Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomechanical comparison of a C1 posterior arch clamp with C1 lateral mass screws in constructs for C1-C2 fusion

The aim of this experimental study was to assess the biomechanical performance of a novel C1 posterior arch (C1PA) clamp compared with C1 lateral mass (C1LM) screws in constructs used to treat atlantoaxial instability. These constructs had either C2 pedicle (C2P) screws or C2 translaminar (C2TL) screws. Eight fresh-frozen human cadaveric ligamentous spine specimens (C0-C3) were tested under six conditions: the intact state, the destabilized state after a simulated odontoid fracture, and when instrumented with four constructs (C1LM-C2P, C1LM-C2TL, C1PA-C2P, C1PA-C2TL). Each specimen was tested in a spinal loading simulator that separately applied axial rotation, flexion-extension and lateral bending. In each test condition, displacement controlled angular motion was applied in both directions at a speed of 2 deg/s until a resulting moment of 1.5 Nm was achieved. The measured ranges of motion (ROM) of the C1-C2 segments were compared for each test condition using nonparametric Friedman tests. The destabilized state had significantly more C1-C2 motion (p < 0.05) than the intact state in all cases, and all constructs greatly reduced this motion. C2 pedicle screw constructs that used the C1PA clamp had significantly less C1-C2 motion (p < 0.05) than those with C1LM screws in flexion-extension as well as axial rotation and no statistically significant difference was detected in lateral bending. C2 translaminar screw constructs that used the C1PA clamp had significantly less C1-C2 motion (p < 0.05) than those with C1LM screws in flexion-extension and no statistically significant difference was detected in axial rotation or in lateral bending. Data from the current study suggested that constructs using the novel C1PA clamp would provide as good, or improved, biomechanical stability to the C1-C2 segment compared with constructs using C1LM screws.
Human Cytomegalovirus and Risk of Incident Cardiovascular Disease in United Kingdom Biobank

Abstract Background Previous studies have yielded conflicting results on the association between human cytomegalovirus (HCMV) and cardiovascular disease (CVD). This study examined associations between HCMV and incident CVD, ischaemic heart disease (IHD) and stroke. Methods This study included 8531 women and men of predominantly white ethnic background, aged 40–69 without prevalent CVD from the population-based UK Biobank study, recruited between 2006–2010 with HCMV antibody levels measured. CVD was ascertained via linkage to health administrative records collected until 2020. Multivariate Cox proportional-hazards models were used to determine associations between HCMV seropositivity and incident CVD, IHD and stroke. HCMV seropositive antibody levels in tertiles were used to assess dose-response associations. Results Over a mean follow-up period of 10.2 years, HCMV seropositivity was not significantly associated with CVD (Cases = 626, Hazard Ratio [HR] =1.01, 95% confidence interval [CI], .86–1.20), IHD (Cases = 539, HR=1.03, 95% CI, .87–1.24) or stroke (Cases = 144, HR = 0.96, 95% CI, .68–1.36). There was no evidence of dose-response associations with any outcome. Conclusions We found no significant association between HCMV seropositivity and risk of CVD, IHD or stroke. Further research within understudied populations, such as those of non-white ethnicity, and CVD subtypes is warranted.
Identification of potential phytochemicals from Citrus Limon against main protease of SARS-CoV-2: molecular docking, molecular dynamic simulations and quantum computations

Abstract The outbreak of coronavirus disease (COVID-19) caused by a novel RNA virus emerged at the end of 2019. Most of the patient’s symptoms are mild to moderate, and influenza, acute respiratory distress syndrome (ARDS) and multi-organ failure are common. The disease is mild to moderate in most patients and is reported in many cases such as pneumonia, ARDS and multi-organ dysfunction. This study’s objective is to evaluate 25 natural compounds from Citrus limon (CL) used by comprehensive molecular docking, density functional theory (DFT) and molecular dynamics analysis against SARS-CoV-2 main protease (Mpro). Among all the experimental compounds, diosmetin has shown the best docking values against the Mpro of SARS-CoV-2 compared to the standard antiviral drug. In DFT calculations, the order associated with biochemical reactivity is as follows: eriodictoyl > quercetin > spinacetin > diosmetin > luteolin > apigenin, whereas the regions of oxygen and hydrogen atoms from the selected isolated compounds are appropriate for electrophilic and nucleophilic attacks, respectively. Also, HOMO-LUMO and global descriptors values indicated a promising result of these compounds. Moreover, a molecular dynamics simulation study revealed the stable conformation and binding pattern in a stimulating environment of natural compounds CL. Considering molecular docking, simulation, and DFT analysis of the selected compounds, notably eriodictoyl, quercetin, and diosmetin showed good potential against SARS-CoV-2 Mpro. Our in silico study revealed promising antiviral activity, which may be considered a potential key factor or a therapeutic target for COVID-19. Communicated by Ramaswamy H. Sarma
Skeletal adverse events in childhood cancer survivors: An Adult Life after Childhood Cancer in Scandinavia cohort study

The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population‐based cohort of childhood cancer survivors. A cohort of 26 334 1‐year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127 531 age‐ and sex‐matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first‐time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared to the expected numbers derived from the comparison cohort. In total, 1987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% confidence interval, 1.29‐1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0‐44.5), osteoporosis, RR 4.53 (3.28‐6.27), fractures, RR 1.27 (1.20‐1.34), osteochondropathies, RR 1.57 (1.28‐1.92) and osteoarthrosis, RR 1.48 (1.28‐1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high‐risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors.
Fluoroquinolone and no risk of Achilles-tendinopathy in childhood pneumonia under eight years of age—a nationwide retrospective cohort

Background The emergence of macrolide-resistant Mycoplasma pneumoniae pneumonia (MRMP) has made its treatment challenging. A few guidelines have recommended fluoroquinolones (FQs) as second-line drugs of choice for treating MRMP in children under the age of eight, but concerns about potential adverse events (i.e., Achilles tendinopathy; AT) have been raised. The aim of this study was to investigate the relationship between the use of FQs and the risk of AT in pneumonia in children under eight years of age. Methods Children hospitalized with pneumonia (total of 2,213,807 episodes) from 2002 to 2017 were enrolled utilizing the Korean National Health Insurance Sharing Service (NHISS) database. The independent risk of FQs for AT was analyzed by a generalized estimating equation with adjustment for age, sex, and underlying diseases. Results Among 2,213,807 episodes of pneumonia hospitalization, children in a total of 6,229 episodes (0.28%) were treated with FQs (levofloxacin 40.9%, ciprofloxacin 36.1%, moxifloxacin 11.6%, and others 11.4%). The FQ-exposure group showed a 0.19% (12/6,229) incidence of AT within 30 days after the first administration of FQ. The use of FQs increased the risk of AT (OR 3.00; 95% CI: 1.71–5.29), but became null after adjusting for age, sex, and underlying diseases (aOR 0.85; 95% CI: 0.48–1.51). All AT related to the use of FQs occurred after the use of ciprofloxacin or levofloxacin, and not in children under eight years of age. Conclusions AT was a rare adverse event of FQ use for childhood pneumonia, particularly under eight years of age. Clinicians could consider using FQs as a second-line option in the treatment of childhood pneumonia when there are no alternative therapeutic options.
The role of early visual experience in the development of spatial‐frequency preference in the primary visual cortex

The mature functioning of the primary visual cortex depends on postnatal visual experience, while the orientation/direction preference is established just after eye‐opening, independently of visual experience. In this study, we find that visual experience is required for the normal development of spatial‐frequency (SF) preference in mouse primary visual cortex. We show that age‐ and experience‐dependent shifts in optimal SFs towards higher frequencies occurred similarly in excitatory neurons and parvalbumin‐positive interneurons. We also show that some excitatory and parvalbumin‐positive neurons preferentially responded to visual stimuli consisting of very high SFs and posterior directions, and that the preference was established at earlier developmental stages than the SF preference in the standard frequency range. These results suggest that early visual experience is required for the development of SF representation and shed light on the experience‐dependent developmental mechanisms underlying visual cortical functions.
Yawning in the history of psychiatry

Yawning is a fascinating physiological behaviour that has been poorly addressed except in old medical books. Whereas the purpose of this behaviour is still not clearly identified, the ancient authors made it a clinical symptom, especially a psychological one. After presenting some current notions about yawning, we review publications on yawning written by physicians, from antiquity to the twentieth century, and, in particular, those dealing with psychological and psychiatric aspects.
New αIIbβ3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains

Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbβ3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbβ3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbβ3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbβ3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419. 3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The β3:p.Gly540Asp substitution allowed αIIbβ3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and β3 legs interaction. The substitution alters the β3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419. 3:c.1752 + 2 T > C and NM_000212. 2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the β3 I-EGF domains might induce constitutive activation of αIIbβ3 without altering the global domain structure.
Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy

ABSTRACT Introduction Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. Methods Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan–Meier survival curves and Cox regression for drug survival. Results The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. Conclusions This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.
Emotional and Cognitive Responses to COVID-19 Information Overload under Lockdown Predict Media Attention and Risk Perceptions of COVID-19

The present study examined positive and negative effects of health communication on the fight against the COVID-19 under lockdown, during the first wave of the pandemic in Greece. An online survey (N = 1,199) examined the relationships among media trust, emotional and cognitive reactions to COVID-19 information overload, media attention, and risk perceptions regarding COVID-19. Participants’ media attention (exposure and attention combined) to information about the pandemic was positively related to their risk perceptions (perceived susceptibility and severity) about the disease. Media attention was dependent on participants’ trust in the media as valid sources of information, but also on their cognitive and emotional reactions to COVID-19 information overload. In response to this overload, they produced negative thoughts and more negative (fear and anger) than positive (protection) emotions. These distinct reactions had differential effects on media attention and risk perceptions. Fear and protection were positively related to media attention and risk perceptions, while anger and negative thinking undermined attention and perceptions. Furthermore, all reactions depended on media trust, which mediated the effect on media attention. These findings highlighted desirable and some undesirable effects of health communication in the fight against COVID-19, which can be used to improve health communication in the future.
Sutureless aortic valve replacement in multivalve procedures

Background Despite the rapid expansion of transcatheter approaches for aortic valve implantation, surgical aortic valve replacement remains the treatment of choice in patients presenting with multiple valvular heart disease. We sought to review our clinical experience with sutureless aortic valve replacement (SU-AVR) in the setting of multivalve procedures, addressing the postoperative outcomes and technical challenges. Methods Between December 2019 and December 2020, 20 consecutive high-risk patients at our institution underwent SU-AVR and concomitant mitral valve procedure for various indications. Results The mean age of the patients at operation was 72.6±9.3 years. Fifty five percent of the patients (n=11) presented with moderate to severe symptomatic aortic valve stenosis, while 35% (n=7) suffered from severe aortic regurgitation. All patients had concomitant moderate to severe mitral valve disease, including regurgitation in 95% (n=19) and stenosis in 25% (n=5). Mean logistic EuroSCORE was 34.3%±24.7%. Cardiopulmonary bypass and cross-clamp times were 101 (88.0–123) minutes and 67.5 (51.7–85.2) minutes, respectively. Optimal sutureless aortic valve prosthesis device success was achieved in 20 patients (100%). One patient (5%) required permanent pacemaker implantation. Thirty-day mortality was 10% and no strokes were detected. Conclusions SU-AVR is a safe and feasible surgical alternative to conventional procedures in patients presenting with multiple valvular heart disease. It provides excellent hemodynamic performance with low risk of paravalvular leakage and low transvalvular gradients, whilst simplifying the surgical procedure. Precise sizing and positioning of the valve prostheses is crucial to ensure optimal postoperative outcome.
Technology Recommendations to Support Person-Centered Care in Long-Term Care Homes during the COVID-19 Pandemic and Beyond

ABSTRACT The COVID-19 pandemic has exposed persistent inequities in the long-term care sector and brought strict social/physical distancing distancing and public health quarantine guidelines that inadvertently put long-term care residents at risk for social isolation and loneliness. Virtual communication and technologies have come to the forefront as the primary mode for residents to maintain connections with their loved ones and the outside world; yet, many long-term care homes do not have the technological capabilities to support modern day technologies. There is an urgent need to replace antiquated technological infrastructures to enable person-centered care and prevent potentially irreversible cognitive and psychological declines by ensuring residents are able to maintain important relationships with their family and friends. To this end, we provide five technological recommendations to support the ethos of person-centered care in residential long-term care homes during the pandemic and in a post-COVID-19 pandemic world.
Erythropoietin and derivatives: Potential beneficial effects on the brain

Erythropoietin (Epo), the main erythropoiesis‐stimulating factor widely prescribed to overcome anemia, is also known nowadays for its cytoprotective action on non‐hematopoietic tissues. In this context, Epo showed not only its ability to cross the blood‐brain barrier, but also its expression in the brain of mammals. In clinical trials, recombinant Epo treatment has been shown to stimulate neurogenesis; improve cognition; and activate antiapoptotic, antioxidant, and anti‐inflammatory signaling pathways. These mechanisms, proposed to characterize a neuroprotective property, opened new perspectives on the Epo pharmacological potencies. However, many questions arise about a possible physiological role of Epo in the central nervous system (CNS) and the factors or environmental conditions that induce its expression. Although Epo may be considered a strong candidate to be used against neuronal damage, long‐term treatments, particularly when high Epo doses are needed, may induce thromboembolic complications associated with increases in hematocrit and blood viscosity. To avoid these adverse effects, different Epo analogs without erythropoietic activity but maintaining neuroprotection ability are currently being investigated. Carbamylated erythropoietin, as well as alternative molecules like Epo fusion proteins and partial peptides of Epo, seems to match this profile. This review will focus on the discussion of experimental evidence reported in recent years linking erythropoietin and CNS function through investigations aimed at finding benefits in the treatment of neurodegenerative diseases. In addition, it will review the proposed mechanisms for novel derivatives which may clarify and, eventually, improve the neuroprotective action of Epo.
Clinical Outcomes of Selective Single-Level Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression of Multilevel Lumbar Spinal Stenosis and Risk Factors of Reoperation

Study Design: Retrospective cohort study. Objectives: To investigate the usefulness of selective single-level lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) in patients with radiological multilevel lumbar spinal stenosis (LSS) and clarify the predictive factors of reoperation. Methods: A total of 128 patients who underwent LE-ULBD of radiological multilevel LSS were retrospectively examined. Single-level decompression was selected clinically and supplemented radiologically. Clinical outcomes were assessed with the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), numeric rating scale (NRS), and Macnab criteria (mean follow-up period, 28.6 months [range, 24-63 months]). Stenosis severity was classified as grades M (moderate) and S (severe) based magnetic resonance imaging findings. Multilevel LSS was classified as SS, SM, and MM according to the number of grade S levels. Results: The follow-up rate was 74.2%. All domains of the JOABPEQ and NRS significantly improved during follow-up. The Macnab outcome classification was “excellent” or “good” in 77.9% of the patients. The reoperation rate was 10.2%. None of the patients with unilateral symptoms required reoperation. The SS type was a significant risk factor of reoperation for multilevel LSS with bilateral symptoms. Additional LE-ULBD was performed for all the reoperation with the “excellent” or “good” results of the Macnab criteria in 69% of the patients. Conclusions: Selective single-level LE-ULBD provided favorable results for multilevel LSS. However, information about the risks of reoperation for multilevel severe stenosis with bilateral symptoms should be shared between surgeons and patients.
Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma

Background To identify potential key genes predicting unfavorable prognosis in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods Gene expression profiles of GSE121248, GSE62232, and GSE55092 from the GEO database were obtained and analyzed. Differentially expressed genes (DEGs) between HBV-associated HCC tissues and adjacent normal tissues were screened by the limma package and Venn diagram software. Functional assessment of DEGs was performed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by the protein-protein interaction (PPI) network and further validated by GSE14520 clinical data. Results A total of 26 up-regulated genes and 76 down-regulated genes were identified by analyzing three databases. GO and KEGG analysis demonstrated that these genes were involved in cell division, metabolism-related biological processes, the p53 pathway, and the cell cycle, among others. PPI network suggested that 14 hub DEGs (TOP2A, HMMR, DTL, CCNB1, NEK2, PBK, RACGAP1, PRC1, CDK1, RRM2, ECT2, BUB1B, ANLN, and ASPM) were most dysregulated and had potential to distinguish between HBV-associated HCC and noncancerous tissues. Further survival analysis of hub genes demonstrated that high expression of TOP2A was significantly associated with poor clinical outcomes of HBV-associated HCC. Conclusions TOP2A might serve as a key gene for prognosis and as a therapeutic target for HBV-associated HCC.