Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma membrane and brain dysfunction of the old: Do we age from our membranes?

One of the characteristics of aging is a gradual hypo-responsiveness of cells to extrinsic stimuli, mainly evident in the pathways that are under hormone control, both in the brain and in peripheral tissues. Age-related resistance, i.e., reduced response of receptors to their ligands, has been shown to Insulin and also to leptin, thyroid hormones and glucocorticoids. In addition, lower activity has been reported in aging for ß-adrenergic receptors, adenosine A2B receptor, and several other G-protein-coupled receptors. One of the mechanisms proposed to explain the loss of sensitivity to hormones and neurotransmitters with age is the loss of receptors, which has been observed in several tissues. Another mechanism that is finding more and more experimental support is related to the changes that occur with age in the lipid composition of the neuronal plasma membrane, which are responsible for changes in the receptors’ coupling efficiency to ligands, signal attenuation and pathway desensitization. In fact, recent works have shown that altered membrane composition—as occurs during neuronal aging—underlies reduced response to glutamate, to the neurotrophin BDNF, and to insulin, all these leading to cognition decay and epigenetic alterations in the old. In this review we present evidence that altered functions of membrane receptors due to altered plasma membrane properties may be a triggering factor in physiological decline, decreased brain function, and increased vulnerability to neuropathology in aging.
On the scarcity of Magellanic Cloud like satellites

We have used Hα narrow-band imaging to search for star-forming satellite galaxies around 143 luminous spiral galaxies, with the goal of quantifying the frequency of occurrence of satellites resembling the Magellanic Clouds, around galaxies comparable to the Milky Way. For two-thirds of the central galaxies, no star-forming satellites are found, down to luminosities and star formation rates well below those of the Magellanic Clouds. A total of 62 satellites are found, associated with 47 of the central galaxies searched. The R-band magnitude difference between central galaxies and their satellites has a median value of 4.6 mag and a maximum value of 10.2 mag. The mean projected separation of the satellites from their central galaxies is 81 kpc, or 98 kpc for systems beyond 30 Mpc. Thus, star-forming satellites are quite rare, and the Milky Way is unusual both for the luminosity and the proximity of its two brightest satellites. We also find that the Clouds themselves are unusual in that they appear to form a bound binary pair; such close satellite pairs, of any luminosity, are also extremely rare in our survey.
Serum lactate is associated with increased illness severity in immunocompromised pediatric hematology oncology patients presenting to the emergency department with fever

Introduction Determining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours. Methods Receiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed. Results Among 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579). Conclusions These data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.
White adipose tissue as a target for cadmium toxicity

Cadmium (Cd) is a widespread heavy metal known as a toxic environmental pollutant. Cd exposure is threatening due to its bioaccumulation trait in living systems that exceeds 35 years without a beneficial biological role. Acute exposure to high Cd doses was reported to impact adipose tissue (AT) function adversely. The main aim of this study is to investigate the effect of low-dose chronic Cd exposure on the genes involved in adipose tissue (AT) functions. Adult male Sprague-Dawley rats were exposed to a low Cd dose (15 mg/kg B.W./day) for 10 weeks. Then, three AT depots-subcutaneous AT (SUB-AT), abdominal AT (AB-AT), and retroperitoneal AT (REtrop-AT) were excised for Cd accumulation measures and gene expression analysis. Adiponectin and leptin gene expression levels were investigated as markers for adipocytes function and homeostasis. Our results showed that Cd accumulated in all the tested adipose depots, but SUB-AT was found to be the depot to most accumulate Cd. Also, it was exhibited that chronic exposure to low Cd doses altered the gene expression of adipocytokines. The levels of adiponectin and leptin mRNA expression were downregulated in all tested AT-depots after Cd exposure. The significant adverse effect on SUB-AT compared to other depots indicates different responses based on AT depots location toward Cd exposure. Collectively, these results suggest a toxic effect of Cd that influenced adipocyte function.
Health-related quality of life of salvage prostate reirradiation using stereotactic ablative radiotherapy with urethral-sparing

Purpose To explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer. Materials and methods Between July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm3 air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria. Results Median follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4-year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 post-treatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time. Conclusion Pursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing.
Adaptive optics in single objective inclined light sheet microscopy enables three-dimensional localization microscopy in adult Drosophila brains

