Multiple-Timescale Representations of Space: Linking Memory to Navigation.

When navigating through space, we must maintain a representation of our position in real time; when recalling a past episode, a memory can come back in a flash. Interestingly, the brain's spatial representation system, including the hippocampus, supports these two distinct timescale functions. How are neural representations of space used in the service of both real-world navigation and internal mnemonic processes? Recent progress has identified sequences of hippocampal place cells, evolving at multiple timescales in accordance with either navigational behaviors or internal oscillations, that underlie these functions. We review experimental findings on experience-dependent modulation of these sequential representations and consider how they link real-world navigation to time-compressed memories. We further discuss recent work suggesting the prevalence of these sequences beyond hippocampus and propose that these multiple-timescale mechanisms may represent a general algorithm for organizing cell assemblies, potentially unifying the dual roles of the spatial representation system in memory and navigation.

Understanding the Coupling Mechanism of Intercalation and Conversion Hybrid Storage in Lithium-Graphite Anode.

Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g-1, its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries.

miR-330-3p alleviates the progression of atherosclerosis by downregulating AQP9.

Atherosclerosis (AS) is the main cause of cardiovascular diseases. However, the role of AQP9 in AS is not well understood. In the present study, we predicted that miR-330-3p might regulate AQP9 in AS through bioinformatics analysis, and we established AS model using ApoE-/- mouse (C57BL/6) with high-fat diet (HFD). Hematoxylin and eosin (H&E) and Oil red O staining were used to determine atherosclerotic lesions. CCK8 and Ethyny1-2-deoxyuridine (EdU) assays were used to investigate human umbilical vein endothelial cells (HUVECs) proliferation after treatment with 100 µg/mL ox-LDL. Wound scratch healing and transwell assays were used to measure the cell invasion and migration ability. Flow cytometry assay was used to determine apoptosis and cell cycle. A dual-luciferase reporter assay was performed to investigate the binding of miR-330-3p and AQP9. We identified that the expression of miR-330-3p in AS mice model decreased while the expression level of AQP9 increased. miR-330-3p overexpression or down-regulation of AQP9 could reduce cell apoptosis, promote cell proliferation, and migration after ox-LDL treatment. Dual-luciferase reporter assay result presented that AQP9 was directly inhibited by miR-330-3p. These results suggest that miR-330-3p inhibits AS by regulating AQP9. miR-330-3p/AQP9 axis may be a new therapeutic target for AS.

Robotic versus laparoscopic surgery for sporadic benign insulinoma: Short- and long-term outcomes.

BACKGROUND: Minimally invasive surgery is the optimal treatment for insulinoma. The present study aimed to compare short- and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma. METHODS: A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted. The demographic, perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups. RESULTS: A total of 85 patients were enrolled, including 36 with laparoscopic approach and 49 with robotic approach. Enucleation was the preferred surgical procedure. Fifty-nine patients (69.4%) underwent enucleation; among them, 26 and 33 patients underwent laparoscopic and robotic surgery, respectively. Robotic enucleation had a lower conversion rate to laparotomy (0 vs. 19.2%, P = 0.013), shorter operative time (102.0 vs. 145.5 min, P = 0.008) and shorter postoperative hospital stay (6.0 vs. 8.5 d, P = 0.002) than laparoscopic enucleation. There were no differences between the groups in terms of intraoperative blood loss, the rates of postoperative pancreatic fistula and complications. After a median follow-up of 65 months, two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence. CONCLUSIONS: Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time, which might lead to a reduction in postoperative hospital stay.

Classification of Fluorescently Labelled Maize Kernels Using Convolutional Neural Networks.

Accurate real-time classification of fluorescently labelled maize kernels is important for the industrial application of its advanced breeding techniques. Therefore, it is necessary to develop a real-time classification device and recognition algorithm for fluorescently labelled maize kernels. In this study, a machine vision (MV) system capable of identifying fluorescent maize kernels in real time was designed using a fluorescent protein excitation light source and a filter to achieve optimal detection. A high-precision method for identifying fluorescent maize kernels based on a YOLOv5s convolutional neural network (CNN) was developed. The kernel sorting effects of the improved YOLOv5s model, as well as other YOLO models, were analysed and compared. The results show that using a yellow LED light as an excitation light source combined with an industrial camera filter with a central wavelength of 645 nm achieves the best recognition effect for fluorescent maize kernels. Using the improved YOLOv5s algorithm can increase the recognition accuracy of fluorescent maize kernels to 96%. This study provides a feasible technical solution for the high-precision, real-time classification of fluorescent maize kernels and has universal technical value for the efficient identification and classification of various fluorescently labelled plant seeds.

