Development and design of intelligent lubricating equipment for feed systems.

Recently, the lubricating devices for the feed systems of computer numerical control (CNC) machine tools supply oil periodically because programmable logic controller and macro are adopted for designing oil supply for the present CNC machine tools, causing lack or overdose lubrication. This study attempts to discuss and design the optimum lubrication cycle timing for the feed system under the experimental conditions of different loads and feed rates. The parameters of the servomotor are monitored by utilizing an intelligent module, the changes in the current and torque of the servomotor are obtained, and then a lubrication module is created with the Stribeck friction model, a modeling that utilizes response surface methodology. The increase in feed rate will cause increasing current and torque, and the current and torque for the load 35 kg were 11 and 13%, respectively. Finally, different loads and feed rates are imported to determine optimal lubrication timing. According to a long-term validation, the oil supply frequency is improved by over 80% without influencing the feed system accuracy, and the traditional lubrication module is compared with the lubrication module. Long time test is 8 h, and the rate of improvement is 87.5%, the cost of lubricating oil is reduced, and green manufacturing is met. An appropriate oil supply system is provided for the circle.

Dorsoventral hippocampus distinctly modulates visceral sensitivity and anxiety behaviors in male IBS-like rats.

Accumulating evidences suggest dysfunctions in the hippocampus are associated with chronic pain. Nevertheless, the role of hippocampal circuitry in pain memories and emotional responses is not yet fully understood. In this study, we utilized a comprehensive approach that combined electromyography (EMG), photochemical genetic techniques, and anxiety-related behavioral paradigms to investigate the involvement of dorsal hippocampus (DH) and ventral hippocampus (VH) in visceral sensitivity and anxiety behaviors in male rats. Our results demonstrated that IBS-like rats exhibited comorbid visceral hypersensitivity and anxiety, along with the number of activated neurons in the VH was higher than that in the DH. Manipulation of glutamatergic neurons in the hippocampus was identified as a crucial mechanism underlying the mediation of both visceral sensitivity and anxiety behaviors. Specifically, optogenetic activation of the DH induced both visceral hypersensitivity and anxiety, while activation of the VH induced anxiety but did not affect visceral sensitivity. Conversely, chemogenetic inhibition of the DH reduced both visceral hypersensitivity and anxiety, whereas inhibition of the VH alleviated anxiety but did not alleviate visceral hypersensitivity in IBS-like rats. Our study highlights the important role of early life stress in inducing visceral hypersensitivity and anxiety, and further elucidates the distinct functional contributions of the DH and VH to these behavioral changes. These findings provide a theoretical basis for the diagnosis and treatment of IBS, and suggest that targeting specific hippocampal neuron subtypes may represent a promising therapeutic approach.

Multiple Field-of-View Based Attention Driven Network for Weakly Supervised Common Bile Duct Stone Detection.

OBJECTIVE: Common bile duct (CBD) stones caused diseases are life-threatening. Because CBD stones locate in the distal part of the CBD and have relatively small sizes, detecting CBD stones from CT scans is a challenging issue in the medical domain. METHODS AND PROCEDURES: We propose a deep learning based weakly-supervised method called multiple field-of-view based attention driven network (MFADNet) to detect CBD stones from CT scans based on image-level labels. Three dominant modules including a multiple field-of-view encoder, an attention driven decoder and a classification network are collaborated in the network. The encoder learns the feature of multi-scale contextual information while the decoder with the classification network is applied to locate the CBD stones based on spatial-channel attentions. To drive the learning of the whole network in a weakly-supervised and end-to-end trainable manner, four losses including the foreground loss, background loss, consistency loss and classification loss are proposed. RESULTS: Compared with state-of-the-art weakly-supervised methods in the experiments, the proposed method can accurately classify and locate CBD stones based on the quantitative and qualitative results. CONCLUSION: We propose a novel multiple field-of-view based attention driven network for a new medical application of CBD stone detection from CT scans while only image-levels are required to reduce the burdens of labeling and help physicians automatically diagnose CBD stones. The source code is available at https://github.com/nchucvml/MFADNet after acceptance. CLINICAL IMPACT: Our deep learning method can help physicians localize relatively small CBD stones for effectively diagnosing CBD stone caused diseases.

