Astrocyte-mediated regulation of BLAWFS1 neurons alleviates risk-assessment deficits in DISC1-N mice.

Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLAWFS1 neurons' NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.

The risk assessment tool for intensive care unit readmission: A systematic review and meta-analysis.

OBJECTIVE: To review and evaluate existing risk assessment tools for intensive care unitreadmission. METHODS: Nine electronic databases (Medline, CINAHL, Web of Science, Cochrane Library, Embase, Sino Med, CNKI, VIP, and Wan fang) were systematically searched from their inception to September 2022. Two authors independently extracted data from the literature included. Meta-analysis was performed under the bivariate modeling and summary receiver operating characteristic curve method. RESULTS: A total of 29 studies were included in this review, among which 11 were quantitatively Meta-analyzed. The results showed Stability and Workload Index for Transfer: Sensitivity = 0.55, Specificity = 0.65, Area under curve = 0.63. And Early warning score: Sensitivity = 0.78, Specificity = 0.83, Area under curve = 0.88. The remaining tools included scores, nomograms, machine learning models, and deep learning models. These studies, with varying reports on thresholds, case selection, data preprocessing, and model performance, have a high risk of bias. CONCLUSION: We cannot identify a tool that can be used directly in intensive care unit readmission risk assessment. Scores based on early warning score are moderately accurate in predicting readmission, but there is heterogeneity and publication bias that requires model adjustment for local factors such as resources, demographics, and case mix. Machine learning models present a promising modeling technique but have a high methodological bias and require further validation. IMPLICATIONS FOR CLINICAL PRACTICE: Using reliable risk assessment tools is essential for the early identification of unplanned intensive care unit readmission risk in critically ill patients.  A reliable risk assessment tool must be developed, which is the focus of further research.

Low-cost diatomite supported binary transition metal sulfates: an efficient reusable solid catalyst for biodiesel synthesis.

Using a simple method of impregnation and then calcination, diatomite supported binary transition metal sulfates (Fe and Zr, designated as Fe2(SO4)3&Zr(SO4)2@diatomite) were prepared and used as a catalyst in the preparation of renewable biofuels. The synthesised Fe2(SO4)3&Zr(SO4)2@diatomite catalyst (Fe2(SO4)3 : Zr(SO4)2 : diatomite = 1 : 2 : 6, mass ratio) was thoroughly characterised using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, microbeam X-ray fluorescence (µ-XRF) spectroscopy and thermogravimetric analysis (TG). The results demonstrated that the sulfate was successfully loaded onto the diatomite with a uniform distribution. The N2 adsorption/desorption analysis indicated that the catalyst's specific surface area was 1.54 m2 g-1. The catalyst exhibited outstanding performance in the preparation of renewable biofuel (biodiesel) from waste fatty acids and the optimal parameters were methanol-to-oil 1.25 : 1, reaction temperature 70 °C, catalyst concentration 10 wt%, reaction time 4 h. The conversion was found to reach 98.90% under optimal parameters, which is better than that of Fe2(SO4)3·xH2O, Zr(SO4)2·4H2O, Fe2(SO4)3@diatomite and Zr(SO4)2@diatomite. Moreover, the catalyst can be recycled by simple filtration and reused for three cycles after regeneration without noticeable reduction in catalytic activity.

Application of a Caries Treatment Difficulty Assessment System in Dental Caries Management.

Dental caries is one of the most common chronic diseases caused by progressive bacteria, affecting all age groups. Today, restorative fillings are widely used for dental caries treatment, but the restorative treatment has a high failure rate. Meanwhile, many researchers have discovered the differences of caries risk among populations by using the caries risk assessment and put forward a new standpoint that caries should be treated individually. Therefore, our research group established a Dental Caries Treatment Difficulty Assessment system in a previous study. This time, we combined the caries risk assessment with the caries treatment difficulty assessment, then used Python to design a Dental Caries Management Software. The purpose of this case report is to present a case applying this software in dental caries management and other data collected in Chengdu, China, with this software on the assessment of caries treatment difficulty. Patients with personalized assessment and management can achieve good treatment results, including reducing the risk and treatment difficulty of dental caries. At the same time, other cases show that the software has good application potential in individual management and group information collection. These cases indicate that the software enables dentists to carry out both the risk assessments and the treatment difficulty assessment of patients, and it has the potential as a tool for epidemiological investigation. It also enables dentists and patients to have a basic understanding of the dental health status of patients and create personalized dental caries treatment, so as to achieve the goal of controlling the progression of dental caries and rebuilding the structure and restoring the function of teeth.

