WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks.

DNA double-strand breaks (DSBs) at RNA polymerase II (RNAPII) transcribed genes lead to inhibition of transcription. The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in transcription inhibition at DSBs by stimulating proteasome-dependent eviction of RNAPII at these lesions. How DNA-PK triggers RNAPII eviction to inhibit transcription at DSBs remains unclear. Here we show that the HECT E3 ubiquitin ligase WWP2 associates with components of the DNA-PK and RNAPII complexes and is recruited to DSBs at RNAPII transcribed genes. In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII. The lack of WWP2 or expression of nonubiquitylatable RPB1 abrogates the binding of nonhomologous end joining (NHEJ) factors, including DNA-PK and XRCC4/DNA ligase IV, and impairs DSB repair. These findings suggest that WWP2 operates in a DNA-PK-dependent shutoff circuitry for RNAPII clearance that promotes DSB repair by protecting the NHEJ machinery from collision with the transcription machinery.

Morphometric Evaluation of the Ampullae of the Oviducts in Prepubertal Gilts Treated With Chorionic Gonadotropins.

This study assessed morphometric traits of the ampulla of the oviducts in prepubertal gilts treated with chorionic gonadotropins. With the day of slaughter as D0, gilts were assigned to four treatments (n = 8 each): control (untreated), eCG (200 IU eCG on D3), eCG+hCG (1200 IU eCG on D6 plus 500 IU hCG on D3), and eCG+hCG+AI (the previous treatment plus artificial insemination on D1). Blood and ampullae samples were collected at slaughter. Serum progesterone concentrations were higher for gilts treated with hCG than for those in the eCG and control treatments (p < 0.001), but estradiol concentrations did not differ (p > 0.05). The epithelium, muscle and lumen areas and the inner and larger ampullae diameters did not differ across treatments (p > 0.05). Therefore, treatment with chorionic gonadotropins did not alter the ampullae morphometry of prepubertal gilts.

The effects of enteric-coated sodium bicarbonate supplementation on 2 km rowing performance in female CrossFit® athletes.

PURPOSE: Sodium bicarbonate (SB) supplementation can improve exercise performance, but few studies consider how effective it is in female athletes. The aim of the study was to establish the effect of individually timed pre-exercise SB ingestion on 2 km rowing time trial (TT) performance in female athletes. METHODS: Eleven female CrossFit® athletes (mean ± SD age, 29 y ± 4 y, body mass, 64.5 kg ± 7.1 kg, height, 1.7 m ± 0.09 m, peak oxygen uptake [VO2peak], 53.8 ± 5.7 mL·kg-1∙min-1). An initial trial identified individual time-to-peak [HCO3-] following enteric-coated 0.3 g·kg-1 BM SB ingestion. Participants then completed a 2 km TT familiarisation followed by a placebo (PLA) or SB trial, using a randomised cross-over design. RESULTS: The ingestion of SB improved rowing performance (514.3 ± 44.6 s) compared to the PLA (529.9 ± 45.4 s) and FAM trials (522.2 ± 43.1 s) (p = 0.001, pη2 = 0.53) which represents a 2.24% improvement compared to the PLA. Individual time-to-peak alkalosis occurred 102.3 ± 22.1 min after ingestion (range 75-150 min) and resulted in increased blood [HCO3-] of 5.5 ± 1.5 mmol⋅L-1 (range = 3.8-7.9 mmol⋅L-1). The change in blood [HCO3-] was significantly correlated with the performance improvement between PLA and SB trials (r = 0.68, p = 0.020). CONCLUSIONS: Ingesting a 0.3 g·kg-1 BM dose of enteric-coated SB improves 2 km rowing performance in female athletes. The improvement is directly related to the extracellular buffering capacity even when blood [HCO3-] does not change ≥ 5.0 mmol⋅L-1.

Psychological and functional impacts associated with restrictions in long-term care facilities (LTCF) due to the COVID-19 pandemic: A multicentre study.