Investigation into the content of red material in EUS-guided pancreatic cancer biopsies.

BACKGROUND AND AIMS: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. METHODS: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. RESULTS: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm2 and 10.74 mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] µg vs .70 [interquartile range, .27-1.24] µg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001). CONCLUSIONS: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.

Tissue Quality Comparison Between Heparinized Wet Suction and Dry Suction in Endoscopic Ultrasound-Fine Needle Biopsy of Solid Pancreatic Masses: A Randomized Crossover Study.

Background/Aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568). Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Methyltransferase-like 3 modulates visceral hypersensitivity through regulating the nuclear export of circKcnk9 in YTHDC1-dependent manner.

Background: Accumulating evidence shows that N6-methyladenosine (m6A) modulators contribute to the process of chronic pain. However, the exact mechanisms of m6A writers involved in visceral hypersensitivity of Irritable bowel syndrome (IBS) remain unclear. This article aimed to reveal a new mechanism for the progression of IBS. Methods: The IBS-like model was established by neonatal colorectal distention (CRD). The relationship between m6A and circKcnk9 was analyzed by bioinformatics, immunofluorescence and RNA fluorescence in situ hybridization (FISH) assays. Visceral hypersensitivity was assessed based on the electromyography (EMG) response of the abdominal external oblique muscle to CRD. In vivo and in vitro studies (including EMG stereotactic infusion, Western blot and qRT-PCR) were utilized to explore the biological functions of related indicators. The bioinformatics, RIP experiments and RNA pull-down assays were used to explore the potential molecular mechanisms. Results: We identified that neonatal CRD increased the level of the m6A via methyltransferase-like 3 (METTL3) in the hippocampal neurons. Subsequently, knockdown of METTL3 could alleviate visceral hypersensitivity in IBS-like rats. By contrast, overexpression of METTL3 could induce visceral hypersensitivity and activate hippocampal neurons in control rats. Moreover, YTHDC1, the only m6A-associated protein predicted by bioinformatics to bind to circKcnk9, modulated visceral hypersensitivity through regulating the nuclear export of circKcnk9 in an m6A-dependent manner. Notably, FISH data suggested that the increased nuclear staining of circKcnk9 caused by siYTHDC1 could be recovered by overexpression of YTHDC1 wild type (WT) but not YTHDC1 negative control (NC) in PC12 cells. Conclusions: Our findings reveal a new regulatory mechanism in progress of IBS, that is, METTL3 modulates visceral hypersensitivity through regulating the nuclear export of circKcnk9 in YTHDC1-dependent manner.

A high-resolution mass spectrometric method for identification and characterization of the in vitro metabolites of senkyunolide H.

RATIONALE: Ligusticum chuanxiong Hort is a well-known herb medicine that has been widely prescribed to treat cardiovascular diseases in China for hundreds of years. Senkyunolide H (SNH) is one of the major bioactive ingredients extracted from L. chuanxiong, and it displayed neuroprotective effects. To fully understand its mechanism of action, the metabolism needs to be investigated. METHODS: In vitro studies were conducted by incubating SNH with rat and human hepatocytes, and the metabolites were identified and characterized using liquid chromatography in combination with hybrid quadrupole Orbitrap mass spectrometry (LC-Orbitrap-MS). The structures of the metabolites were proposed by accurate mass analysis of respective precursor ions, indicative product ions, and elemental compositions. RESULTS: Under the current conditions, a total of 10 metabolites were identified, and among these metabolites, M3 and M4 were the most abundant metabolites both in rat and human hepatocytes. Our results demonstrated that hydroxylation, hydration, glucuronidation, and GSH conjugation were the primary metabolic pathways of SNH. CONCLUSIONS: The present study provides new information on the metabolism of SNH, which would help prospects of the disposition of SNH.

