Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of DISC1 on Alzheimer’s disease cell models assessed by iTRAQ proteomics analysis

Abstract Alzheimer’s disease (AD) is a form of neurodegenerative disease in the elderly with no cure at present. In a previous study, we found that the scaffold protein, disrupted in Schizophrenia 1 (DISC1) is down-regulated in the AD brains, and ectopic expression of DISC1 can delay the progression of AD by protecting synaptic plasticity and down-regulating BACE1. However, the underlying mechanisms remain not to be elucidated. In the present study, we compared the proteomes of normal and DISC1high AD cells expressing the amyloid precursor protein (APP) using isobaric tag for relative and absolute quantitation (iTRAQ) and mass spectrometry (MS). The differentially expressed proteins (DEPs) were identified, and the protein–protein interaction (PPI) network was constructed to identify the interacting partners of DISC1. Based on the interaction scores, NDE1, GRM3, PTGER3 and KATNA1 were identified as functionally or physically related to DISC1, and may therefore regulate AD development. The DEPs were functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases with the DAVID software, and the Non-supervised Orthologous Groups (eggNOG) database was used to determine their evolutionary relationships. The DEPs were significantly enriched in microtubules and mitochondria-related pathways. Gene set enrichment analysis (GSEA) was performed to identify genes and pathways that are activated when DISC1 is overexpressed. Our findings provide novel insights into the regulatory mechanisms underlying DISC1 function in AD.
Addressing dyslipidemic risk beyond LDL-cholesterol

Despite the success of LDL-lowering drugs in reducing cardiovascular disease (CVD), there remains a large burden of residual disease due in part to persistent dyslipidemia characterized by elevated levels of triglyceride-rich lipoproteins (TRLs) and reduced levels of HDL. This form of dyslipidemia is increasing globally as a result of the rising prevalence of obesity and metabolic syndrome. Accumulating evidence suggests that impaired hepatic clearance of cholesterol-rich TRL remnants leads to their accumulation in arteries, promoting foam cell formation and inflammation. Low levels of HDL may associate with reduced cholesterol efflux from foam cells, aggravating atherosclerosis. While fibrates and fish oils reduce TRL, they have not been uniformly successful in reducing CVD, and there is a large unmet need for new approaches to reduce remnants and CVD. Rare genetic variants that lower triglyceride levels via activation of lipolysis and associate with reduced CVD suggest new approaches to treating dyslipidemia. Apolipoprotein C3 (APOC3) and angiopoietin-like 3 (ANGPTL3) have emerged as targets for inhibition by antibody, antisense, or RNAi approaches. Inhibition of either molecule lowers TRL but respectively raises or lowers HDL levels. Large clinical trials of such agents in patients with high CVD risk and elevated levels of TRL will be required to demonstrate efficacy of these approaches.
“I Surrendered”: Metaphors in Residents’ Stories about Communication Challenges

ABSTRACT It is well-known that communication with patients can be challenging for residents. Although some studies have focused on residents’ experiences of communication challenges, few, if any, have investigated the language residents use when describing such challenges. In this study, we explore the metaphors residents use when asked to share stories about challenging communication situations. Metaphor has been the focus of research in a variety of health-related disciplines; here, we use it to gain an understanding of why these situations are seen as challenging. Methodologically, we draw on metaphor-led discourse analysis, which facilitates a systematic approach to the identification and analysis of metaphors. The empirical material consists of 138 Danish residents’ 259 narratives about communication challenges. We identified more than 700 metaphors used in connection with accounting for communication challenges with patients. The metaphors are primarily driven by vehicles belonging to four groups, namely: “Location,” “Movement,” “Games and play,” and “Battle and warfare. ” We discuss the implications of these metaphors in relation to residents’ conceptualizations of communication and challenges.
Time in range, as measured by continuous glucose monitor, as a predictor of microvascular complications in type 2 diabetes: a systematic review

