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Objective: To examine temporal changes in coverage with a complete primary series of coronavirus disease 2019 (COVID-19) vaccination and staffing shortages among healthcare personnel (HCP) working in nursing homes in the United States before, during, and after the implementation of jurisdiction-based COVID-19 vaccination mandates for HCP. Sample and setting: HCP in nursing homes from 15 US jurisdictions. Design: We analyzed weekly COVID-19 vaccination data reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network from June 7, 2021, through January 2, 2022. We assessed 3 periods (preintervention, intervention, and postintervention) based on the announcement of vaccination mandates for HCP in 15 jurisdictions. We used interrupted time-series models to estimate the weekly percentage change in vaccination with complete primary series and the odds of reporting a staffing shortage for each period. Results: Complete primary series vaccination among HCP increased from 66.7% at baseline to 94.3% at the end of the study period and increased at the fastest rate during the intervention period for 12 of 15 jurisdictions. The odds of reporting a staffing shortage were lowest after the intervention. Conclusions: These findings demonstrate that COVID-19 vaccination mandates may be an effective strategy for improving HCP vaccination coverage in nursing homes without exacerbating staffing shortages. These data suggest that mandates can be considered to improve COVID-19 coverage among HCP in nursing homes to protect both HCP and vulnerable nursing home residents.

Background Hexavalent chromium can promote centrosome amplification (CA) as well as tumorigenesis. Since CA can lead to tumorigenesis, it is plausible that the chromium promotes the development of cancer via CA. In the present study, we investigated the signaling pathways of the chromium-induced CA. Results Our results showed that sub-toxic concentration of chromium was able to cause CA in HCT116 cells, and decreased the expression of TMOD2 and NPM2. Furthermore, TMOD2 and NPM2 interacted to each other via their C-terminal and the N-terminal, respectively, which was inhibited by the chromium. Overexpression of TMOD2 and NPM2 increased their binding and significantly attenuated the CA. Moreover, TMOD2 and NPM2 were co-localized with the centrosomes. The chromium inhibited the centrosomeal localization of NPM2, which is reversed by the overexpression of TMOD2, C-termianl of TMOD2, but not the N-terminal of NPM2. Conclusion Our results suggest that the chromium induces CA via inhibiting the binding between TMOD2 and NPM2, and the dissociation of NPM2 from centrosomes.

This study investigated the role of curcumin nanocarriers carrying TAR-RNA binding protein (TRBP) in hepatocellular carcinoma (HCC). We conducted a retrospective analysis of 60 HCC tissue samples and 30 normal liver tissues. TRBP level was measured in HCC. Disease-free survival (DFS) and overall survival (OS) were calculated to analyze correlation between TRBP expression and diagnostic sensitivity of HCC. Survival factors were analyzed using cyclo-oxygen-ase (COX) univariate and multivariate survival analysis. The curcumin nanocarriers-loaded siRNA (si)-TRBP were transfected into HCC cells during in vitro experiments to detect HCC cell proliferation and invasion, whilst flow cytometry measured apoptosis rate of cancer cells. TRBP was highly expressed in 60 HCC tissues and positively associated with diagnostic sensitivity of HCC, with lower DFS and OS in HCC patients with higher TRBP expression, and FIGO stage and TRBP were indicated as risk factors for DFS and OS. High TRBP expression coexisted with increased HCC cell proliferation and invasion. Moreover, transfection of curcumin nanocarriers-loaded si-TRBP dramatically decreased cell viability and invasion, downregulated cleaved caspase-3 and caspase-9, while upregulating Bcl-2. Collectively, this study demonstrated TRBP is upregulated in HCC and curcumin nanocarriers carrying si-TRBP, significantly suppressing growth of HCC cells, providing a theoretical basis for treatment of HCC.