Objectives: To analyze the impacts of the restrictions implemented in LTCF during the COVID-19 pandemic on the psychological and functional status of older adults. Design: A retrospective multicentre study is designed. We hypothesize that the negative effects of the restrictions will lead to a higher rate of decline between the measures taken immediately before and after the lockdown than between the two measures taken before the lockdown. Setting and participants: 365 participants recruited in four Spanish LTCFs in Galicia and Valencia.Methods: Impacts of restrictions on cognitive (MMSE), affective (GDS) and functional status (Barthel index, Tinetti) were analyzed by Linear Mixed Models with random intercepts, random slopes, and personal and contextual factors as covariates.Results: Social measures covaried significantly with the cognitive and functional status but did not predict longitudinal change. MMSE, Barthel index and Tinetti scores decreased significantly across pre- and post-lockdown measurement times, but only the Tinetti scores showed a specific impact of the restrictions.Conclusions: Only performance-based functional measures showed the real impact of restrictions. The findings highlight the importance of having data from several pre-lockdown measurements to enable identification of changes that can be causally attributed to the restrictions. The findings also support the resilience of older adults in mitigating the effect of the restrictions.

Protective effects of a chemically characterized extract from solanum torvum leaves on acetaminophen-induced liver injury.

Distinct parts of Solanum torvum Swartz. (Solanaceae) are popularly used for a variety of therapeutic purposes. This study determined the phytochemical composition of a phenolic fraction of S. torvum leaf aqueous extract and investigated its antioxidant and liver-protective properties. A phenolic compound-enriched fraction, or phenolic fraction (STLAE-PF) of an infusion (STLAE) of S. torvum leaves, was tested in vitro (antagonism of H2O2 in cytotoxicity and DCF assays with HepG2/C3A cells), and in vivo for antioxidant activity and protective effects against acetaminophen (APAP)-induced liver injury in mice. Thirty-eight compounds (flavonoids, esters of hydroxycinnamic acid, and chlorogenic acid isomers) were tentatively identified (high-performance liquid chromatography coupled to high-resolution electrospray mass spectrometry) in the STLAE-PF fraction. In vitro assays in HepG2/C3A cells showed that STLAE-PF and some flavonoids contained in this phenolic fraction, at noncytotoxic levels, antagonized in a concentration-dependent manner the effects of a powerful oxidant agent (H2O2). In C57BL/6 mice, oral administration of STLAE (600 and 1,200 mg/kg bw) or STLAE-PF (300 mg/kg bw) prevented the rise in serum transaminases (ALT and AST), depletion of reduced glutathione (GSH) and elevation of thiobarbituric acid reactive species (TBARs) levels in the liver caused by APAP (600 mg/kg bw, i.p.). The hepatoprotective effects of STLAE-PF (300 mg/kg bw) against APAP-caused liver injury were comparable to those of N-acetyl-cysteine (NAC 300 or 600 mg/kg bw i.p.). These findings indicate that a phenolic fraction of S. torvum leaf extract (STLAE-PF) is a new phytotherapeutic agent potentially useful for preventing/treating liver injury caused by APAP overdosing.

[Feasibility study of immediate breast reconstruction with fusion fascia combined with implants].

Objective: To investigate the oncologic and surgical safety of the fused fascia method for immediate breast reconstruction with implants. Methods: The clinical data of 343 patients with immediate breast reconstruction with implants in Tianjin Medical University Cancer Hospital from 2014-2017 were retrospectively analyzed to compare the 5-year local recurrence-free survival, 5-year disease-free survival and 5-year overall survival of patients with breast reconstruction by fusion fascia and other methods, and to analyze the complication incidences of implant removal between different implant groups. Results: Of the 343 patients with breast reconstruction, 95 were in the fused fascia group (fascia group) and 248 were in the non-fascia group (25 in the bovine pericardial patch group and 223 in the muscle flap group). At a median follow-up of 49 months, the differences in 5-year local recurrence-free survival (90.1% and 94.9%, respectively), 5-year disease-free survival (89.2% and 87.6%, respectively), and 5-year overall survival (95.2% and 95.1%, respectively) between patients in the fascial and non-fascial groups were not statistically significant (P>0.05). The complication incidence of implant removal was 24.0% (6/25) in the patch group and 2.1% (2/95) and 2.2% (5/223) in the fascia and muscle flap groups, respectively. Conclusion: Immediate breast reconstruction with fused fascial combined with implant is safe and feasible, less invasive than muscle flaps, more economical and with fewer complications than patches.

