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Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to end-stage renal disease, necessitating long-term dialysis or kidney transplantation. Alleviating inflammation responses has become the standard approach in CKD management. Medications such as statins, metformin, and GLP-1 agonists, initially developed for treating metabolic dysregulation, demonstrate promising renal therapeutic benefits. The rising popularity of herbal remedies and supplements, perceived as natural antioxidants, has spurred investigations into their potential efficacy. Notably, lactoferrin, Boerhaavia diffusa, Amauroderma rugosum, and Ganoderma lucidum are known for their anti-inflammatory and antioxidant properties and may support kidney function preservation. However, the mechanisms underlying the effectiveness of Western medications and herbal remedies in alleviating inflammation and oxidative stress occurring in renal dysfunction are not completely known. This review aims to provide a comprehensive overview of CKD treatment strategies and renal function preservation and critically discusses the existing literature's limitations whilst offering insight into the potential antioxidant effects of these interventions. This could provide a useful guide for future clinical trials and facilitate the development of effective treatment strategies for kidney functions.

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INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

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Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.

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Artificial intelligence (AI) is a rapidly evolving field of computer science that involves the development of computational programs that can mimic human intelligence. In particular, machine learning and deep learning models have enabled the identification and grouping of patterns within data, leading to the development of AI systems that have been applied in various areas of hematology, including digital pathology, alpha thalassemia patient screening, cytogenetics, immunophenotyping, and sequencing. These AI-assisted methods have shown promise in improving diagnostic accuracy and efficiency, identifying novel biomarkers, and predicting treatment outcomes. However, limitations such as limited databases, lack of validation and standardization, systematic errors, and bias prevent AI from completely replacing manual diagnosis in hematology. In addition, the processing of large amounts of patient data and personal information by AI poses potential data privacy issues, necessitating the development of regulations to evaluate AI systems and address ethical concerns in clinical AI systems. Nonetheless, with continued research and development, AI has the potential to revolutionize the field of hematology and improve patient outcomes. To fully realize this potential, however, the challenges facing AI in hematology must be addressed and overcome.

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BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

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Speaking with a foreign accent has often been thought to carry several disadvantages. Here, we probe a potential social advantage of non-native compared to native speakers using spoken utterances that either obey or violate the pragmatic principle of Informativeness. In Experiment 1, we show that listeners form different impressions of native and non-native speakers with identical pragmatic behavior: in a context in which omitting information could be deceptive, people rated underinformative speakers more negatively on trustworthiness and interpersonal appeal compared to informative speakers, but this tendency was mitigated for speakers with foreign accents. Furthermore, this mitigating effect was strongest for less proficient non-native speakers who were presumably not fully responsible for their linguistic choices. In Experiment 2, social lenience for non-native speakers emerged even in a non-deceptive context. Contrary to previous studies, there was no consistent global bias against non-native speakers in either experiment, despite their lower intelligibility. Thus the fact that non-native speakers have imperfect control of the linguistic signal affects pragmatic inferences and social evaluation in ways that can lead to surprising social benefits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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The outbreak of COVID-19 has positively impacted the NGS market recently. Targeted sequencing (TS) has become an important routine technique in both clinical and research settings, with advantages including high confidence and accuracy, a reasonable turnaround time, relatively low cost, and fewer data burdens with the level of bioinformatics or computational demand. Since there are no clear consensus guidelines on the wide range of next-generation sequencing (NGS) platforms and techniques, there is a vital need for researchers and clinicians to develop efficient approaches, especially for the molecular diagnosis of diseases in the emergency of the disease and the global pandemic outbreak of COVID-19. In this review, we aim to summarize different methods of TS, demonstrate parameters for TS assay designs, illustrate different TS panels, discuss their limitations, and present the challenges of TS concerning their clinical application for the molecular diagnosis of human diseases.

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The implementation of DP will revolutionize current practice by providing pathologists with additional tools and algorithms to improve workflow. Furthermore, DP will open up opportunities for development of AI-based tools for more precise and reproducible diagnosis through computational pathology. One of the key features of AI is its capability to generate perceptions and recognize patterns beyond the human senses. Thus, the incorporation of AI into DP can reveal additional morphological features and information. At the current rate of AI development and adoption of DP, the interest in computational pathology is expected to rise in tandem. There have already been promising developments related to AI-based solutions in prostate cancer detection; however, in the GI tract, development of more sophisticated algorithms is required to facilitate histological assessment of GI specimens for early and accurate diagnosis. In this review, we aim to provide an overview of the current histological practices in AP laboratories with respect to challenges faced in image preprocessing, present the existing AI-based algorithms, discuss their limitations and present clinical insight with respect to the application of AI in early detection and diagnosis of GI cancer.

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Many different prosodic cues can help listeners predict upcoming speech. However, no research to date has assessed listeners' processing of preceding prosody from different speakers. The present experiments examine (1) whether individual speakers (of the same language variety) are likely to vary in their production of preceding prosody; (2) to the extent that there is talker variability, whether listeners are flexible enough to use any prosodic cues signaled by the individual speaker; and (3) whether types of prosodic cues (e.g., F0 versus duration) vary in informativeness. Using a phoneme-detection task, we examined whether listeners can entrain to different combinations of preceding prosodic cues to predict where focus will fall in an utterance. We used unsynthesized sentences recorded by four female native speakers of Australian English who happened to have used different preceding cues to produce sentences with prosodic focus: a combination of pre-focus overall duration cues, F0 and intensity (mean, maximum, range), and longer pre-target interval before the focused word onset (Speaker 1), only mean F0 cues, mean and maximum intensity, and longer pre-target interval (Speaker 2), only pre-target interval duration (Speaker 3), and only pre-focus overall duration and maximum intensity (Speaker 4). Listeners could entrain to almost every speaker's cues (the exception being Speaker 4's use of only pre-focus overall duration and maximum intensity), and could use whatever cues were available even when one of the cue sources was rendered uninformative. Our findings demonstrate both speaker variability and listener flexibility in the processing of prosodic focus.

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INTRODUCTION: In situ hybridization (ISH) plays an important role in the field of molecular diagnostics, especially in an anatomical pathology laboratory. ISH is a technique that can detect the targeted DNA or RNA sequences in tissue sections from frozen or fixed materials with labeled DNA or RNA probes. Radioactive and non-radioactive probes are the two major probes that can be used to label the targeted nucleic acids. AREAS COVERED: Two decades after the Human Genome Project, ISH has not only simply been applied to identify the chromosomal location of a human gene but has also been extensively applied to gene expressions studies and utilized for clinical diagnosis, especially for the determination of biomarkers for breast and ovarian cancers - human epidermal growth factor receptor 2. Duchenne muscular dystrophy, Cri-du-chat syndrome, Angelman syndrome, PraderWilli syndrome, cystic fibrosis, and trisomy are diseases that can also be detected by ISH. In this review, the basic principles, historical development, advantages and disadvantages, enhancement in reporting molecules and probes, advancement in detection methods, in situ PCR, clinical applications and novel applications of ISH will be discussed. EXPERT OPINION: With the advancement in ISH technologies and appropriate training, diagnosis can be improved in Anatomical Pathology.

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Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.

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In English and Dutch, listeners entrain to prosodic contours to predict where focus will fall in an utterance. Here, we ask whether this strategy is universally available, even in languages with very different phonological systems (e.g., tone versus non-tone languages). In a phoneme detection experiment, we examined whether prosodic entrainment also occurs in Mandarin Chinese, a tone language, where the use of various suprasegmental cues to lexical identity may take precedence over their use in salience. Consistent with the results from Germanic languages, response times were facilitated when preceding intonation predicted high stress on the target-bearing word, and the lexical tone of the target word (i.e., rising versus falling) did not affect the Mandarin listeners' response. Further, the extent to which prosodic entrainment was used to detect the target phoneme was the same in both English and Mandarin listeners. Nevertheless, native Mandarin speakers did not adopt an entrainment strategy when the sentences were presented in English, consistent with the suggestion that L2 listening may be strained by additional functional load from prosodic processing. These findings have implications for how universal and language-specific mechanisms interact in the perception of focus structure in everyday discourse.

