Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Dynamical Differences in the Spike Protein RBD in the SARS-CoV-2 Variants B.1.1.7 and B.1.351

The novel coronavirus (SARS-CoV-2) pandemic that started in late 2019 is responsible for hundreds of millions of cases worldwide and millions of fatalities. Though vaccines are available, the virus is mutating to form new strains among which are the variants B.1. 1.7 and B.1. 351 that demonstrate increased transmissivity and infectivity. In this study, we performed molecular dynamics simulations to explore the role of the mutations in the interaction of the virus spike protein receptor binding domain (RBD) with the host receptor ACE2. We find that the hydrogen bond networks are rearranged in the variants and also that new hydrogen bonds are established between the RBD and ACE2 as a result of mutations. We investigated three variants: the wild-type (WT), B.1. 1.7, and B.1. 351. We find that the B.1. 351 variant (also known as 501Y.V2) shows larger flexibility in the RBD loop segment involving residue K484, yet the RBD–ACE2 complex shows higher stability. Mutations that allow a more flexible interface that can result in a more stable complex may be a factor contributing to the increased infectivity of the mutated variants.
Cotargeting of miR‐126‐3p and miR‐221‐3p inhibits PIK3R2 and PTEN, reducing lung cancer growth and metastasis by blocking AKT and CXCR4 signalling

Lung cancer is the leading cause of cancer‐related death worldwide. Late diagnosis and metastatic dissemination contribute to its low survival rate. Since microRNA (miRNA) deregulation triggers lung carcinogenesis, miRNAs might represent an interesting therapeutic tool for lung cancer management. We identified seven miRNAs, including miR‐126‐3p and miR‐221‐3p, that are deregulated in tumours compared with normal tissues in a series of 38 non‐small‐cell lung cancer patients. A negative correlation between these two miRNAs was associated with poor patient survival. Concomitant miR‐126‐3p replacement and miR‐221‐3p inhibition, but not modulation of either miRNA alone, reduced lung cancer cell viability by inhibiting AKT signalling. PIK3R2 and PTEN were validated as direct targets of miR‐126‐3p and miR‐221‐3p, respectively. Simultaneous miRNA modulation reduced metastatic dissemination of lung cancer cells both in vitro and in vivo through CXCR4 inhibition. Systemic delivery of a combination of miR‐126‐3p mimic and miR‐221‐3p inhibitor encapsulated in lipid nanoparticles reduced lung cancer patient‐derived xenograft growth through blockade of the PIK3R2–AKT pathway. Our findings reveal that cotargeting miR‐126‐3p and miR‐221‐3p to hamper both tumour growth and metastasis could be a new therapeutic approach for lung cancer.
Corneal Changes in Acanthamoeba Keratitis at Various Levels of Severity: An In Vivo Confocal Microscopic Study

Purpose To investigate the relationship between Acanthamoeba cysts and inflammatory cells in Acanthamoeba keratitis (AK) by in vivo confocal microscopy (IVCM). Methods A case-control study included 30 patients with AK and 20 normal controls. The severity of the AK was divided into mild, moderate, and severe. The central cornea and four standard quadrants of the peripheral cornea were imaged by IVCM. The cyst infiltration and dendritic cell (DC) density and maturity (size, length, field, and number of dendrites) were quantified. The relationship between clinical severity, cyst density, and DC alterations was characterized by Spearman correlation analysis. Results The maximum cyst density in the mild, moderate, and severe groups was 31.3 cysts/mm2 (17.2–32.8), 62.5 cysts/mm2 (59.3–103.1), and 162.5 cysts/mm2 (65.6–215.6), respectively. Compared to normal participants, a significant increase in the mean corneal DC density was detected in patients with AK (290.2 ± 97.0 vs. 25.3 ± 8.3 cells/mm2; P < 0.001). Patients with AK presented an increase in median DC size (178.3 vs. 63.6 µm2/cell, P < 0.001), median DC field (518.1 vs. 256.6 µm2/cell, P = 0.008), and median DC dendrite length (42.3 vs. 14.7 µm/cell, P < 0.001). Increased AK severity was correlated with an increase in cyst density, DC size, and dendrite length (all P < 0.05). An increase in cyst density was significantly correlated with an increase in DC density (β = 0.484, P = 0.026) and DC size (β = 0.557, P = 0.009). Conclusions Cyst density and depth of infiltration as well as maturity of the surrounding DC increased significantly with the severity of AK. Translational Relevance Quantitative analysis of cyst density and DC maturity may provide a new method of evaluating the severity of AK.
Prophylactic Antibiotics Do Not Prevent Infectious Complications of Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Cysts

