Therapy-induced APOBEC3A drives evolution of persistent cancer cells.

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1-4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer1. However, clinical responses to FGFR inhibitors have remained variable1-9, emphasizing the need to better understand which FGFR2 alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening10,11 and tumour modelling in mice12,13, and find that the truncation of exon 18 (E18) of Fgfr2 is a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2 alterations, including rearrangements, E1-E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing the transcription of E18-truncated FGFR2 (FGFR2ΔE18). Functional in vitro and in vivo examination of a compendium of FGFR2ΔE18 and full-length variants pinpointed FGFR2-E18 truncation as single-driver alteration in cancer. By contrast, the oncogenic competence of FGFR2 full-length amplifications depended on a distinct landscape of cooperating driver genes. This suggests that genomic alterations that generate stable FGFR2ΔE18 variants are actionable therapeutic targets, which we confirmed in preclinical mouse and human tumour models, and in a clinical trial. We propose that cancers containing any FGFR2 variant with a truncated E18 should be considered for FGFR-targeted therapies.

The mental health of Australians bereaved during the first two years of the COVID-19 pandemic: a latent class analysis.

BACKGROUND: The COVID-19 pandemic disrupted many areas of life, including culturally accepted practices at end-of-life care, funeral rites, and access to social, community, and professional support. This survey investigated the mental health outcomes of Australians bereaved during this time to determine how these factors might have impacted bereavement outcomes. METHODS: An online survey indexing pandemic and bereavement experiences, levels of grief, depression, anxiety, and health, work, and social impairment. Latent class analysis (LCA) was used to identify groups of individuals who shared similar symptom patterns. Multinomial regressions identified pandemic-related, loss-related, and sociodemographic correlates of class membership. RESULTS: 1911 Australian adults completed the survey. The LCA identified four classes: low symptoms (46.8%), grief (17.3%), depression/anxiety (17.7%), and grief/depression/anxiety (18.2%). The latter group reported the highest levels of health, work, and social impairment. The death of a child or partner and an inability to care for the deceased due to COVID-19 public health measures were correlated with grief symptoms (with or without depression and anxiety). Preparedness for the person's death and levels of pandemic-related loneliness and social isolation differentiated all four classes. Unemployment was associated with depression/anxiety (with or without grief). CONCLUSIONS: COVID-19 had profound impacts for the way we lived and died, with effects that are likely to ricochet through society into the foreseeable future. These lessons learned must inform policymakers and healthcare professionals to improve bereavement care and ensure preparedness during and following future predicted pandemics to prevent negative impacts.

Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment.

CONTEXT: Klinefelter syndrome (KS) is associated with hypergonadotropic hypogonadism, which contributes to characteristic phenotypical manifestations including metabolic alterations. Extensive research has demonstrated important associations between androgens and liver function. OBJECTIVES: Investigation of the association between metabolic parameters, sex hormones and liver function in males with KS, both treated (T-KS) and untreated (U-KS) and healthy control males. METHODS: A total of 65 KS males were recruited, of which 32 received testosterone replacement therapy (TRT). Also, 69 healthy controls were recruited. We used alanine aminotransferase (ALAT), alkaline phosphatase and PP (prothrombin-proconvertin time ratio) as the main liver markers. Multivariable regression was performed within the three groups. All statistics were calculated using STATA. Principal component analysis was utilized to demonstrate the interconnected patterns among all measured biomarkers, and to elucidate how the different groups were linked to these patterns. RESULTS: Higher levels of main liver markers were observed in U-KS compared to controls, with no significant differences between U-KS and T-KS. T-KS had lower abdominal fat, total cholesterol, and LDL cholesterol than U-KS. Using multivariable models, variation in ALAT in U-KS was explained by HOMA2%S; in T-KS by BMI and SHBG; and in controls by hip circumference and estradiol. We found no multivariable models explaining variation in PP in U-KS; in T-KS, PP was explained by BMI and LDL cholesterol, and in controls by total cholesterol. Using principal component analysis U-KS was positively associated to D1 (an obese profile, which also included ALAT) and controls negatively associated with D1 (non-obese profile). CONCLUSION: KS males have mild liver dysfunction reflected by a significant increase in the main liver markers and decrease in albumin. The presented data underscore a primary role of metabolic conditions including obesity, insulin resistance and unfavourable lipid profile, in the elevated liver function markers seen in males with KS. Whether TRT can improve liver function in KS warrants further studies. Our findings, highlight that an evaluation of the liver function should be part of the clinical care in males with KS.

