Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort.

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Surveillance Colonoscopy Findings in Older Adults With a History of Colorectal Adenomas.

Importance: Postpolypectomy surveillance is a common colonoscopy indication in older adults; however, guidelines provide little direction on when to stop surveillance in this population. Objective: To estimate surveillance colonoscopy yields in older adults. Design, Setting, and Participants: This population-based cross-sectional study included individuals 70 to 85 years of age who received surveillance colonoscopy at a large, community-based US health care system between January 1, 2017, and December 31, 2019; had an adenoma detected 12 or more months previously; and had at least 1 year of health plan enrollment before surveillance. Individuals were excluded due to prior colorectal cancer (CRC), hereditary CRC syndrome, inflammatory bowel disease, or prior colectomy or if the surveillance colonoscopy had an inadequate bowel preparation or was incomplete. Data were analyzed from September 1, 2022, to February 22, 2024. Exposures: Age (70-74, 75-79, or 80-85 years) at surveillance colonoscopy and prior adenoma finding (ie, advanced adenoma vs nonadvanced adenoma). Main Outcomes and Measures: The main outcomes were yields of CRC, advanced adenoma, and advanced neoplasia overall (all ages) by age group and by both age group and prior adenoma finding. Multivariable logistic regression was used to identify factors associated with advanced neoplasia detection at surveillance. Results: Of 9740 surveillance colonoscopies among 9601 patients, 5895 (60.5%) were in men, and 5738 (58.9%), 3225 (33.1%), and 777 (8.0%) were performed in those aged 70-74, 75-79, and 80-85 years, respectively. Overall, CRC yields were found in 28 procedures (0.3%), advanced adenoma in 1141 (11.7%), and advanced neoplasia in 1169 (12.0%); yields did not differ significantly across age groups. Overall, CRC yields were higher for colonoscopies among patients with a prior advanced adenoma vs nonadvanced adenoma (12 of 2305 [0.5%] vs 16 of 7435 [0.2%]; P = .02), and the same was observed for advanced neoplasia (380 of 2305 [16.5%] vs 789 of 7435 [10.6%]; P < .001). Factors associated with advanced neoplasia at surveillance were prior advanced adenoma (adjusted odds ratio [AOR], 1.65; 95% CI, 1.44-1.88), body mass index of 30 or greater vs less than 25 (AOR, 1.21; 95% CI, 1.03-1.44), and having ever smoked tobacco (AOR, 1.14; 95% CI, 1.01-1.30). Asian or Pacific Islander race was inversely associated with advanced neoplasia (AOR, 0.81; 95% CI, 0.67-0.99). Conclusions and Relevance: In this cross-sectional study of surveillance colonoscopy yield in older adults, CRC detection was rare regardless of prior adenoma finding, whereas the advanced neoplasia yield was 12.0% overall. Yields were higher among those with a prior advanced adenoma than among those with prior nonadvanced adenoma and did not increase significantly with age. These findings can help inform whether to continue surveillance colonoscopy in older adults.

[Net survival analysis of cancer in Zhongshan City of Guangdong Province in China, 1970 to 2014].

