Nanomaterials in the treatment and diagnosis of rheumatoid arthritis: Advanced approaches.

Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

Factors associated with sleep quality in patients undergoing cardiac surgery: A longitudinal study.

BACKGROUND: Poor sleep quality is associated with multiple factors in cardiac surgery patients. AIM: To examine the trajectory of sleep quality and its associated factors over 3 months in Taiwanese patients undergoing cardiac surgery. STUDY DESIGN: A longitudinal study. This study enrolled 95 patients undergoing cardiac surgery in northern Taiwan. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before surgery, at discharge, and at 1 month and 3 months postsurgery. RESULTS: The majority of participants reported poor sleep quality before cardiac surgery (76.8%) and at discharge (81.6%), and they showed significant improvements in sleep quality at 1 month (B = -0.93, p = .023) and 3 months postsurgery (B = -1.50, p < .001). Significant daytime sleepiness was reported by 25.3% of patients before cardiac surgery, and this proportion significantly decreased at 3 months postsurgery (B = -2.59, p < .001). The significant predictors of sleep quality in cardiac surgery patients were symptom distress, sleep medications, occupation, left ventricular ejection fraction, ACE-I drugs and potassium ions, which explained 53.7% of the total variance in sleep quality. Having a nap habit was an independent predictor of daytime sleepiness in cardiac surgery patients, which could explain 3.7% of the total variation. CONCLUSION: Poor sleep quality was common in patients undergoing cardiac surgery and was associated with multiple factors, including symptom distress, cardiac function, medications, and psychosocial and environmental factors. RELEVANCE TO CLINICAL PRACTICE: Poor sleep quality was observed in cardiac surgical patients before surgery and at discharge postsurgery. Patient education on symptom management, medication adherence and sleep hygiene are suggested to improve sleep quality in patients undergoing cardiac surgery.

Engineering stable and non-immunogenic immunoenzymes for cancer therapy via in situ generated prodrugs.

Engineering human enzymes for therapeutic applications is attractive but introducing new amino acids may adversely affect enzyme stability and immunogenicity. Here we used a mammalian membrane-tethered screening system (ECSTASY) to evolve human lysosomal beta-glucuronidase (hBG) to hydrolyze a glucuronide metabolite (SN-38G) of the anticancer drug irinotecan (CPT-11). Three human beta-glucuronidase variants (hBG3, hBG10 and hBG19) with 3, 10 and 19 amino acid substitutions were identified that display up to 40-fold enhanced enzymatic activity, higher stability than E. coli beta-glucuronidase in human serum, and similar pharmacokinetics in mice as wild-type hBG. The hBG variants were two to three orders of magnitude less immunogenic than E. coli beta-glucuronidase in hBG transgenic mice. Intravenous administration of an immunoenzyme (hcc49-hBG10) targeting a sialyl-Tn tumor-associated antigen to mice bearing human colon xenografts significantly enhanced the anticancer activity of CPT-11 as measured by tumor suppression and mouse survival. Our results suggest that genetically-modified human enzymes represent a good alternative to microbially-derived enzymes for therapeutic applications.

Safety, Tolerability, and Preliminary Efficacy of Serplulimab, a Novel Anti-PD-1 Antibody, in Patients with Metastatic or Recurrent Solid Tumors: A Phase I Study.

BACKGROUND: Serplulimab is a novel, recombinant, humanized, monoclonal, anti-programmed death 1 antibody with a similar or better affinity and pre-clinical antitumor activity than pembrolizumab and nivolumab. OBJECTIVE: This phase I, open-label, dose-escalation study evaluated serplulimab in patients with advanced solid tumors. The second interim analysis of the dose-finding phase is reported here. METHODS: Adult patients with histologically confirmed metastatic/recurrent solid tumors who had progressed on, or were intolerant to/clinically unsuitable for standard treatment, were enrolled. Four intravenous serplulimab dose levels were evaluated: 0.3, 1.0, 3.0, and 10.0 mg/kg every 2 weeks in 28-day cycles for up to 2 years. Primary endpoints were the incidence of treatment-emergent adverse events and the maximum tolerated dose. RESULTS: By 27 July, 2020 (data cut-off), 29 patients with stage IV disease (34.5% with lung cancer) received one or more doses of serplulimab. One (3.4%) patient had completed treatment and 26 (89.7%) had discontinued from the study. The maximum tolerated dose was not reached. Twenty-two (75.9%) patients experienced treatment-emergent adverse events related to serplulimab, most frequently nausea (24.1%), with no notable differences in incidence between dose cohorts; of these, grade ≥ 3 events occurred in four (13.8%) patients. Pharmacokinetic data demonstrated minimal accumulation of serplulimab after repeated administration. Functional programmed death 1 blockade was observed across dose levels. Objective response and disease control rates were 8.0 and 60.0%, respectively. CONCLUSIONS: Serplulimab was well tolerated and demonstrated antitumor activity. These data support further study of serplulimab in larger patient populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03468751 (19 March, 2018).

Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month.

PURPOSE: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.

Epigenetic downregulation of O6-methylguanine-DNA methyltransferase contributes to chronic hexavalent chromium exposure-caused genotoxic effect and cell transformation.

Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer and other types of cancer in humans, although the mechanism of Cr(VI) carcinogenesis remains elusive. Cr(VI) has been considered as a genotoxic carcinogen, but accumulating evidence indicates that Cr(VI) also causes various epigenetic toxic effects that play important roles in Cr(VI) carcinogenesis. However, it is not clear how Cr(VI)-caused epigenetic dysregulations contributes to Cr(VI) carcinogenesis. This study investigates whether Cr(VI) epigenetic toxic effect has an impact on its genotoxic effect. It was found that chronic low dose of Cr(VI) exposure time-dependently down-regulates the expression of a critical DNA damage repair protein O6-methylguanine-DNA methyltransferase (MGMT), leading to the increases of the levels of the highly mutagenic and carcinogenic DNA lesion O6-methylguanine (O6-MeG) in human bronchial epithelial BEAS-2B cells. Moreover, the levels of MGMT and O6-MeG in chronic Cr(VI) exposure-caused human lung cancer tissues are also significantly lower and higher than that in the adjacent normal lung tissues, respectively. It was further determined that chronic low dose of Cr(VI) exposure-transformed BEAS-2B cells display impaired DNA damage repair capacity and a high sensitivity to the toxicity of the alkylating chemotherapeutic drug Temozolomide. In contrast, stably overexpressing MGMT in parental BEAS-2B cells reverses chronic low dose of Cr(VI) exposure-caused DNA damage repair deficiency and significantly reduces cell transformation by Cr(VI). Further mechanistical studies revealed that chronic low dose of Cr(VI) exposure down-regulates MGMT expression through epigenetic mechanisms by increasing DNA methylation and histone H3 repressive modifications. Taken together, these findings suggest that epigenetic down-regulation of a crucial DNA damage repair protein MGMT contributes significantly to the genotoxic effect and cell transformation caused by chronic low dose of Cr(VI) exposure.

Studying Cell Migration (Random and Wound Healing) Parameters with Imaging and MATLAB Analysis.

Cell migration is an essential biological process for organisms, in processes including embryonic development, immune response, and cancer metastasis. To elucidate the regulatory machinery of this vital process, methods that mimic in vivo migration, including in vitro wound healing assay and random migration assay, are widely used for cell behavior investigation. However, several concerns are raised with traditional cell migration experiment analysis. First, a manually scratched wound often presents irregular edges, causing the speed analysis difficult. Second, only the migration speed of leading cells is considered in the wound healing assay. Here, we provide a reliable analysis method to trace each cell in the time-lapse images, eliminating the concern about wound shape and creating a more comprehensive understanding of cell migration-not only of collective migration speed but also single-cell directionality and coordination between cells.

Studying Cellular Focal Adhesion Parameters with Imaging and MATLAB Analysis.

Cell signaling is highly integrated for the process of various cell activities. Although previous studies have shown how individual genes contribute to cell migration, it remains unclear how the integration of these signaling pathways is involved in the modulation of cell migration. In our two-hit migration screen, we revealed that serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) worked synergistically, and the suppression of both genes could further lead to suppression in cell migration. Furthermore, based on our analysis of cellular focal adhesion (FA) parameters using MATLAB analysis, we are able to find out the synergistic reduction of STK40 and MAPK that further abolished the increased FA by shSTK40. While FA identification in previous studies includes image analysis using manual selection, our protocol provides a semi-automatic manual selection of FAs using MATLAB. Here, we provide a method that can shorten the amount of time required for manual identification of FAs and increase the precision for discerning individual FAs for various analyses, such as FA numbers, area, and mean signals.

An interference model for visual and verbal working memory.

