Miracle-dz/UniFAR-FTUs huggingface dataset:
Theory and simulations for RNA folding in mixtures of monovalent and divalent cations

Significance RNA molecules require ions to fold. The problem of how ions of differing sizes and valences drive the folding of RNA molecules is unsolved. Here, we take a major step in its solution by creating a method, based on the theory of polyatomic liquids, to calculate the potential between divalent ions and the phosphate groups. The resulting model, accounting for inner and outer sphere coordination of Mg2+ and Ca2+ to phosphates, when used in coarse-grained molecular simulations, predicts folding free energies for a number of RNA molecules in the presence of both divalent and monovalent ions that are in excellent agreement with experiments. This work sets the stage for probing sequence and ion effects on DNA and synthetic polyelectrolytes. RNA molecules cannot fold in the absence of counterions. Experiments are typically performed in the presence of monovalent and divalent cations. How to treat the impact of a solution containing a mixture of both ion types on RNA folding has remained a challenging problem for decades. By exploiting the large concentration difference between divalent and monovalent ions used in experiments, we develop a theory based on the reference interaction site model (RISM), which allows us to treat divalent cations explicitly while keeping the implicit screening effect due to monovalent ions. Our theory captures both the inner shell and outer shell coordination of divalent cations to phosphate groups, which we demonstrate is crucial for an accurate calculation of RNA folding thermodynamics. The RISM theory for ion–phosphate interactions when combined with simulations based on a transferable coarse-grained model allows us to predict accurately the folding of several RNA molecules in a mixture containing monovalent and divalent ions. The calculated folding free energies and ion-preferential coefficients for RNA molecules (pseudoknots, a fragment of the rRNA, and the aptamer domain of the adenine riboswitch) are in excellent agreement with experiments over a wide range of monovalent and divalent ion concentrations. Because the theory is general, it can be readily used to investigate ion and sequence effects on DNA properties.
HMGB1–C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis

Significance Monocyte to macrophage differentiation is critical to inflammation and resolution of inflammation and can be regulated by high-mobility group box 1 (HMGB1) and HMGB1 plus C1q, respectively. These are 2 evolutionarily old and highly conserved molecules. While HMGB1 causes a positive-feedback loop between the proinflammatory lipid mediator leukotriene B4 (LTB4) and IRF5, an important regulator of inflammatory macrophage polarization, HMGB1 plus C1q increases production of specialized proresolving lipid mediators (SPMs) lipoxin A4, resolvin D1, and resolvin D2, which prevent IRF5 transcription. As nonresolving inflammation is a common condition, we designed an HMGB1–C1q mimetic peptide that can polarize monocytes to an antiinflammatory phenotype in vitro and in vivo. Macrophage polarization is critical to inflammation and resolution of inflammation. We previously showed that high-mobility group box 1 (HMGB1) can engage receptor for advanced glycation end product (RAGE) to direct monocytes to a proinflammatory phenotype characterized by production of type 1 IFN and proinflammatory cytokines. In contrast, HMGB1 plus C1q form a tetramolecular complex cross-linking RAGE and LAIR-1 and directing monocytes to an antiinflammatory phenotype. Lipid mediators, as well as cytokines, help establish a milieu favoring either inflammation or resolution of inflammation. This study focuses on the induction of lipid mediators by HMGB1 and HMGB1 plus C1q and their regulation of IRF5, a transcription factor critical for the induction and maintenance of proinflammatory macrophages. Here, we show that HMGB1 induces leukotriene production through a RAGE-dependent pathway, while HMGB1 plus C1q induces specialized proresolving lipid mediators lipoxin A4, resolvin D1, and resolvin D2 through a RAGE- and LAIR-1–dependent pathway. Leukotriene exposure contributes to induction of IRF5 in a positive-feedback loop. In contrast, resolvins (at 20 nM) block IRF5 induction and prevent the differentiation of inflammatory macrophages. Finally, we have generated a molecular mimic of HMGB1 plus C1q, which cross-links RAGE and LAIR-1 and polarizes monocytes to an antiinflammatory phenotype. These findings may provide a mechanism to control nonresolving inflammation in many pathologic conditions.
Tracking and Blurring the Face in a Video File

This paper shows how to detect, track and blur a face in video frame using the Viola-Jones detection algorithm for detection and KLT algorithm to tracks a set of feature points across the video frames. First, the detection locates the face, and then identifies feature points that can be reliably tracked. A blurring filter is applied after detection and tracking the face and very good results are obtained that can be useful to blurring the face; for example, when showing a painful view that includes distorted faces in wars reports or crimes.
Mucin Pools Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Supplemental Digital Content is available in the text. Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.
Experimental and Theoretical Investigations of the Constitutive Relations of Artificial Frozen Silty Clay

The strength and deformation characteristics of artificial frozen soils are quite sensitive to temperature, confining pressure, and water content. To investigate these effects, a series of triaxial compressive tests on frozen Harbin silty clay were conducted at temperatures of −5 °C, −10 °C, and −15 °C under different confining pressures and water contents. From the stress–strain curves under lower water content and confining pressure, strain–softening behavior was observed. The modified Duncan–Chang (MDC) model was employed to describe the constitutive relations of artificial frozen silty clay while considering the strain–softening effects. After introducing statistical damage (SD) theory, an SD constitutive model with the failure strain as a random variable was proposed, which is able to overcome the drawbacks of the MDC model. The predicted SD model results are found to be consistent with the experimental results.
The implication of lncRNA expression pattern and potential function of lncRNA RP4‐576H24.2 in acute myeloid leukemia

Recent studies have revealed that long noncoding RNAs (lncRNAs) may hold crucial triggers of the pathogenesis of hematological malignancies, while the studies evaluating the expression pattern of lncRNA in acute myeloid leukemia (AML) are few. Thus, this study aimed to investigate the implication of lncRNA expression pattern in AML development and progression.
Ethical, philosophical, and practical considerations in adherence to therapy in sleep medicine.

PURPOSE OF REVIEW We consider a series of linked philosophical issues created by non-adherence to therapy in sleep medicine. RECENT FINDINGS First, the difficulty of measuring rates of adherence creates an epistemic problem regarding the efficacy of prescribed treatments. Secondly, as diseases are often classified as refractory based on apparent failure of standard medicines, the validity of this classification faces a similar epistemic crisis. This in turn produces ethical issues when therapies are restricted to cases deemed refractory. It also calls into question, if the patient does not take the medicines as prescribed, what they do with them; and the prospect of potential drug diversion arises. Education of patients seems to be of limited help in addressing these issues; what may be needed is a revision of the patient-prescriber relationship to move away from blame when nonadherence occurs. We close by revisiting an ancient debate in the philosophy of action, which may shed light on what such a revised relationship would require. SUMMARY More honest and trusting patient-physician relationships, and a much more accurate sense of when nonadherence is occurring and why, may result from a better practical and philosophical understanding of the patient's decision-making.
Intra‐Annual Variability in Responses of a Canopy Forming Kelp to Cumulative Low Tide Heat Stress: Implications for Populations at the Trailing Range Edge

Anthropogenic climate change is driving the redistribution of species at a global scale. For marine species, populations at trailing edges often live very close to their upper thermal limits and, as such, poleward range contractions are one of the most pervasive effects of ongoing and predicted warming. However, the mechanics of processes driving such contractions are poorly understood. Here, we examined the response of the habitat forming kelp, Laminaria digitata, to realistic terrestrial heatwave simulations akin to those experienced by intertidal populations persisting at the trailing range edge in the northeast Atlantic (SW England). We conducted experiments in both spring and autumn to determine temporal variability in the effects of heatwaves. In spring, heatwave scenarios caused minimal stress to L. digitata but in autumn all scenarios tested resulted in tissue being nonviable by the end of each assay. The effects of heatwave scenarios were only apparent after consecutive exposures, indicating erosion of resilience over time. Monthly field surveys corroborated experimental evidence as the prevalence of bleaching (an indication of physiological stress and tissue damage) in natural populations was greatest in autumn and early winter. Overall, our data showed that L. digitata populations in SW England persist close to their upper physiological limits for emersion stress in autumn. As the intensity of extreme warming events is likely to increase with anthropogenic climate change, thermal conditions experienced during periods of emersion will soon exceed physiological thresholds and will likely induce widespread mortality and consequent changes at the population level.
Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age‐matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413–420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77–84, 2019. © 2019 Wiley Periodicals, Inc.
Pharmacological reversal of renal cysts from secretion to absorption suggests a potential therapeutic strategy for managing autosomal dominant polycystic kidney disease

