Publications by authors named "Wen Ye"

217 Publications

Probable fondaparinux-associated bullous hemorrhagic dermatosis.

CMAJ 2021 May;193(22):E801-E804

Department of Medicine (Lovatt, Ye, Yousuf), Faculty of Health Sciences, McMaster University; Hamilton Health Sciences (Yousuf), Hamilton, Ont.

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http://dx.doi.org/10.1503/cmaj.202747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177931PMC
May 2021

Orexin-A Attenuates Inflammatory Responses in Lipopolysaccharide-Induced Neural Stem Cells by Regulating NF-KB and Phosphorylation of MAPK/P38/Erk Pathways.

J Inflamm Res 2021 18;14:2007-2017. Epub 2021 May 18.

Department of Rehabilitation, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People's Republic of China.

Background: Neuronal damage is the main cause of neurological diseases. Neural stem cells (NSCs) have the functions of cell repair and replacement of neurons, secretion of neurotrophic factors, and immune regulation of the neural microenvironment.

Objective: Previous study found that Orexin-A had a protective effect on neurons in the central nervous system, but it is lacking in making great efforts on the function of Orexin-A on NSCs. This study aimed to investigate the anti-inflammatory responses and signaling mechanisms of Orexin-A on lipopolysaccharide (LPS)-induced NSCs.

Methods: Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Signaling pathway-related protein expression was detected by Western blot. The proliferation and migration of NSCs were investigated by Cell Counting Kit-8 (CCK-8) detection kit and transwell assay. Besides, the staining of hematoxylin and eosin (HE) was performed to study the morphology of cell.

Results: Orexin-A decreased the pro-inflammatory cytokines of IL-1β, TNF-α, and IL-6 induced by LPS by regulating nuclear factor-k-gene binding (NF-kB) and phosphorylation of P38/Erk-mitogen-activated protein kinases (MAPKs) pathways, but not p-JNK signaling.

Conclusion: Our findings indicate that Orexin-A can alleviate the inflammatory response of NSC. It can provide beneficial help in neural stem cell therapy applications.
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http://dx.doi.org/10.2147/JIR.S308078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140926PMC
May 2021

Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children with Monogenic Cholestasis.

J Pediatr Gastroenterol Nutr 2021 Jun 3. Epub 2021 Jun 3.

Texas Children's Hospital, Baylor College of Medicine, Houston TX University of California, San Francisco, San Francisco CA King's College London, London UK Arbor Research Collaborative for Health, Ann Arbor MI University of Michigan Hospitals and Health Centers, Ann Arbor MI UPMC Children's Hospital of Pittsburgh, Pittsburgh PA Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago IL Cincinnati Children's Hospital Medical Center, Cincinnati OH Johns Hopkins Medicine, Baltimore MD Indiana University-Riley Hospital for Children, Indianapolis IN Seattle Children's Hospital, Seattle WA Emory University School of Medicine, Atlanta GA Washington University, St. Louis Children's Hospital, St. Louis MO University of Colorado School of Medicine, Children's Hospital Colorado, Aurora CO Children's Hospital Los Angeles, University of Southern California, Los Angeles CA The Children's Hospital of Philadelphia, Philadelphia PA Hospital for Sick Children, University of Toronto, Toronto ON.

Objectives: To advance our understanding of monogenic forms of intrahepatic cholestasis.

Methods: Analyses included participants with pathogenic biallelic mutations in ABCB11 (bile salt export pump; BSEP) or ATP8B1 (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in ABCB4 (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between 11/2007-12/2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data.

Results: Ninety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including 4 monoallelic) deficiency were analyzed. Thirty-five had surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported.

Conclusions: In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require study of larger cohorts.

An infographic is available for this article at: http://links.lww.com/MPG/C343.
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http://dx.doi.org/10.1097/MPG.0000000000003153DOI Listing
June 2021

Live poultry feeding and trading network and the transmission of avian influenza A(H5N6) virus in a large city in China, 2014-2015.

Int J Infect Dis 2021 May 14;108:72-80. Epub 2021 May 14.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian Province, People's Republic of China. Electronic address:

Objectives: To understand the transmission mechanisms of the avian influenza A(H5N6) virus.

Methods: This study explored the live poultry feeding and trading network (LPFTN) around Changsha city, China. Field epidemiological investigations were performed in Changsha to investigate the LPFTN with the environmental samples systematically collected during 2014-2015 to monitor and analyze the spread of the A(H5N6) virus. Two surveillance systems were also applied to find possible human cases of A(H5N6) infection.

Result: The information of all the 665 live poultry farming sites, five wholesale markets, and 223 retail markets in Changsha was collected to investigate the LPFTN. Moreover, about 840 environmental samples were systematically collected from the LPFTN during 2014-2015 to monitor the spread of the A(H5N6) virus, with 8.45% (71/840) positive for the N6 subtype. Furthermore, the full genome sequences of 10 A(H5N6) viruses detected from the environmental samples were obtained, which were then characterized and phylogenetically analyzed with the corresponding gene segments of the A(H5N6) virus obtained from GenBank, to determine the source of human infection.