Periodontitis and Chronic Obstructive Pulmonary Disease: A bidirectional Mendelian randomization study.

OBJECTIVE: Observational studies have suggested an association between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD). This study aimed to determine whether there is a causal relationship between CP and COPD incidence. DESIGN: Two­sample Mendelian Randomization (MR) analysis using summary statistics from two genome­wide association studies (GWASs) of European ancestry. Single nucleotide polymorphisms (SNPs) associated with COPD were obtained from the FinnGen database, which included 16,380,382 SNPs. The diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2023). We also obtained SNPs associated with CP from the FinnGen database, which included 16,380,378 SNPs. RESULTS: Sixteen eligible SNPs were extracted to analyze the causal effect of CP on COPD incidence. There was no causal correlation between CP and COPD using the inverse variance-weighted method (IVW) (OR=0.97, 95%CI= 0.91-1.05; p=0.482). Seven eligible SNPs were extracted to analyze the causal effect of COPD on CP incidence. Again, there was also no causal correlation between using IVW (OR=1.09, 95%CI=0.93-1.28; p=0.279). CONCLUSION: We did not demonstrate a causal relationship between genetically predicted CP and COPD, or between genetically predicted COPD and CP.

Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells.

Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7(-/-)) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival.

[Analysis of the change in human resources of centers for disease control and prevention in different regions of China from 2010 to 2020].

Objective: To analyze the change in human resources within China's Centers for Disease Control and Prevention (CDC) from 2010 to 2020. Methods: The self-reported information from provincial, prefectural (city), and county (district) levels of China's CDC, covering employee counts, staff composition, professional qualifications, educational backgrounds, technical titles, and tenure, were extracted from the China Disease Prevention and Control Information System. The demographic context was provided by the annual population figures from the China Statistical Yearbook (2010-2020). The profile of CDC personnel was described, and the average annual percentage rate change (AAPC), average annual percentage rate change (APC), human resource agglomeration degree (HRAD) and the difference between HRAD and population agglomeration degree (PAD) were calculated. The Joinpoint regression model was used to analyze the time trend. Results: The decade under review witnessed a net increase of 17 300 active and 18 300 enrolled personnel in the CDC, surpassing the national population growth rate with AAPCs of 0.93% and 1.03%, respectively. This upward trajectory was statistically significant (P<0.05). The ratio of disease control personnel per 10 000 population escalated from 1.14 to 1.21. An initial decline in active CDC workforce density (from 1.31 to 1.27 per 10 000 population between 2010 and 2017) was followed by an increase (from 1.28 to 1.37 between 2018 and 2020), with APCs of -0.40% and 3.73%, respectively. The proportion of professional and technical staff in 2019 was highest in the eastern region (86.01%), followed by the western (83.75%) and central regions (79.54%). The period also saw an enhancement in the average academic degree (from 1.91 to 2.43 points) and professional title scores (from 1.39 to 1.53 points) of CDC personnel. While the average tenure in the eastern and western regions showed a slight decline, the central region experienced an increase, with HRAD values indicating a higher concentration in the eastern and central regions compared to the western region. The HRAD-PAD discrepancy revealed a negative value in the eastern region, nearing zero in the central and western regions. Conclusion: Between 2010 and 2020, China's CDC experienced notable growth in human resources and underwent structural optimization, albeit with significant regional disparities in concentration.

Facile preparation of porphyrin@g-C3N4/Ag nanocomposite for improved photocatalytic degradation of organic dyes in aqueous solution.

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.

Enabling early detection of knee osteoarthritis using diffusion-relaxation correlation spectrum imaging.

