Miracle-dz/UniFAR-FTUs huggingface dataset:
How the size of exogenous attentional cues alters visual performance: From response gain to contrast gain

The normalisation model of attention (NMoA) predicts that the attention gain pattern is mediated by changes in the size of the attentional field and stimuli. However, existing studies have not measured gain patterns when the relative sizes of stimuli are changed. To investigate the NMoA, the present study manipulated the attentional field size, namely, the exogenous cue size. Moreover, we assessed whether the relative rather than the absolute size of the attentional field matters, either by holding the target size constant and changing the cue size (Experiments 1–3) or by holding the cue size constant and changing the target size (Experiment 4), in a spatial cueing paradigm of psychophysical procedures. The results show that the gain modulations changed from response gain to contrast gain when the precue size changed from small to large relative to the target size (Experiments 1–3). Moreover, when the target size was once again made larger than the precue size, there was still a change in response gain (Experiment 4). These results suggest that the size of exogenous cues plays an important role in adjusting the attentional field and that relative changes rather than absolute changes to exogenous cue size determine gain modulation. These results are consistent with the prediction of the NMoA and provide novel insights into gain modulations of visual selective attention.
Structural and functional characterization of multiple myeloma associated cytoplasmic poly(A) polymerase FAM46C

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non‐canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non‐canonical PAP and how MM‐related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation‐related MM occurrence.
Inhibiting Brd4 alleviated PTSD‐like behaviors and fear memory through regulating immediate early genes expression and neuroinflammation in rats

Post‐traumatic stress disorder (PTSD) is characterized by depression/anxiety and memory failure, primarily fear memory. According to the reports, neuroinflammation and synaptic plasticity can play a role in the neurophysiological mechanisms underlying PTSD. Bromodomain‐containing protein 4 (Brd4) intriguingly affects regulating of inflammatory responses and learning and memory. This study aimed to explore the effect of inhibiting Brd4 on depression/anxiety‐like behaviors, spatial and fear memory, and underlying mechanisms in a model of PTSD. Inescapable foot shocks (IFS) with a sound reminder in 6 days were used to induce PTSD‐like behaviors which were tested using contextual and cue fear tests, sucrose preference test, open‐field test, elevated plus maze test, and Y‐maze test. Meanwhile, the Brd4 inhibitor JQ1 was used as an intervention. The results found that IFS induced PTSD‐like behaviors and indicated obvious Brd4 expression in microglia of the prefrontal cortex (PFC), hippocampus, and amygdala, pro‐inflammatory cytokines over‐expression, microglial activation, and nuclear factor‐kappa B over‐expression in PFC and hippocampus but not in amygdala. Meanwhile, the alterations of immediate early genes (IEGs) were found in PFC, hippocampus, and amygdala. Besides, dendritic spine density was reduced in PFC and hippocampus but was elevated in amygdala of rats with IFS. In addition, treatment with JQ1 significantly reduced freezing time in the contextual and cue fear test, reversed the behavioral impairment, decreased the elevated neuroinflammation, and normalized the alteration in IEGs and dendritic spine densities. The results suggested that Brd4 was involved in IFS‐induced PTSD‐like behaviors through regulating neuroinflammation, dynamics of IEGs, and synaptic plasticity.
Polymorphisms in the CYP2A6 and ABCC4 genes are associated with a protective effect on chronic myeloid leukemia in the Brazilian Amazon population

Susceptibility to Chronic Myeloid Leukemia (CML) may be modulated by genetic variables. However, the majority of previous investigations have focused on genetically homogeneous populations, resulting in a lack of evidence on how genetic factors may influence the development of CML in miscegenated populations. We analyzed 30 polymorphisms in genes related to DNA repair, folate metabolism, transmembrane transport, xenobiotic metabolism, and pyrimidine synthesis in relation to their potential role in the susceptibility of the individual to CML.
Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT

Visual Abstract Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of 68Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent 68Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the 68Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate 68Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate 68Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUVmax (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion: 68Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.
Diabetes Mellitus and Oral Lichen Planus: A systematic review and meta-analysis.

