Miracle-dz/UniFAR-FTUs huggingface dataset:
Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessus

Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. ABSTRACT Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections. In this context, rifabutin (RFB) has been shown to be active against M. abscessus and has raised renewed interest in using rifamycins for the treatment of M. abscessus pulmonary diseases. Here, we compared the in vitro and in vivo activity of RFB against the smooth and rough variants of M. abscessus, differing in their susceptibility profiles to several drugs and physiopathologial characteristics. While the activity of RFB is greater against rough strains than in smooth strains in vitro, suggesting a role of the glycopeptidolipid layer in susceptibility to RFB, both variants were equally susceptible to RFB inside human macrophages. RFB treatment also led to a reduction in the number and size of intracellular and extracellular mycobacterial cords. Furthermore, RFB was highly effective in a zebrafish model of infection and protected the infected larvae from M. abscessus-induced killing. This was corroborated by a significant reduction in the overall bacterial burden, as well as decreased numbers of abscesses and cords, two major pathophysiological traits in infected zebrafish. This study indicates that RFB is active against M. abscessus both in vitro and in vivo, further supporting its potential usefulness as part of combination regimens targeting this difficult-to-treat mycobacterium.
Asymptomatic Rotavirus Infections among Children in Maiduguri, Borno State, Northeast, Nigeria

Background: Rotavirus remains one of the main causative agents of gastroenteritis in young children. This happens, especially in countries (e.g., Nigeria) that have not yet introduced the vaccine into the national immunization program. A significant prevalence of Rotavirus infection both in children and adults without major symptoms has earlier been reported. This study aimed at defining the prevalence of asymptomatic Rotavirus infection from apparently healthy children in Maiduguri, Borno State, Northeastern Nigeria. Methods: A total of 269 stool samples were randomly collected from apparently healthy children <15 years of age from July 2017 to June 2018. All samples were screened using a commercially available enzyme-linked immunosorbent assay kit for the presence of Rotavirus antigen. The Rotavirus-positive samples were further subjected to polyacrylamide gel electrophoresis (PAGE) to determine their RNA electropherotypes. Results: A total of 59 stool samples (19.9%) were Rotavirus positive with peaks observed in the cold dry season, among male children, and 6–10 years of age group. A total of 50 randomly selected Rotavirus-positive samples were subjected to PAGE, and none of the samples showed either long or short profiles. Conclusion: This study shows that Rotavirus can be shed into environments without any signs and symptoms. In view of this, the Rotavirus vaccine should be considered a priority and be introduced in the existing national immunization program in Nigeria, particularly in Borno State.
Minimal but not meaningless: Seemingly arbitrary category labels can imply more than group membership.

Minimal group paradigms tend to involve contrived group distinctions, such as dot estimation tendencies and aesthetic preferences. Researchers assume that these novel category distinctions lack informational value. Our research tests this notion. Specifically, we used the classic overestimator versus underestimator and Klee versus Kandinsky minimal group paradigms to assess how category labels influence minimal group responses. In Study 1, we show that participants represented ingroup faces more favorably than outgroup faces, but also represented overestimator and underestimator category labels differently. In fact, the category label effect was larger than the intergroup effect, even though participants were told that estimation tendencies were unrelated to other cognitive tendencies or personality traits. In Study 2, we demonstrate that Klee and Kandinsky were also represented differently, but in this case, the intergroup effect was stronger than the category label effect. In Studies 3 and 4, we examined effects of category labels on how participants allocate resources to, evaluate, and ascribe traits to ingroup and outgroup members. We found both category label and intergroup effects when participants were assigned to overestimator and underestimator groups. However, we found only the intergroup effect when participants were assigned to Klee and Kandinsky groups. Together, this work advances but does not upend understanding of minimal group effects. We robustly replicate minimal intergroup bias in mental representations of faces, evaluations, trait inferences, and resource allocations. At the same time, we show that seemingly arbitrary category labels can imply characteristics about groups that may influence responses in intergroup contexts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
General Versus Local Anesthesia With Conscious Sedation in Transcatheter Aortic Valve Implantation