Objective: To analyze survival data of cancer from 1970 to 2014 in Zhongshan City, Guangdong Province, and provide scientific basis for cancer prevention and control in Zhongshan City. Methods: The tumor incidence data of Zhongshan City, Guangdong Province from 1970 to 2014 were collected from Zhongshan Cancer Registry, and all patients were followed up to December 31, 2019. The standardized 5-year net survival rates and their annual percentage change (APC) and average annual percentage change (AAPC) for total and major cancers at different times were used to describe statistical analysis. The standardized survival rates were weighted using the International Cancer Survival Standard Age Coefficients. Results: There were 78 854 cancer patients eligible for the study in Zhongshan City of Guangdong Province from 1970 to 2014, among which lung cancer (13 466 cases, 17.08%), nasopharyngeal cancer (9715 cases, 12.32%) and liver cancer (9707 cases, 12.31%) were the main types of cancer. The morphology verification was 69.87% in the whole of cancers and the ranges were 21.07% to 97.00% in major cancers. From 2010 to 2014, the 5-year age-standardized net survival rates of cancers for all, males and females in Zhongshan City were 39.74%, 30.92% and 52.47%, in which were 97.98% for thyroid cancer, 74.29% for brain and central nervous system tumors, 73.92% for nasopharyngeal cancer, 50.23% for colorectal cancer, 81.38% for female breast cancer, 78.81% for uterine body cancer, 68.57% for cervical cancer, 49.33% for prostate cancer, 16.19% for lung cancer , 12.14% for liver cancer, and 11.78% for esophageal cancer, respectively. The survival rates of all cancers in Zhongshan City showed an increasing trends in 1970-2014 (AAPC=1.5%, P=0.025), and it was higher in female cancers than that of male in all periods. Conclusion: The standardized 5-year net survival rates of all and major cancers in Zhongshan City of Guangdong Province show an increasing trend from 1970 to 2014, but they are still at a medium-low levels compared with the countries and regions participating in CONCORD-3 project, suggesting that Zhongshan should continue to strengthen cancer prevention and control.

[Analysis on the characteristics of natural foci of hemorrhagic fever with renal syndrome in Gansu Province, 2012-2022].

Objective: To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province. Methods: The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus. Results: A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions: The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

Sleep and Epilepsy.

The relationship between sleep and epilepsy is both intimate and bidirectional. The molecular mechanisms which control circadian rhythm and the sleep/wake cycle are dysregulated in epileptogenic tissue and are themselves effected by molecular pathways for epilepsy. Sleep affects the frequency of interictal epileptiform discharges and recent research has raised new questions regarding the impact of discharges on sleep function and cognition. Epileptiform discharges themselves affect sleep architecture and increase the risk of sleep disorders. Several sleep-related epilepsy syndromes have undergone changes in their classification which highlights their intimate relationship to sleep and novel screening tools have been developed to help clinicians better differentiate epileptic seizures from sleep-related paroxysmal events. Improving sleep and addressing sleep disorders has been associated with improved seizure control and increased well-being in people with epilepsy. These interactions are discussed in detail in this review.

Sophora tonkinensis: response and adaptation of physiological characteristics, functional traits, and secondary metabolites to drought stress.

The medicinal plant Sophora tonkinensis is a characteristic Chinese shrub of karst areas. The arid climate in karst areas produces high-quality S. tonkinensis; however, the mechanisms of drought tolerance are not clear, which restricts sustainable plantings of S. tonkinensis. This study involved a 20-day drought stress experiment with potted S. tonkinensis and threee soil water regimes: control (CK), mild drought (MDT), and severe drought (SDT). Plant morphology, biomass, physiological indicators, alkaloid content, and other changes under drought stress were monitored. The content of soluble sugars and proteins, and activity of antioxidant enzymes in leaves and roots were higher under drought than CK, indicating that S. tonkinensis is tolerant to osmotic stress in early drought stages. Content of matrine and oxymatrine increased gradually with increasing drought duration in the short term. The epidermis of S. tonkinensis leaves have characteristics of desert plants, including upper epidermal waxy layer, lower epidermal villi, and relatively sunken stomata, suggesting that S. tonkinensis has strong drought tolerance. In conclusion, drought stress changed the cell structure of S. tonkinensis, induced antioxidant enzyme activity and increased its resistance to drought.

[MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN].

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION: Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.

Impact of a scalable training program on the quality of colonoscopy performance and risk of postcolonoscopy colorectal cancer.