Fan Hu,1,2,* Meng-Lu Lin,1,2,* Juan-Li Mou,1,2,* Jia-Hui Feng,1,2 Kai Huang,1,2 Yao-Jia Lao,1,2 Jie Cheng,1,2 Jun Lin1,2 1Department of Gastroenterology/Hepatology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2The Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Lin, Email linjun64@126.comBackground: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance.Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain’s identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology.Results: The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049.Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.Keywords: Klebsiella pneumoniae, carbapenemases, whole-genome sequencing, resistance genes, virulence factor

Due to the excessive exploitation of traditional energy sources, the attention paid to water energy has increased in recent years. As an important means to effectively utilize water energy, reservoirs play an important role in drinking water, irrigation, flood control, and drought resistance. However, utilizing reservoirs often led to water quality issues resulting from the interaction of nutrients and hydrological conditions, especially due to the special structure of karst areas. Because of the change of hydrological conditions by the effect of dam construction, the dynamic of water quality will be more obvious in karst areas with a fast exchange of water and contaminants between underground and surface streams. In the present study, the change in water quality of a karst reservoir, the Muzhu Reservoir in the Houzhai Catchment, was studied. Long-term monitored datasets (1981-2002) and water quality datasets of more recent years were used to assess the effect on the water quality of reservoir expansion from the underground reservoir to the surface reservoir in a karst area. Long-term series datasets had shown that the hydro-chemistry type had been changed from HCO

Respirogram technology has been widely applied for aerobic process, however, the response of respirogram to anoxic denitrification is still unclear. To reveal such response may help to design a new method for the evaluation of the performance of denitrification. The size distribution of flocs measured at different denitrification moments demonstrated a clear expansion of flocs triggered by denitrification, during which higher specific endogenous and quasi-endogenous respiration rates (SOUR

Gold nanoparticles (AuNPs) colorimetric assays based on distance-dependent optical characteristics have been widely employed for bioanalysis. However, this assay is not effective for visually detecting low-concentration targets due to the faint color change. Here, we developed a handheld nano-centrifugal device which could separate the crosslinked and non-crosslinked AuNPs. Results showed that the handheld nano-centrifugal device could easily reach more than 6000 r/min within 10 s simply by stretching and tightening the coiled rope in an appropriate rhythm. Further, combined with the CRISPR/Cas12a nucleic acids recognition system, a field-deployable colorimetric platform termed handheld nano-centrifugal device assisted CRISPR/Cas12a (Hand-CRISPR) has been validated. Moreover, clinical diagnostics applications for Epstein-Barr virus (EBV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection with high sensitivity and accuracy (100% consistency with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) test results) have been demonstrated. Overall, the Hand-CRISPR platform showed great promise in point-of-care-test (POCT) application, expected to become a powerful supplement to the standard nucleic acid testing method in remote or poverty-stricken areas.The online version contains supplementary material available at 10.1007/s41664-022-00232-0.

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbβ3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

Cup-shaped ear is a common congenital auricle deformity. There are many specific surgical methods, such as V-Y method, Barsky method, Musgrave method, etc., but there is no unified treatment method. The authors used the outer helix reconstruction method for cup-shaped ear and achieved remarkable therapeutic effects.The authors performed the outer helix reconstruction on 30 patients with cup-shaped ear. The authors followed up the patients after the stage II operation. The authors used the SPSAU data science analysis platform (https://spssau.com/) for statistical analysis of the data.The mean follow-up time was 14.43±4.5 months. The mean preoperative perimeter of auricle was 8.19±0.56 cm. The mean postoperative perimeter of auricle was 10.82±0.49 cm. The mean perimeter of the healthy auricle was 10.89±0.44 cm. Through data analysis, the authors found that the comparison between preoperative and postoperative auricle perimeters was statistically significant (P0.05). The comparison between postoperative auricle perimeter and the perimeter of the healthy auricle was not statistically significant (P0.05). In terms of postoperative satisfaction of patients and their families, the satisfaction rate was 100%. In terms of postoperative complications, there were 1 case of incision dehiscence, 0 cases of incision infection, 2 cases of incision hematoma, and 0 cases of postoperative skin flap ischemia and necrosis.The outer helix reconstruction method is suitable for most cup-shaped ears, and the operation is simple and the effect is remarkable. It is worthy of promotion and application in plastic surgery clinical.