Intraoperative Ultrasound Guided Robotic Pancreatic Enucleation, Does a Distance of 3mm Still Matters?

Background: A minimal distance of 3 mm to main pancreatic duct (MPD) was generally considered to be necessary for pancreatic enucleation (PE). This study was designed to report the safety and feasibility of PE for tumors located in 3 mm to MPD Under the intraoperative ultrasound (IOUS) guidance.Methods: The data of patients who received IOUS guided robotic PE from January 2018 to May 2019 in the second department of hepato-pancreato-biliary surgery were reviewed in this study. According to the distance to MPD (less than 3 mm or not), patients were divided in 2 groups, and the short-term operative outcomes were compared.Statistics: Students' t-test and Mann-Whitney U test were used for comparing continuous variables, and Chi-squared test was used for comparing categorical variables.Results: And a total of 56 patients were analyzed, and a minimal distance less than 3 mm between the tumor and pancreatic duct measured by IOUS was found in 12 patients. The tumors and MPD were clearly revealed intraoperatively in all the cases. The operative duration was significantly longer in patients with tumors located in 3 mm from MPD (143.25 ± 40.89 min vs 107.14 ± 37.73 min, t = 2.756, P=.014). There was no significant difference between the rate of post-operative pancreatic fistula and other complications in the different groups (χ2 =.924, P=.48).Discussion and conclusion: robotic PE could be safely performed under IOUS guidance for benign or low-grade malignant tumors located less than 3 mm to the MPD.

Early Drain Removal is Safe in Patients With Low or Intermediate Risk of Pancreatic Fistula After Pancreaticoduodenectomy: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: This multicenter randomized controlled trial was designed to test the hypothesis that early drain removal (EDR) could decrease the incidence of grade 2 to 4 complications for patients undoing pancreaticoduodenectomy (PD) with low or intermediate risk of postoperative pancreatic fistula (POPF). BACKGROUND: The safety and effects of EDR on postoperative complications after PD are still controversial. METHODS: A multicenter randomized controlled trial at 6 tertiary referral hospitals was carried out (NCT03055676). Patients who met the inclusion criteria, including drain amylase level less than 5000 U/L on postoperative day (POD) 1 and POD 3, and drain output less than 300 mL per day within 3 days after surgery, were enrolled. Patients were then randomized to the EDR group or the routine drain removal (RDR) group. In the EDR group, all drainage tubes were removed on POD3. In the RDR group, drainage tubes were removed on POD 5 or beyond. Primary outcome was the incidence of Clavien-Dindo grade 2 to 4 complications. Secondary outcomes were comprehensive complication index, grade B/C POPF, total medical expenses and postoperative in-hospital stay etc, within 90 days after surgery. RESULTS: A total of 692 patients were screened, and 312 patients were eligible for randomization. Baseline characteristics were well balanced between the 2 groups and 96.8% of these 312 patients had low or intermediate risk of POPF, according to the 10-point fistula risk score. A total of 20.5% of the patients in the EDR group suffered at least 1 grade 2 to 4 complication, versus 26.3% in the RDR group (P = 0.229). Multi-variate analysis showed older age (>65 years old) and blood transfusion were independent risk factors for grade 2 to 4 complications. The rate of grade B/C POPF was low in either group (3.8% vs 6.4%, P = 0.305). The comprehensive complication index of the 2 groups was also comparable (20.9 vs 20.9, P = 0.253). Total medical expenses were not significantly different. Postoperative in-hospital stay was clinically similar (15 days vs 16 days, P = 0.010). CONCLUSIONS: Nearly half of the patients undergoing PD met the inclusion criteria, predicting low incidence of grade B/C POPF and major complications. EDR was safe in these patients but did not significantly decrease major complications.

Profile of Patients with Isolated Distal Deep Vein Thrombosis versus Proximal Deep Vein Thrombosis or Pulmonary Embolism: RE-COVERY DVT/PE Study.

