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The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the “super fungus”, C. auris.

Introduction: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods: Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). Interpretation: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

Objective: Percutaneous nephrolithotomy (PCNL) is the main method for pyonephrosis or lithotripsy in urology. However, it often comes with high risk, as the inaccurate puncture inevitably causes bleeding, intra- and post-operative complications. So, a new inter-disciplinary approach is needed to perform the puncture more accurately. Methods: 3 signs made of lead were marked onto the skin of the posterior side of the waist of a domestic pig or a patient, which was scanned by computed tomography (CT). Based on the CT images, the computer design and the 3D printing, a navigation template made of the transparent resin material is constructed. They were attached onto the surgical area on pig or patient according to the signs. During the PCNL, with this template, the puncture position, angle and depth were optimized in order to precisely enter the targeted renal pelvis or calices. Results: With the 3D navigation templates, 18G puncture needles were used to enter the renal pelvis upon performing the PCNL on a porcine model and a patient. On the porcine model, the urine outflow was observed with minimal complication. Post-operative CT scans revealed that the needle was located in the renal pelvis. For the patient case, the puncture point was designed to target the calix with stone. No obvious bleeding and complication was found in renal puncture with template. Conclusions: The navigation template was made with the combination of 3D printing, CT images and computer design. This template allows for accurate puncture of the renal pelvis or calix. Surgical improvement in kidney stones and pyonephrosis was observed in porcine model and patient case. In the future, prospective, trandomized, controlled clinical trials are needed to further confirm its advantage.

Abstract Background Core stability exercise (CSE) is a globally acknowledged intervention for managing chronic low back pain. However, the sustained adherence of patients with chronic low back pain to CSE can be challenging, mainly due to the absence of supervision and guidance from physical therapists during home-based exercise sessions. Consequently, exercise compliance tends to decline, resulting in suboptimal long-term effectiveness of the intervention. In this trial, our primary aim is to evaluate the potential therapeutic equivalence between home-based rehabilitation training employing key point identification technology and exercise guidance administered in a hospital setting. Methods In this trial, we will randomly assign 104 adults with chronic low back pain (CLBP) to either an intervention or control group, with 52 participants in each group. Both interventions will consist of three weekly 0.5-h sessions of core stability exercise (CSE). The intervention group will engage in home rehabilitation training utilizing key identification technology for movement, while the control group will perform supervised exercises in a hospital setting. Outcome assessments will be conducted at 4 weeks and 16 weeks after randomization. The primary outcome measure will be the change in pain intensity based on numeric rating scale (NRS scores) from baseline to 4 weeks. Secondary outcomes will include changes in physical function (measured by the Oswestry Disability Index (ODI)) and lumbar spine mobility as well as activity participation and treatment satisfaction. Discussion If home-based rehabilitation method is demonstrated to be non-inferior or even superior to traditional face-to-face exercise guidance, it could significantly advance the adoption of digital medical care and contribute to improving the overall health of the population. Trial registration NCT05998434 . Registered on 16 August 2023.

