among reptiles, even between closely related species. Conclusions Our results demonstrate dynamic karyotypic evolution across Reptilia, with frequent inferred splits, fusions, and rearrangements that have resulted in shuffling of chromosomal blocks between macrochromosomes and microchromosomes. Our analyses also provide new evidence for distinct gene content and chromosomal structure between microchromosomes and macrochromosomes within reptiles.
Linking functional connectome gradient to individual creativity.

INTRODUCTION Human brain network is organized as a hierarchical organization, exhibiting various connectome gradients. The principal gradient is anchored by the modality-specific primary areas and the transmodal regions. Previous studies have suggested that the unimodal-transmodal gradient in the functional connectome may offer an overarching framework for high-order cognitions of human brain. However, there is still a lacking of direct evidence to associate these two. OBJECTIVES Therefore, we aim to explore the association between creativity, a typical human high-order cognitive function, and unimodal-transmodal gradient, using two independent datasets of young adults. METHODS For each individual, we identified the unimodal-transmodal gradient in functional connectome and calculated its global measures. Then we correlated the individual creativity score with measures of unimodal-transmodal gradient at global-brain, subsystem, and regional level. RESULTS The results suggested that better creative performance was associated with greater distance between primary areas and transmodal regions in gradient axes, and less distance between ventral attention network and default mode network. Individual creativity was also found positively correlated with regional gradients in ventral attention network, and negatively correlated with gradients of regions in visual cortex. CONCLUSION Together, these findings directly link the unimodal-transmodal gradient to individual creativity, providing empirical evidence for the cognitive implications of functional connectome gradient.
Early Sexual Debut and Neighborhood Social Environment in Latinx Youth

OBJECTIVES To examine whether social aspects of the neighborhood environment are associated with early sexual initiation in a California agricultural community of predominantly Latinx adolescents. METHODS In a prospective cohort study of 599 eighth graders recruited from middle schools in Salinas, California (2015–2019), participants completed five interviews over 2 years. Social environment measures included neighborhood social dynamics (neighborhood disorder, social cohesion, and social network gang exposure); experiences of discrimination; and school connectedness. We estimated associations between baseline social environment and early sexual initiation (<15 years) using Poisson regression with robust standard errors. We compared contraceptive self-efficacy and attitudes by sexual initiation status using ANOVA. RESULTS Most youth were Latinx (94%) and age 13 (70%) at enrollment; 53% were female and 49% had a parent employed in agriculture. Additionally, 14% reported first vaginal sex before age 15. Neighborhood disorder (relative risk [RR], 1.13; 95% confidence interval [CI], 1.05–1.21), social network gang exposure (RR, 2.23; 95% CI, 1.49–3.33), and experiences of discrimination (RR, 1.67 [1–2 events versus none], 95% CI, 1.09–2.55; RR, 2.33 [3+ events versus none], 95% CI, 1.07–4.64) were associated with early sexual initiation. School connectedness was protective (RR, 0.44, 95% CI, 0.29–0.69). Youth who initiated sex before age 15 had more negative birth control attitudes and expressed lower motivation to use contraceptives. CONCLUSIONS Findings underscore opportunities to promote early adolescent sexual health through strengthening supportive and safe neighborhood environments with the promise of addressing disparities in unintended pregnancy and sexually transmitted infection rates in later adolescence.
Inference of the SARS-CoV-2 generation time using UK household data

The distribution of the generation time (the interval between individuals becoming infected and transmitting the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to data from the early months of the COVID-19 pandemic (December 2019-March 2020) compared to existing models (Hart et al., 2021). However, few estimates of the generation time exist based on data from later in the pandemic. Here, using data from a household study conducted from March to November 2020 in the UK, we provide updated estimates of the generation time. We considered both a commonly used approach in which the transmission risk is assumed to be independent of when symptoms develop, and our mechanistic model in which transmission and symptoms are linked explicitly. Assuming independent transmission and symptoms, we estimated a mean generation time (4.2 days, 95% credible interval 3.3–5.3 days) similar to previous estimates from other countries, but with a higher standard deviation (4.9 days, 3.0–8.3 days). Using our mechanistic approach, we estimated a longer mean generation time (5.9 days, 5.2–7.0 days) and a similar standard deviation (4.8 days, 4.0–6.3 days). As well as estimating the generation time using data from the entire study period, we also considered whether the generation time varied temporally. Both models suggest a shorter mean generation time in September-November 2020 compared to earlier months. Since the SARS-CoV-2 generation time appears to be changing, further data collection and analysis is necessary to continue to monitor ongoing transmission and inform future public health policy decisions.
RAD51 protects against nonconservative DNA double-strand break repair through a nonenzymatic function

Abstract Selection of the appropriate DNA double-strand break (DSB) repair pathway is decisive for genetic stability. It is proposed to act according to two steps: 1-canonical nonhomologous end-joining (C-NHEJ) versus resection that generates single-stranded DNA (ssDNA) stretches; 2-on ssDNA, gene conversion (GC) versus nonconservative single-strand annealing (SSA) or alternative end-joining (A-EJ). Here, we addressed the mechanisms by which RAD51 regulates this second step, preventing nonconservative repair in human cells. Silencing RAD51 or BRCA2 stimulated both SSA and A-EJ, but not C-NHEJ, validating the two-step model. Three different RAD51 dominant-negative forms (DN-RAD51s) repressed GC and stimulated SSA/A-EJ. However, a fourth DN-RAD51 repressed SSA/A-EJ, although it efficiently represses GC. In living cells, the three DN-RAD51s that stimulate SSA/A-EJ failed to load efficiently onto damaged chromatin and inhibited the binding of endogenous RAD51, while the fourth DN-RAD51, which inhibits SSA/A-EJ, efficiently loads on damaged chromatin. Therefore, the binding of RAD51 to DNA, rather than its ability to promote GC, is required for SSA/A-EJ inhibition by RAD51. We showed that RAD51 did not limit resection of endonuclease-induced DSBs, but prevented spontaneous and RAD52-induced annealing of complementary ssDNA in vitro. Therefore, RAD51 controls the selection of the DSB repair pathway, protecting genome integrity from nonconservative DSB repair through ssDNA occupancy, independently of the promotion of CG.
Análise da Custo-Efetividade da Angiotomografia Coronariana no SUS, em Comparação com Outros Métodos Não Invasivos na Suspeita de DAC Estável

Resumo Fundamento Atualmente o sistema de saúde público brasileiro (SUS) não contempla a angiotomografia de coronárias. Objetivos Ranquear sob a perspectiva do SUS, a custo-efetividade de estratégias diagnósticas combinando teste ergométrico, cintilografia miocárdica, ecocardiograma por estresse e angiotomografia de coronárias para o diagnóstico de doença arterial coronariana em uma coorte hipotética de pacientes com probabilidade pré-teste intermediária. Métodos Análise de custo-efetividade por meio de árvore de decisão. Foram analisados a relação de custo-efetividade incremental e o benefício líquido em saúde das estratégias diagnósticas, com a adoção de múltiplos limiares de disposição a pagar entre 0,05 e 1 PIB per capita por diagnóstico correto. Nos casos de testes sequenciais, um segundo teste confirmatório era realizado quando o primeiro fosse positivo. Resultados Após exclusão das estratégias diagnósticas dominadas ou com dominância estendida, a fronteira de eficiência foi composta por três estratégias: teste ergométrico, teste ergométrico seguido de ecocardiograma de estresse, e ecocardiograma de estresse seguido de angiotomografia de coronárias, sendo esta última a estratégia mais custo-efetiva. Pelo critério do benefício líquido, o ranqueamento das estratégias mais custo-efetivas variou conforme a disposição a pagar. Conclusão Utilizando conceitos atuais de avaliação de tecnologias em saúde, este estudo fornece um ranqueamento para a tomada de decisão sobre qual estratégia diagnóstica utilizar, em uma população com risco pré-teste intermediário para DAC. Com estimativa factível de custos para a ATC, o impacto da inclusão desta ao rol do arsenal diagnóstico representaria uma estratégia custo-efetiva na maioria dos cenários avaliados nas variações de disposição a pagar.
Model misspecification in stepped wedge trials: Random effects for time or treatment