Isolated distal deep vein thrombosis (IDDVT) is presumed to be more benign than proximal DVT (PDVT) or pulmonary embolism (PE), suggesting a need for different management approaches. This subgroup analysis of the RE-COVERY DVT/PE global, observational study investigated patient characteristics, hospitalization details, and anticoagulant therapy in patients with IDDVT in real-world settings in 34 countries enrolled from January 2016 to May 2017. Data were analyzed descriptively according to the type and location of the index venous thromboembolism (VTE): IDDVT, PDVT ± distal DVT (DDVT), and PE ± DVT. Of the 6,095 eligible patients, 323 with DVT located outside the lower limb and no PE were excluded. Of the remaining 5,772 patients, 17.6% had IDDVT, 39.9% had PDVT ± DDVT, and 42.5% had PE ± DVT. IDDVT patients were younger and had fewer risk factors for VTE than the other groups. Other comorbidities were less frequent in the IDDVT group, except for varicose veins, superficial thrombophlebitis, and venous insufficiency. IDDVT patients were less likely to be diagnosed in an emergency department (22.3 vs. 29.7% for PDVT ± DDVT and 45.4% for PE ± DVT) or hospitalized for VTE (29.2 vs. 48.5% for PDVT ± DDVT and 75.0% for PE ± DVT). At hospital discharge or 14 days after diagnosis (whichever was later), non-vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (55.6% for IDDVT, 54.7% for PDVT ± DDVT, and 52.8% for PE ± DVT). Although differences in patient characteristics, risk factors, and clinical management were identified, anticoagulant treatment of IDDVT was almost equal to that of PDVT or PE. Prospective studies should investigate whether, in a global perspective, this is an appropriate use of anticoagulants.

Network Meta-Analysis of All Available Regimens Based on Drug-Coated Balloon Angioplasty and Laser Atherectomy for Femoropopliteal In-Stent Restenosis.

PURPOSE: Drug-coated balloon (DCB) angioplasty and laser atherectomy (LA) have been frequently utilized to treat femoropopliteal in-stent restenosis (ISR); however, no studies have concurrently compared available regimens, including DCB, LA+DCB, and LA + plain balloon angioplasty (PB). Therefore, we conducted this network meta-analysis to determine whether there were significant differences in outcomes among these regimens. MATERIALS AND METHODS: A comprehensive search was conducted in PubMed, EMBASE, and the Cochrane library to identify all randomized controlled trials comparing DCB or LA-based regimes with POBA or each other for treating femoropopliteal in-stent restenosis (ISR) from their inception until March 2021. The primary outcome measure was binary restenosis, and secondary outcome measures were target lesion revascularization (TLR) and mortality, evaluated at 6 and 12 months, respectively. Statistical analysis was performed using Aggregate Data Drug Information System (ADDIS) 1.4 software, and all data were graphically summarized using Microsoft Excel software. RESULTS: The final analysis included 11 studies, of which 6 studies compared DCB with PB, 2 studies compared PB vs LA+PB, 2 studies compared DCB vs LA+DCB, and 1 study compared LA+DCB with LA+PB. DCB was better than PB in decreasing binary restenosis at 6 (odds ratio [OR]: 0.22, 95% credible interval [CrI]: 0.04-0.91) and 12 (OR: 0.26, 95% CrI: 0.12-0.50) months. DCB was associated with lower TLR than PB at 6 months (OR: 0.31, 95% CrI: 0.13-0.69). LA+DCB was also superior to PB in treating binary restenosis at 12 months (OR: 6.10, 95% CrI: 1.94-24.41) and TLR at 6 months (OR: 5.32, 95% CrI: 1.43-28.06). There was no statistical difference in mortality between PB, DCB, and LA+PB. DCB and LA+DCB were the first 2 options for reducing binary restenosis and TLR. CONCLUSION: The current network meta-analysis demonstrates that both DCB and LA+DCB are superior to PB alone, and that DCB and LA+DCB may be the preferred treatment options for reducing binary restenosis and TLR. CLINICAL IMPACT: The treatment for femoropopliteal in-stent restenosis (ISR) remains challenging clinical practice. One important reason is that no optimal treatment strategy was available. Drug-coated balloon angioplasty (DCB) and laser atherectomy (LA) have been extensively utilized to treat ISR; however, different combinations of these treatments further confused the clinicians' choices. This network meta-analysis systematically investigated the difference between the currently available treatments regarding therapeutic effects and safety, indicating that DCB and LA+DCB may be the optimal treatment for decreasing the risk of binary restenosis and target lesion revascularization. The results of the current network meta-analysis help to resolve the confusion of clinicians in making the decision.

Value of Conventional Ultrasound-based Scoring System in Distinguishing Adenomatous Polyps From Cholesterol Polyps.