OBJECTIVE To undertake a meta-analysis of the association of Oral Lichen Planus (OLP) with diabetes, two diseases with an important impact on public health and the economy, but the evidence of which about their association is inconsistent. METHODS Relevant studies were localized by searching MEDLINE, EMBASE, Conference Proceedings, and other databases from inception to October 2020, without restrictions. The reference lists of included studies and of related reviews were also inspected. Global pooled odds ratios were calculated, and predefined subgroup analyses were performed. The heterogeneity between studies and publication bias were assessed and sensitivity analysis was carried out. RESULTS Thirty-two studies were included in the meta-analysis. Pooled ORs showed a moderate association between diabetes and OLP [OR: 1.87 (95%CI: 1.57, 2.34)]. The association is limited to studies carried out on adults only [OR: 2.12 (95%CI: 1.75, 2.57)] and is observed in all study designs. Globally, the heterogeneity was low to moderate. Studies carried out in European populations show a stronger association of diabetes and OLP than Asiatic studies [OR: 2.49 (95%CI: 1.87, 3.32) and 1.60 (95%CI: 1.25, 2.03), respectively]. CONCLUSIONS Diabetes and OLP are moderately associated. Systematic diagnosis of diabetes in OLP patients could prove useful.
The healing myocardium mobilises a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism.

AIMS Recent studies have revealed that B-cells and antibodies can influence inflammation and remodelling following a myocardial infarction (MI) and culminating in heart failure-but the mechanisms underlying these observations remain elusive. We therefore conducted in mice a deep phenotyping of the post-MI B-cell responses in infarcted hearts and mediastinal lymph nodes, which drain the myocardium. Thereby, we sought to dissect the mechanisms controlling B-cell mobilisation and activity in situ. METHODS AND RESULTS Histological, flow cytometry and single-cell RNA-sequencing (scRNA-seq) analyses revealed a rapid accumulation of diverse B-cell subsets in infarcted murine hearts, paralleled by mild clonal expansion of germinal centre B-cells in the mediastinal lymph nodes. The repertoire of cardiac B-cells was largely polyclonal and showed no sign of antigen-driven clonal expansion. Instead, it included a distinct subset exclusively found in the heart, herein termed "heart-associated B-cells" (hB) that expressed high levels of Cd69 as an activation marker, C-C-chemokine receptor type 7 (Ccr7), CXC-chemokine receptor type 5 (Cxcr5) and transforming growth factor beta 1 (Tgfb1). This distinct signature was not shared with any other cell population in the healing myocardium. Moreover, we detected a myocardial gradient of CXC-motif chemokine ligand 13 (CXCL13, the ligand of CXCR5) on days 1 and 5 post-MI. When compared to wild type controls, mice treated with a neutralising CXCL13-specific antibody as well as CXCR5-deficient mice showed reduced post-MI infiltration of B-cells and reduced local Tgfb1 expression but no differences in contractile function nor myocardial morphology were observed between groups. CONCLUSIONS Our study reveals that polyclonal B-cells showing no sign of antigen-specificity readily infiltrate the heart after MI via the CXCL13-CXCR5 axis and contribute to local TGF-ß1 production. The local B-cell responses are paralleled by mild antigen-driven germinal centre reactions in the mediastinal lymph nodes that might ultimately lead to the production of specific antibodies.
Mitochondria, oxidative stress and nonalcoholic fatty liver disease: A complex relationship

According to the ‘multiple‐hit’ hypothesis, several factors can act simultaneously in nonalcoholic fatty liver disease (NAFLD) progression. Increased nitro‐oxidative (nitroso‐oxidative) stress may be considered one of the main contributors involved in the development and risk of NAFLD progression to nonalcoholic steatohepatitis (NASH) characterized by inflammation and fibrosis. Moreover, it has been repeatedly postulated that mitochondrial abnormalities are closely related to the development and progression of liver steatosis and NAFLD pathogenesis. However, it is difficult to determine with certainty whether mitochondrial dysfunction or oxidative stress are primary events or a simple consequence of NAFLD development. On the one hand, increasing lipid accumulation in hepatocytes could cause a wide range of effects from mild to severe mitochondrial damage with a negative impact on cell fate. This can start the cascade of events, including an increase of cellular reactive nitrogen species (RNS) and reactive oxygen species (ROS) production that promotes disease progression from simple steatosis to more severe NAFLD stages. On the other hand, progressing mitochondrial bioenergetic catastrophe and oxidative stress manifestation could be considered accompanying events in the vast spectrum of abnormalities observed during the transition from NAFL to NASH and cirrhosis. This review updates our current understanding of NAFLD pathogenesis and clarifies whether mitochondrial dysfunction and ROS/RNS are culprits or bystanders of NAFLD progression.
An evaluation tool to strengthen the collaborative process of the public-private partnership in the veterinary domain