[The predictive value of microvascular obstruction for adverse left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a prospective study].

Objectives: Microvascular obstruction (MVO) is a specific cardiac magnetic resonance (CMR) imaging feature in patients with acute myocardial infarction. The purpose of this study was to elucidate the predictive value of MVO in left ventricular adverse remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 167 patients with STEMI undergoing primary PCI in the Chinese PLA General Hospital from 2016 to 2020 were enrolled in this prospective cohort study, the average age of study patients was 57±10 years old, with 151 males (90.4%) and 16 females (9.6%). The patients were divided into the MVO group (n=81) and non-MVO group (n=86) according to the presence or absence of MVO on CMR imaging, respectively. The primary endpoint of the study was the occurrence of left ventricular adverse remodeling, which was defined as an increase in left ventricular end diastolic volume (LVEDV) by >20% at 6 months after primary PCI compared with the baseline. Patients who completed follow-up were diagnosed as left ventricular adverse remodeling or no left ventricular adverse remodeling according to CMR. The baseline data, perioperative data, and related data of end points were compared between the MVO group and non-MVO group. Finally, the predictive value of MVO in left ventricular adverse remodeling was calculated by receiver operating characteristic curve analysis. Results: In the baseline data, preoperative thrombolysis in myocardial infarction (TIMI) flow (χ2=13.74, P=0.003) and postoperative TIMI flow (χ2=14.87, P=0.001) were both obviously decreased in the MVO group. After 6 months of follow-up, the incidence of left ventricular adverse remodeling in the MVO group was significantly higher than that in the non-MVO group [37.0%(27/73) vs. 18.9%(14/74), χ2=5.96, P=0.015]. The left ventricular end systolic volume at 6 months post infarction in the MVO group was significantly larger than that in the non-MVO group [(94±32) vs. (68±20) ml, t=-5.98, P<0.001], as well as the LVEDV [(169±38) vs. (143±29) ml, t=-4.74, P<0.001]. Receiver operating characteristic curve showed that the area under the curve of MVO size for predicting left ventricular adverse remodeling was 0.637. Conclusion: The risk of left ventricular adverse remodeling is significantly increased in patients with MVO after primary PCI for acute STEMI.

[Diagnostic value of anti-Sa antibody and anti-carbamylated protein antibody for rheumatoid arthritis].