AIM: To present a technique that enables detection of early stage OA of the knee using diffusion-relaxation correlation spectrum imaging (DR-CSI). MATERIALS AND METHODS: Fifty-five early osteoarthritis patients (OA, Kellgren-Lawrence [KL] score 1 to 2; mean age, 56.4 years) and 49 healthy volunteers (mean age, 56.7 years) were underwent magnetic resonance imaging (MRI) with T2-mapping and DR-CSI techniques. Maps of mean apparent diffusion coefficient (ADC), T2 relaxation time and volume fraction Vi for DR-CSI compartment i (A, B, C, D) sensitivity, specificity, and positive and negative likelihood ratio (PLR, NLR) were assessed to determine the diagnostic accuracy for detection of early-stage degeneration of knee articular cartilage. The structural abnormalities of articular cartilage were evaluated using modified Whole-Organ MR Imaging Scores (WORMS). RESULTS: All intra- and interobserver agreements for DR-CSI compartment volume fractions and modified WORMS of cartilage were excellent. Early OA versus the controls had higher VC, lower VA and VB (p<0.001), but comparable VD (p>0.05). VA, VB and VC had a moderate association with WORMS. No significant correlation was identified between VD and WORMS. VC had better ability than VA,VB, VD, T2 and ADC to discriminate early OA patients from healthy controls (area under the curve, 0.898). Sensitivity, specificity, PLR, and NLR of VC with a cut-off value of 29.9% were 81.8% (95% confidence interval [CI], 69.1-90.9%), 95.9% (86-99.5%), 20.05% (5.13-78.34%), and 0.19% (0.11-0.33%). CONCLUSIONS: DR-CSI compartment volume fractions may be sensitive indicators for detecting early-stage degeneration in knee articular cartilage.

Evaluation of a national clinical programme for the management of self-harm in hospital emergency departments: impact on patient outcomes and the provision of care.

BACKGROUND: Emergency departments are important points of intervention, to reduce the risk of further self-harm and suicide. A national programme to standardise the management of people presenting to the emergency department with self-harm and suicidal ideation (NCPSHI) was introduced in Ireland in 2014. The aim of this study was to evaluate the impact of the NCPSHI on patient outcomes and provision of care. METHODS: Data on self-harm presentations were obtained from the National Self-Harm Registry Ireland from 2012 to 2017. The impacts of the NCPSHI on study outcomes (3-month self-harm repetition, biopsychosocial assessment provision, admission, post-discharge referral, and self-discharge) were examined at an individual and aggregate (hospital) level, using a before and after study design and interrupted time series analyses, respectively. The 15 hospitals that implemented the programme by January 2015 (of a total of 24 between 2015 and 2017) were included in the analyses. RESULTS: There were 31,970 self-harm presentations during the study period. In hospitals with no service for self-harm (n = 4), risk of patients not being assessed reduced from 31.8 to 24.7% following the introduction of the NCPSHI. Mental health referral in this hospital group increased from 42.2 to 59.0% and medical admission decreased from 27.5 to 24.3%. Signs of a reduction in self-harm repetition were observed for this hospital group, from 35.1 to 30.4% among individuals with a history of self-harm, but statistical evidence was weak. In hospitals with a pre-existing liaison psychiatry service (n = 7), risk of self-discharge was lower post-NCPSHI (17.8% vs. 14.8%). In hospitals with liaison nurse(s) pre-NCPSHI (n = 4), medical admission reduced (27.5% vs. 24.3%) and there was an increase in self-harm repetition (from 5.2 to 7.8%. for those without a self-harm history). CONCLUSION: The NCPSHI was associated with improvements in the provision of care across hospital groups, particularly those with no prior service for self-harm, highlighting the need to consider pre-existing context in implementation planning. Our evaluation emphasises the need for proper resourcing to support the implementation of clinical guidelines on the provision of care for people presenting to hospital with self-harm.

Can vibrotactile stimulation and tDCS help inefficient BCI users?