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with hemoglobin A1c (A1c) among patients with type 2 diabetes mellitus (T2DM); however, there is a paucity of data evaluating its association with microvascular complications. We conducted this systematic review to examine the association between TIR and microvascular complications of diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). We conducted a comprehensive literature search on PubMed, Scopus, and Web of Science online databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text original articles that evaluated the association between CGM-derived TIR and risk of microvascular complications and were published between 2010 and June 2021 were included in our systematic review. The quality of the included studies was evaluated using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were analyzed using qualitative synthesis. Eleven studies on a total of 13 987 patients were included in the systematic review. The median sample size, baseline A1c, and diabetes duration were 466 patients (range: 105–5901), 8.2% (SD 0.5%), and 11.3 years (1.0), respectively. Majority of the studies were conducted in Asia (10 out of 11). Four studies evaluated the relationship between CGM-derived TIR and DR and CGM-derived TIR and DN, while seven studies evaluated the relationship between CGM-derived TIR and DPN. A 10% increase in TIR was associated with a reduction in albuminuria, severity of DR, and prevalence of DPN and cardiac autonomic neuropathy. In addition, an association was observed between urinary albumin to creatinine ratio but not with estimated glomerular filtration rate. This review summarizes recent evidence supporting an association between CGM-derived TIR and microvascular complications among patients with T2DM. A larger-scale multicenter investigation that includes more diverse participants is warranted to further validate the utility of TIR as a predictor of diabetic microvascular complications.
How I investigate acquired megaloblastic anemia

In this review of megaloblastic anemia (MA), an overview of vitamin B12 and folate body requirements, biochemical pathways, and laboratory testing strategies will be provided. However, the focus of this review is the classic and unique features of MA in blood and bone marrow. Acquired MA is a benign disorder for many, but can be detrimental for some. The clinical presentation can vary considerably, and the spectrum of symptoms and signs is diverse and quite broad. Prompt recognition and therapy are critical to prevent potential irreversible damage and clinical sequelae, especially in patients with vitamin B12 deficiency. A delay in diagnosis of vitamin B12 deficiency can result in significant neurologic sequelae that may not fully resolve with treatment, including in neonates and young infants. The blood and bone marrow features in MA can closely mimic thrombocytopenic purpura, myelodysplasia, and other myeloid neoplasms. Both pancytopenia and normal MCV at presentation are common in MA and raise unique challenges for the diagnostician. Partially treated MA is also a significant diagnostic “trap”. MA is highly responsive to treatment, and patients tend to improve rapidly upon treatment initiation. However, the broad range of clinical and hematologic features makes the rapid, successful diagnosis of MA a unique challenge for the hematopathologist. Even in the era of state‐of‐the‐art laboratory testing, a high suspicion is required.
Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis

Key Points Blinatumomab was associated with low incidence of grade 3 or 4 cytokine release syndrome (n = 2; 1.8%) and neurologic events (n = 4; 3.6%). The best blinatumomab outcomes were seen in patients achieving CR with no MRD who received alloHSCT, independent of genetic abnormalities.
Teacher professional development in integrating digital fabrication technologies into teaching and learning

ABSTRACT The potential of digital fabrication technology (DFT) in education has attracted the attention of many educational stakeholders over the last decade. However, there is scant literature on how in-service teachers take part in teacher professional development (TPD) to equip themselves with necessary DFT skills and knowledge. In response, this qualitative exploratory study aimed to identify characteristics of effective DFT-related TPD and the current status of the implementation of DFT in K–12 education in Hong Kong through interviews with local teachers and stakeholders. The findings reveal that DFT-related TPDs have had positive effects on teachers’ skills and knowledge overall, but they were found to lack in-depth hands-on training and guidance on pedagogical aspects with practical class models. Teachers flexibly adopted formal and informal TPD depending on their own backgrounds, competencies, and needs. In addition, the following barriers to applying TPD learning outcomes to classroom practices were identified: limited hardware availability and access as well as a lack of open-learning classrooms, technical support and sustained professional development for teachers, technology integration into different subjects, and government-provided guidelines and frameworks. However, these limitations were found to afford new opportunities with respect to student-centered and collaborative teaching and learning environments.
A revised lower estimate of ozone columns during Earth’s oxygenated history