Single-molecule localization microscopy (SMLM) enables the high-resolution visualization of organelle structures and the precise localization of individual proteins. However, the expected resolution is not achieved in tissue as the imaging conditions deteriorate. Sample-induced aberrations distort the point spread function (PSF), and high background fluorescence decreases the localization precision. Here, we synergistically combine sensorless adaptive optics (AO), in-situ 3D-PSF calibration, and a single-objective lens inclined light sheet microscope (SOLEIL), termed (AO-SOLEIL), to mitigate deep tissue-induced deteriorations. We apply AO-SOLEIL on several dSTORM samples including brains of adult Drosophila. We observed a 2x improvement in the estimated axial localization precision with respect to widefield without aberration correction while we used synergistic solution. AO-SOLEIL enhances the overall imaging resolution and further facilitates the visualization of sub-cellular structures in tissue.
A MODEL FOR THE ORIGIN OF HIGH DENSITY IN LOOPTOP X-RAY SOURCES

Super-hot (SH) looptop sources, detected in some large solar flares, are compact sources of HXR emission with spectra matching thermal electron populations exceeding 30 MK. High observed emission measure (EM) and inference of electron thermalization within the small source region both provide evidence of high densities at the looptop, typically more than an order of magnitude above ambient. Where some investigators have suggested such density enhancement results from a rapid enhancement in the magnetic field strength, we propose an alternative model, based on Petschek reconnection, whereby looptop plasma is heated and compressed by slow magnetosonic shocks generated self-consistently through flux retraction following reconnection. Under steady conditions such shocks can enhance density by no more than a factor of four. These steady shock relations (Rankine–Hugoniot relations) turn out to be inapplicable to Petschek's model owing to transient effects of thermal conduction. The actual density enhancement can in fact exceed a factor of 10 over the entire reconnection outflow. An ensemble of flux tubes retracting following reconnection at an ensemble of distinct sites will have a collective EM proportional to the rate of flux tube production. This rate, distinct from the local reconnection rate within a single tube, can be measured separately through flare ribbon motion. Typical flux transfer rates and loop parameters yield EMs comparable to those observed in SH sources.
Communicative universal convertibility Matter-Energy-Information

The research aims to reveal and prove the thesis of the neutral and convertibility relationship between constituent constructive elements of the universe: matter, energy and information. The approach perspective is a computationally-communicative-neutrosophic one. We configure a coherent and cohesive ideation line. Matter, energy and information are fundamental elements of the world. Among them, there is an inextricable multiple, elastic and evolutionary connection. The elements are defined by the connections between them. Our hypothesis is that the relationship between matter, energy and information is a neutral one. This relationship is not required by the evidence. At this level, it does not give up in front of the evidence intelligibility. Neutral relationship is revealed as a law connection. First, the premise that matter, energy and information never come into contradiction is taken as strong evidence. Their law-like-reciprocal obligations are non contradictory. Being beyond the contrary, matter, energy and information maintain a neutral relationship. Therefore, on the basis of the establishment and functioning of the universe or multi-verse, there is neutrality. Matter, energy and information are primary-founder neutralities. Matter, energy and information are neutral because they are related to inexorable legitimate. They are neutral because they are perfectly bound to one another. Regularity and uniformity are the primary forms of neutrality. The study further radiographies the relational connections, and it highlights and renders visible the attributes and characteristics of the elements (attributes are essential features of elements and characteristics are their specific features). It explains the bilateral relationships matter-energy, information-matter and energy-information. Extension method of Cai Wen (1999) is utilized to clarify relationships between Matter, Energy and Information. It finally results that reality is an ongoing and complex process of bilateral and multi-lateral convertibility. Thus, it is formulated the neutrosophic principle of Interconvertibility Matter-Energy-Information (NPI_MEI).
Effects of laccase and lactic acid bacteria on the fermentation quality, nutrient composition, enzymatic hydrolysis, and bacterial community of alfalfa silage

Ensiling has long been as a mainstream technology of preserving forage for ruminant production. This study investigated the effects of bioaugmented ensiling with laccase and Pediococcus pentosaceus on the fermentation quality, nutritive value, enzymatic hydrolysis, and bacterial community of alfalfa. The application of laccase and Pediococcus pentosaceus combination was more potent in modulating the fermentation quality of silage than laccase and Pediococcus pentosaceus alone, as indicated by higher lactic acid contents and lactic acid to acetic acid ratios, and lower pH, dry matter losses, and ammonia nitrogen contents. Moreover, treatments with additive enhanced protein preservation and structural carbohydrate degradation, while increasing true protein and water-soluble carbohydrate contents. By promoting lignin degradation, treatments containing laccase further facilitated the release of sugars from cellulose compared with treatment with Pediococcus pentosaceus alone. The additive treatments reduced the bacterial diversity and optimized the bacterial community composition of silage, with an increase in the relative abundance of desirable Lactobacillus and a decrease in the relative abundance of undesirable Enterobacter and Klebsiella. PICRUSt functional prediction based on Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed that PL and LPL treatments increased the metabolism of membrane transport, carbohydrate, and terpenoids and polyketides related to fermentation activities. It can be concluded that bioaugmented ensiling with laccase and Pediococcus pentosaceus combination can be an effective and practical strategy to improve silage fermentation and nutrient preservation of alfalfa silage.
Diversity in people's reluctance to use medical artificial intelligence: Identifying subgroups through latent profile analysis

Medical artificial intelligence (AI) is important for future health care systems. Research on medical AI has examined people's reluctance to use medical AI from the knowledge, attitude, and behavioral levels in isolation using a variable-centered approach while overlooking the possibility that there are subpopulations of people who may differ in their combined level of knowledge, attitude and behavior. To address this gap in the literature, we adopt a person-centered approach employing latent profile analysis to consider people's medical AI objective knowledge, subjective knowledge, negative attitudes and behavioral intentions. Across two studies, we identified three distinct medical AI profiles that systemically varied according to people's trust in and perceived risk imposed by medical AI. Our results revealed new insights into the nature of people's reluctance to use medical AI and how individuals with different profiles may characteristically have distinct knowledge, attitudes and behaviors regarding medical AI.
Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 19 (COVID-19) has numerous risk factors leading to severe disease with high mortality rate. Oxidative stress with excessive production of reactive oxygen species (ROS) that lower glutathione (GSH) levels seems to be a common pathway associated with the high COVID-19 mortality. GSH is a unique small but powerful molecule paramount for life. It sustains adequate redox cell signaling since a physiologic level of oxidative stress is fundamental for controlling life processes via redox signaling, but excessive oxidation causes cell and tissue damage. The water-soluble GSH tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) is present in the cytoplasm of all cells. GSH is at 1–10 mM concentrations in all mammalian tissues (highest concentration in liver) as the most abundant non-protein thiol that protects against excessive oxidative stress. Oxidative stress also activates the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) redox regulator pathway, releasing Nrf2 to regulate the expression of genes that control antioxidant, inflammatory and immune system responses, facilitating GSH activity. GSH exists in the thiol-reduced and disulfide-oxidized (GSSG) forms. Reduced GSH is the prevailing form accounting for >98% of total GSH. The concentrations of GSH and GSSG and their molar ratio are indicators of the functionality of the cell and its alteration is related to various human pathological processes including COVID-19. Oxidative stress plays a prominent role in SARS-CoV-2 infection following recognition of the viral S-protein by angiotensin converting enzyme-2 receptor and pattern recognition receptors like toll-like receptors 2 and 4, and activation of transcription factors like nuclear factor kappa B, that subsequently activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) expression succeeded by ROS production. GSH depletion may have a fundamental role in COVID-19 pathophysiology, host immune response and disease severity and mortality. Therapies enhancing GSH could become a cornerstone to reduce severity and fatal outcomes of COVID-19 disease and increasing GSH levels may prevent and subdue the disease. The life value of GSH makes for a paramount research field in biology and medicine and may be key against SARS-CoV-2 infection and COVID-19 disease.
A rigorous in silico genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders

Genome-wide chromosomal microarray is extensively used to detect copy number variations (CNVs), which can diagnose microdeletion and microduplication syndromes. These small unbalanced chromosomal structural rearrangements ranging from 1 kb to 10 Mb comprise up to 15% of human mutations leading to monogenic or contiguous genomic disorders. Albeit rare, CNVs at 1p13.3 cause a variety of neurodevelopmental disorders (NDDs) including development delay (DD), intellectual disability (ID), autism, epilepsy, and craniofacial anomalies (CFA). Most of the 1p13.3 CNV cases reported in the pre-microarray era encompassed a large number of genes and lacked the demarcating genomic coordinates, hampering the discovery of positional candidate genes within the boundaries. In this study, we present four subjects with 1p13.3 microdeletions displaying DD, ID, autism, epilepsy, and CFA. In silico comparative genomic mapping with three previously reported subjects with CNVs and 22 unreported DECIPHER CNV cases has resulted in the identification of four different sub-genomic loci harboring five positional candidate genes for DD, ID, and CFA at 1p13.3. Most of these genes have pathogenic variants reported, and their interacting genes are involved in NDDs. RT-qPCR in various human tissues revealed a high expression pattern in the brain and fetal brain, supporting their functional roles in NDDs. Interrogation of variant databases and interacting protein partners led to the identification of another set of 11 potential candidate genes, which might have been dysregulated by the position effect of these CNVs at 1p13.3. Our studies define 1p13.3 as a genomic region harboring 16 NDD candidate genes and underscore the critical roles of small CNVs in in silico comparative genomic mapping for disease gene discovery. Our candidate genes will help accelerate the isolation of pathogenic heterozygous variants from exome/genome sequencing (ES/GS) databases.