Public-private partnerships (PPPs) in the veterinary domain are widely implemented worldwide and can help to strengthen the capacities of Veterinary Services. Few analyses have been made of these initiatives. This study is aimed at developing an evaluation tool based on participatory approaches and focusing on the quality of PPP processes in the veterinary domain. The tool was divided into ten sections relevant to PPP process organisation and activities. The 44 evaluation criteria and six quality attributes (operationality, relevance, acceptability, inclusiveness, adaptability, and stability) were identified based on literature review and case-study application. The tool was adjusted during four regional PPP training workshops bringing together stakeholders from both public and private sectors. Finally, the tool was validated through an experts’ elicitation process and applied in the field in Paraguay. The tool was developed in a non-normative perspective to help the partners adapt the PPP to their specific context, to maximize the opportunities and minimize the risks of such collaborations, and to formulate adapted recommendations to strengthen and improve the PPP collaborative process and thus the outcomes. In an ex-ante perspective, this tool would also help public and private actors to engage and develop a PPP process following the best possible practices. The aim of this tool is to help decision making in terms of PPP development and implementation in the veterinary domain to ensure the added value and relevance of such a collaborative approach in different countries worldwide.
New Daily Persistent Headache in a Pediatric Population

Introduction: New daily persistent headache (NDPH) is a primary headache disorder characterized by an intractable, daily, and unremitting headache lasting for at least 3 months. Currently, there are limited studies in the pediatric population describing the characteristics of NDPH. Objective: The objective of the current study is to describe the characteristics of NDPH in pediatric patients presenting to a headache program at a tertiary referral center. Methods: The participants in the current study were pediatric patients who attended the Headache Clinic at Children’s National Hospital between 2016 and 2018. All patients seen in the Headache Clinic were enrolled in an institutional review board–approved patient registry. Results: Between 2016 and 2018, NDPH was diagnosed in 245 patients, representing 14% of the total headache population. NDPH patients were predominantly female (78%) and white (72%). The median age was 14.8 years. The median pain intensity was 6 of 10 (standard deviation = 1.52). Most patients reported experiencing migrainous features, namely, photophobia (85%), phonophobia (85%), and a reduced activity level (88%). Overall, 33% of patients had failed at least 1 preventive medication, and 56% had failed at least 1 abortive medication. Furthermore, 36% of patients were additionally diagnosed with medication overuse headache. Conclusion: NDPH is a relatively frequent disorder among pediatric chronic headache patients. The vast majority of these patients experience migrainous headache characteristics and associated symptoms and are highly refractory to treatment—as evidenced by a strong predisposition to medication overuse headache and high rates of failed preventive management.
Analysis of off-target effects in CRISPR-based gene drives in the human malaria mosquito

CRISPR-Cas9 nuclease-based gene drives have been developed toward the aim of control of the human malaria vector Anopheles gambiae. Gene drives are based on an active source of Cas9 nuclease in the germline that promotes super-Mendelian inheritance of the transgene by homology-directed repair (“homing”). Understanding whether CRISPR-induced off-target mutations are generated in Anopheles mosquitoes is an important aspect of risk assessment before any potential field release of this technology. We compared the frequencies and the propensity of off-target events to occur in four different gene-drive strains, including a deliberately promiscuous set-up, using a nongermline restricted promoter for SpCas9 and a guide RNA with many closely related sites (two or more mismatches) across the mosquito genome. Under this scenario we observed off-target mutations at frequencies no greater than 1.42%. We witnessed no evidence that CRISPR-induced off-target mutations were able to accumulate (or drive) in a mosquito population, despite multiple generations’ exposure to the CRISPR-Cas9 nuclease construct. Furthermore, judicious design of the guide RNA used for homing of the CRISPR construct, combined with tight temporal constriction of Cas9 expression to the germline, rendered off-target mutations undetectable. The findings of this study represent an important milestone for the understanding and managing of CRISPR-Cas9 specificity in mosquitoes, and demonstrates that CRISPR off-target editing in the context of a mosquito gene drive can be reduced to minimal levels.
Proteome dynamics in persisting and resuscitating bacterial cells

Bacterial persister cells become transiently tolerant to antibiotics by restraining their growth and metabolic activity. Detailed molecular characterization of bacterial persistence is hindered by low count of persisting cells and the need for their isolation. Here we used sustained addition of stable isotope-labeled lysine to selectively label the proteome of hipA-induced persisting and hipB-induced resuscitating E. coli cells in minimal medium after antibiotic treatment. Time-resolved, 24-hour measurement of label incorporation allowed detection of over 500 newly synthetized proteins in persister cells, demonstrating low but widespread protein synthesis. Many essential proteins were newly synthesized and several ribosome-associated proteins showed unusually high synthesis levels, pointing to their roles in maintenance of persistence. At the onset of resuscitation, cells synthesized ABC transporters, restored translation machinery and resumed metabolism by inducing glycolysis and biosynthesis of amino acids. This dataset provides an unprecedented insight into the processes governing persistence and resuscitation of bacterial cells.
Estimates of Cases and Hospitalizations Averted by COVID-19 Case Investigation and Contact Tracing in 14 Health Jurisdictions in the United States

Supplemental Digital Content is Available in the Text. Context: The implementation of case investigation and contact tracing (CICT) for controlling COVID-19 (caused by SARS-CoV-2 virus) has proven challenging due to varying levels of public acceptance and initially constrained resources, especially enough trained staff. Evaluating the impacts of CICT will aid efforts to improve such programs. Objectives: Estimate the number of COVID-19 cases and hospitalizations averted by CICT and identify CICT processes that could improve overall effectiveness. Design: We used data on the proportion of cases interviewed, contacts notified or monitored, and days from testing to case and contact notification from 14 jurisdictions to model the impact of CICT on cumulative case counts and hospitalizations over a 60-day period. Using the Centers for Disease Control and Prevention's COVIDTracer Advanced tool, we estimated a range of impacts by assuming either contacts would quarantine only if monitored or would do so upon notification of potential exposure. We also varied the observed program metrics to assess their relative influence. Results: Performance by jurisdictions varied widely. Jurisdictions isolated between 12% and 86% of cases (including contacts that became cases) within 6 to 10 days after infection. We estimated that CICT-related reductions in transmission ranged from 0.4% to 32%. For every 100 remaining cases after other nonpharmaceutical interventions were implemented, CICT averted between 4 and 97 additional cases. Reducing time to case isolation by 1 day increased averted case estimates by up to 15 percentage points. Increasing the proportion of cases interviewed or contacts notified by 20 percentage points each resulted in at most 3 or 6 percentage point improvements in averted cases. Conclusions: We estimated that CICT reduced the number of COVID-19 cases and hospitalizations among all jurisdictions studied. Reducing time to isolation produced the greatest improvements in impact of CICT.
Robotic Versus Laparoscopic Surgery for Colorectal Cancer: a Case-control Study

Abstract Background Robotic resections represent a novel approach to treatment of colorectal cancer. The aim of our study was to critically assess the implementation of robotic colorectal surgical program at our institution and to compare it to the established laparoscopically assisted surgery. Patients and methods A retrospective case-control study was designed to compare outcomes of consecutively operated patients who underwent elective laparoscopic or robotic colorectal resections at a tertiary academic centre from 2019 to 2020. The associations between patient characteristics, type of operation, operation duration, conversions, duration of hospitalization, complications and number of harvested lymph nodes were assessed by using univariate logistic regression analysis. Results A total of 83 operations met inclusion criteria, 46 robotic and 37 laparoscopic resections, respectively. The groups were comparable regarding the patient and operative characteristics. The operative time was longer in the robotic group (p < 0.001), with fewer conversions to open surgery (p = 0.004), with less patients in need of transfusions (p = 0.004) and lower reoperation rate (p = 0.026). There was no significant difference between the length of stay (p = 0.17), the number of harvested lymph nodes (p = 0.24) and the overall complications (p = 0.58). Conclusions The short-term results of robotic colorectal resections were comparable to the laparoscopically assisted operations with fewer conversions to open surgery, fewer blood transfusions and lower reoperation rate in the robotic group.
Online Service Quality Determinants and E-trust in Internet Shopping: A Psychometric Approach

explain online shopping behaviour. A consumer survey was carried out with a questionnaire, which was empirically validated by employing confirmatory factor analysis (CFA). A sample of 660 respondents was non-randomly drawn from a population of online consumers in Jammu and Kashmir. Structural equation modelling (SEM) was adopted to analyze data and test hypotheses. Results revealed that online service quality determinants and perceived usefulness directly affect e-trust, and perceived usefulness has a mediating effect on e-trust. The study’s findings are useful for website developers and online retailers in crafting innovative and effective designs to maximize trust and perceived usefulness. The study adds to the understanding of e-commerce by developing a revised trust-based consumer online shopping model to describe various factors that influence consumers’ online shopping attitudes and how perceived usefulness mediates the relationship among the variables
Students’ Interpretations of a Persuasive Multimodal Video About Vaccines

The present study investigated students’ (N = 404) interpretations of the main message and use of modes in a persuasive multimodal video on vaccines. It also examined whether students’ topic knowledge, language arts grades, and self-identified gender were associated with their interpretations. Students analyzed a YouTube video in which two entertainers demonstrated the importance of vaccinating children. Students’ interpretations of the usefulness of vaccines varied in terms of quality of reasoning, which was associated with students’ topic knowledge. Notably, many students’ interpretations of the use of modes were incomplete, or they did not even mention certain modes in their response. The results suggest that students should be explicitly taught how to interpret different modes and their uses for argumentative purposes.