Transferrin and Prealbumin Identify Esophageal Cancer Patients with Malnutrition and Poor Prognosis in Patients with Normal Albuminemia: A Cohort Study.

In this study, we aimed to analyze whether serum prealbumin and transferrin have a higher sensitivity than albumin for detecting malnutrition and predicting survival in esophageal cancer patients. A total of 212 patients were prospectively enrolled. Serum albumin, prealbumin, and transferrin were analyzed by enzyme-linked immunosorbent assays. The association of nutritional markers with survival was analyzed. We found that malnutrition was presented in 44.5% of the patients, while 56.6% were unaware of their body weight change. The area under the curve for diagnosing malnutrition was largest for prealbumin, followed by transferrin and albumin, with optimal breakpoints of 21 mg/dL, 206 mg/dL, and 4.3 g/dL, respectively, for diagnosing malnutrition. The diagnostic sensitivity for malnutrition was 34.1-63.4% with a single marker and this increased to 80.5% with all 3 markers. In patients with normal albuminemia (≥ 4.3 g/dL), a low level of prealbumin and/or transferrin predicted malnutrition and poor prognosis. Multivariate Cox regression analysis confirmed that a low level of the nutritional marker was an independent poor prognostic factor. In conclusion, serum prealbumin and transferrin outperformed albumin in identifying esophageal cancer patients with malnutrition and poor prognosis. Checking all three markers will help with the early diagnosis of malnutrition and enable timely intervention.

Endoscopic ultrasound avoids adverse events in high probability choledocholithiasis patients with a negative computed tomography.

BACKGROUND: The current guideline recommends patients who meet high probability criteria for choledocholithiasis to receive endoscopic retrograde cholangiopancreatography (ERCP). However, adverse events can occur during ERCP. Our goal is to determine whether endoscopic ultrasound (EUS) before ERCP can avoid unnecessary ERCP complications, especially in patients with a negative CT scan. METHODS: A total of 604 patients with high probability of choledocholithiasis were screened and 104 patients were prospectively enrolled. Patients with malignant biliary obstruction, altered GI anatomy, and choledocholithiasis on CT scan were excluded. Among them, 44 patients received EUS first, and ERCP if choledocholithiasis present (EUS-first group). The other 60 patients received ERCP directly (ERCP-first group). The baseline characteristics, presence of choledocholithiasis, and complications were compared between groups. All patients were followed for 3 months to determine the difference in recurrent biliary event rate. Cost-effectiveness was compared between the two strategies. RESULTS: There was no marked difference in age, sex, laboratory data, presenting with pancreatitis, and risk factors for choledocholithiasis. Overall, 51 patients (49.0%) had choledocholithiasis, which did not justify the risk of direct ERCP. In the EUS-first group, 27 (61.4%) ERCP procedures were prevented. The overall complication rate was significantly lower in the EUS-first group compared to the ERCP-fist group (6.8% vs. 21.7%, P = 0.04). The number-needed-to-treat to avoid one unnecessary adverse event was 6.71. After a 3-month follow-up, the cumulative recurrence biliary event rates were similar (13.6% vs. 15.0%, P = 0.803). EUS-first strategy was more cost-effective than the ERCP-first strategy (mean cost 2322.89$ vs. 3175.63$, P = 0.002). CONCLUSIONS: In high-probability choledocholithiasis patients with a negative CT, the EUS-first strategy is cost-effective, which can prevent unnecessary ERCP procedures and their complications.

Transcutaneous Electrical Acustimulation Improved the Quality of Life in Patients With Diarrhea-Irritable Bowel Syndrome.

