bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data
Authors: Sommerlad Andrew , Werbeloff Nomi , Perera Gayan , Smith Tanya , Costello Harry , Mueller Christoph , Kormilitzin Andrey , Broadbent Matthew , Nevado‐Holgado Alejo , Lovestone Simon , Stewart Robert , Livingston Gill
Published: September 2021

Objectives

Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants.

Methods

Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex‐adjusted Mini‐mental state examination (MMSE) change in people with all‐cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non‐vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random‐effects meta‐analysis.

Results

We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow‐up. There was no difference in adjusted cognitive decline in people with all‐cause or non‐vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta‐analysis, we found greater mean MMSE decline in people with all‐cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses.

Conclusions

There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.
Living well with dementia: What is possible and how to promote it
Authors: Quinn Catherine , Pickett James A. , Litherland Rachael , Morris Robin G. , Martyr Anthony , Clare Linda ,   On behalf of the IDEAL Programme Team
Published: September 2021

Key points

The focus on living well with dementia encourages a more positive and empowering approach

The right support can improve the experience of living with dementia

An holistic approach to assessing the needs of people with dementia and identifying the factors that impact on their well‐being is essential

Enabling people to live better requires a broad approach that encompasses both health and social systems and the wider community
Identification of flood seasonality and drivers across Canada
Authors: Singh Jitendra , Ghosh Subimal , Simonovic Slobodan P. , Karmakar Subhankar
Published: September 2021

Floods are the most frequently occurring natural hazard in Canada. An in‐depth understanding of flood seasonality and its drivers at a national scale is essential. Here, a circular, statistics‐based approach is implemented to understand the seasonality of annual‐maximum floods (streamflow) and to identify their responsible drivers across Canada. Nearly 80% and 70% of flood events were found to occur during spring and summer in eastern and western watersheds across Canada, respectively. Flooding in the eastern and western watersheds was primarily driven by snowmelt and extreme precipitation, respectively. This observation suggests that increases in temperature have led to early spring snowmelt‐induced floods throughout eastern Canada. Our results indicate that precipitation (snowmelt) variability can exert large controls on the magnitude of flood peaks in western (eastern) watersheds in Canada. Further, the nonstationarity of flood peaks is modelled to account for impact of the dynamic behaviour of the identified flood drivers on extreme‐flood magnitude by using a cluster of 74 generalized additive models for location scale and shape models, which can capture both the linear and nonlinear characteristics of flood‐peak changes and can model its dependence on external covariates. Using nonstationary frequency analysis, we find that increasing precipitation and snowmelt magnitudes directly resulted in a significant increase in 50‐year streamflow. Our results highlight an east–west asymmetry in flood seasonality, indicating the existence of a climate signal in flood observations. The understating of flood seasonality and flood responses under the dynamic characteristics of precipitation and snowmelt extremes may facilitate the predictability of such events, which can aid in predicting and managing their impacts.
Weak numerical comparability of ISO‐7027‐compliant nephelometers. Ramifications for turbidity measurement applications
Authors: Davies‐Colley Rob , Hughes Andrew O. , Vincent Alex G. , Heubeck Stephan
Published: September 2021

Nephelometric turbidity, a measure of light scattering by particles suspended in water, is commonly used for indicating water clarity or suspended particulate matter (SPM) concentration. Different turbidity sensors have long been known to respond differently to the same suspensions. Design standards have been introduced to improve comparability of turbidity sensors, notably the ISO‐7027 standard adopted by a number of manufacturers. We compared six ISO‐7027‐compliant nephelometers in river silt, kaolinite (layer clay) and algae‐laden pond water, with rigorous tank experiments over a wide (100‐fold) concentration range. The responses of four different field‐type (in situ) and two cuvette instruments, all calibrated to the same freshly made formazin standards, were very strongly linearly correlated, but ranged about twofold in magnitude. Apparently, even sensors meeting the same design standard (ISO‐7027) cannot be relied on to output numerically similar formazin nephelometric unit (FNU) values. This weak numerical comparability highlights the futility of treating turbidity as an absolute quantity, for example in environmental standards or studies of fine SPM effects on aquatic life. Indeed, reporting of turbidity in informal units such as FNU is best avoided. Turbidity records should be converted, by site‐specific calibrations, to quantities of ultimate interest such as SPM concentration or total phosphorus. For performance monitoring of field nephelometers, we advocate routine site‐specific calibration, not to formazin, but to the light beam attenuation coefficient (beam‐c; units: m−1). Beam‐c is a proper (SI) physical quantity that can be precisely measured by beam transmissometry, as in our experiments, and is accurately convertible to visual clarity.
Changes in streamflow regimes and their responses to different soil and water conservation measures in the Loess Plateau watersheds, China
Authors: Zhang Shuyu , Zhao Guangju , Mu Xingmin , Tian Peng , Gao Peng , Sun Wenyi
Published: September 2021

