Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-RBM Mutations Impaired SARS-CoV-2 Spike Protein Regulated to the ACE2 Receptor Based on Molecular Dynamic Simulation

The emergence of novel coronavirus mutants is a main factor behind the deterioration of the epidemic situation. Further studies into the pathogenicity of these mutants are thus urgently needed. Binding of the spinous protein receptor binding domain (RBD) of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor was shown to initiate coronavirus entry into host cells and lead to their infection. The receptor-binding motif (RBM, 438–506) is a region that directly interacts with ACE2 receptor in the RBD and plays a crucial role in determining affinity. To unravel how mutations in the non-RBM regions impact the interaction between RBD and ACE2, we selected three non-RBM mutant systems (N354D, D364Y, and V367F) from the documented clinical cases, and the Q498A mutant system located in the RBM region served as the control. Molecular dynamics simulation was conducted on the mutant systems and the wild-type (WT) system, and verified experiments also performed. Non-RBM mutations have been shown not only to change conformation of the RBM region but also to significantly influence its hydrogen bonding and hydrophobic interactions. In particular, the D364Y and V367F systems showed a higher affinity for ACE2 owing to their electrostatic interactions and polar solvation energy changes. In addition, although the binding free energy at this point increased after the mutation of N354D, the conformation of the random coil (Pro384-Asp389) was looser than that of other systems, and the combined effect weakened the binding free energy between RBD and ACE2. Interestingly, we also found a random coil (Ala475-Gly485). This random coil is very sensitive to mutations, and both types of mutations increase the binding free energy of residues in this region. We found that the binding loop (Tyr495-Tyr505) in the RBD domain strongly binds to Lys353, an important residue of the ACE2 domain previously identified. The binding free energy of the non-RBM mutant group at the binding loop had positive and negative changes, and these changes were more obvious than that of the Q498A system. The results of this study elucidate the effect of non-RBM mutation on ACE2-RBD binding, and provide new insights for SARS-CoV-2 mutation research.
Lateralization of Motor Signs Affects Symptom Progression in Parkinson Disease

Background: Asymmetry of motor signs is a cardinal feature of Parkinson disease which may impact phenotypic expression. Objective: To investigate the relationship between lateralization of motor signs and symptom progression and severity during longitudinal observation for up to 4 years in a naturalistic study. Methods: We analyzed data prospectively collected during the NINDS Parkinson Disease Biomarker Project (PDBP). We defined the Movement Disorder Society Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part II as the primary measure of symptom progression. Left side predominant subjects were those whose lateralized motor scores on the MDS-UPDRS part III were ≥2 points higher on the left side than on the right side of the body. Multiple regression models (controlled for age, gender, education years, ethnicity, levodopa equivalent daily dose (LEDD) at baseline, and years with PD) were used to estimate the rate of symptom progression comparing left predominant (LPD) with non-left predominant (NLPD) subjects. A sensitivity analysis was performed using the same multiple regression models in the subgroups of low (0–26) or high (>27) MDS-UPDRS II score at baseline to determine if PD severity influenced the results. Results: We included 390 participants, 177 LPD and 213 NLPD. We found that MDS-UPDRS part II progression from baseline to 48 months was faster in LPD compared to NLPD (0.6 points per year faster in LPD, p = 0.05). Additionally, the LPD group was statistically significantly worse at baseline and at 48 months in several subparts of the MDS-UPDRS and the Parkinson's Disease Questionnaire-39 (PDQ-39) mobility score. Significantly slower progression (difference of −0.8, p = 0.01) and lower score at 48 months (difference of −3.8, p = 0.003) was seen for NLPD vs. LPD in the group with lower baseline MDS-UPDRS part II score. Conclusion: Left side lateralization was associated with faster symptom progression and worse outcomes in multiple clinical domains in our cohort. Clinicians should consider using motor predominance in their counseling regarding prognosis.
Unified Model for Learning Style Recommendation