BACKGROUND AND AIMS: Endoscopist adenoma detection rates (ADRs) vary widely and are associated with patients' risk of postcolonoscopy colorectal cancers (PCCRCs). However, few scalable physician-directed interventions demonstrably both improve ADR and reduce PCCRC risk. METHODS: Among patients undergoing colonoscopy, we evaluated the influence of a scalable online training on individual-level ADRs and PCCRC risk. The intervention was a 30-minute, interactive, online training, developed using behavior change theory, to address factors that potentially impede detection of adenomas. Analyses included interrupted time series analyses for pretraining versus posttraining individual-physician ADR changes (adjusted for temporal trends) and Cox regression for associations between ADR changes and patients' PCCRC risk. RESULTS: Across 21 endoscopy centers and all 86 eligible endoscopists, ADRs increased immediately by an absolute 3.13% (95% confidence interval [CI], 1.31-4.94) in the 3-month quarter after training compared with .58% per quarter (95% CI, .40-.77) and 0.33% per quarter (95% CI, .16-.49) in the 3-year pretraining and posttraining periods, respectively. Posttraining ADR increases were higher among endoscopists with pretraining ADRs below the median. Among 146,786 posttraining colonoscopies (all indications), each 1% absolute increase in screening ADR posttraining was associated with a 4% decrease in their patients' PCCRC risk (hazard ratio, .96; 95% CI, .93-.99). An ADR increase of ≥10% versus <1% was associated with a 55% reduced risk of PCCRC (hazard ratio, .45; 95% CI, .24-.82). CONCLUSIONS: A scalable, online behavior change training intervention focused on modifiable factors was associated with significant and sustained improvements in ADR, particularly among endoscopists with lower ADRs. These ADR changes were associated with substantial reductions in their patients' risk of PCCRC.

[Observation of the efficacy of autologous mucosal transplantation to prevent esophageal stricture after near-circumferential endoscopic submucosal dissection for early esophageal cancer].

Objective: To investigate the efficacy of autologous mucosal transplantation to prevent esophageal stricture after near-circumferential endoscopic submucosal dissection (ESD) for early esophageal cancer. Methods: The case data of 33 patients, who underwent near-circumferential ESD for early esophageal cancer and were followed up regularly in the First Affiliated Hospital of Zhengzhou University from April 2017 to July 2022, were analyzed retrospectively, including 14 males and 19 females, aged (66.4±7.4) (47-77) years. According to the different treatment methods, they were divided into 4 groups: group A (6 cases) were treated with autologous mucosa transplantation and fully covered metal stent implantation, combined with oral, intravenous and local injection of hormone; Group B (8 cases) were treated with autologous mucosa transplantation and fully covered metal stent implantation; Group C (11 cases) were treated with fully covered metal stent implantation combined with oral or intravenous hormone; Group D (8 cases) were treated with fully covered metal stent implantation. After the operation, the growth of the transplanted mucosa, esophageal stricture and surgical complications were observed by endoscopy, so as to understand the efficacy of automucosa transplantation in preventing esophageal stricture after near-circumferential ESD for early esophageal cancer. Results: The gastroscopic operation was successful in 33 patients. The times of expansion in groups B, C and D were more than that in group A, and the times of expansion [M(Q1,Q3)] in group A were 0(0, 1.8) times, while the times of expansion in group B, C and D were 5.5(4.3, 6.8), 4.0(4.0, 7.0) and 5.5(3.5, 10.8) times, respectively, with statistical significance (all P<0.05). There was no significant difference in times of expansion among groups B, C and D (all P>0.05). The stent placement time [M(Q1,Q3)] in group B [7.5(6.3, 8.8) days] was shorter than that in group A [64.5(41.5, 75.5) days] (P=0.006). There was no significant difference in stent placement time between group C [38.0(28.0, 50.0) days] and group D [31.5(27.3, 66.3) days] and group A (both P>0.05). The stent placement time in group C was longer than that in group B (P<0.05).There was no significant difference in stent placement time between group B, C and D (all P>0.05). There was no significant difference in the incidence of complications among the groups (all P>0.05). Conclusions: Autologous mucosal transplantation is safe and effective in preventing stenosis after near-circumferential ESD for early esophageal cancer. The effect of autologous mucosal transplantation combined with fully covered metal stent placement, systemic and local steroid application in preventing esophageal stricture after near-circumferential ESD for early esophageal cancer is better than that of single application.

Immune characterization of a xenogeneic human lung cross-circulation support system.

Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed for the growing population with end-stage lung disease. Cross-circulation (XC) of whole blood between swine and explanted human lungs has previously been reported to enable the extracorporeal recovery of donor lungs that declined for transplantation due to acute, reversible injuries. However, immunologic interactions of this xenogeneic platform have not been characterized, thus limiting potential translational applications. Using flow cytometry and immunohistochemistry, we demonstrate that porcine immune cell and immunoglobulin infiltration occurs in this xenogeneic XC system, in the context of calcineurin-based immunosuppression and complement depletion. Despite this, xenogeneic XC supported the viability, tissue integrity, and physiologic improvement of human donor lungs over 24 hours of xeno-support. These findings provide targets for future immunomodulatory strategies to minimize immunologic interactions on this organ support biotechnology.

Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

Mn substitution in the topological metal Zr2Te2P.

Results are reported for Mn intercalated Zr2Te2P, where x-ray diffraction , energy dispersive spectroscopy, and transmission electron microscopy measurements reveal that the van der Waals bonded Te-Te layers are partially filled by Zr and Mn ions. This leads to the chemical formulas Zr0.07Zr2Te2P and Mn0.06Zr0.03Zr2Te2P for the parent and substituted compounds, respectively. The impact of the Mn ions is seen in the anisotropic magnetic susceptibility, where Curie-Weiss fits to the data indicate that the Mn ions are in the divalent state. Heat capacity and electrical transport measurements reveal metallic behavior, but the electronic coefficient of the heat capacity (γMn≈ 36.6 mJ (mol·K2)-1) is enhanced by comparison to that of the parent compound. Magnetic ordering is seen atTM≈4 K, where heat capacity measurements additionally show that the phase transition is broad, likely due to the disordered Mn distribution. This transition also strongly reduces the electronic scattering seen in the normalized electrical resistance. These results show that Mn substitution simultaneously introduces magnetic interactions and tunes the electronic state, which improves prospects for inducing novel behavior in Zr2Te2P and the broader family of ternary tetradymites.

[MiR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote colorectal cancer cell metastasis].

OBJECTIVE: To investigate whether miR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote metastasis of colorectal cancer cells. METHODS: We detected the differential expression of miR-372-5p using RT-qRCR in colorectal cancer and adjacent tissues, colorectal cancer cells and normal intestinal epithelial cells. Bioinformatic analysis and double luciferase assay were performed for verification of the targeting relationship between miR-372-5p and PTEN. Western blotting was used to assess the effects of transfection with miR-372-5p inhibitor and miR-372-5p mimics alone, co-transfection with miR-372-5p inhibitor and si-PTEN, and co-transfection with miR-372-5p mimics and PI3K inhibitor on the expressions of PTEN and CXCL12 and the activation of PI3K/AKT signal pathway; Transwell assay and scratch assay were used to examine the changes in the migration ability of the transfected cells, the cells co-transfected with miR-372-5p mimics and si-CXCL12, and the cells treated with conditioned medium from HCT116 cells transfected with miR-372-5p mimics. RESULTS: The expression of miR-372-5p was significantly higher in colorectal cancer tissues than in adjacent tissues, and higher in HCT116 and SW620 cells than in NCM460 cells (P < 0.01). Double luciferase assay confirmed that PTEN was a potential target gene of miR-372-5p (P < 0.05). Transfection of HCT116 cells with miR-372-5p mimics obviously decreased PTEN protein expression, increase CXCL12 expression and the phosphorylation level of AKT, and lowered the cell migration ability, while transfection with miR-372-5p inhibitor produced the opposite effects (P < 0.05); si-PTEN obviously neutralized the effect of miR-372-5p inhibitor (P < 0.01). PI3K inhibitor significantly decreased CXCL12 expression and inhibited the cell migration (P < 0.05), and this effect was mitigated by miR-372-5p mimics (P < 0.01). Treatment with the conditioned medium from HCT116 cells transfected with miR-372-5p mimics significantly enhanced the migration ability of NCM460 cells, and this effect was suppressed by transfection with si-CXCL12 (P < 0.01). CONCLUSION: MiR-372-5p activates PI3K/AKT signaling pathway by targeting PTEN and up-regulates CXCL12 expression to promoting metastasis of colorectal cancer cells.