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Correct counting respects the stable order principle whereby the count terms are recited in a fixed order every time. The 4 experiments reported here tested whether precounting infants recognize and prefer correct stable-ordered counting. The authors introduced a novel preference paradigm in which infants could freely press two buttons to activate videos of counting events. In the "correct" counting video, number words were always recited in the canonical order ("1, 2, 3, 4, 5, 6"). The "incorrect" counting video was identical except that the number words were recited in a random order (e.g., "5, 3, 1, 6, 4, 2"). In Experiment 1, 18-month-olds (n = 21), but not 15-month-olds (n = 24), significantly preferred to press the button that activated correct counting events. Experiment 2 revealed that English-learning 18-month-olds' (n = 21) preference for stable-ordered counting disappeared when the counting was done in Japanese. By contrast, Experiment 3 showed that multilingual 18-month-olds (n = 24) preferred correct stable-ordered counting in an unfamiliar foreign language. In Experiment 4, multilingual 18-month-olds (N = 21) showed no preference for stable-ordered alphabet sequences, ruling out some alternative explanations for the Experiment 3 results. Overall these findings are consistent with the idea that implicit recognition of the stable order principle of counting is acquired by 18 months of age, and that learning more than one language may accelerate infants' understanding of abstract counting principles. (PsycINFO Database Record

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BACKGROUND: Clinical practice guidelines (CPGs) aim to improve patient care, but their use remains variable. We explored attitudes that influence CPG use amongst newly qualified doctors. METHODS: A self-completed, anonymous questionnaire was sent to all Foundation Doctors in England and Wales between December 2012 and May 2013. We included questions designed to measure the 11 domains of the validated Theoretical Domains Framework (TDF). We correlated these responses to questions assessing current and future intention to use CPGs. RESULTS: A total of 13,138 doctors were invited of which 1693 [corrected] (13 %) responded. 1,035 (62.5 %) reported regular CPG use with 575 (34.4 %) applying CPGs 2-3 times per week. A significant minority of 606 (36.6 %) declared an inability to critically appraise evidence. Despite efforts to design a questionnaire that captured the domains of the TDF, the domain scales created had low internal reliability. Using previously published studies and input from an expert statistical group, an alternative model was sought using exploratory factor analysis. Five alternative domains were identified. These were judged to represent: "confidence", "familiarity", "commitment and duty", "time" and "perceived benefits". Using regression analyses, the first three were noted as consistent predictors of both current and future intentions to use CPGs in decreasing strength order. CONCLUSIONS: In this large survey of newly qualified doctors, "confidence", "familiarity" and "commitment and duty" were identified as domains that influence use of CPGs in frontline practice. Additionally, a significant minority were not confident in critically appraising evidence. Our findings suggest a number of approaches that may be taken to improve junior doctors' commitment to CPGs through processes that increase their confidence and familiarity in using CPGs. Despite limitations of a self-reported survey and potential non-response bias, these findings are from a large representative sample and a review of existing implementation strategies may be warranted based on these findings.

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A random walk with exponentially varying step, modeling damped or amplified diffusion, is studied. Each step is equal to the previous one multiplied by a step factor s (01/s relating different processes. For s<1/2 and s>2, the process is retrodictive (i.e., every final position can be reached by a unique path) and the set of all possible final points after infinite steps is fractal. For step factors in the interval [1/2,2], some cases result in smooth density distributions, other cases present overlapping self-similarity and there are values of the step factor for which the distribution is singular without a density function.