The history of molecular oxygen (O2) in Earth’s atmosphere is still debated; however, geological evidence supports at least two major episodes where O2 increased by an order of magnitude or more: the Great Oxidation Event (GOE) and the Neoproterozoic Oxidation Event. O2 concentrations have likely fluctuated (between 10−3 and 1.5 times the present atmospheric level) since the GOE ∼2.4 Gyr ago, resulting in a time-varying ozone (O3) layer. Using a three-dimensional chemistry-climate model, we simulate changes in O3 in Earth’s atmosphere since the GOE and consider the implications for surface habitability, and glaciation during the Mesoproterozoic. We find lower O3 columns (reduced by up to 4.68 times for a given O2 level) compared to previous work; hence, higher fluxes of biologically harmful UV radiation would have reached the surface. Reduced O3 leads to enhanced tropospheric production of the hydroxyl radical (OH) which then substantially reduces the lifetime of methane (CH4). We show that a CH4 supported greenhouse effect during the Mesoproterozoic is highly unlikely. The reduced O3 columns we simulate have important implications for astrobiological and terrestrial habitability, demonstrating the relevance of three-dimensional chemistry-climate simulations when assessing paleoclimates and the habitability of faraway worlds.
Structural Behaviour of Green Geopolymer Concrete Beams and Columns Made with Waste Wood Ash a Partial Substitution Binder

On the demand of reducing the global warming due to cement production which is used as main constituent in the production of concrete and minimizing the environmental impact caused by the waste and its disposal methods, this study was aimed. This study looked in to detail insight view on effective utilization of waste wood ash in the production of geopolymer concrete beams and columns to alternate the conventional reinforced concrete elements in construction industry. Waste wood ash is a waste by product produced in the nearby hotel and factories by burning the waste wood collected from timber industries and the ash are thrown in to land which creates a major environmental pollution. Geopolymer is a novel inorganic eco-friendly binding agent derived from alkaline solution that stimulates aluminosilicate source material (such as metakaolin, fly ash and GGBS). In this research, behaviour of beams in deflection, ductility factor, flexural strength and toughness index and columns in load carrying ability, stress strain behaviour and load-deflection behaviours were examined for three types of concretes (30% WWA – 70% Fly ash Geo-polymer concrete, Fly ash Geo-polymer concrete and Reinforced Cement Concrete). The results showed that inclusion of waste wood ash in geopolymer concrete helped in enhancing the load carrying capacity of beam and column by 42% and 28%. Further, the behaviour of structural elements in stiffness, ductility and toughness were also improved with the replacement of waste wood ash.
An Effective Designing of Supercapacitor Mitigating Self-Discharge

Supercapacitor is a kind of effective energy storage device with merits such as high power density, long cycling life and so on, but their application is limited nowadays compared to the application of batteries. One important restriction is because of the serious self-discharge in supercapacitors, and how to conquer the self-discharge problem is an important issue. In this article we propose an effective way to reduce self-discharge of the supercapacitor by carefully designing of activated carbon (ACs) electrodes and water-in salt electrolyte. The electrochemical characterization shows that our supercapacitor can have the ability to reduce self-discharge.
Experimental Investigation on Fresh and Hardened Properties of High Calcium Flyash Based Geopolymer Concrete