Conclusion: It was demonstrated that the LPFTN provided a platform for the H5N6 transmission, and formed an infectious pool for the spread of the virus to humans.
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http://dx.doi.org/10.1016/j.ijid.2021.05.022DOI Listing
May 2021

[Carrier screening model for Duchenne muscular dystrophy for women of reproductive age based on a pre-pregnancy birth defect control platform].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 May;38(5):485-487

Hangzhou Health Service Center for Children and Women, Hangzhou, Zhejiang 310006, China.

Objective: To establish a screening model for females of reproductive age carrying Duchenne muscular dystrophy (DMD) variants based on a current community health examination platform.

Methods: A total of 61 870 participants were recruited between October 2017 and October 2019. Serum creatine kinase (CK) was measured with a Roche Cobasc 701/702 using an enzymatic rate method. Genetic testing was offered to those with a CK level of ≥ 200 U/L. For carriers of DMD variants, genetic counseling and follow up were provided.

Results: For the 61 870 females participating in the program, 1078 were found with raised serum CK (≥ 200 U/L), of which 618 (57.33%) accepted CK re-measurement after at least a two-week interval. One hundred and twenty cases were found with sustained serum CK elevation, of which 6 were confirmed to be definite DMD carriers regardless of family history. Genetic testing was provided to 33 females with a family history for DMD, and 13 were determined as definite carriers. An affected fetus was detected by prenatal diagnosis. After genetic counseling, the parents had opted induced abortion.

Conclusion: Large-scale DMD carrier screening through a three-step approach based on the current community health examination platform is both feasible and cost effective.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200331-00223DOI Listing
May 2021

Surfactant-Free, One-Step Synthesis of Lead-Free Perovskite Hollow Nanospheres for Trace CO Detection.

Adv Mater 2021 May 7:e2100674. Epub 2021 May 7.

College of Chemistry Chemical Engineering and Materials Science, Collaborative Innovation Center of Suzhou Nano Science and Technology, National United Engineering Laboratory of Functionalized Environmental Adsorption Materials, Soochow University, Suzhou, 215123, P. R. China.

Owing to their special photoelectric properties, halide perovskites have always attracted research attention. Hollow-structured halide perovskites have many practical applications but are challenging to prepare as most template methods violate their poor chemical and thermal stability. In this study, novel halide perovskite Cs PdBr hollow nanospheres are prepared using a template-free method; specifically, large quantities of highly pure lead-free halide perovskite Cs PdBr hollow nanospheres are produced at 30 °C without a surfactant. These ultrapure nanospheres exhibit superiority in chemresistive detection of CO with a detection limit of 50 ppb, which is the lowest among all the reported CO sensing materials. Moreover, in situ sum-frequency-generation spectra and density functional theory calculations reveal that the high sensitivity is attributable to the large specific surface area and surfactant-free surface of rich Br vacancies that favor CO binding. Overall, this work provides insight on regulation of the halide perovskite structure and the use of hollow spheres in gas-sensing applications.
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http://dx.doi.org/10.1002/adma.202100674DOI Listing
May 2021

Cost-Effectiveness of a Diabetes Self-Management Education and Support Intervention Led by Community Health Workers and Peer Leaders: Projections From the Racial and Ethnic Approaches to Community Health Detroit Trial.

Diabetes Care 2021 May 6;44(5):1108-1115. Epub 2021 May 6.

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI.

Objective: To simulate the long-term cost-effectiveness of a peer leader (PL)-led diabetes self-management support (DSMS) program following a structured community health worker (CHW)-led diabetes self-management education (DSME) program in reducing risks of complications in people with type 2 diabetes (T2D).

Research Design And Methods: The trial randomized 222 Latino adults with T2D to ) enhanced usual care (EUC); ) a CHW-led, 6-month DSME program and 6 months of CHW-delivered monthly telephone outreach (CHW only); or ) a CHW-led, 6-month DSME program and 12 months of PL-delivered weekly group sessions with telephone outreach to those unable to attend (CHW PL). Empirical data from the trial and the validated Michigan Model for Diabetes were used to estimate cost and health outcomes over a 20-year time horizon from a health care sector perspective, discounting both costs and benefits at 3% annually. The primary outcome measure was the incremental cost-effectiveness ratio (ICER).

Results: Over 20 years, the CHW + PL intervention had an ICER of $28,800 and $5,900 per quality-adjusted life-year (QALY) gained compared with the EUC and CHW-only interventions, respectively. The CHW-only intervention had an ICER of $430,600 per QALY gained compared with the EUC intervention. In sensitivity analyses, the results comparing the CHW + PL with EUC and CHW-only interventions were robust to changes in intervention effects and costs.

Conclusions: The CHW + PL-led DSME/DSMS intervention improved health and provided good value compared with the EUC intervention. The 6-month CHW-led DSME intervention without further postintervention CHW support was not cost effective in Latino adults with T2D.
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http://dx.doi.org/10.2337/dc20-0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132331PMC
May 2021

Prediction of transient ischemic attack and minor stroke in people with type 2 diabetes mellitus.

J Diabetes Complications 2021 Jul 17;35(7):107911. Epub 2021 Mar 17.

School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.

Aims: People with type 2 diabetes (T2DM) have an increased risk of transient ischemic attack and minor stroke (TIA) which are frequently followed by an ischemic stroke. We aimed to develop a predictive model for incident TIA in people with T2DM.

Methods: We pooled data from two longitudinal cohort studies, Atherosclerosis Risk in Communities (ARIC) and the Cardiovascular Health Study (CHS), using a two-stage approach. First, we used a random effects model to interpolate risk factors of individuals between follow-up exams. Second, we used forward selection to develop a proportional hazards model for time to incident TIA. We internally validated our model using 10-fold cross-validation.

