Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying and revealing different brain neural activities of cognitive subtypes in early course schizophrenia

Background Cognitive subtypes of schizophrenia may exhibit different neurobiological characteristics. This study aimed to reveal the underlying neurobiological features between cognitive subtypes in the early course of schizophrenia (ECS). According to prior studies, we hypothesized to identify 2–4 distinct cognitive subtypes. We further hypothesized that the subtype with relatively poorer cognitive function might have lower brain spontaneous neural activity than the subtype with relatively better cognitive function. Method Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Resting-state functional magnetic resonance imaging scanning was conducted for each individual. There were 155 ECS individuals and 97 healthy controls (HCs) included in the subsequent analysis. Latent profile analysis (LPA) was used to identify the cognitive subtypes in ECS individuals, and amplitude of low-frequency fluctuations (ALFFs) was used to measure brain spontaneous neural activity in ECS individuals and HCs. Results LPA identified two cognitive subtypes in ECS individuals, containing a severely impaired subtype (SI, n = 63) and a moderately impaired subtype (MI, n = 92). Compared to HCs, ECS individuals exhibited significantly increased ALFF in the left caudate and bilateral thalamus and decreased ALFF in the bilateral medial prefrontal cortex and bilateral posterior cingulate cortex/precuneus (PCC/PCu). In ECS cognitive subtypes, SI showed significantly higher ALFF in the left precentral gyrus (PreCG) and lower ALFF in the left PCC/PCu than MI. Furthermore, ALFFs of left PreCG were negatively correlated with several MCCB cognitive domains in ECS individuals, while ALFF of left PCC/PCu presented opposite correlations. Conclusion Our findings suggest that differences in the brain spontaneous neural activity of PreCG and PCC/PCu might be the potential neurobiological features of the cognitive subtypes in ECS, which may deepen our understanding of the role of PreCG and PCC/PCu in the pathogenesis of cognitive impairment in schizophrenia.
A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma: Implications for the COVID19 pandemic and beyond

Purpose The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC. Methods We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed. Results We identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09–1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96–1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19–2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50–4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery. Conclusions A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.
Mid-IR Properties of Seyferts: Spitzer IRS Spectroscopy of the IRAS 12 μm Seyfert Sample

Abstract We performed an analysis of the mid-infrared properties of the 12 μm Seyfert sample, a complete unbiased 12 μm flux limited sample of local Seyfert galaxies selected from the IRAS Faint Source Catalog based on low-resolution spectra obtained with the Infrared Spectrograph (IRS) on-board Spitzer Space Telescope. A detailed presentation of this analysis is discussed by Wu et al. (2009). We find that, on average, the 15–30 μm slope of the continuum is 〈 α15–30〉 = −0.85 ± 0.61 for Seyfert 1s and −1.53 ± 0.84 for Seyfert 2s, and there is substantial scatter in each type. Moreover, nearly 32% of Seyfert 1s, and 9% of Seyfert 2s, display a peak in the mid-infrared spectrum at 20 μm, which is attributed to an additional hot dust component. The polycyclic aromatic hydrocarbon (PAH) equivalent width decreases with increasing dust temperature, as indicated by the global infrared color of the host galaxies. However, no statistical difference in PAH equivalent width is detected between the two Seyfert types of the same bolometric luminosity. Finally, we propose a new method to estimate the AGN contribution to the integrated 12 μm galaxy emission, by subtracting the “star formation” component in the Seyfert galaxies, making use of the tight correlation between PAH 11.2 μm luminosity and 12 μm luminosity for star forming galaxies.
EXOTIME: searching for planets and measuring Pdot in sdB pulsators

We review the status of the EXOTIME project (EXOplanet search with the TIming MEthod). The two main goals of EXOTIME are to search for sub-stellar companions to sdB stars in wide orbits, and to measure the secular variation of the pulsation periods, which are related to the evolutionary change of the stellar structure. Now, after four years of dense monitoring, we start to see some results and present the brown dwarf and exoplanet candidates V1636 Ori b and DW Lyn b.
Long-term morphological and functional dynamics of human stem cell-derived neuronal networks on high-density micro-electrode arrays

Comprehensive electrophysiological characterizations of human induced pluripotent stem cell (hiPSC)-derived neuronal networks are essential to determine to what extent these in vitro models recapitulate the functional features of in vivo neuronal circuits. High-density micro-electrode arrays (HD-MEAs) offer non-invasive recording with the best spatial and temporal resolution possible to date. For 3 months, we tracked the morphology and activity features of developing networks derived from a transgenic hiPSC line in which neurogenesis is inducible by neurogenic transcription factor overexpression. Our morphological data revealed large-scale structural changes from homogeneously distributed neurons in the first month to the formation of neuronal clusters over time. This led to a constant shift in position of neuronal cells and clusters on HD-MEAs and corresponding changes in spatial distribution of the network activity maps. Network activity appeared as scarce action potentials (APs), evolved as local bursts with longer duration and changed to network-wide synchronized bursts with higher frequencies but shorter duration over time, resembling the emerging burst features found in the developing human brain. Instantaneous firing rate data indicated that the fraction of fast spiking neurons (150–600 Hz) increases sharply after 63 days post induction (dpi). Inhibition of glutamatergic synapses erased burst features from network activity profiles and confirmed the presence of mature excitatory neurotransmission. The application of GABAergic receptor antagonists profoundly changed the bursting profile of the network at 120 dpi. This indicated a GABAergic switch from excitatory to inhibitory neurotransmission during circuit development and maturation. Our results suggested that an emerging GABAergic system at older culture ages is involved in regulating spontaneous network bursts. In conclusion, our data showed that long-term and continuous microscopy and electrophysiology readouts are crucial for a meaningful characterization of morphological and functional maturation in stem cell-derived human networks. Most importantly, assessing the level and duration of functional maturation is key to subject these human neuronal circuits on HD-MEAs for basic and biomedical applications.
Inorganic nanoparticle empowered biomaterial hybrids: Engineered payload release

There are many challenges in delivering active pharmaceutical ingredients from biomaterials, including retention of payload activity, accurate temporal release, and precise spatial administration, to name only a few. With our constantly increasing knowledge of biology and physiology, pathologies that require therapeutic interventions are becoming more understood. While the desired temporal and spatial administration of a therapy might be theorized, the ability to deliver an active therapeutic in a precise location during a specific time frame is often challenging. This has led researchers to develop hybrid biomaterials containing inorganic nanoparticles in order to combine the advantages of both inorganics and organics in payload delivery applications. Organic materials have many beneficial properties, including the ability to form networks and matrices to create three-dimensional structures from the nanometer to centimeter scale, biodegradability, the versatility to use both synthetic and natural precursors, and ease of chemical modifications, while inorganic materials offer highly controllable nanoscale features, can entrap and protect therapeutics, and have degradation properties that can be tightly regulated. Here in, we discuss the current state-of-the-art in active pharmaceutical ingredient delivery from biomaterial hybrids, demonstrate the added levels of control that these hybrid biomaterials offer, and give our perspective on future innovations in the field.
Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes

Background In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D. Methods A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices. Results There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported. Conclusions Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.
Novel saccharin analogs as promising antibacterial and anticancer agents: synthesis, DFT, POM analysis, molecular docking, molecular dynamic simulations, and cell-based assay

Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide (1) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ6,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide (5), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against Staphylococcus and Escherichia coli , and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30–35 mm . In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC50 values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds’ theoretical studies.
Simultaneous visualization of RNA transcripts and proteins in whole-mount mouse preimplantation embryos using single-molecule fluorescence in situ hybridization and immunofluorescence microscopy

Whole-mount single-molecule RNA fluorescence in situ hybridization (smRNA FISH) in combination with immunofluorescence (IF) offers great potential to study long non-coding RNAs (lncRNAs): their subcellular localization, their interactions with proteins, and their function. Here, we describe a step-by-step, optimized, and robust protocol that allows detection of multiple RNA transcripts and protein molecules in whole-mount preimplantation mouse embryos. Moreover, to simultaneously detect protein and enable RNA probe penetration for the combined IF/smRNA FISH technique, we performed IF before smRNA FISH. We removed the zona pellucida, used Triton X-100 to permeabilize the embryos, and did not use a proteinase digestion step so as to preserve the antigens. In addition, we modified the IF technique by using RNase-free reagents to prevent RNA degradation during the IF procedure. Using this modified sequential IF/smRNA FISH technique, we have simultaneously detected protein, lncRNA, and mRNA in whole-mount preimplantation embryos. This reliable and robust protocol will contribute to the developmental biology and RNA biology fields by providing information regarding 3D expression patterns of RNA transcripts and proteins, shedding light on their biological function.
Inhibition of phosphodiesterase: A novel therapeutic target for the treatment of mild cognitive impairment and Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia and is ranked as the 6th leading cause of death in the US. The prevalence of AD and dementia is steadily increasing and expected cases in USA is 14.8 million by 2050. Neuroinflammation and gradual neurodegeneration occurs in Alzheimer’s disease. However, existing medications has limitation to completely abolish, delay, or prevent disease progression. Phosphodiesterases (PDEs) are large family of enzymes to hydrolyze the 3’-phosphodiester links in cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in signal-transduction pathways for generation of 5’-cyclic nucleotides. It plays vital role to orchestrate several pharmacological activities for proper cell functioning and regulating the levels of cAMP and cGMP. Several evidence has suggested that abnormal cAMP signaling is linked to cognitive problems in neurodegenerative disorders like AD. Therefore, the PDE family has become a widely accepted and multipotential therapeutic target for neurodegenerative diseases. Notably, modulation of cAMP/cGMP by phytonutrients has a huge potential for the management of AD. Natural compounds have been known to inhibit phosphodiesterase by targeting key enzymes of cGMP synthesis pathway, however, the mechanism of action and their therapeutic efficacy has not been explored extensively. Currently, few PDE inhibitors such as Vinpocetine and Nicergoline have been used for treatment of central nervous system (CNS) disorders. Considering the role of flavonoids to inhibit PDE, this review discussed the therapeutic potential of natural compounds with PDE inhibitory activity for the treatment of AD and related dementia. Graphical Abstract PDE inhibitors for the treatment of Alzheimer’s disease.
Function of Vitellogenin receptor gene in reproductive regulation of Zeugodacus cucurbitae (Coquillett) after short-term high-temperature treatment

Climate change has increased the frequency of extreme heat events. Zeugodacus cucurbitae (Coquillett) is an important tropical pest that typically changes its reproductive strategies in response to extremely high temperatures. Newly emerged adults of three consecutive generations (F1, F2, and F3) of Z. cucurbitae (Coquillett) were exposed to 25°C, 33°C, 37°C, 41°C, and 45°C treatments for 1 h to clarify the effects of short-term high temperatures on its reproduction. The influence of these temperatures on reproduction was evaluated using indicators, such as egg number. Newly emerged adults were exposed to 25°C and 45°C treatments for 1 h, and the expression of Vitellogenin receptor (VgR) gene in females was interfered with siRNA, and silencing efficiency of RNAi was evaluated. Results showed that short-term high temperatures, except for F1 treated at 45°C for 1 h to stimulate oviposition, exert a general adverse effect on the reproduction of Z. cucurbitae (Coquillett). All F3 died after the 45°C treatment for 1 h. Silencing of the VgR gene resulted in the significant downregulation of VgR gene expression at both 24 and 72 h. The egg number, oviposition days, and hatchability of eggs were significantly lower than those of other treatment groups after interference, and the inhibition effect of egg number was the most evident, with a decrease of 88.4% and 95.2% at 25°C and 45°C, respectively, compared with that of the Control Check (CK). Ovarian development speed and diameter were also significantly lower than those of other treatment groups after the interference. The results of this study can provide a theoretical reference for the integrated control of Z. cucurbitae (Coquillett) during high-temperature seasons.
Identification of long non-coding RNAs involved in floral scent of Rosa hybrida

Long non-coding RNAs (lncRNAs) were found to play important roles in transcriptional, post-transcriptional, and epigenetic gene regulation in various biological processes. However, lncRNAs and their regulatory roles remain poorly studied in horticultural plants. Rose is economically important not only for their wide use as garden and cut flowers but also as important sources of natural fragrance for perfume and cosmetics industry, but presently little was known about the regulatory mechanism of the floral scent production. In this paper, a RNA-Seq analysis with strand-specific libraries, was performed to rose flowers in different flowering stages. The scented variety ‘Tianmidemeng’ (Rosa hybrida) was used as plant material. A total of 13,957 lncRNAs were identified by mining the RNA-Seq data, including 10,887 annotated lncRNAs and 3070 novel lncRNAs. Among them, 10,075 lncRNAs were predicted to possess a total of 29,622 target genes, including 54 synthase genes and 24 transcription factors related to floral scent synthesis. 425 lncRNAs were differentially expressed during the flowering process, among which 19 were differentially expressed among all the three flowering stages. Using weighted correlation network analysis (WGCNA), we correlate the differentially-expressed lncRNAs to synthesis of individual floral scent compounds. Furthermore, regulatory function of one of candidate lncRNAs for floral scent synthesis was verified using VIGS method in the rose. In this study, we were able to show that lncRNAs may play important roles in floral scent production in the rose. This study also improves our understanding of how plants regulate their secondary metabolism by lncRNAs.
The impact of BMI on long-term anthropometric and metabolic outcomes in girls with idiopathic central precocious puberty treated with GnRHas

Background Gonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes. Methods This was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau’s method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese). Results Fifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 ± 0.81 vs. 7.06 ± 1.61 years, respectively; p < 0.05). In the study population, nFH/FH was in line with the target height (TH) (p = 0.54), with a mean absolute height gain of 11.82 ± 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 ± 2.15 vs. 2.10 ± 0.81 years, respectively; p < 0.05) and the age at menarche was younger (group A vs. group B: 10.56 ± 1.01 vs. 11.44 ± 0.85 years, respectively; p < 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (p = 0.012), despite the fact that BMI SDS significantly increased in group A only (p < 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (p = 0.030). Conclusions Our results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI.