Miracle-dz/UniFAR-FTUs huggingface dataset:
Microglial large extracellular vesicles propagate early synaptic dysfunction in Alzheimer’s disease

Abstract Synaptic dysfunction is an early mechanism in Alzheimer’s disease that involves progressively larger areas of the brain over time. However, how it starts and propagates is unknown. Here we show that amyloid-β released by microglia in association with large extracellular vesicles (Aβ-EVs) alters dendritic spine morphology in vitro, at the site of neuron interaction, and impairs synaptic plasticity both in vitro and in vivo in the entorhinal cortex–dentate gyrus circuitry. One hour after Aβ-EV injection into the mouse entorhinal cortex, long-term potentiation was impaired in the entorhinal cortex but not in the dentate gyrus, its main target region, while 24 h later it was also impaired in the dentate gyrus, revealing a spreading of long-term potentiation deficit between the two regions. Similar results were obtained upon injection of extracellular vesicles carrying Aβ naturally secreted by CHO7PA2 cells, while neither Aβ42 alone nor inflammatory extracellular vesicles devoid of Aβ were able to propagate long-term potentiation impairment. Using optical tweezers combined to time-lapse imaging to study Aβ-EV–neuron interaction, we show that Aβ-EVs move anterogradely at the axon surface and that their motion can be blocked through annexin-V coating. Importantly, when Aβ-EV motility was inhibited, no propagation of long-term potentiation deficit occurred along the entorhinal–hippocampal circuit, implicating large extracellular vesicle motion at the neuron surface in the spreading of long-term potentiation impairment. Our data indicate the involvement of large microglial extracellular vesicles in the rise and propagation of early synaptic dysfunction in Alzheimer’s disease and suggest a new mechanism controlling the diffusion of large extracellular vesicles and their pathogenic signals in the brain parenchyma, paving the way for novel therapeutic strategies to delay the disease.
Impact of biliary stenting in endoscopic ultrasound‐guided tissue acquisition among patients with pancreatic cancer

Pancreatic malignancies represent highly fatal diseases with poor prognosis and constantly increasing incidence despite modern diagnostic and therapeutic options. Both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are regarded as mainstays in pancreatic cancer management. The present study aims to evaluate whether accuracy EUS with fine‐needle aspiration or biopsy (FNA or FNB) in pancreatic cancer diagnosis is influenced by prior biliary stenting or by technical or anatomical features (stent type, number of needle passes, common bile duct or Wirsung's diameter, topographical characteristics and diameter of the pancreatic tumor).
Epidemiology, Secondary School Curricula, and Preparing the Next Generation for Global Citizenship

Because COVID-19 and other emerging infectious diseases are likely to play an increasingly important role in shaping American and global society in years to come, there is a need to prepare young people to make informed decisions in this changing global context. One way to do so is teaching and learning about basic principles of epidemiology in secondary schools. Improved understanding about the agent of infection, mechanisms of transmission, factors that increase or decrease susceptibility, place variation and environmental factors that facilitate or hinder transmission, reservoirs of infection (where the agent lives and multiplies), and when the disease is more or less likely to occur comprise the main facts about an infectious disease relevant to prevention and control. Improved understanding of these basic concepts could help future generations make informed decisions in a changing global context with emerging infectious diseases and a plethora of widely disseminated misinformation and disinformation. This viewpoint considers why learning about epidemiology in secondary school would benefit population health using COVID-19 as an illustration.
Predicting Long-term Survival After Allogeneic Hematopoietic Cell Transplantation in Patients With Hematologic Malignancies: Machine Learning–Based Model Development and Validation

Background Scoring systems developed for predicting survival after allogeneic hematopoietic cell transplantation (HCT) show suboptimal prediction power, and various factors affect posttransplantation outcomes. Objective A prediction model using a machine learning–based algorithm can be an alternative for concurrently applying multiple variables and can reduce potential biases. In this regard, the aim of this study is to establish and validate a machine learning–based predictive model for survival after allogeneic HCT in patients with hematologic malignancies. Methods Data from 1470 patients with hematologic malignancies who underwent allogeneic HCT between December 1993 and June 2020 at Asan Medical Center, Seoul, South Korea, were retrospectively analyzed. Using the gradient boosting machine algorithm, we evaluated a model predicting the 5-year posttransplantation survival through 10-fold cross-validation. Results The prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.788 (SD 0.03). Furthermore, we developed a risk score predicting probabilities of posttransplantation survival in 294 randomly selected patients, and an agreement between the estimated predicted and observed risks of overall death, nonrelapse mortality, and relapse incidence was observed according to the risk score. Additionally, the calculated score demonstrated the possibility of predicting survival according to the different transplantation-related factors, with the visualization of the importance of each variable. Conclusions We developed a machine learning–based model for predicting long-term survival after allogeneic HCT in patients with hematologic malignancies. Our model provides a method for making decisions regarding patient and donor candidates or selecting transplantation-related resources, such as conditioning regimens.
Role of cellular retinol‐binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi‐omic approach