Objective: To investigate the diagnostic value of anti-Sa antibody and anti-carbonylated protein (CarP) antibody for rheumatoid arthritis (RA). Methods: A retrospective selection of 180 patients with RA who came to Qinghai Provincial People's Hospital from September 2022 to February 2023. Grouped according to the Disease Activity Score of 28 joints (DAS28), 101 of them were patients with RA in high activity (RAH group), 24 males and 77 females, aged 18-79 (53.2±12.2), and 79 patients with RA in low activity (RAL group), 23 males and 56 females, aged 24-78 (49.0±12.9).A total of 90 patients with other autoimmune diseases in the hospital in the same period were choosed as the other immune disease group, and 90 healthy physical examiners were as the healthy control group. The levels of serum anti-Sa and anti-CarP antibodies were measured by ELISA, RF by immunoscattering turbidimetry, anti-CCP by chemiluminescence, and ESR by Weil's method in four groups of patients. The area under the subject operating characteristic (ROC) curve (AUC) was applied to assess the sensitivity and specificity of each index alone or in combination for the diagnosis of RA. Results: In the RAH group, RAL group, other immune disease group, and healthy control group, the RF levels were 117.6 (61.0, 161.1), 92.7 (48.1, 92.7), 10.1 (5.3, 24.6), and 8.1 (6.0, 12.8) U/ml, anti-CCP antibody levels were 202.7 (67.1, 594.4), 212.9 (98.3, 416.2), 9.4 (6.6, 11.8), 1.9 (0.8, 4.9) U/ml, anti-Sa antibody levels were 305.3 (120.4, 614.9), 235.8 (161.6, 336.9), 123.9 (41.8, 240.5), 165.1 (71.1, 237.5) U/ml, and anti-CarP antibody levels were 11.7 (7.9, 21.6), 5.2 (3.3, 7.7), 5.1 (3.9, 6.5), and 5.8 (3.8, 7.5) mg/L, respectively, and their differences were statistically significant (all P<0.001). The level of anti-CarP antibody was higher in the RAH group than in the RAL group (P<0.001), and the difference in anti-Sa antibody was not statistically significant (P>0.05). The critical value of anti-Sa antibody at 181.45 µg/L showed a sensitivity of 67.2%, specificity of 65.6% and AUC of 0.710 (95%CI: 0.645-0.775); The sensitivity was 52.8% and the specificity was 88.9% with an AUC of 0.706 (95%CI: 0.646-0.766) at a critical value of 7.98 U/ml for the anti-CarP antibody. The AUC for the combined RF, anti-CCP antibody and anti-CarP antibody assay was 0.986 (95%CI: 0.977-0.996). Conclusion: Anti-CarP antibody is clinically significant in distinguishing active RA. RF, anti-CCP, and anti-CarP antibodies can be detected together with high AUC results, suggesting the potential for developing an improved method for diagnosing RA.

[Correlation of extracellular enzymes activity of Candida glabrata clinical isolates with in vivo pathogenicity in Galleria mellonella larvae].

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.

[Epidemiologic characteristics and drug resistance of isolated from blood culture escherichia coli in a hospital in Qinghai Province from 2016 to 2022].

Objective: To explore the drug resistance of Isolated From Blood Culture Escherichia coli (E. coli) in a hospital in Qinghai over the past seven years, to evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the homologous origin of E. coli, and to establish a protein fingerprint library to match with it, adjuvant clinical experience medication so as to provide the basis for the prevention and control of hospital-acquired infections. Methods: Retrospective analysis of blood cultures sent to hospitals from January 2016 to December 2022. Drug resistance and resistance changes in E. coli.A total of 1 841 E. coli strains were isolated from Qinghai Provincial People's Hospital from January 2016 to December 2022; all strains were identified by MALDI-TOF MS, and the VITEK2.0 drug sensitivity analyzer was applied for drug sensitivity analysis of the strains, and the mass spectrometry homology analysis and self-constructed protein fingerprint library were carried out by MALDI-Biotyper software; the protein fingerprint library was built by using WHONET5.6 software was used to statistically analyze the drug sensitivity results, SPSS23.0 software was used to analyze the relationship between fingerprint typing and drug sensitivity, and the χ2 test was used for intergroup comparisons. Results: A total of 1 841 strains of E. coli were detected in 4 582 positive blood culture specimens from January 2016 to December 2022, with a detection rate of 40.17%; the resistance rate of E. coli from blood sources to piperacillin/tazobactam and ceftriaxone was on the rise, and it was slightly decreased to cefepime, amikacin, levofloxacin, and sulfamethoxazole, and there was not much change to the rest of the drugs; After MALDI-Biotyper clustering analysis, the 1841 E. coli strains from Isolated From Blood Culture were classified into two major clusters and five subtypes, of which type Ⅰa1 accounted for about 40%, type Ⅰa2 accounted for about 2.7%, type Ⅰb accounted for about 3.8, type Ⅱa accounted for about 46%, and type Ⅱb accounted for about 7.5%. The detection rate of type Ⅰa1 E. coli was higher in general surgery (50.45%) and emergency surgery (50.92%), and the detection rate of type Ⅰb E. coli was higher in emergency medicine(10.05%)than in other departments. The drug sensitivity results of different subtypes were compared with each other, the resistance rate of type Ⅰa1 E. coli to cefepime was 21.3% higher than that of the remaining four types, and the difference was statistically significant (χ2=37.74,P=0.000); the resistance rate of type Ⅱ E. coli(>60%) to sulfamethoxazole was higher than that of type Ⅰ (<60%) as a whole, and the difference was statistically significant (χ2=15.248,P=0.004); and a preliminary database of homologous protein fingerprints of E. coli has been established E. coli homologous protein fingerprint library and validated. The drug susceptibility results of 1 288 E. coli strains in the validation set were statistically analyzed and compared with those in the training set. There was no significant difference(P>0.05). Conclusion: In recent years, the resistance rate of E. coli isolated from a hospital in Qinghai province to piperacillin/Tazobactam, cefepime, amicacin and other antibiotics has changed greatly. A fingerprint database of E. coli homologous protein was established, and it was found that the drug sensitivity data of E. coli were different among different fingerprint types. According to drug sensitivity, drug use could assist clinical experience and provide evidence for prevention and control of hospital illness.