IntroductionCOVID-19 vaccines are safe, effective, and widely available, but many adults in the U.S. have not been vaccinated for COVID-19. This study examined the associations between behavioral and social drivers of vaccination with COVID-19 vaccine uptake in the U.S. adults and their prevalence by region.MethodsA nationally representative sample of U.S. adults participated in a cross-sectional telephone survey in August-November 2021; the analysis was conducted in January 2022. Survey questions assessed self-reported COVID-19 vaccine initiation, demographics, and behavioral and social drivers of vaccination.ResultsAmong the 255,763 respondents, 76% received their first dose of COVID-19 vaccine. Vaccine uptake was higher among respondents aged ≥75 years (94%), females (78%), and Asian non-Hispanic people (94%). The drivers of vaccination most strongly associated with uptake included higher anticipated regret from nonvaccination, risk perception, and confidence in vaccine safety and importance, followed by work- or school-related vaccination requirements, social norms, and provider recommendation (all p

Predictor information and NO2 predictions per model per city (Amsterdam, Bayreuth, Hamburg, and Utrecht) at a 100m resolution

Triploids are rare in nature because of difficulties in meiotic and gametogenic processes, especially in vertebrates. The Carassius complex of cyprinid teleosts contains sexual tetraploid crucian carp/goldfish (C. auratus) and unisexual hexaploid gibel carp/Prussian carp (C. gibelio) lineages, providing a valuable model for studying the evolution and maintenance mechanism of unisexual polyploids in vertebrates. Here we sequence the genomes of the two species and assemble their haplotypes, which contain two subgenomes (A and B), to the chromosome level. Sequencing coverage analysis reveals that C. gibelio is an amphitriploid (AAABBB) with two triploid sets of chromosomes; each set is derived from a different ancestor. Resequencing data from different strains of C. gibelio show that unisexual reproduction has been maintained for over 0.82 million years. Comparative genomics show intensive expansion and alterations of meiotic cell cycle-related genes and an oocyte-specific histone variant. Cytological assays indicate that C. gibelio produces unreduced oocytes by an alternative ameiotic pathway; however, sporadic homologous recombination and a high rate of gene conversion also exist in C. gibelio. These genomic changes might have facilitated purging deleterious mutations and maintaining genome stability in this unisexual amphitriploid fish. Overall, the current results provide novel insights into the evolutionary mechanisms of the reproductive success in unisexual polyploid vertebrates.

With the rapid development of music streaming media service industry, users can easily hear any song on mobile devices. Internet has become a huge music storage platform. With the development of network and large-scale digital music industry, the acquisition and listening of music are presented to users in a more convenient way. How to find the music loved by users from the massive Internet digital music data has become the key problem and main goal to be solved in the field of music information retrieval. Personalized music recommendation system can accurately find and push songs that users may be interested in from tens of millions of huge music libraries according to users’ information under the condition that users only have vague demand for listening to songs. Relying on the traditional search method to find the music that you are interested in can no longer meet the needs of users, so the current music recommendation system needs to dig out the music that has no clear needs in the long tail to help people find their favorite songs.

Background: Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation has been implicated in pulmonary arterial hypertension (PAH), whereas the role of platelet in the pathogenesis of PAH remains unclear. Methods: First, we explored the platelet function of semaxanib‚ a inhibitor of VEGF receptor (SU5416)/hypoxia mice and monocrotaline-injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cell aerobic glycolysis after being treated with platelet supernatant. TGF (transforming growth factor)-βRI, pyruvate kinase muscle 2, and other antagonists were applied to identify the underlying mechanism. In addition, platelet-specific deletion TGF-β1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling, and aerobic glycolysis of pulmonary arterial smooth muscle cell were determined. Results: Here, we demonstrate that platelet-released TGF-β1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing pyruvate kinase muscle 2 expression. Mechanistically, platelet-derived TGF-β1 regulate spyruvate kinase muscle 2 expression through mTOR (mammalian target of rapamycin)/c-Myc/PTBP-1(polypyrimidine tract binding protein 1)/hnRNPA-1(heterogeneous nuclear ribonucleoprotein A1) pathway. Platelet TGF-β1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia–induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4cre + Tgfb1 fl/fl mice, pulmonary arterial smooth muscle cells showed lower glycolysis capacity and their pyruvate kinase muscle 2 expression decreased. Conclusions: Our data demonstrate that TGF-β1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH.