Association of Blood Pressure Indices with Right and Left Cardio-Ankle Vascular Index (CAVI) and Its Mathematically Corrected Form (CAVI0) for the Evaluation of Atherosclerosis.

BACKGROUND AND OBJECTIVES: The cardio-ankle vascular index (CAVI) is an index for arterial stiffness that is theoretically independent of blood pressure. CAVI0 is the mathematically corrected formula of CAVI that has been claimed to be less dependent on blood pressure changes. The association of right and left CAVI and CAVI0 with blood pressure indices can reveal the importance of considering the blood pressure of the patient despite their theoretical independency. In this study, we assessed the right and left CAVI and CAVI0 and evaluated the main effect of blood pressure indices on them with respect to age. MATERIALS AND METHODS: We collected the following data of 136 community-dwelling individuals: age; sex; weight; height; body mass index; right and left CAVI and CAVI0; and systolic (SBP), diastolic (DBP), and mean blood pressure (MBP). The association of right and left CAVI and CAVI0 with blood pressure indices was evaluated using regression analysis. RESULTS: Regression analysis revealed that SBP, DBP, and MBP were associated with right and left CAVI (independent of age). Moreover, SBP was associated with both right and left CAVI0 (independent of age), whereas DBP was not associated with right or left CAVI0. CONCLUSION: Right and left arterial stiffness measured using CAVI has no different associations with SBP, DBP, and MBP. Both right and left CAVI0 were independently associated with SBP, whereas neither left nor right CAVI0 was independently associated with DBP. MBP was only associated with the right-side CAVI0 in community-dwelling individuals.

Hamiltonian Engineering with Multicolor Drives for Fast Entangling Gates and Quantum Crosstalk Cancellation.

Quantum computers built with superconducting artificial atoms already stretch the limits of their classical counterparts. While the lowest energy states of these artificial atoms serve as the qubit basis, the higher levels are responsible for both a host of attractive gate schemes as well as generating undesired interactions. In particular, when coupling these atoms to generate entanglement, the higher levels cause shifts in the computational levels that lead to unwanted ZZ quantum crosstalk. Here, we present a novel technique to manipulate the energy levels and mitigate this crosstalk with simultaneous off-resonant drives on coupled qubits. This breaks a fundamental deadlock between qubit-qubit coupling and crosstalk. In a fixed-frequency transmon architecture with strong coupling and crosstalk cancellation, additional cross-resonance drives enable a 90 ns CNOT with a gate error of (0.19±0.02)%, while a second set of off-resonant drives enables a novel CZ gate. Furthermore, we show a definitive improvement in circuit performance with crosstalk cancellation over seven qubits, demonstrating the scalability of the technique. This Letter paves the way for superconducting hardware with faster gates and greatly improved multiqubit circuit fidelities.

[Epidemiological characteristics of 2019-nCoV Delta variant in Gansu province].

