Miracle-dz/UniFAR-FTUs huggingface dataset:
New insights into the interplay between long non‐coding RNAs and RNA‐binding proteins in cancer

With the development of proteomics and epigenetics, a large number of RNA‐binding proteins (RBPs) have been discovered in recent years, and the interaction between long non‐coding RNAs (lncRNAs) and RBPs has also received increasing attention. It is extremely important to conduct in‐depth research on the lncRNA‐RBP interaction network, especially in the context of its role in the occurrence and development of cancer. Increasing evidence has demonstrated that lncRNA‐RBP interactions play a vital role in cancer progression; therefore, targeting these interactions could provide new insights for cancer drug discovery. In this review, we discussed how lncRNAs can interact with RBPs to regulate their localization, modification, stability, and activity and discussed the effects of RBPs on the stability, transport, transcription, and localization of lncRNAs. Moreover, we explored the regulation and influence of these interactions on lncRNAs, RBPs, and downstream pathways that are related to cancer development, such as N6‐methyladenosine (m6A) modification of lncRNAs. In addition, we discussed how the lncRNA‐RBP interaction network regulates cancer cell phenotypes, such as proliferation, apoptosis, metastasis, drug resistance, immunity, tumor environment, and metabolism. Furthermore, we summarized the therapeutic strategies that target the lncRNA‐RBP interaction network. Although these treatments are still in the experimental stage and various theories and processes are still being studied, we believe that these strategies may provide new ideas for cancer treatment.
Active RB causes visible changes in nuclear organization

Krishnan et al. use FISH to show that specific forms of RB induce changes in the organization of euchromatin and heterochromatin domains. These changes are visible under the microscope, occur after cell cycle arrest, are separable from senescence, and represent an E2F-independent activity of RB.
Neurobiological Mechanisms of Nicotine Reward and Aversion

Neuronal nicotinic acetylcholine receptors (nAChRs) regulate the rewarding actions of nicotine contained in tobacco that establish and maintain the smoking habit. nAChRs also regulate the aversive properties of nicotine, sensitivity to which decreases tobacco use and protects against tobacco use disorder. These opposing behavioral actions of nicotine reflect nAChR expression in brain reward and aversion circuits. nAChRs containing α4 and β2 subunits are responsible for the high-affinity nicotine binding sites in the brain and are densely expressed by reward-relevant neurons, most notably dopaminergic, GABAergic, and glutamatergic neurons in the ventral tegmental area. High-affinity nAChRs can incorporate additional subunits, including β3, α6, or α5 subunits, with the resulting nAChR subtypes playing discrete and dissociable roles in the stimulatory actions of nicotine on brain dopamine transmission. nAChRs in brain dopamine circuits also participate in aversive reactions to nicotine and the negative affective state experienced during nicotine withdrawal. nAChRs containing α3 and β4 subunits are responsible for the low-affinity nicotine binding sites in the brain and are enriched in brain sites involved in aversion, including the medial habenula, interpeduncular nucleus, and nucleus of the solitary tract, brain sites in which α5 nAChR subunits are also expressed. These aversion-related brain sites regulate nicotine avoidance behaviors, and genetic variation that modifies the function of nAChRs in these sites increases vulnerability to tobacco dependence and smoking-related diseases. Here, we review the molecular, cellular, and circuit-level mechanisms through which nicotine elicits reward and aversion and the adaptations in these processes that drive the development of nicotine dependence. Significance Statement Tobacco use disorder in the form of habitual cigarette smoking or regular use of other tobacco-related products is a major cause of death and disease worldwide. This article reviews the actions of nicotine in the brain that contribute to tobacco use disorder.
Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center

The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios. ABSTRACT Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.
Development of an enzymatic method for the evaluation of protein deposition on contact lenses

Abstract The aim of this study was to evaluate a new digestion method to quantify protein deposition on contact lenses. Four silicone hydrogel and one hydrogel contact lens material were incubated in lactoferrin, lysozyme, immunoglobulin A, and bovine serum albumin solutions at approximate physiological concentrations and temperature. Immobilized trypsin was used to digest the protein deposits from the contact lens surfaces. The total protein absorbed to lenses was extracted and digested using sequencing grade trypsin. The tryptic peptides were quantified using selected reaction monitoring mass spectrometry. The concentration of surface protein deposits was either lower than or the same as the total protein for all lens types and proteins. Immobilised trypsin can digest protein deposits from the surface of contact lenses. This ability to analyse the amount of protein at a contact lens surface may help in elucidating the effect of surface deposition on clinical outcomes during lens wear.
An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables

ABSTRACT Introduction When pediatric data are not available for a drug, allometric and other methods are applied to scale drug clearance across the pediatric age-range from adult values. This is applied when designing first-in-child studies, but also for off-label drug prescription. Areas covered This review provides an overview of the systematic accuracy of allometric and other pediatric clearance scaling methods compared to gold-standard PBPK predictions. The findings are summarized in decision tables to provide a priori guidance on the selection of appropriate pediatric clearance scaling methods for both novel drugs for which no pediatric data are available and existing drugs in clinical practice. Expert opinion While allometric scaling principles are commonly used to scale pediatric clearance, there is no universal allometric exponent (i.e. 1, 0.75, or 0.67) that can accurately scale clearance for all drugs from adults to children of all ages. Therefore, pediatric scaling decision tables based on age, drug elimination route, binding plasma protein, fraction unbound, extraction ratio, and/or isoenzyme maturation are proposed to a priori select the appropriate (allometric) clearance scaling method, thereby reducing the need for full PBPK-based clearance predictions. Guidance on allometric scaling when estimating pediatric clearance values is provided as well.
Regional Distribution of Brain Injury After Cardiac Arrest

Background and Objectives Disorders of consciousness, EEG background suppression, and epileptic seizures are associated with poor outcome after cardiac arrest. Our objective was to identify the distribution of diffusion MRI–measured anoxic brain injury after cardiac arrest and to define the regional correlates of disorders of consciousness, EEG background suppression, and seizures. Methods We analyzed patients from a single-center database of unresponsive patients who underwent diffusion MRI after cardiac arrest (n = 204). We classified each patient according to recovery of consciousness (command following) before discharge, the most continuous EEG background (burst suppression vs continuous), and the presence or absence of seizures. Anoxic brain injury was measured with the apparent diffusion coefficient (ADC) signal. We identified ADC abnormalities relative to controls without cardiac arrest (n = 48) and used voxel lesion symptom mapping to identify regional associations with disorders of consciousness, EEG background suppression, and seizures. We then used a bootstrapped lasso regression procedure to identify robust, multivariate regional associations with each outcome variable. Last, using area under receiver operating characteristic curves, we then compared the classification ability of the strongest regional associations to that of brain-wide summary measures. Results Compared to controls, patients with cardiac arrest demonstrated ADC signal reduction that was most significant in the occipital lobes. Disorders of consciousness were associated with reduced ADC most prominently in the occipital lobes but also in deep structures. Regional injury more accurately classified patients with disorders of consciousness than whole-brain injury. Background suppression mapped to a similar set of brain regions, but regional injury could no better classify patients than whole-brain measures. Seizures were less common in patients with more severe anoxic injury, particularly in those with injury to the lateral temporal white matter. Discussion Anoxic brain injury was most prevalent in posterior cerebral regions, and this regional pattern of injury was a better predictor of disorders of consciousness than whole-brain injury measures. EEG background suppression lacked a specific regional association, but patients with injury to the temporal lobe were less likely to have seizures. Regional patterns of anoxic brain injury are relevant to the clinical and electrographic sequelae of cardiac arrest and may hold importance for prognosis. Classification of Evidence This study provides Class IV evidence that disorders of consciousness after cardiac arrest are associated with widely lower ADC values on diffusion MRI and are most strongly associated with reductions in occipital ADC.
CO2 laser-assisted sclerectomy surgery in the treatment of open-angle glaucoma in Chinese patients

Purpose: To evaluate the efficacy and safety of CO2-Laser Assisted Sclerectomy Surgery (CLASS) with 5-fluorouracil (5-FU) in treating open-angle glaucoma (OAG) in Chinese patients. Methods: This was a retrospective, uncontrolled, interventional case series. All patients from 2016 to 2017 who received CLASS were recruited in this study. The primary outcome was the change in intraocular pressure (IOP) and the number of IOP-lowering medications over a 12-month follow-up period. Adverse events were evaluated as secondary outcomes. Results: Data were collected from forty-two eyes of 31 patients. The average preoperative IOP was 31.33 ± 7.60mmHg. The mean percentage of IOP reduction from baseline at postoperative months (POM) 1, 3, 6, 9, and, 12 were 48.1% ± 24.6%, 51.4% ± 19.3%, 51.2% ± 17.2%, 50.9% ± 15.0%, 49.2% ± 16.3%, respectively (all P < 0.001). The number of glaucoma medications decreased from a baseline of 3.02 ± 0.81 to 0.05 ± 0.22, 0.10 ± 0.37, 0.12 ± 0.40, 0.17 ± 0.44, and 0.24 ± 0.58 at POM 1, 3, 6, 9, and 12, respectively (all P < 0.001). At POM 1, 3, 6, 9, and 12, complete success rates were 66.7%, 73.8%, 76.2%, 69.1%, and 71.4%, respectively. At POM 1, 3, 6, 9, and 12, qualified success rates were 71.4%, 82.0%, 85.3%, 83.3%, and 90.5%, respectively. Major postoperative complications include peripheral iris synechia, iris incarceration, and anterior chamber shallowing. Conclusions: CLASS with 5-FU shows safety and efficacy for decreasing IOP and the number of IOP-lowering medications over a 12-month follow-up period. It could be an alternative treatment for patients with OAG.
Beyond Good and Evil: Molecular Mechanisms of Type I and III IFN Functions

IFNs are comprised of three families of cytokines that confer protection against pathogen infection and uncontrolled cellular proliferation. The broad role IFNs play in innate and adaptive immune regulation has placed them under heavy scrutiny to position them as “friend” or “foe” across pathologies. Genetic lesions in genes involving IFN synthesis and signaling underscore the disparate outcomes of aberrant IFN signaling. Abrogation of the response leads to susceptibility to microbial infections whereas unabated IFN induction underlies a variety of inflammatory diseases and tumor immune evasion. Type I and III IFNs have overlapping roles in antiviral protection, yet the mechanisms by which they are induced and promote the expression of IFN-stimulated genes and inflammation can distinguish their biological functions. In this review, we examine the molecular factors that shape the shared and distinct roles of type I and III IFNs in immunity.
HELICAL COMPUTERIZED TOMOGRAPHY CAN MEASURE SUBCUTANEOUS, VISCERAL AND TOTAL FAT AREAS?

ABSTRACT Background: Abdominal obesity or android obesity, that is, the increase in adipose tissue in the abdominal region, is considered a risk factor for several morbidities. Different ways of quantifying it have been proposed, one method is the measurement of the abdominal fat area by computed tomography. Aim: To establish correspondence between the groups defined by degree of obesity in relation to the total, subcutaneous and visceral fat area. Methods: Cross-sectional observational study carried out through the analysis of tomographic examinations. Horos v3.3. 5 medical image visualization software was used, with abdominal tomography in a single cut including the L4 vertebral body and the umbilical scar, to obtain the areas of total, visceral and subcutaneous fat. Results: Of the 40 patients, 10 had grade II obesity, 23 grade III and 7 superobese. The amount of total fat showed an increase in relation to the degree of obesity. Visceral fat did not show significant differences between the degrees of obesity, but the data showed a lower average in the group of obesity grade II. The area of subcutaneous fat, as well as total fat, showed an increase in its measurements, according to the progression of the patients’ BMI, but there was no statistical significance in this difference between the groups of grade II and super-obese individuals. Conclusion: The area of total and subcutaneous fat showed an increase in its measurements according to the progression of the BMI groups, which did not happen with visceral fat.
Zinc finger protein 277 is an intestinal transit-amplifying cell marker and colon cancer oncogene

Sustained proliferative signaling and resisting cell death are hallmarks of cancer. Zinc finger protein 277 (ZNF277; murine Zfp277), a transcription factor regulating cellular senescence, is overexpressed in colon cancer, but its actions in intestinal homeostasis and neoplasia are unclear. Using human and murine intestine, human colon cancer cells, and ApcMin/+ mice with dysregulated β-catenin signaling and exuberant intestinal neoplasia, we explored the actions of ZNF277/Zfp277 and defined the underlying mechanisms. In normal human and murine intestine, ZNF277/Zfp277 was expressed uniquely in early stem cell progenitors, undifferentiated transit-amplifying cells (TACs). Zfp277 was overexpressed in the ApcMin/+ mouse colon, implicating ZNF277/Zfp277 as a transcriptional target of β-catenin signaling. We confirmed this by showing β-catenin knockdown reduced ZNF277 expression and, using chromatin IP, identified 2 β-catenin binding sites in the ZNF277 promoter. Zfp277 deficiency attenuated intestinal epithelial cell proliferation and tumor formation, and it strikingly prolonged ApcMin/+ mouse survival. RNA-Seq and PCR analyses revealed that Zfp277 modulates expression of genes in key cancer pathways, including β-catenin signaling, the HOXD family that regulates development, and p21WAF1, a cell cycle inhibitor and tumor suppressor. In both human colon cancer cells and the murine colon, ZNF277/Zfp277 deficiency induced p21WAF1 expression and promoted senescence. Our findings identify ZNF277/Zfp277 as both a TAC marker and colon cancer oncogene that regulates cellular proliferation and senescence, in part by repressing p21WAF1 expression.
Benefits of auditory-verbal intervention for adult cochlear implant users: perspectives of users and their coaches

Abstract Objective Post-implant rehabilitation is limited for adult cochlear implant (CI) recipients. The objective of this research was to capture the perspectives of CI users and their coaches regarding their experiences with auditory-verbal intervention as an example of post-implant rehabilitation and their views on perceived benefits and challenges related to the intervention. Design This qualitative study involved semi-structured focus group interviews with adult CI users and their coaches who accompanied them in a 24-week auditory-verbal intervention program. Study sample A total of 17 participants (eight CI users and nine coaches) contributed to the interviews. Results Three key topic areas emerged from the interviews capturing CI users’ and coaches’ experiences related to the intervention program: (1) benefits of the intervention, (2) factors affecting experiences, and (3) challenges and barriers. Benefits included increased confidence in hearing, communication, social participation, and new knowledge about technology and hearing. Factors affecting the experience were participants’ motivation and the therapist’s skills. The primary challenge was the time commitment for weekly therapy. Conclusions Both CI users and coaches perceived a focussed auditory-verbal intervention to be beneficial in improving speech understanding, confidence in using hearing, social interaction, and knowledge about technology. Participants recommended reducing the intensity of intervention to facilitate participation.
Determinants of the temperature adaptation of mRNA degradation

Abstract The rate of chemical reactions increases proportionally with temperature, but the interplay of biochemical reactions permits deviations from this relation and adaptation. The degradation of individual mRNAs in yeast increased to varying degrees with temperature. We examined how these variations are influenced by the translation and codon composition of mRNAs. We developed a method that revealed the existence of a neutral half-life above which mRNAs are stabilized by translation but below which they are destabilized. The proportion of these two mRNA subpopulations remained relatively constant under different conditions, even with slow cell growth due to nutrient limitation, but heat shock reduced the proportion of translationally stabilized mRNAs. At the same time, the degradation of these mRNAs was partially temperature-compensated through Upf1, the mediator of nonsense-mediated decay. Compensation was also promoted by some asparagine and serine codons, whereas tyrosine codons promote temperature sensitization. These codons play an important role in the degradation of mRNAs encoding key cell membrane and cell wall proteins, which promote cell integrity.
Site-Specific Traffic Load Assessment Recommendations

Traffic load is identified as one of the greatest sources of uncertainty in the assessment of bridges. In recent years, simulation techniques, using measured traffic data, have been used to predict the characteristic traffic load effects on bridges. However, the techniques are complex, sensitive to the assumptions adopted and require specialist statistical expertise. This work presents a simplified site-specific traffic load model that generates comparable load effects to the corresponding results from a full simulation. While the simplified model is still sensitive to the underlying assumptions, these can be carefully reviewed prior to the method being approved. Further, the simplified method can be employed by practicing engineers for bridge assessment.
A new method for high resolution curvature measurement applied to stress monitoring in thin films

By combining the well-known grid reflection method with a digital image correlation algorithm and a geometrical optics model, a new method is proposed for measuring the change of curvature of a smooth reflecting substrate, a common reporter of stress state of deposited layers. This tool, called Pattern Reflection for Mapping of Curvature (PReMC), can be easily implemented for the analysis of the residual stress during deposition processes and is sufficiently accurate to follow the compressive-tensile-compressive stress transition during the sputtering growth of a Ag film on a Si substrate. Unprecedented resolution below 10−5 m−1 can be reached when measuring a homogeneous curvature. A comparison with the conventional laser-based tool is also provided in terms of dynamical range and resolution. In addition, the method is capable of mapping local variations in the case of a non-uniform curvature as illustrated by the case of a Mo film of non-uniform film thickness under high compressive stress. PReMC offers interesting perspectives for in situ accurate stress monitoring in the field of thin film growth.