Studying computer programming requires not only an understanding of theories and concepts but also coding adeptness. Success in studying or conducting such a course is definitely a challenge. This paper proposes a systematic learning style recommendation. The model is designed to evaluate students’ attributes and ongoing or formative learning outcomes for suggesting the effective style-fit strategy that facilitates learners to enhance their learning performances in terms of knowledge and skill. A two-stage association analysis was designed and conducted on a dataset collected from IT major students who enrolled in the Introduction to Computer Programming course. The first stage of association rules is to analyze and discover important relationships amongst learning styles, students’ attribute, and learning performance. The second stage of moderation analysis is then applied to probe the moderation effect of the different learning preferences on the relationship between student attributes and learning achievement. Experiments expose many insights, for example, mathematics and logical thinking are powerful assets of success in computer programming study. Association rules can effectively identify associations of learning styles and the learning performance in terms of knowledge or skills. By moderation analysis, students in the “Excellent” cluster have a broad learning style than other students. Two types of significant moderators, the universal and specific, exemplify how lecturers can flexibly post style-fit teaching strategies for a class-wide and specific group, respectively.
Structure of Long-Range Direct and Indirect Spinocerebellar Pathways as Well as Local Spinal Circuits Mediating Proprioception

Proprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways are wired. Defining the anatomy of secondary neurons in the spinal cord that integrate and relay proprioceptive and potentially cutaneous information from the periphery to the cerebellum is fundamental to understanding how proprioceptive circuits function. Here, we define the unique anatomic trajectories of long-range direct and indirect spinocerebellar pathways as well as local intersegmental spinal circuits using genetic tools in both male and female mice. We find that Clarke's column neurons, a major contributor to the direct spinocerebellar pathway, has mossy fiber terminals that diversify extensively in the cerebellar cortex with axons terminating bilaterally, but with no significant axon collaterals within the spinal cord, medulla, or cerebellar nuclei. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus and spino-olivary pathways, are in part, derived from cervical Atoh1-lineage neurons, whereas thoracolumbar Atoh1-lineage neurons project mostly locally within the spinal cord. Notably, while cervical and thoracolumbar Atoh1-lineage neurons connect locally with motor neurons, no Clarke's column to motor neuron connections were detected. Together, we define anatomic differences between long-range direct, indirect, and local proprioceptive subcircuits that likely mediate different components of proprioceptive-motor behaviors. SIGNIFICANCE STATEMENT We define the anatomy of long-range direct and indirect spinocerebellar pathways as well as local spinal proprioceptive circuits. We observe that mossy fiber axon terminals of Clarke's column neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides, sending no significant collaterals within the spinal cord, medulla, or cerebellar nuclei. Strikingly, we find that cervical spinal cord Atoh1-lineage neurons form mainly the indirect spino-lateral reticular nucleus and spino-olivary tracts and thoracolumbar Atoh1-lineage neurons project locally within the spinal cord, whereas only a few Atoh1-lineage neurons form a direct spinocerebellar tract.
Brain Angiopathy and Impaired Glucose Logistics in Mice with Psychosis-related Higher Brain Dysfunction

Psychiatric disorders are considered to be associated with metabolic dysfunction; however, it is unclear whether our current high-sugar diet contributes to pathogenesis. We demonstrate that a high-sucrose diet during adolescence induces psychosis-related phenotypes, such as hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function, particularly in mice deficient for glyoxalase-1, an enzyme involved in detoxification of sucrose metabolites. Further, the high-sucrose diet induced microcapillary impairment and reduced brain glucose uptake. Aspirin protected against this angiopathy, enhanced brain glucose uptake, and prevented abnormal behavioral phenotypes. The brains of patients with schizophrenia and bipolar disorder exhibited similar angiopathy. Psychiatric disorders are associated with microvascular brain damage, possibly due to various environmental stresses including metabolic stress.
Solid-state Studies of the Crystalline/Amorphous Character in Linear Poly(ethylenimine hydrochloride) (PEI·HCl) Polymers and Their Copper Complexes

Linear poly(ethylenimine hydrochloride) (PEI·HCl) polymers with different molecular weights (22, 87, and 217 kDa) and their copper complexes (Cu–PEI) were studied with particular attention to the crystalline/amorphous character of the polymeric chains in lyophilized and crystallized samples by using 1D and 2D solid-state nuclear magnetic resonance, X-ray photoelectron spectroscopy, and X-ray diffraction techniques. Different 13C{1H} cross-polarization and magic angle spinning experiments using delayed contact time, 1H dipolar filter and 1H spin-lock filter were crucial to determine the different mobility domains in the crystallized and lyophilized samples of PEI·HCl and Cu–PEI. 13C direct polarization experiments allowed the quantification of the crystalline/amorphous segments in each sample. The lyophilization process produced an increase in the amorphous fraction, even when some ordered domains were present, whereas the coordination of copper/sulfate ions produced a significant decrease in the mobility .
Impact of treated wastewater on groundwater quality in the region of Tiznit (Morocco)

The Tiznit region has an arid to semi-arid climate. Rainfall is scarce and the reuse of wastewater for crop irrigation is common, and consequently groundwater can be contaminated by chemical and biological pollutants. A wastewater treatment plant is constructed with the aim of producing water suitable for reuse in agriculture and reducing groundwater pollution. The aim of this study is to assess the impact of factors that may influence groundwater quality, namely wastewater reuse and fertilizer use in the region. Groundwater was collected monthly over one year from five shallow wells (P1–P5) and analysed for a range of physicochemical and microbiological parameters. Concentrations frequently exceeded the WHO standards for potable water. The average concentration of nitrate was 98 mg/L. Conductivity varied from 1,930 to 2,500 μS/cm over four of the wells but was 11,703 in P3, which was close to the treatment plant. Bacteriological contamination was also found with total coliforms varying from 0 at P1 to 9,000 cfu/100 mL at P4 and fecal coliforms (FC) 0 in P1, P2, P3 and P5 but up to 250 FC/100 mL at P4. Fecal streptococci (FS) varied from 0 to 3,500 FS/100 mL at P4. These values widely exceeded the limit for bacteria in water (0 units/100 mL).
Ozone mass transfer in water treatment: hydrodynamics and mass transfer modeling of ozone bubble columns

Most of the mathematical models that are employed to model the performance of bubble columns are based on the assumption that either plug flow or complete mixing conditions prevail in the liquid phase. Although due to the liquid-phase axial dispersion, the actual flow pattern in bubble columns is usually closer to being mixed flow rather than plug flow, but still not completely mixed flow. Therefore, the back flow cell model (BFCM), that hypothesises both back flow and exchange flow to characterise the liquid-phase axial dispersion, is presented as an alternative approach to describe the hydrodynamics and mass transfer of ozone bubble columns. BFCM is easy to formulate and solve. It is an accurate and reliable design model. Transient BFCM consists of N BFCM ordinary-first-order differential equations in which N BFCM unknowns (Y j ) are to be determined. That set of equations was solved numerically as N BFCM linear algebraic equations. Steady-state BFCM consists of 3 × N BFCM non-linear algebraic equations in which 3 × N BFCM unknowns (q G,j , X j , and Y j ) are to be determined. Those non-linear algebraic equations were solved numerically using Newton–Raphson technique. Steady-state BFCM was initially tested using the pilot-scale experimental data of Zhou. BFCM provided excellent predictions of the dissolved ozone profiles under different operating conditions for both counter and co-current flow modes.
Formative assessment that bites

It is now an established fact that the learning cycle is greatly enhanced by timely and effective feedback. Formative assessment has become an indispensable vehicle to facilitate student engagement in the feedback process, even if they do not recognise they are receiving feedback. This paper, based on the winning entry to the Institution of Structural Engineers Excellence in Structural Engineering Education Award 2020, presents a review of some formative feedback events in which civil engineering students at the University of Salford participate. The cohorts studied cross six years (200+ students), and three programmes at FHEQ level 7. The study indicates that carefully designed feedback events can have a significant impact upon understanding of structural behaviour for students preparing for professional status.
Efficacy of combined naikan and morita therapies on psychological distress and posttraumatic growth in Chinese patients with advanced cancer