BACKGROUND AND AIM: Ultrasound has increased the detection of gallbladder polyps, but it has limitations in evaluating the nature of gallbladder polyps, especially the maximum size of 1.0 to 1.5 cm. We assessed the value of ultrasound scoring system based on independent predictive parameters in distinguishing adenomatous polyps from cholesterol polyps with the maximum size of 1.0 to 1.5 cm. MATERIALS AND METHODS: We enrolled 163 patients with gallbladder polyps (1.0 to 1.5 cm) who underwent ultrasonography and cholecystectomy. Ultrasound image characteristics were compared between cholesterol polyps and adenomatous polyps in the training cohort from April 2018 to January 2020. An ultrasound scoring system was constructed in the training cohort, and its diagnostic performance was evaluated in the validation cohort from February 2020 to February 2021. RESULTS: Maximum size, height/width ratio, stone or sludge, vascularity, and hyperechoic spot were significantly different between cholesterol polyps and adenomatous polyps in the training cohort ( P <0.05). The independent predictive parameters for adenomatous polyps were lower height/width ratio, presence of vascularity and absence of hyperechoic spot. The total score was as follows: (height/width ratio, <0.9=4, ≥0.9=0) + (vascularity, present=3, absent=0) + (hyperechoic spot, absent=2, present=0). The sensitivity, specificity and accuracy of ultrasound scoring system ≥5 for diagnosis of adenomatous polyps in the validation cohort were 73.33%, 80.49%, and 78.57%, respectively. CONCLUSIONS: The ultrasound scoring system aids in distinguishing adenomatous polyps from cholesterol polyps, and effectively decreasing unnecessary cholecystectomy.

Safety and effectiveness of dabigatran in routine clinical practice: the RE-COVERY DVT/PE study.

RE-COVERY DVT/PE is a two-phase, international, observational study of anticoagulant therapy in patients with deep vein thrombosis and/or pulmonary embolism (DVT/PE). The objective of the second phase was to compare the safety and effectiveness of dabigatran versus a vitamin K antagonist (VKA) over 1 year of follow-up. Primary safety and effectiveness outcomes were major or clinically relevant nonmajor bleeding events (MBE/CRNMBEs) and symptomatic recurrent venous thromboembolism (VTE) (including deaths related to recurrent VTE). To minimize bias due to unbalanced patient characteristics, only patients in an overlapping range of estimated propensity scores were included (analytic set), and propensity score weighting was applied to compare outcomes. Outcome analysis used an as-treated approach, censoring patients after they stopped or switched their initial anticoagulant. Overall, 3009 patients enrolled from 2016 to 2018 were eligible: 60% were diagnosed with DVT alone, 21% with PE alone, and 19% with DVT plus PE. The analytic set consisted of 2969 patients. The incidence rate in %/year (95% confidence interval [CI]) of MBE/CRNMBEs was 2.63 (1.79-3.74) with dabigatran versus 4.48 (3.23-6.06) with warfarin; hazard ratio 0.63 (95% CI 0.32-1.25). For symptomatic recurrent nonfatal or fatal VTE the incidence rate was 1.53 (0.91-2.42) with dabigatran versus 2.01 (1.21-3.14) with VKAs; hazard ratio 0.78 (95% CI 0.30-2.02). In conclusion, we found lower annualized rates of MBE/CRNMBEs with dabigatran than VKA, although the difference was not statistically significant. Annualized rates of symptomatic VTE or related mortality were similar with dabigatran and VKA. These observational results with 1 year of follow-up reflect those of the randomized clinical trials. Trial registration: ClinicalTrials.gov identifier NCT02596230, first registered November 4, 2015.

Value of high frame rate contrast-enhanced ultrasound in distinguishing gallbladder adenoma from cholesterol polyp lesion.