The most important cause of the climate changes in the past few decades are due to the emission of CO2.It may be due to human or natural processes such as disposal of waste material from the thermal power plant, consuming natural resources or production of cement etc. Due to increase in infrastructure created the demand of more construction industries. Increasing importance of environmental protection and energy storage has led to the investigation of alternative binders to replace the cement. Geopolymers are an alternative binder for cement concrete production because of their superior mechanical properties. In the present investigation, for developing the Geopolymer concrete (GPC), high calcium fly ash is used as an alternative binder with Na2SiO3 and NaOH as alkaline liquids. Fresh and hardened properties of GPC are examined by appropriate experiments. Alkaline liquid to High calcium Fly ash ratio (AL: HCF) of 0.45, 0.55,0.6 and 0.65 are used with 8M of NaOH and the developed GPC is kept in ambient curing for 7 days, 28 days, and 56 days. It was observed that with an increase of AL to HCF ratio in the fresh GPC increased the workability of GPC. Increase of AL to HCF ratio in GPC mix increased the compressive strength, tensile strength and flexural strength up to a certain limit.
Influence of Substrate Temperature on Structural and Optical Properties of Co-Evaporated Cu2SnS3/ITO Thin Films

In this study report the structural and optical properties of Copper Tin Sulfide (Cu2SnS3) thin films on indium tin oxide (ITO) substrate using co-evaporation technique. High purity of copper, tin and sulfur were taken as source materials to deposit Cu2SnS3 (CTS) thin films at different substrate temperatures (200-350 °C). Further, the effect of different substrate temperature on the crystallographic, morphological and optical properties of CTS thin films was investigated. The deposited CTS thin films shows tetragonal phase with preferential orientation along (112) plane confirmed by X-ray diffraction. Micro-Raman studies reveled the formation of CTS thin films. The surface morphology, average grain size and rms values of the deposited films are examined by Scanning electron spectroscopy (SEM) and Atomic Force Microscopy (AFM). The Energy dispersive spectroscopy (EDS) shows the presence of copper, tin and sulfur with a nearly stoichiometric ratio. The optical band gap (1.76-1.63 eV) and absorption coefficient (~105 cm-1) of the films was calculated by using UV-Vis-NIR spectroscopy. The values of refractive index, extinction coefficient and permittivity of the deposited films were calculated from the optical transmittance data.
Preliminary Chemical, Total Phenolic Content, Flavonoid Content, and Antioxidant Activity of some Plants Used in Vietnam Folk Medicine

Crinum latifolium , Eclipta prostrata , Ocimum gratissimum , Phyllanthus urinar ia and Streptocaulon juventas have been used in Vietnam traditional medicine practices for anti-inflammatory, anti-cancer effects and antioxidant activities since prehistoric times. Ethanol and aqueous extracts from five medicinal herbs were evaluated for their antioxidative, free radical scavenging activities and phytochemical screening. Research results showed that these medicinal herbs all had rich chemical composition, such as alkaloids, coumarins, flavonoids, phenols, etc. Among ten extracts, C.latifolium ethanol extract showed the significantly highest total phenolic content (66.8 ± 4.14 mgGAE/g) and total flavonoids content (99.69 ± 9.88 mgQE/g). Both ethanol extracts from O.gratissimum and P.urinaria were showed the most elevated antioxidant potentials in DPPH and ABTS assays. These findings suggest that the rich phytochemical content and the good antioxidant activity of five herbal plants may be responsible for its popular and wide traditional use.
TESTIS ABNORMALITIES IN A POPULATION OF SOUTH AUSTRALIAN KOALAS (PHASCOLARCTOS CINEREUS)

