Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex Differences on Montreal Cognitive Assessment and Mini-Mental State Examination Scores and the Value of Self-Report of Memory Problems among Community Dwelling People 70 Years and above: The HUNT Study

Introduction: The aims were to examine if the total and item scores on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and self-reported memory problems differed between older women and men, and if self-reported memory problems were associated with scores on the 2 tests. Methods: We included 309 home-dwelling people aged 70 years and older, 155 women, mean age 75.6 (SD 4.1) years, and 154 men, mean age 76.0 (SD 4.6) years. They were examined with MoCA and MMSE, and they answered 2 questions: “have you experienced any memory problems” and “have you experienced significant memory problems the last 5 years? ” Results: The participants scored significantly higher on the MMSE (women 28.0 [1.8], men 28.4 [1.4]) than on MoCA (women 24.6 [3.3], men 24.3 [3.1]). Spearman’s rho was 0.36 between the tests. Women scored significantly higher than men on delayed recall of MoCA (3.0 [1.6] vs. 2.4 [1.6]), whereas men scored significantly higher on visuoconstruction (3.8 [1.2] vs. 3.5 [1.0]) and serial subtraction on MoCA (2.7 [0.6] vs. 2.5 [0.8]) and serial sevens on MMSE (4.5 [0.8] vs. 4.1 [1.1]). Multivariate linear regression analyses revealed that female sex, younger age, and higher education were associated with a higher score on MoCA, whereas age and education were associated with a higher score on MMSE. About half of the participants (no sex difference) had experienced significant memory problems the last 5 years, and they had significantly lower scores on both tests. Conclusions: The MoCA score was associated with sex, age, and education, whereas sex did not influence the MMSE score. The question “have you experienced significant memory problems the last 5 years? ” may be useful to evaluate older people’s cognition.
Parallel force assay for protein interactions

A protein’s biological function is reflected in the interactions it forms with other molecules. Proteins can be regarded as the workhorses of the cell and are involved in most tasks performed in and by the cell. Investigation of these interactions will thus contribute to decipher the complex processes of biological life. Due to the variety of biomolecules with which proteins can interact, a range of interdisciplinary methods have been developed to identify and characterize these interactions. Different physical techniques have evolved that are able to determine the forces that control protein interactions on a single-molecule level, the most prominent example being the atomic force microscope (AFM). A common drawback of these techniques is their low troughput contrasting with the excessive number of proteins and thus possible interactions. A method that allows for the parallelization of single-molecule measurements is the Molecular Force Assay (MFA). This technique determines the mechanical stability of a molecular complex by comparing it to a known reference complex and has been applied e.g. to the investigation of DNA mechanics and protein-DNA interaction. In the present thesis, the principle of the MFA is adapted and developed further to enable targeting of protein interactions with the other major classes of biomolecules besides DNA, namely RNA and other proteins. The ability of MFA to act as a screening assay for the binding of RNA ligands and the selective inhibition of the activity of protein Dicer by these ligands is demonstrated in a proof-of-principle study. The nuclease Dicer is a key element of the RNA interference pathway as it matures small regulatory RNAs by cleaving their precursor molecules into pieces. The identification of small molecule ligands for specific regulatory RNAs that are able to interfere with Dicer cleavage can pave the way for future therapies, as elevated levels of such matured functional RNAs have been related to severe diseases. In order to measure protein-protein interactions with the MFA, covalently coupled protein-DNA chimeras have to be generated. Here, the ybbR-tag/Sfp system has been identified to provide very high efficiency and variable site-specificity. Those chimeras are useful for many other applications in bionanotechnology, such as for the controlled arrangement of proteins at angstrom level by Single-Molecule Cut & Paste. With the model system of the nanobody Enhancer binding to different variants of GFP, the adaption of the MFA technique for the characterization of protein-protein interactions is established. The mechanical stability of the protein complex is hereby compared to a
Vimentin affects colorectal cancer proliferation, invasion, and migration via regulated by activator protein 1

Uncontrolled recurrence and metastasis are important reasons for the high mortality rate of malignant tumors. Vimentin is positively correlated with the degree of malignancy of cancer cells. Vimentin is also highly expressed in colorectal cancer (CRC) cells and plays a critical role in the metastasis and prognosis of CRC. However, the molecular mechanism of vimentin in the progression of CRC is incompletely understood. Therefore, the most active regions (nucleotides: 785–1085 nt) of the vimentin promoter in CRC were identified using luciferase experiments. By transcription factor sequence search and mutation analysis, the activator protein 1 (AP‐1) binding site in the region of 785–1085 nt was confirmed. The vimentin promoter activity was enhanced by overexpression of AP‐1. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that the binding site was recognized by AP‐1. By cell proliferation assay, colony‐forming assay, scratch‐wound assay, cell migration assay, and cell invasion assay, we demonstrated that the AP‐1 overexpression increased CRC cell proliferation, migration, and invasion. However, when vimentin was knocked down by vimentin small hairpin RNA in the CRC cell of AP‐1 overexpression, this trend disappeared. Animal experiments and immunohistochemistry showed that AP‐1 promoted tumor growth by regulating the vimentin gene. In summary, AP‐1 affected metastasis, invasion of CRC cells in vitro, and tumor growth in vivo by activating the vimentin promoter. This study might provide new insights into the molecular mechanisms of the development of CRC and provide potential therapeutic targets for CRC.
Optimal Management of Gastric Outlet Obstruction in Unresectable Malignancies

The aim of this article is to review the different treatment options for malignant gastric outlet obstruction (GOO) and compare their safety and efficacy. We describe the history and evolution of gastrojejunostomy (GJ), endoscopic stenting and endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) and analyze the current evidence regarding these three methods available in the literature, comparing their applicability, safety, complications and cost when used for the treatment of malignant GOO. We conclude that given the benefits of endoscopic techniques and the ability to place a stent away from the tumor, EUS-GE is a promising technique that may yield an efficacy similar to that of surgical GJ and duodenal stenting, with lower reintervention rates and fewer adverse events.
Reply

We appreciate the letter by Mortezavi et. al. describing vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID Vaccine Guidance Task Force was aware of the two studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et. al., patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo-treated patients (68.4%), a difference of 23.3%, 95% CI -36.6 to -9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of -30.2%, 95% CI -47.3 to -11.4%) compared to methotrexate monotherapy.
Deep exploration of random forest model boosts the interpretability of machine learning studies of complicated immune responses and lung burden of nanoparticles

A proposed machine learning method capable of mining feature interactions reveals the mechanisms of bio-nano interactions. The development of machine learning provides solutions for predicting the complicated immune responses and pharmacokinetics of nanoparticles (NPs) in vivo. However, highly heterogeneous data in NP studies remain challenging because of the low interpretability of machine learning. Here, we propose a tree-based random forest feature importance and feature interaction network analysis framework (TBRFA) and accurately predict the pulmonary immune responses and lung burden of NPs, with the correlation coefficient of all training sets >0.9 and half of the test sets >0.75. This framework overcomes the feature importance bias brought by small datasets through a multiway importance analysis. TBRFA also builds feature interaction networks, boosts model interpretability, and reveals hidden interactional factors (e.g., various NP properties and exposure conditions). TBRFA provides guidance for the design and application of ideal NPs and discovers the feature interaction networks that contribute to complex systems with small-size data in various fields.
What are friends for? The impact of friendship on communicative efficiency and cortisol response during collaborative problem solving among younger and older women

ABSTRACT Conversation is a skilled activity that depends on cognitive and social processes, both of which develop through adulthood. We examined the effects of age and partner familiarity on communicative efficiency and cortisol reactivity. Younger and older women interacted with familiar or unfamiliar partners in a dyadic collaborative conversation task (N = 8 in each group). Regardless of age, referential expressions among familiar and unfamiliar partners became more efficient over time, and cortisol concentrations were lower for speakers interacting with familiar partners. These findings suggest that communicative effectiveness is largely preserved with age, as is the stress-buffering effect of a familiar partner.
Anchoring and Judgment Bias: Disregarding Under Uncertainty

The current investigation examined the nature of the cognitive processes that underlie decision-making behavior. The focus of this project centered on the effects of utilizing heuristics that pertain to the availability of information stored in memory. Anchoring effects demonstrate that people will use any available information sampled from memory as a reference for making judgments of frequency. The specific aim of the experiment was to examine whether people exhibit patterns of behavior consistent with anchoring effects, revealed by corrupted subjective judgments, despite explicit notice of instruction to disregard the experimenter-supplied information (the anchor). Subjects failed to demonstrate an ability to disregard a relatively high anchor even when the instruction to do so was explicit. However, in contrast, subjects demonstrated an ability to disregard a relatively low anchor. More broadly, subjects instructed to disregard demonstrated a reduced effect of anchoring. Implications are considered within the context of the availability heuristic and the directly related effects of anchoring. The results may be interpreted within the framework of a dual-process model, two-system view that distinguishes intuition from reasoning. The present findings fit with well-supported theoretical explanations of anchoring effects, such as selective accessibility and numerical priming.
In-vitro assessment of β-tricalcium phosphate/bredigite-ciprofloxacin (CPFX) scaffolds for bone treatment applications