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.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

Yield of Adding chest CT to Abdominal CT to Detect COVID-19 in Patients Presenting With Acute Gastrointestinal Symptoms (SCOUT-3): Multicenter Study.

OBJECTIVE: To determine the incremental yield of standardized addition of chest CT to abdominal CT to detect COVID-19 in patients presenting with primarily acute gastrointestinal symptoms requiring abdominal imaging. Summary Background Data: Around 20% of patients with COVID-19 present with gastrointestinal symptoms. COVID-19 might be neglected in these patients, as the focus could be on finding abdominal pathology. During the COVID-19 pandemic, several centers have routinely added chest CT to abdominal CT to detect possible COVID-19 in patients presenting with gastrointestinal symptoms. However, the incremental yield of this strategy is unknown. METHODS: This multicenter study in 6 Dutch centers included consecutive adult patients presenting with acute nontraumatic gastrointestinal symptoms, who underwent standardized combined abdominal and chest CT between March 15, 2020 and April 30, 2020. All CT scans were read for signs of COVID-19 related pulmonary sequelae using the СО-RADS score. The primary outcome was the yield of high COVID-19 suspicion (СО-RADS 4-5) based on chest CT. RESULTS: A total of 392 patients were included. Radiologic suspicion for COVID-19 (СО-RADS 4-5) was present in 17 (4.3%) patients, eleven of which were diagnosed with COVID-19. Only 5 patients with СО-RADS 4-5 presented without any respiratory symptoms and were diagnosed with COVID-19. No relation with community prevalence could be detected. CONCLUSION: The yield of adding chest CT to abdominal CT to detect COVID-19 in patients presenting with acute gastrointestinal symptoms is extremely low with an additional detection rate of around 1%.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

Multimetallic Permethylpentalene Hydride Complexes.

The synthesis and characterization of group 4 permethylpentalene (Pn* = C8Me6) hydride complexes are explored; in all cases, multimetallic hydride clusters were obtained. Group 4 lithium metal hydride clusters were obtained when reacting the metal dihalides with hydride transfer reagents such as LiAlH4, and these species featured an unusual hexagonal bipyramidal structural motif. Only the zirconium analogue was found to undergo hydride exchange in the presence of deuterium. In contrast, a trimetallic titanium hydride cluster was isolated on reaction of the titanium dialkyl with hydrogen. This diamagnetic, mixed valence species was characterized in the solid state, as well as by solution electron paramagnetic resonance and nuclear magnetic resonance spectroscopy. The structure was further probed and corroborated by density functional theory calculations, which illustrated the formation of a metal-cluster bonding orbital responsible for the diamagnetism of the complex. These permethylpentalene hydride complexes have divergent structural motifs and reactivity in comparison with related classical cyclopentadienyl analogues.

