Miracle-dz/UniFAR-FTUs huggingface dataset:
Optical coherence tomography angiography biomarkers of microvascular alterations in RVCL-S

Background The brain and retina share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in patients with a monogenic vasculopathy using optical coherence tomography angiography (OCTA). OCT-A is a novel precise non-invasive imaging method that may provide biomarkers suitable for diagnosis and follow-up of small vessel diseases. Methods In this exploratory cross-sectional study, eleven RVCL-S patients and eleven age-matched healthy control participants were included. The size of the foveal avascular zone (FAZ) and the vascular density of the superficial capillary networks in the retina were measured by OCT-A. Results The symptomatic and presymptomatic patients showed significantly lower vascular density values than controls in the foveal region [median (IQR) 18.2% (15.8–18.6) vs. 24.4% (21.5–26.8) (p < 0.001), 29.8% (29.6–30.8) vs. 33.2% (32.0–33.6) (p = 0.002), respectively]. The FAZ was significantly larger in the symptomatic RVCL-S patients than in the control group [13,416 square pixels [7,529–22,860] vs. 1,405 square pixels [1,344–2,470] (p < 0.001)]. No significant difference was identified in measurements of FAZ comparing presymptomatic and controls. Conclusion Our findings with OCT-A demonstrated that RVCL-S causes an increase in the size of the FAZ in symptomatic RVCL-S patients compared to healthy participants. Moreover, there is a decrease in vessel density in the superficial capillary networks in both symptomatic and presymptomatic patients. In the future, newly developed precise objective instruments such as OCT (-A) may provide important tools in determining disease activity for follow up of common small vessel diseases.
Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4+ T cells: A pooled data-analysis

The main obstacle to cure HIV-1 is the latent reservoir. Antiretroviral therapy effectively controls viral replication, however, it does not eradicate the latent reservoir. Latent CD4+ T cells are extremely rare in HIV-1 infected patients, making primary CD4+ T cell models of HIV-1 latency key to understanding latency and thus finding a cure. In recent years several primary CD4+ T cell models of HIV-1 latency were developed to study the underlying mechanism of establishing, maintaining and reversing HIV-1 latency. In the search of biomarkers, primary CD4+ T cell models of HIV-1 latency were used for bulk and single-cell transcriptomics. A wealth of information was generated from transcriptome analyses of different primary CD4+ T cell models of HIV-1 latency using latently- and reactivated HIV-1 infected primary CD4+ T cells. Here, we performed a pooled data-analysis comparing the transcriptome profiles of latently- and reactivated HIV-1 infected cells of 5 in vitro primary CD4+ T cell models of HIV-1 latency and 2 ex vivo studies of reactivated HIV-1 infected primary CD4+ T cells from HIV-1 infected individuals. Identifying genes that are differentially expressed between latently- and reactivated HIV-1 infected primary CD4+ T cells could be a more successful strategy to better understand and characterize HIV-1 latency and reactivation. We observed that natural ligands and coreceptors were predominantly downregulated in latently HIV-1 infected primary CD4+ T cells, whereas genes associated with apoptosis, cell cycle and HLA class II were upregulated in reactivated HIV-1 infected primary CD4+ T cells. In addition, we observed 5 differentially expressed genes that co-occurred in latently- and reactivated HIV-1 infected primary CD4+ T cells, one of which, MSRB2, was found to be differentially expressed between latently- and reactivated HIV-1 infected cells. Investigation of primary CD4+ T cell models of HIV-1 latency that mimic the in vivo state remains essential for the study of HIV-1 latency and thus providing the opportunity to compare the transcriptome profile of latently- and reactivated HIV-1 infected cells to gain insights into differentially expressed genes, which might contribute to HIV-1 latency.
Sexually transmitted pathogens causing urethritis: A mini-review and proposal of a clinically based diagnostic and therapeutic algorithm

The purpose of this mini-review was to provide the latest information and concepts on diagnosis and treatment of the most common sexually transmitted pathogens causing urethritis. The incidence of several sexually transmitted infections that cause urethritis is increasing, and this genitourinary syndrome is among the most common reason young men see clinical care. The authors performed a literature search including the currently valid guidelines, and an overview of the most relevant pathogens is given. Moreover, the authors developed a clinically applicable diagnostic and therapeutic algorithm, because early diagnosis and correct treatment can sometimes prevent infected individuals from significant morbidity. Future research will focus on new methods to combat pathogens that cause urethritis, including vaccination.
Belief or disbelief in feedback influences the detection efficiency of the feedback concealed information test