OBJECTIVES: To compare the diagnostic value of high frame rate contrast-enhanced ultrasound (H-CEUS) in distinguishing gallbladder adenomas from cholesterol polyp lesions with that of CEUS. METHODS: This study enrolled 94 patients with gallbladder polyp lesions (GPLs) who underwent laparoscopic cholecystectomy. CEUS and H-CEUS were performed before surgery. The perfusion features of GPLs and the final diagnosis as determined by both technologies were compared. RESULTS: There were differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on H-CEUS (p < 0.05), while there were no differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on CEUS (p > 0.05). In the cholesterol polyp lesion group, there were no differences in vascular types between CEUS and H-CEUS (p > 0.05), while the vascular types were different between CEUS and H-CEUS in the gallbladder adenoma group (p < 0.05). The diagnostic value of H-CEUS in distinguishing gallbladder adenomas from cholesterol polyp lesions was better than that of CEUS. CONCLUSIONS: H-CEUS improved the time resolution by increasing the frame rate, which helped to accurately reflect the difference in the microcirculation of GPLs and improved the ability of a differential diagnosis between cholesterol polyp lesions and adenomas. H-CUES may provide an effective means of imaging for patients with GPLs regarding the choice of treatment options. KEY POINTS: • High frame rate CEUS improves the time resolution of CEUS by increasing the frame rate. • High frame rate CEUS is helpful to accurately evaluate the microvascular morphology of a gallbladder polyp lesion in the arterial phase. • High frame rate CEUS helps patients with gallbladder polyp lesions to choose the appropriate treatment means.

Profile of patients diagnosed with acute venous thromboembolism in routine practice according to age and renal function: RE-COVERY DVT/PE study.

In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft-Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT02596230. Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.

Patient perceptions of anticoagulant treatment with dabigatran or a vitamin K antagonist for stroke prevention in atrial fibrillation according to region and age: an exploratory analysis from the RE-SONANCE study.

BACKGROUND: The oral anticoagulant dabigatran offers an effective alternative to vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF), yet patient preference data are limited. The prospective observational RE-SONANCE study demonstrated that patients with AF, newly initiated on dabigatran, or switching to dabigatran from long-term VKA therapy, reported improved treatment convenience and satisfaction compared with VKA therapy. This pre-specified sub-study aimed to assess the impact of country and age on patients' perceptions of dabigatran or VKA therapy in AF. METHODS: RE-SONANCE was an observational, prospective, multi-national study (NCT02684981) that assessed treatment satisfaction and convenience in patients switching from VKAs to dabigatran (Cohort A), or newly diagnosed with AF receiving dabigatran or VKAs (Cohort B), using the PACT-Q questionnaire. Pre-specified exploratory outcomes: variation in PACT-Q2 scores by country and age (< 65, 65 to < 75, ≥ 75 years) (both cohorts); variation in PACT-Q1 responses at baseline by country and age (Cohort B). RESULTS: Patients from 12 countries (Europe/Israel) were enrolled in Cohort A (n = 4103) or B (n = 5369). In Cohort A, mean (standard deviation) PACT-Q2 score increase was highest in Romania (convenience: 29.6 [23.6]) and Hungary (satisfaction: 26.0 [21.4]) (p < 0.001). In Cohort B, mean (standard error) increase in PACT-Q2 scores between dabigatran and VKAs was highest in Romania (visit 3: 29.0 [1.3]; 24.5 [0.9], p < 0.001). Mean PACT-Q2 score increase by age (all p < 0.001) was similar across ages. PACT-Q1 responses revealed lowest expectations of treatment success in Romania and greatest concerns about payment in Estonia, Latvia, and Romania, but were similar across ages. CONCLUSIONS: Treatment satisfaction and convenience tended to favor dabigatran over VKAs. Regional differences in treatment expectations exist across Europe. TRIAL AND CLINICAL REGISTRY: Trial registration number: ClinicalTrials.gov NCT02684981. Trial registration date: February 18, 2016.

Three-channel ion chromatograph for improved metabolic evaluation of urolithiasis.

BACKGROUND: Urolithiasis is a multi-etiological disease resulting from a combination of environmental and genetic factors. One of the most challenging aspects of this disease is its high recurrence rate. For most patients, an in-depth metabolic evaluation may reveal the presence of urinary stones. The fact that different urinary stone-related compounds (USRCs) are measured by different methods renders the metabolic evaluation of urolithiasis quite tedious and complex. METHODS: A three-channel ion chromatograph (IC) that automatically measures the concentration of common metabolic indicators of urolithiasis in urine (i.e., oxalate, citrate, uric acid, calcium, and magnesium) was developed to improve the efficiency. To validate its precision and specificity, standard curves were prepared using working solution of these indicators. 100 standard solutions of these indicators were measured with our new IC and three other ICs as the control instruments; analyte concentrations in 100 24-h urine samples from volunteers and 135 calculi patients were also measured. RESULTS: All analytes had good linear relationships in concentration ranges of 0-10 mg/L. The precision experiments in the standard and urine samples showed that the measurement errors of the newly developed IC were all less than 5%. In urine, the recovery rate ranged from 99.6 to 100.4%, the coefficient of variation ranged from 1.39 to 2.99%, and the results matched between our newly developed IC and the control ICs. The results of the efficiency test showed that we can finish the analysis at the average number of 14 people per day with the new IC. While the average number in the control group is 3.85/day (p = 0.000). CONCLUSIONS: Overall, this multi-channel system significantly improves the efficiency of metabolic evaluation while retaining accuracy and precision.