Objective To summarize the characteristics of cognitive function and sleep structure in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and to explore the correlation between them. Methods Total 73 patients with iRBD who visited Fujian Medical University Union Hospital from August 2018 to August 2021 were included, all of whom underwent neuropsychological tests and polysomnography monitoring. Pearson and partial correlation analyses were used to explore correlation between cognitive function and sleep structure parameters. Results 1) Neuropsychological tests: iRBD patients had lower Mini ⁃ Mental State Examination (MMSE; t = ⁃ 3.703, P = 0.000), Montreal Cognitive Assessment (MoCA; t = ⁃ 4.811, P = 0.000), Verbal Fluency Test (VFT)⁃number of correct words (t = ⁃ 2.171, P = 0.032) than control group. Trail Making Test (TMT)⁃A (t = 2.500, P = 0.014), TMT⁃B (t = 2.430, P = 0.016) and Stroop Color Word Test (SCWT)⁃A (t = 2.507, P = 0.013), SCWT⁃B (t = 15.042, P = 0.000), SCWT⁃ C (t = 27.228, P = 0.000) completion times were longer than control group. 2) Polysomnography monitoring: total sleep time (t = 2.699, P = 0.008), sleep efficiency (Z = ⁃ 2.103, P = 0.035), number of sleep stage transitions (t = 3.965, P = 0.000), proportion of non⁃rapid eye movement sleep stage 1 (N1 stage) to total sleep time (t = 2.887, P = 0.005), periodic limb movement of sleep index (PLMSI; t = ⁃ 2.917, P = 0.004), periodic limb movement⁃related arousal index (Z = ⁃ 2.291, P = 0.022), and total arousal index (Z = ⁃ 2.609, P = 0.009) were higher than those in control group, and the time of wakefulness after sleep was less than those in control group (t = ⁃ 2.230, P = 0.027). 3) Correlation between cognitive function and sleep structure parameters: MoCA score was negatively correlated with the percentage of N1 stage (r = ⁃ 0.184, P = 0.035), and positively correlated with the percentage of N2 stage (r = 0.173, P = 0.049); SCWT⁃B completion time was negatively correlated with the number of awakenings (r = ⁃ 0.186, P = 0.033); SCWT⁃C completion time was positively correlated with the number of sleep phase transitions (r = 0.212, P = 0.015) and the percentage of N1 stage (r = 0.181, P = 0.039); VFT⁃number of correct words was negatively correlated with the periodic limb movement of wake index (PLMWI; r = ⁃ 0.216, P = 0.018); the number of correct China⁃Rey Auditory Verbal Learning Test (C⁃RAVLT) immediate recall was positively correlated with the rapid eye movement (REM) sleep latency (r = 0.183, P = 0.045); the number of correct C⁃RAVLT delay recall was negatively correlated with the PLMWI (r = ⁃ 0.196, P = 0.032) and PLMSI (r = ⁃ 0.180, P = 0.049); the Clock Drawing Test was positively correlated with sleep latency (r = 0.192, P = 0.035) and REM sleep latency (r = 0.199, P = 0.029), and negatively correlated with the percentage of REM sleep (r = ⁃ 0.189, P = 0.038). The Beck Depression Inventory (BDI) score was positively correlated with total sleep time (r = 0.347, P = 0.000), sleep efficiency (r = 0.319, P = 0.000) and the percentage of REM sleep (r = 0.204, P = 0.026), and negatively correlated with the time of wakefulness after sleep (r = ⁃ 0.280, P = 0.002) and the percentage of N1 stage (r = ⁃ 0.299, P = 0.001). Conclusions Patients with iRBD have cognitive dysfunction mainly manifested by decreased attention, executive function and language function, and sleep structural disorders may affect the cognitive function of such patients.

IntroductionCandida palmioleophila is a rare human pathogenic fungus, which has been poorly characterized at the genome level. In this study, we reported the first fatal case of C. palmioleophila infection in China and investigate the microevolution of C. palmioleophila in the human host environment.MethodsA series of C. palmioleophila stains were collected from the patient at different time points for routine microbial and drug sensitivity testing. The first C. palmioleophila isolate 07202534 was identified by de novo whole genome sequencing. The in vitro and in vivo genetic evolutionary characteristics of C. palmioleophila were discussed based on the analysis of bioinformatics data.ResultsThe six C. palmioleophila isolates displayed dose-dependent sensitivity to fluconazole. The C. palmioleophila genome contained homologous genes such as CDR1 and MDR1, which were recognized to be related to azole resistance. In addition, amino acid variation was detected at F105L and other important sites of ERG11. In addition, the mean divergence time between C. palmioleophila and Scheffersomyces stipites CBS 6054 was 406.04 million years, indicating that C. palmioleophila originated earlier than its closest relative. In addition, the six strains of C. palmioleophila isolated form the patient had higher homology and fewer mutation sites, which indicated the stability in C. palmioleophila genome. We also found that C. palmioleophila had a wide natural niche and may evolve slowly.DiscussionWe believe that this study will contribute to improve our understanding of the genetic evolution, pathogenicity, and drug resistance of C. palmioleophila and will aid in the prevention and control of its spread.