Supplemental digital content is available in the text. Abstract Despite limited evidence, endoscopic societies recommend routine use of antibiotic prophylaxis for endoscopic ultrasound fine-needle aspiration of pancreatic cystic lesions. Recent studies suggest lack of benefit in this setting. Our objective is to conduct a systematic review and meta-analysis to assess the efficacy of antibiotics in prevention of infectious complications after ultrasound fine-needle aspiration of pancreatic cystic lesions. A bibliographic search of digital dissertation databases was performed from inception until March 2020. Randomized controlled trials, cohort, and case-control studies that compared prophylactic antibiotics with placebo or no therapy were included in the analysis. The primary outcome was the development of cyst infections. Secondary outcomes were incidence of fever; procedural complications such as bile leak, pancreatitis, or bleeding; and medication-related adverse events. Six studies with a total of 1683 patients were included. The overall incidence of cyst infections was 0.53%. For the primary outcome, there was no significant difference between the 2 groups (odds ratio, 0.54; 95% confidence interval, 0.16–1.82; P = 0.32). No significant difference was noted regarding other complications like fever, pancreatitis, or bile leak. In conclusion, the rate of infectious complications is very low, and antibiotic prophylaxis does not seem to confer any additional benefit in their prevention.
Characterization of submicron aerosols influenced by biomass burning at asite in the Sichuan Basin, southwestern China

Abstract. Severe air pollution in Asia is often the consequence of a combination of large anthropogenic emissions and adverse synoptic conditions. However, limited studies on aerosols have been conducted under high emission intensity and under unique geographical and meteorological conditions. In this study, an Aerodyne high-resolution time-of-flight aerosol mass spectrometry (HR-ToF-AMS) and other state-of-the-art instruments were utilized at a suburban site, Ziyang, in the Sichuan Basin during December 2012 to January 2013. The chemical compositions of atmospheric submicron aerosols (PM1) were determined, the sources of organic aerosols (OA) were apportioned, and the aerosol secondary formation and aging process were explored as well. Due to high humidity and static air, PM1 maintained a relatively stable level during the whole campaign, with the mean concentration of 59.7 ± 24.1 µg m−3. OA was the most abundant component (36 %) in PM1, characterized by a relatively high oxidation state. Positive matrix factorization analysis was applied to the high-resolution organic mass spectral matrix, which deconvolved OA mass spectra into four factors: low-volatility (LV-OOA) and semivolatile oxygenated OA (SV-OOA), biomass burning (BBOA) and hydrocarbon-like OA (HOA). OOA (sum of LV-OOA and SV-OOA) dominated OA as high as 71 %. In total, secondary inorganic and organic formation contributed 76 % of PM1. Secondary inorganic species correlated well (Pearson r = 0.415–0.555, p
Targeting the T-Cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune-Modulatory Signaling Pathways

The peripheral T-cell lymphomas (PTCL) could be considered the prototypical epigenetic disease. As a disease, they are uniquely sensitive to histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors, both alone and in combination, are characterized by a host of mutations in epigenetic genes, and can develop spontaneously in genetically engineered murine models predicated on established recurring mutations in (RHOAG17V) and TET2, an epigenetic gene governing DNA methylation. Given the clinical benefit of HDAC inhibitors (HDACi) and hypomethlyation agents alone and in combination in PTCL, we sought to explore a mechanistic basis for these agents in PTCL. Herein, we reveal profound class synergy between HDAC and DNMT inhibitors in PTCL, and that the combination induces degrees of gene expression that are substantially different and more extensive than that observed for the single agents. A prominent signature of the combination relates to the transcriptional induction of cancer testis antigens and genes involved in the immune response. Interestingly, TBX21 and STAT4, master regulators of TH1 differentiation, were among the genes upregulated by the combination, suggesting the induction of a TH1-like phenotype. Moreover, suppression of genes involved in cholesterol metabolism and the matrisome were also identified. We believe that these data provide a strong rationale for clinical studies, and future combinations leveraging an immunoepigenetic platform.
Effectiveness of xenogeneic and synthetic bone-block substitute materials with/without recombinant human bone morphogenetic protein-2: A preclinical study using a rabbit calvarium model.

