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This research investigates (1) the significance and function of the consumer protection and anti-monopoly division within the Industry and Trade Office in supporting business entities, and (2) the measures that the Industry and Trade Office should adopt moving forward to address regulatory needs, particularly concerning anti-monopoly and business competition, in Kendari. This study employs Conflict Theory and Symbolic Interaction Theory as its theoretical framework. The findings reveal that (1) the relevant division plays a crucial role in conducting Consumer Protection Socialization as a program managed by the Industry and Trade Office of Southeast Sulawesi Province, involving business entities, consumers, community members, and university students; (2) activities centered around consumer protection and anti-monopoly implemented by the relevant division are as described by the Head of the Consumer Protection and Trade Order Division: The Consumer Protection Monitoring System serves as a medium for consumer complaints and information related to consumer protection to be integrated into the system at the Provincial Office responsible for trade, aiming to enhance service to consumers in lodging complaints from those who feel wronged.

The SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as an approximation for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays identified substitutions which conferred strong nirmatrelvir resistance and others that compromised activity. On the other hand, N142A and the P132H mutation, carried by the Omicron variant, caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.

β-Lactams are the most widely prescribed class of antibiotics that inhibit penicillin-binding proteins (PBPs), particularly transpeptidases that function in peptidoglycan synthesis. A major mechanism of antibiotic resistance is the production of β-lactamase enzymes, which are capable of hydrolyzing β-lactam antibiotics. There have been many efforts to counter increasing bacterial resistance against β-lactams. These studies have mainly focused on three areas: discovering novel inhibitors against β-lactamases, developing new β-lactams less susceptible to existing resistance mechanisms, and identifying non-β-lactam inhibitors against cell wall transpeptidases. Drug discovery in the β-lactam field has afforded a range of research opportunities for academia. In this review, we summarize the recent new findings on both β-lactamases and cell wall transpeptidases because these two groups of enzymes are evolutionarily and functionally connected. Many efforts to develop new β-lactams have aimed to inhibit both transpeptidases and β-lactamases, while several promising novel β-lactamase inhibitors have shown the potential to be further developed into transpeptidase inhibitors. In addition, the drug discovery progress against each group of enzymes is presented in three aspects: understanding the targets, screening methodology, and new inhibitor chemotypes. This is to offer insights into not only the advancement in this field but also the challenges, opportunities, and resources for future research. In particular, cyclic boronate compounds are now capable of inhibiting all classes of β-lactamases, while the diazabicyclooctane (DBO) series of small molecules has led to not only new β-lactamase inhibitors but potentially a new class of antibiotics by directly targeting PBPs. With the cautiously optimistic successes of a number of new β-lactamase inhibitor chemotypes and many questions remaining to be answered about the structure and function of cell wall transpeptidases, non-β-lactam transpeptidase inhibitors may usher in the next exciting phase of drug discovery in this field.

There is a trend toward formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment in rehabilitation wards. So far, literature about the principles of CRE is scarce. This study aims to explore the opinions of rehabilitants and informal caregivers regarding CRE, through a qualitative study between 2019 and 2020. Three telephone interviews were conducted with informal caregivers, and also 3 focus groups with 15 rehabilitants and 3 informal caregivers, all with recent experience in rehabilitation. Nine themes emerged regarding the rehabilitation process: (1) rehabilitant (attention for resilience, motivation, cognitive and emotional aspects), (2) rehabilitant centered (goal setting, physical and cognitive functioning and coping), (3) informal caregivers (involving and attention for resilience and relation), (4) communication (aligning the rehabilitation process), (5) exercise (increasing intensity by using task-oriented exercise, patient-regulated exercise, and group training), (6) peer support (learning experiences and recognition), (7) daily schedule (influence on the planning and activities outside therapy), (8) nutrition (energy for rehabilitation), and (9) eHealth (makes rehabilitation more challenging and fun). Regarding organizational processes, 4 themes were identified: (1) environmental aspects (single bedrooms, shared room for activities and therapy options on the ward), (2) staff aspects (small team with an emphatic supportive and motivating attitude), (3) organizational aspects (organized in an efficient way), and (4) return home (the discharge process should be well prepared for instance with home visits). Organizing excellent rehabilitation care requires a thorough understanding of the concept of CRE, as it is a complex and comprehensive concept that concerns the whole rehabilitation process. Its effectiveness and efficiency should be researched in prospective studies.

Wei Chen, Ning Wang, Minxue Lian Department of Neurosurgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shanxi Province, 710061, People’s Republic of ChinaCorrespondence: Minxue LianDepartment of Neurosurgery, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an City, Shanxi Province, 710061, People’s Republic of ChinaEmail MinxueLianShanxi@163.comBackground: CircRNA circPTK2 plays opposite roles in different cancers, while its role in glioblastoma is unknown. The aim of this study was to explore the involvement of circPTK2 in glioblastoma.Methods: Expression of circPTK2, mature miR-23a, and premature miR-23a in paired cancer and non-cancer tissues from glioblastoma patients (n = 60) was analyzed by RT-qPCR. Pearson’s correlation coefficient was used to analyze the correlations between gene expressions. The effects of circPTK2 overexpression on miR-23a maturation were analyzed by transfecting circPTK2 expression vector into glioblastoma cells, followed by determining the expression of mature miR-23a and premature miR-23a by RT-qPCR. Transwell assays were carried out to explore the role of circPTK2 and miR-23a in regulating glioblastoma cell invasion and migration.Results: We found that circPTK2 was downregulated in GBM and was inversely correlated with mature miR-23a, but not premature miR-23a. GBM cells transfected with circPTK2 expression vector showed significantly downregulated mature miR-23a, but not premature miR-23a. Transwell assay analysis showed that circPTK2 overexpression decreased cell invasion and migration, while miR-23a increased cell invasion and migration. Moreover, miR-23a overexpression reversed the inhibitory effects of circPTK2 overexpression on cell behaviors.Conclusion: CircPTK2 might suppress cancer cell invasion and migration by inhibiting the maturation of miR-23a.Keywords: glioblastoma, circPTK2, miR-23a, maturation, invasion, migration