BACKGROUND AND AIM: Patients with diarrhea-dominant irritable bowel syndrome (IBS-D) experience abdominal pain and reduced quality of life and need effective treatments. This study aimed to evaluate whether transcutaneous electrical acustimulation (TEA) at two acupuncture points, LI4 and ST36, could improve pain and quality of life of patients with IBS-D. MATERIALS AND METHODS: A total of 42 patients with IBS-D who met the Rome IV criteria were randomly divided into two groups: TEA and sham-TEA. TEA was performed through acupoints Hegu (LI4) and Zusanli (ST36) for one hour twice daily for one month, using previously established parameters; sham-TEA was delivered in the same way as TEA but without actual electrical current stimulation. RESULTS: The sham-TEA group showed a significantly higher rate of drop-out than the TEA group (29% vs 0%, p = 0.021). TEA, but not sham-TEA, significantly improved quality of life (before: 78.55 ± 9.62, after: 85.97 ± 9.49, p < 0.0001). Both TEA and sham-TEA reduced abdominal pain; however, TEA was more potent than sham-TEA (p = 0.014). The IBS symptom severity scale score was reduced by both TEA and sham-TEA. Autonomic functions assessed by plasma norepinephrine and pancreatic polypeptide were not altered with TEA, nor was interleukin 10 or interleukin 6. CONCLUSIONS: TEA at LI4 and ST36 improves abdominal pain and quality of life of patients with IBS-D, probably mediated by mechanisms other than autonomic function or inflammatory cytokines.

Chiral-Selective Tamm Plasmon Polaritons.

Chiral-selective Tamm plasmon polariton (TPP) has been investigated at the interface between a cholesteric liquid crystal and a metasurface. Different from conventional TPP that occurs with distributed Bragg reflectors and metals, the chiral-achiral TPP is successfully demonstrated. The design of the metasurface as a reflective half-wave plate provides phase and polarization matching. Accordingly, a strong localized electric field and sharp resonance are observed and proven to be widely tunable.

Confirming Whether Fine Needle Biopsy Device Shortens the Learning Curve of Endoscopic Ultrasound-Guided Tissue Acquisition Without Rapid Onsite Evaluation.

BACKGROUND/AIMS: Endoscopic ultrasonography (EUS)-guided tissue acquisition requires a long learning curve. We aimed to compare the skill maturation curves between fine needle aspiration (FNA) and biopsy (FNB) for tissue acquisition. METHODS: The initial 60 procedures performed by the trainee endosonographer (30 FNA vs. 30 FNB) were consecutively enrolled. The difference in procedure performance was compared between the two groups. Learning curves were assessed. Twenty additional cases were subsequently enrolled to assess the consistency of performance in the FNB group. RESULTS: The FNB group acquired larger tissue samples (2.35 vs. 0.70 mm2; p<0.001) with lower blood content (p=0.001) and higher tissue quality (p=0.017) compared with the FNA group. In addition, the FNB group required less needle pass to establish a diagnosis (2.43 vs. 2.97; p=0.006). A threshold diagnostic sensitivity of ≥80% was achieved after performing 10 FNB procedures. The number of needle passes significantly decreased after conducting 20 FNB procedures (1.80 vs. 2.70; p=0.041). The diagnostic sensitivity and number of needle passes remained the same in the subsequent FNB procedures. By contrast, this skill maturation phenomenon was not observed after performing 30 FNA procedures. CONCLUSION: In EUS-guided tissue acquisition, the FNB needle was more efficient and thus shortened the learning curve of EUS-guided tissue acquisition in trainee endosonographers.

Whole genome sequencing and assembly data of Moricandia moricandioides and M. arvensis.

Moricandia is a genus belonging to the family Brassicaceae. C3 and C3-C4 photosynthesis Moricandia species exist in a close phylogenetic proximity, as well as to Brassica crops. Here, we performed PacBio genome sequencing on M. moricandioides and M. arvensis. The genomes were assembled using Flye assembler, then polished with Illumina reads and reduced duplication with Purge Haplotigs. The total length of genome assemblies of M. moricandioides and M. arvensis was 498 Mbp and 759 Mbp, respectively. These data will be useful for studies of the genetic control of C3-C4 characteristics, therefore gaining new insights into the early evolutionary steps of C4 photosynthesis. Further, it can be integrated into Brassica crop breeding. The data can be accessed at ENA under the project number PRJEB39764.

Intense L-Band Solar Radio Bursts Detection Based on GNSS Carrier-To-Noise Ratio Decrease over Multi-Satellite and Multi-Station.

Intense solar radio bursts (SRBs) can increase the energy noise and positioning error of the bandwidth of global navigation satellite system (GNSS). The study of the interference from intense L-band SRBs is of great importance to the steady operation of GNSS receivers. Based on the fact that intense L-band SRBs lead to a decrease in the carrier-to-noise ratio (C/N0) of multiple GNSS satellites over a large area of the sunlit hemisphere, an intense L-band SRB detection method without the aid of a radio telescope is proposed. Firstly, the valley period of a single satellite at a single monitoring station is detected. Then, the detection of SRBs is achieved by calculating the intersection of multiple satellites and multiple stations. The experimental results indicate that the detection rates of GPS L2 and GLONASS G2 are better than those of GPS L1 L5, GLONASS G1, and Galileo E1 E5. The detection rate of SRBs can reach 80% with a flux density above 800 solar flux unit (SFU) at the L2 frequency of GPS. Overall, the detection rate is not affected by the satellite distribution relative to the Sun. The proposed detection method is low-cost and has a high detection rate and low false alarm rate. This method is a noteworthy reference for coping with interference in GNSS from intense L-band SRBs.

Radiation dose escalation can improve local disease control and survival among esophageal cancer patients with large primary tumor volume receiving definitive chemoradiotherapy.

BACKGROUND: This study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome. METHODS: We retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival. RESULTS: Patients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3). CONCLUSION: Large primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted.

Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen.

PURPOSE: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. METHODS: We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. RESULTS: The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025). CONCLUSION: Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.

Framework for determining optimal strategy for sustainable remediation of contaminated sediment: A case study in Northern Taiwan.

Contaminated sediment may pose a serious threat to human health and ecosystems. However, sediment remediation is typically an expensive and time-consuming process. Therefore, an effective decision-making process for the remediation of contaminated sediment is essential for identifying the optimal approach. Since a single assessment for sediment remediation may be insufficient, combining different analytical approaches is highly recommended. The objective of this study was to develop a comprehensive assessment framework based on the concept of green and sustainable remediation that considers various environmental, economic, and social aspects for the management of contaminated sediment. We propose a framework based on human health risk assessment (HHRA) and cost-benefit analysis (CBA) and apply the multicriteria decision analysis (MCDA) technique to implement integrated and sustainable strategies for sediment management. We used the framework to determine the best alternative for managing heavy-metal-contaminated sediment in a river in Northern Taiwan. The results of the pre-remediation HHRA indicated an unacceptably high cancer risk to children, while the CBA revealed that a remediation project was economically feasible. Moreover, the results of the MCDA revealed that a strategy involving in-situ capping with anthracite-based activated carbon would be relatively inexpensive and result in low risk to human health. In addition, this strategy would have a higher environmental impact and greater public acceptance as compared to a method involving the dredging and washing of soil. Thus, in this case study, in-situ capping using anthracite-based activated carbon was identified as the preferable remediation alternative from multiple perspectives. The proposed framework should allow decision-makers to choose the optimal integrated management strategy for similar river sites with contaminated sediment.

Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics.

Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long-term ulcer rebleeding: A 3.5-year prospective longitudinal study.

BACKGROUND AND AIM: Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long-term outcomes deserve follow-up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5-year longitudinal cohort. METHODS: Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding. RESULTS: The proportion of patients with rebleeding during the 3.5-year follow-up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5-fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person-year, P = 0.012, log-rank test). CONCLUSIONS: Patients with Rockall scores ≥6 are at risk of long-term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5-fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6.

Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

BACKGROUND/PURPOSE: Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. METHODS: The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding. RESULTS: The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05). CONCLUSION: Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083).