Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Enterobacteriaceae Isolates Producing Extended-Spectrum β-Lactamases from U.S. Hospitals

The activities of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators were evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum β-lactamase (ESBL) genes detected by whole-genome sequencing analysis. Isolates were collected during 2017 in U.S. ABSTRACT The activities of ceftazidime-avibactam, ceftolozane-tazobactam, and comparators were evaluated for 733 isolates displaying resistance to broad-spectrum cephalosporins and carrying extended-spectrum β-lactamase (ESBL) genes detected by whole-genome sequencing analysis. Isolates were collected during 2017 in U.S. hospitals. The ESBL producers were 486 Escherichia coli, 190 Klebsiella pneumoniae, and 42 Enterobacter cloacae isolates and isolates from 3 other species. The most common groups of ESBL-encoding genes were blaCTX-M-15-like (n = 491 isolates) and blaCTX-M-15 alone (n = 168) or plus blaOXA-1 (n = 260), followed by blaCTX-M-14-like (n = 162), which included blaCTX-M-27 and blaCTX-M-14 (104 and 51 isolates, respectively), and blaSHV-12 and blaSHV-7 (48 and 22 isolates, respectively). ESBL producers carried other β-lactamases, including 1 E. cloacae harboring blaKPC-3. All ESBL-producing isolates were susceptible to ceftazidime-avibactam, and 90.2/83.9% (CLSI/EUCAST breakpoints) were susceptible to ceftolozane-tazobactam. Tigecycline (98.1/95.8% susceptible) and colistin (99.2%) were comparators that displayed the greatest activity against these isolates. Ceftolozane-tazobactam inhibited 91.4/83.9% of isolates carrying blaCTX-M-15-like and 97.5/95.1% of isolates carrying blaCTX-M-14-like, and its activity was more limited against the 91 isolates carrying blaSHV (66.7/61.1% susceptible). Ceftolozane-tazobactam inhibited 95.5% of the E. coli isolates but only 83.0%, 64.3%, and 80.0% of K. pneumoniae, E. cloacae, and other species harboring ESBL-encoding genes (CLSI breakpoints), respectively. Outer membrane protein sequences for ceftolozane-tazobactam-nonsusceptible isolates did not exhibit significant differences compared to those in genetically related ceftolozane-tazobactam-susceptible isolates. Ceftazidime-avibactam was more active than other agents tested, including ceftolozane-tazobactam, and the activity of this combination was stable regardless of species or ESBL gene carried.
Clinical Pearls and Advances in Molecular Researches of Epilepsy-Associated Tumors

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.
Signatures of stress: Pilot study of accentuated laminations in porcine enamel.

OBJECTIVES To examine the correspondence between histology of defective enamel and documented developmental stressors using a pig proxy; with the ultimate goal of differentiating, within enamel, stressor types including birth, weaning, surgery, and social disruption. MATERIALS AND METHODS Lower first molars were removed from five female and four male domestic pigs, thin-sectioned and examined with phase-contrast microscopy for daily and accentuated laminations. Known stressor events include birth; processing (nonanesthetized clipping of needle teeth, tail docking, and castration) within 5 days of birth; weaning in nursery; penned vaccination 2-4 days later; transfer to grower barn; additional vaccination. Timing of accentuated laminations was derived from counts of daily laminations from birth and between accentuated laminations; or, more commonly, from measurements between accentuated laminations divided by average daily lamination width. RESULTS Acknowledging our small sample, we confirm daily periodicity of laminations in pig enamel. Lamination width varies among sexes (males wider), cusps, crown decile, and enamel depth (wider toward surface). Accentuated laminations occurred at reconstructed median ages of 3.7 days after birth (cf. up to 5 days for "processing"), 19.7 days (cf. 18-25 days for weaning), 4.5 days (cf. 2-4 days for vaccination) and ~39.5 days (cf. 63 days for transfer). DISCUSSION Encouragingly, the timing of known stressors (birth, surgical processing, weaning, and vaccination) can be determined with high precision, in good thin sections, from accentuated laminations in pig enamel. Timing of transfer was poorly estimated, likely reflecting lesser severity and the occurrence of undocumented stress events in the nursery.
Subcutaneous tocilizumab: recent advances for the treatment of rheumatoid arthritis

ABSTRACT Introduction: Tocilizumab (TCZ) is a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody that is widely used to treat rheumatic arthritis (RA). When initially introduced, TCZ was administered by intravenous infusion. Since 2013, subcutaneous administration of TCZ has also been offered. Currently, we can choose the TCZ administration route according to patient preference. Areas covered: We summarize TCZ therapy and review recent advances of TCZ-SC therapy. Initially, three pre-clinical phase III randomized controlled trials – MUSASHI, SUMMACTA, and BREVACTA – demonstrated the similar effectiveness and safety between subcutaneous TCZ (TCZ-SC) and intravenous TCZ (TCZ-IV). Several real-world TCZ-SC studies further confirmed these findings. These studies also focused on the influence of body weight. Since TCZ-SC is a fixed dose therapy, the efficacy of TCZ-SC 162 mg q2w was sometimes inadequate in high body weight patients. By contrast, TCZ-SC 162 mg qw therapy achieved a higher trough serum concentration of TCZ than TCZ-IV 8 mg/kg q4w. No additional safety concerns were noted. Finally, possible differences between the IL-6 inhibitor and IL-6 receptor inhibitor are discussed. Expert opinion: There are no appreciable differences between TCZ-SC and TCZ-IV in clinical practice. Thus, TCZ-SC is an attractive option for RA patients.
DNA methylation modifications induced by hexavalent chromium

Abstract Hexavalent chromium [Cr (VI)] contributes a significant health risk and causes a number of chronic diseases and cancers. While the genotoxic and carcinogenic effects of hexavalent chromium exposure are explicit and better-characterized, the exact mechanism underlying the carcinogenic process of Cr (VI) is still a matter of debate. In recent years, studies have shown that epigenetic modifications, especially DNA methylation, may play a significant role in Cr (VI)-induced carcinogenesis. The aim of this review is to summarize our understanding regarding the effects of Cr (VI) on global and gene-specific DNA methylation.
Sugar-Binding Proteins Potently Inhibit Dendritic Cell Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Dendritic-Cell-Directed HIV-1 Transfer

ABSTRACT Both endocytic uptake and viral fusion can lead to human immunodeficiency virus type 1 (HIV-1) transfer to CD4+ lymphocytes, either through directional regurgitation (infectious transfer in trans [I-IT]) or through de novo viral production in dendritic cells (DCs) resulting in a second-phase transfer to CD4+ lymphocytes (infectious second-phase transfer [I-SPT]). We have evaluated in immature monocyte-derived DCs both pathways of transfer with regard to their susceptibilities to being blocked by potential microbicidal compounds, including cyanovirin (CNV); the plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Urtica dioica agglutinin, and Cymbidium hybrid agglutinin; and the glycan mannan. I-IT was a relatively inefficient means of viral transfer compared to I-SPT at both high and low levels of the viral inoculum. CNV was able to completely block I-IT at 15 μg/ml. All other compounds except mannan could inhibit I-IT by at least 90% when used at doses of 15 μg/ml. In contrast, efficient inhibition of I-SPT was remarkably harder to achieve, as 50% effective concentration levels for plant lectins and CNV to suppress this mode of HIV-1 transfer increased significantly. Thus, our findings indicate that I-SPT may be more elusive to targeting by antiviral drugs and stress the need for drugs affecting the pronounced inhibition of the infection of DCs by HIV-1.
Efficacy and challenges of a culturally relevant intervention to improve attitudes to aging

Objectives: Attitudes to aging have been linked with important health outcomes. It is unclear whether interventions to improve attitudes to aging are effective across cultural contexts. This study investigated the efficacy of an intervention among women of either Australian or Chinese backgrounds. Methods: Among 96 women who provided baseline measures, 86 attended a single, 90-min group session on either healthy aging or healthy diet. Measures of three domains of attitudes to aging were collected at baseline, then immediately and 8 weeks after the intervention. Results: The intervention improved attitudes in the psychological growth domain, but not the physical change or psychosocial loss domains. Cultural identification did not moderate intervention efficacy. Discussion: The findings suggest that brief, culturally inclusive interventions may be partially effective at improving attitudes to aging. Furthermore, research is needed to investigate if the intervention would be more effective when baseline attitudes to aging are less positive.
Factors related to condomless anal intercourse between men who have sex with men: results from a European bio-behavioural survey

Abstract Background Relationship status is an important factor associated with condomless anal intercourse (CAI) amongst men who have sex with men (MSM). Methods A multi-centre bio-behavioural survey with MSM was conducted in 13 European cities (n = 4901) exploring factors associated with CAI via bivariate and multivariate multilevel logistic regression analyses. Results Likelihood of CAI with casual partners was associated with being ‘out’ to a majority (AOR = 1.19;95% CI 1,1.42); knowing their HIV status (AOR = 1.86; 95% CI 1.25,2.76); using substances (1–2 AOR = 1.39; 95% CI 1.16,1.63, 2+ AOR = 1.81; 95% CI 1.35,2.42); being older (AOR = 0.98; 95% CI 0.97,0.99); successful sero-communication (AOR = 0.79; 95% CI 0.67,0.94); and, not having a recent HIV test (AOR = 0.78; 95% CI 0.66,0.92). CAI with steady partners was associated with successful sero-communication (AOR = 2.72; 95% CI 2.72,3.66); not having a recent HIV test (AOR = 1.26; 95% CI 1.09,1.46), and; being older (AOR = 0.99; 95% CI 0.98,0.99). Conclusions Understandings of partner type and/or relationship status in relation to CAI amongst MSM can potentially play an important role in the development of culturally appropriate HIV/STI prevention and risk-reduction efforts targeting at-risk MSM. Our results speak to the need to consider segmented and tailored public health and health promotion initiatives for MSM with differing CAI behaviours and relationship profiles.
Prognostic Relevance of Histomolecular Classification of Diffuse Adult High‐Grade Gliomas with Necrosis

Diffuse adult high‐grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into “anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO,” restricted to tumors showing intermingled astrocytic and oligodendroglial component, and “GBM/GBMO” based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co‐deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10−4). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co‐deleted AO, IDH1 R132H‐GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.
UMD‐predictor, a new prediction tool for nucleotide substitution pathogenicity—application to four genes: FBN1, FBN2, TGFBR1, and TGFBR2

Approximately half of gene lesions responsible for human inherited diseases are due to an amino acid substitution, showing that this mutational mechanism plays a large role in diseases. Distinguishing neutral sequence variations from those responsible for the phenotype is of major interest in human genetics. Because in vitro validation of mutations is not always possible in diagnostic settings, indirect arguments must be accumulated to define whether a missense variation is causative. To further differentiate neutral variants from pathogenic nucleotide substitutions, we developed a new tool, UMD‐Predictor®. This tool provides a combinatorial approach that associates the following data: localization within the protein, conservation, biochemical properties of the mutant and wild‐type residues, and the potential impact of the variation on mRNA. To evaluate this new tool, we compared it to the SIFT, PolyPhen, and SNAP software, the BLOSUM62 and Yu's Biochemical Matrices. All tools were evaluated using variations from well‐validated datasets extracted from four UMD–LSDB databases (UMD–FBN1, UMD–FBN2, UMD–TGFBR1, and UMD–TGFBR2) that contain all published mutations of the corresponding genes, that is, 1,945 mutations, among which 796 different substitutions corresponding to missense mutations. Our results show that the UMD‐Predictor® algorithm is the most efficient tool to predict pathogenic mutations in this context with a positive predictive value of 99.4%, a sensitivity of 95.4%, and a specificity of 92.2%. It can thus enhance the interpretation of variations in these genes, and could easily be applied to any other disease gene through the freely available UMD® generic software (http://www.umd.be). Hum Mutat 30:1–8, 2009. © 2009 Wiley‐Liss, Inc.
Intrathecal synthesis of immunoglobulin G antibodies to Taenia solium scolex antigens in neurocysticercosis

574 Neurology India | Volume 67 | Issue 2 | March‐April 2019 phase cancel each other. It is also known as the black boundary, India-ink etching, bounce point, or phase cancellation artifact. [2] The differential diagnoses of a T1-hyperintense foci include a dermoid, melanin deposits, a thrombosed berry aneurysm, calcifications, proteinaceous cysts, and a white epidermoid. [3] In their large review for intracranial lipomas, Kemmling et al., deduced that the dark fringe (India ink artifact) in the periphery of T1-weighted hyperintense lesions is characteristic of a lipoma on TOF source images and helps to avoid potential diagnostic pitfalls like diagnosing a thrombosed aneurysm. [4] Though MRI artifacts usually cause a diagnostic confusion or hinder the image quality, they may sometimes help in establishing the diagnosis, as evidenced above. India ink artifact can be used to confirm the presence of fat in a structure or a lesion and can substitute for fat-saturated T1-weighted images.
Molecular docking and spectroscopic studies on the interaction of new fifth-generation antibacterial drug ceftobiprole with calf thymus DNA

Abstract The interaction of the cefobiprole drug with calf thymus DNA (ct-DNA) at physiological pH was investigated by UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, circular dichroism spectroscopy and molecular modeling. The binding constant obtained of UV–visible was 4 × 104 L mol−1. Moreover, the results of circular dichroism (CD) and viscosity measurements displayed that the binding of the cefobiprole to ct-DNA can change the conformation of ct-DNA. Furthermore, thermodynamic parameters indicated that hydrogen bond and van der waals play main roles in the binding of cefobiprole to ct-DNA. Optimal results of docking, it can be concluded that ceftobiprole-DNA docked model is in approximate correlation with our experimental results.
Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis

Background This study explored whether antagonism of orexin receptors might be an effective mechanism for migraine prevention. Methods We conducted a randomized, double-blind, placebo-controlled, pilot trial. Patients experiencing four to 14 days with migraine during a one-month baseline period were randomized to the orexin receptor antagonist filorexant 10 mg nightly or placebo for three months. Efficacy was assessed by mean monthly migraine days (headache plus at least one associated migraine symptom) and headache days. Safety and tolerability were assessed by adverse event reports and laboratory tests. Results Of 120 patients treated with filorexant and 115 treated with placebo, 97 (81%) and 101 (88%), respectively, completed the trial. There was no statistically significant difference between treatments for change from baseline in mean monthly migraine days (filorexant = −1.7, placebo = −1.3, difference = −0.4 (95% CI: −1.3, 0.4)) or headache days (filorexant = −1.7, placebo = −1.2, difference = −0.5 (95% CI: −1.4, 0.4)). Filorexant was generally well tolerated but was associated with a higher proportion of patients who reported adverse events than placebo (47% vs 37%), particularly somnolence (13% vs 4%). Conclusions These data fail to provide evidence that antagonism of orexin receptors with filorexant, when administered at night, is effective for migraine prophylaxis.
Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery

Background: Antiepileptic drugs are routinely given after craniotomy. Though phenytoin (PHT) is still the most commonly used agent, levetiracetam (LEV) is increasingly administered for this purpose. This retrospective study compared the use of LEV and PHT as monotherapy prophylaxis following supratentorial neurosurgery. Methods: Patients receiving LEV monotherapy after supratentorial craniotomy were reviewed and compared to a control group of patients receiving PHT monotherapy. Results: One of 105 patients taking LEV and 9/210 patients taking PHT had seizures within 7 days of surgery (p = 0.17). Adverse drug reactions requiring change in therapy during hospitalization occurred in 1/105 patients taking LEV and 38/210 patients taking PHT (p < 0.001). Among patients followed for at least 12 months, 11/42 (26%) treated with LEV vs 42/117 (36%) treated with PHT developed epilepsy (p = 0.34); 64% remained on LEV, while 26% remained on PHT (p = 0.03). Conclusions: Both levetiracetam (LEV) and phenytoin (PHT) were associated with a low risk of early postoperative seizures and a moderate risk of later epilepsy. LEV was associated with significantly fewer early adverse reactions than PHT and with a higher retention rate in patients who were followed for at least 1 year and developed epilepsy.
The Optimum Class-Selective Rejection Rule

Class-selective rejection is an extension of simple rejection. That is, when an input pattern cannot be reliably assigned to one of the N classes in an N-class problem, it is assigned to a subset of classes that are most likely to issue the pattern, instead of simply being rejected. By selecting more classes, the risk of making an error can be reduced, at the price of subsequently having a larger remaining number of classes. The optimality of class-selective rejection is therefore defined as the best trade-off between error rate and average number of selected classes. Formally, the trade-off study is embedded in the framework of decision theory. The average expected loss is expressed as a linear combination of error rate and average number of classes. The minimization of the average expected loss, therefore, provides the best trade-off. The complexity of the resulting optimum rule is reduced, via a discrete convex minimization, to be linear in the number of classes. Upper-bounds on error rate and average number of classes are derived. An example is provided to illustrate various aspects of the optimum decision rule. Finally, the implications of the new decision rule are discussed.
Cat Kidney Glomeruli and Tubules Evaluated by Design‐Based Stereology

Renal function is related to its structure and three‐dimensional structural parameters correlate better with the kidney function than two‐dimensional structural parameters. Stereology is the current gold‐standard technique for the morphometrical evaluation of kidney structures. This study describes morphometric features of the kidney of the cat using design‐based stereological techniques aimed to introduce the cat as a translational model in nephrology and provide basic findings for diagnosis and treatment of kidney diseases in this species. Left kidneys of four cats were included in the present study. The kidney volume, volume fraction of cortex and medulla, glomerular volume, glomerular mean volume, glomerular number, and proximal convoluted tubule (PCT) and distal convoluted tubule (DCT) length were estimated. The kidney volume was estimated to 11.4 ± 1.3 cm3. The volume fraction of cortex and medulla was 65.6 ± 2% and 34.2 ± 2%, respectively. The total number of glomeruli was estimated to be 186 ± 11 × 103 using the physical disector/fractionator method. The mean glomerular volume was estimated to be 1.54 ± 0.06 × 106 μm3 and the glomerular volume was covering 2.13 ± 0.34% of the whole kidney. The total length of PCT and DCT was estimated to be 2.26 ± 0.48 km and 505 ± 43 m, respectively. Our data might contribute to the knowledge of kidneys in mammals and provide a comparison with available data on human and other mammals. Anat Rec, 302:1846–1854, 2019. © 2019 American Association for Anatomy