AIM To investigate new bone (NB) formation by using bone-block substitute materials with/without recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS Three synthetic bone-block substitute materials [biphasic calcium phosphate (BCP); nanostructured hydroxyapatite (NH); 3D-printed tricalcium phosphate/hydroxyapatite (3DP)] and one xenogeneic deproteinized bovine bone mineral (DBBM) block substitute were affixed to rabbit calvarium using osteosynthesis screws, either with rhBMP-2 (n = 12) or without rhBMP-2 (n = 16). At 2 or 12 weeks (n = 6 with rhBMP-2 and n = 8 without rhBMP-2 for each week), histologic, histomorphometric and microcomputed tomography analyses were performed. RESULTS The application of rhBMP-2 increased NB formation in all experimental groups at both weeks. DBBM resulted in a greater area of NB compared with synthetic blocks either with or without rhBMP-2 at 2 weeks (2.8 ± 0.9 vs. 1.4 ± 0.5-1.9 ± 1.4 mm2 ; 1.4 ± 1.0 vs. 0.6 ± 0.3-0.9 ± 0.5 mm2 ) and without rhBMP-2 at 12 weeks (3.0 ± 0.8 vs. 1.7 ± 0.7-2.6 ± 1.5 mm2 ) (p > 0.05). NB formation did not differ significantly for DBBM and the three types of synthetic block with rhBMP-2 at 12 weeks (4.5 ± 2.0 vs. 3.8 ± 0.7-5.1 ± 1.1 mm2 ; p > 0.05). CONCLUSIONS rhBMP-2 enhanced NB in all blocks. DBBM blocks yielded more NB than synthetic blocks without rhBMP-2. The application of rhBMP-2 appears to compensate for differences in late healing.
Importance of Low-Fidelity Training on Personal Protective Equipment Use for Perioperative Workforce During COVID-19: Continuing Professional Development Imagination in Action

In March 2020, the World Health Organization (WHO) declared a global pandemic because of the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Worldwide, the highly contagious nature of SARS-CoV-2 became an imminent safety concern for all health care workers (HCWs) involved in the care of a patient with coronavirus disease of 2019 (COVID-19). When ongoing transmission of SARS-CoV-2 was apparent in the United States, our perioperative staff expressed a significant amount of apprehension regarding patient safety measures surrounding the care of these patients. The perioperative health care workers at our large, quaternary care center were appropriately concerned about their ability to properly use PPE with the associated risk of becoming contaminated with SARS-CoV-2. For staff in the operating room, exposure to aerosolizing generating procedures (AGPs) places them at a higher risk for SARS-CoV-2 transmission in comparison with other HCWs, with an associated odds ratio (OR) as high as 6.2. Intubation, airway suctioning, cardiopulmonary resuscitation, and extubation are routine AGPs in the perioperative environment that situates numerous personnel in proximity to the infected individual. In severe COVID-19 cases, the viral load may be 60 times greater than mild cases, which further emphasizes the need for the proper use of personal protective equipment (PPE) for all HCWs near an AGP. As such, public health experts from the Centers for Disease Control and Prevention and WHO have published PPE guidelines for droplet and airborne precautions. Standard PPE includes the use of a National Institute for Occupational Safety and Healthcertified N95 face mask, eye protection (goggles or face shield), disposable gowns, and gloves. As a pediatric hospital with a strong academic affiliation, our institution was equipped to address the previously described concerns of HCWs and AGPs. In response, our Pediatric Anesthesiology Simulation team was tasked with creating a continuing professional development (CPD) program to rapidly teach perioperative HCWs unfamiliar safety considerations, PPE donning/doffing procedures, and newly created workflows associated with the care of a COVID-19–positive patient. This education had to both be developed and delivered in a compressed time frame along with avoidance of using actual PPE products during educational training to preserve the scarce supply of PPE. It was apparent that training more than 780 perioperative staff members would quickly consume the limited PPE supply; therefore, modifications would be required to accomplish this training.
Effect of depression awareness and management training on the attitudes of rural primary health care workers.