Quality Assessment of Cancer Pain Clinical Practice Guidelines.

Introduction: Several clinical practice guidelines (CPGs) for cancer pain have been published; however, the quality of these guidelines has not been evaluated so far. The purpose of this study was to evaluate the quality of CPGs for cancer pain and identify gaps limiting knowledge. Methods: We systematically searched seven databases and 12 websites from their inception to July 20, 2021, to include CPGs related to cancer pain. We used the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist to assess the methodology and reporting quality of eligible CPGs. The overall agreement among reviewers with the intraclass correlation coefficient (ICC) was calculated. The development methods of CPGs, strength of recommendations, and levels of evidence were determined. Results: Eighteen CPGs published from 1996 to 2021 were included. The overall consistency of the reviewers in each domain was acceptable (ICC from 0.76 to 0.95). According to the AGREE II assessment, only four CPGs were determined to be recommended without modifications. For reporting quality, the average reporting rates for all seven domains of CPGs was 57.46%, with the highest domain in domain 3 (evidence, 68.89%) and the lowest domain in domain 5 (review and quality assurance, 33.3%). Conclusion: The methodological quality of cancer pain CPGs fluctuated widely, and the complete reporting rate in some areas is very low. Researchers need to make greater efforts to provide high-quality guidelines in this field to clinical decision-making.

Current practice and barriers to ICU-acquired weakness assessment: a cross-sectional survey.

BACKGROUND: Intensive-care-unit-acquired weakness (ICU-AW) not only leads to difficulty weaning off mechanical ventilation, prolonged hospital stay and increased medical costs, but also reduces the patient's quality of life after discharge and increases the 1-year mortality rate. Early identification and intervention can improve the prognosis of critically ill patients. However, much remains unknown about current clinical practice for ICU-AW assessment by ICU staff in China. OBJECTIVES: To investigate current practices and barriers to ICU-AW assessment among ICU staff, and provide insights to improve ICU-AW assessment in ICUs in China. METHODS: Qualitative interviews were used to construct a survey questionnaire (test-retest reliability 0.92, validity 0.96). This survey was subsequently completed by 3206 ICU staff from 31 provinces, municipalities and autonomous regions in China. RESULTS: In total, 3206 ICU staff responded to the survey (response rate 90%): 616 doctors (19%), 2371 nurses (74%), 129 respiratory therapists (4%), 51 physiotherapists (2%) and 39 dieticians (1%). Only 27% of the respondents had treated/cared for patients with ICU-AW. Reported methods for ICU-AW assessment were clinical experience (53%), ICU-AW assessment tools (12%), and physiotherapy consultation (35%). Forty-three percent of respondents felt that their ICU-AW-related knowledge did not meet clinical needs, only 10% had received ICU-AW-related training, and 19% proactively assessed whether their patients had ICU-AW. In terms of frequency of assessment, 42%, 16% and 11% of respondents considered that ICU-AW should be assessed daily, every 3 days, and on ICU admission and discharge, respectively. The Medical Research Council scale, electrophysiological assessment and the Manual Muscle Testing scale were considered to be optimal tools for ICU-AW diagnosis by 79%, 70%, and 73% of respondents, respectively. The main reported barriers to ICU-AW assessment were lack of knowledge, cognitive impairment among patients, and lack of ICU-AW assessment guidelines and procedures. CONCLUSION: Current practices for ICU-AW assessment are non-specific, and the main barriers include lack of skills and knowledge.

Chinesisation, adaptation and validation of the Chelsea Critical Care Physical Assessment Tool in critically ill patients: a cross-sectional observational study.