Autosomal-dominant polycystic kidney disease (ADPKD) induces a secretory phenotype, resulting in multiple fluid-filled cysts. We have previously demonstrated that VX-809, a corrector of the cystic fibrosis transmembrane conductance regulator (CFTR), reduces cyst growth. Here, we show that in normal mice CFTR is located within the cells and also at the apical and basolateral membranes. However, in polycystic kidney disease (pkd1)-knockout mice, CFTR was located at the plasma membrane, consistent with its role in cAMP-dependent fluid secretion. In cystic mice, VX-809 treatment increased CFTR levels at the apical membrane and reduced its association with the endoplasmic reticulum. Surprisingly, VX-809 treatment significantly increased CFTR's co-localization with the basolateral membrane in cystic mice. Na+/H+ exchanger 3 (NHE3) is present in pkd1-knockout and normal mice and in proximal tubule-derived, cultured pkd1-knockout cells. VX-809 increased the expression, activity, and apical plasma membrane localization of NHE3. Co-localization of epithelial sodium channel (ENaC) with the plasma membrane was reduced in cysts in pkd1-knockout mice, consistent with an inability of the cysts to absorb fluid. Interestingly, in the cystic mice, VX-809 treatment increased ENaC levels at the apical plasma membrane consistent with fluid absorption. Thus, VX-809 treatment of pkd1-null mouse kidneys significantly affected CFTR, NHE3, and ENaC, altering the cyst phenotype from one poised toward fluid secretion toward one more favorable for absorption. VX-809 also altered the location of CFTR but not of NHE3 or ENaC in normal mice. Given that VX-809 administration is safe, it may have potential utility for treating patients with ADPKD.
Rare purulent pericarditis caused by carbapenem-resistant Acinetobacter baumannii

Abstract Background: Pericardial infection caused by Acinetobacter baumannii is rare, particularly that of carbapenem-resistant A baumannii (CRAB). Case presentation: We describe a rare case of purulent pericarditis due to CRAB in a 76-year-old man with acute myocardial infarction and acute kidney injury. The man was admitted to the intensive care unit for a catheter-related bloodstream infection. Pericardial effusion was detected via the bedside X-ray and ultrasound, and pericardiocentesis was performed. Cultures of the pericardial fluid, catheter tip, and blood independently revealed the presence of CRAB. These findings confirmed a diagnosis of purulent pericarditis. Conclusions: Clinicians should be reminded that CRAB infection can lead to purulent pericarditis, particularly in patients with congestive heart failure or renal insufficiency.
Imaging Retinal Ganglion Cell Death and Dysfunction in Glaucoma.

Glaucoma is a progressive degenerative optic neuropathy that results in visual field defects and eventually blindness. More than 60.5 million people in the world are affected by glaucoma and it is the leading cause of irreversible blindness in the world.1 It is characterized by death of retinal ganglion cells (RGCs) in the inner retina and loss of their axons in the optic nerve. This leads to structural thinning of the retinal nerve fiber layer (RNFL) and excavation of the optic cup that can be detected clinically by ophthalmoscopy and imaging devices such as optical coherence tomography (OCT) and laser scanning polarimetry.2 Functionally, RGC loss leads to visual field defects that often start in the periphery and gradually encroach on central vision.3 However, atrophy of the RNFL precedes visual field loss.4 Up to 40% of the RNFL can be lost before visual field defects can be detected by conventional perimetry.5 Hence, detection of RGC damage is critical for early identification and monitoring of disease and prevention of vision loss. In recent years, promising approaches of imaging RGC death and dysfunction in vivo have been developed. The detection of apoptotic retinal cells (DARC) technology can be used for in vivo quantification of RGC apoptosis and has the potential of identifying patients with glaucoma before irreversible vision loss.6 Another technique is TcapQ, a cell-penetrating probe that has been validated in animal models in vivo to detect RGC apoptosis. In addition, flavoprotein fluorescence (FPF) has been used to detect mitochondrial dysfunction in glaucoma patients, while adaptive optics can be used to visualize individual RGCs in vivo in humans. In this review, we discuss recent developments in these techniques and discuss the implications for the diagnosis and management of glaucoma.
Multiple Binding Configurations of Fis Protein Pairs on DNA: Facilitated Dissociation versus Cooperative Dissociation