OBJECTIVE To measure the effect of depression awareness and management training on the attitudes of rural primary health care workers. DESIGN A repeated measures design in which participants acted as their own controls. SETTING The training program occurred in 6 locations across rural South Australia. PARTICIPANTS The study enrolled primary care workers in general practitioner surgeries, Aboriginal Community Controlled Health Organisations, community health centres, public hospitals, regional health services and non-government organisations. INTERVENTION A six-session training workshop that was informed by the National Institute for Health and Care Excellence guidelines for the treatment and care of people with depression. MAIN OUTCOME MEASURE The 22-item Revised Depression Attitude Questionnaire comprised the main outcome measure. Participants were assessed 12 weeks before the training, again on the day of commencement of the training and after the training. RESULTS Seventy-two primary health workers completed the training program in depression awareness, building therapeutic relationships, working with ambivalence, and goal setting. Between the 2 pre-training assessments mean scores showed no significant difference. There were statistically significant improvements on the overall attitudes and the subscales therapeutic optimism and professional confidence between pre-training and post-training. CONCLUSION Training rural primary health care workers in depression may improve their attitudes to working with people living with depression.
Self-compassion and Shame Among Rape Survivors

Women are at increased risk for post-traumatic stress disorder (PTSD) and depression associated with rape, and shame plays a vital role in the development and maintenance of PTSD and depression. Thus, there is a need to identify factors that may decrease shame among female survivors of adult rape. Self-compassion may be one such factor. The present study used path analysis in MPlus version 7.3 to examine the indirect effect of self-compassion on PTSD and depression via rape-related shame. We hypothesized that higher levels of self-compassion would be associated with lower levels of rape-related shame, which in turn would be associated with lower levels of PTSD and depression. College women (N = 305) who reported experiencing rape completed anonymous online surveys assessing rape, self-compassion, rape-related shame, PTSD, and depression. Consistent with our hypothesis, results indicated that self-compassion was negatively associated with assault-related shame, which in turn was positively associated with PTSD and depression. There was also a significant indirect effect of self-compassion on PTSD and depression via rape-related shame. Further, rape-related shame fully explained the relation between self-compassion and PTSD. Findings suggest that self-compassion may be an appropriate target to reduce rape-related shame and may subsequently facilitate reductions in PTSD and depression symptoms.
Diaphragm neurostimulation during mechanical ventilation reduces atelectasis and transpulmonary plateau pressure, preserving lung homogeneity and PaO2/FiO2.

Tidal volume delivered by mechanical ventilation to a sedated patient is distributed in a non-physiological pattern, causing atelectasis (underinflation) and overdistension (overinflation). Activation of the diaphragm during mechanical ventilation provides a way to reduce atelectasis and alveolar inhomogeneity, protecting the lungs from ventilator-induced lung injury while also protecting the diaphragm by preventing ventilator-induced diaphragm dysfunction. We studied the hypothesis that diaphragm contractions elicited by transvenous phrenic nerve stimulation, delivered in synchrony with volume-control ventilation, would reduce atelectasis and lung inhomogeneity in a healthy, normal-lung pig model. Twenty-five large pigs were ventilated for 50 hours with lung-protective volume-control ventilation combined with synchronous transvenous phrenic-nerve neurostimulation on every breath, or every second breath. This was compared to lung-protective ventilation alone. Lung mechanics and ventilation pressures were measured using esophageal pressure manometry and electrical impedance tomography. Alveolar homogeneity was measured using alveolar chord length of preserved lung tissue. Lung injury was measured using inflammatory cytokine concentration in bronchoalveolar lavage fluid and serum. We found that diaphragm neurostimulation on every breath preserved PaO2/FiO2 and significantly reduced the loss of end-expiratory lung volume after 50 hours of mechanical ventilation. Neurostimulation on every breath reduced plateau and driving pressures, improved both static and dynamic compliance and resulted in less alveolar inhomogeneity. These findings support that temporary transvenous diaphragm neurostimulation during volume-controlled, lung-protective ventilation may offer a potential method to provide both lung- and diaphragm-protective ventilation.
Are isokinetic leg torques and kick velocity reliable predictors of competitive level in taekwondo athletes?