The role of replay and theta sequences in mediating hippocampal-prefrontal interactions for memory and cognition.

Sequential activity is seen in the hippocampus during multiple network patterns, prominently as replay activity during both awake and sleep sharp-wave ripples (SWRs), and as theta sequences during active exploration. Although various mnemonic and cognitive functions have been ascribed to these hippocampal sequences, evidence for these proposed functions remains primarily phenomenological. Here, we briefly review current knowledge about replay events and theta sequences in spatial memory tasks. We reason that in order to gain a mechanistic and causal understanding of how these patterns influence memory and cognitive processing, it is important to consider how these sequences influence activity in other regions, and in particular, the prefrontal cortex, which is crucial for memory-guided behavior. For spatial memory tasks, we posit that hippocampal-prefrontal interactions mediated by replay and theta sequences play complementary and overlapping roles at different stages in learning, supporting memory encoding and retrieval, deliberative decision making, planning, and guiding future actions. This framework offers testable predictions for future physiology and closed-loop feedback inactivation experiments for specifically targeting hippocampal sequences as well as coordinated prefrontal activity in different network states, with the potential to reveal their causal roles in memory-guided behavior.

Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury.

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4-L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.

Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis.

Aim: To assess time-to-treatment failure (TTF) in US patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib-osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0-34.1). Median overall survival was 47.6 months (90% CI: 35.5-51.5). Conclusion: Sequential afatinib-osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov).

Long noncoding RNA myocardial infarction associated transcript promotes the development of thoracic aortic by targeting microRNA-145 via the PI3K/Akt signaling pathway.

The main aim of our study was to investigate the roles and molecular basis of long noncoding RNA myocardial infarction associated transcript (MIAT) in the development of thoracic aortic aneurysm. RT-qPCR assay was performed to measure the expressions of MIAT, microRNA-145 (miR-145), along with Bcl-2 and Bcl-xl messenger RNAs. Western blot assay was conducted to determine protein levels of Bcl-2, Bcl-xl, phosphorylated-Akt (p-Akt), and total Akt (t-Akt). Cell viability was detected by the (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The relationship of MIAT and miR-145 was examined by bioinformatics analysis and luciferase reporter assay. MIAT expression was significantly increased, and miR-145 expression was markedly reduced in thoracic aortic aneurysms compared with normal thoracic aortic tissues. MIAT overexpression or miR-145 depletion improved cell viability and inhibited cell apoptosis in human aortic vascular smooth muscle cells (h-VSMCs). Further exploration revealed that MIAT could inhibit miR-145 expression by direct interaction. And miR-145 upregulation abrogated MIAT-induced viability increase and apoptosis inhibition in h-VSMCs. Moreover, MIAT inhibited the activation of Akt signaling, while this effect was abated by miR-145 overexpression in h-VSMCs. The inhibition of the Akt pathway by MK-22062HCl resulted in the reduction of cell viability and the increase of cell apoptotic activity in h-VSMCs. Akt activation by HY-18749 improved cell viability and suppressed cell apoptosis in h-VSMCs. And the introduction of HY-18749 raised cell viability and curbed cell apoptosis in h-VSMCs cotransfected with MIAT overexpression plasmid and miR-145 mimic. lncRNA-MIAT could target miR-145 to affect the viability and apoptosis of h-VSMCs, which was implicated in the regulation of the PI3K/Akt signaling pathway.

Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for memory during sleep and waking states.

It is widely believed that memories that are encoded and retrieved during waking behavior are consolidated during sleep. Recent studies on the interactions between the hippocampus and the prefrontal cortex have greatly advanced our understanding of the physiological bases of these memory processes. Although hippocampal-prefrontal network activity differs in many aspects during waking and sleep states, here we review evidence that hippocampal sharp-wave ripples (SWRs) emerge as a common neurophysiological pattern in both states, facilitating communication between these two regions via coordinated reactivation of stored memory information. We further consider whether sleep and awake reactivation mediate similar memory processes or have different mnemonic functions, and the mechanistic role of this cross-regional dialogue in learning and memory. Finally, we provide an integrated view of how these two forms of reactivation might work together to support spatial learning and memory.