Background: In clinical practice, local anesthesia with conscious sedation (CS) is performed in roughly 50% of patients undergoing transcatheter aortic valve replacement. However, no randomized data assessing the safety and efficacy of CS versus general anesthesia (GA) are available. Methods: The SOLVE-TAVI (Comparison of Second-Generation Self-Expandable Versus Balloon-Expandable Valves and General Versus Local Anesthesia in Transcatheter Aortic Valve Implantation) trial is a multicenter, open-label, 2×2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement comparing CS versus GA. The primary efficacy end point was powered for equivalence (equivalence margin 10% with significance level 0.05) and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury at 30 days. Results: The primary composite end point occurred in 27.2% of CS and 26.4% of GA patients (rate difference, 0.8 [90% CI, −6.2 to 7.8]; Pequivalence=0.015). Event rates for the individual components were as follows: all-cause mortality, 3.2% versus 2.3% (rate difference, 1.0 [90% CI, −2.9 to 4.8]; Pequivalence<0.001); stroke, 2.4% versus 2.8% (rate difference, −0.4 [90% CI, −3.8 to 3.8]; Pequivalence<0.001); myocardial infarction, 0.5% versus 0.0% (rate difference, 0.5 [90% CI, −3.0 to 3.9]; Pequivalence<0.001), infection requiring antibiotics 21.1% versus 22.0% (rate difference, −0.9 [90% CI, −7.5 to 5.7]; Pequivalence=0.011); acute kidney injury, 9.0% versus 9.2% (rate difference, −0.2 [90% CI, −5.2 to 4.8]; Pequivalence=0.0005). There was a lower need for inotropes or vasopressors with CS (62.8%) versus GA (97.3%; rate difference, −34.4 [90% CI, −41.0 to −27.8]). Conclusions: Among patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement, use of CS compared with GA resulted in similar outcomes for the primary efficacy end point. These findings suggest that CS can be safely applied for transcatheter aortic valve replacement. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT02737150.
Neuroimaging in Zoonotic Outbreaks Affecting the Central Nervous System: Are We Fighting the Last War?

SUMMARY: When preparing for the coronavirus disease 2019 pandemic and its effects on the CNS, radiologists should be familiar with neuroimaging appearances in past zoonotic infectious disease outbreaks. Organisms that have crossed the species barrier from animals to humans include viruses such as Hendra, Nipah, Severe Acute Respiratory Syndrome, and influenza, as well as bacteria and others. Brain CT and MR imaging findings have included cortical abnormalities, microinfarction in the white matter, large-vessel occlusion, and features of meningitis. In particular, the high sensitivity of diffusion-weighted MR imaging in detecting intracranial abnormalities has been helpful in outbreaks. Although the coronaviruses causing the previous Severe Acute Respiratory Syndrome outbreak and the current coronavirus disease 19 pandemic are related, it is important to be aware of their similarities as well as potential differences. This review describes the neuroimaging appearances of selected zoonotic outbreaks so that neuroradiologists can better understand the current pandemic and potential future outbreaks.
A Plant Virus Ensures Viral Stability in the Hemolymph of Vector Insects through Suppressing Prophenoloxidase Activation

Large ratios of vector-borne plant viruses circulate in the hemolymph of their vector insects before entering the salivary glands to be transmitted to plants. The stability of virions in the hemolymph is vital in this process. Activation of the proteolytic prophenoloxidase (PPO) to produce active phenoloxidase (PO) is one of the major innate immune pathways in insect hemolymph. How a plant virus copes with the PPO immune reaction in its vector insect remains unclear. Here, we report that the PPO affects the stability of rice stripe virus (RSV), a notorious rice virus, in the hemolymph of a vector insect, the small brown planthopper. RSV suppresses PPO activation using viral nonstructural protein. Once the level of PO activity is elevated, RSV is melanized and eliminated from the hemolymph. Our work gives valuable clues for developing novel strategies for controlling the transmission of vector-borne plant viruses. ABSTRACT Most plant viruses require vector insects for transmission. Viral stability in the hemolymph of vector insects is a prerequisite for successful transmission of persistent plant viruses. However, knowledge of whether the proteolytic activation of prophenoloxidase (PPO) affects the stability of persistent plant viruses remains elusive. Here, we explored the interplay between rice stripe virus (RSV) and the PPO cascade of the vector small brown planthopper. Phenoloxidase (PO) activity was suppressed by RSV by approximately 60%. When the PPO cascade was activated, we found distinct melanization around RSV particles and serious damage to viral stability in the hemolymph. Viral suppression of PO activity was derived from obstruction of proteolytic cleavage of PPOs by binding of the viral nonstructural protein NS3. These results indicate that RSV attenuates the PPO response to ensure viral stability in the hemolymph of vector insects. Our research provides enlightening cues for controlling the transmission of vector-borne viruses. IMPORTANCE Large ratios of vector-borne plant viruses circulate in the hemolymph of their vector insects before entering the salivary glands to be transmitted to plants. The stability of virions in the hemolymph is vital in this process. Activation of the proteolytic prophenoloxidase (PPO) to produce active phenoloxidase (PO) is one of the major innate immune pathways in insect hemolymph. How a plant virus copes with the PPO immune reaction in its vector insect remains unclear. Here, we report that the PPO affects the stability of rice stripe virus (RSV), a notorious rice virus, in the hemolymph of a vector insect, the small brown planthopper. RSV suppresses PPO activation using viral nonstructural protein. Once the level of PO activity is elevated, RSV is melanized and eliminated from the hemolymph. Our work gives valuable clues for developing novel strategies for controlling the transmission of vector-borne plant viruses.
Susceptibility of Clinical Isolates of Escherichia coli to Fosfomycin as Measured by Four In Vitro Testing Methods