The aim of this study is to analyze how isokinetic knee and hip peak torques and roundhouse kick velocities are related to expertise level (elite vs. sub-elite) in taekwondo athletes. Seven elite and seven sub-elite athletes were tested for kick-specific variables (KSV, composed of kinematic variables and power of impact) and for concentric isokinetic peak torque (PT) at 60°/s and 240°/s. First, KSVs and PTs were compared between groups, then PTs were correlated with KSVs. Parametric variables with larger effect sizes (Cohen’s d) were entered in a stepwise linear discriminant analysis (LDA), generating an equation to estimate competitive level. Between-group differences were found in hip flexors (p = 0.04, d = 0.92) and extensors (p = 0.04, d = 0.96) with PT at 240°/s. Hip flexion PT at 60°/s and 240°/s correlated negatively with kick time (R = –0.46, p = 0.0499 and R = –0.62, p = 0.01 respectively). Hip flexion torque at 60°/s correlated positively (R = 0.52, p = 0.03) with peak linear velocity of the foot (LVF) and power of impact (R = 0.51, p = 0.03). Peak torque of hip extension at 60°/s and hip abduction at 240°/s also correlated with LVF (R = 0.56, p = 0.02 and R = 0.46, p = 0.0499). Hip extension at 60°/s correlated positively with peak linear velocity of the knee (R = 0.48, p = 0.04). The LDA showed an accuracy of 85.7% (p = 0.003) in predicting expertise level based on hip flexion and extension torques at 240°/s and on knee extension velocity during the kick. The study demonstrates that hip muscle strength is probably the dominant muscular factor for determining kick performance. Knee angular velocity combined with hip torques is the best discriminator for competitive level in taekwondo athletes.
The burden and etiology of lower respiratory tract infections in children under five years of age in Indonesia.

INTRODUCTION Lower respiratory tract infections (LRTI) are a substantial threat for children worldwide. Currently, there is a lack of knowledge about the burden and etiology of LRTI in children under five years of age in Indonesia. METHODOLOGY We have systematically searched the available English and Indonesian scientific literature to review and summarize data on LRTI and LRTI-associated invasive disease, and bacterial carriage in the upper respiratory tract in children under five years of age in Indonesia. RESULTS Overall, data on the burden and etiology of LRTI in children under five years of age in Indonesia is very limited. The data are primarily collected in Java. Data from other parts of Indonesia, including Sumatra, Kalimantan, and Sulawesi, are scarce. The case fatality rate (CFR) of LRTI in children under five years of age in Indonesia was 0.11%. Influenza was the most commonly reported viral etiological agent of LRTI in children under five years of age in Indonesia. Klebsiella pneumoniae was the most frequently reported bacterial agent of LRTI. Streptococcus pneumoniae showed the highest carriage rates. CONCLUSIONS Surveillance and diagnostic studies are urgently needed and should be conducted in different parts of Indonesia to improve insight in the burden and etiology of LRTI in Indonesia. These data are pivotal to increase the effectiveness of public health strategies, including vaccination and prevention of antimicrobial resistance.
Stochastic Stability of Markovian Neural Networks With Generally Hybrid Transition Rates

This article studies the problem of the stability for Markovian neural networks (MNNs) with time delay. The transition rate is considered to be generally hybrid, which treats those existing ones as its special cases. The introduced generally hybrid transition rates (GHTRs) make these systems more general and practical. Apropos of the GHTRs, a double-boundary approach rather than the traditional estimation method is introduced to make full use of the error information in GHTRs. In order to fully capture system information, a parameter-type-delay-dependent-matrix (PTDDM) approach is proposed, in which the PTDDM approach removes some zero components on slack matrices in previous works. Thus, the PTDDM approach can fully link the relationship among time delay and state-related vectors. Based on these ingredients, a novel stochastic stability condition is proposed for MNNs with GHTRs. A numerical example is illustrated to demonstrate the effectiveness of the proposed approaches.