The feedback concealed information test (fCIT) is a new variant of the CIT that added feedback about participants’ concealing performances in the classical CIT. The advantage of the fCIT is that the resulting feedback related event-related potentials (ERPs) can be used to detect concealed information. However, the detection efficiency of feedback-based ERPs varies across studies. The present experiment examined whether the extent participants believed the feedback influenced their detection efficiency. Specifically, participants did a mock crime and were then tested in a fCIT. Following the fCIT, participants were asked to report how much they believed the feedback was accurate. Results showed that there were no significant correlations between the amplitude of the feedback related negativity (FRN), feedback P300, and participants’ self-report at the group level. However, individual analyses showed that the detection efficiency of both the FRN and feedback P300 were influenced by participants’ belief about the presented feedback. The detection efficiency of the FRN and the feedback P300 was higher among participants who believed the feedback. These findings suggest that the fCIT is dependent to some extent on the participants’ level of belief in the feedback.
Altered membrane properties but unchanged intrinsic excitability and spontaneous postsynaptic currents in an aged APPswe/PS1dE9 model of Alzheimer’s disease

Neuronal hyperexcitability in Alzheimer’s disease (AD) models is thought to either contribute to the formation of amyloid beta plaques or result from their formation. Neuronal hyperexcitability has been shown in the cerebral cortex of the widely used young APPswe/PS1dE9 mice, which have accelerated plaque formation. However, it is currently unclear if hyperexcitability also occurs in CA1 hippocampal neurons of aged animals in this model. In the present work, we have compared intrinsic excitability and spontaneous synaptic inputs from CA1 pyramidal cells of 8-month-old APPswe/PS1dE9 and wildtype control mice. We find no change in intrinsic excitability or spontaneous postsynaptic currents (PSCs) between groups. We did, however, find a reduced input resistance and an increase in hyperpolarization-activated sag current. These results are consistent with findings from other aged AD model mice, including the widely used 5xFAD and 3xTg. Together these results suggest that neuronal hyperexcitability is not a consistent feature of all AD mouse models, particularly at advanced ages.
Acidic urine is associated with poor prognosis in patients with bladder cancer undergoing radical cystectomy

Purpose To assess the prognostic value of acidic urine (low urine pH) in patients with bladder cancer undergoing radical cystectomy. Materials and methods We reviewed patients enrolled in the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Cystectomy (SUPER-UC-Cx) who underwent radical cystectomy for bladder cancer between March 2016 and December 2020 at the Seoul National University Hospital. During this period, 368 patients were registered in our database. To eliminate confounding factors, we excluded patients diagnosed with non-urothelial cancer and end-stage renal disease. Results A total of 351 patients with a mean age of 69.8 ± 10.5 years and median follow-up of 16.0 months were eligible for the analysis. The mean preoperative urine pH was 6.0. The patients were divided into low (pH ≤ 5.5) and high (pH≥6.0) urine pH groups for comparison. All clinicopathological features, including the tumor size, grade, and stage were comparable between the low and high urine pH groups. A Cox regression analysis was performed to assess the independent effect of acidic urine on patient survival. A multivariate analysis showed that high T stage (T3-4) (hazard ratio (HR) 5.18, P<0.001), decreased renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2) (HR 2.29, P=0.003), and low urine pH (≤5.5) (HR 1.69, P=0.05) were associated with shortened recurrence-free survival (RFS). Regarding the overall survival (OS), high T stage (T3-4) (HR 7.15, P<0.001) and low urine pH (≤5.5) (HR 2.66, P=0.029) were significantly associated with shortened survival. A Kaplan–Meier analysis demonstrated that the acidic urine group showed shorter RFS (P=0.04) and OS (P=0.028) than the other groups. Conclusions Acidic urine was independently associated with reduced RFS and OS in patients with bladder cancer undergoing radical cystectomy. Acidic urine contributing to an acidic tumor environment may promote aggressive behavior in bladder cancer.
Wolstenholme's theorem: Its Generalizations and Extensions in the last hundred and fifty years (1862--2012)

In 1862 Wolstenholme proved that for any prime $p\ge 5$ the numerator of the fraction $$ 1+\frac 12 +\frac 13+. +\frac{1}{p-1} $$ written in reduced form is divisible by $p^2$, $(2)$ and the numerator of the fraction $$ 1+\frac{1}{2^2} +\frac{1}{3^2}+. +\frac{1}{(p-1)^2} $$ written in reduced form is divisible by $p$. The first of the above congruences, the so called {\it Wolstenholme's theorem}, is a fundamental congruence in combinatorial number theory. In this article, consisting of 11 sections, we provide a historical survey of Wolstenholme's type congruences and related problems. Namely, we present and compare several generalizations and extensions of Wolstenholme's theorem obtained in the last hundred and fifty years. In particular, we present more than 70 variations and generalizations of this theorem including congruences for Wolstenholme primes. These congruences are discussed here by 33 remarks. The Bibliography of this article contains 106 references consisting of 13 textbooks and monographs, 89 papers, 3 problems and Sloane's On-Line Enc. of Integer Sequences. In this article, some results of these references are cited as generalizations of certain Wolstenholme's type congruences, but without the expositions of related congruences. The total number of citations given here is 189.
Movement and olfactory signals: Sexually dimorphic antennae and female flightlessness in moths

Darwin argued a role for sexual selection in the evolution of male sensory structures, including insect antennae, the strength of which will depend upon the importance of early arrival at receptive females. There is remarkable variation in the nature and degree of sexual dimorphism in moth antennae, with males of some species having spectacular, feathery antennae. Although it is widely assumed that these elaborate structures provide greater sensitivity to chemical signals (sex pheromones), the factors underlying the interspecific diversity in male antennal structure and size are poorly understood. Because male antennal morphology may be affected by several female life–history traits, including flight ability, we conducted a phylogenetic comparative analysis to test how these traits are linked, using data from 93 species of moths across 11 superfamilies. Our results reveal that elaborate antennae in males have evolved more frequently in species where females are monandrous. Further, female loss of flight ability evolved more frequently in species where males have elaborate antennae. These results suggest that elaborate antennae have evolved in response to more intense male competition, arising from female monandry, and that the evolution of elaborate antennae in males has, in turn, shaped the evolution of female flightlessness.
Metabolome and RNA-seq Analysis of Responses to Nitrogen Deprivation and Resupply in Tea Plant (Camellia sinensis) Roots

Nitrogen (N) is an important contributor in regulating plant growth and development as well as secondary metabolites synthesis, so as to promote the formation of tea quality and flavor. Theanine, polyphenols, and caffeine are important secondary metabolites in tea plant. In this study, the responses of Camellia sinensis roots to N deprivation and resupply were investigated by metabolome and RNA-seq analysis. N deficiency induced content increase for most amino acids (AAs) and reduction for the remaining AAs, polyphenols, and caffeine. After N recovery, the decreased AAs and polyphenols showed a varying degree of recovery in content, but caffeine did not. Meanwhile, theanine increased in content, but its related synthetic genes were down-regulated, probably due to coordination of the whole N starvation regulatory network. Flavonoids-related pathways were relatively active following N stress according to KEGG enrichment analysis. Gene co-expression analysis revealed TCS2, AMT1;1, TAT2, TS, and GOGAT as key genes, and TFs like MYB, bHLH, and NAC were also actively involved in N stress responses in C. sinensis roots. These findings facilitate the understanding of the molecular mechanism of N regulation in tea roots and provide genetic reference for improving N use efficiency in tea plant.
Novel application of microdissection tungsten needle in total thyroidectomy with central neck dissection for papillary thyroid carcinoma