Results: Among 3575 participants with T2DM, mean (SD) age was 60 (10) years and body mass index was 30 (6) kg/m2. Sixty-nine incident TIAs occurred during 38,364 person-years of follow-up. The multivariable model included age at diagnosis of diabetes (hazard ratio 1.13 (95% confidence interval: 1.05,1.21) per year), systolic blood pressure (1.25 (1.04,1.49) per 10 mmHg), a quadratic function of diastolic blood pressure, and history of congestive heart failure (2.08 (1.26, 3.42)). The median cross-validated Harrell's C-index was 0.80.

Conclusion: Blood pressure and heart failure are risk factors for the earliest stages of cerebrovascular disease.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169622PMC
July 2021

Pazopanib in patients with metastatic renal cell carcinoma: a single-center, real-world, retrospective Chinese study.

Transl Androl Urol 2021 Mar;10(3):1321-1331

Department of Urology, Fujian Medical University Union Hospital, Fuzhou, China.

Background: The efficacy and safety of pazopanib in patients diagnosed with metastatic renal cell carcinoma (mRCC) have been demonstrated by a Chinese subgroup analysis of the COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial. However, the real-world data are still unknown. This single-center, retrospective study was designed to verify the real-world effects of pazopanib in Chinese patients with mRCC.

Methods: Patients with mRCC and a clinical decision to initiate pazopanib as first-line therapy were eligible. The primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and safety being evaluated as secondary endpoints. The effectiveness according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model, number of risk factors in the intermediate risk group, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and the number and site of organ metastasis were also assessed.

Results: A total of 32 patients were enrolled, including 23 (71.9%) males and 9 (28.1%) females. The median age was 57 years (range 29-75 years). With a median follow-up time of 23.8 months, a median PFS of 18.3 months, and an ORR of 37.5%. Median OS was not reached, and the 1-, 2-, and 3-year overall survival rates were 90.6%, 78.1, and 65.6%, respectively. According to IMDC risk model, 37.5% were placed in the favorable risk (FR) subgroup, 56.2% (the majority) were placed in the intermediate risk (IR) subgroup, and 6.3% were placed in the poor risk (PR) subgroup. Compared with the IR and PR groups, the FR group achieved the best ORR (58.3%) and median PFS (22.1 months). Having 1 risk factor, ECOG PS <2, 1 organ metastasis site, and only lung metastasis associated with a higher ORR and better median PFS. The IMDC risk model and number of metastases were associated with PFS. The most common adverse events were change in hair color (69.0%), diarrhea (63%), and hypertension (50%).

Conclusions: Pazopanib showed efficacy and safety in real-world Chinese mRCC patients.
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http://dx.doi.org/10.21037/tau-21-111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039632PMC
March 2021

The efficacy and safety of interscalene blockade versus local infiltration analgesia in primary total shoulder arthroplasty?: A protocol for systematic review and meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Mar;100(12):e25201

Department of Anesthesiology.

Background: None of review has been conducted to compare the efficacy of interscalene blockade (ISB) with that of local infiltration analgesia (LIA) in patients undergoing total shoulder arthroplasty (TSA). We thus conduct a high-quality meta-analysis of randomized controlled trials (RCTs) to investigate which analgesic provides better pain relief.

Methods: A comprehensive search of the published literature in PUBMED, Scopus, EMBASE, and Cochrane Library databases will be performed. Only RCTs evaluating LIA versus ISB in TSA are included in this study. The primary outcome was pain score. Secondary outcome measures included opioid consumption, postoperative adverse event, and length of stay. The Cochrane risk of bias tool is used to evaluate the risk of bias of included RCTs by 2 independent reviewers.

Results: The results of this research will be delivered in a peer-reviewed journal.

Conclusions: This study expects to provide credible and scientific evidence for the efficacy and safety of ISB and LIA for early postoperative pain control after TSA.

Systematic Review Registration Number: 10.17605/OSF.IO/S3MBP.

Ethical Approval: Since this study is on the basis of published or registered RCTs, ethical approval and informed consent of patients are not required.
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http://dx.doi.org/10.1097/MD.0000000000025201DOI Listing
March 2021

Cost-effectiveness of Community-Based Depression Interventions for Rural and Urban Adults With Type 2 Diabetes: Projections From Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II.

Diabetes Care 2021 Apr 19;44(4):874-882. Epub 2021 Feb 19.

University of Michigan, Ann Arbor, MI.

Objective: We estimated the cost-effectiveness of the Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II community-based exercise (EXER), cognitive behavioral therapy (CBT), and EXER+CBT interventions in adults with type 2 diabetes and depression relative to usual care (UC) and each other.

Research Design And Methods: Data were integrated into the Michigan Model for Diabetes to estimate cost and health outcomes over a 10-year simulation time horizon from the health care sector and societal perspectives, discounting costs and benefits at 3% annually. Primary outcome was cost per quality-adjusted life-year (QALY) gained.

Results: From the health care sector perspective, the EXER intervention strategy saved $313 (USD) per patient and produced 0.38 more QALY (cost saving), the CBT intervention strategy cost $596 more and gained 0.29 more QALY ($2,058/QALY), and the EXER+CBT intervention strategy cost $403 more and gained 0.69 more QALY ($585/QALY) compared with UC. Both EXER and EXER+CBT interventions dominated the CBT intervention. Compared with EXER, the EXER+CBT intervention strategy cost $716 more and gained 0.31 more QALY ($2,323/QALY). From the societal perspective, compared with UC, the EXER intervention strategy saved $126 (cost saving), the CBT intervention strategy cost $2,838/QALY, and the EXER+CBT intervention strategy cost $1,167/QALY. Both EXER and EXER+CBT interventions still dominated the CBT intervention. In comparison with EXER, the EXER+CBT intervention strategy cost $3,021/QALY. Results were robust in sensitivity analyses.

Conclusions: All three Program ACTIVE II interventions represented a good value for money compared with UC. The EXER+CBT intervention was highly cost-effective or cost saving compared with the CBT or EXER interventions.
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http://dx.doi.org/10.2337/dc20-1639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985429PMC
April 2021

A simple-to-use web-based calculator for survival prediction in Parkinson's disease.

Aging (Albany NY) 2021 02 1;13(4):5238-5249. Epub 2021 Feb 1.

Department of Rehabilitation Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

Background: To establish and validate a nomogram and corresponding web-based calculator to predict the survival of patients with Parkinson's disease (PD).

Methods: In this cohort study, we retrospectively evaluated patients (n=497) with PD using a two-stage design, from March 2004 to November 2007 and from July 2005 to July 2015. Predictive variables included in the model were identified by univariate and multiple Cox proportional hazard analyses in the training set.

Results: Independent prognostic factors including age, PD duration, and Hoehn and Yahr stage were determined and included in the model. The model showed good discrimination power with the area under the curve (AUC) values generated to predict 4-, 6-, and 8-year survival in the training set being 0.716, 0.783, and 0.814, respectively. In the validation set, the AUCs of 4- and 6-year survival predictions were 0.85 and 0.924, respectively. Calibration plots and decision curve analysis showed good model performance both in the training and validation sets. For convenient application, we established a web-based calculator (https://tangyl.shinyapps.io/PDprognosis/).

Conclusions: We developed a satisfactory, simple-to-use nomogram and corresponding web-based calculator based on three relevant factors to predict prognosis and survival of patients with PD. This model can aid personalized treatment and clinical decision-making.
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http://dx.doi.org/10.18632/aging.202443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950310PMC
February 2021

Pulmonary involvement in acquired immunodeficiency syndrome-associated Kaposi's sarcoma: a descriptive analysis of thin-section manifestations in 29 patients.

Quant Imaging Med Surg 2021 Feb;11(2):714-724

Department of Radiology, Shenzhen Center for Chronic Disease Control, Shenzhen, China.

Background: Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS) was the first malignant neoplasm to be described as being related to AIDS. The lungs are the most common visceral site of AIDS-KS. This study aimed to analyze the computed tomography (CT) manifestations of pulmonary involvement in AIDS-KS.

Methods: Twenty-nine male patients were enrolled in this retrospective study. Imaging evaluation parameters included lesion distribution, the flame sign, interlobular septal thickening, peribronchovascular interstitium thickening, ground-glass opacity (GGO), dilated blood vessels in lesions, and pleural effusion.

Results: A peribronchovascular distribution was observed in all patients, predominantly in the lower lobes. Of the patients, 58.62% (17/29) exhibited the flame sign, 75.86% (22/29) had interlobular septal thickening, 72.41% (21/29) had peribronchovascular interstitium thickening, 82.76% (24/29) had GGO, and 34.48% (10/29) had pleural effusion. Enlarged lymph nodes with a short-axis diameter >1.0 cm were found in 41.38% (12/29) of the patients. Of the 12 patients who underwent contrast-enhanced CT (CECT), 90.91% (11/12) had dilated blood vessels, and nodules, consolidations, and lymph nodes were observed to be strongly enhanced. Intrapulmonary lesions decreased in size or number after appropriate treatment during follow-up.

Conclusions: Common CT manifestations of pulmonary AIDS-KS include the flame sign, peribronchovascular distribution, peribronchovascular interstitium thickening, interlobular septa thickening, GGO, dilated blood vessel, and strong enhancement of nodules, consolidations, and lymph nodes. It is helpful to follow up the therapeutic effect of pulmonary AIDS-KS by chest CT.
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http://dx.doi.org/10.21037/qims-20-284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779939PMC
February 2021

Costs implications of pneumococcal vaccination of adults aged 30-60 with a recent diagnosis of diabetes.

Vaccine 2021 02 23;39(8):1333-1338. Epub 2021 Jan 23.

Centers for Disease Control and Prevention, United States.

Objective: The 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease.

Research Design And Methods: We used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005 to 2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes.

Results: Overall rates of pneumococcal polysaccharide vaccination among adults 30-60 years old were <1%/year. Rates of pneumococcal polysaccharide vaccination were higher for adults with diabetes. Pneumococcal polysaccharide vaccination rates more than doubled from 2.9% per year in 2005 to 6.0% per year in 2014 for adults vaccinated during the same year as their diabetes diagnosis. Using a two-part differences-in-differences model on a propensity-score matched dataset, pneumococcal polysaccharide vaccination may reduce average annual per-person pneumococcal disease costs by $90.54 [95% CI: $183.59, -$2.49, (p = 0.056)] in persons with diabetes from two years before to two years after vaccination.

Conclusions: Non-elderly adults with diabetes have low but rising rates of pneumococcal polysaccharide vaccination. Pneumococcal polysaccharide vaccination has a modest impact reducing overall costs of pneumococcal disease in this population.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.060DOI Listing
February 2021

The LipoxinA4 receptor agonist BML-111 ameliorates intestinal disruption following acute pancreatitis through the Nrf2-regulated antioxidant pathway.

Free Radic Biol Med 2021 Feb 28;163:379-391. Epub 2020 Dec 28.

Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China. Electronic address:

Acute pancreatitis (AP) is characterized by excessive release of pro-inflammatory cytokines and provokes multiorgan dysfunction. Disruption of the intestinal epithelium often occurs during and following acute pancreatitis and may aggravate systemic organ injuries. Although it has been widely investigated, to date, there is no satisfactory clinical therapy to restore the inflammatory damage. BML-111 is an endogenous lipid mediator that is analogous to LipoxinA4. It has been shown that BML-111 has a stable and potent anti-inflammatory ability. However, it is unclear whether BML-111 is involved in the process of relieving acute pancreatitis and its induced intestinal barrier damage, and the underlying mechanism of this effect. Here, we demonstrated that BML-111 could enhance the expression of E-cadherin, alleviate apoptosis, and mitigate the accumulation of reactive oxygen species in intestinal epithelial cells, thereby contributing to the anti-inflammatory efficacy in vitro and in vivo. Mechanistically, BML-111 upregulates the expression of Nrf2, which is a key regulator of the antioxidant response, and activates its downstream HO-1/NQO-1 pathway to protect against oxidative stress-induced cell death and tissue injury, consequently ameliorating pancreatitis and intestinal epithelium injury. In Nrf2-deficient cell and Nrf2-knockout mouse models, the depletion of Nrf2 blocked BML-111-induced antioxidant effects and thus was unable to exert protective effects in tissue. Taken together, BML-111 attenuated AP-related intestinal injury via an Nrf2-dependent antioxidant mechanism. Targeting this pathway is a potential therapeutic approach for AP-related intestinal injury.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.232DOI Listing
February 2021

Outcomes of Childhood Cholestasis in Alagille Syndrome: Results of a Multicenter Observational Study.

Hepatol Commun 2020 Mar 22;4(3):387-398. Epub 2020 Jan 22.

University of Colorado School of Medicine Children's Hospital Colorado Aurora CO.

Alagille syndrome (ALGS) is an autosomal dominant multisystem disorder with cholestasis as a defining clinical feature. We sought to characterize hepatic outcomes in a molecularly defined cohort of children with ALGS-related cholestasis. Two hundred and ninety-three participants with ALGS with native liver were enrolled. Participants entered the study at different ages and data were collected retrospectively prior to enrollment, and prospectively during the study course. Genetic analysis in 206 revealed mutations in 91% and mutations in 4%. Growth was impaired with mean height and weight -scores of <-1.0 at all ages. Regression analysis revealed that every 10 mg/dL increase in total bilirubin was associated with a decrease in height -score by 0.10 ( = 0.03) and weight -score by 0.15 ( = 0.007). Total bilirubin was higher for younger participants ( = 0.03) with a median of 6.9 mg/dL for those less than 1 year old compared with a median of 1.3 mg/dL for participants 13 years or older. The median gamma glutamyl transferase also dropped from 612 to 268 in the same age groups. After adjusting for age, there was substantial within-individual variation of alanine aminotransferase. By 20 years of age, 40% of participants had developed definite portal hypertension. Estimated liver transplant-free survival at the age of 18.5 years was 24%. : This is the largest multicenter natural history study of cholestasis in ALGS, demonstrating a previously underappreciated burden of liver disease with early profound cholestasis, a second wave of portal hypertension later in childhood, and less than 25% of patients reaching young adulthood with their native liver. These findings will promote optimization of ALGS management and development of clinically relevant endpoints for future therapeutic trials.
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http://dx.doi.org/10.1002/hep4.1468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049675PMC
March 2020

Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age.

Hepatol Commun 2020 Dec 3;4(12):1824-1834. Epub 2020 Oct 3.

Emory University School of Medicine Atlanta GA.

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%-30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health-supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0-13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%-32.0%). Twenty-seven experienced either new-onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%-29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C-index of 0.88 (range, 0.86-0.89). A cause-specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C-index of 0.81 (range, 0.80-0.84). Internal model validity was assessed using Harrell's C-index with cross-validation. Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.
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http://dx.doi.org/10.1002/hep4.1602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706301PMC
December 2020

Do Parental Feeding Rate and Feeding Synchrony Affect Nest Survival in a Songbird?