Abstract: Testis asymmetry, in which the testes in an individual differ in size, has recently been reported in koalas (Phascolarctos cinereus) in the Mount Lofty Ranges population of South Australia. We describe the morphology and histology of both testes from affected individuals in this population (n=56) and the parameters of koalas with normal-sized testes based on age and breeding season (n=56). Morphologic measurements included testis weight, length, width, and volume; histologic parameters included seminiferous tubule diameter, seminiferous epithelial height, and seminiferous tubule (interstitial tissue ratio and presence or absence of spermatozoa). Of the 56 koalas with intraindividual variation in testes size, 47 were classified as asymmetric and nine as microtestes. For koalas with asymmetric testes, all morphologic parameters were significantly decreased in the smaller testes compared with normal-sized testes, but for the histologic parameters, only seminiferous tubule diameter was significantly less. Histopathologic examination of the asymmetric testes showed 38 with normal parenchyma histologically indistinguishable between intraindividual testes, four with degeneration and atrophy, and three with hypoplasia, whereas examination of microtestes showed degeneration and atrophy in seven, hypoplasia in one, and aplasia in one. No association of testis size difference with Chlamydia pecorum infection was found in a subset of animals. For the 56 koalas with normal-sized testes, morphologic parameters were found to increase with age, and juvenile and young adults were found to have smaller seminiferous tubule diameters than adults. No differences were found between testes of koalas in the breeding and nonbreeding season. Overall, these findings indicate that testis asymmetry in koalas from the Mount Lofty Ranges population is common but not associated with decreased function, except where testis malformations such as hypoplasia or aplasia occur or when parenchyma has been disrupted by acquired disease.
Prolonged exposure for pain and comorbid PTSD: a single-case experimental study of a treatment supplement to multiprofessional pain rehabilitation

Abstract Objectives It is unclear how to address PTSD in the context of chronic pain management. Here we examine the potential benefits of an addition of prolonged exposure (PE) therapy for PTSD for adults attending multidisciplinary CBT for chronic pain. Methods Four adults seeking treatment for chronic pain from a specialized pain rehabilitation service were offered PE for PTSD using a replicated, randomized, single-case experimental phase design, prior to commencing a 5-week multidisciplinary CBT program for chronic pain. Pre-, post-, follow-up, and daily measures allowed examination of PTSD and pain outcomes, potential mediators, and the trajectory of these outcomes and potential mediators during the subsequent pain-focused CBT program. Results Visual inspection of the daily data demonstrated changes in all outcome variables and potential mediators during the PE phase. Changes came at different times and at different rates for the four participants, highlighting the individual nature of putative change mechanisms. Consistent with expectation, PE produced reliable change in the severity of PTSD symptoms and trauma-related beliefs for all four participants, either by the end of the PE phase or the PE follow-up, with these gains maintained by the end of the 5-week pain-focused CBT program. However, few reductions in pain intensity or pain interference were seen either during the PE phase or after. Conclusions Although “disorder specific” approaches have dominated the conceptualising, study, and treatment of conditions like PTSD and chronic pain, such approaches may not be optimal. It may be better instead to approach cases in an individual and process-focused fashion. Ethical committee number 2013/381.
Asymmetric habitat isolation and sexual isolation predicted by the cost of migration and hybridization generate novel signatures of reinforcing selection

Reinforcement is an evolutionary process whereby increased prezygotic reproductive isolation evolves in response to the cost of hybridization. Despite theory predicting that multiple prezygotic barriers can evolve via reinforcement, most empirical studies examine a single barrier. We test novel predictions for the reinforcement of both habitat isolation and sexual isolation between ecologically divergent lineages under asymmetric migration—the lineage that emigrates more should evolve stronger habitat isolation due to the lower fitness of immigrants in the alternative habitat, while the lineage that receives more immigrants should exhibit stronger sexual isolation due to the lower fitness of hybrids. We found both signatures of reinforcement in two sympatric sister species of gall wasps that are host specific to the southern live oaks, Quercus virginiana and Q. geminata, respectively. Specifically, we observed stronger habitat isolation in the species with higher emigration rates, Belonocnema treatae, and stronger sexual isolation in the species facing more immigrants, B. fossoria. In contrast, comparisons of both species to a third, allopatric, species showed that B. kinseyi exhibited both lower habitat isolation and sexual isolation than the sympatric species, consistent with the classic predictions of reinforcement. Our study provides a rare examination of the interplay of ecology and geography in the evolution of multiple reproductive barriers to gene flow. Given that asymmetric migration between ecologically divergent lineages increasingly appears to be the rule rather than the exception, concomitant asymmetries in the strength of habitat and sexual isolation could be more widespread than currently understood.