Background Energy-based devices (EBD) have been popularized in thyroidectomy worldwide. Microdissection tungsten needle (MDTN) is characterized by the ultra-sharp tip providing safe and meticulous dissection with effective hemostasis. However, little study has applied MDTN in thyroidectomy. Methods This retrospective study compared clinical data of the patients who underwent total thyroidectomy (TT) with central neck dissection (CND) using MDTN, harmonic scalpel (HS), and conventional electrocautery (CE). We assessed outcomes related to surgical efficacy and safety. The injury degree of tissue was assessed by biochemical indicators and early-stage inflammatory factors in the drainage fluid. Histological sections of the thyroid specimens were evaluated to compare levels of thermal damage by the three EBD. Results There was a significant decrease in the intraoperative blood loss, operation time and 24-hour drainage volume in the MDTN group compared to the CE group. The total drainage volume, duration of drainage, and average length of stay of the MDTN group were less compared to the CE group though they did not reach statistical significance. No disparity was observed between the MDTN group and HS group in these variables. Total costs were not significantly different among these groups. The incidence of recurrent laryngeal nerve (RLN) injury was the lowest using MDTN compared to the CE (P = 0.034) and HS (not significant). No statistical differences were observed among these groups regarding postoperative wound pain and infection, hypoparathyroidism, and postoperative hemorrhage. Analysis of biochemical indicators showed a lower level of hemoglobin in the MDTN and HS group than the CE group (P = 0.046 and 0.038, respectively) and less triglyceride in the HS group than the MDTN and CE group (P = 0.002 and 0.029, respectively) but no significant difference in cholesterol level in these groups. Early-stage inflammatory factors including TNF-α and IL-6 showed significantly higher concentration in the CE group than the MDTN and HS group. Histological sections of thyroid specimens revealed that MDTN caused the lowest degree of thermal damage followed by HS then CE. Conclusion MDTN exhibited comparable surgical efficacy and safety outcomes as HS in thyroidectomy. Therefore, MDTN is a safe and viable alternative for hemostasis in thyroidectomy.
Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV

Background Increased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marker for CVD in the general population. Methods We cross-sectionally analyzed plasma of 95 PLWH on ART and 52 controls. We measured GDF-15, fibroblast growth factor-21 (FGF-21), glucagon-like peptide-2 (GLP-2), soluble urokinase plasminogen activator receptor (suPAR), CRP, and anti-CMV and anti-EBV IgG levels. All participants had no clinical CVD and underwent coronary CT angiography with the 3D reconstruction of coronary artery atherosclerotic plaques. Total plaque volume (TPV) and low attenuation plaque volume (LAPV, defined as density <30 Hounsfield Units) were calculated (mm3). Results In both PLWH and controls, GDF-15 levels were increased in participants with presence of coronary plaque vs. without (p = 0.04 and p < 0.001, respectively) and correlated with TPV (r = 0.27, p = 0.009 and r = 0.62, p < 0.001, respectively) and LAPV (r = 0.28, p = 0.008, r = 0.60, p < 0.001, respectively). However, in a multivariate model, GDF-15 was independently associated with LAPV in controls only (adjusted OR 35.1, p = 0.04) and not in PLWH, mainly due to confounding by smoking. Other markers were not independently associated with plaque volume, except for anti-EBV IgGs in controls (adjusted OR 3.51, p = 0.02). Conclusion In PLWH, GDF-15 and smoking seemed to synergistically contribute to coronary plaque volume. Conversely, increased GDF-15 levels were associated with the presence of coronary artery plaques in people without HIV, independently of CV risk factors.
Machine learning-based screening of an epithelial-mesenchymal transition-related long non-coding RNA signature reveals lower-grade glioma prognosis and the tumor microenvironment and predicts antitumor therapy response

Epithelial-mesenchymal transition (EMT) confers high invasive and migratory capacity to cancer cells, which limits the effectiveness of tumor therapy. Long non-coding RNAs (lncRNAs) can regulate the dynamic process of EMT at different levels through various complex regulatory networks. We aimed to comprehensively analyze and screen EMT-related lncRNAs to characterize lower-grade glioma (LGG) tumor biology and provide new ideas for current therapeutic approaches. We retrieved 1065 LGG samples from the Cancer Genome Atlas and Chinese Glioma Genome Atlas by machine learning algorithms, identified three hub lncRNAs including CRNDE, LINC00665, and NEAT1, and established an EMT-related lncRNA signature (EMTrLS). This novel signature had strong prognostic value and potential clinical significance. EMTrLS described LGG genomic alterations and clinical features including gene mutations, tumor mutational burden, World Health Organization (WHO) grade, IDH status, and 1p/19q status. Notably, stratified analysis revealed activation of malignancy-related and metabolic pathways in the EMTrLS-high cohort. Moreover, the population with increased EMTrLS scores had increased cells with immune killing function. However, this antitumor immune function may be suppressed by increased Tregs and macrophages. Meanwhile, the relatively high expression of immune checkpoints explained the immunosuppressive state of patients with high EMTrLS scores. Importantly, we validated this result by quantifying the course of antitumor immunity. In particular, EMTrLS stratification enabled assessment of the responsiveness of LGG to chemotherapeutic drug efficacy and PD1 blockade. In conclusion, our findings complement the foundation of molecular studies of LGG, provide valuable insight into our understanding of EMT-related lncRNAs, and offer new strategies for LGG therapy.
2-(1,2,4-triazole-5-yl)-1,3,4-oxadiazole as a novel building block for energetic materials

The exploration of novel nitrogen-rich heterocyclic building blocks is of importance in the field of energetic materials. A series of 2-(1,2,4-triazole-5-yl)-1,3,4-oxadiazole derivatives based on a new energetic skeleton have been first synthesized by a simple synthetic strategy. All three compounds are well-characterized by IR spectroscopy, NMR spectroscopy and thermal analysis. The compounds 5 and 8 are further characterized by single-crystal X-ray diffraction analysis. 8 and its salts (8a-8c) possess relative high decomposition temperature and low sensitivity, while 5 exhibits low decomposition temperature and high sensitivity. According to EXPLO5 calculation results of detonation performance, both 5 and 8 display acceptable detonation velocities (D) of 8450 m/s and 8130 m/s and detonation pressures (P) of 31.6 GPa and 29.2 GPa, respectively. Furthermore, 5 containing a rare diazonium ylide structure shows high impact sensitivity (4.5 J), making it has a potential as a primary explosive. Graphical Abstract
A platform for automated and label-free monitoring of morphological features and kinetics of spheroid fusion

Spheroids are widely applied as building blocks for biofabrication of living tissues, where they exhibit spontaneous fusion toward an integrated structure upon contact. Tissue fusion is a fundamental biological process, but due to a lack of automated monitoring systems, the in-depth characterization of this process is still limited. Therefore, a quantitative high-throughput platform was developed to semi-automatically select doublet candidates and automatically monitor their fusion kinetics. Spheroids with varying degrees of chondrogenic maturation (days 1, 7, 14, and 21) were produced from two different cell pools, and their fusion kinetics were analyzed via the following steps: (1) by applying a novel spheroid seeding approach, the background noise was decreased due to the removal of cell debris while a sufficient number of doublets were still generated. (2) The doublet candidates were semi-automatically selected, thereby reducing the time and effort spent on manual selection. This was achieved by automatic detection of the microwells and building a random forest classifier, obtaining average accuracies, sensitivities, and precisions ranging from 95.0% to 97.4%, from 51.5% to 92.0%, and from 66.7% to 83.9%, respectively. (3) A software tool was developed to automatically extract morphological features such as the doublet area, roundness, contact length, and intersphere angle. For all data sets, the segmentation procedure obtained average sensitivities and precisions ranging from 96.8% to 98.1% and from 97.7% to 98.8%, respectively. Moreover, the average relative errors for the doublet area and contact length ranged from 1.23% to 2.26% and from 2.30% to 4.66%, respectively, while the average absolute errors for the doublet roundness and intersphere angle ranged from 0.0083 to 0.0135 and from 10.70 to 13.44°, respectively. (4) The data of both cell pools were analyzed, and an exponential model was used to extract kinetic parameters from the time-series data of the doublet roundness. For both cell pools, the technology was able to characterize the fusion rate and quality in an automated manner and allowed us to demonstrate that an increased chondrogenic maturity was linked with a decreased fusion rate. The platform is also applicable to other spheroid types, enabling an increased understanding of tissue fusion. Finally, our approach to study spheroid fusion over time will aid in the design of controlled fabrication of “assembloids” and bottom-up biofabrication of living tissues using spheroids.