Investigating the changes in streamflow regimes in response to various influencing factors contributes to our understanding of the mechanisms of hydrological processes in different watersheds and to water resource management strategies. This study examined streamflow regime changes by applying the indicators of hydrologic alteration method and eco‐flow metrics to daily runoff data (1965–2016) from the Sandu, Hulu and Dali Rivers on the Chinese Loess Plateau, and then determined their responses to terracing, afforestation and damming. The Budyko water balance equation and the double mass curve method were used to separate the impacts of climate change and human activities on the mean discharge changes. The results showed that the terraced and dammed watersheds exhibited significant decreases in annual runoff. All hydrologic metrics indicated that the highest degree of hydrologic alteration was in the Sandu River watershed (terraced), where the monthly and extreme flows reduced significantly. In contrast, the annual eco‐deficit increased significantly, indicating the highest reduction in streamflow among the three watersheds. The regulation of dams and reservoirs in the Dali River watershed has altered the flow regime, and obvious decreases in the maximum flow and slight increases in the minimum flow and baseflow indices were observed. In the Hulu River watershed (afforested), the monthly flow and extreme flows decreased slightly and were categorized as low‐degree alteration, indicating that the long‐term delayed effects of afforestation on hydrological processes. The magnitude of the eco‐flow metrics varied with the alteration of annual precipitation. Climate change contributed 67.47% to the runoff reduction in the Hulu River watershed, while human activities played predominant roles in reducing runoff in the Sandu and Dali River watersheds. The findings revealed distinct patterns and causes of streamflow regime alteration due to different conservation measures, emphasizing the need to optimize the spatial allocation of measures to control soil erosion and utilize water resources on the Loess Plateau.
The “Carousel”: a new simulation model for assessing the female pelvic examination in medical education
Authors: Sartorao Filho Carlos Izaias , Barbosa Angelica Mercia Pascon , Rudge Marilza Vieira Cunha
Published: September 2021

The authors developed a simulator device to teach and improve the comprehension and accuracy of the pelvic examination during obstetric trainee education.
Baseline lncRNA PCAT1 high expression and its longitude increment during induction therapy predict worse prognosis in multiple myeloma patients
Authors: Zhao Peng , Zhao Xiaohong
Published: September 2021

Background

Long noncoding RNA PCAT1 (lnc‐PCAT1) involves in the proliferation and drug sensitivity of multiple myeloma (MM), while its prognostic role in MM patients is still obscure. This study aimed to explore the association of lnc‐PCAT1 with MM risk, clinical characteristics, treatment response, progression‐free survival (PFS), and overall survival (OS).

Methods

A total of 83 symptomatic MM patients were enrolled in this study. Additionally, 30 healthy bone marrow donors as health controls were also recruited. Bone marrow plasma cell samples of MM patients and health donors were collected. Lnc‐PCAT1 in bone marrow plasma cells was detected by reverse transcription‐quantitative polymerase chain reaction.