Supplemental Digital Content is available in the text Abstract Background: Advanced cancer (AC) patients experience serious physical and psychological problems with the disease progression. When approaching the end of life, these patients have to cope with not only the bodily illness, but also the spiritual crisis. Conventional psychological treatments reduce distress to a certain extent, but for patients with AC, especially when they face progressive illness and are approaching death, their psychological problems are complex, and no simple solutions are in sight. Therefore, we designed this study to evaluate the efficacy of the combined Naikan therapy (NT) and Morita therapy (MT) on psychological distress and posttraumatic growth in patients with AC. Method: One hundred thirty patients newly diagnosed with AC were allocated randomly into treatment (n = 65) and control (n = 65) groups. Patients in the treatment group received combined NT and MT for 7 consecutive weeks, while the control group received normal medical treatments without NT and MT. Patients were assessed before and after the therapies. The primary outcome measures include distress thermometer (DT) and posttraumatic growth, and the secondary outcome measure contains the list of distress problems. Results: At the post-treatment stage, the treatment group displayed a decreased score of psychological distress as compared to that in the control group, which accompanied by a higher post-traumatic growth total score and subscale scores in relationship to others, new possibilities, personal strength, spiritual changes, and appreciation of life. A significant decrease in fear, sleeping difficulty/insomnia, nervousness/anxiety, and loss of appetite was also observed in the treatment group. Conclusion: The results proved that the combined Naikan and Morita therapies decreased the psychological distress and improved the posttraumatic growth of the patients with AC. Trial Registration: ChiCTR1900026691.
The changes of Lp-PLA2 in patients with gestational diabetes and its clinical significance

Abstract Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and associated with adverse pregnancy outcomes. The aim of this study was to investigate the changes of lipoprotein-associated phospholipaseA2 (Lp-PLA2) level and its correlation with biochemical indexes in patients with GDM. This observational cross-sectional study was performed among 52 GDM and 48 healthy pregnant women. Automatic biochemical analyzer was employed to test the biochemical indexes, including fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The lipoprotein-associated phospholipaseA2 (Lp-PLA2) level was evaluated by enzyme-linked immunosorbent assay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. The levels of FPG, HbA1c, HOMA-IR, TG, TC and LDL-C were significantly increased while high-density lipoprotein cholesterol (HDL-C) level was significantly decreased in the GDM group when compared with those in the control group. Lp-PLA2 level in maternal blood in the GDM group was significantly higher than that in the control group (199.125 ± 23.494 vs165.825 ± 15.576 ng/mL, P < .05) and logistic regression analysis further confirmed the association of Lp-PLA2 levels with GDM. Furthermore, Lp-PLA2 positively correlated with HOMA-IR, TC, and LDL-C. Our results confirmed the association of Lp-PLA2 with GDM. This broadens our knowledge on the pathophysiology of GDM and provides insights into the development of new targets for the prevention and treatment of GDM.
Early steroid pulse therapy for children with suspected acute encephalopathy

Abstract Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels. We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy. Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier. Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition.
Changes in lipidomic profile by anti-retroviral treatment regimen

Supplemental Digital Content is available in the text Abstract High cardiovascular disease risk in people living with HIV is partly attributed to antiretroviral therapy (ART). Lipid response to ART has been extensively studied, yet, little is known how small molecule lipids respond to Integrase inhibitor-based (INSTI-based) compared to Protease inhibitor-based (PI-based) ART regimens. Ancillary study to a phase 3, randomized, open-label trial [AIDS Clinical Trial Group A5257 Study] in treatment-naive HIV-infected patients randomized in a 1:1:1 ratio to receive ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r) (both PI-based), or raltegravir with Tenofovir Disoproxil Fumarate-TDF plus emtricitabine (RAL, INSTI-based). We examined small molecule lipid response in a subcohort of 75 participants. Lipidomic assays of plasma samples collected pre- and post-ART treatment (48 weeks) were conducted using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. The effect of ART regimens was regressed on lipid species response adjusting for the baseline covariates (lipids, age, sex, race, CD4 level, BMI, and smoking). Results were validated in the Centers for AIDS Research Network of Integrated Clinical Systems study (N = 16). Out of 417 annotated lipids, glycerophospholipids (P = .007) and sphingolipids (P = .028) had a higher response to ATV/r and DRV/r compared to RAL. The lysophosphatidylcholine (LPCs(16:1),(17:1),(20:3)) and phosphophatidylcholine species (PCs(40:7),(38:4)) had an opposite response to RAL versus ATV/r in the discovery and validation cohort. The INSTI-based regimen had an opposite response of ceramide species ((d38:1), (d42:2)), PCs((35:2), (38:4)), phosphatidylethanolamines (PEs(38:4), (38:6)), and sphingomyelin(SMd38:1) species compared with the PI-based regimens. There were no differences observed between 2 PI-based regimens. We observed differences in response of small molecule lipid species by ART regimens in treatment-naive people living with HIV.