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. METHODS AND RESULTS: This was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131-3.136]), C-reactive protein (1.046 [1.020-1.073]), blood pressure >140/90 mmHg (2.686 [1.506-4.791]), fibrates (2.032 [1.160-3.562]), calcium channel blockers (2.082 [1.158-3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240-4.721]), heart failure (2.139 [1.032-4.433]), LDL-C >70 mg/dL (4.594 [1.401-15.069]), and diuretics (3.328 [1.677-6.605]) were associated with cardiovascular mortality. CONCLUSIONS: The composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

Frailty among older Hispanics living in the United States: A scoping review.

A scoping review was conducted to identify the available evidence about frailty among older Hispanics living in the U.S. using the Integral Model of Frailty. A not time-limited search was conducted in five peer-reviewed databases. Identified factors associated with frailty among older Hispanics are presented in four categories: (1) Characteristics and prevalence of frailty, (2) Life course determinants of frailty, (3) Comorbidities associated with frailty, and (4) Adverse outcomes of frailty. A total of 1030 articles were identified, and 37 articles were included in the scoping review. Most studies measured frailty based on the Fried Frailty Phenotype (59.5%, n= 22) and had a longitudinal design (64.9%, n= 24). The overall prevalence of frailty among Hispanics ranged from 4.3% to 37.1% (n= 20 studies). Further research is needed that targets Hispanics from different backgrounds in the U.S., particularly those that are high in number (i.e., Mexicans, Puerto Ricans, and Central Americans).

[Application value of plasma proteomics in the diagnosis and pathogenesis of high altitude polycythemia].

Objective: To explore the application value of plasma proteomics in the diagnosis and pathogenesis of high altitude polycythemia (HAPC). Methods: Ten patients with HAPC in Qinghai Provincial People's Hospital from January 2020 to January 2021 were selected as the experimental group, including 4 males and 6 females, aged (46±4) years. Ten healthy controls at the same altitude in the same period were selected as the control group, including 5 males and 5 females, aged (44±4) years. The differential proteins were identified and quantified by high performance liquid chromatography-mass spectrometry (HPLC-MS), and the gene ontology (GO) functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and interaction network analysis were conducted for the selected differential proteins. Results: A total of 117 differential proteins with quantitative values were screened from the experimental group and the control group, 45 significantly up-regulated proteins with quantitative values only in the experimental group, 40 significantly down-regulated proteins with quantitative values only in the control group, and 32 differentially expressed proteins with quantitative values in both experimental and control groups were detected. Compared with the control group, 11 of the 32 differentially expressed proteins in the experimental group were down-regulated and 21 were up-regulated. The results of GO functional enrichment analysis showed that the biological processes involved by differential proteins mainly included immune response, complement activation, activated protein cascade and coagulation system. The results of KEGG function enrichment analysis showed that the main biochemical metabolic pathways and signal transduction pathways involved by differential proteins were axon guidance, lysosomes, cell adhesion molecules, lipid and atherosclerosis, hematopoietic cell lineage and cholesterol metabolism. The abundant domains are mainly in immunoglobulin-like domain, EGF-like domain, fibronectin type Ⅲ superfamily, serine proteases, Sushi/SCR/CCP superfamily. The results of differential protein interaction analysis showed that the interaction score was>700, and the top 10 differential proteins with the largest number of nodes were MPO, RPS27A, ARG1, GM2A, TIMP1, CRP, FABP5, HBB, S100A7 and RHOA, respectively. Conclusion: Plasma proteomics analysis technique is helpful to identify the related protein markers in the development of HAPC, and provide reference for the diagnosis and pathogenesis of HAPC.

[Application of cortical bone trajectory screw and sacral alar screw internal fixation for surgical treatment of lumbar adjacent segment degeneration].