Brain-computer interface (BCI) has helped people by allowing them to control a computer or machine through brain activity without actual body movement. Despite this advantage, BCI cannot be used widely because some people cannot achieve controllable performance. To solve this problem, researchers have proposed stimulation methods to modulate relevant brain activity to improve BCI performance. However, multiple studies have reported mixed results following stimulation, and the comparative study of different stimulation modalities has been overlooked. Accordingly, this study was designed to compare vibrotactile stimulation and transcranial direct current stimulation's (tDCS) effects on brain activity modulation and motor imagery BCI performance among inefficient BCI users. We recruited 44 subjects and divided them into sham, vibrotactile stimulation, and tDCS groups, and low performers were selected from each stimulation group. We found that the latter's BCI performance in the vibrotactile stimulation group increased significantly by 9.13% (p < 0.01), and while the tDCS group subjects' performance increased by 5.13%, it was not significant. In contrast, sham group subjects showed no increased performance. In addition to BCI performance, pre-stimulus alpha band power and the phase locking values (PLVs) averaged over sensory motor areas showed significant increases in low performers following stimulation in the vibrotactile stimulation and tDCS groups, while sham stimulation group subjects and high performers showed no significant stimulation effects across all groups. Our findings suggest that stimulation effects may differ depending upon BCI efficiency, and inefficient BCI users have greater plasticity than efficient BCI users.

Characterisation of admissions and readmissions after 20 days of illness among COVID-19 patients.

INTRODUCTION: There has been an observed number of readmissions after an index COVID-19 admission, including admissions after an initial home quarantine. The purpose of this study was to identify the clinical characteristics and outcomes of COVID-19 patients who were readmitted or admitted after an initial home quarantine between 21 and 90 days of illness. MATERIALS AND METHODS: This was a single-centre retrospective cohort study comprising patients admitted to a state hospital in Selangor, Malaysia, between August and October 2021. The demographic data, clinical characteristics, presenting complaints, laboratory tests, organ dysfunction, use of invasive ventilation, intensive care unit (ICU) admissions, length of hospitalisation and mortality were collected and analysed. RESULTS: The analysis involved a total of 195 cases. More than a quarter of the cases (52 [26.7%]) were related to the initial COVID-19 infection. Nine cases (4.6%) required mechanical ventilation, while eight cases (4.1%) were admitted to the ICU. The overall mortality was 17 cases (8.7%). Surviving patients were younger (49.5 vs. 58.4 years), less likely to have diabetes mellitus (48.3% vs. 82.4%), or chronic kidney disease (12.9% vs. 41.2%); had higher levels of admission haemoglobin (12.6 vs. 9.1g/dL) and albumin (33.0 vs. 21.0g/L); lower white blood cells (10.2 vs. 13.0 × 109/L), creatinine (81.2 vs. 151.9µmol/L) and C-reactive protein (18.2 vs. 135.0mg/L) at admission; less likely to have MI (6.7% vs. 23.5%), sepsis (3.4% vs. 47.1%), or acute kidney injury (3.4% vs. 17.6%) and organ dysfunction (25.3% vs. 94.1%). CONCLUSION: Approximately a quarter of patients were admitted or readmitted due to direct COVID-19 complications between 21 and 90 days of illness. The baseline oxygen requirements at admission were independently associated with mortality, invasive mechanical ventilation and ICU admissions. Further research is needed to establish a risk model for patients returning to a hospital to predict their risk of post-COVID complications.

Epithelial-mesenchymal transition profiles in triple negative breast carcinoma may explain its aggressive nature.

Epithelial-mesenchymal transition (EMT) is increasingly explored in cancer progression. Considering that triple negative (TN) breast cancer has the poorest survival among molecular subtypes, we investigated 49 TN, 45 luminal and 25 HER2-enriched female breast carcinomas for EMT expression (using E-cadherin and vimentin immunohistochemistry) against lymphovascular and/or lymph node invasion. E-cadherin and vimentin expressions were semi-quantitated for positive- cancer cells (0=0-<1%, 1=1-10%, 2 =11-50%, 3=>50%) and staining intensity (0=negative, 1=weak, 2=moderate, 3=strong), with final score (low=0-4 and high=6-9) derived by multiplying percentage and intensity scores for each marker. Low E-cadherin and/or high vimentin scores defined EMT positivity. Low E-cadherin co-existing with high vimentin defined "complete" (EMT-CV), while low E-cadherin (EMT-C) or high vimentin (EMT-V) occurring independently defined "partial" subsets. 38 (31.9%) cancers expressed EMT, while 59.2 % TN, 13.3% luminal and 12% HER2-enriched cancers expressed EMT (p<0.05). Among the cancers with lymphovascular and/or lymph node invasion, EMT positivity by molecular types were 66.7% TN, 7.4% luminal and 11.8% HER2-enriched (p<0.05). Although EMT-V, associated with stem-cell properties was the dominant TN EMT profile, EMT-CV, a profile linked to vascular metastases, was encountered only in TN. EMT appears important in TN cancer and different EMT profiles may be associated with its aggressive nature.

[Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique].

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

[Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease].

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

[Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR].

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

On the Relationship Between Oceanic Plate Speed, Tectonic Stress, and Seismic Anisotropy.

Seismic radial anisotropy (the squared ratio between the speeds of horizontally and vertically polarized shear waves, ξ = V S H 2 V S V 2 ) is a powerful tool to probe the direction of mantle flow and accumulated strain. While previous studies have confirmed the dependence of azimuthal anisotropy on plate speed, the first order control on radial anisotropy is unclear. In this study, we develop 2D ridge flow models combined with mantle fabric calculations to report that faster plates generate higher tectonics stresses and strain rates which lower the dislocation creep viscosity and lead to deeper anisotropy than beneath slower plates. We apply the SGLOBE-rani tomographic filter, resulting in a flat depth-age trend and stronger anisotropy beneath faster plates, which correlates well with 3D global anisotropic mantle models. Our predictions and observations suggest that as plate speed increases from 2 to 8 cm/yr, radial anisotropy increases by ∼0.01-0.025 in the upper 100-200 km of the mantle between 10 and 60 Ma.

The efficiency of potential food waste-degrading bacteria under harsh conditions.

AIMS: Investigate the impact of highly adapted bacterial strains and their ability in waste degradation under a wide range of temperatures. METHODS AND RESULTS: Bacteria isolated from soil and food waste were grown in various media under fluctuated temperatures. After screening for organic compound degradation, the seven strongest bacterial strains have been selected for further experiments. Their enzyme activities were expressed in terms of the size of the hydrolysis zone in a wide temperature range of 2·5-70°C. The enzyme production assay was carried out for each protease, cellulase and amylase. The waste degradation was determined with a maximum 80% decrease in the volume of food waste in 21 days compared to the control in lab scale with enriched bacterial cultures and soil bacteria as additives at room temperature around 18-20°C. CONCLUSION: These seven bacteria are promising candidates for food waste biodegradation in composting especially in the winter without heating expense for maintaining ambient temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: It is necessary to coax the uncultured bacteria from the various environments into the laboratory for investigating their valuable functions. Herein, using enrichment culture of consortium and additive of soil has illustrated the significant mean in food waste degradation.

Novel pure α-, ß-, and mixed-phase α/ß-Bi2O3 photocatalysts for enhanced organic dye degradation under both visible light and solar irradiation.

Combining the pure α- and ß-phases of bismuth oxide enhances its photocatalytic activity under both visible and solar irradiation. α-Bi2O3, ß-Bi2O3, and α/ß-Bi2O3 were synthesized by a solvothermal calcination method. The structural, optical, and morphological properties of the as-synthesized catalysts were analyzed using XRD, UV-DRS, XPS, SEM, TEM, and PL. The bandgaps of α/ß-Bi2O3, α-Bi2O3, and ß-Bi2O3 were calculated to be 2.59, 2.73, and 2.34 eV, respectively. The photocatalytic activities of the catalysts under visible and solar irradiation were examined by the degradation of carcinogenic reactive blue 198 and reactive black 5 dyes. The kinetic plots of the degradation reactions followed pseudo-first-order kinetics. α/ß-Bi2O3 exhibited higher photocatalytic activity (∼99%) than α-Bi2O3 and ß-Bi2O3 under visible and solar irradiation. The TOC and COD results confirmed the maximum degradation ability of α/ß-Bi2O3, and the decolorization percentage remained above 90%, even after five cycles under visible irradiation. The photocatalytic dye degradation mechanism employed by α/ß-Bi2O3 was proposed based on active species trapping experiments.