Clinical isolates of Escherichia coli (n = 554) were tested against fosfomycin using agar dilution, disk diffusion, and Etest. Agar dilution (reference method) identified few isolates with fosfomycin MICs of 64 (n = 3), 128 (n = 4), and ≥256 μg/ml (n = 2). Applying CLSI (M100, 2020) and EUCAST (v. 10.0, 2020) breakpoints, 98.9% and 98.4% (agar dilution), 99. ABSTRACT Clinical isolates of Escherichia coli (n = 554) were tested against fosfomycin using agar dilution, disk diffusion, and Etest. Agar dilution (reference method) identified few isolates with fosfomycin MICs of 64 (n = 3), 128 (n = 4), and ≥256 μg/ml (n = 2). Applying CLSI (M100, 2020) and EUCAST (v. 10.0, 2020) breakpoints, 98.9% and 98.4% (agar dilution), 99.3% and 99.1% (disk diffusion), and 99.1% and 98.9% (Etest) of isolates were fosfomycin susceptible, respectively. Essential agreement (agar dilution versus Etest) was low (40.8%); 59.3% (131/221) of isolates with agar dilution MICs of 2 to 128 μg/ml tested 2 to 4 doubling dilutions lower by Etest. Applying CLSI breakpoints, categorical agreement was >99% for both disk diffusion and Etest; no major errors (MEs) or very major errors (VMEs) were identified, and rates of minor errors (mEs) were <1%. EUCAST breakpoints yielded categorical agreements of >99% and no MEs for both disk diffusion and Etest; however, VMEs occurred at unacceptable rates of 44.4% (disk diffusion) and 33.3% (Etest). All isolates with agar dilution MICs of ≥32 μg/ml (n = 12) and a subset of isolates with MICs of ≤16 μg/ml (n = 49) were also tested using the Vitek 2 AST-N391 card and generated fosfomycin MICs 1 to ≥3 doubling dilutions lower than agar dilution for 11/12 isolates with agar dilution MICs of ≥32 μg/ml. We conclude that performing fosfomycin disk diffusion or Etest on urinary isolates of E. coli and interpreting results using CLSI breakpoints reliably identified fosfomycin-susceptible isolates regardless of differences in endpoint reading criteria. EUCAST breakpoints generated excessive rates of VMEs for our isolate collection of high fosfomycin susceptibility.
Regional Mechanical Thrombectomy Imaging Protocol in Patients Presenting with Acute Ischemic Stroke during the COVID-19 Pandemic

BACKGROUND AND PURPOSE: Chest CT is a rapid, useful additional screening tool for coronavirus disease 2019 (COVID-19) in emergent procedures. We describe the feasibility and interim outcome of implementing a modified imaging algorithm for COVID-19 risk stratification across a regional network of primary stroke centers in the work-up of acute ischemic stroke referrals for time-critical mechanical thrombectomy. MATERIALS AND METHODS: We undertook a retrospective review of 49 patients referred to the regional neuroscience unit for consideration of mechanical thrombectomy between April 14, 2020, and May 21, 2020. During this time, all referring units followed a standard imaging protocol that included a chest CT in addition to a head CT and CT angiogram to identify Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infective pulmonary changes. RESULTS: Overall, 2 patients had typical COVID-19 radiologic features and tested positive, while 7 patients had indeterminate imaging findings and tested negative. The others had normal or atypical changes and were not diagnosed with or suspected of having COVID-19. There was an overall sensitivity of 100%, specificity of 74.1%, negative predictive value of 100%, and positive predictive value of 22.2% when using chest CT to diagnose COVID-19 in comparison with the real-time reverse transcriptase–polymerase chain reaction test. The mean additional time and radiation dose incurred for the chest CT were 184 ± 65.5 seconds and 2.47 ± 1.03 mSv. Multiple cardiovascular and pulmonary incidental findings of clinical relevance were identified in our patient population. CONCLUSIONS: Chest CT provides a pragmatic, rapid additional tool for COVID-19 risk stratification among patients referred for mechanical thrombectomy. Its inclusion in a standardized regional stroke imaging protocol has enabled efficient use of hospital resources with minimal compromise or delay to the overall patient treatment schedule.
Higher TIGIT+CD226- γδ T cells in Patients with Acute Myeloid Leukemia

ABSTRACT The diverse structural and functional heterogeneity of γδ T cells is related to their distinct role in cancer immunity. The different phenotypes of γδ T cells in patients with acute myeloid leukemia (AML) is far from clear. In particular, the expression pattern of co-inhibitory and co-stimulatory receptors on γδ T cells remains unknown. In this study, we analyzed the distribution of γδ T cell subsets by expression of the immune checkpoint co-inhibitor TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) and its competing co-stimulatory receptor CD226 in AML patients of different clinical statuses (including de novo AML, AML in non-remission (NR), and AML in complete remission (CR)). Our data demonstrated an imbalanced distribution of TIGIT and CD226 on γδ T cells with a decrease in CD226+ γδ T cells and an increase in TIGIT+ γδ T cells in de novo AML patients, while TIGIT−CD226+ γδ T cells were restored in AML patients who achieved CR after chemotherapy. Moreover, the patients who had higher TIGIT+CD226− γδ T cells showed lower overall survival rate for non-M3 AML, which may be considered a novel prognostic immune biomarker. In conclusion, our study reveals for the first time that imbalance in the TIGIT/CD226 axis might be related to different clinical outcomes for AML patients. Abbreviations: AML: acute myeloid leukemia; CR: complete remission; ICs: immune checkpoints; PD-1: programmed death-1; γδ T cells: gamma delta T cells; TCR: T cell receptor; MHC: major histocompatibility complex; TIGIT: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain; NK: natural killer; PB: Peripheral blood; NR: non-remission; FAB: French-American-British; WHO: World Health Organization; HIs: healthy individuals; OS: overall survival
Divergence of rodent and primate medial frontal cortex functional connectivity

Significance The question of the whether rodent and primate medial frontal cortex (MFC) share similar functional organization, and whether the rodent medial frontal cortex is functionally analogous to the primate lateral prefrontal cortex (LPFC) is a contentious issue. Here, we probe this long-standing question by comparing whole-brain functional connectivity of the MFC in rodents, nonhuman primates (marmosets), and humans. The results demonstrated a remarkably similar intrinsic functional organization of the MFC across the three species, but clear differences between rodent and primate MFC whole-brain connectivity. Furthermore, in contrast to the common proposal that the rat MFC is functionally analogous with the primate LFC, our results demonstrate clear differences between the rodent MFC and primate LFC interareal functional connectivity. With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity “fingerprints” of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.
Embryogenic callus induction and Agrobacterium-mediated genetic transformation of 'Shine Muscat' grape.

We established a method for embryogenic callus induction and highly efficient Agrobacterium-mediated genetic transformation of a table grape cultivar 'Shine Muscat' (Vitis labruscana). Embryogenic calli were induced using flower bud filaments from a dormant cane. Agrobacterium strain LBA4404 harboring the binary plasmid pBin19-sgfp, which contains the sgfp and nptII genes, was used to infect embryogenic calli. Infected calli were selected on 1/2 MS medium containing 5% maltose and 2% agar supplemented with 15 mg l-1 kanamycin. Efficiency of transformation of regenerated plants reached nearly 100% as determined by PCR and Southern blot analyses. The developed method will open a new avenue for genome editing of 'Shine Muscat' and contribute to the advancement of grape breeding.
Potentially inappropriate prescribing in older adults with advanced chronic kidney disease

Background Older adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices. Methods Retrospective cohort study using linked administrative databases. We included patients with an eGFR ≤30 mL/min/1.73 m2 ≥66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction. Results There were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ≥1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction. Conclusions Potentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial.