Evaluation of Rapid Immunochromatographic Tests for Norovirus in Neonatal and Infant Faecal Specimens

Objectives: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. Methods: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. Results: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged Conclusions: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period

Resting-state functional connectivity-based biomarkers and functional MRI-based neurofeedback for psychiatric disorders: a challenge for developing theranostic biomarkers

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., theranostic biomarker) is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce recent approach for creating a theranostic biomarker, which consists mainly of two parts: (i) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (ii) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use.Comment: 46 pages, 5 figure

The right temporoparietal junction during a cooperation dilemma: An rTMS study

Cooperation enhances interpersonal communication and nurtures society. However, efforts to socially cooperate may often evoke conflict. Individuals may selfishly pursue a greater reward or success by exploiting the efforts of other individuals or taking unnecessary risk to oneself. Such a cooperation dilemma is highly prevalent in real life; thus, it has been studied in various disciplines. Although published functional magnetic resonance imaging studies have shown the involvement of the right temporoparietal junction (TPJ) in resolving a dilemma through cooperation, a causal relationship between the two has rarely been explored. Hence, we investigated this issue by combining repetitive transcranial magnetic stimulation with a priority game task (modified snowdrift game). In this game task, participants and opponent players jointly faced a problem whereby their collaboration was anticipated to defuse the situation. This conflicted with a choice in the participant's self-interest that was more rewarding but risky. We further included conditions with and without explicit social cues using figures describing elderly/pregnant passengers in the game opponent's car, and measured participants' prosocial traits to examine any cue-induced effect as well as the personality-cooperation relationship, respectively. The cooperation ratio was not statistically different in both the no-cue and with-cue conditions between the sham stimulation and inhibitory continuous theta burst stimulation (cTBS). However, after cTBS, in the no-cue condition, the strength of the association between cooperation ratio and empathy traits decreased significantly. These results add to our knowledge about the right TPJ's role in social cognition, which may be extraordinarily complex. This topic is deserving of further examination

Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases

Tanaka M., Shirakura K., Takayama Y., et al. Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases. Communications Biology 7, 599 (2024); https://doi.org/10.1038/s42003-024-06317-z .Accumulating evidence suggests that endothelial cells can be useful therapeutic targets. One of the potential targets is an endothelial cell-specific protein, Roundabout4 (ROBO4). ROBO4 has been shown to ameliorate multiple diseases in mice, including infectious diseases and sepsis. However, its mechanisms are not fully understood. In this study, using RNA-seq analysis, we found that ROBO4 downregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2. Mechanistic analysis reveals that ROBO4 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1) and TNF receptor-associated factor 7 (TRAF7), a ubiquitin E3 ligase. In this complex, ROBO4 enhances IQGAP1 ubiquitination through TRAF7, inhibits prolonged RAC1 activation, and decreases PTGS2 expression in inflammatory endothelial cells. In addition, Robo4-deficiency in mice exacerbates PTGS2-associated inflammatory diseases, including arthritis, edema, and pain. Thus, we reveal the molecular mechanism by which ROBO4 suppresses the inflammatory response and vascular hyperpermeability, highlighting its potential as a promising therapeutic target for inflammatory diseases

Seven-Signal Proteomic Signature for Detection of Operable Pancreatic Ductal Adenocarcinoma and Their Discrimination from Autoimmune Pancreatitis

There is urgent need for biomarkers that provide early detection of pancreatic ductal adenocarcinoma (PDAC) as well as discrimination of autoimmune pancreatitis, as current clinical approaches are not suitably accurate for precise diagnosis. We used mass spectrometry to analyze protein profiles of more than 300 plasma specimens obtained from PDAC, noncancerous pancreatic diseases including autoimmune pancreatitis patients and healthy subjects. We obtained 1063 proteomic signals from 160 plasma samples in the training cohort. A proteomic signature consisting of 7 mass spectrometry signals was used for construction of a proteomic model for detection of PDAC patients. Using the test cohort, we confirmed that this proteomic model had discrimination power equal to that observed with the training cohort. The overall sensitivity and specificity for detection of cancer patients were 82.6% and 90.9%, respectively. Notably, 62.5% of the stage I and II cases were detected by our proteomic model. We also found that 100% of autoimmune pancreatitis patients were correctly assigned as noncancerous individuals. In the present paper, we developed a proteomic model that was shown able to detect early-stage PDAC patients. In addition, our model appeared capable of discriminating patients with autoimmune pancreatitis from those with PDAC