Objective: To explore the application of cortical bone trajectory screw (CBTS) and sacral alar screw (SAS) internal fixation in the treatment of lumbar adjacent segment degeneration (ASD) and evaluate its clinical effect. Methods: Data of 24 patients who were diagnosed with ASD and treated by CBTS or SAS in Beijing Chaoyang Hospital were retrospectively reviewed. There were 14 males and 10 females with a mean age of (67.9±8.2) years. The patients were followed-up for (2.6±0.4) years. Perioperative parameters including operation time, intraoperative blood loss and postoperative time on the ground were counted. All patients were followed-up for at least 2 years. Visual analogue scale (VAS) and the Oswestry disability index (ODI) were compared between pre-operation and at the last follow-up. The internal fixation-related complications, pseudarthrosis and adjacent re-degeneration were evaluated in the follow-up. Results: There were 14 proximal ASD patients, 8 distal ASD patients, 1 both ends ASD patient and 1 ASD patient in between the fusion surgeries. Bone mineral density (BMD) T score of the adjacent vertebrae was -1.98±0.91 on average. The ASD patients were re-operated with CBTS and SAS internal fixation technique. A small incision was made in the revision surgery and the original fixation was not completely cut open and removed. The mean operation time was (125±36) min, mean blood loss was (85±33) ml. The postoperative ambulation time was (3.1±1.9) days, and the hospitalization time was (9.0±2.6) days. Before the operation, the average VAS (back pain) score was 5.2±1.0, the average of VAS (leg pain) score was 6.8±1.9 and ODI was 56.6%±12.8%. VAS score was reduced to 1.4±0.6 (waist pain) and 0.9±0.4 (leg pain). ODI was improved to 13.8%±6.3%. All the difference between preoperative and the last follow-up was statically significant (all P<0.01). No internal fixation failure, pseudarthrosis and adjacent re-degeneration were observed in the final follow-up. Conclusion: The application of CBTS and SAS internal fixation techniques in the surgical treatment of lumbar ASD has the advantages of less trauma, faster postoperative recovery, reliable internal fixation, and fewer complications, especially in patients with low bone mineral density.

Heterodinuclear Zn(II), Mg(II) or Co(III) with Na(I) Catalysts for Carbon Dioxide and Cyclohexene Oxide Ring Opening Copolymerizations.

A series heterodinuclear catalysts, operating without co-catalyst, show good performances for the ring opening copolymerization (ROCOP) of cyclohexene oxide and carbon dioxide. The complexes feature a macrocyclic ligand designed to coordinate metals such as Zn(II), Mg(II) or Co(III), in a Schiff base 'pocket', and Na(I) in a modified crown-ether binding 'pocket'. The 11 new catalysts are used to explore the influences of the metal combinations and ligand backbones over catalytic activity and selectivity. The highest performance catalyst features the Co(III)Na(I) combination, [N,N'-bis(3,3'-triethylene glycol salicylidene)-1,2-ethylenediamino cobalt(III) di(acetate)]sodium (7), and it shows both excellent activity and selectivity at 1 bar carbon dioxide pressure (TOF=1590 h-1 , >99 % polymer selectivity, 1 : 10: 4000, 100 °C), as well as high activity at higher carbon dioxide pressure (TOF=4343 h-1 , 20 bar, 1 : 10 : 25000). Its rate law shows a first order dependence on both catalyst and cyclohexene oxide concentrations and a zeroth order for carbon dioxide pressure, over the range 10-40 bar. These new catalysts eliminate any need for ionic or Lewis base co-catalyst and instead exploit the coordination of earth-abundant and inexpensive Na(I) adjacent to a second metal to deliver efficient catalysis. They highlight the potential for well-designed ancillary ligands and inexpensive Group 1 metals to deliver high performance heterodinuclear catalysts for carbon dioxide copolymerizations and, in future, these catalysts may also show promise in other alternating copolymerization and carbon dioxide utilizations.