Zoolog Sci 2020 Dec;37(6):580-585

School of Ecology and Nature Conservation, Beijing Forestry University, Beijing 100083, China,

Nest predation risk is an important factor that may promote the evolution of adaptive parental reproductive strategies in animals. In altricial birds, where parents feed their offspring at the nest for a period of time, parent birds must balance the benefit from increased nest visits and the cost from increased nest predation resulting from their nest visits being detected by predators. Empirical evidence has shown a relationship between parental nest visits and nest predation risks, and parents have been found to be able to reduce the chance of being detected by predators by synchronizing their feeding visits while maintaining feeding rate unchanged. However, it remains poorly understood whether the relationships are universal to all species. We investigated whether nest survival is correlated with parental feeding rate and feeding synchrony in the silver-throated tit (), a songbird endemic to China. We found that parental feeding rate varied by brood size, nestling age and the time during the day, but feeding synchrony was unrelated to the above factors. Moreover, we showed no effect of parental feeding rate or synchrony on nest survival. The failure to find a relationship between parental feeding synchrony and nest survival seems exceptional because it is contrary to findings of previous studies. While there was likely a publication bias regarding previous studies, it is also possible that the evolution of feeding synchrony in different species has different explanations, or the complexity of the predator community and other factors affecting nest survival need to be considered in the analyses.
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http://dx.doi.org/10.2108/zs200039DOI Listing
December 2020

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk, severity, and mortality risk.

Braz J Med Biol Res 2020 27;54(2):e10271. Epub 2020 Nov 27.

Hand and Foot Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.
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http://dx.doi.org/10.1590/1414-431X202010271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695447PMC
January 2021

A high-precision and high-order error model for airborne distributed POS transfer alignment.

Sci Rep 2020 Nov 24;10(1):20489. Epub 2020 Nov 24.

Harbin Institute of Technology, Harbin, 150001, China.

Distributed position and orientation systems (DPOSs) can provide abundant time-spatial information for interferometric synthetic aperture radar (InSAR) in airborne earth observation systems. However, some key error terms have not been taken into consideration in the traditional low-order error model, which suppresses the performance of the slave POS and further cannot meet the compensation precision of InSAR. To improve the compensation precision, a precise high-order error model with 45 dimensions was derived. Not only does it take into account the influence of scale factor errors and installation errors of the gyro and accelerometer, but it also makes use of random constants and a first-order Markov process model to describe the gyro drift and accelerometer bias. In addition, the flexure angle and its angular rate were added to the state variables of the transfer alignment model. Based on the model, a measurement equation for attitude errors that considers flexure was deduced. Then, a transfer alignment model based on the matching algorithm including position-velocity-attitude was designed. Finally, the proposed model was validated by simulated and real tests, and the experimental results show that its performance is obviously better than that of the traditional model.
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http://dx.doi.org/10.1038/s41598-020-77595-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686323PMC
November 2020

Nonfasted Liver Stiffness Correlates with Liver Disease Parameters and Portal Hypertension in Pediatric Cholestatic Liver Disease.

Hepatol Commun 2020 Nov 5;4(11):1694-1707. Epub 2020 Aug 5.

University of Michigan Ann Arbor MI USA.

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well-characterized multi-institutional cohort. Children with biliary atresia (BA), alpha-1 antitrypsin deficiency (A1ATD), or Alagille syndrome (ALGS) followed in a prospective longitudinal network study were eligible for enrollment in a prospective investigation of transient elastography (FibroScan). Studies were performed in participants who were nonfasted and nonsedated. Liver stiffness measurements (LSMs) were correlated with standard clinical and biochemical parameters of liver disease along with a research definition of clinically evident portal hypertension (CEPH) graded as absent, possible, or definite. Between November 2016 and August 2019, 550 participants with a mean age of 8.8 years were enrolled, 458 of whom had valid LSMs (BA, n = 254; A1ATD, n = 104; ALGS, n = 100). Invalid scans were more common in participants <2 years old. There was a positive correlation between LSM and total bilirubin, international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), GGT to platelet ratio (GPR), pediatric end-stage liver disease score, AST to platelet ratio index, and spleen size, and a negative correlation with albumin and platelet count in BA, with similar correlations for A1ATD (except AST, ALT, and albumin) and ALGS (except for INR, GGT, GPR, and ALT). Possible or definite CEPH was more common in BA compared to ALGS and A1ATD. LSM was greater in definite versus absent CEPH in all three diseases. Disease-specific clinical and biochemical characteristics of the different CEPH grades were observed. : It is feasible to obtain LSMs in children, especially over the age of 2 years. LSM correlates with liver parameters and portal hypertension, although disease-specific patterns exist.
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http://dx.doi.org/10.1002/hep4.1574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603532PMC
November 2020

Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis.

Eur Neurol 2020 30;83(6):555-565. Epub 2020 Oct 30.

Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang City, China,

Objective: Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis.

Methods: A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review.

Results: The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63-1.12, p < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39-0.61) and 0.86 (95% CI: 0.71-0.94).

Conclusions: The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.
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http://dx.doi.org/10.1159/000509801DOI Listing
May 2021

Population-Wide Duchenne Muscular Dystrophy Carrier Detection by CK and Molecular Testing.

Biomed Res Int 2020 27;2020:8396429. Epub 2020 Sep 27.

Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum genetic testing in subjects with hyperCKemia, defined as CK > 200 U/L. The calculated upper reference limit (97.5 percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. genetic testing was conducted on 62 subjects with sustained serum CK > 200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.
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http://dx.doi.org/10.1155/2020/8396429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537677PMC
April 2021

Design of the Redefining Therapy in Early COPD Study.

Chronic Obstr Pulm Dis 2020 Oct;7(4):382-389

Division of Pulmonary and Critical Care, University of California, San Francisco.

