[Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia].

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).

[Colorectal cancer with ß-catenin protein expression deficiency: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and molecular characteristics of ß-catenin-deficient colorectal cancer. Methods: The clinical, pathological and molecular features of 11 colorectal cancers with ß-catenin protein loss diagnosed at the 960th Hospital of People's Liberation Army of China, from January 2012 to November 2022 were analyzed. Results: Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. ß-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of ß-catenin protein expression. Conclusion: ß-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

Validation and use of the Second Victim Experience and Support Tool questionnaire: a scoping review.

OBJECTIVES: Patient safety incidents can impact not only patients and families but also healthcare providers, who may experience negative emotions and symptoms, such as anxiety, guilt, stress, and loss of confidence. To identify and support these "second victims," a screening tool called the Second Victim Experience and Support Tool (SVEST) has been developed. This scoping review aims to map our current knowledge of the SVEST in terms of its scope of use, validation and limitations. STUDY DESIGN: Scoping review. METHODS: In accordance with the framework outlined by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews, we conducted a literature search in MEDLINE, CINAHL, Cochrane Library, SCOPUS, Embase and PsycINFO databases from database inception up till 1 March 2023. RESULTS: A total of 31 studies were reviewed. The SVEST has been cross-culturally adapted from English into other languages. The SVEST has been successfully used in different contexts and with various healthcare professionals, including doctors, nurses, allied health professionals, midwives and pharmacists. The tool has been used to assess the impact of second victim experiences and the effectiveness of support interventions in addressing the phenomenon. Validity assessment of translated versions of SVEST in the reviewed studies revealed good content validity in most cases, although some studies did not report clear values for scale-level Content Validity Index. On the whole, SVEST is generally a reliable and valid tool, although further refinements and modifications may improve its validity and reliability. CONCLUSIONS: The review highlights the significance of SVEST as a crucial resource for healthcare providers and organisations that prioritise well-being and safety in health care. It also underscores the importance of recognising the needs of second victims and offering them appropriate interventions to manage the aftermath of adverse events.

Association between Sarcopenia and Cognitive Trajectories among Middle-Aged and Older Adults in China: A Nationally Representative Cohort Study.

OBJECTIVES: The relationship between sarcopenia and cognitive function has been extensively studied, but is usually explored at a single time point. We used repeatedly measured cognitive data to examine the relationship between sarcopenia and cognitive trajectories over time among middle-aged and older Chinese adults. DESIGN: A nationally representative cohort study. SETTING AND PARTICIPANTS: Data were from three waves (2011, 2013 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 8963 participants with complete baseline data (wave 1) and at least two cognitive function tests (waves 1-3) were enrolled in this study. MEASUREMENTS: Sarcopenia was diagnosed at baseline (wave 1). The wave 1-3 data were used to analyze cognitive trajectories over time by constructing a latent class trajectory model (LCTM). Logistic regression model was used to analyze the association between sarcopenia and cognitive trajectories. RESULTS: Among 8693 participants, we identified two trajectories of cognitive function development, including a persistent low trajectory (n= 4856, 55.86%) and a persistent high trajectory (n= 3837, 44.14%). Sarcopenia was associated with persistently low cognitive trajectory of global cognitive (OR: 1.248, 95%CI: 1.046-1.490) after adjustment for other covariates. This association was still observed when stratified by age, gender, educational level, marital status, social activity, smoking status and drinking status. Mediation analysis showed that body mass index (BMI) mediated efficacy accounting for 42.32% of the relationship. CONCLUSIONS: Our study showed two trajectory groups of global cognitive function. Sarcopenia was associated with a persistent low trajectory over time and BMI mediated the relationship between sarcopenia and cognitive trajectories among middle-aged and older Chinese adults.

Enhanced photocatalytic activity of Fe-, S- and N-codoped TiO2 for sulfadiazine degradation.

The composite material based on N-, S-, and Fe-doped TiO2 (NSFe-TiO2) synthesized by wet impregnation was used as a photocatalyst to rapidly degrade sulfadiazine. The photocatalytic degradation behavior and mechanism of sulfadiazine on NSFe-TiO2 were investigated for revealing the role of degradation under ultraviolet light. The results showed that compared with TiO2, NSFe-TiO2 markedly improved the efficiency in photocatalytic degradation of sulfadiazine: more than 90% of sulfadiazine could be removed within 120 min by NSFe-TiO2 dosage of 20 mg L-1. The process conformed to first-order reaction kinetics model. The parameters such as loaded amount of NSFe-TiO2, solution pH value, humic acid concentration and recycle numbers on removal efficiency were also studied. Compared to neutral and alkaline conditions, acidic condition was not conducive to the photocatalysis. HA, Ca2+, Cu2+ and Zn2+ in the actual water body had mild inhibition on sulfadiazine degradation in UV/NSFe-TiO2 system. Fragments screened by high-resolution mass spectrometry were conducted to explore the oxidation mechanism and pathways of sulfadiazine degradation. On the whole, UV/NSFe-TiO2 photocatalysis has a good effect on sulfadiazine removal. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-04771-6.

