Primary clear cell adenocarcinoma of the bladder with recurrence: a case report and literature review

Clear cell carcinoma of the bladder is a rare tumor of the bladder. There are few reports available on this rare disease, and no cases with recurrence were reported. Here we present a case of 68-year-old woman with primary clear cell carcinoma of the bladder, who underwent repeat TUR-BT and tumor recurrence. We also reviewed the previous treatments and prognoses in previous case reports and evaluate the proper treatment for this disease. Once the diagnosis is determined, the radical surgery should be recommended. The recurrence is not prevented based on post-TUR intravesical therapy

Improving Factual Consistency of Text Summarization by Adversarially Decoupling Comprehension and Embellishment Abilities of LLMs

Despite the recent progress in text summarization made by large language models (LLMs), they often generate summaries that are factually inconsistent with original articles, known as "hallucinations" in text generation. Unlike previous small models (e.g., BART, T5), current LLMs make fewer silly mistakes but more sophisticated ones, such as imposing cause and effect, adding false details, overgeneralizing, etc. These hallucinations are challenging to detect through traditional methods, which poses great challenges for improving the factual consistency of text summarization. In this paper, we propose an adversarially DEcoupling method to disentangle the Comprehension and EmbellishmeNT abilities of LLMs (DECENT). Furthermore, we adopt a probing-based efficient training to cover the shortage of sensitivity for true and false in the training process of LLMs. In this way, LLMs are less confused about embellishing and understanding; thus, they can execute the instructions more accurately and have enhanced abilities to distinguish hallucinations. Experimental results show that DECENT significantly improves the reliability of text summarization based on LLMs

SpokenWOZ: A Large-Scale Speech-Text Benchmark for Spoken Task-Oriented Dialogue Agents

Task-oriented dialogue (TOD) models have made significant progress in recent years. However, previous studies primarily focus on datasets written by annotators, which has resulted in a gap between academic research and real-world spoken conversation scenarios. While several small-scale spoken TOD datasets are proposed to address robustness issues such as ASR errors, they ignore the unique challenges in spoken conversation. To tackle the limitations, we introduce SpokenWOZ, a large-scale speech-text dataset for spoken TOD, containing 8 domains, 203k turns, 5.7k dialogues and 249 hours of audios from human-to-human spoken conversations. SpokenWOZ further incorporates common spoken characteristics such as word-by-word processing and reasoning in spoken language. Based on these characteristics, we present cross-turn slot and reasoning slot detection as new challenges. We conduct experiments on various baselines, including text-modal models, newly proposed dual-modal models, and LLMs, e.g., ChatGPT. The results show that the current models still have substantial room for improvement in spoken conversation, where the most advanced dialogue state tracker only achieves 25.65% in joint goal accuracy and the SOTA end-to-end model only correctly completes the user request in 52.1% of dialogues. The dataset, code, and leaderboard are available: https://spokenwoz.github.io/SpokenWOZ-github.io/

Non-volatile Components and Filamentary Morphology of Fresh Leaves of Zigui Simian Tea

To investigate the characteristics of quality formation of Simian tea, the non-volatile components, mineral elements and filamentary structure of fresh leaves from different positions of ‘Simian Tucha’ tea plants, endemic to Zigui, were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), inductively coupled plasma optical emission spectrometry (ICP-OES), and scanning electron microscopy (SEM). The results showed that the non-volatile components were more abundant in the leaves with higher tenderness, with amino acids, alkaloids, catechins, and aroma glycosides being mainly concentrated in the first (L1) and second leaves (L2). Theanine, organic acids, and flavonoids were mainly concentrated in the third leaf (L3), while the content of non-volatile components in the older leaves was relatively lower. The accumulation of mineral elements greatly varied among tea leaves with different tenderness. The contents of nitrogen, phosphorus, potassium, zinc, and copper in L1 (32.41 mg/g, 4.53 mg/g, 15.65 mg/g, 45.45 μg/g, and 10.75 μg/g, respectively) and L2 (30.60 mg/g, 3.70 mg/g, 14.12 mg/g, 35.82 μg/g, 9.02 μg/g, respectively) were higher than those in older leaves. The contents of iron, manganese, and calcium were higher in mature leaves. Through SEM observation, it was found that the filamentary structure of Simian tea leaves consisted of two forms, triple-stranded coil and single-stranded coil, and was distributed in the internal thread or ringed vessels of the xylem in the vascular bundles in the midvein and lateral veins, and the number of filamentary structures was higher in the second, third and fourth leaves than that in buds and L1

Genome-wide Analysis of the Interplay Between Chromatin-associated Rna and 3d Genome Organization in Human Cells

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization

Brain Structural Alterations in Left-Behind Children: A Magnetic Resonance Imaging Study

Parental migration has caused millions of children left behind, especially in China and India. Left-behind children (LBC) have a high risk of mental disorders and may present negative life outcomes in the future. However, little is known whether there are cerebral structural alterations in LBC in relative to those with parents. This study is to explore the effect of parental migration on brain maturation by comparing gray matter volume (GMV) and fractional anisotropy (FA) of LBC with well-matched non-LBC. Thirty-eight LBC (21 boys, age = 9.60 ± 1.8 years) and 30 non-LBC (19 boys, age = 10.00 ± 1.95 years) were recruited and underwent brain scans in 3.0 T MR. Intelligence quotient and other factors including family income, guardians’ educational level and separation time were also acquired. GMV and FA were measured for each participant and compared between groups using 2-sample t-tests with atlas-based analysis. Compared to non-LBC, LBC exhibited greater GMV in emotional and cortico-striato-thalamo-cortical circuits, and altered FA in bilateral superior occipitofrontal fasciculi and right medial lemniscus (p < 0.05, Cohen’s d > 0.89, corrected for false-discovery rate). Other factors including family income, guardians’ educational level and separation time were not associated with these brain changes. Our study provides empirical evidence of altered brain structure in LBC compared to non-LBC, responsible for emotion regulation and processing, which may account for mental disorders and negative life outcome of LBC. Our study suggests that absence of direct biological parental care may impact children’s brain development. Therefore, public health efforts may be needed to provide additional academic and social/emotional supports to LBC when their parents migrate to seeking better economic circumstances, which has become increasingly common in developing countries

Characterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR

mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival, and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here, we report the characterization of Torin2, a second-generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors. Torin2 inhibited mTORC1-dependent T389 phosphorylation on S6K (RPS6KB1) with an EC[subscript 50] of 250 pmol/L with approximately 800-fold selectivity for cellular mTOR versus phosphoinositide 3-kinase (PI3K). Torin2 also exhibited potent biochemical and cellular activity against phosphatidylinositol-3 kinase–like kinase (PIKK) family kinases including ATM (EC[subscript 50], 28 nmol/L), ATR (EC[subscript 50], 35 nmol/L), and DNA-PK (EC[subscript 50], 118 nmol/L; PRKDC), the inhibition of which sensitized cells to Irradiation. Similar to the earlier generation compound Torin1 and in contrast to other reported mTOR inhibitors, Torin2 inhibited mTOR kinase and mTORC1 signaling activities in a sustained manner suggestive of a slow dissociation from the kinase. Cancer cell treatment with Torin2 for 24 hours resulted in a prolonged block in negative feedback and consequent T308 phosphorylation on Akt. These effects were associated with strong growth inhibition in vitro. Single-agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitor AZD6244 yielded a significant growth inhibition. Taken together, our findings establish Torin2 as a strong candidate for clinical evaluation in a broad number of oncologic settings where mTOR signaling has a pathogenic role

Initiation of the Hypothalamic–Pituitary–Gonadal Axis in Young Girls Undergoing Central Precocious Puberty Exerts Remodeling Effects on the Prefrontal Cortex

Central precocious puberty (CPP) has been shown to exert significant effects on psychosocial development. These early puberty-related hormones and psychosocial functional changes are considered to be associated with specific brain development. However, the biological mechanisms underlying the sculpting of human brain architecture and modulation of psychosocial transformation by puberty-related hormonal maturation remain elusive, especially during the early phase of CPP. The current investigation aims to specify the brain regions in which early hormone-related maturation effects occur during CPP and their relationships with psychological functions. 65 young girls (aged 4.3–8.0 years) underwent structural imaging on a 3T MR system, completed psychological tests and performed the gonadotropin-releasing hormone (GnRH) stimulation test to identify hormonal manifestations of hypothalamic–pituitary–gonadal axis (HPG axis) activation. Based on the GnRH test, 28 young girls were identified with CPP, whereas the other 37 girls were identified with non-central precocious puberty (NCPP). Cortical parameters were calculated and compared between the two groups after adjusting for age, weight, and height. Brain regions showing group differences were extracted and correlated with serum hormone levels and psychological parameters. The CPP girls showed thinner cortices primarily in the right rostral middle frontal cortex. This morphological difference was positively correlated with stimulated estradiol (E2) levels. Further, higher E2 levels were significantly associated with higher hyperactivity scores. Premature HPG axis activation in CPP girls at an early stage appears to exert remodeling effects on brain anatomy, primarily in the prefrontal cortex, which may affect psychological development following the emergence of robust changes in sex hormones