PURPOSE: To translate and adapt the Chelsea Critical Care Physical Assessment Tool (CPAx) into Chinese version ('CPAx-Chi'), test the reliability and validity of CPAx-Chi, and verify the cut-off point for the diagnosis of intensive care unit-acquired weakness (ICU-AW). STUDY DESIGN: Cross-sectional observational study. METHODS: Forward and back translation, cross-cultural adaptation and pretesting of CPAx into CPAx-Chi were based on the Brislin model. Participants were recruited from the general ICU of five third-grade class-A hospitals in western China. Two hundred critically ill adult patients (median age: 53 years; 64% men) with duration of ICU stay ≥48 hours and Glasgow Coma Scale ≥11 were included in this study. Two researchers simultaneously and independently assessed eligible patients using the Medical Research Council Muscle Score (MRC-Score) and CPAx-Chi. RESULTS: The content validity index of items was 0.889. The content validity index of scale was 0.955. Taking the MRC-Score scale as standard, the criterion validity of CPAx-Chi was r=0.758 (p<0.001) for researcher A, and r=0.65 (p<0.001) for researcher B. Cronbach's α was 0.939. The inter-rater reliability was 0.902 (p<0.001). The area under the receiver operating characteristic curves of CPAx-Chi for diagnosing ICU-AW based on MRC-Score ≤48 were 0.899 (95% CI 0.862 to 1.025) and 0.874 (95% CI 0.824 to 0.925) for researcher B. The best cut-off point for CPAx-Chi for the diagnosis of ICU-AW was 31.5. The sensitivity was 87% and specificity was 77% for researcher A, whereas it was 0.621, 31.5, 75% and 87% for researcher B, respectively. The consistency was high when taking CPAx-Chi ≤31 and MRC-Score ≤48 as the cut-off points for the diagnosis of ICU-AW. Cohen's kappa=0.845 (p=0.02) in researcher A and 0.839 (p=0.04) for researcher B. CONCLUSIONS: CPAx-Chi demonstrated content validity, criterion-related validity and reliability. CPAx-Chi showed the best accuracy in assessment of patients at risk of ICU-AW with good sensitivity and specificity at a recommended cut-off of 31.

[Current practice and obstacle factors of intensive care unit-acquired weakness assessment].

OBJECTIVE: To investigate the current status of intensive care unit-acquired weakness (ICU-AW) assessment, analyze the assessment barriers, and to provide reference to improve ICU-AW assessment. METHODS: A convenient sampling cross-sectional survey was conducted. First, an interview outline which based on related domestic and international literatures and combining with the research purpose of this study were designed. Thirteen medical personnel (8 ICU nurses, 3 ICU doctors, 1 respiratory therapist and 1 physiotherapist) who worked in the intensive care unit (ICU) of the First Hospital of Lanzhou University were enrolled with convenience sampling method to interview. Second, the topics were comprehensively analyzed and extracted, and then a questionnaire was constructed, and the reliability and validity was assessed. Finally, the questionnaire survey including the general situation of ICU medical staffs, the current practices of ICU-AW and influencing factors was implemented in China. RESULTS: The retest reliability was 0.92 and expert validity was 0.96 of the questionnaire. There were 3 563 respondents in 31 provinces, municipalities and autonomous regions which eliminated 357 unqualified questionnaires, including 173 respondents from neonatal or pediatric ICU, 89 respondents whose working time was less than 6 months, and 95 invalid respondents, and then there were finally 3 206 valid questionnaires and the response rate were 90.0%. Those 3 206 respondents included 616 doctors (19.2%), 2 371 nurses (74.0%), 129 respiratory therapists (4.0%), 51 physiotherapist (1.6%) and 39 dietitians (1.2%). The mean age was (30.7±6.3) years old. Most of them had bachelor's degree (65.9%), master and above was 14.1%. Associate senior physician and above was 8.0%; ICU working time was (5.94±4.50) years. In clinical practice, only 26.5% of the ICU medical staffs confirmed that they had treated or taken care for ICU-AW patients; 52.9% of medical staffs evaluated ICU-AW only based on clinical experience, and only 12.3% used ICU-AW assessment tools. The majority of respondents believed that ICU-AW knowledge training should be performed (81.8%), ICU-AW assessment should be as important as other complications (pressure sore, infected ventilator associated pneumonia, etc., 75.1%), and ICU-AW assessment should be part of daily treatment and care activities (61.2%). However, only 10.2% of respondents had received ICU-AW related knowledge training, and 42.7% respondents believed that their ICU-AW related knowledge could not meet clinical needs. Only 18.7% respondents would actively assess whether patients suffered from ICU-AW or not, and 42.3% respondents thought that ICU-AW should be assessed every day, and the assessment tools were also inconsistent. There were 44.0% respondents considered the Medical Research Council Muscle score (MRC-score) scale was the optimal tool for diagnosing ICU-AW, the following were neuro-electrophysiological examination (17.2%) and manual muscle strength (MMT, 11.1%). The main cause of the ICU-AW assessment barriers was the lack of ICU-AW related knowledge (88.1%), and the following were lack of ICU-AW assessment guidelines (76.5%), patients' cognitive impairment or limited understanding ability (84.6%), unable to cooperate with the assessment due to critical illness (83.0%), and inadequate attention to ICU-AW assessment by the department (77.5%). CONCLUSIONS: The current status of ICU-AW assessment were unsatisfying in China, and the main barriers were lack of skills and knowledge.

Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression.

PURPOSE: The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. METHODS: The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. RESULTS: A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004). CONCLUSIONS: Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. KEY POINTS: • More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

Improving High-Throughput Phenotyping Using Fusion of Close-Range Hyperspectral Camera and Low-Cost Depth Sensor.

Hyperspectral sensors, especially the close-range hyperspectral camera, have been widely introduced to detect biological processes of plants in the high-throughput phenotyping platform, to support the identification of biotic and abiotic stress reactions at an early stage. However, the complex geometry of plants and their interaction with the illumination, severely affects the spectral information obtained. Furthermore, plant structure, leaf area, and leaf inclination distribution are critical indexes which have been widely used in multiple plant models. Therefore, the process of combination between hyperspectral images and 3D point clouds is a promising approach to solve these problems and improve the high-throughput phenotyping technique. We proposed a novel approach fusing a low-cost depth sensor and a close-range hyperspectral camera, which extended hyperspectral camera ability with 3D information as a potential tool for high-throughput phenotyping. An exemplary new calibration and analysis method was shown in soybean leaf experiments. The results showed that a 0.99 pixel resolution for the hyperspectral camera and a 3.3 millimeter accuracy for the depth sensor, could be achieved in a controlled environment using the method proposed in this paper. We also discussed the new capabilities gained using this new method, to quantify and model the effects of plant geometry and sensor configuration. The possibility of 3D reflectance models can be used to minimize the geometry-related effects in hyperspectral images, and to significantly improve high-throughput phenotyping. Overall results of this research, indicated that the proposed method provided more accurate spatial and spectral plant information, which helped to enhance the precision of biological processes in high-throughput phenotyping.

Introducing an antibiotic stewardship program in a pediatric center in China.

BACKGROUND: This study aimed to investigate the effect of antibiotic stewardship programs (ASP) on reducing antimicrobial resistance rate, antibiotics consumption and multi-drug resistance bacterial infections in the pediatric patients. METHODS: This study was carried out in the Pediatric Center of a tertiary hospital of Shandong Province, China. The study duration was separated into two periods according to introduction of ASP (began from April 2011). Before intervention: from April 2009 to March 2011; after intervention: from April 2012 to March 2014. The consumption of antibiotics, defined daily dose (DDD), isolation of multidrug-resistant organisms (MDRO) and resistance rate of antibiotics were analyzed and compared between the two study periods. RESULTS: Total antibiotics consumption (DDDs) reduced from 56,725 in 2011 to 31,380 in 2014; antibiotic use density (AUD) reduced from 93.8 to 43.5; mean (± SD) antibiotic costs per patient (per quarter) decreased from 637 (± 29) RMB to 462 (± 49) RMB; and the mean total drug consumption (g)/DDD (DDDs) for inpatients decreased from 90.4 (± 3.3) to 56.4 (± 9.5). Multidrug-resistant microorganisms isolation reduced significantly from 463 (20.0) to 216 (6.9%). Resistance rate of general spectrum antibiotics reduced remarkably after intervention. The proportion of patients colonized or infected with Carbapenems-resistant Acinetobacter baumannii was correlated with DDDs of carbapenem. CONCLUSIONS: Implementation of ASP leads to reduced medical expense, decrease of improper and abuse of antibiotics, and reduced antibiotics resistance rate and MDRO isolation. Continuous efforts to improve antibiotic use are required.

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine.