Narcissistic personality disorder is a severance mental health issue, and affect person from both biological and social aspects. The article reviewed the latest international researches about the etiology, subtypes of narcissistic personality disorder, and related treatment strategies of narcissistic personality disorder. Narcissistic personality disorder is defined by an inflated self-importance, eagerness for admiration, and lack of compassion. It encompasses two subtypes, grandiose and vulnerable. Impact of narcissism on individuals' self-esteem, Self Control was examined through reviewing prior research on Chinese population. Moreover, correlation between parenting style, narcissistic personality and parent child relationship was also discussed. The result revealed that the formation of narcissistic personality disorder was influenced by environmental and social factors. Long-term psychological therapy is the main treatment for narcissistic personality disorder. Medication is not a primary treatment option, and certain antidepressants may exacerbate symptoms. The challenge and study directions have been identified in the end, abundant clinical trails on biological study of narcissistic personality disorder are needed, and the further researches on subtypes of narcissistic personality disorder are expected

Aiming at the disconnection between theory and practice in the experimental teaching of electrical and electronic technology courses, students do not have a deep understanding of knowledge and cannot exercise their practical ability. This paper puts forward the application of simulation software to the experimental teaching process of electrical and electronic technology to form an experimental teaching model combining theory, simulation and practice. The results show that the proposed teaching method can deepen the students' understanding of theoretical knowledge, improve their interest in learning, enhance their innovative application ability, and significantly improve the teaching quality.

Abstract Background Osteoporotic vertebral fractures are often clinically silent and unrecognized. The present study aimed to determine whether routine chest radiographs could be a potential screening tool for identifying missed vertebral fractures in men aged over 50 years or postmenopausal women, especially those with type 2 diabetes mellitus (T2DM). In this study, we aimed to determine the prevalence of undetected vertebral fractures in elderly Chinese patients with and without T2DM. Methods Clinical data and chest radiographs of 567 individuals with T2DM (T2DM group) and 583 without diabetes (nondiabetic group) at a tertiary hospital in central south China were extracted from the records. Vertebral fractures were specifically looked for on chest radiographs and classified using the Genant semi-quantitative scale. Prevalence was compared between the two groups. Results Mean age and sex composition were comparable between the two groups. Mean weight and body mass index were significantly lower in the T2DM group. In both groups, fractures mostly involved the T11–12 and L1 vertebrae. Moderate/severe fractures were identified in 33.3% individuals in the T2DM group (31.4% men and 36.0% women) versus 23.2% individuals (20.9% men and 25.5% women) in the nondiabetic group. Conclusions Routine chest radiographs could be a useful screening tool for identifying asymptomatic vertebral fractures. Trial registration The study was designed as an observational retrospective study, therefore a trial registration was not necessary.

Objective To investigate the incidence and risk factors for impulsive control disorders (ICDs) in Parkinson's disease (PD). Methods A total of 201 patients with PD were included from May 2016 to September 2017. ICDs were assessed by Questionnaire for Impulsive⁃Compulsive Disorders in Parkinson's Disease (QUIP). Mentation, behavior and mood, activities of daily living, motor function, and complications for therapy were assessed by Unified Parkinson's Disease Rating Scale (UPDRS). Disease severity was assessed by Hoehn⁃Yahr staging, and depression was assessed by Geriatric Depression Scale (GDS). Univariate and multivariate forward Logistic regression analyses were used to analyze the risk factors for PD patients with ICDs. Results Among 201 PD patients, 41 patients (20.40%) were diagnosed with ICDs, including 17 cases of compulsive medicine use (8.46%), 15 cases of compulsive eating (7.46%), 13 cases of punding (6.46%), 8 cases of compulsive shopping (3.98%), 3 cases of pathological gambing (1.49%) and one case of hypersexuality (0.49%). Logistic regression analysis showed that the longer treatment duration (OR=1.237, 95%CI: 1.038-1.474; P=0.018), severe complications for therapy (high UPDRS Ⅳ score; OR=1.389, 95%CI: 1.077-1.790, P=0.011), depression (OR=2.417, 95%CI: 0.174-0.984; P=0.046) were the risk factors for PD patients with ICDs. Conclusions The incidence of ICDs in PD is high, which is affected by many factors. The risk of ICDs can be evaluated by the QUIP scale to guide medication.

Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.

Location-based Service has become the fastest growing activity related service that people use in their daily life due to the boom of location-aware mobile devices. In edge computing along with the benefits brought by LBS, privacy preservation becomes a more challenging issue because of the nature of the paradigm, in which peers may cooperate with each other to collect and analyze user's location data. To avoid potential information leakage and usage, user's exact location should not be exposed to the edge node. In this paper, we propose a stochastic location privacy protection scheme for edge computing, in which the geographical distribution of surrounding users is obtained by analyzing proposed long-term density map and short-term density map. The cloaking scheme transfers user's exact location to a cloaked location to satisfy predefined probability of having k-users in that area. Our scheme does not reveal any exact location information, thus it is practicable for the real scenario when edge computing is honest but curious. Extensive experimental results are conducted to verify the efficiency and effectiveness of our method. By varying the privacy protection requirements, the corresponding performance have been examined and discussed.

During the “14th Five-Year Plan” period (2021-2025), China will enter the era of mass tourism, and the development of tourism industry is still in an important strategic opportunity period, but there are new opportunities and challenges. The article analyses the development status of cultural tourism in China and the development trend of China’s cultural tourism industry, and proposes countermeasures for the problems faced by China’s cultural tourism industry during the “14th Five-Year Plan” period from the aspects of theme development, industry chain building, resource utilization and cultural creativity.

Quantum dots (QDs) are promising candidates for the next-generation optical and electronic devices due to the outstanding photoluminance efficiency, tunable bandgap and facile solution synthesis. Nevertheless, the limited optoelectronic performance and poor lifetime of QDs devices hinder their further applications. As a gas-phase surface treatment method, atomic layer deposition (ALD) has shown the potential in QDs surface modification and device construction owing to the atomic-level control and excellent uniformity/conformality. In this perspective, the attempts to utilize ALD techniques in QDs modification to improve the photoluminance efficiency, stability, carrier mobility, as well as interfacial carrier utilization are introduced. ALD proves to be successful in the photoluminance quantum yield (PLQY) enhancement due to the elimination of QDs surface dangling bonds and defects. The QDs stability and devices lifetime are improved greatly through the introduction of ALD barrier layers. Furthermore, the carrier transport is ameliorated efficiently by infilling interstitial spaces during ALD process. Attributed to the ultra-thin and dense coating on the interface, the improvement on optoelectronic performance is achieved. Finally, the challenges of ALD applications in QDs at present and several prospects including ALD process optimization, in-situ characterization and computational simulations are proposed.

HELLP syndrome is a combination of symptoms described as hemolysis, elevated liver enzymes and low platelets. HELLP is a common life-threatening complication of pregnancy thought to be a variant or complication of preeclampsia. In this case report, we aimed to present a woman with acute postpartum HELLP syndrome complicated by pulmonary edema after caesarean section following severe preeclampsia. Our experience suggests that early detection of HELLP syndrome and timely management will bring good outcomes.

Based on combined data from Baccalaureate & Beyond (B&B:16/17), Integrated Postsecondary Education Data System (IPEDS), and Barron's Profiles of American Colleges, this study utilizes zero-inflated beta regression methods and analyzes individual and institutional factors that predict debt burden by gender. Results show that women are less likely than men to have a zero debt burden one year after college graduation. Interaction effect tests show that the relationship between gender and zero debt burden differs by race/ethnicity. Additional analyses disaggregating the debt and earnings components indicate that women's salary is significantly lower than men's salary. The combined results of lower probability of zero debt and lower salary for women than for men are concerning and demonstrate gendered inequities within current systems. Policy attention is needed to address these issues.