Guofeng Xiong,1,2 Jiaming Chen,1 Zhen Wu,1 Shizhi He,1 Meng Lian,1 Jugao Fang1 1Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Wenzhou Central Hospital, Wenzhou 325000, People’s Republic of ChinaCorrespondence: Meng Lian; Jugao Fang Department of OtorhinolaryngologyHead and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 8 Chongwenmen Inner Street, Dongcheng District (East District), Beijing 100730, People’s Republic of ChinaTel/Fax +86-010-58266699Email lianmeng_3@163.com; jugaofang03162@163.comBackground: Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules.Methods: LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 (ADAM10) were predicted on a bioinformatics system and then validated through luciferase reporter gene assays. Expression of miR-493 and ADAM10 in TC cells was determined. Gain- and loss-of functions of LUCAT1, miR-493 and ADAM10 were performed to explore their influences on the behaviors of TC cells. Xenograft tumors were induced in nude mice for in vivo studies.Results: LUCAT1 and ADAM10 were highly expressed, while miR-493 was poorly expressed in TC cell lines. LUCAT1 served as a miR-493 sponge to upregulate ADAM10 expression. Silencing of LUCAT1 discouraged proliferation, invasion, and migration but triggered apoptosis of TC cells. By contrast, these changes were abrogated by further miR-493 inhibition or ADAM10 upregulation. The in vitro experiment results were reproduced in vivo. In addition, miR-493 inhibition or ADAM10 overexpression was found to increase the phosphorylation of STAT3 in cells.Conclusion: This study evidenced that LUCAT1 increases ADAM10 expression through sequestering miR-493, leading to JAK-STAT activation and TC cell growth and metastasis. LUCAT1 and ADAM10 may serve as therapeutic targets for TC treatment.Keywords: long non-coding RNA LUCAT1, microRNA-493, ADAM10, thyroid carcinoma, JAK-STAT signaling pathway

Sandip Patil,1,2 Hongyu Chen,2 Xiaoli Zhang,2 Ma Lian,2 Pei-Gen Ren,1 Feiqiu Wen2 1Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, People’s Republic of China; 2Shenzhen Children’s Hospital, Futian District, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Feiqiu WenShenzhen Children’s Hospital, 7019 Yitian Road, Futian District, Shenzhen, Guangdong Province 518038, People’s Republic of ChinaTel +86 18938690333Fax +86-755 83009888Email fwen62@163.comIntroduction: The emergence of multi-drug-resistant Gram-negative bacteria (GNB) is a concern in China and globally. This study investigated antimicrobial resistance traits and resistance determinant detection in GNB isolates from paediatric patients in China.Methods: In the present study, a total of 170 isolates of GNB including the most prevalent Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii were collected from Shenzhen Children’s Hospital, China. ESBLs production was confirmed by using the combination disc diffusion method, and carbapenemase production was confirmed by using a carbapenem inactivation method followed by antimicrobial susceptibility. In addition, β-lactamase-encoding genes and co-existence of plasmid-borne colistin resistance mcr-1 gene were determined by PCR and sequencing.Results: Overall, 170 etiological agents (GNB) were recovered from 158 paediatric patients. The most prevalent species was E. coli 40% (n=68), followed by K. pneumoniae 17.64% (n=30), and Enterobacter cloacae 14.11% (n=24). Of 170 GNB, 71.76% (n=122) were multi-drug-resistant, 12.35% (n=21) extreme-drug resistant, and 7.64% (n=13) single-drug-resistant, while 8.23% (n=14) were sensitive to all of the studied antibiotics. The prevalence of ESBLs and carbapenemase producers were 60% and 17%, respectively. blaCTX-M was the most prevalent resistance gene (59.42%), followed by blaTEM (41.17%), blaSHV (34.270%), blaKPC (34.11%), blaOXA-48 (18.82%) and blaNDM-1 (17.64%).Conclusion: The present study provides insights into the linkage between the resistance patterns of GNB to commonly used antibiotics and their uses in China. The findings are useful for understanding the genetics of resistance traits and difficulty in tackling of GNB in paediatric patients.Keywords: Gram-negative bacteria, antimicrobial susceptibility, ESBLs, carbapenemase, molecular characterization

Tao-Yan Lin,1,* Yan Chen,1,* Jun-Shuang Jia,1,* Chen Zhou,2 Mei Lian,3 Yue-Ting Wen,1 Xiao-Yan Li,3 Heng-Wei Chen,3 Xiao-Lin Lin,1 Xiao-Ling Zhang,4 Sheng-Jun Xiao,2 Yan Sun,5 Dong Xiao1,31Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 3Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, People’s Republic of China; 5Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workPurpose: The correlation of cold-inducible RNA-binding protein (Cirbp) expression with clinicopathological features including patient prognosis in nasopharyngeal carcinoma (NPC) was investigated.Methods: The expression of Cirbp in NPC cell lines and tissue specimens was examined by qRT-PCR or immunohistochemistry (IHC).Results: Immunohistochemistry (IHC) results showed that high Cirbp expression was detected in 61 of 61 non-cancerous nasopharyngeal squamous epithelial biopsies, whereas the significantly reduced expression of Cirbp was observed in NPC specimens. In addition, IHC assay for Cirbp protein illustrated that the cells of 177 NPC samples and nasopharyngeal squamous epithlial cells displayed strong signals in nuclei and faint signals in cytoplasm, whereas Cirbp protein is mainly detected in the cell’s cytoplasm in many other cancers. More importantly, TNM classification displayed that the low expression of Cirbp was more frequently observed in T3-T4, N2-N3, M1 and III-IV NPC biopsies, and undifferentiated carcinoma (UDC) than T1-T2, N0-N1, M0 and I-II tumors, and differentiated nonkeratinizing carcinoma (DNKC), suggesting that Cirbp loss is a key molecular event in advanced cases of NPC. Kaplan–Meier survival analysis indicated that NPC patients showing lower Cirbp expression had a significantly shorter overall survival time than those with high Cirbp expression. Multivariate analysis suggested that the level of Cirbp expression was an independent prognostic indicator for NPC survival. Finally, we revealed a significant positive association between Cirbp expression and E-cadherin, and a notable negative correlation between Cirbp expression and Ki67 labeling index in NPC biopsies.Conclusion: Collectively, these findings demonstrate that loss of Cirbp expression is correlated with malignant progression and poor prognosis in NPC.Keywords: cirbp, nasopharyngeal carcinoma; NPC, TNM stage, prognosis, E-cadherin, Ki67

Sandip Patil,1,2 Xiaowen Chen,1,2 Ma Lian,2 Feiqiu Wen1,21Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province 518038, People’s Republic of China; 2Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province 518038, People’s Republic of ChinaAims and Objectives: The emergence and spread of extended-spectrum β-lactamases (ESBLs) particularly CTX-M producing multi-drug-resistant (MDR) Escherichia coli (E. coli) is one of the greatest challenges for community health globally. The study investigated the phenotypic and genotypic characteristics of ESBLs-producing E. coli recovered from pediatric patients from Shenzhen Children’s Hospital, China.Materials and methods: Present study, a total of 2,670 isolates of E. coli were collected from Shenzhen Children’s Hospital, China of which 950 were ESBLs producer. ESBLs production was confirmed by using the combination disc diffusion method, and antimicrobial susceptibility test was detected. In addition, β-lactamase-producing genes and co-existence of carbapenem/colistin resistance genes were determined by PCR assay and sequencing. The diversity and phylogenetic relationship were determined by multi-locus sequence typing method.Results: Thirty-five percent (n=950) prevalence of ESBLs-producing E. coli we reported in Shenzhen, China of which 50 ESBLs producing E. coli were randomly selected for a further characterization. All 50 ESBLs- producing E. coli isolates revealed MDR phenotype and 100% were resistant to Ampicillin/sulbactam, Ampicillin, Cefazolin, and Ceftriaxone. All 50 ESBLs producers harbored at least one type of β-lactamase gene particular blaCTX-M. The PCR and sequencing revealed the most common CTX-M subtype was blaCTX-M-15 (n=18), followed by blaCTX-M-14 (n=16), blaCTX-M-90 (n=9), blaCTX-M-55 (n=3), blaCTX-M-27, blaCTX-M-101, and blaCTX-M-211 each (n=1). Co-existence of blaCTX-M with blaTEM, blaSHV, blaGES, and blaVEB was detected in few isolates. Among identified sequence types, ST131 (12%) was more dominant in ESBLs-producing E. coli. Phylogenetic group A was the most prominent group among the ESBLs-producing E. coli based on multiplex PCR.Conclusion: Our study shows the prevalence of blaCTX-M gene in ESBLs-producing E. coli in pediatric patients in Shenzhen, China. We highlight the importance to monitor the emergence and trends of ESBLs-producing isolates in a pediatric healthcare setting.Keywords: Antimicrobial resistance, molecular characterization, MLST, ESBLs, Escherichia coli

Guolin Hong,1 Gang Rui,2 Dongdong Zhang,1 Mingjian Lian,1 Yuanyuan Yang,1 Ping Chen,1 Huijing Yang,3 Zhichao Guan,4 Wei Chen,5 Yan Wang6 1Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361005, People’s Republic of China; 2Department of Orthopaedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361005, People’s Republic of China; 3Department of Clinical Medicine, Fujian Medical University, Fuzhou 350108, People’s Republic of China; 4Department of Research and development, Xiamen Passtech Co.,Ltd., Xiamen 361101, People’s Republic of China; 5Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou 350004, People’s Republic of China; 6Department of Cardiology, the Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, People’s Republic of China Background: Acute myocardial infarction (AMI), usually caused by atherosclerosis of coronary artery, is the most severe manifestation of coronary artery disease which results in a large amount of death annually. A new diagnosis approach with high accuracy, reliability and low measuring-time-consuming is essential for AMI quick diagnosis. Purpose: The objective of this study was to develop a new point-of-care testing system with high accuracy and reliability for AMI quick diagnosis.Patients and methods: 50 plasma samples of acute myocardial infarction patients were analyzed by developed Smartphone-Assisted Pressure-Measuring-Based Diagnosis System (SPDS). The concentration of substrate was firstly optimized. The effect of antibody labeling and matrix solution on measuring result were then evaluated. And standard curves for cTnI, CK-MB and Myo were built for clinical sample analysis. The measuring results of 50 clinical samples were finally evaluated by comparing with the measuring result obtained by CLIA. Results: The concentration of substrate H2O2 was firstly optimized as 30% to increase measuring signal. A commercial serum matrix was chosen as the matrix solution to dilute biomarkers for standard curve building to minimize matrix effect on the accuracy of clinical plasma sample measuring. The standard curves for cTnI, CK-MB and Myo were built, with measuring dynamic range of 0–25 ng/mL, 0–33 ng/mL and 0–250 ng/mL, and limit of detection of 0.014 ng/mL, 0.16 ng/mL and 0.85 ng/mL respectively. The measuring results obtained by the developed system of 50 clinical plasma samples for three biomarkers matched well with the results obtained by chemiluminescent immunoassay.Conclusion: Due to its small device size, high sensitivity and accuracy, SPDS showed a bright potential for point-of-care testing (POCT) applications. Keywords: acute myocardial infarction, diagnosis, pressure sensor, smartphone, Pt nanoparticle

Quality of care is an essential aspect of geriatric rehabilitation. Usually, there are national standards for the quality of care or indicators to measure the quality of care. However, this is not the case for geriatric rehabilitation. Therefore, the aim of this study was to develop structure, process, and outcome indicators to measure the quality of geriatric rehabilitation. To develop quality indicators for geriatric rehabilitation, a literature search was performed to identify indicators for all types of rehabilitation that can also be suitable for geriatric rehabilitation. Thereafter, in the qualitative phase, different stakeholders were inte. Indicators from the literature and indicators developed based on the interviews were merged and processed in a questionnaire. Through this questionnaire, elderly care physicians and managers of geriatric rehabilitation facilities were asked to rate the indicators on relevance and feasibility. Indicators that were considered relevant and feasible by the respondents were included in the final quality indicator set for geriatric rehabilitation. Thirty-six indicators suitable for geriatric rehabilitation were identified from the literature. Additionally, 55 quality indicators were developed based on the interviews. Merging the indicators and omitting duplicates resulted in 69 quality indicators. Analysis of the data from the questionnaires resulted in a final set of 27 quality indicators for geriatric rehabilitation that consists of 17 structure, 8 process, and 2 outcome indicators. This study contributes to the quality of geriatric rehabilitation by providing a first set of quality indicators ready to use in practice. Follow-up research is recommended and may include an assessment of the applicability, reliability, and validity of the developed indicator set. [ABSTRACT FROM AUTHOR]