The main active metabolite of Vitamin A, all‐trans retinoic acid (RA), is required for proper cellular function and tissue organization. Heart development has a well‐defined requirement for RA, but there is limited research on the role of RA in the adult heart. Homeostasis of RA includes regulation of membrane receptors, chaperones, enzymes, and nuclear receptors. Cellular retinol‐binding protein, type 1 (CRBP1), encoded by retinol‐binding protein, type 1 (Rbp1), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis and protecting it from non‐specific oxidation. In this work, a multi‐omics approach was used to characterize the effect of CRBP1 loss using the Rbp1−/− mouse. Retinoid homeostasis was disrupted in Rbp1−/− mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild‐type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high‐throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential abundance between Rbp1−/− and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2606 unique proteins were identified, with 340 proteins having differential expression between Rbp1−/− and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1−/− mice. Together, these studies characterize the effect of CRBP1 loss and reduced RA in the adult heart.
Cross-sectoral collaboration: comparing complex child service delivery systems

Purpose To help ensure that children with social and behavioral health problems get the support services they need, organizations collaborate in cross-sectoral networks. In this article, the authors explore and compare the structure of these complex child service delivery networks in terms of differentiation (composition) and integration (interconnection). In particular, the authors investigate the structure of client referral and identify which organizations are most prominent within that network structure and could therefore fulfill a coordinating role. Design/methodology/approach The authors used a comparative case study approach and social network analysis on three interorganizational networks consisting of 65 to 135 organizations within the Dutch child service delivery system. Semi-structured interviews with the network managers were conducted, and an online questionnaire was sent out to the representatives of all network members. Findings The networks are similarly differentiated into 11 sectors with various tasks. Remarkably, network members have contact with an average of 20–26 organizations, which is a fairly high number to be handled successfully. In terms of integration, the authors found a striking diversity in the structures of client referral and not all organizations with a gatekeeper task hold central positions. Originality/value Due to the scarcity of comparative whole network research in the field, the strength of this study is a deeper understanding of the differentiation and integration of complex child service delivery systems. These insights are crucial in order to deliver needed services and to minimize service silos and fragmentation.
Pioglitazone, Bladder Cancer and the Presumption of Innocence.

BACKGROUND Thiazolidinediones are potent exogenous agonists of PPAR-γ, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue. Pioglitazone, the main thiazolidinedione in clinical practice, has shown cardiovascular and renal benefits in patients with type 2 diabetes, durable reduction of glycated hemoglobulin levels, important improvements of several components of the metabolic syndrome and beneficial effects of non-alcoholic fatty liver disease. OBJECTIVE Despite all of its established advantages, the controversy for an increased risk of developing bladder cancer, combined with the advent of newer drug classes that achieved major cardiorenal effects have significantly limited its use spreading a persistent shadow of doubt for its future role. METHODS Pubmed, Google and Scope databases have been thoroughly searched and relevant studies were selected. RESULTS This paper explores thoroughly both in vitro and in vivo (animal models and humans) studies that investigated the possible association of pioglitazone with bladder cancer. CONCLUSION Currently the association of pioglitazone with bladder cancer cannot be based on solid evidence. This evidence cannot justify its low clinical administration, especially in the present era of individualised treatment strategies. Definite clarification of this issue is imperative and urgently anticipated from future high quality and rigorous pharmacoepidemiologic research, keeping in mind its unique mechanism of action and its significant pleiotropic effects.
Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis

Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
Aeroheating measurements on a reentry capsule model in free-piston shock tunnel HIEST

Aeroheating of an Apollo CM model was measured in the free-piston shock tunnel HIEST. The primary purpose of the measurement was to obtain benchmark data for numerical codes validation under high-enthalpy high-Reynolds number conditions. The model was made of SUS-304 stainless steel and had a diameter of 250mm. The windward surface of the model was equipped with 84 miniature co-axial Chromel-Constantan thermocouples that were manufactured in-house at JAXA. Twelve thermocouples and two Piezo-resistive pressure transducers were also mounted aft on the model and were used to determine the establishment of flow around the model. In this test campaign, heat flux data were measured for angles of attack 0o and 30o. Stagnation enthalpy and stagnation pressure were varied from H0=4MJ/kg to 21MJ/kg, and from P0=14MPa to 58MPa, respectively. Aeroheating characteristics were observed with a fully laminar boundary layer and with a transition boundary layer. Measured heat flux was normalized by the product of the Stanton number and the square-root of the Reynolds number for correlation with other wind tunnel results and flight results. The normalized heat flux value did not change remarkably when stagnation enthalpy was changed from H0=4MJ/kg to 12MJ/kg, implying that the boundary layer flow was usually laminar. However, shots under high enthalpy and high Reynolds number conditions (H0 over 18MJ/kg and P0 approximately 50MPa) showed that the measured heat flux was approximately 40% higher than that obtained in other conditions.
Aspergillus terreus and the Interplay with Amphotericin B: from Resistance to Tolerance?

Aspergillus terreus is an opportunistic causative agent of invasive aspergillosis and, in most cases, it is refractory to amphotericin B (AMB) therapy. Notably, AMB-susceptible Aspergillus terreus sensu stricto (s.s.) representatives exist which are also associated with poor clinical outcomes. ABSTRACT Aspergillus terreus is an opportunistic causative agent of invasive aspergillosis and, in most cases, it is refractory to amphotericin B (AMB) therapy. Notably, AMB-susceptible Aspergillus terreus sensu stricto (s.s.) representatives exist which are also associated with poor clinical outcomes. Such findings may be attributable to drug tolerance, which is not detectable by antifungal susceptibility testing. Here, we tested in vitro antifungal susceptibility (AFST) and the fungicidal activity of AMB against 100 clinical isolates of A. terreus species complex in RPMI 1640 and antibiotic medium 3 (AM3). MICs ranged from 0.5 to 16 μg/mL for RPMI 1640 and from 1 to >16 mg/L for AM3. AMB showed medium-dependent activity, with fungicidal effects only in antibiotic medium 3, not in RPMI 1640. Furthermore, the presence of AMB-tolerant phenotypes of A. terreus has been examined by assessing the minimum duration for killing 99% of the population (MDK99) and evaluating the data obtained in a Galleria mellonella infection model. A time-kill curve analysis revealed that A. terreus with AMB MICs of ≤1 mg/L (susceptible range) displayed AMB-tolerant phenotypes, exhibiting MDK99s at 18 and 36 h, respectively. Survival rates of infected G. mellonella highlighted that AMB was effective against susceptible A. terreus isolates, but not against tolerant or resistant isolates. Our analysis reveals that A. terreus isolates which are defined as susceptible based on MIC may comprise tolerant phenotypes, which may, in turn, explain the worse outcome of AMB therapy for phenotypically susceptible isolates.
A review of the AURORA and BLISS trials: will it revolutionize the treatment of lupus nephritis?

Purpose of review Renal involvement in patients with systemic lupus erythematosus can lead to significant complications including end-stage renal disease. Treatment of lupus nephritis has evolved over the last several decades, but despite this evolution, many patients fail to achieve remission and often progress to end-stage kidney disease or carry a burden of adverse side effects related to treatment. Recent findings The recent findings from AURORA 1 and BLISS LN trials led the FDA to approve voclosporin and belimumab for the treatment of lupus nephritis. The AURORA 1 trial demonstrated that voclosporin, a second-generation calcineurin inhibitor, effectively lowers proteinuria in patients with lupus nephritis, when added to mycophenolate mofetil with a better safety profile, compared with other calcineurin inhibitors. The BLISS LN trial revealed better control of disease and lower risk of progression to end stage kidney disease (ESKD) and relapses in patients treated with belimumab in addition to standard therapy. Summary Both voclosporin and belimumab are costly and have not shown any early evidence to revolutionize practice in the management of lupus nephritis. Until more data are made available with future studies or other cost-effective treatment options become available, the widespread adoption and utility of these novel agents remains limited.
A Review on Biodegradable Packaging Films from Vegetative and Food Waste

Plastics around the globe have been a matter of grave concern due to the unavoidable habits of human mankind. Taking waste statistics in India for the year 2019–20 into account, the data of 60 major cities show that the generation of plastic waste stands tall at around 26,000 tonnes/day, of which only about 60 % is recycled. A majority of the non‐recycled plastic waste is petrochemical‐based packaging materials that are non‐biodegradable in nature. Vegetative/food waste is another global issue, evidenced by vastly populated countries such as China and India accounting for 91 and 69 tonnes of food wastage, respectively in 2019. The mitigation of plastic packaging issues has led to key scientific developments, one of which is biodegradable materials. However, there is a way that these two waste‐related issues can be fronted as the analogy of “taking two shots with the same arrow”. The presence of various bio‐compounds such as proteins, cellulose, starch, lipids, and waxes, etc., in food and vegetative waste, creates an opportunity for the development of biodegradable packaging films. Although these flexible packaging films have limitations in terms of mechanical, permeation, and moisture absorption characteristics, they can be fine‐tuned in order to convert the biobased raw material into a realizable packaging product. These strategies could work in replacing petrochemical‐based non‐biodegradable packaging plastics which are used in enormous quantities for various household and commercial packaging applications to combat the ever‐increasing pollution in highly populated countries. This paper presents a systematic review based on modern scientific tools of the literature available with a major emphasis on the past decade and aims to serve as a standard resource for the development of biodegradable packaging films from food/vegetative waste.
Modeling Flutter Response of a Flexible Morphing Wing for UAV

This paper is concerned with flutter instability of a novel morphing wing at low mission speeds for different morphing configurations. In view of the flexibility of the wing, it is highly desirable to determine the conditions that trigger flutter instability. Flutter boundary was predicted using the p-k method. Structural dynamics of the wing is obtained using lumped mass method and unsteady aerodynamic using the strip model is used to evaluate corresponding aerodynamic forces and moments. The results indicate that the newly designed flexible concept of the morphing wing increases the critical flutter velocity.
Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior

The pineal gland is a neuroendocrine structure in the brain, which produces and secretes the hormone melatonin at nighttime and is considered a key element in the circadian clock system. Early morphogenesis of the gland is controlled by a number of transcription factors, some of which remain active in adult life. One of these is the brain‐specific homeobox (Bsx), a highly conserved homeodomain transcription factor with a developmental role in the pineal gland of several species, including zebrafish, and regulatory roles in mature pinealocytes of the rat. To determine the role of Bsx in circadian biology, we here examined the effects of a bsx loss‐of‐function mutation on the pineal gland in adult zebrafish and on behavioral circadian rhythms in larvae. In pineal cell type‐specific Gfp/Egfp reporter zebrafish lines, we did not detect fluorescence signals in the pineal area of homozygous (bsx−/−) mutants. Interestingly, a nonpigmented area on the dorsal surface of the head above the gland, known as the pineal window, was pigmented in the homozygous mutants. Furthermore, a structure corresponding to the pineal gland was not detectable in the midline of the adult brain in histological sections analyzed by Nissl staining and S‐antigen immunohistochemistry. Moreover, the levels of pineal transcripts were greatly reduced in bsx−/− mutants, as revealed by quantitative real‐time polymerase chain reaction analysis. Notably, analysis of locomotor activity at the larval stage revealed altered circadian rhythmicity in the bsx mutants with periods and phases similar to wildtype, but severely reduced amplitudes in locomotor activity patterns. Thus, Bsx is essential for full development of the pineal gland, with its absence resulting in a phenotype of morphological pineal gland ablation and disrupted circadian behavior.
Transcriptomics analysis of cashmere fineness functional genes

Abstract Liaoning cashmere goat (LCG) is a famous cashmere goat breed in China. Cashmere fineness, as an important index to evaluate cashmere quality, is also one of the problems to be improved for Liaoning cashmere goats. Transcriptome studies all mRNA transcribed by a specific tissue or cell in a certain period. It is a key link in the study of gene expression regulation. It plays an important role in the analysis of biological growth and disease. Transcriptome is spatio-temporal specific, that is, gene expression varies in different tissues or at different times. Three coarser and three fine LCG skin samples were sequenced by RNA-seq technology, and a total of 427 differentially expressed genes were obtained, including 291 up-regulated genes and 136 down-regulated genes. In the experiment, we screened out 16 genes that had significant differences in the expression of coarse and fine cashmere of Liaoning cashmere goats, so it was inferred that these 16 genes might have regulatory effects on cashmere fineness. Moreover, GO gene set enrichment analysis revealed that differential genes mainly consist of immune response, MHC protein complex, Heme binding and other pathways. KEGG analysis showed that transplant-versus-host disease and allograft rejection were the main pathways of differential genes.