Research on working memory (WM) has followed two largely independent traditions: One concerned with memory for sequentially presented lists of discrete items, and the other with short-term maintenance of simultaneously presented arrays of objects with simple, continuously varying features. Here we present a formal model of WM, the interference model (IM), that explains benchmark findings from both traditions: The shape of the error distribution from continuous reproduction of visual features, and how it is affected by memory set size; the effects of serial position for sequentially presented items, the effect of output position, and the intrusion of nontargets as a function of their distance from the target in space and in time. We apply the model to two experiments combining features of popular paradigms from both traditions: Lists of colors (Experiment 1) or of nonwords (Experiment 2) are presented sequentially and tested through selection of the target from a set of candidates, ordered by their similarity. The core assumptions of the IM are: Contents are encoded into WM through temporary bindings to contexts that serve as retrieval cues to access the contents. Bindings have limited precision on the context and the content dimension. A subset of the memory set-usually one item and its context-is maintained in a focus of attention with high precision. Successive events in an episode are encoded with decreasing strength, generating a primacy gradient. With each encoded event, automatic updating of WM reduces the strength of preceding memories, creating a recency gradient and output interference. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan.

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

Challenges and complications and their management of the transarterial microembolization for chronic musculoskeletal pain.

Transarterial microembolization (TAME) is an increasingly well-known novel and minimally invasive treatment option for painful chronic musculoskeletal diseases that is gaining popularity. Although the safety and effectiveness of TAME have been established, limited knowledge of intraarticular and musculocutaneous arterial anatomy may lead to challenges and complications. This article aims to present cases illustrating these challenges and complications, based on multicenter experiences and a comprehensive literature review. Furthermore, the article also provides preventive tips, solutions, and follow-up strategies to reduce the learning curve for interventional radiologists and facilitate familiarity with post-TAME follow-up images for diagnostic radiologists. CLINICAL RELEVANCE STATEMENT: This article illustrates the intra- and post-interventional complications of transarterial microembolization (TAME) through detailed pictorial reviews, including how to distinguish them from normal angiographic findings. It provides strategies for their prevention, management, and follow-up, which can further improve clinical outcomes. KEY POINTS: • Transarterial microembolization for chronic musculoskeletal pain may result in intrainterventional challenges (IIC) and postinterventional complications (PIC), and their importance may be underestimated. • The intrainterventional challenges include microarterial perforation, arterial dissection, and catheter tip fracture, whereas postinterventional complications include tissue ischemia-related complications, puncture site hemorrhage, and arterial injury. • Being familiar with the intrainterventional challenges and postinterventional complications may help minimize the procedure risk and improve outcomes.

Unraveling the Link between Periodontitis and Coronavirus Disease 2019: Exploring Pathogenic Pathways and Clinical Implications.

Periodontitis involves the inflammation of the periodontal tissue, leading to tissue loss, while coronavirus disease 2019 (COVID-19) is a highly transmissible respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is amplified by poor systemic health. Key facilitators of SARS-CoV-2's entry into host cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). This review reveals that periodontal pockets can serve as a hotspot for virus accumulation, rendering surrounding epithelia more susceptible to infection. Given that ACE2 is expressed in oral mucosa, it is reasonable to suggest that poor periodontal health could increase the risk of COVID-19 infection. However, recent studies have not provided sufficient evidence to imply a significant effect of COVID-19 on periodontal health, necessitating further and more long-term investigations. Nevertheless, there are hypotheses linking the mechanisms of the two diseases, such as the involvement of interleukin-17 (IL-17). Elevated IL-17 levels are observed in both COVID-19 and periodontitis, leading to increased osteoclast activity and bone resorption. Lastly, bidirectional relationships between periodontitis and systemic diseases like diabetes are acknowledged. Given that COVID-19 symptoms may worsen with these conditions, maintaining good oral health and managing systemic diseases are suggested as potential ways to protect against COVID-19.

Development and Fabrication of Biocompatible Ti-Based Bulk Metallic Glass Matrix Composites for Additive Manufacturing.

Ti-based metallic glasses have a high potential for implant applications. The feasibility of a new biocompatible Ti-based bulk metallic glass composite for selective laser melting (SLM) had been examined. Therefore, it is necessary to design a high-glass-forming-ability Ti-based metallic glass (∆Tx = 81 K, γ = 0.427, γm = 0.763), to fabricate a partial glass-formable spherical powder (the volume fraction of the amorphous phase in the atomized Ti-based powders being 73% [size < 25 µm], 61% [25-37 µm], and 50% [37-44 µm]), and establish an SLM parameter (a scan rate of 600 mm/s, a power of 120 W, and an overlap of 10%). The Ti42Zr35Si5Co12.5Sn2.5Ta3 bulk metallic glass composite was successfully fabricated through SLM. This study demonstrates that the TiZrSiCoSnTa system constitutes a promising basis for the additive manufacturing process in terms of preparing biocompatible metallic glass composites into complicated graded foam shapes.