Virtual monitoring for stable chronic hepatitis B patients does not reduce adherence to medications: A randomised controlled study.

INTRODUCTION: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB. METHODS: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1-10. RESULTS: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients - 76 (80.9%) in VMC group and 74 (75.5%) in control group - had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group (p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively (p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm. DISCUSSION: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients.

Using Split Luminescent Biosensors for SARS-CoV-2 Antibody Detection in Serum, Plasma, and Blood Samples.

Antibody detection assays are essential for evaluating immunity of individuals against a given virus, and this has been particularly relevant during the COVID-19 pandemic. Current serology assays either require a laboratory setting and take >1 hr (i.e., enzyme-linked immunosorbent assay [ELISA]) or are rapid but only qualitative in nature and cannot accurately track antibody levels over time (i.e., lateral flow assay [LFA]). Therefore, there is a need for development of a rapid and simple but also quantitative assay that can evaluate antibody levels in patients accurately over time. We have developed an assay that uses a split nanoluciferase fused to the spike or nucleocapsid proteins of the SARS-CoV-2 virus to enable luminescent-based detection of spike- or nucleocapsid-binding antibodies in serum, plasma, and whole blood samples. The resulting approach is simple, rapid, and quantitative and is highly amenable to low-/medium-throughput scale using plate-based assays, high-throughput scale using robotics, and point-of-care applications. In this article, we describe how to perform the assay in a laboratory setting using a plate reader or liquid-handling robotics and in a point-of-care setting using a handheld, battery-powered luminometer. Together, these assays allow antibody detection to be easily performed in multiple settings by simplifying and reducing assay time in a laboratory or clinical environment and by allowing for antibody detection in point-of-care, nonlaboratory settings. © 2022 Wiley Periodicals LLC. Basic Protocol: SARS-CoV-2 antibody detection using the split-luciferase assay on a medium-throughput scale with a laboratory luminometer Alternate Protocol 1: High-throughput-based protocol for SARS-CoV-2 antibody detection using a robotic platform Alternate Protocol 2: Point-of-care-based protocol for SARS-CoV-2 antibody detection using a handheld luminometer Support Protocol: Determining positive/negative cutoffs for test samples and standardizing the assay between days.

Impact of COVID-19 on environmental services workers in healthcare settings: a scoping review.

BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, demand for deep cleaning and environmental services workers grew exponentially. Although there is extant literature examining the impact of the COVID-19 pandemic on healthcare workers, less emphasis has been placed on environmental services workers, who play an equally important front-line role. AIM: To examine the impact of the COVID-19 pandemic on environmental services workers employed in healthcare settings. METHODS: Scoping review methodology. A search strategy was developed, in consultation with a medical information specialist, employing various combinations of the keywords [(environmental services worker OR health attendant OR housekeeping) AND (COVID OR coronavirus OR pandemic OR epidemic)]. Four bibliographical databases were searched from inception to 5th July 2022: OVID Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Database. RESULTS: In total, 24 studies were included in this review. The studies were generally cross-sectional in design. Seroprevalence studies highlighted significantly higher rates of COVID-19 among environmental services workers (housekeeping, cleaning and janitorial staff) compared with other clinical and non-clinical staff in the same institutions. In addition, based on qualitative interviews, environmental services workers experienced greater psychological stress working during the pandemic. CONCLUSIONS: Environmental services workers were particularly vulnerable to increased work stress and COVID-19 during the pandemic. Health systems need to do more to support these workers. Further research could investigate specific policy and procedural changes to benefit this under-recognized group in the greater healthcare workforce.

Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions.

Protein-protein interactions (PPIs) form complex networks to drive cellular signaling and cellular functions. Precise modulation of a target PPI helps explain the role of the PPI in cellular events and possesses therapeutic potential. For example, valosin-containing protein (VCP/p97) is a hub protein that interacts with more than 30 adaptor proteins involved in various cellular functions. However, the role of each p97 PPI during the relevant cellular event is underexplored. The development of small-molecule PPI modulators remains challenging due to a lack of grooves and pockets in the relatively large PPI interface and the fact that a common binding groove in p97 binds to multiple adaptors. Here, we report an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C (p47). We engineered these antibody modulators by phage display against the p97-interacting domain of p47 and minimizing binding to other p97 adaptors. The selected antibody fragment modulators specifically disrupt the intracellular p97/p47 interaction. The potential of this antibody platform to develop PPI inhibitors in therapeutic applications was demonstrated through the inhibition of Golgi reassembly, which requires the p97/p47 interaction. This study presents a unique approach to modulate specific intracellular PPIs using engineered antibody fragments, demonstrating a method to dissect the function of a PPI within a convoluted PPI network.