Objective: To analyze the epidemiological characteristics of COVID-19 caused by 2019-nCoV Delta variant (B.1.617.2) in Gansu province, and provide evidence for the prevention and control of COVID-19. Methods: The information of COVID-19 cases, including demographic characteristics, epidemiological history, onset date, diagnosis date, exposure place, detection way and infection source, in Gansu from 17 October to 25 November, 2021 were collected. Software Excel 2016,SPSS 22 and ArcGIS 10.7 were used for data process and analysis. Results: As of November 25, 2021, a total of 146 COVID-19 cases had been reported in Gansu and the epidemic affected 10 counties (districts) in 5 cities. The epidemic of COVID-19 in Gansu had three stages: imported case stage,imported-local case stage and local case stage. The age of cases ranged from 1 to 87 years,and the cases in age group 18-59 years accounted for 59.59% (87/146). The male to female ratio of the cases was 1∶1.12 (69∶77). The cases were mainly people engaged in business services (17.12%, 25/146),retirees (15.75%, 23/146),students (13.70%, 20/146),the jobless and unemployed (12.33%, 18/146). In 3 epidemic stages, the cases aged 18-59 years accounted for 44.44%,54.41% and 70.00% respectively,showing an upward trend,and there were differences among different populations (trend χ2=23.24, P<0.001). Also, the incubation period of the cases tended to decrease, and severe cases accounted for 33.33% (6/18), 19.12% (13/68) and 3.33% (2/60) respectively, showing a downward trend. Community screening (25.34%, 37/146) and close contact screening were the main ways to detect cases,the cases detected by close contact screening in 3 epidemic stages accounted for 50.00% (9/18), 66.18% (45/68) and 86.67% (52/60) respectively. The epidemic had obvious case clustering in confined places,and the main exposure modes were living together (24.66%), working/studying together (11.64%), taking same transportation (9.59%) and dining together (9.59%). Conclusions: The COVID-19 epidemic in Gansu was caused by 2019-nCoV Delta variant from imported cases. The virus was mainly transmitted through travel, sharing transportation, dining together and home contact. The characteristics of COVID-19 epidemic in Gansu changed with time, the case's clinical symptoms were not obvious and the incubation period became shorter. The infections mainly occurred in group aged 18 years and above.

Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer.

Importance: Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. Objective: To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Design, Setting, and Participants: Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. Exposures: The adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. Main Outcomes and Measures: The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Results: Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Conclusions and Relevance: Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.

SARS-CoV-2 variants - Evolution, spike protein, and vaccines.

Despite the rising natural and vaccines mediated immunity, several countries have experienced a resurgence of the Coronavirus disease of 2019 (COVID-19) due to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. From Alpha to Omicron, the variants of concern (VOC) have evolved several spike protein mutations that may have an impact on virus characteristics, such as transmissibility and antigenicity. In this review, we describe the evolution of SARS-CoV-2, summarize current knowledge of epidemiological and clinical features of the variants, and discuss the response strategies in terms of vaccines to reduce the burden of COVID-19.

[Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells].

Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 µmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-ß1 (DMY+ TGF-ß1), transforming growth factor-ß1 (TGF-ß1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 µmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-ß1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-ß1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-ß1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-ß1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-ß1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-ß1 group were lower than those in DMY+ TGF-ß1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-ß1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-ß1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-ß1 group were higher than those in DMY+ TGF-ß1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-ß1 and promote cell apoptosis.

Large body movements on video polysomnography are associated with daytime dysfunction in children with restless sleep disorder.

Restless sleep disorder (RSD) is a newly defined sleep-related movement disorder characterized by large muscle movements (LMM) in sleep. We examined the sleep study, clinical characteristics, and daytime functioning in children with RSD and compared them to children with periodic limb movement disorder (PLMD) or restless legs syndrome (RLS). Video polysomnography from 47 children with restless sleep was retrospectively reviewed for LMM and age- and sex-matched to 34 children with PLMD and 12 children with RLS. Data examined included PSG characteristics, ferritin, Pediatric Quality of Life (PedsQL), and Epworth Sleepiness Scale (ESS). Fourteen children met the clinical criteria for RSD with an LMM index of 5 or more per hour of sleep. Mean ESS was elevated in patients with RSD compared to either the PLMD or RLS groups though the result did not reach statistical significance (RSD = 10.20 ± 6.81, PLMD = 6.19 ± 4.14, RLS = 6.25 ± 4.90). The PedsQL score was significantly decreased in the RLS group compared to RSD and was reduced overall in all three groups (PedsQL Total RSD = 70.76 ± 18.05, PLMD = 57.05 ± 20.33, RLS = 53.24 ± 16.97). Serum ferritin values were similar in all three groups (RSD = 26.89 ± 10.29, PLMD = 33.91 ± 20.31, RLS = 23.69 ± 12.94 ng/mL, p = ns). Children with RSD demonstrate increased daytime sleepiness compared to PLMD or RLS and all three disease groups showed decreased quality of life. Further studies are needed to examine long-term consequences of RSD.