Mixed models are commonly used to analyze stepped wedge trials (SWTs) to account for clustering and repeated measures on clusters. One critical issue researchers face is whether to include a random time effect or a random treatment effect. When the wrong model is chosen, inference on the treatment effect may be invalid. We explore asymptotic and finite‐sample convergence of variance component estimates when the model is misspecified and how misspecification affects the estimated variance of the treatment effect. For asymptotic results, we rely on analytical solutions rather than simulation studies, which allow us to succinctly describe the convergence of misspecified estimates, even though there are multiple roots for each misspecified model. We found that both direction and magnitude of the bias associated with model‐based standard errors depends on the study design and magnitude of the true variance components. We identify some scenarios in which choosing the wrong random effect has a large impact on model‐based inference. However, many trends depend on trial design and assumptions about the true correlation structure, so we provide tools for researchers to investigate specific scenarios of interest. We use data from an SWT on disinvesting from weekend services in hospital wards to demonstrate how these results can be applied as a sensitivity analysis, which quantifies the impact of misspecification under a variety of settings and directly compares the potential consequences of different modeling choices. Our results will provide guidance for prespecified model choices and supplement sensitivity analyses to inform confidence in the validity of results.
Effects of low dose doxycycline and caffeic acid phenethyl ester on sclerostin and bone morphogenic protein-2 expressions in experimental periodontitis

ABSTRACT We investigated the effects of caffeic acid phenethyl ester (CAPE) and low-dose doxycycline (LDD) on sclerostin and bone morphogenic protein (BMP)-2 expression in experimental periodontitis. We used male rats in groups as follows: control group (C), periodontitis + CAPE group (PC), periodontitis + LDD group (PD), periodontitis + LDD + CAPE group (PCD) and periodontitis group (P). We administered 10 µmol/kg/day CAPE by an intraperitoneal (i.p.) injection and 10 mg/kg/day LDD by oral gavage. Histopathological changes among groups were evaluated and compared. Sclerostin and BMP-2 expression was analyzed using immunohistochemistry. LDD and/or CAPE treatment ameliorated pathology. The highest sclerostin and lowest BMP-2 expressions were found in P group. Group PC exhibited the highest BMP-2 expression scores and the most significant improvement among the treatment groups. The lowest sclerostin expression was observed in the PD group. We found that preventing sclerostin activity may be a useful treatment alternative for bone resorption, especially in cases of periodontitis and peri-implantitis. We found that CAPE and/or LDD may act as anti-sclerostin agents.
N-Acetyltransferase 2, glutathione S-transferase gene polymorphisms and susceptibility to hepatocellular carcinoma in an Algerian population

Abstract This study was conducted to investigate the potential association of genetic polymorphisms of glutathione S-transferase M1/T1 (GSTM1, GSTT1), and N-acetyltransferase 2 (NAT2) genes and epidemiological parameters with the risk of HCC in the Algerian population. A case-control study including 132 confirmed HCC patients and 141 cancer-free controls was performed. Genotyping analysis was performed using conventional multiplex PCR and PCR-RFLP. Statistical analysis was performed using the Chi-square test. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% CI). GSTM1 null and NAT2 slow acetylator genotypes confer an increased risk to HCC (OR = 1.88, 95% CI 1.16–3.05; OR = 2.30, 95% CI 1.26–4.18, respectively). This association was prevalent in smokers (OR = 2.00, 95% CI 1.05–3.8 and OR = 2.55, 95% CI 1.22–5.34, respectively). No significant association was observed for GSTT1 null genotype in the contribution to HCC risk (OR = 0.76, 95% CI 0.46–1.27). In conclusion, the GSTM1 and NAT2 gene polymorphisms are positively associated with the risk of HCC in older men and especially in smokers.