Optical regulation of endogenous RhoA reveals selection of cellular responses by signal amplitude.

How protein signaling networks respond to different input strengths is an important but poorly understood problem in cell biology. For example, RhoA can promote focal adhesion (FA) growth or disassembly, but how RhoA activity mediates these opposite outcomes is not clear. Here, we develop a photoswitchable RhoA guanine nucleotide exchange factor (GEF), psRhoGEF, to precisely control endogenous RhoA activity. Using this optical tool, we discover that peak FA disassembly selectively occurs upon activation of RhoA to submaximal levels. We also find that Src activation at FAs selectively occurs upon submaximal RhoA activation, identifying Src as an amplitude-dependent RhoA effector. Finally, a pharmacological Src inhibitor reverses the direction of the FA response to RhoA activation from disassembly to growth, demonstrating that Src functions to suppress FA growth upon RhoA activation. Thus, rheostatic control of RhoA activation by psRhoGEF reveals that cells can use signal amplitude to produce multiple responses to a single biochemical signal.

[Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit].

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

[The application value of plasma heterogeneous nuclear ribonucleoprotein A2/B1, Aß42 and P-tau in the preoperative diagnosis of mild cognitive dysfunction].

Objective: To explore the application value of plasma heterogeneous nuclear ribonucleoprotein A2/B1(hnRNP A2B1), ß-amyloid 42(Aß42) and phosphorylated tau protein(P-tau) levels in elderly patients in the preoperative diagnosis of mild cognitive impairment(MCI). Methods: A total of 200 patients who underwent elective surgery at Tianjin Third Central Hospital from June 2020 to March 2021were Enrolled, regardless of gender, age 65-80 years old. According to the international MCI working group standards and the European Alzheimer's Disease Federation working group standards, patients were divided into MCI group and control group. There were 58 males and 42 females in each group. The patient's plasma hnRNP A2/B1, Aß42 and P-tau levels were detected before operation. The sensitivity, specificity and accuracy of the diagnosis of MCI were calculated. The receiver operating characteristic curve were drew to evaluate the diagnostic value of each index. Results: The plasma levels of hnRNP A2/B1, Aß42 and P-tau in the MCI group were 310.0 (275.1, 344.2), 34.5 (24.9, 42.5), 190.4 (150.4, 301.7) ng/L, respectively, which were significantly higher than those of the control group [272.7 (239.6, 291.5), 18.7 (14.7, 26.6), 140.0 (101.8, 217.5) ng/L]. The differences were statistically significant (all P<0.05). Taking the international MCI working group standard as the gold standard, the sensitivity, specificity and area under the ROC curve (AUC) of plasma hnRNP A2/B1 for predicting MCI were 80%, 61%, and 0.781, respectively. The sensitivity, specificity and AUC of plasma Aß42 for predicting MCI were 78%, 73%, and 0.744. The sensitivity, specificity, and AUC of P-tau for predicting MCI were 51%, 79%, and 0.675, respectively. The sensitivity, specificity and AUC of hnRNP A2/B1 and Aß42 in predicting MCI were not statistically significant (all P>0.05), but the sensitivity of both were higher than P-tau (all P<0.001). Compared with P-tau, the AUC of plasma hnRNP A2/B1 was higher when predicting MCI (P<0.05). When the three indicators were combined, the sensitivity was 82%, and the AUC was 0.842, both of which were the highest, but the specificity reduced (71%) (all P<0.05). Conclusions: Plasma hnRNP A2/B1 combined with Aß42 and P-tau levels can improve the sensitivity and accuracy of MCI diagnosis in elderly MCI patients before surgery, and have the greatest diagnostic efficiency. It has certain application value.

A musculoskeletal ultrasound program as an intervention to improve disease modifying anti-rheumatic drugs adherence in rheumatoid arthritis: a randomized controlled trial.

Objectives: To evaluate the effect of a musculoskeletal ultrasound programme (MUSP) applying real-time ultrasonography with reinforcement of findings by a rheumatologist on improving disease-modifying anti-rheumatic drugs (DMARDs) adherence in rheumatoid arthritis (RA).Method: Eligible RA patients with low adherence score (< 6) on the 8-item Morisky Medication Adherence Scale (MMAS-8) were randomized to either an intervention group (receiving MUSP at baseline) or a control group (no MUSP), and followed up for 6 months. Adherence measures (patient-reported and pharmacy dispensing records) and clinical efficacy data were collected. The MUSP's feasibility and acceptability were assessed.Results: Among 132 recruited RA patients, six without baseline visits were excluded; therefore, 126 patients were analysed (62 intervention and 64 control). The primary outcome (proportion of patients with 1 month MMAS-8 score < 6) was significantly smaller (p = 0.019) in the intervention (35.48%) than the control group (56.25%). However, 3 and 6 month adherence and clinical efficacy outcomes were not significantly different between the two groups (all p > 0.05). All 62 patients completed the MUSP (mean time taken, 9.2 min), with the majority reporting moderately/very much improved understanding of their joint condition (71%) and the importance of regularly taking their RA medication(s) (79%). Most patients (90.3%) would recommend the MUSP to another RA patient.Conclusions: The MUSP improved RA patients' DMARDs adherence in the short term and was feasible and well accepted by patients. Future studies could evaluate whether repeated feedback using MUSP could help to sustain the improvement in DMARD adherence in RA patients, and whether this may be clinically impactful and cost-effective.