Redefining Therapy in Early COPD (RETHINC) is a 12-week multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily in symptomatic current and former smokers with respiratory symptoms as defined by COPD Assessment Test (CAT) score ≥ 10 despite preserved spirometry defined by post-bronchodilator forced expiratory volume in 1 second (FEV) to forced vital capacity (FVC) ratio ≥ 0.70. Recruitment began in July 2017 with the goal of enrolling 580 participants. The baseline examination includes spirometry (with slow and forced maneuvers) and symptom questionnaires. A follow-up phone call at 4 weeks assesses symptoms and safety. The second and final visit at week 12 includes spirometry before and after study drug (hourly over 3 hours) and follow-up symptom questionnaires. The primary endpoint is the proportion of individuals who experience a 4-unit improvement in St George's Respiratory Questionnaire (SGRQ) score at 12 weeks without treatment failure, defined as an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilators, corticosteroids or antibiotics. Key secondary endpoints include the proportion of individuals with a 2-unit improvement in the CAT score; 1-unit improvement in the Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI), both a 4-unit improvement in SGRQ and a 1-unit improvement in BDI/TDI; and mean change in SGRQ, CAT and BDI/TDI. Other secondary endpoints include area under the curve 0-3 hours for FEV after study drug, change from baseline in trough inspiratory capacity, forced expiratory flow 25%-75% of FVC (FEF) iso-volume FEF and mean change in symptoms and rescue medication use based on daily diary. We anticipate results to be available in 2021. This paper describes the RETHINC study and explains the rationale behind it.
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http://dx.doi.org/10.15326/jcopdf.7.4.2020.0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883914PMC
October 2020

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value Health 2020 09 6;23(9):1163-1170. Epub 2020 Aug 6.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Centre for Health Policy, School of Population and Global Health, The University of Melbourne, Victoria, Australia. Electronic address:

Objectives: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication.

Methods: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class.

Results: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME-calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit.

Conclusions: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed.
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http://dx.doi.org/10.1016/j.jval.2020.04.1832DOI Listing
September 2020

Factors associated with unfavorable treatment outcomes among pediatric tuberculosis cases in Harare, Zimbabwe during 2013-2017.

Int J Infect Dis 2020 Dec 2;101:403-408. Epub 2020 Sep 2.

University of Michigan, School of Public Health, Epidemiology Department, USA. Electronic address:

Background: Historical neglect of pediatric tuberculosis (TB), compounding the absence of a universally effective vaccine, highlights the importance of successful treatment in combating the global epidemic. Furthermore, compliance with international standards of pediatric TB treatment remains unknown in many high-burden, resource-limited settings.

Methods: In this cross-sectional study, using TB surveillance data, we assessed the treatment outcomes among 853 pediatric TB cases (<15 years old), a study sample that represented all the pediatric TB cases with treatment outcome records in Harare, Zimbabwe during 2013-2017. We also identified factors associated with treatment outcome by multivariate logistic regression.

Results: Of these 853 analyzed cases, 57% were either cured or had completed treatment. In a model accounting for confounding variables, hospital center and pretreatment sputum smear were associated with unfavorable treatment outcome. Cases from Beatrice Road Infectious Disease Hospital were four times as likely to have an unfavorable outcome compared with those from Wilkins Infectious Disease Hospital (adjusted odds ration [aOR]: 4.0; 95% CI 2.9-5.5). Children whose pretreatment sputum smear was positive were 2.4 times as likely to have an unfavorable outcome as those who were negative (aOR: 2.4; 95% CI 1.7-3.6).

Conclusion: Pediatric TB case management needs to be improved, especially among those with a positive pretreatment sputum smear. Efforts to address TB treatment outcome disparities between clinical settings in high-burden settings, such as Harare, Zimbabwe, are essential in improving global TB control.
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http://dx.doi.org/10.1016/j.ijid.2020.08.079DOI Listing
December 2020

Vagus Nerve Stimulation Attenuates Early Traumatic Brain Injury by Regulating the NF-κB/NLRP3 Signaling Pathway.

Neurorehabil Neural Repair 2020 09 10;34(9):831-843. Epub 2020 Aug 10.

Department of Rehabilitation Medicine, First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Oxidative stress, inflammation, and apoptosis are vital pathophysiological features post-TBI.

Objectives: Research has shown that vagus nerve stimulation (VNS) can attenuate oxidative stress in various diseases. However, the critical role of VNS in TBI is still not completely understood. This study investigated the protective effects and potential mechanism of VNS on TBI.

Methods: Male Sprague-Dawley rats were randomized into 3 groups: sham, TBI, and TBI + VNS. The TBI model was induced in rats by the free-fall drop method. The vagal nerve trunk was separated, and VNS was performed after establishing the TBI model.

Results: The results showed that VNS significantly ameliorated tissue damage, neurological deficits, and cerebral edema, compared with the sham VNS group. Additionally, VNS alleviated oxidative stress, inflammation, and apoptosis in the pericontusive cortex of rats after TBI. VNS also significantly suppressed expression of the nuclear factor-κB (NF-κB) protein in the nucleus and activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome.

Conclusions: Taken together, the present study indicates that VNS may attenuate brain damage after TBI by inhibiting oxidative stress, inflammation, and apoptosis, possibly through the NF-κB/NLRP3 signaling pathway.
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http://dx.doi.org/10.1177/1545968320948065DOI Listing
September 2020

Multidrug resistant organism predicts ulcer recurrence following surgical management of diabetic foot osteomyelitis.