In the present study, β-tricalcium phosphate (β-TCP) scaffolds with various amounts of bredigite (Bre) were fabricated by the space holder method. The effect of bredigite content on the structure, mechanical properties, in vitro bioactivity, and cell viability was investigated. The structural assessment of the composite scaffolds presented interconnected pores with diameter of 300–500 μm with around 78%–82% porosity. The results indicated that the compressive strength of the scaffolds with 20% bredigite (1.91 MPa) was improved in comparison with scaffolds with 10% bredigite (0.52 MPa), due to the reduction of the average pore and grain sizes. Also, the results showed that the bioactivity and biodegradability of β-TCP/20Bre were better than that of β-TCP/10Bre. Besides, in this study, the release kinetics of ciprofloxacin (CPFX) loaded β-TCP/Bre composites as well as the ability of scaffolds to function as a sustained release drug carrier was investigated. Drug release pattern of β-TCP/bredigite-5CPFX scaffolds exhibited the rapid burst release of 43% for 3 h along with sustained release (82%) for 32 h which is favorable for bone infection treatment. Antibacterial tests revealed that the antibacterial properties of β-TCP/bredigite scaffolds are strongly related to the CPFX concentration, wherein the scaffold containing 5% CPFX showed the most significant zone of inhibition (33 ± 0.5 mm) against Staphylococcus aureus. The higher specific surface areas of nanostructure β-TCP/bredigite scaffolds containing CPFX lead to an initial rapid release followed by constant drug delivery. MTT assay showed that the cell viability of β-TCP/bredigite scaffold loading with up to 1%–3% CPFX (95 ± 2%), is greater than for scaffolds containing 5% CPFX (84 ± 2%). In Overall, it may suggested that β-TCP/bredigite containing 1%–3% CPFX possesses great cell viability and antibacterial activity and be employed as bactericidal biomaterials and bone infection treatment.
Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation

Hypertension is a leading risk factor for death and dependency after ischaemic stroke. However, administering anti-hypertensive medications post-stroke remains contentious with concerns regarding deleterious effects on cerebral blood flow and infarct expansion. This study sought to determine the effect of glyceryl trinitrate (GTN) treatment in both lissencephalic and gyrencephalic pre-clinical stroke models. Merino sheep underwent middle cerebral artery occlusion (MCAO) followed by GTN or control patch administration (0.2 mg/h). Monitoring of numerous physiologically relevant measures over 24 h showed that GTN administration was associated with decreased intracranial pressure, infarct volume, cerebral oedema and midline shift compared to vehicle treatment (p < 0.05). No significant changes in blood pressure or cerebral perfusion pressure were observed. Using optical imaging spectroscopy and laser speckle imaging, the effect of varying doses of GTN (0.69–50 µg/h) on cerebral blood flow and tissue oxygenation was examined in mice. No consistent effect was found. Additional mice undergoing MCAO followed by GTN administration (doses varying from 0–60 µg/h) also showed no improvement in infarct volume or neurological score within 24 h post-stroke. GTN administration significantly improved numerous stroke-related physiological outcomes in sheep but was ineffective in mice. This suggests that, whilst GTN administration could potentially benefit patients, further research into mechanisms of action are required.
Emotion regulation by attentional deployment moderates bilinguals’ language-dependent emotion differences

ABSTRACT Unbalanced bilinguals react differently to emotional stimuli in their first (L1) and second (L2) language. However, the size and direction of the emotion difference varies across emotions and tasks, so that its causes are controversial. Therefore, we investigated if the attentional resources bilinguals allocate to emotion processing moderate their language-dependent emotions. In two experiments, we crossed language and emotion regulation. Study 1 compared effects of distraction and concentration on bilingual emotion-word valence ratings. Study 2 induced positive emotion-focused rumination (or not) prior to a simulated, video-based online-dating activity. It measured emotional attraction to dating candidates speaking the participant’s L1 or L2 in pupillary, eye-fixation and self-report responses. The studies found reduced L2 emotions when emotion processing was distracted or when its level was low to start with. Yet, if bilinguals concentrated or had ruminated on their emotions, their self-reported and physiological emotionality was comparable or even stronger in L2, relative to L1. The findings suggest that bilinguals’ language-dependent emotions vary with differential language-processing automaticity. We propose that the observed emotion-regulation moderation generates further testable predictions about where and when language choice is relevant for bilinguals’ emotions.
Driving Performance Under Treatment of Most Frequently Prescribed Drugs for Mental Disorders: A Systematic Review of Patient Studies