Results

Lnc‐PCAT1 was increased in MM patients than in health donors (p < 0.001), and receiver operating characteristic (ROC) curve showed that lnc‐PCAT1 had excellent capability of discriminating MM patients from health donors (area under curve: 0.932, 95% confidence interval: 0.889–0.976). In MM patients, lnc‐PCAT1 was correlated with bone lesion (p = 0.024), higher β2‐MG (p = 0.005), LDH (p = 0.037), and presence of Del (17p) (p = 0.029). Lnc‐PCAT1 was also associated with poor ISS stage (p = 0.013) and R‐ISS stage (p = 0.005). Besides, lnc‐PCAT1 was reduced after treatment (p < 0.001); meanwhile, lnc‐PCAT1 before treatment was correlated with lower CR (p = 0.046) but not ORR (p = 0.185). Additionally, lnc‐PCAT1 after treatment was associated with lower CR (p = 0.003) and ORR (p = 0.010). Furthermore, baseline Inc‐PCAT1 high and Inc‐PCAT1 increase after treatment were correlated with worse PFS and OS (all p < 0.05).

Conclusion

Lnc‐PCAT1 dysregulation serves as a biomarker for diagnosis and prognosis for MM.
Long‐Acting Lipoglycopeptides Can Interfere With Vancomycin Therapeutic Drug Monitoring
Authors: Smelter Dan F. , Trisler Michael J. , McCreary Erin K. , Baker Matthew , Copeland Kenneth , Dilworth Thomas J. , Rose Warren E.
Published: September 2021

Oritavancin and dalbavancin are long‐acting lipoglycopeptides with activity against susceptible gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus. Though similar in structure to traditional glycopeptide antibiotics like vancomycin, these antibiotics have terminal half‐lives >10 days, and, as a result, there is potential for administration of vancomycin to a patient while oritavancin or dalbavancin are still appreciably present in serum. Given the structural similarities, this creates an opportunity for lab assay interference when performing therapeutic drug monitoring for vancomycin. Following higher‐than‐expected serum vancomycin concentrations in a patient who received both oritavancin and vancomycin within a short time frame, we evaluated the potential for lipoglycopeptide interference with clinical vancomycin assays. Five platforms covering 3 immunoassay technologies were used to quantify vancomycin concentrations in serum spiked with oritavancin or dalbavancin. Oritavancin generated spurious vancomycin concentrations (20%‐84% increase) in both enzyme‐multiplied immunoassay technique and a particle‐enhanced turbidimetric inhibition immunoassay. However, the improper detection of oritavancin was not consistent across all particle‐enhanced turbidimetric inhibition immunoassay platforms. Dalbavancin interference was not detected on any of the platforms tested. The interference from oritavancin may result in falsely elevated vancomycin concentrations and, subsequently, inappropriately adjusted vancomycin doses.
Influence of different calcium hydroxide removal protocols on the bond strength of epoxy resin‐based sealer in long oval root canals
Authors: Escobar Patrícia Maria , Lopes Fabiane Carneiro , Carvalho Kleber , Fretes Vicente , Hadid Gabriela Gavilán , Mazzi‐Chaves Jardel Francisco , Sousa‐Neto Manoel Damião
Published: September 2021

This study evaluated the effect of different protocols for Ca(OH)2 removal on the bond strength (BS) of epoxy resin‐based sealer in long oval root canals. Forty‐eight mandibular incisors with long oval root canals were selected by CBCT. Biomechanical preparation was performed, the samples were filled with Ca(OH)2 paste and distributed in four groups (n = 12): G‐without Ca(OH)2 paste (C); G2‐syringe/needle (SN); G3‐SN + XP‐Endo® Finisher (XPF); G4‐SN + passive ultrasonic irrigation (PUI). After 7 days, Ca(OH)2 was removed and teeth were filled using AHPlus and guttapercha. In four samples from each group, the sealer was manipulated with 0.1% rhodamine to assess sealer penetration by fluorescent laser confocal microscopy (FLCM). Samples were sectioned in slices for BS, scanning electron microscopy, and FLCM analysis. The BS data were analyzed by ANOVA and Tukey tests (α = 0.05). The lowest BS values were found for the SN group (12.89 ± 4.36) compared to C (35.55 ± 10.05), while PUI group presented intermediate values (28.57 ± 9.35) and the XPF group (31.34 ± 9.8) showed values that were sometimes similar to C group and sometimes similar to PUI group (p > .05). The analysis of the adhesive interface showed evident gaps, with the presence of residues between the dentin and the filling material for the SN group, and for C, XPF and PUI groups juxtaposed adhesive interface. FLCM images showed sealer penetration in the dentinal tubules along the entire perimeter for C, XPF, and PUI groups. Ca(OH)2 removal with XPF and PUI from long oval root canals resulted in higher bond strength values compared to SN, besides better sealer penetration on dentinal tubules and juxtaposed adhesive interface.
The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis
Authors: Ranea‐Robles Pablo , Chen Hongjie , Stauffer Brandon , Yu Chunli , Bhattacharya Dipankar , Friedman Scott L. , Puchowicz Michelle , Houten Sander M.
Published: September 2021

Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω‐oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this work, we studied an Abcd3 KO mouse model generated by CRISPR‐Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in hepatic DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid homeostasis. The Abcd3 KO mouse presents with increased hepatic long‐chain DCAs, increased urine medium‐chain DCAs, lipodystrophy, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial fatty acid β‐oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.
Deep Generative Medical Image Harmonization for Improving Cross‐Site Generalization in Deep Learning Predictors
Authors: Bashyam Vishnu M. , Doshi Jimit , Erus Guray , Srinivasan Dhivya , Abdulkadir Ahmed , Singh Ashish , Habes Mohamad , Fan Yong , Masters Colin L. , Maruff Paul , Zhuo Chuanjun , Völzke Henry , Johnson Sterling C. , Fripp Jurgen , Koutsouleris Nikolaos , Satterthwaite Theodore D. , Wolf Daniel H. , Gur Raquel E. , Gur Ruben C. , Morris John C. , Albert Marilyn S. , Grabe Hans J. , Resnick Susan M. , Bryan Nick R. , Wittfeld Katharina , Bülow Robin , Wolk David A. , Shou Haochang , Nasrallah Ilya M. , Davatzikos Christos ,   The iSTAGING and PHENOM consortia
Published: September 2021

Background

In the medical imaging domain, deep learning‐based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may benefit from increased cross‐site generalizability.

Purpose

To develop and evaluate a deep learning‐based image harmonization method to improve cross‐site generalizability of deep learning age prediction.

Study Type

Retrospective.

Population

Eight thousand eight hundred and seventy‐six subjects from six sites. Harmonization models were trained using all subjects. Age prediction models were trained using 2739 subjects from a single site and tested using the remaining 6137 subjects from various other sites.

Field Strength/Sequence

Brain imaging with magnetization prepared rapid acquisition with gradient echo or spoiled gradient echo sequences at 1.5 T and 3 T.

Assessment

StarGAN v2, was used to perform a canonical mapping from diverse datasets to a reference domain to reduce site‐based variation while preserving semantic information. Generalization performance of deep learning age prediction was evaluated using harmonized, histogram matched, and unharmonized data.

Statistical Tests

Mean absolute error (MAE) and Pearson correlation between estimated age and biological age quantified the performance of the age prediction model.

Results

Our results indicated a substantial improvement in age prediction in out‐of‐sample data, with the overall MAE improving from 15.81 (±0.21) years to 11.86 (±0.11) with histogram matching to 7.21 (±0.22) years with generative adversarial network (GAN)‐based harmonization. In the multisite case, across the 5 out‐of‐sample sites, MAE improved from 9.78 (±6.69) years to 7.74 (±3.03) years with histogram normalization to 5.32 (±4.07) years with GAN‐based harmonization.

Data Conclusion

While further research is needed, GAN‐based medical image harmonization appears to be a promising tool for improving cross‐site deep learning generalization.

Level of Evidence

4

Technical Efficacy

Stage 1
Secondary organizing pneumonia after recovery of mild COVID‐19 infection
Authors: Golbets Evgeny , Kaplan Alon , Shafat Tali , Yagel Yael , Jotkowitz Alan , Awesat Jenan , Barski Leonid
Published: September 2021

A 36‐year‐old male with diffuse large B‐cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X‐ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID‐19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID‐19. Comprehensive biochemical, radiological, and pathological evaluation including 18‐fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post‐COVID‐19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID‐19. We hope that this case may contribute to gaining more knowledge about this growing patient population.
Utilizing Plackett–Burman design and response surface analysis to optimize ultrasonic cleaning of pesticide residues from rape
Authors: Li Xiaohan , Xu Hui , Liu Fengmao , Peng Qingrong , Chen Fei , Guo Yangyang
Published: September 2021

