Publications by authors named "Tianhao Wang"

69 Publications

Neuropathologic Correlates of Human Cortical Proteins in Alzheimer Disease and Related Dementias.

Neurology 2021 Dec 22. Epub 2021 Dec 22.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Background And Objectives: Alzheimer's dementia is a complex clinical syndrome that can be defined broadly as an amnestic multidomain dementia. We previously reported human cortical proteins that are implicated in Alzheimer's dementia. To understand the pathologic correlates of these proteins for underlying disease mechanisms, we investigated cortical protein associations with common age-related neuropathologies.

Methods: Participants were community-dwelling older adults from two cohort studies of aging and dementia. All underwent detailed annual clinical evaluations, and brain autopsies were performed after death. We refer Alzheimer's disease (AD) to pathologically defined disease, and refer Alzheimer's dementia to the clinical syndrome. Indices for AD, cortical Lewy bodies, limbic predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), hippocampal sclerosis, macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis and arteriolosclerosis were quantified during uniform structured neuropathologic evaluations. High-throughput protein abundances from frozen dorsolateral prefrontal cortex were quantified using mass spectrometry based tandem mass tag proteomics analysis. Eleven human cortical proteins implicated in Alzheimer's dementia, including ACE, CHSP1, CATH, DOC2A, ICA1L, LACTB, PKHA1, RTF2, SNX32, STX4, and STX6, were previously identified using an integrative approach. Logistic regression analysis examined the association of protein expression with each of the neuropathologic indices.

Results: A total of 391 older adults were included. We did not observe associations of these protein targets with pathologic diagnosis of AD. By contrast, multiple proteins were associated with non-AD neurodegenerative and cerebrovascular conditions. In particular, higher CHSP1 expression was associated with cortical Lewy bodies and macroscopic infarcts, and higher CATH expression was associated with LATE-NC and arteriolosclerosis. Further, while higher STX6 expression increased the risk of Alzheimer's dementia, the protein was not associated with any of the neuropathologic indices investigated.

Discussion: Cortical proteins implicated in Alzheimer's dementia do not necessarily work through AD pathogenesis; rather, non-AD neurodegenerative and vascular diseases, as well as other pathways are at play. Further, some proteins are pleiotrophic and associated with both neurodegenerative and cerebrovascular pathologies.
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http://dx.doi.org/10.1212/WNL.0000000000013252DOI Listing
December 2021

North American biliary stricture management strategies in children post liver transplant: multicenter analysis from the SPLIT Registry.

Liver Transpl 2021 Nov 27. Epub 2021 Nov 27.

Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Background: Biliary strictures affect 4-12% of pediatric liver transplants (P-LT). Biliary strictures can contribute to graft loss if left untreated, however there remains no consensus on the best course of treatment. Study objectives included analyses of outcomes associated with biliary stricture management strategies via PTC, ERCP or surgery.

Methods: We identified P-LT recipients (2011-2016) with biliary strictures from the Society of Pediatric Liver Transplantation (SPLIT) registry and retrieved imaging, procedural and operative reports from individual centers. Sub-analyses were performed to specifically evaluate PTC and ERCP for "Optimal Biliary Outcome" (OBO), defined as survival with stricture resolution without recurrence or surgery.

Results: 113 children with median 3.9 years of follow-up had strictures diagnosed 100 days (IQR 30, 290) post LT; 81% were isolated anastomotic strictures. Stricture resolution was achieved in 92% within 101 days, more frequently with isolated anastomotic strictures (96%). 20% of strictures recurred, more commonly in association with hepatic artery thrombosis (32%). Patient and graft survival at 1- and 3-years were 99%, 98% and 94%, 92% respectively. In a subgroup analysis of 79 patients with extrahepatic strictures managed by PTC/ERCP: 59% achieved OBO following a median 4 PTC, and 75% following a median 3 ERCP (P=0.0003). Among patients with OBO, those with ERCP had longer time intervals between successive procedures (41, 47, 54, 62, 71 days) than for PTC (27, 31, 36, 41, 48 days; P=0.0006).

Conclusions: Allograft salvage was successful across all interventions. Stricture resolution was achieved in 92%, with 20% risk of recurrence. Resolution without recurrence was highest in patients with isolated anastomotic strictures and without HAT.
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http://dx.doi.org/10.1002/lt.26379DOI Listing
November 2021

Activation of cannabinoid receptor 2 alleviates glucocorticoid-induced osteonecrosis of femoral head with osteogenesis and maintenance of blood supply.

Cell Death Dis 2021 10 30;12(11):1035. Epub 2021 Oct 30.

Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

In glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3β/β-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.
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http://dx.doi.org/10.1038/s41419-021-04313-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556843PMC
October 2021

Influence of microflow on hepatic sinusoid blood flow and red blood cell deformation.

Biophys J 2021 11 16;120(21):4859-4873. Epub 2021 Sep 16.

School of Mechanical Engineering, Tianjin University, Tianjin, China. Electronic address:

Hepatic sinusoids present complex anatomical structures such as the endothelial sieve pores and the Disse space, which govern the microscopic blood flow in the sinusoids and are associated with structural variations in liver fibrosis and cirrhosis. However, the contributions of the permeability of endothelial and collagen layers and the roughness of hepatocyte microvilli to the features of this microflow remain largely unknown. Here, an immersed boundary method coupled with a lattice Boltzmann method was adopted in an in vitro hepatic sinusoidal model, and flow field and erythrocyte deformation analyses were conducted by introducing three new source terms including permeability of the endothelial layer, resistance of hepatocyte microvilli and collagen layers, and deformation of red blood cells (RBCs). Numerical calculations indicated that alterations in endothelial permeability could significantly affect the flow velocity and flow rate distributions in hepatic sinusoids. Interestingly, a biphasic regulating pattern of shear stress occurred simultaneously on the surface of hepatocytes and the lower side of endothelium, i.e., the shear stress increased with increased thickness of hepatocyte microvilli and collagen layer when the endothelial permeability was high but decreased with the increase of the thickness at low endothelial permeability. Additionally, this specified microflow manipulates typical RBC deformation inside the sinusoid, yielding one-third of the variation of deformable index with varied endothelial permeability. These simulations not only are consistent with experimental measurements using in vitro liver sinusoidal chip but also elaborate the contributions of endothelial and collagen layer permeability and wall roughness. Thus, our results provide a basis for further characterizing this microflow and understanding its effects on cellular migration and deformation in the hepatic sinusoids.
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http://dx.doi.org/10.1016/j.bpj.2021.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595567PMC
November 2021

Plant Growth-Promoting Rhizobacteria HN6 Induced the Change and Reorganization of Microflora in the Rhizosphere of Banana Seedlings to Construct a Healthy Banana Microflora.

Front Microbiol 2021 20;12:685408. Epub 2021 Jul 20.

Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests, Ministry of Education, School of Plant Protection, Hainan University, Haikou, China.

HN6 was isolated in our previous study and effectively controlled banana wilt. We explored the role of HN6 in constructing a healthy rhizosphere microflora of banana seedlings. The method of antibiotic resistance was used to determine the colonization ability of HN6. The effect of HN6 on the rhizosphere microbial communities was assessed using culture-dependent and high-throughput sequencing. The effect of HN6 on the infection process of the pathogen was evaluated using a pot experiment and confocal laser scanning microscopy. The results showed that HN6 could prevent pathogen infection; it increased the nutrient content and diversity of the bacterial community in the rhizosphere, promoted plant growth, and decreased the mycotoxin fusaric acid content and abundance of pathogens in the banana rhizosphere. Thus, HN6 decreased the relative abundance of species, increased the diversity of fungi, and increased the relative abundance of bacteria in the rhizosphere. HN6 induced the change and reorganization of the microbial community dominated by in the rhizosphere of banana seedlings, and it evolved into a community dominated that was not conducive to the occurrence of diseases, shaping the rhizosphere microflora and promoting the growth of banana.
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http://dx.doi.org/10.3389/fmicb.2021.685408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329250PMC
July 2021

Risk Potential for Organ Dysfunction Associated With Sodium Bicarbonate Therapy in Critically Ill Patients With Hemodynamic Worsening.

Front Med (Lausanne) 2021 7;8:665907. Epub 2021 Jul 7.

Critical Care Medicine Department, Peking University Third Hospital, Beijing, China.

The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients. We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly "developed or exacerbated organ dysfunction" (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis. A total of 1,765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8 vs. 44.6%, < 0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); = 0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), < 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), < 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), = 0.046] compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis. Our findings did not demonstrate an association between SBT and outcomes in critically ill patients with metabolic acidosis. However, patients with either worsening or unchanged hemodynamic status in initial resuscitation had a significantly higher risk potential of newly d/eOD subsequent to SBT.
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http://dx.doi.org/10.3389/fmed.2021.665907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292723PMC
July 2021

Cognitive Activity and Onset Age of Incident Alzheimer Disease Dementia.

Neurology 2021 08 14;97(9):e922-e929. Epub 2021 Jul 14.

From the Rush Alzheimer's Disease Center (R.S.W., T.W., L.Y., F.G., D.A.B., P.A.B.), Department of Neurological Sciences (R.S.W., T.W., L.Y., F.G., D.A.B.), and Department of Psychiatry and Behavioral Sciences (R.S.W., P.A.B.), Rush University Medical Center, Chicago, IL.

Objective: To test the hypothesis that higher level of cognitive activity predicts older age at dementia onset in Alzheimer disease (AD) dementia.

Methods: As part of a longitudinal cohort study, 1,903 older persons without dementia at enrollment reported their frequency of participation in cognitively stimulating activities. They had annual clinical evaluations to diagnose dementia and AD, and the deceased underwent neuropathologic examination. In analyses, we assessed the relation of baseline cognitive activity to age at diagnosis of incident AD dementia and to postmortem markers of AD and other dementias.

Results: During a mean of 6.8 years of follow-up, 457 individuals were diagnosed with incident AD at a mean age of 88.6 (SD 6.4, range 64.1-106.5) years. In an extended accelerated failure time model, higher level of baseline cognitive activity (mean 3.2, SD 0.7) was associated with older age at AD dementia onset (estimate 0.026; 95% confidence interval 0.013-0.039). Low cognitive activity (score 2.1, 10th percentile) was associated with a mean onset age of 88.6 years compared to a mean onset age of 93.6 years associated with high cognitive activity (score 4.0, 90th percentile). Results were comparable in subsequent analyses that adjusted for potentially confounding factors. In 695 participants who died and underwent a neuropathologic examination, cognitive activity was unrelated to postmortem markers of AD and other dementias.

Conclusion: A cognitively active lifestyle in old age may delay the onset of dementia in AD by as much as 5 years.
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http://dx.doi.org/10.1212/WNL.0000000000012388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408511PMC
August 2021

Purpose in Life May Delay Adverse Health Outcomes in Old Age.

Am J Geriatr Psychiatry 2021 May 21. Epub 2021 May 21.

Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.

Objective: Test the hypothesis that a higher level of purpose in life is associated with an older age of Alzheimer's dementia onset and later mortality.

Design: Prospective cohort studies of aging and Alzheimer's dementia.

Setting: Community-based.

Participants: Two thousand five hundred fifty-eight older adults initially free of dementia underwent assessments of purpose in life and detailed annual clinical evaluations to document incident Alzheimer's dementia and mortality. General accelerated failure time models examined the relation of baseline purpose in life with age at Alzheimer's dementia diagnosis and mortality.

Exposures: Purpose in life was assessed at baseline.

Main Outcomes: Alzheimer's dementia diagnosis was documented annually based on detailed clinical evaluations and mortality was documented via regular contacts and annual evaluations.

Results: During a mean of 6.89 years of follow-up, 520 individuals were diagnosed with incident Alzheimer's dementia at a mean age of 88 (SD = 6.7; range: 64.1-106.5). They had a mean baseline level of purpose in life of 3.7 (SD = 0.47; range: 1-5). A higher level of purpose in life was associated with a considerably later age of dementia onset (estimate = 0.044; 95% CI: 0.023, 0.065); specifically, individuals with high purpose (90th percentile) developed Alzheimer's dementia at a mean age of about 95 compared to a mean age of about 89 for individuals with low purpose (10th percentile). Further, the estimated mean age of death was about 89 for individuals with high purpose compared to 85 for those with low purpose. Results persisted after controlling for sex and education.

Conclusion And Relevance: Purpose in life delays dementia onset and mortality by several years. Interventions to increase purpose in life among older persons may increase healthspan and offer considerable public health benefit.
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http://dx.doi.org/10.1016/j.jagp.2021.05.007DOI Listing
May 2021

The "cognitive clock": A novel indicator of brain health.

Alzheimers Dement 2021 Dec 1;17(12):1923-1937. Epub 2021 Jun 1.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

Introduction: We identified a "cognitive clock," a novel indicator of brain health that provides person-specific estimates of cognitive age, and tested the hypothesis that cognitive age is a better predictor of brain health than chronological age in two independent datasets.

Methods: The initial analyses were based on 1057 participants from the Rush Memory and Aging Project and the Religious Orders Study who began without impairment and underwent cognitive assessments up to 24 years. A shape invariant model characterized the latent pattern of cognitive decline, conceptualized here as the "cognitive clock," and yielded person-specific estimates of cognitive age. Survival analyses examined cognitive versus chronological age for predicting Alzheimer's disease dementia, mild cognitive impairment and mortality, and regression analyses examined associations of cognitive versus chronological age with neuropathology and brain atrophy. Finally, we applied the cognitive clock to an independent validation sample of 2592 participants from the Chicago Health and Aging Project, a biracial population-based study, to confirm the predictive utility of cognitive age.

Results: The "cognitive clock" showed that cognition remained stable until a cognitive age of about 80, then declined moderately until 90, then declined precipitously. In the initial dataset, cognitive age was a better predictor of dementia, mild cognitive impairment and mortality than chronological age, and was more strongly associated with neuropathology and brain atrophy. Application of the cognitive clock to the independent validation sample provided further support for the utility of cognitive age as a strong prognostic indicator of adverse outcomes.

Discussion: Cognitive age is a robust prognostic indicator of adverse health outcomes and may serve as a useful biomarker in aging research.
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http://dx.doi.org/10.1002/alz.12351DOI Listing
December 2021

Transpedicular bi-vertebrae wedge osteotomy in treatment of post-tubercular spinal deformity: a retrospective study.

BMC Musculoskelet Disord 2021 Apr 12;22(1):345. Epub 2021 Apr 12.

Department of Orthopedics, General Hospital of Chinese People's Liberation Army, 100853, Beijing, China.

Background: In the late stage of spinal tuberculosis, the bony destruction and vertebral collapse often leads to significant kyphosis, presenting clinically as a painful gibbus deformity, with increased instability, vertebral body translations and increased risk of neurologic involvement. Spinal osteotomy is thought to be suitable for most patients with severe rigid kyphosis. The aim of this study was to evaluate the efficacy of transpedicular bi-vertebrae osteotomy technique in the patients with Pott's kyphosis and other post-tubercular spinal deformity.

Methods: Between January 2012 and December 2015, 18 patients with post-tubercular spinal deformity underwent the transpedicular bi-vertebrae wedge osteotomy, with a minimum follow up of 27.0 months. Preoperative and postoperative kyphotic angle, sagittal plane parameters (TK for thoracic deformity, TLK for thoracolumbar and LL for lumbar deformity) and sagittal vertical axis (SVA) were measured. Oswestry Disability Index (ODI), Visual analog scale (VAS) and modified American Spinal Injury Association grading (ASIA) of preoperative and final follow-up were documented and compared.

Results: The average operation time was 305 minutes (range, 200-430 minutes) with a mean intraoperative blood loss of 425 mL (range, 200-700 mL). The kyphotic angles decreased from 80.3° (range, 28.5°-130.8°) preoperatively to 26.1° (range, 7.0°-63.3°) at the final follow-up (P<0.01). The mean VAS score was reduced from preoperative 5.2(range, 2-9) to 0.9(range, 0-2, P<0.01) and the ODI improved from 55.3% (range, 46%-76%) to 6.3% (range, 2%-18%, P<0.01). At final follow-up, there was radiographic evidence of solid fusion at the osteotomy site and fixed segments in all patients. Neurological function improved from ASIA scale D to E in 7 patients, C to D in 3 patients.

Conclusions: Our results suggest that transpedicular bi-vertebrae wedge osteotomy is a safe and effective treatment option for post-tubercular spinal deformity. This technique achieves satisfying correction and fusion rates with adequate decompression of neurological elements.
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http://dx.doi.org/10.1186/s12891-021-04220-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042881PMC
April 2021

To what degree is late life cognitive decline driven by age-related neuropathologies?

Brain 2021 08;144(7):2166-2175

Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL 60612, USA.

The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer's disease, non- Alzheimer's disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, P < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P < 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer's disease-related indices accounted for 30-36% of the variation, non-Alzheimer's disease neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.
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http://dx.doi.org/10.1093/brain/awab092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370442PMC
August 2021

Motor function is the primary driver of the associations of sarcopenia and physical frailty with adverse health outcomes in community-dwelling older adults.

PLoS One 2021 2;16(2):e0245680. Epub 2021 Feb 2.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States of America.

Background: This study tested the hypothesis that sarcopenia and its constituent components, reduced lean muscle mass and impaired motor function, are associated with reduced survival and increased risk of incident disabilities.

Methods: 1466 community-dwelling older adults underwent assessment of muscle mass with bioelectrical impedance analysis (BIA), grip strength, gait speed and other components of physical frailty and annual self-report assessments of disability. We used Cox proportional hazards models that controlled for age, sex, race, education and height to examine the associations of a continuous sarcopenia metric with the hazard of death and incident disabilities.