β-Lactams are the most widely prescribed class of antibiotics that inhibit penicillin-binding proteins (PBPs), particularly transpeptidases that function in peptidoglycan synthesis. A major mechanism of antibiotic resistance is the production of β-lactamase enzymes, which are capable of hydrolyzing β-lactam antibiotics. There have been many efforts to counter increasing bacterial resistance against β-lactams. These studies have mainly focused on three areas: discovering novel inhibitors against β-lactamases, developing new β-lactams less susceptible to existing resistance mechanisms, and identifying non-β-lactam inhibitors against cell wall transpeptidases. Drug discovery in the β-lactam field has afforded a range of research opportunities for academia. In this review, we summarize the recent new findings on both β-lactamases and cell wall transpeptidases because these two groups of enzymes are evolutionarily and functionally connected. Many efforts to develop new β-lactams have aimed to inhibit both transpeptidases and β-lactamases, while several promising novel β-lactamase inhibitors have shown the potential to be further developed into transpeptidase inhibitors. In addition, the drug discovery progress against each group of enzymes is presented in three aspects: understanding the targets, screening methodology, and new inhibitor chemotypes. This is to offer insights into not only the advancement in this field but also the challenges, opportunities, and resources for future research. In particular, cyclic boronate compounds are now capable of inhibiting all classes of β-lactamases, while the diazabicyclooctane (DBO) series of small molecules has led to not only new β-lactamase inhibitors but potentially a new class of antibiotics by directly targeting PBPs. With the cautiously optimistic successes of a number of new β-lactamase inhibitor chemotypes and many questions remaining to be answered about the structure and function of cell wall transpeptidases, non-β-lactam transpeptidase inhibitors may usher in the next exciting phase of drug discovery in this field. [ABSTRACT FROM AUTHOR]

Abstract Esophageal squamous cell carcinoma (ESCC) is a common fatal malignant tumor of the digestive tract; however, its pathogenic mechanism is unknown and lacks specific molecular diagnosis and treatment. Therefore, it is particularly important to identify new tumor biomarkers to enhance the early diagnosis and molecular-targeted therapy of ESCC. Here, we found that the E3 ubiquitin ligase Tripartitemotif-containing33 (TRIM33) is highly expressed in ESCC tissues and cell lines, and is associated with adverse clinical outcomes. We determined that TRIM33 drives aerobic glycolysis to promote tumor growth in vivo and in vitro. In terms of mechanism, TRIM33 binds to p53 to inhibit its stability and promote the expression of downstream glycolysis target genes GLUT1, HK2, PKM2, and LDHA. In addition, TRIM33 promotes the polyubiquitination of P53 K48-linked and proteasome degradation. Further studies have shown that the K351 site of P53 is the key site mediating the ubiquitination of P53 K48-linked to promote aerobic glycolysis in ESCC and tumor cell growth. Our results reveal that the TRIM33-P53 signal axis regulates glycolysis during ESCC and may provide a new perspective for the diagnosis and treatment of ESCC.

The SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as an approximation for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays identified substitutions which conferred strong nirmatrelvir resistance and others that compromised activity. On the other hand, N142A and the P132H mutation, carried by the Omicron variant, caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used. Author summary: The SARS-CoV-2 virus has proven to be highly adept at evading the newly developed vaccines. Antiviral drugs provide an important alternative that can reduce disease severity. Nirmatrelvir, an orally available drug approved by the FDA to treat COVID-19, inhibits the SARS-CoV-2 main or 3C-like protease (Mpro or 3CLpro) and reduces the severity of COVID-19 infections. However, continued use of nirmatrelvir will likely drive the emergence of drug resistant Mpro mutations. Our study reports a rapid, inexpensive, and non-pathogenic system using baker's yeast that can determine if potential Mpro mutations may confer drug resistance. Furthermore, we solve the structures of two Mpro mutants first characterized in yeast that provide insights into how E166 can change to drive resistance versus leading to inactivity. Our results can aid in advancing our understanding of resistance mechanisms that will be important as nirmatrelvir and other protease inhibitors become more widely used. [ABSTRACT FROM AUTHOR]

Abstract Background Cysticercosis is a zoonotic parasitic disease that poses a serious threat to public health. It is widely distributed and has a high incidence rate in China. Reports of disseminated cysticercosis worldwide are rare. This article presents a case of disseminated cysticercosis in the Guangxi Zhuang Autonomous Region of southwestern China. Case presentation The patient, a 46-year-old male belonging to the Miao ethnic group, hailed from a region in Guangxi Zhuang Autonomous Region known for its high incidence of cysticercosis. He had a habit of consuming raw pork and beef. With a history of recurrent consciousness disturbances and limb convulsions for five years, he presented with headaches and dizziness nine days prior. Comprehensive examinations were conducted on the patient. Ultimately, based on epidemiological history, imaging findings, pathogen testing, and pathological results, he was diagnosed with disseminated cysticercosis. Following anthelmintic treatment, the patient was discharged with clear consciousness, free from headaches, dizziness, nausea, vomiting, and seizures. The patient is currently under follow-up care. Conclusion It is crucial to enhance public awareness, promote health education, and cultivate good hygiene habits, as these are essential measures in reducing the incidence of cysticercosis.

Abstract Background The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial. Methods One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed. Results The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2). Conclusions Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

Abstract Background Alveolar soft part sarcoma (ASPS) occurs most often in the deep muscles or fascia of the extremities in adults, with only 3.4% of these tumours originating from the head, face and neck. To date, only 17 cases of buccal ASPS have been reported, including the case presented here. Only one case of ASPS recurrence at the primary site, similar to our case, has been reported thus far. Immune checkpoint inhibitors (ICPis)-associated diabetes, with an estimated incidence of 0.43%, is usually seen in older cancer patients and has not been reported in younger people or in patients with ASPS. Case presentation A 24-year-old male patient presented with a slowly progressing right cheek mass with a clinical history of approximately 28 months. Sonographic imaging revealed a hypoechoic mass, which was considered a benign tumour. However, a pathological diagnosis of ASPS was made after excision of the mass. Five days later, functional right cervical lymph node dissection was performed. No other adjuvant therapy was administered after surgery. In a periodic follow-up of the patient six months later, blood-rich tumour growth was noted at the primary site, and Positron emission tomography-computedtomography (PET-CT) ruled out distant metastasis in other areas. The patient was referred to the Ninth People’s Hospital of Shanghai Jiaotong University. Due to the large extent of the mass, the patient received a combination of a Programmed Cell Death Ligand 1(PD-L1) inhibitor and a targeted drug. Unfortunately, the patient developed three episodes of severe diabetic ketoacidosis after the administration of the drugs. A confirmed diagnosis of ICPis-associated diabetes was confirmed. After the second operation, the postoperative pathological diagnosis was ASPS, and the margins were all negative. Therefore, we made a final clinical diagnosis of ASPS recurrence at the primary site. Currently in the follow-up, the patient is alive, has no distant metastases, and undergoes multiple imaging examinations every 3 months for the monitoring of their condition. Conclusions In analysing the characteristics of all previously reported cases of buccal ASPS, it was found that the clinical history ranged from 1 to 24 months, with a mean of approximately 3 to 9 months. Tumour recurrence at the primary site has been reported in only one patient with buccal ASPS, and the short-term recurrence in our patient may be related to the extraordinarily long 28-month history. ICPis-associated diabetes may be noted in young patients with rare tumours, and regular insulin level monitoring after use is necessary.

Quality of care is an essential aspect of geriatric rehabilitation. Usually, there are national standards for the quality of care or indicators to measure the quality of care. However, this is not the case for geriatric rehabilitation. Therefore, the aim of this study was to develop structure, process, and outcome indicators to measure the quality of geriatric rehabilitation. To develop quality indicators for geriatric rehabilitation, a literature search was performed to identify indicators for all types of rehabilitation that can also be suitable for geriatric rehabilitation. Thereafter, in the qualitative phase, different stakeholders were inte. Indicators from the literature and indicators developed based on the interviews were merged and processed in a questionnaire. Through this questionnaire, elderly care physicians and managers of geriatric rehabilitation facilities were asked to rate the indicators on relevance and feasibility. Indicators that were considered relevant and feasible by the respondents were included in the final quality indicator set for geriatric rehabilitation. Thirty-six indicators suitable for geriatric rehabilitation were identified from the literature. Additionally, 55 quality indicators were developed based on the interviews. Merging the indicators and omitting duplicates resulted in 69 quality indicators. Analysis of the data from the questionnaires resulted in a final set of 27 quality indicators for geriatric rehabilitation that consists of 17 structure, 8 process, and 2 outcome indicators. This study contributes to the quality of geriatric rehabilitation by providing a first set of quality indicators ready to use in practice. Follow-up research is recommended and may include an assessment of the applicability, reliability, and validity of the developed indicator set. [ABSTRACT FROM AUTHOR]

Primary osteosarcoma of the breast (POB) is an aggressive and exceedingly rare tumor, and cases with onset during lactation are extremely rare. The exact mechanism of POB development remains unclear. They may originate from totipotent mesenchymal cells in the breast stroma or may be the result of neoplastic transformation of prior breast lesions. Here, we present the case of a 40-year-old Chinese woman who was found with a palpable tumor measuring approximately 3 cm in diameter in her right breast while breastfeeding 4 months post-partum. The lactating woman was misdiagnosed with lactational mastitis during her initial visit to a community hospital. However, due to negative bacterial cultures and ineffective anti-infective treatment, later on the patient was taken to a more advanced hospital where a tissue biopsy was taken. The superior hospital considered that it might be a malignant tumor and performed local excision of the breast mass, leading to a final pathological diagnosis of POB. This is the first reported case of primary osteosarcoma during breastfeeding. We hope that this case report will improve readers’ understanding of the diagnosis and differential diagnosis of POB, especially for patients with atypical clinical symptoms and imaging findings, which should not be taken lightly.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease, which is characterized by the immune system attacking astrocytes in the central nervous system, resulting in inflammation and damage to the nervous system. We reported a 41-year-old female patient with only drowsiness for 3 months, who was, otherwise, healthy with no other signs of meningoencephalitis or myelitis. There were no obvious abnormalities in her neurological and ophthalmic tests. Brain magnetic resonance imaging (MRI) plain scan + enhancement with the gadolinium contrast agent revealed patchy hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, hyperintensity on T2-weighted fluid-attenuated inversion recovery in the left basal ganglia, corona radiata, and local septum pellucida, with no enhancement in the enhanced lesions. Cerebrospinal fluid (CSF) revealed white blood cell count of 5.00 × 106/L, CSF protein of 828.53 mg/L, and glucose of 2.83 mmol/L. Aquaporin-4 (AQP4) antibody, N-methyl-D-aspartate receptor (NMDAR) antibody and GFAP antibody were all positive, whereas the remaining autoimmune encephalitis antibody tests were negative. Oncology screening [including head, chest, and whole-abdomen (involving the pelvic cavity) CT and tumor markers] did not reveal any obvious evidence of tumor presence. The patient received systemic treatment with high-dose intravenous injection of steroids combined with immunosuppressive agents, and the clinical and imaging features of the patients improved. To the best of our knowledge, reports on overlapping positivity of AQP4 antibody and NMDAR antibody in patients with GFAP astrocytopathy were still very rare. We hope to supplement the existing literature on this topic, review the relevant literature, and strive to increase the understanding toward GFAP astrocytopathy with overlapping autoimmune syndrome so as to enable early diagnosis and early treatment and to improve the clinical outcome of patients.