BACKGROUND

Pesticide residues in fruits and vegetables threaten food safety. Cleaning before eating is a usual way to remove pesticide residues, so it is very important to find the most efficient cleaning conditions for public health. However, many previous cleaning studies only focused on a single variable which required a large amount of time manpower and material resources. Plackett–Burman design (PBD) and response surface methodology can avoid the earlier‐mentioned problems and have potential in studying the influence and interaction of multiple factors. In this study, the effect of five factors on the removal of triadimefon and boscalid from rape by ultrasonic washing was evaluated through PBD: pH of water, ultrasonic cleaning time, water temperature, initial residual concentration and volume of water.

RESULTS

Temperature had a significant effect on the rate of triadimefon removal while the other four factors impacted boscalid removal greatly. A higher temperature was better for the removal rate of triadimefon. Under alkaline environment, when initial residual concentration and cleaning time increased with decreasing water volume, the removal rate of boscalid increased. Furthermore, the interactions among factors were obtained. The regression coefficients of fitting equations about triadimefon and boscalid were 0.9657 and 0.9738, respectively.

CONCLUSION

Changing pH of water, cleaning time, water volume and temperature during the washing process of rape through PBD designed experiments represents a valid strategy for improving the removal rate of two pesticides residue. This study provides a reference for ultrasonic cleaning conditions by a sink dishwasher, which has a positive effect on food safety. © 2021 Society of Chemical Industry.
The Prediction of In‐Hospital Mortality in Decompensated Cirrhosis with Acute‐on‐Chronic Liver Failure
Authors: Wong Florence , Reddy K. Rajender , Tandon Puneeta , Lai Jennifer C. , Jagarlamudi Nishita , Weir Vanessa , Kok Beverley , Kalainy Sylvia , Srisengfa Yanin T. , Albhaisi Somaya , Reuter Bradley , Acharya Chathur , Shaw Jawaid , Thacker Leroy R. , Bajaj Jasmohan S.
Published: September 2021

Acute‐on‐chronic liver failure (ACLF) is a condition in cirrhosis associated with organ failure (OF) and high short‐term mortality. Both the European Association for the Study of the Liver‐Chronic Liver Failure (EASL‐CLIF) and North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) ACLF definitions have been shown to predict ACLF prognosis. The aim of this study was to compare the ability of the EASL‐CLIF versus NACSELD systems over baseline clinical and laboratory parameters in the prediction of in‐hospital mortality in admitted patients with decompensated cirrhosis. Five NACSELD centers prospectively collected data to calculate EASL‐CLIF and NACSELD‐ACLF scores for admitted patients with cirrhosis who were followed for the development of OF, hospital course, and survival. Both the number of OFs and the ACLF grade or presence were used to determine the impact of NACSELD versus EASL‐CLIF definitions of ACLF above baseline parameters on in‐hospital mortality. A total of 1031 patients with decompensated cirrhosis (age, 57 ± 11 years; male, 66%; Child‐Pugh‐Turcotte score, 10 ± 2; Model for End‐Stage Liver Disease [MELD] score, 20 ± 8) were enrolled. Renal failure prevalence (28% versus 9%, P < 0.001) was more common using the EASL‐CLIF versus NACSELD definition, but the prevalence rates for brain, circulatory, and respiratory failures were similar. Baseline parameters including age, white cell count on admission, and MELD score reasonably predicted in‐hospital mortality (area under the curve, 0.76). The addition of number of OFs according to either system did not improve the predictive power of the baseline parameters for in‐hospital mortality, but the presence of NACSELD‐ACLF did. However, neither system was better than baseline parameters in the prediction of 30‐ or 90‐day outcomes. The presence of NACSELD‐ACLF is equally effective as the EASL‐CLIF ACLF grade, and better than baseline parameters in the prediction of in‐hospital mortality in patients with cirrhosis, but not superior in the prediction of longer‐term 30‐ or 90‐day outcomes.
Seroconversion After Coronavirus Disease 2019 Vaccination in Patients Awaiting Liver Transplantation: Fact or Fancy?
Authors: Calleri Alberto , Saracco Margherita , Pittaluga Fabrizia , Cavallo Rossana , Romagnoli Renato , Martini Silvia
Published: September 2021

Chronic liver disease increased the risk of severe coronavirus disease 2019 (COVID‐19). Trials to assess efficacy/safety of COVID‐19 vaccines in liver disease are underway. We evaluated the humoral immune response and safety of anti–COVID‐19 vaccination among patients waiting liver transplantation (LT). We enrolled all pre‐LT adults who completed anti‐COVID‐19 vaccination between January 2021‐August 2021 as study group. Patients with histories of COVID‐19 received 1 vaccine dose, and all others received 2 doses. Patients were tested for COVID‐19 immunoglobulin G (IgG) within 1 and 2 months after vaccination. Safety was evaluated with telephone interviews/outpatient visits. A control group of 30 healthcare workers who underwent vaccination in January 2021 and tested for IgG after 4 months was included. In the 89 pre‐LT patients, at T1 (23 days after vaccination), seroconversion rate was 94.4%, and median IgG value was 1980 binding antibody units/mL (interquartile range 646‐2080), and at T2 (68 days after vaccination) was 92.0%, with IgG value of 1450 (577‐2080); (T1 versus T2, P = 0.38). In the 10/89 patients who received 1 vaccine dose, the median IgG value was 274 (68‐548) before vaccine (T0), 2080 (1165‐2080) at T1, and 2030 (964‐2080) at T2 (T0 versus T1, P = 0.03; T1 versus T2, P = 0.99). All controls tested positive at 4 months after vaccination, with a median value of 847 (509‐1165; P < 0.001 versus T1 and P = 0.04 versus T2 in the study group). No serious adverse event was reported in both groups. Our data from 89 pre‐LT patients suggest a high rate of immunization (94.4%) after a median time of 23 days from safe COVID‐19 vaccine. None of the patients developed COVID‐19.
Evaluating Outcomes Related to Donor and Recipient Metabolic Environment: Macrosteatotic Allografts and Nonalcoholic Steatohepatitis
Authors: Altshuler Peter J. , Dang Hien , Frank Adam M. , Shah Ashesh P. , Glorioso Jaime , Zhan Tingting , Rios Diaz Arturo , Shaheen Osama , Ramirez Carlo B. , Maley Warren R. , Bodzin Adam S.
Published: September 2021

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non‐NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%‐29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score–matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long‐term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high‐risk macrosteatotic allografts to negatively affect outcomes.
Molecular Features of Parkinson's Disease in Patient‐Derived Midbrain Dopaminergic Neurons
Authors: Ren Yong , Jiang Houbo , Pu Jiali , Li Li , Wu Jianbo , Yan Yaping , Zhao Guohua , Guttuso Thomas J. , Zhang Baorong , Feng Jian
Published: September 2021

Background

Despite intense efforts to develop an objective diagnostic test for Parkinson's disease, there is still no consensus on biomarkers that can accurately diagnose the disease.

Objective

Identification of biomarkers for idiopathic Parkinson's disease (PD) may enable accurate diagnosis of the disease. We tried to find molecular and cellular differences in dopaminergic (DA) neurons derived from healthy subjects and idiopathic PD patients with or without rest tremor at onset.

Methods

We measured the expression of genes controlling dopamine synthesis, sequestration, and catabolism as well as the levels of corresponding metabolites and reactive oxygen species in midbrain DA neurons differentiated from induced pluripotent stem cells (iPSCs) of healthy subjects and PD patients with or without rest tremor.

Results

Significant differences in DA‐related gene expression, metabolites, and oxidative stress were found between midbrain DA neurons derived from healthy subjects and patients with PD. DA neurons derived from PD patients with or without rest tremor at onset exhibited significant differences in the levels of some of these transcripts, metabolites, and oxidative stress.

Conclusion

The unique combination of these quantifiable molecular and cellular traits in iPSC‐derived midbrain DA neurons can distinguish healthy subjects from idiopathic PD patients and segregate PD patients with or without rest tremor at onset. The strategy may be used to develop an objective diagnostic test for PD.
An adaptive eigenfunction basis strategy to reduce design dimension in topology optimization
Authors: Sanders Clay , