Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of anti-tumor necrosis factor agents on the risk of colorectal cancer in patients with ulcerative colitis: nationwide French cohort study.

BACKGROUND AND AIMS Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer. Anti-tumor necrosis factor agents (anti-TNF) aim to reduce chronic colonic inflammation and may lower the risk of colorectal cancer (CRC), but the impact of anti-TNF exposure has not yet been assessed in population-based cohort studies. The aim of this nationwide study was to assess the risk of CRC in patients with UC exposed to anti-TNF. METHODS Based on the French health insurance database, patients aged 18 years or older with a diagnosis of UC, previously exposed to or initiating immunosuppressive treatment were followed from 1 January 2009 until 31 December 2018. The risk of CRC associated with anti-TNF exposure was assessed using marginal structural Cox proportional hazard models adjusting for baseline and time-varying comorbidities including primary sclerosing cholangitis, UC disease activity, colonoscopic surveillance, and other medications. RESULTS Among 32,403 patients with UC, 15,542 (48.0%) were exposed to anti-TNF. During a median follow-up of 6.1 years (198,249 person-years), 246 incident CRC occurred (incidence rate per 1000 person-years, 1.24; 95% CI, 1.10-1.41). While the risk of CRC associated with anti-TNF exposure was not decreased in the overall group of patients with UC (HR, 0.85; 95% CI, 0.58-1.26), anti-TNF exposure was associated with a decreased risk of CRC in patients with long- standing colitis (disease duration ≥ 10 years) (HR, 0.41; 95% CI, 0.20-0.86). CONCLUSIONS In a nationwide cohort of patients with UC, anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis.
Improvement of the performance of anticancer peptides using a drug repositioning pipeline

The use of anticancer peptides (ACPs) as an alternative/complementary strategy to conventional chemotherapy treatments has been shown to decrease drug resistance and/or severe side effects. However, the efficacy of the positively‐charged ACP is inhibited by elevated levels of negatively‐charged cell‐surface components which trap the peptides and prevent their contact with the cell membrane. Consequently, this decreases ACP‐mediated membrane pore formation and cell lysis. Negatively‐charged heparan sulphate (HS) and chondroitin sulphate (CS) have been shown to inhibit the cytotoxic effect of ACPs.
Strategies to Move Entry-Level Nurse Practitioner Education to the Doctor of Nursing Practice Degree by 2025

Background The National Organization of Nurse Practitioner Faculties (NONPF) has made the commitment to move all entry-level nurse practitioner (NP) education to the Doctor of Nursing Practice (DNP) degree by 2025. Problem Although there are more than 250 DNP NP programs throughout the United States, many other NP programs have yet to transition to the doctoral level. Approach Leaders representing licensure, accreditation, certification, education, and practice organizations attended a NONPF 2017 Summit to discuss the DNP degree as entry into NP practice. Summit participants strategized on building collective strengths and addressed barriers to implementation. A solution-oriented discussion with action items has been operationalized for the last 4 years. Outcomes Four workgroups were created to address education, outcomes, capacity, and messaging related to moving all entry-level NP education to the DNP degree. Conclusion Ongoing collaborative efforts are critical to facilitate advancing all NP education programs to the DNP degree by 2025.
Effect of conventional transcranial direct current stimulation devices and electrode sizes on motor cortical excitability of the quadriceps muscle.

BACKGROUND There is a growing concern among the scientific community that the effects of transcranial direct current stimulation (tDCS) are highly variable across studies. The use of different tDCS devices and electrode sizes may contribute to this variability; however, this issue has not been verified experimentally. OBJECTIVE To evaluate the effects of tDCS device and electrode size on quadriceps motor cortical excitability. METHODS The effect of tDCS device and electrode size on quadriceps motor cortical excitability was quantified across a range of TMS intensities using a novel evoked torque approach that has been previously shown to be highly reliable. In experiment 1, anodal tDCS-induced excitability changes were measured in twenty individuals using two devices (Empi and Soterix) on two separate days. In experiment 2, anodal tDCS-induced excitability changes were measured in thirty individuals divided into three groups based on the electrode size. A novel Bayesian approach was used in addition to the classical hypothesis testing during data analyses. RESULTS There were no significant main or interaction effects, indicating that cortical excitability did not differ between different tDCS devices or electrode sizes. The lack of pre-post time effect in both experiments indicated that cortical excitability was minimally affected by anodal tDCS. Bayesian analyses indicated that the null model was more favored than the main or the interaction effects model. CONCLUSIONS Motor cortical excitability was not altered by anodal tDCS and did not differ by devices or electrode sizes used in the study. Future studies should examine if behavioral outcomes are different based on tDCS device or electrode size.
Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.
Structure of Aedes aegypti carboxypeptidase B1‐inhibitor complex uncover the disparity between mosquito and non‐mosquito insect carboxypeptidase inhibition mechanism

Metallocarboxypeptidases (MCPs) in the mosquito midgut play crucial roles in infection, as well as in mosquito dietary digestion, reproduction, and development. MCPs are also part of the digestive system of plant‐feeding insects, representing key targets for inhibitor development against mosquitoes/mosquito‐borne pathogens or as antifeedant molecules against plant‐feeding insects. Notably, some non‐mosquito insect B‐type MCPs are primarily insensitive to plant protease inhibitors (PPIs) such as the potato carboxypeptidase inhibitor (PCI; MW 4 kDa), an inhibitor explored for cancer treatment and insecticide design. Here, we report the crystal structure of Aedes aegypti carboxypeptidase‐B1 (CPBAe1)‐PCI complex and compared the binding with that of PCI‐insensitive CPBs. We show that PCI accommodation is determined by key differences in the active‐site regions of MCPs. In particular, the loop regions α6‐α7 (Leu242‐Ser250) and β8‐α8 (Pro269‐Pro280) of CPBAe1 are replaced by α‐helices in PCI‐insensitive insect Helicoverpa zea CPBHz. These α‐helices protrude into the active‐site pocket of CPBHz, restricting PCI insertion and rendering the enzyme insensitive. We further compared our structure with the only other PCI complex available, bovine CPA1‐PCI. The potency of PCI against CPBAe1 (Ki = 14.7 nM) is marginally less than that of bovine CPA1 (Ki = 5 nM). Structurally, the above loop regions that accommodate PCI binding in CPBAe1 are similar to that of bovine CPA1, although observed changes in proteases residues that interact with PCI could account for the differences in affinity. Our findings suggest that PCI sensitivity is largely dictated by structural interference, which broadens our understanding of carboxypeptidase inhibition as a mosquito population/parasite control strategy.
Night‐to‐night variability of sleep apnea detected by cyclic variation of heart rate during long‐term continuous ECG monitoring

Sleep apnea is common in patients with cardiovascular disease and is a factor that worsens prognosis. Holter 24‐h ECG screening for sleep apnea is beneficial in the care of these patients, but due to high night‐to‐night variability of sleep apnea, it can lead to misdiagnosis and misclassification of disease severity.
Neuroticism and Extraversion Are Related to Changes in Postural Stability During Anatomically-Related Cognitive Tasks

Abstract The relationship between personality and postural stability has received little attention. This study addressed whether neuroticism and extraversion correlate with changes in postural stability while performing cognitive tasks related to brain regions selectively associated with neuroticism and extraversion. Thirty-two adults stood on a foam mat in tandem stance and completed a 2-back task and a weather prediction task (WPT). As predicted, higher neuroticism was related to increased dual task sway during the 2-back task, r = 0.40, p = 0.023, and lower extraversion was related to increased dual task sway during the WPT, r = –0.43, p = 0.013, suggesting that personality is related to postural stability in healthy young adults and that personality could be considered in the prediction and treatment of individuals with balance difficulties.
Vision Evaluation Tools for Adults With Acquired Brain Injury: A Scoping Review

Background. Unrecognized visual deficits (VDs) following an acquired brain injury (ABI) may impact clients’ rehabilitation. Little is known about evaluation tools used in vision rehabilitation. Purpose. To systematically explore the literature describing evaluation tools used for VD on adults with ABI. Method. Using a scoping review methodology, we searched in MEDLINE(Ovid), Embase, CINAHL, PsycINFO, and the grey literature from inception to 2020. Quantitative and thematic analyses were performed. Findings. Of the 83 studies reporting on 86 evaluation tools, 47% used multiple tools to assess VD. Tools were mostly used by occupational therapists and psychologists to evaluate intermediate, intermediate to high, and high-level visual skills. Clinicians tend to select specific tools that focus on different levels of the hierarchy of visual skills. Implications. Future research should investigate the optimal timeframe for assessment of VD and the psychometric properties of tools to ensure comprehensive VD evaluation.
The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses

Abstract Bacteria have evolved a multitude of systems to prevent invasion by bacteriophages and other mobile genetic elements. Comparative genomics suggests that genes encoding bacterial defence mechanisms are often clustered in ‘defence islands’, providing a concerted level of protection against a wider range of attackers. However, there is a comparative paucity of information on functional interplay between multiple defence systems. Here, we have functionally characterised a defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a suite of thirty environmentally-isolated coliphages, we demonstrate multi-layered and robust phage protection provided by a plasmid-encoded defence island that expresses both a type I BREX system and the novel GmrSD-family type IV DNA modification-dependent restriction enzyme, BrxU. We present the structure of BrxU to 2.12 Å, the first structure of the GmrSD family of enzymes, and show that BrxU can utilise all common nucleotides and a wide selection of metals to cleave a range of modified DNAs. Additionally, BrxU undergoes a multi-step reaction cycle instigated by an unexpected ATP-dependent shift from an intertwined dimer to monomers. This direct evidence that bacterial defence islands can mediate complementary layers of phage protection enhances our understanding of the ever-expanding nature of phage-bacterial interactions.
Neuropsychiatric and cognitive symptoms in people with hypertension: An examination with the NINDS-CSN consensus protocol

Abstract Hypertension has been associated with risk of cognitive impairments. The American Heart Association recommended the use of the harmonized neuropsychological protocol suggested by the National Institute of Neurologic Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN) for studying related cognitive impairments. Initially designed for vascular cognitive impairment, empirical data of results from NINDS-CSN protocol has not been well-established in hypertension. The present study recruited 58 adults diagnosed with hypertension and 44 normotensive controls. Tests from the NINDS-CSN protocol were given in three lengths, including neuropsychological tests and neuropsychiatric inventories. The results showed higher proportions of hypertensive adults with impairments on tests of memory and executive functions and that they performed worse as a group on several tests from the 30-minute protocol, but not on the other additional tests in the full-length version, nor on cognitive screening test in the 5-minute protocol such as the Mini-Mental State Examination or the Montreal Cognitive Assessment. There was no significant group difference on neuropsychiatric symptoms. These findings suggested that the 30-minute version of the NINDS-CSN protocol with the two supplemental tests was able to reveal selective cognitive deficits in hypertensive adults and provide a practical solution for related studies, balancing between the requirement of sensitivity, domain variety, and brevity.
Real‐Time, In Vivo Measurement of Protein Kinase A Activity in Deep Brain Structures Using Fluorescence Lifetime Photometry (FLiP)

The biochemical state of neurons, and of cells in general, is regulated by extracellular factors, including neurotransmitters, neuromodulators, and growth hormones. Interactions of an animal with its environment trigger neuromodulator release and engage biochemical transduction cascades to modulate synapse and cell function. Although these processes are thought to enact behavioral adaption to changing environments, when and where in the brain they are induced has been mysterious because of the challenge of monitoring biochemical state in real time in defined neurons in behaving animals. Here, we describe a method allowing measurement of activity of protein kinase A (PKA), an important intracellular effector for neuromodulators, in freely moving mice. To monitor PKA activity in vivo, we use a genetically targeted sensor (FLIM‐AKAR) and fluorescence lifetime photometry (FLiP). This article describes how to set up a FLiP system and obtain robust recordings of net PKA phosphorylation state in vivo. The methods should be generally useful to monitor other pathways for which fluorescence lifetime reporters exist. © 2021 Wiley Periodicals LLC.
Functional (un-)Coupling: Impairment, Compensation, and Future Progression in Alzheimer's Disease

Background: Functional (un-)coupling (task-related change of functional connectivity) between different sites of the brain is a mechanism of general importance for cognitive processes. In Alzheimer's disease (AD), prior research identified diminished cortical connectivity as a hallmark of the disease. However, little is known about the relation between the amount of functional (un-)coupling and cognitive performance and decline in AD. Method: Cognitive performance (based on CERAD-Plus scores) and electroencephalogram (EEG)-based functional (un-)coupling measures (connectivity changes from rest to a Face-Name-Encoding task) were assessed in 135 AD patients (age: M = 73.8 years; SD = 9.0). Of these, 68 patients (M = 73.9 years; SD = 8.9) participated in a follow-up assessment of their cognitive performance 1.5 years later. Results: The amounts of functional (un-)coupling in left anterior-posterior and homotopic interhemispheric connections in beta1-band were related to cognitive performance at baseline (β = .340; p < .001; β = .274; P = .001, respectively). For both markers, a higher amount of functional coupling was associated with better cognitive performance. Both markers also were significant predictors for cognitive decline. However, while patients with greater functional coupling in left anterior-posterior connections declined less in cognitive performance (β = .329; P = .035) those with greater functional coupling in interhemispheric connections declined more (β = −.402; P = .010). Conclusion: These findings suggest an important role of functional coupling mechanisms in left anterior–posterior and interhemispheric connections in AD. Especially the complex relationship with cognitive decline in AD patients might be an interesting aspect for future studies.
Association of a Sweetened Beverage Tax With Soda Consumption in High School Students.

Importance Sweetened beverage taxes are one policy approach to reduce intake of added sugars. Soda is the leading source of added sugars in the US diet, but few studies have examined how such taxes influence sweetened beverage intake in youth. Objective To estimate the association between the Philadelphia, Pennsylvania, beverage tax and adolescent soda intake. Design, Setting, and Participants This economic evaluation of school district-level Youth Risk Behavior Surveillance System data from September 2013 to December 2019 compared weekly soda intake in high school students in Philadelphia, a city with a sweetened beverage tax, with that in 7 comparison cities without beverage taxes. Difference-in-differences regression modeling was used to estimate change in soda intake in Philadelphia compared with control cities. Secondary analyses compared 100% juice and milk intake to explore potential substitution associations. Subgroup analyses evaluated differences by race and ethnicity and weight status (obesity and overweight or obesity). Analyses were performed between August 20 and October 20, 2020. School districts that had weighted data and a survey question on weekly soda intake from 2013 to 2019 were included. The study included high school students, grades 9 to 12, in school districts participating in the Youth Risk Behavior Surveillance System from 2013 to 2019. Exposures Implementation of a sweetened beverage tax in Philadelphia, Pennsylvania, in January 2017. Main Outcomes and Measures Reported weekly servings of soda, 100% juice, and milk. Results A total of 86 928 participants (weighted mean [SD] age, 15.8 [1.3] years; 49% female) from 8 US cities (including Philadelphia) were included. Before the tax, adolescents in the 7 comparison cities had a mean intake of 4 servings of soda per week compared with 5.4 servings per week in Philadelphia. Philadelphia's tax was associated with a reduction of 0.81 servings of soda per week (95% CI, -1.48 to -0.14 servings; P = .02) 2 years after tax implementation. There was no significant difference in 100% juice or milk intake, although Philadelphia adolescents consumed more juice than those in nontaxed cities. In subgroup analyses, the tax was associated with a reduction of 1.13 servings per week in Hispanic/Latinx adolescents (95% CI, -2.04 to -0.23 servings; P = .01) and 1.2 servings per week in adolescents with obesity (95% CI, -2.33 to -0.13 servings; P = .03). Conclusions and Relevance This economic evaluation found that a sweetened beverage tax was associated with a reduction in soda intake among adolescents, providing evidence that such taxes can improve dietary behaviors.
Synthesis, biological–pharmacological evaluation and molecular docking studies of Schiff base analogues of transition metal (II) complexes of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one

Abstract Novel tridentate Schiff base [CuL2], [NiL2], [CoL2], [MnL2] and [ZnL2] complexes have been prepared with Schiff base resulting from acetophenylidene-4-iminoantipyrine and tyrosine. Microanalytical data, IR, UV–vis, 1H, 13C-NMR, powder XRD, SEM, cyclic voltammetry, ESR, and mass spectral techniques confirmed the structural features of the chelates. The general formula of the complexes [ML2] was confirmed from elemental analysis, mass and 1H-NMR spectral studies. Octahedral geometry of the chelates is confirmed by electronic absorption spectra and FT-IR spectra. The magnetic susceptibility and low conductance values reveal that the complexes are monomeric and non-electrolytic nature, respectively. Powder XRD and SEM images confirm the crystalline structure of the complexes. At 300 and 77 K, the X-band ESR spectra of [CuL2] complex in DMSO solution were recorded and their salient features have been reported. The binding of [CuL2] with CT-DNA study reveals that interactions occur through intercalation. Analgesic, anti-inflammatory and CNS activities and antimicrobial activities of Schiff base and its complexes reveal that the chelates have higher potent than free ligand. The molecular docking studies have been performed with DNA and 6COX enzyme using Hex 8.0 software which recognizes the biological activities and nature of binding of the complexes. Communicated by Ramaswamy H. Sarma
Incidence, hospitalization and mortality and their changes over time in people with a first ever diabetic foot ulcer

A diabetic foot ulcer (DFU) is a severe condition associated with morbidity and mortality. Population‐based studies are rare and limited by access to reliable data. Without this data, efforts in primary prevention cannot be evaluated. Therefore, we examined the incidence and changes over time for the first DFU in people with diabetes. We also examined hospitalization and all‐cause mortality and their changes over time.