Cardiac Dose Predicts the Response to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients' clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden's index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders (n = 50) vs. non-responders (n = 36) with a significant difference in OS. In multivariate LR, cardiac dose-volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

Development and Validation of a Novel Risk Score for All-Cause Mortality Risk Stratification Prior to Permanent Pacemaker Implantation in Octogenarians or Older.

Background and Objectives: The demand for permanent pacemaker (PPM) implantation for extremely old patients is increasing. Prior to implanting PPMs, life expectancy evaluation is essential but difficult. We aimed to develop and validate a scoring system for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80. Materials and Methods: A total of 210 patients aged ≥80 who received PPM implantation were included. Multivariable analysis was performed to assess the effects of different variables on all-cause mortality in a derivation cohort (n = 100). We developed the MELODY score for stratifying all-cause mortality prior to PPM implantation and tested the scoring system in a validation cohort (n = 102). Results: After 4.0 ± 2.7 years of follow-up, 54 patients (54%) had died. The 0.5-, 1- and 2-year all-cause mortality rates were 7%, 10% and 24%, respectively. The MELODY score based on body mass index <21 kg/m2 (HR: 2.21, 95% CI: 1.06-4.61), estimated glomerular filtration rate <30 mL/min/1.73 m2 (3.35, 1.77-6.35), length of hospitalization before PPM implantation >7 days (1.87, 1.02-3.43) and dyspnea as the major presenting symptom (1.90, 1.03-3.50) successfully distinguished patients at high risk of mortality. Patients with MELODY scores ≥3 had a higher risk of mortality compared to those with MELODY scores <3 (8.49, 4.24-17.00). The areas under the receiver operating characteristic curves in predicting 0.5, 1 and 2 years mortality rates were 0.86, 0.81 and 0.74, respectively. The predictive value of the model was confirmed in a validation cohort. Conclusions: The novel scoring system is a simple and effective tool for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80.

Predicting portal venous anomalies by left-sided gallbladder or right-sided ligamentum teres hepatis: A large scale, propensity score-matched study.

BACKGROUND: Right-sided ligamentum teres (RSLT) is often associated with portal venous anomalies (PVA) and is regarded as a concerning feature for hepatobiliary intervention. Most studies consider RSLT to be one of the causes of left-sided gallbladder (LGB), leading to the hypothesis that LGB must always be present with RSLT. However, some cases have shown that right-sided gallbladder (RGB) can also be present in livers with RSLT. AIM: To highlight the rare variation that RSLT may not come with LGB and to determine whether ligamentum teres (LT) or gallbladder location is reliable to predict PVA. METHODS: This study retrospectively assessed 8552 contrast-enhanced abdominal computed tomography examinations from 2018 to 2021 [4483 men, 4069 women; mean age, 59.5 ± 16.2 (SD) years]. We defined the surrogate outcome as major PVAs. The cases were divided into 4 subgroups according to gallbladder and LT locations. On one hand, we analyzed PVA prevalence by LT locations using gallbladder location as a controlled variable (n = 36). On the other hand, we controlled LT location and computed PVA prevalence by gallbladder locations (n = 34). Finally, we investigated LT location as an independent factor of PVA by using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: We found 9 cases of RSLT present with RGB. Among the LGB cases, RSLT is associated with significantly higher PVA prevalence than typical LT [80.0% vs 18.2%, P = 0.001; OR = 18, 95% confidence interval (CI): 2.92-110.96]. When RSLT is present, we found no statistically significant difference in PVA prevalence for RGB and LGB cases (88.9 % vs 80.0%, P > 0.99). Both PSM and IPTW yielded balanced cohorts in demographics and gallbladder locations. The RSLT group had a significantly higher PVA prevalence after adjusted by PSM (77.3% vs 4.5%, P < 0.001; OR = 16.27, 95%CI: 2.25-117.53) and IPTW (82.5% vs 4.7%, P < 0.001). CONCLUSION: RSLT doesn't consistently coexist with LGB. RSLT can predict PVA independently while the gallbladder location does not serve as a sufficient predictor.

A subset of cholinergic mushroom body neurons blocks long-term memory formation in Drosophila.

Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, weak learning after a single training session in an olfactory aversive task typically does not induce protein-synthesis-dependent LTM. Instead, strong learning after multiple spaced training sessions is required. Here, we report that pre-synaptic active-zone protein synthesis and cholinergic signaling from the early α/ß subset of mushroom body (MB) neurons produce a downstream inhibitory effect on LTM formation. When we eliminated inhibitory signaling from these neurons, weak learning was then sufficient to form LTM. This bidirectional circuit mechanism modulates the transition between distinct memory phase functions in different subpopulations of MB neurons in the olfactory memory circuit.