Results: Mean baseline age was about 80 years old and follow-up was 5.5 years. In a proportional hazards model controlling for age, sex, race, education and baseline sarcopenia, each 1-SD higher score on a continuous sarcopenia scale was associated with lower hazards of death (HR 0.70, 95%CI [0.62, 0.78]), incident IADL (HR 0.80,95%CI [0.70, 0.93]), incident ADL disability (HR 0.80 95%CI [71, 91]) and incident mobility disability (HR 0.81, 95%CI [0.70, 0.93]). Further analyses suggest that grip strength and gait speed rather than muscle mass drive the associations with all four adverse health outcomes. Similar findings were observed when controlling for additional measures used to assess physical frailty including BMI, fatigue and physical activity.

Conclusions: Motor function is the primary driver of the associations of sarcopenia and physical frailty with diverse adverse health outcomes. Further work is needed to identify other facets of muscle structure and motor function which together can identify adults at risk for specific adverse health outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245680PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853482PMC
July 2021

Co-introduction of precipitate hardening and TRIP in a TWIP high-entropy alloy using friction stir alloying.

Sci Rep 2021 Jan 15;11(1):1579. Epub 2021 Jan 15.

Department of Materials Science and Engineering, University of North Texas, Denton, TX, 76207, USA.

Tuning deformation mechanisms is imperative to overcome the well-known strength-ductility paradigm. Twinning-induced plasticity (TWIP), transformation-induced plasticity (TRIP) and precipitate hardening have been investigated separately and have been altered to achieve exceptional strength or ductility in several alloy systems. In this study, we use a novel solid-state alloying method-friction stir alloying (FSA)-to tune the microstructure, and a composition of a TWIP high-entropy alloy by adding Ti, and thus activating site-specific deformation mechanisms that occur concomitantly in a single alloy. During the FSA process, grains of the as-cast face-centered cubic matrix were refined by high-temperature severe plastic deformation and, subsequently, a new alloy composition was obtained by dissolving Ti into the matrix. After annealing the FSA specimen at 900 °C, hard Ni-Ti rich precipitates formed to strengthen the alloy. An additional result was a Ni-depleted region in the vicinity of newly-formed precipitates. The reduction in Ni locally reduced the stacking fault energy, thus inducing TRIP-based deformation while the remaining matrix still deformed as a result of TWIP. Our current approach presents a novel microstructural architecture to design alloys, an approach that combines and optimizes local compositions such that multiple deformation mechanisms can be activated to enhance engineering properties.
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http://dx.doi.org/10.1038/s41598-021-81350-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810985PMC
January 2021

Interfacial reaction during friction stir assisted scribe welding of immiscible Fe and Mg alloy system.

Sci Rep 2021 Jan 15;11(1):1588. Epub 2021 Jan 15.

Applied Materials and Manufacturing Group, Pacific Northwest National Laboratory, Richland, WA, USA.

We report on interfacial characteristics and chemistry of bonded Mg-Fe interfaces welded using friction stir assisted scribe technique (FaST). Two pairs of dissimilar joints: (AZ31-DP590) and (Pure Mg-DP590) were studied to shed light on joining mechanisms responsible for bonding of "immiscible" pairs of Mg and Fe. We present first direct experimental evidence of presence of oxide layer, Al segregation by atom probe tomography and nano steel grains close to interface by transmission electron microscopy study.
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http://dx.doi.org/10.1038/s41598-021-81266-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810708PMC
January 2021

Dynamic Shear Deformation of a Precipitation Hardened AlCoCrFeNi Eutectic High-Entropy Alloy Using Hat-Shaped Specimen Geometry.

Entropy (Basel) 2020 Apr 10;22(4). Epub 2020 Apr 10.

Department of Materials Science and Engineering, University of North Texas, Denton, TX 76207, USA.

Lamellar eutectic structure in AlCoCrFeNi high-entropy alloy (HEA) is emerging as a promising candidate for structural applications because of its high strength-ductility combination. The alloy consists of a fine-scale lamellar + B2 microstructure with high flow stresses > 1300 MPa under quasi-static tensile deformation and >10% ductility. The response to shear loading was not investigated so far. This is the first report on the shear deformation of a eutectic structured HEA and effect of precipitation on shear deformation. A split-Hopkinson pressure bar (SHPB) was used to compress the hat-shaped specimens to study the local dynamic shear response of the alloy. The change in the width of shear bands with respect to precipitation and deformation rates was studied. The precipitation of L1 phase did not delay the formation of adiabatic shear bands (ASB) or affect the ASB width significantly, however, the deformed region around ASB, consisting of high density of twins in phase, was reduced from 80 µm to 20 µm in the stronger precipitation strengthened condition. We observe dynamic recrystallization of grains within ASBs and local mechanical response of individual eutectic lamellae before and after shear deformation and within the shear bands was examined using nano-indentation.
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http://dx.doi.org/10.3390/e22040431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516913PMC
April 2020

Microstructural Assessment of a Multiple-Intermetallic-Strengthened Aluminum Alloy Produced from Gas-Atomized Powder by Hot Extrusion and Friction Extrusion.

Materials (Basel) 2020 Nov 25;13(23). Epub 2020 Nov 25.

Pacific Northwest National Laboratory, Department of Energy, 902 Battelle Blvd., Richland, WA 99354, USA.

An aluminum (Al) matrix with various transition metal (TM) additions is an effective alloying approach for developing high-specific-strength materials for use at elevated temperatures. Conventional fabrication processes such as casting or fusion-related methods are not capable of producing Al-TM alloys in bulk form. Solid phase processing techniques, such as extrusion, have been shown to maintain the microstructure of Al-TM alloys. In this study, extrusions are fabricated from gas-atomized aluminum powders (≈100-400 µm) that contain 12.4 wt % TM additives and an Al-based matrix reinforced by various Al-Fe-Cr-Ti intermetallic compounds (IMCs). Two different extrusion techniques, conventional hot extrusion and friction extrusion, are compared using fabricating rods. During extrusion, the strengthening IMC phases were extensively refined as a result of severe plastic deformation. Furthermore, the quasicrystal approximant IMC phase (70.4 wt % Al, 20.4 wt % Fe, 8.7 wt % Cr, 0.6 wt % Ti) observed in the powder precursor is replaced by new IMC phases such as AlFe and AlCr-type IMCs. The AlTi-type IMC phase is partially dissolved into the Al matrix during extrusion. The combination of linear and rotational shear in the friction extrusion process caused severe deformation in the powders, which allowed for a higher extrusion ratio, eliminated linear voids, and resulted in higher ductility while maintaining strength comparable to that resulting from hot extrusion. Results from equilibrium thermodynamic calculations show that the strengthening IMC phases are stable at elevated temperatures (up to ≈ 600 °C), thus enhancing the high-temperature strength of the extrudates.
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http://dx.doi.org/10.3390/ma13235333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728062PMC
November 2020

Antibody profiling and prevalence in US patients during the SARS-CoV2 pandemic.

PLoS One 2020 19;15(11):e0242655. Epub 2020 Nov 19.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States of America.

Background: Antibody diagnostics play an important role in disease detection and can potentially aid in monitoring of the immune responses to see if an individual has developed immunity. Developing high throughput diagnostics which does not involve handling of infectious material becomes imperative in the case of pandemics such as the recent outbreak of SARS-CoV2.

Methods: A protein microarray technology was used to detect the plurality of antibody response to four novel antigens namely S1 glycoprotein, Receptor binding domain (RBD), S2 glycoprotein and Nucleoprotein of the novel coronavirus named SARS-CoV2 using serum samples. A DBS card was additionally used to compare its performance with a venipuncture-based serum separator tube (SST) draw.

Results: The three main subclasses of antibodies IgM, IgA and IgG were analyzed to see the variations in immune responses in the affected population and compared to their microbial RT-PCR based NP swab results. The clinical sensitivity and specificity were determined to be 99.67% and 99.77%. In the matrix comparison study, which would enable patients to test without risk of transmitting the virus, DBS (Dried Blood Spot) matched with higher than 98% accuracy to a venipuncture-based SST collection.

Conclusion: Multiplex testing enables higher sensitivity and specificity which is essential while establishing exposure on a population scale. This flexible platform along with a discrete collection methodology would be crucial and broadly useful to scale up testing in current and future pandemics. Minimum sample volume that can be collected using DBS cards can be processed in this multiplex pillar plate format enabling the capacity to provide the reliability of high throughput analyzers while having the ease of collection similar to rapid tests.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242655PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676701PMC
December 2020

An ultra-high-density protein microarray for high throughput single-tier serological detection of Lyme disease.

Sci Rep 2020 10 22;10(1):18085. Epub 2020 Oct 22.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.

Current serological immunoassays have inherent limitations for certain infectious diseases such as Lyme disease, a bacterial infection caused by Borrelia burgdorferi in North America. Here we report a novel method of manufacturing high-density multiplexed protein microarrays with the capacity to detect low levels of antibodies accurately from small blood volumes in a fully automated system. A panel of multiple serological markers for Lyme disease are measured using a protein microarray system, Lyme Immunochip, in a single step but interpreted adhering to the standard two-tiered testing algorithm (enzyme immunoassay followed by Western blot). Furthermore, an enhanced IgM assay was supplemented to improve the test's detection sensitivity for early Lyme disease. With a training cohort (n = 40) and a blinded validation cohort (n = 90) acquired from CDC, the Lyme Immunochip identified a higher proportion of Lyme disease patients than the two-tiered testing (82.4% vs 70.6% in the training set, 66.7% vs 60.0% in the validation set, respectively). Additionally, the Immunochip improved sensitivity to 100% while having a lower specificity of 95.2% using a set of investigational antigens which are being further evaluated with a large cohort of blinded samples from the CDC and Columbia University. This universal microarray platform provides an unprecedented opportunity to resolve a broad range of issues with diagnostic tests, including multiplexing, workflow simplicity, and reduced turnaround time and cost.
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http://dx.doi.org/10.1038/s41598-020-75036-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581523PMC
October 2020

Brain pathologies are associated with both the rate and variability of declining motor function in older adults.

Acta Neuropathol 2020 10 14;140(4):587-589. Epub 2020 Aug 14.

Rush Alzheimer's Disease Center, Rush University Medical Center, 1750 West Harrison Street, Jelke Building, Suite 100, Chicago, IL, 60612, USA.

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http://dx.doi.org/10.1007/s00401-020-02212-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501086PMC
October 2020

A study of knowledge, attitudes, and practices of primary care physicians toward anticoagulant therapy in patients with non-valvular atrial fibrillation in Shanghai, China.

BMC Fam Pract 2020 08 15;21(1):165. Epub 2020 Aug 15.

Department of General Practice, Zhongshan Hospital, Fudan University, No 111 Yixueyuan Rd, Shanghai, China.

Background: As a large number of Community Health Service (CHS) centers in China face the majority of patients with non-valvular atrial fibrillation (NVAF), primary care physicians (PCPs) play a primary role in the prevention of embolization. Therefore, an awareness of anticoagulant management in patients with NVAF must be brought into focus among PCPs in China. This study investigated PCPs' knowledge, attitudes, and practices toward anticoagulant therapy in patients with NVAF, to help them understand their shortcomings regarding oral anticoagulant (OAC) therapy in preventing embolization.

Method: This was a cross-sectional observational study of 462 PCPs in CHS centers across Shanghai. We used a self-administered questionnaire to collect data from September to December 2017. A stratified random cluster sampling was adopted in the 90 CHS centers with the family medicine residency program.