Abstract Background Mobility is important for daily life functioning, with particular challenges regarding road safety under pharmacological treatment in patients with a psychiatric disease. Methods According to PRISMA guidelines, a systematic literature search on PubMed database (January 1970 to December 2020) was performed. Primary endpoints were driving performance in on-road tests, driving simulator performance, or psychomotor and visual perception functions assessed to estimate fitness to drive according to legal regulations in patient studies. Results Forty studies were identified (1533 patients, 38% female, median age 45 years), of which more than 60% were cross-sectional and open-label trials. Under steady-state medication, 31% (range 27%–42.5%) of schizophrenic or schizoaffective patients under antipsychotics and 18% (range 16%–20%) of unipolar and bipolar patients under antidepressants showed severe impairment in skills relevant for driving. Data point to an advantage of second-generation antipsychotics compared with first-generation antipsychotics as well as modern antidepressants over tricyclic antidepressants with respect to driving. Most patients significantly improved or stabilized in driving skills within 2–4 weeks of treatment with non-sedative or sedative antidepressants. Diazepam significantly worsened driving the first 3 weeks after treatment initiation, whereas medazepam (low dose), temazepam, and zolpidem did not impair driving. In long-term users of sedating antidepressants or benzodiazepines, impairments in on-road tests were not evident. Conclusion The available evidence suggests that psychopharmacologic medicines improve or at least stabilize driving performance of patients under long-term treatment when given on clinical considerations. To enhance treatment compliance, existing classification systems of medicinal drugs concerning impact on driving performance should also incorporate information about effects of long-term-treatment.
Bismuth subsalicylate incorporated in polycaprolactone-gelatin membranes by electrospinning to prevent bacterial colonization

Periodontitis is a chronic, multifactorial, inflammatory disease characterized by the progressive destruction of the periodontal tissues. Guided tissue regeneration (GTR), involving the use of barrier membranes, is one of the most successful clinical procedures for periodontal therapy. Nevertheless, rapid degradation of the membranes and membrane-related infections are considered two of the major reasons for GTR clinical failure. Recently, integration of non-antibiotic, antimicrobial materials to the membranes has emerged as a novel strategy to face the bacterial infection challenge, without increasing bacterial resistance. In this sense, bismuth subsalicylate (BSS) is a non-antibiotic, metal-based antimicrobial agent effective against different bacterial strains, that has been long safely used in medical treatments. Thus, the aim of the present work was to fabricate fibrillar, non-rapidly bioresorbable, antibacterial GTR membranes composed of polycaprolactone (PCL), gelatin (Gel), and BSS as the antibacterial agent. PCL-G-BSS membranes with three different BSS concentrations (2 wt./v%, 4 wt./v%, and 6 wt./v%) were developed by electrospinning and their morphology, composition, water wettability, mechanical properties, Bi release and degradation rate were characterized. The Cytotoxicity of the membranes was studied in vitro using human osteoblasts (hFOB) and gingival fibroblasts (HGF-1), and their antibacterial activity was tested against Aggregatibacter actinomycetemcomitans, Escherichia coli, Porphyromonas gingivalis and Staphylococcus aureus. The membranes obtained exhibited adequate mechanical properties for clinical application, and appropriate degradation rates for allowing periodontal defects regeneration. The hFOB and HGF-1 cells displayed adequate viability when in contact with the lixiviated products from the membranes, and, in general, displayed antibacterial activity against the four bacteria strains tested. Thus, the PCL-G-BSS membranes showed to be appropriate as potential barrier membranes for periodontal GTR treatments.
Virtual Reality for Sedation During Atrial Fibrillation Ablation in Clinical Practice: Observational Study

Background Connected devices are dramatically changing many aspects in health care. One such device, the virtual reality (VR) headset, has recently been shown to improve analgesia in a small sample of patients undergoing transcatheter aortic valve implantation. Objective We aimed to investigate the feasibility and effectiveness of VR in patients undergoing atrial fibrillation (AF) ablation under conscious sedation. Methods All patients who underwent an AF ablation with VR from March to May 2020 were included. Patients were compared to a consecutive cohort of patients who underwent AF ablation in the 3 months prior to the study. Primary efficacy was assessed by using a visual analog scale, summarizing the overall pain experienced during the ablation. Results The AF cryoablation procedure with VR was performed for 48 patients (mean age 63.0, SD 10.9 years; n=16, 33.3% females). No patient refused to use the device, although 14.6% (n=7) terminated the VR session prematurely. Preparation of the VR headset took on average 78 (SD 13) seconds. Compared to the control group, the mean perceived pain, assessed with the visual analog scale, was lower in the VR group (3.5 [SD 1.5] vs 4.3 [SD 1.6]; P=.004), and comfort was higher in the VR group (7.5 [SD 1.6] vs 6.8 [SD 1.7]; P=.03). On the other hand, morphine consumption was not different between the groups. Lastly, complications, as well as procedure and fluoroscopy duration, were not different between the two groups. Conclusions We found that VR was associated with a reduction in the perception of pain in patients undergoing AF ablation under conscious sedation. Our findings demonstrate that VR can be easily incorporated into the standard ablation workflow.