BackgroundThe appearance of cerebral venous sinus thrombosis (CVST) in childhood acute lymphocytic leukemia (ALL) is a rare life-threatening disease that can cause significant morbidity, neurological sequelae, and potentially poor outcomes.Case presentationWe present the case of a 13-year-old boy with ALL who developed CVST and intrinsic hemorrhage approximately 30 days after receiving chemotherapy with vincristine, dexamethasone, daunorubicin, and pegylated-asparaginase (PEG-Asp). He complained of a severe headache and then developed a generalized seizure at night. T1- and T2-weighted magnetic resonance imaging (MRI) and cerebral magnetic resonance venography sequences revealed superior sagittal sinus thrombosis and intrinsic hemorrhagic changes in the bilateral frontoparietal lobes. He received nadroparin calcium as the anticoagulant treatment and was switched to Erwinia asparaginase (Erwinia Asp) rather than PEG-Asp. Oxcarbazepine and clonazepam were started with good seizure control. Intrathecal treatment was delayed until 1 month later. Anticoagulation treatment was stopped for 24 h before and 6 h after lumbar puncture. Platelet transfusion was administered to ensure the platelet count remained at >50 × 109/L. Oral acetazolamide (500–1,000 mg, daily) was administered to relieve headache and reduce intracranial pressure. Three months later, brain MRI showed a complete resolution of or significant improvement in the filling defect. Nadroparin calcium was administered for 1 week after switching to Erwinia Asp to prevent clot recurrence. He completed the 6-month chemotherapy and is doing well with no neurological sequelae and no recurrence of bleeding or thrombosis.ConclusionsNadroparin calcium therapy appears to be safe and effective for pediatric CVST with ALL. The reintroduction of Erwinia Asp should be accompanied by anticoagulant therapy with nadroparin calcium.

【Objective】Natural disasters such as earthquakes have the characteristics of persistence and wide range. During the occurrence of disasters, the link resources of the optical network will be continuously damaged, resulting in the constant change of the link risk. In the face of constantly changing link risks, improper service recovery planning may cause service failures. From a service perspective, repeated faults will interrupt data transmission many times, and the subsequent link status damage may be aggravated after a disaster occurs. From the perspective of network management and control, repeated recovery wastes route calculation resources and occupies the recovery resources of other services. At the same time, different services have different requirements for transmission reliability because of the importance of the data to be transmitted. When a fault occurs, the high-importance services should be recovered first. Therefore, in the scenario of a large-scale persistent disaster, it is a problem worth studying to comprehensively consider the sustained impact of the disaster on link risk and the difference in path reliability requirements of different services for service recovery. To solve this problem, this paper proposes a link risk-aware service recovery algorithm-Dynamic Link Risk Reroute Algorithm (DLRRA) under persistent disasters.【Methods】Firstly, according to the service importance and link risk, we establish the service importance evaluation model and link risk evaluation model. Then we propose the optimization target route reliability. The DLRRA, combined with the optimization objective, fully considers the change of link risk degree caused by the impact of disasters on the continuity of links. By preferentially allocating low-risk recovery resources to the fault services of high importance, the risk of secondary failure of the same high-importance services is avoided during the continuous occurrence of disasters.【Results】The simulation results show that the second failure probability of DLRRA recovery is reduced by 11% compared with the traditional algorithm, and the average importance of DLRRA recovery under the high load is increased by 10%.【Conclusion】Therefore, the algorithm effectively avoids the loss caused by multiple service interruptions caused, and ensures the continuous and stable operation of important services in the disaster environment.

There is a trend towards the formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment on rehabilitation wards. So far, literature on the principles of the CRE is scarce. This study aims to explore the perspectives regarding the CRE of healthcare professionals through a qualitative study. Therefore, between 2018 and 2020, six international and 69 Dutch professionals were interviewed in focus groups, and 180 professionals attended workshops on two Dutch congresses. Data were thematically analyzed using ATLAS.ti. Seven themes emerged regarding the rehabilitation processes: (1) rehabilitant (attention for cognitive functioning and resilience); (2) goals (setting personal goals); (3) exercise (increasing exercise intensity); (4) daily schedule (following the daily rhythm); (5) involving the client system (involving informal caregivers); (6) nutrition (influences rehabilitation capability); and (7) technology (makes rehabilitation more safe and challenging). Regarding organizational aspects, four main themes were identified: (1) environmental aspects (encourages exercises); (2) staff aspects (interdisciplinary team); (3) organizational aspects (implementing CRE requires a shared vision); and (4) factors outside the ward (a well-prepared discharge process). To offer effective rehabilitation, all elements of the CRE should be applied. To improve the CRE, specific interventions need to be developed and implemented. Consequently, the effectiveness and efficiency of the CRE need to be measured with validated tools. [ABSTRACT FROM AUTHOR]

There is a trend toward formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment in rehabilitation wards. So far, literature about the principles of CRE is scarce. This study aims to explore the opinions of rehabilitants and informal caregivers regarding CRE, through a qualitative study between 2019 and 2020. Three telephone interviews were conducted with informal caregivers, and also 3 focus groups with 15 rehabilitants and 3 informal caregivers, all with recent experience in rehabilitation. Nine themes emerged regarding the rehabilitation process: (1) rehabilitant (attention for resilience, motivation, cognitive and emotional aspects), (2) rehabilitant centered (goal setting, physical and cognitive functioning and coping), (3) informal caregivers (involving and attention for resilience and relation), (4) communication (aligning the rehabilitation process), (5) exercise (increasing intensity by using task-oriented exercise, patient-regulated exercise, and group training), (6) peer support (learning experiences and recognition), (7) daily schedule (influence on the planning and activities outside therapy), (8) nutrition (energy for rehabilitation), and (9) eHealth (makes rehabilitation more challenging and fun). Regarding organizational processes, 4 themes were identified: (1) environmental aspects (single bedrooms, shared room for activities and therapy options on the ward), (2) staff aspects (small team with an emphatic supportive and motivating attitude), (3) organizational aspects (organized in an efficient way), and (4) return home (the discharge process should be well prepared for instance with home visits). Organizing excellent rehabilitation care requires a thorough understanding of the concept of CRE, as it is a complex and comprehensive concept that concerns the whole rehabilitation process. Its effectiveness and efficiency should be researched in prospective studies. [ABSTRACT FROM AUTHOR]