Result: Among 462 participants, 69.3% (320/462) of females received a medical bachelor's degree and over 50% of participants had more than 10 years of work experience. Each section for knowledge, attitude, and practice were categorized as poor (≤39.0%), fair (40.0-69.0%), and good (≥70.0%). The level of knowledge of OAC therapy for patients with NVAF among PCPs was insufficient in over half (75.8%) of the participants. The majority (89.8%) of PCPs had a positive attitude and 68.0% had modest performance in the anticoagulant management of patients with NVAF.

Conclusions: The knowledge and behaviors of PCPs were insufficient for OAC therapy to prevent embolization in patients with NVAF. The study also revealed that there is good potential for PCPs' educational interventions to positively impact the care of patients with NVAF.
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http://dx.doi.org/10.1186/s12875-020-01236-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429456PMC
August 2020

A hybrid therapeutic approach for decreasing postoperative complications in patients with adult lumbar degenerative scoliosis.

Medicine (Baltimore) 2020 Jul;99(30):e21221

The General Hospital of Chinese People's Liberation Army (301 Hospital).

To decrease postoperative complications in patients with adult lumbar degenerative scoliosis (ALDS), short-segment fusion surgery was used in this study. However, the incidence of adjacent segment disease was found to be remarkable. Therefore, we applied the hybrid treatment (short-segment fusion for responsibility levels plus nonfusion stabilization of lumbar segments, which was called the Wallis system, for the proximal level) to patients enrolled into this study. The purpose of this study was to investigate the feasibility of a novel hybrid therapeutic approach for treating patients with ALDS.From January 2011 to January 2017, a retrospective study was conducted consisting of 16 patients with ALDS who were treated with hybrid treatment. All patients were treated with short-segment decompression and fusion for responsibility levels and nonfusion stabilization of lumbar segments for the proximal levels. The imaging outcomes were evaluated preoperatively and at the time of follow-up.The mean visual analog score for back pain decreased from 6.1 ± 2.0 preoperatively to 2.1 ± 0.7 at 2-year follow-up (P < .05), and the mean visual analog score for leg pain reduced from 8.1 ± 0.6 preoperatively to 1.3 ± 0.8 at 2-year follow-up (P < .05). The Oswestry disability index scores improved from 65.4 ± 16.3% preoperatively to 18.3 ± 5.6% at 2-year follow-up (P < .05). The mean Cobb angle was 22.1 ± 6.2° preoperatively, and 13.8 ± 6.8° at 2-year follow-up (P < .05). The lumbar lordosis changed from -40.4 ± 14.8° to -43.5 ± 11.2° at 2-year follow-up (P < .05). Solid fusion was achieved in all the patients, and no incidence of adjacent segment disease was noted as well.The proposed hybrid treatment for patients with ALDS can achieve favorable clinical outcomes and a lower incidence of ALDS. However, the correction of deformity is still limited that highlights the necessity of further study.
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http://dx.doi.org/10.1097/MD.0000000000021221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386975PMC
July 2020

Relationship between postoperative lordosis distribution index and adjacent segment disease following L4-S1 posterior lumbar interbody fusion.

J Orthop Surg Res 2020 Apr 3;15(1):129. Epub 2020 Apr 3.

Department of Orthopedics, Chinese PLA General Hospital, Fuxing Road, Beijing, China.

Background: Adjacent segment disease (ASD) is an acknowledged problem of posterior lumbar interbody fusion (PLIF). Many studies have been reported concerning the role of lordosis distribution index (LDI) in spinal biomechanics. However, few reports have been published about the impact of LDI on ASD following L4-S1 PLIF.

Methods: The study enrolled 200 subjects who underwent L4-S1 PLIF for degenerative spine disease from 2009 to 2014. The average follow-up term was 84 months. Several lower lumbar parameters were measured, including lower lumbar lordosis (LLL), lumbar lordosis (LL), pelvic incidence (PI), and LDI on the pre and postoperative radiograph. Perioperative information, comorbidities, and operative data were documented. Kaplan-Meier curves were plotted for the comparisons of ASD-free survival of 3 different types of postoperative LDI subgroups.

Results: The incidence of ASD was found to be 8.5%. LL and LLL increased by 3.96° (38.71° vs 42.67°; P < 0.001) and 3.60° (26.22° vs 28.82°; P < 0.001) after lower lumbar fusion surgery, respectively. Lordosis distribution index (LDI) increased by 0.03 (0.66 vs 0.69, P = 0.004) postoperatively. A significant difference (P = 0.001) was observed when comparing the incidence of ASD among postoperative LDI subgroups. The Kaplan-Meier curves showed a marked difference in ASD-free survival between low and moderate LDI subgroup (log-rank test, P = 0.0012) and high and moderate LDI subgroup (log-rank test, P = 0.0005).

Conclusion: Patients with abnormal postoperative LDI were statistically more likely to develop ASD than those who had normal postoperative LDI. Moreover, patients with low postoperative LDI were at greater risk for developing ASD than those with high postoperative LDI over time.
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http://dx.doi.org/10.1186/s13018-020-01630-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119009PMC
April 2020

Increasing pelvic incidence is associated with more global sagittal imbalance in ankylosing spondylitis with thoracolumbar kyphosis: an observational retrospective study of 94 cases.

BMC Musculoskelet Disord 2020 Mar 27;21(1):192. Epub 2020 Mar 27.

Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, China.

Background: Ankylosing spondylitis (AS) patients with kyphosis have an abnormal spinopelvic alignment and pelvic morphology. Most studies focus on the relationship of pelvic tilt (PT) or sacral slope (SS) and deformity, and relatively few studies have addressed the relationship between pelvic incidence (PI) and kyphosis in AS patients. The purpose of this study is to analyze the correlation between pelvic incidence (PI) and the spinopelvic parameters describing local deformity or global sagittal balance in AS patients with thoracolumbar kyphosis.

Methods: A total of 94 patients with AS (91 males and 3 females) and 30 controls (27 males and 3 females) were reviewed. The mean age was 36.8 years in AS patients and 34.4 years in controls. Gender ratios and mean age were similar in both group. Sagittal spinopelvic parameters, including PI, PT, SS, thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA), the first thoracic vertebra pelvic angle (TPA), spinosacral angle (SSA) and spinopelvic angle (SPA) were measured. The same spine surgeons measured all the parameters of the AS and control group. All the sagittal spinopelvic parameters were compared between the groups. The relationship between PI and other spinopelvic parameters was analyzed with Pearson correlation (r) and unary linear regression model.

Results: All the sagittal parameters were found to be significantly different between AS patients and controls. Compared with the control group, the AS patients had significantly higher PI(47.4° vs. 43.2°, P < 0.001). Correlation analysis revealed that PI in AS patients was significantly positively correlated with TPA(r = 0.533, R = 0.284, P < 0.001), and negatively correlated with SPA(r = - 0.504, R = 0.254, P < 0.001). However, no correlations were found between PI and SVA, SSA, TK, TLK or LL in AS patients.

Conclusion: This study revealed that increasing PI was significantly correlated with more global sagittal imbalance, not with the local deformity in AS patients with thoracolumbar kyphosis.
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http://dx.doi.org/10.1186/s12891-020-03226-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102437PMC
March 2020

Preparation of Foam-like Network Structure of Polypyrrole/Graphene Composite Particles Based on Cellulose Nanofibrils as Electrode Material.

ACS Omega 2020 Mar 5;5(10):4778-4786. Epub 2020 Mar 5.

Beijing Key Laboratory of Lignocellulosic Chemistry, MOE Engineering Research Center of Forestry Biomass Materials and Bioenergy, Beijing Forestry University, No. 35 Tsinghua East Road, Haidian District, Beijing 100083, P. R. China.

Unusual polypyrrole/graphene/cellulose nanofibril (PPy/GR/CNF) composite particles were fabricated by introducing an in situ oxidative polymerization approach. Structural characterization of the composite particles showed foam-like network morphology with a large surface area of 621 m/g. The PPy/GR/CNF sample exhibited remarkable capacitance behavior in 1 M NaSO. It showed a high specific capacitance of 264.3 F/g at 0.25 A/g, which represents a 51.7% increase compared to that of PPy/GR and a high capacitance of 155.5 F/g even at a high current density of 5 A/g. Meanwhile, it possessed high rate capability and good cycling performance (85.7% capacitance retention even after 1000 cycles). These excellent electrochemical performances were attributed to the structure of PPy/GR/CNF that can provide large surface areas and shorten electron diffusion pathways. More importantly, the CNF stabilized the structure of PPy and prevented chain breakdown during the charge/discharge process, which improved the cycling performance. Hence, this PPy/GR/CNF composite shows great potential for the fabrication of high-capacitance and low-cost supercapacitor electrode materials with good cycling performance.
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http://dx.doi.org/10.1021/acsomega.9b03006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081294PMC
March 2020

Normative Cognitive Decline in Old Age.

Ann Neurol 2020 06 14;87(6):816-829. Epub 2020 Mar 14.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.

Objective: To characterize trajectories of normative cognitive aging.

Methods: Older persons without dementia at study enrollment (n = 1,010) had annual cognitive testing for up to 24 years (mean = 9.9 years, standard deviation = 5.0), died, and underwent a neuropathologic examination to quantify 9 postmortem markers of common neurodegenerative and cerebrovascular conditions. To accommodate the heterogeneity in cognitive trajectories, we used functional mixed effects models, which allow individuals to have different patterns of cognitive decline under a unified model structure.

Results: In a functional mixed effects model, postmortem markers (Alzheimer disease pathology, Lewy bodies, transactive response DNA-binding protein 43 pathology, hippocampal sclerosis, atherosclerosis, gross infarcts) were associated with global cognitive decline. Residual global cognitive decline after adjustment for neuropathologic burden was weakly related to age at death; it occurred in only about one-third of participants, mostly proximate to death. Results were comparable after eliminating the initial cognitive assessments to minimize retest learning or controlling for frailty proximate to death. Analyses were also conducted with composite measures of episodic memory and perceptual speed. Residual decline not attributable to neuropathologic burden was confined to a subset for each outcome and was most evident proximate to death. Age at death was unrelated to residual decline in episodic memory but was related to residual decline in perceptual speed.

Interpretation: Late life cognitive loss mainly reflects non-normative pathologic and mortality-related processes rather than normative age-related processes. ANN NEUROL 2020;87:816-829.
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http://dx.doi.org/10.1002/ana.25711DOI Listing
June 2020

Enhanced permeability, mechanical and antibacterial properties of cellulose acetate ultrafiltration membranes incorporated with lignocellulose nanofibrils.

Int J Biol Macromol 2020 May 13;151:159-167. Epub 2020 Feb 13.

Department of Chemistry and Chemical Engineering, MOE Engineering Research Center of Forestry Biomass Materials and Bioenergy, Beijing Forestry University, Beijing 100083, China. Electronic address:

Cellulose acetate (CA) ultrafiltration membranes are attracting more attention in wastewater purification due to its biodegradability and eco-friendly. The application of CA membranes, however, is limited by high susceptibility to bacterial corrosion and lack of mechanical tolerance that results in loss of life. To solve the above problems, we first fabricated the CA-based composite membranes incorporated with bamboo-based lignocellulose nanofibrils (LCNFs) by a strategy of phase inversion. LCNFs was prepared by using a combined method of one-step chemical pretreatment and acid hydrolysis coupled with high-pressure homogenization. The as-prepared CA/LCNFs composite membranes with 4 wt% lignin in the LCNFs exhibited high tensile strength of 7.08 MPa and strain-at-break of 12.21%, and high filtration permeability of 188.23 L·m·h as ultrafiltration membranes for wastewater treatment, which could obviously inhibit the growth of Escherichia coli.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.124DOI Listing
May 2020

Design and performance of a superconducting neutron resonance spin flipper.

Rev Sci Instrum 2020 Jan;91(1):015117

Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, USA.

Despite the challenges, neutron resonance spin echo still holds the promise to improve upon neutron spin echo for the measurement of slow dynamics in materials. We present a bootstrap, radio frequency neutron spin flipper using high temperature superconducting technology capable of flipping neutron spin with either nonadiabatic or adiabatic modes. A frequency of 2 MHz has been achieved, which would achieve an effective field integral of 0.35 T m for a meter of separation in a neutron resonance spin echo spectrometer at the current device specifications. In bootstrap mode, the self-cancellation of Larmor phase aberrations can be achieved with the appropriate selection of the polarity of the gradient coils.
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http://dx.doi.org/10.1063/1.5124681DOI Listing
January 2020

Evaluation of the Vibrant DNA microarray for the high-throughput multiplex detection of enteric pathogens in clinical samples.

Gut Pathog 2019 18;11:51. Epub 2019 Oct 18.

Vibrant Sciences LLC, San Carlos, CA USA.

Background: Rapid detection of a wide range of etiologic agents is essential for appropriate treatment and control of gastrointestinal (GI) infections. A variety of microbial species including bacteria, viruses, parasites, and fungi have been recognized as diarrheagenic enteric pathogens. However, multiplex testing of various targets in a single reaction needs further improvement because of its limitation in species and throughput.

Results: This study aims at developing and evaluating a DNA microarray-based qualitative multiplexed polymerase chain reaction (PCR) assay, Vibrant GI pathogen panel (GPP), for simultaneous detection of 27 enteric GI pathogenic targets (16 bacteria, 5 viruses, 4 parasites, and 2 fungi) directly from stool specimens. Limits of detection ranged from 10 to 10 cells/mL for bacteria, 10 to 10 cells/mL for parasites, 10 to 10 RNA copies/mL for viruses, and 10 to 10 cells/mL for fungi. Performance characteristics were determined using 27 Quantitative Genomic DNAs, 212 spiked stool specimens, 1067 clinical and archived stool specimens. Overall sensitivity was 95.9% (95% CI 92.4-98.1) and specificity was 100% (95% CI 99.9-100). Polymicrobial detections contained either two or three organisms was 20.2% (35/173) of positive clinical specimens and 3.3% (35/1055) of all clinical specimens.

Conclusion: The Vibrant GPP is a comprehensive, high-throughput, and rapid DNA microarray to provide etiologic diagnosis of GI infections in the laboratory setting.
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http://dx.doi.org/10.1186/s13099-019-0329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798489PMC
October 2019

Common age-related neuropathologies and yearly variability in cognition.

Ann Clin Transl Neurol 2019 11 30;6(11):2140-2149. Epub 2019 Sep 30.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.

Objective: Cognitive variability is a potentially important source of heterogeneity in longitudinal cognitive profiles. We examined the extent to which common age-related neuropathologies including Lewy bodies and Alzheimer's disease (AD) contribute to yearly variability in late life cognition.

Methods: Data came from 1321 community-dwelling older adults who were followed annually for up to 23 years, died and underwent brain autopsy. Cognition was assessed via a comprehensive testing battery. Uniform neuropathologic evaluations assessed burdens of Lewy bodies, AD, infarcts, TDP, hippocampal sclerosis, amyloid angiopathy, atherosclerosis, and arteriolosclerosis. Using mixed effects models, yearly variability in cognition, characterized as within-person variability of annual cognitive scores, was regressed on the nine neuropathologic indices.

Results: The average age of decedents was 90 years and 69% were female. At autopsy, about two thirds met the pathologic criteria for AD. Neocortical Lewy bodies were present in 13% of the individuals. Other neuropathologic conditions also were common. All neuropathologic indices except for microinfarcts were associated with cognitive decline. Individuals with neocortical Lewy bodies had almost twice the yearly variability in cognition compared to those without. Individuals with AD had about 70% more variability compared to those without. Yearly variability was present among persons with vascular diseases but to a lesser degree than neocortical Lewy bodies and AD.

Interpretation: Lewy body pathology is associated with pronounced variability in annual cognitive assessments but this finding is not unique to this pathology. Comparable variability is present among persons with AD pathology and to a lesser extent among persons with cerebrovascular pathologies.
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http://dx.doi.org/10.1002/acn3.50857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856601PMC
November 2019

Significance of Anti-TPO as an Early Predictive Marker in Thyroid Disease.

Autoimmune Dis 2019 28;2019:1684074. Epub 2019 Jul 28.

Vibrant Sciences LLC., San Carlos, CA, USA.

Even though most thyroid subjects are undiagnosed due to nonspecific symptoms, universal screening for thyroid disease is not recommended for the general population. In this study, our motive is to showcase the early appearance of thyroid autoantibody, anti-TPO, prior to the onset of thyroid hormone disruption; hence the addition of anti-TPO in conjunction with traditional thyroid markers TSH and FT4 would aid to reduce the long-term morbidity and associated health concerns. Here, a total of 4581 subjects were tested multiple times for TSH, FT4, anti-TPO, and anti-Tg and followed up for 2 years. We streamlined our subjects into two groups, A1 (euthyroid at first visit, but converted to subclinical/overt hypothyroidism in follow-up visits) and A2 (euthyroid at first visit, but converted to hyperthyroidism in follow-up visits). According to our results, 73% of hypothyroid subjects (from group A1) and 68.6% of hyperthyroid subjects (from group A2) had anti-TPO 252 (±33) and 277 (±151) days prior to the onset of the thyroid dysfunction, respectively. Both subclinical/overt hypothyroidism and hyperthyroidism showed a significantly higher percentage of subjects who had anti-TPO prior to the onset of thyroid dysfunction compared to the combined control group. However, there was no significant difference in the subjects who had anti-Tg earlier than the control group. Further assessment showed that only anti-TPO could be used as a standalone marker but not anti-Tg. Our results showcase that anti-TPO appear prior to the onset of thyroid hormone dysfunction; hence testing anti-TPO in conjunction with TSH would greatly aid to identify potentially risk individuals and prevent long-term morbidity.
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http://dx.doi.org/10.1155/2019/1684074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699358PMC
July 2019
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