Human papillomavirus is considered the causative factor for cervical cancer, which accounts for approximately 5% of the global cancer burden and more than 600,000 new cases annually that are attributable to HPV infection worldwide. The first-generation prophylactic HPV vaccines, Gardasil® and Cervarix®, were licensed approximately a decade ago. Both vaccines contain the most prevalent high-risk types, HPV16 and 18, which are associated with 70% of cervical cancer. To further increase the type coverage, 5 additional oncogenic HPV types (31, 33, 45, 52 and 58) were added to the existing Gardasil-4 to develop a 9-valent HPV vaccine (9vHPV), Gardasil 9®, increasing the potential level of protection from ∼70% to ∼90%. The efficacy of the vaccine lies primarily in its ability to elicit type-specific and neutralizing antibodies to fend off the viral infection. Therefore, type-specific and neutralizing murine monoclonal antibodies (mAbs) were used to quantitate the antigenicity of the individual vaccine antigens and to measure the antibody levels in the serum samples from vaccinees in a type- and epitope-specific manner in a competitive immunoassay. Assays for 9vHPV are extended from the proven platform used for 4vHPV by developing and adding new mAbs against the additional types. In Phase III clinical trials, comparable safety profile and immunogenicity against the original 4 types were demonstrated for the 9vHPV vaccine, and these were comparable to the 4vHPV vaccine. The efficacy of the 9vHPV vaccine was established in trials with young women. Immunobridging for younger boys and girls was performed, and the results showed higher immunogenicity in the younger age group. In a subsequent clinical trial, the 2-dose regimen of the 9vHPV vaccine used among girls and boys aged 9-14 y showed non-inferior immunogenicity to the regular 3-dose regimen for young women (aged 16-26 years). Overall, the clinical data and cost-effectiveness analysis for the 9vHPV vaccine support its widespread use to maximize the impact of this important, life-saving vaccine.

Association of quantitative assessment of the intrafollicular proliferation index with outcome in follicular lymphoma.

The role of the proliferation index (PI) as an outcome predictor in follicular lymphoma (FL) isn't clear. We have previously demonstrated that quantitative image analysis (QIA) is a robust tool for PI determination and the present study aimed to determine the significance of the PI for outcome in low-grade FL. One hundred and twenty-nine patients with grade 1-2 FL were retrospectively analysed. Slides were scanned digitally and follicle/tumour-involved areas were annotated. The intrafollicular PI was estimated by analysing a median of 10 follicles per case. Patients were divided into two groups: PI < 30%, PI ≥ 30% and clinical outcome was analysed. Among the 129 patients analysed, intrafollicular PI ranged from 0·6 to 63·2% with a median of 23·3%. Overall survival was not influenced by PI group. Among those patients initially observed, intrafollicular PI < 30% was associated with longer time to first therapy compared to patients with a PI ≥ 30%. In the group of patients that were treated at diagnosis, PI was not predictive of time to treatment failure (TTTF). Intrafollicular PI is an important predicator of TTFT for patients who are candidates for observation. Further confirmation in an independent cohort of patients is necessary to determine the clinical validity of the results.

Real-time intraoperative computed tomography assessment of quality of permanent interstitial seed implantation for prostate cancer.

OBJECTIVES: To evaluate the use of real-time kilovoltage cone-beam computed tomography (CBCT) during prostate brachytherapy for intraoperative dosimetric assessment and correcting deficient dose regions. METHODS: A total of 20 patients were evaluated intraoperatively with a mobile CBCT unit immediately after implantation while still anesthetized. The source detector system was enclosed in a circular CT-like geometry with a bore that accommodates patients in the lithotomy position. After seed deposition, the CBCT scans were obtained. The dosimetry was evaluated and compared with the standard postimplantation CT-based assessment. In 8 patients, the deposited seeds were localized in the intraoperative CBCT frame of reference and registered to the intraoperative transrectal ultrasound images. With this information, a second intraoperative plan was generated to ascertain whether additional seeds were needed to achieve the planned prescription dose. The final dosimetry was compared with the postimplantation scan assessment. RESULTS: The mean differences between the dosimetric parameters from the intraoperative CBCT and postimplant CT scans were < .5% for percentage of volume receiving 100% of the prescription dose, minimal dose received by 90% of the prostate, and percentage of volume receiving 150% of the prescription dose. The minimal dose received by 5% (maximal dose) of the urethra differed by 8% on average and for the rectum an average difference of approximately 18% was observed. After fusion of the implanted seed coordinates from the intraoperative CBCT scans to the intraoperative transrectal ultrasound images, the dosimetric outcomes were not significantly different from the postimplantation CT dosimetric results. CONCLUSIONS: Intraoperative CT-based dosimetric evaluation of prostate permanent seed implantation before anesthesia reversal is feasible and might avert misadministration of dose delivery. The dosimetric measurements using the intraoperative CBCT scans were dependable and correlated well with the postimplant diagnostic CT findings.