Low temperature is one of the most severe abiotic stress factors that limit chrysanthemum growth and development. Natural temperature changes are more complex, and cold stress from a laboratory incubator cannot accurately represent the natural temperature stress. Here, nine separate high-throughput mRNA sequencing technology (RNA-Seq) libraries were generated from the RNA sample of roots from different temperatures, including chilling (Ch), freezing (Fr), and control (CK). The 7 069 and 3 952 differentially transcribed genes were identified as CK vs. Ch and CK vs. Fr, respectively. The Kyoto encyclopedia of genes and genomes pathway (KEGG) enrichment analysis showed that significantly different flavonoid biosynthesis and linolenic acid pathways commonly appeared in CK vs. Ch and CK vs. Fr. Arginine and proline metabolism, lipid metabolism, fatty acid degradation, and fructose and mannose metabolism pathways were found in CK vs. Ch, and only in the CK vs. Fr enrichment metabolic pathway included steroid biosynthesis and monoterpenoid biosynthesis. The transcription of genes on differential metabolic pathways and MYBs were successfully validated using quantitative real-time PCR. At the same time, the antioxidant activity, malondialdehyde, and proline content were analyzed under low temperature. These datasets may aid in understanding and carrying out future studies on the molecular basis of cold stress and contribute to chrysanthemum breeding. [ABSTRACT FROM AUTHOR]

Summary: Background: Sepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described. Methods: We included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI. Findings: There were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p = 0.01) and APS (0.78 vs. 0.74, p = 0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20–1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97–1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI. Interpretation: BPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment. Funding: Fundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

Abstract Background There is a great challenge to sedation for infants with cleft lip and palate undergoing CT scan, because there is the younger age and no consensus on the type, dosage, and route of drug administration. Objective This study aimed to evaluate the efficacy of intranasal administration of dexmedetomidine combined with midazolam as a sedative option for infants with cleft lip and palate under imaging procedures. Methods Infants scheduled for cleft lip and palate repair surgery were randomly assigned to the IND group (intranasal dexmedetomidine 2 µg/kg alone) and the INDM group (intranasal dexmedetomidine 2 µg/kg combined with midazolam 0.05 mg/kg). The primary outcome was the proportion of infants underwent successful computed tomography (CT) scans under intranasal sedation. The secondary outcomes included onset time and duration of sedation, recovery time, Ramsay sedation scale, hemodynamic parameters during sedation, and adverse events. Data analyses involved the unpaired t-test, the repeated-measures analysis of variance test, and the continuity correction χ2 test. Results One hundred five infants were included in the analysis. The proportion of infants underwent successful CT scans under sedation was significantly greater in the INDM group than in the IND group (47 [95.9%] vs. 45 [80.4%], p = 0.016). Additionally, the INDM group had a shorter onset time and a longer duration of sedation statistically (12 [8.5, 17] min vs. 16 [12, 20] min, p = 0.001; 80 [63.6, 92.5] min vs. 68.5 [38, 89] min, p = 0.014, respectively), and their recovery time was significantly longer (43 [30, 59.5] min vs. 31.5 [20.5, 53.5] min, p = 0.006). The difference in Ramsay sedation scale values 20 min after administration was statistically significant between the groups. No statistically significant difference was found between the groups in changes in heart rate and respiratory rate. Conclusion Intranasal administration of dexmedetomidine in combination with midazolam resulted in higher sedation success in comparison with sole dexmedetomidine. However, it has a relatively prolonged duration of sedation and recovery time. Trial registration ChiCTR2100049122, Clinical trial first registration date: 21/07/2021.

Abstract Background GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. Methods GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT–PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT–PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT–PCR analysis, Western blot analysis, and cell functional experiments. Results The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P

For the coil misalignment problem in the charging process of automatic guidance vehicles (AGVs), this paper proposes an optimization method for the bilateral LCC compensation network parameters based on quadruple-D quadrature (4DQ) coils. By introducing two coefficients $K_{\text {T}}$ and $K_{\text {f1}}$ , the compensation capacitors $C_{\text {T}}$ and $C_{\text {f1}}$ are optimized, achieving smaller output power fluctuations. Firstly, the capacitor values $C_{\text {T}}$ and $C_{\text {f1}}$ at resonance in the SS and PS equivalent circuit topology are obtained, meanwhile, the relationship between the output power $P_{\text {out}}$ and the coupling coefficient $k$ , represented by the coefficients $K_{\text {T}}$ and $K_{\text {f1}}$ , is obtained. Furthermore, with the transmission efficiency as the limiting condition, the output power fluctuation is effectively suppressed by adjusting $K_{\text {T}}$ and $K_{\text {f1}}$ . Finally, the experimental results show that after optimization the output power is 427.08W, and the transmission efficiency is 93.506% when the coupling coil are aligned, the system can still maintain a power output of at least 382.36W with a coil offset of 0-153mm in the X/Y axis directions, and the transmission efficiency is always above 89.472%. At the same time, the maximum deviation value $\Delta P_{{\text {abs}\_{}\text{max}}}$ decreased from 213.1W before optimization to 111.0W after optimization, a decrease of 47.91%, effectively suppressing the power fluctuation and improving anti-offset performance.

Purpose: To establish dynamic prediction models by machine learning using daily multidimensional data for coronavirus disease 2019 (COVID-19) patients. Methods: Hospitalized COVID-19 patients at Peking Union Medical College Hospital from Nov 2nd, 2022, to Jan 13th, 2023, were enrolled in this study. The outcome was defined as deterioration or recovery of the patient's condition. Demographics, comorbidities, laboratory test results, vital signs, and treatments were used to train the model. To predict the following days, a separate XGBoost model was trained and validated. The Shapley additive explanations method was used to analyze feature importance. Results: A total of 995 patients were enrolled, generating 7228 and 3170 observations for each prediction model. In the deterioration prediction model, the minimum area under the receiver operating characteristic curve (AUROC) for the following 7 days was 0.786 (95% CI 0.721–0.851), while the AUROC on the next day was 0.872 (0.831–0.913). In the recovery prediction model, the minimum AUROC for the following 3 days was 0.675 (0.583–0.767), while the AUROC on the next day was 0.823 (0.770–0.876). The top 5 features for deterioration prediction on the 7th day were disease course, length of hospital stay, hypertension, and diastolic blood pressure. Those for recovery prediction on the 3rd day were age, D-dimer levels, disease course, creatinine levels and corticosteroid therapy. Conclusion: The models could accurately predict the dynamics of Omicron patients’ conditions using daily multidimensional variables, revealing important features including comorbidities (e.g., hyperlipidemia), age, disease course, vital signs, D-dimer levels, corticosteroid therapy and oxygen therapy.

ObjectiveThis meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson’s disease(PD).MethodsFour databases (Medline, Embase, Web of Science and CENTRAL) were searched from establishment of database to 23 March 2024, for articles studying robot-assisted DBS in patients diagnosed with PD. Meta-analyses of vector error, complication rate, levodopa-equivalent daily dose (LEDD), Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, and UPDRS IV were performed.ResultsA total of 15 studies were included in this meta-analysis, comprising 732 patients with PD who received robot-assisted DBS. The pooled results revealed that the vector error was measured at 1.09 mm (95% CI: 0.87 to 1.30) in patients with Parkinson’s disease who received robot-assisted DBS. The complication rate was 0.12 (95% CI, 0.03 to 0.24). The reduction in LEDD was 422.31 mg (95% CI: 68.69 to 775.94). The improvement in UPDRS, UPDRS III, and UPDRS IV was 27.36 (95% CI: 8.57 to 46.15), 14.09 (95% CI: 4.67 to 23.52), and 3.54 (95% CI: −2.35 to 9.43), respectively.ConclusionRobot-assisted DBS is a reliable and safe approach for treating PD. Robot-assisted DBS provides enhanced accuracy in contrast to conventional frame-based stereotactic techniques. Nevertheless, further investigation is necessary to validate the advantages of robot-assisted DBS in terms of enhancing motor function and decreasing the need for antiparkinsonian medications, in comparison to traditional frame-based stereotactic techniques.Clinical trial registration: PROSPERO(CRD42024529976).

Abstract Brugen af digitale devices såsom bærbare computere, tablets og mobiltelefoner i undervisningssituationer er genstand for ophedet debat i det aktuelle politiske landskab. I didaktiske kredse hersker der ligeledes stor interesse for emnet. I denne artikel diskuterer vi, hvilken rolle timeouts fra brugen af digitale devices (digital detox) spiller for graden af aktivitet og oplevet trivsel blandt universitetsstuderende. Vi sammenligner to undervisningsforløb: et med ureguleret brug af digitale devices og et med kraftigt reguleret, dvs. hvor studerende overhovedet ikke benytter sådanne enheder i undervisningen. Disse forløb undersøges igennem videoetnografiske metoder, deltagerobservation, interview, survey, samt videoassisterede interview. Studies resultater er ikke entydige, men indikerer dog, at digitale timeouts og regulering a) ikke nødvendigvis i selv medfører højere aktivitetsniveau, men b) kan føre til oplevelser af styrket trivsel.

In response to the problem of excessive dust concentration at the coal mine heading face, a new type of internal and external dual swirl air curtain generator was designed. Numerical simulations and similar tests were carried out to investigate the characteristics of the wind flow field and the dust dispersion pattern at the heading face before and after the application of the device. The results show that the dust concentration at the driver’s position decreases first and then increases with the increase of the jet outlet airflow velocity of air curtain generator, and the empirical relationship between the dust concentration at the driver’s position and the jet outlet airflow velocity is proposed, and a critical wind speed of 35 m/s was determined for effective dust control. The wind curtain generator can form a funnel-shaped swirling air curtain to prevent dust from spreading outwards, and divide the working face into two parts of dust control area and work area. The swirl air curtain reduces the diffusion speed of dust particles by 84% and has a better dust control effect for respirable dust below 5 μm; after the installation of the new swirl air curtain generator, the dust concentration at the driver’s position of the road header is reduced from 337 mg/m3 to 38 mg/m3.

Orostachys cartilaginous of Crassulaceae family is a plant native to the Changbai Mountain area, China. Although O. cartilaginous has various medicinal values, its product development and production are restricted by the insufficient resource available. O. cartilaginous cell cultures possess an efficient antibacterial effect against Bacillus subtilis, but the underlying mechanism is not clear yet. Therefore, this study investigated the effects of extract from bioreactor cultured O. cartilaginous cells (OE) on B. subtilis cell permeability and respiratory metabolism to provide a reference for the further utilization of O. cartilaginous cell cultures. Results showed alkaline phosphatase activity, electrical conductivity, nucleic acid and protein contents in B. subtilis suspensions were significantly increased (p < 0.01) by OE treatment, indicating the occurrence of cell damage or increase in cell permeability. OE inhibited B. subtilis respiration, and the combination groups of OE + iodoacetic acid (IA) and OE + sodium phosphate (SP) showed low superposition rates (approximately 35 %), revealing that OE likely affected IA- and SP-represented metabolic pathways. The activities of B. subtilis enzymes, specifically, hexokinase and pyruvate kinase in the embden-meyerhof-parnas (EMP) pathway and glucose-6-phosphate dehydrogenase in the hexose monophosphate (HMP) pathway, decreased after OE treatment. This result proved that OE inhibited B. subtilis respiration by regulating the EMP and HMP pathways. Key message: Extract from Orostachys cartilaginous cell cultures inhibited Bacillus subtilis growth. Bacterial cell contents leaked out after extract treatment. Extract inhibited bacterial respiration by regulating embden-meyerhof and hexose monophosphate pathways. [ABSTRACT FROM AUTHOR]