Current experiments show that the TATB-based polymer bonded explosives (PBX) will experience irreversible growth when suffered temperature cycling load. Although some studies have already been done on this, the cause of irreversible growth is still confusing, and the mechanism is not clear. In order to study the irreversible growth of PBX under temperature cycling load, an thermal-viscoelastic model is established, Based on the Burgers model which considering the influence of different temperatures on the creep properties of PBX. The analysis shows that the irreversible growth of PBX produced by the different creep properties of high and low temperature during the thermal cycling. Comparing with low temperature, the creep rate of PBX is faster and the deformation is larger at high temperature, which lead to the irreversible growth of PBX.

After years of research and practice, ICD well completion technology has become a relatively mature completion technology, and has been successfully applied in hundreds of horizontal Wells abroad. However, due to many factors affecting ICD effect, mature evaluation methods have not been completely established. At present, the main index of ICD water control development effect is to balance inflow profile and inhibit water production, and the evaluation factors involve reservoir, process and equipment structure. This paper summarizes the factors influencing the effects of ICD, using orthogonal experiment design method to carry on the comprehensive evaluation, and puts forward the corresponding Suggestions

In the downhole operation of horizontal Wells, the pipe string is subjected to the combined action of many kinds of loads. The pipe string may bend sinusoidal or spiral under the action of axial compressive stress, which will also increase the friction between the pipe string and the wellbore wall. Because of the existence of friction, to the milling, salvage, unstuck, sand and other construction to bring adverse effects. This paper describes the characteristics of horizontal well in fishing, sand washing, unlocking and casing milling. The paper introduces the development of horizontal well application, such as drilling technology matching for complex structure wells, high-level completion of lateral Wells, radial lateral wells in low permeability reservoirs and supporting technology for completion and production of horizontal wells.

In the friction stir welding (FSW) of ultra-thin dissimilar metal sheets, different physical material properties, the reduction of plastic metal in the weld zone, and insufficient plastic metal flow lead to poor weld seam shapes and joint qualities. Therefore, it is necessary to study the flow behavior during the FSW of ultrathin sheets. In this study, micro friction stir welding (μFSW) was conducted and analyzed for the butt welding of 0.6-mm-thick ultrathin brass (H62-H) and pure copper (T2-Y) sheets. By analyzing the electric signals of the temperature and force during the welding process, testing the mechanical properties, and analyzing the metallography of the joint, the influences of the process parameters on the metal flow behavior during μFSW were studied. In the proper process conditions, the material preferentially migrated and concentric vortex flow occurred in the vicinity of the shoulder and tool pin action areas. The copper was pushed from the retreating side (RS) to the advancing side (AS) of the weld, allowing it to flow more fully. A mixture of both materials formed at the bottom of the weld nugget, and less migration occurred in the heat-affected zone of the AS at this time. The highest tensile strength can reach 194 MPa, accounting for 82.6% of the copper. The presence of brittle phases Cu5Zn8, AgZn3 and AgZn caused the hardness to fluctuate slightly.

The payment card industry has grown increasingly with the development of online business. However, payment card fraud has become a serious problem around the world. Companies and banks lost huge amounts of dollars annually due to fraud. It is necessary to investigate a learning algorithm to detect fraud in finance transaction automatically. In this paper, we put forward a fraud detection algorithm by using neural network. The neural network model and final result will be described to show the superiority of this model.

In response to the global energy crisis, the integrated energy system has become an important part of the energy revolution. Aiming at the economic operation of the Integrated Energy System (IES), this paper proposes a system optimization planning model that takes the economic and environmental optimization as the goal and establishes a coupled capacity planning system, and jointly optimizes the capacity configuration and configuration of a single energy supply module. Power output to pursue maximum benefit. In order to illustrate the advantages of this method, on the basis of simulation, a dynamic programming method is used to solve the model. Finally, the simulation results show the effectiveness of the planning optimization model proposed in this paper, and provide a new path for solving the optimization problem of integrated energy system planning.