As a master transcription regulator, Fis protein influences over two hundred genes of E-coli. Fis protein’s non-specific binding to DNA is widely acknowledged, and its kinetics of dissociation from DNA is strongly influenced by its surroundings: the dissociation rate increases as the concentration of Fis protein in the solution-phase increases. In this study, we use computational methods to explore the global binding energy landscape of the Fis1:Fis2:DNA ternary complex. The complex contains a binary-Fis molecular dyad whose formation relies on complex structural rearrangements. The simulations allow us to distinguish several different pathways for the dissociation of the protein from DNA with different functional outcomes, and involving different protein stoichiometries: 1. Simple exchange of proteins and 2. Cooperative unbinding of two Fis proteins to yield bare DNA. In the case of exchange, the protein on the DNA is replaced by solution-phase protein through competition for DNA binding sites. This process seen in fluorescence imaging experiments has been called facilitated dissociation. In the latter case of cooperative unbinding of pairs, two neighboring Fis proteins on DNA form a unique binary-Fis configuration via protein-protein interactions, which in turn leads to the co-dissociation of both molecules simultaneously, a process akin to the “molecular stripping” seen in the NFκB/IκB genetic broadcasting system. This simulation shows that the existence of multiple binding configurations of transcription factors can have a significant impact on the kinetics and outcome of transcription factor dissociation from DNA, with important implications for the systems biology of gene regulation by Fis.
The "Psychosocial Aspects in Hereditary Cancer" questionnaire in women attending breast cancer genetic clinics: Psychometric validation across French-, German- and Spanish-language versions.

BACKGROUND We performed a comprehensive assessment of the psychometrics of the "Psychosocial Aspects in Hereditary Cancer" (PAHC) questionnaire in French, German and Spanish. METHODS Women consecutively approached in Cancer Genetic Clinics completed the PAHC, distress and satisfaction questionnaires at pre-testing (T1) and after test result disclosure (T2). In addition to standard psychometric attributes, we assessed the PAHC ability to respond to change (i.e. improvement or deterioration from T1 to T2) in perceived difficulties and computed minimal important differences (MID) in PAHC scores as compared with self-reported needs for additional counselling. RESULTS Of 738 eligible counselees, 214 (90%) in France (Paris), 301 (92%) in Germany (Cologne) and 133 (77%) in Spain (Barcelona) completed the PAHC. A six-factor revised PAHC model yielded acceptable CFA goodness-of-fit indexes and good all scales internal consistencies. PAHC scales demonstrated expected conceptual differences with distress and satisfaction with counselling. Different levels of psychosocial difficulties were evidenced between counselees' subgroups and over time (p-values < .05). MID estimates ranged from 8 to 15 for improvement and 9 to 21 for deterioration. CONCLUSION The PAHC French, German and Spanish versions are reliable and valid for evaluating the psychosocial difficulties of women at high BC risk attending genetic clinics.
Body Composition in Patients with Atrial Fibrillation.

Background Obesity is a risk factor for cardiovascular diseases, however evidence is mainly based on body mass index (BMI) analysis. The aim of this study was to estimate body composition using bioelectrical impedance analysis (BIA) and its prognostic value in patients with atrial fibrillation (AF) during one year of follow-up. Methods Medical history, anthropometric and biochemical examinations, and BIA were performed in 120 inpatients with AF and 240 patients hospitalized due to other cardiovascular disorders. Results Compared to the control group, the patients with AF had a significantly greater body mass, BMI, excess body mass in relation to ideal body mass, larger waist circumference, higher values of BIA parameters such as fat and fat-free mass, visceral adiposity, total body water (total water content in the body), metabolic rate and age, and lower percentage of skeletal muscle mass. Higher prevalence rates of obesity and sarcopenia were observed in the patients with AF compared to the control group, and in the patients with the paroxysmal form compared to those with the permanent form of AF. In logistic regression analysis, the percentage of fat mass was associated with a higher risk of AF (odds ratio, 1.10; 95% confidence interval, 1.05-1.15; p < 0.001). Conclusions Body composition parameters were associated with the occurrence and form of AF in our study cohort. However, further studies are needed to clarify the relationships due to an imbalance in comorbidities.
Effects of Physical Damage in the Intermediate Phase on the Progression of Amyloid bFibrillization.

Understanding the mechanism responsible for the progression of amyloid deposition is important for developing methods to suppress this process in the treatment of Alzheimer's disease. The effects of physical damage during the transition phase of amyloid b fibril formation are unclear. In this study, we used high-speed atomic force microscopy to investigate the effects of damage to the intermediates of amyloid b in real time. Ph ysical damage to intermediates did not suppress, but instead promoted, fibrillization. This progression was accompanied by morphological changes from the globular oligomer to protofibril. These results suggest that the properties of the intermediates, such as structural fragility and stability, are highly related to the rate of fibrillization.