[Application value of superb microvascular imaging for diagnosis of different size renal solid tumors].

Objective: To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes. Methods: A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow. Results: In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors (P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors (P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow (P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI (P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference (P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance (P=0.858). Conclusions: SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

[Application of superb microvascular imaging in focal liver lesions].

Objective: To investigate the ability of superb-microvascular imaging (SMI) to detect microvascular characteristics of focal liver lesions (FLLs) and analyze the relationship between vascular index (VI) and microvascular density (MVD) and Ki-67 levels. Methods: The imaging data of patients diagnosed as FLLs at Tianjin Medical University Cancer Hospital in 2018 were collected. A total of 166 FLLs patients were divided into non-hepatocellular liver cancer (non-HCC group, 96) and HCC group (70), respectively. The whole group of patients were subjected to color Doppler blood flow imaging (CDFI) and SMI examination. The patient's Adler's semi-quantitative grading (0 to 3 levels) and vascular morphological characteristics (a-f type) were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the detection ability of HCC with SMI and CDFI blood flow characteristics, The Pearson correlation analysis was used to evaluate the correlation between HCC patients VI and MVD and the Spearman correlation analysis was used to evaluate the correlation between VI and Ki-67. Results: In HCC group, SMI detected 50 cases of high-level blood flow (Adler's semi-quantitative grade 2 to 3) patients, higher than 22 cases of CDFI (P=0.033). In HCC group, SMI detected 52 cases of blood-rich mode (e, f type), higher than 18 cases of CDFI (P<0.001). In non-HCC group, the difference of blood flow characteristics detection between CDFI and SMI was not statistically significant. In HCC group, SMI detected 52 cases of rich blood supply patterns, which was higher than 14 cases of non-HCC group (P<0.001). The area under the ROC curve of SMI was 0.760 (sensitivity was 74.3%, specificity was 85.4%), and the SMI rich blood supply mode had the best diagnostic effect on HCC based on the blood-rich mode as the HCC diagnostic standard. In HCC group, VI was positively correlated with MVD and Ki-67 (r=0.698 and r=0.669, respectively, P<0.05). Conclusions: SMI has better detection ability than CDFI for HCC microvascular characteristics, HCC has more blood-rich mode than non-HCC. In HCC, VI is positively correlated with MVD and Ki-67 expression levels.

SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay.

Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection.

Current serology tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies mainly take the form of enzyme-linked immunosorbent assays, chemiluminescent microparticle immunoassays or lateral flow assays, which are either laborious, expensive or lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost, solution-based assay to detect antibodies in serum, plasma, whole blood and to a lesser extent saliva, using rationally designed split luciferase antibody biosensors. This new assay, which generates quantitative results in 30 min, substantially reduces the complexity and improves the scalability of coronavirus disease 2019 (COVID-19) antibody tests. This assay is well-suited for point-of-care, broad population testing, and applications in low-resource settings, for monitoring host humoral responses to vaccination or viral infection.

Bispecific VH/Fab antibodies targeting neutralizing and non-neutralizing Spike epitopes demonstrate enhanced potency against SARS-CoV-2.

Numerous neutralizing antibodies that target SARS-CoV-2 have been reported, and most directly block binding of the viral Spike receptor-binding domain (RBD) to angiotensin-converting enzyme II (ACE2). Here, we deliberately exploit non-neutralizing RBD antibodies, showing they can dramatically assist in neutralization when linked to neutralizing binders. We identified antigen-binding fragments (Fabs) by phage display that bind RBD, but do not block ACE2 or neutralize virus as IgGs. When these non-neutralizing Fabs were assembled into bispecific VH/Fab IgGs with a neutralizing VH domain, we observed a ~ 25-fold potency improvement in neutralizing SARS-CoV-2 compared to the mono-specific bi-valent VH-Fc alone or the cocktail of the VH-Fc and IgG. This effect was epitope-dependent, reflecting the unique geometry of the bispecific antibody toward Spike. Our results show that a bispecific antibody that combines both neutralizing and non-neutralizing epitopes on Spike-RBD is a promising and rapid engineering strategy to improve the potency of SARS-CoV-2 antibodies.