Prostate cancer (PCa) is a common malignant tumor of the male urinary system and ranks the second in the causes of tumor-related deaths. Differential display code 3 (DD3) is a noncoding gene that is specifically expressed in PCa. High expression of sperm-associated antigen 9 (SPAG9) is closely related to tumorigenesis of PCa, and SPAG9 is a therapeutic target for PCa. In this study, a new oncolytic adenovirus DD3-ZD55-SPAG9 was constructed by using DD3 promoter to enhance the efficacy and safety of adenovirus. The combined use of DD3-ZD55-SPAG9 and docetaxel showed that DD3-ZD55-SPAG9 significantly improved the anti-tumor efficacy of docetaxel in PCa both in vitro and in vivo. The mechanism was related to the induction of tumor cell apoptosis and the inhibition of tumor cell invasion. In conclusion, DD3-ZD55-SPAG9 combined with docetaxel is an effective strategy for PCa therapy.

Background. BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods. Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results. The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS−). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS−/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and

A new individualized, cost-effective, modified semi-computer-assisted surgery (MSCAS) concept for free fibular flap mandibular reconstruction is reported and compared with the computer-assisted surgery (CAS) concept. Patients were divided into two groups and retrospectively reviewed. In the MSCAS and CAS groups, intraoperative guides were created using computer-aided design with manual fabrication and computer-aided design and manufacturing, respectively. Differences in specific linear and angular parameters on pre- and postoperative computed tomography scans were calculated for morphometric comparison, and clinical parameters and efficiency were analysed. RESULTS: Eighteen patients (CAS, 7; MSCAS, 11), were included. The morphometric comparison showed no significant differences between the groups. The mean deviation of the mandibular ramus length, body length, width 1 and width 2 was 0.82 ± 0.29 mm, 1.84 ± 0.43 mm, 1.89 ± 0.61 mm and 1.45 ± 0.61 mm in the CAS group versus 1.56 ± 0.54 mm, 1.72 ± 0.33 mm, 2.24 ± 0.55 mm and 2.36 ± 0.50 mm in the MSCAS group (p = 0.7804, p = 0.9997, p = 0.9814 and p = 0.6334). The mean deviation of the sagittal, axial and coronal mandibular angles was 1.56 ± 0.48°, 1.93 ± 0.50° and 2.15 ± 0.72° in the CAS group versus 2.19 ± 0.35°, 1.86 ± 0.35° and 1.94 ± 0.55° in the MSCAS group (p = 0.7594, p = 0.9996 and p = 0.9871). There were no significant differences in clinical parameters, efficiency or postoperative complications between the groups. CONCLUSION: The accuracy and operative efficiency of the MSCAS concept are comparable to those of the more expensive CAS concept. Therefore, in times of increasing clinical costs, this concept might be an adequate and inexpensive alternative to preoperative CAS.

Abstract: Protein-ligand interactions are necessary for majority protein functions. Adenosine- 5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is costineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

ObjectiveConsidering the non-specific nature of muscle symptoms, studies of statin-induced myopathy (SIM) in electronic health records require accurate algortihms that can reliably identify true statinrelated cases. However, prior algorithms have been constructed in study populations that preclude broad applicability. Here we developed and validated an algorithm that accurately defines SIM from electronic health records using structured data elements and conducted a study of determinants of SIM after applying the algorithm.Materials and MethodsWe used electronic records from an integrated health care delivery system (including comprehensive pharmacy dispensing records) and defined SIM as elevated creatine kinase (CK) ≥4 x upper limit of normal. A diverse cohort of participants receiving a variety of statin regimens met the criteria for study inclusion.ResultsWe identified multiple conditions strongly associated with elevated CK independent of statin use. A 2-step algorithm was developed using these all-cause conditions as secondary causes (step 1) along with evidence of a statin regimen change (step 2). We identified 1,262 algorithm-derived statininduced elevated CK cases. Gold standard SIM cases determined from manual chart reviews on a random subset of the all-cause elevated CK cases were used to validate the algorithm, which had a 76% sensitivity and 77% specificity for detecting the most certain cases. Pravastatin use was associated with a 2.18 odds (95% confidence interval 1.39-3.40, P=0.0007) for statin-induced CK elevation compared to lovastatin use after adjusting for dose and other factors.ConclusionsWe have produced an efficient, easy-to-apply methodological tool that can improve the quality of future research on statin-induced myopathy.

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of human ALS motor neurons. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and extends animal lifespan.