Int Wound J 2020 Dec 7;17(6):1634-1641. Epub 2020 Jul 7.

Division of Infectious Diseases, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.

Diabetic foot ulcers commonly precede diabetic foot osteomyelitis (DFO) and once the latter occurs, surgical management is often performed. The presence of osteomyelitis is an independent risk factor for the development of re-ulceration. We investigated the relationship between causative organisms in osteomyelitis and 1-year diabetic foot outcomes (re-ulceration, amputation, and death) following surgical management in an observational cohort of 223 patients. Univariate and multivariate analyses were performed for available demographic, clinical, and laboratory data. In addition, random forest plots were used to identify microbiologic predictors of 1-year outcomes. Patients with osteomyelitis managed surgically were younger and exhibited more painful peripheral neuropathy than outpatients with diabetes alone (both P < .0001). Osteomyelitis proximal margin cultures were diverse, at times polymicrobial, and included multidrug-resistant organisms in 13.9% of the cohort. In patients who underwent surgery, 44.5% experienced a re-ulceration on the same foot within 12 months of surgery. The presence of multidrug-resistant organisms on proximal bone culture was found to be a significant predictor of diabetic foot ulcer recurrence in univariate modelling (P < .001) and importance rankings. This is the first study to use prediction modelling to identify a relationship between multidrug-resistant organisms and diabetic foot ulcer recurrence following DFO.
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http://dx.doi.org/10.1111/iwj.13439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736527PMC
December 2020

Human Amniotic Epithelial Cells Promote the Proliferation of Human Corneal Endothelial Cells by Regulating Telomerase Activity via the Wnt/β-catenin Pathway.

Curr Eye Res 2021 Feb 13;46(2):159-167. Epub 2020 Jul 13.

Ophthalmic Center, The Second Affiliated Hospital of Guangzhou Medical University , Guangzhou, China.

Purpose: Human amniotic epithelial cells (HAECs) have regenerative properties and low immunogenicity, which have enabled their use without immune rejection in regenerative medicine applications, such as wound repair, corneal surgery and burn repair. The aim of this study was to explore the potential role of HAECs in the proliferation of human corneal endothelial cells (HCEnCs) and the possible mechanism of regulation.

Methods: HAECs and HCEnCs were isolated from donated tissue samples and were cultured; the collected HAEC culture medium (HAEC-Me) was added to the human corneal endothelium medium (CEM) to establish the HAEC-CM system. HCEnCs were cultured in CEM, 20%HAEC-Me, 20% HAEC-CM, 20% HAEC-CM supplemented with a GSK-3β inhibitor TWS119 or CEM supplemented with TWS119. Then, cell proliferation, apoptosis, cell cycle progression, telomerase activity, and Wnt/β-catenin pathway-related protein levels were assessed.

Results: We found that the HCEnCs cultured in the 20% HAEC-CM had increased proliferative capacity, telomerase activity and β-catenin and Tcf4 expression levels, and they had a decrease in the rate of apoptosis and α-SMA expression when they were compared with the HCEnCs cultured in the 20% HAEC-Me. After GSK-3β was inhibited by TWS119, HCEnCs cultured in CEM or 20% HAEC-CM had an increased proliferative capacity, telomerase activity, β-catenin/Tcf4 expression and a decreased α-SMA expression, and they had a decreased apoptotic rate.

Conclusions: These data indicate that the human amniotic epithelial cells microenvironment can promote the proliferation of human corneal endothelial cells, which may be related to regulating telomerase activity and epithelial-to-mesenchymal transition (EMT) via the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1080/02713683.2020.1792508DOI Listing
February 2021

miR-196a-mediated downregulation of p27 protein promotes prostate cancer proliferation and relates to biochemical recurrence after radical prostatectomy.

Prostate 2020 09 6;80(12):1024-1037. Epub 2020 Jul 6.

Department of Urology, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Dysregulation of microRNAs has performed vital gene regulatory functions in the genesis, progression, and prognosis of multiple malignant tumors. This study aimed to elucidate the regulatory mechanism of miR-196a in prostate cancer (PCa) and explore its clinical significance.

Methods: Quantitative real-time polymerase chain reaction was implemented to examine miR-196a and p27 messenger RNA expression in PCa. Cell proliferation was evaluated via Cell Counting Kit-8, colony formation, and nude mouse tumorigenicity assays. Luciferase reporter assay was applied to identify target genes. p27 protein expression in PCa was investigated using Western blot analysis and immunohistochemistry.

Results: There was a dramatic upregulation of miR-196a in PCa. Upregulated miR-196a was related to worse Gleason score (GS), later pathological stage, and poor biochemical recurrence (BCR)-free survival. In vivo and in vitro experiments exhibited that miR-196a promoted PCa proliferation and expedited G1/S-phase progression through the downregulation of p27 protein. Additionally, p27 protein was distinctly downregulated in PCa. Low p27 protein expression had a strong correlation with increased GS and was an independent predictor of BCR after radical prostatectomy (RP).

Conclusions: Excessive expression of miR-196a and subsequent downregulation of p27 protein play essential roles in promoting PCa proliferation and leading to BCR after RP. miR-196a and its target p27 may become novel molecular biomarkers and therapeutic targets for PCa.
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http://dx.doi.org/10.1002/pros.24036DOI Listing
September 2020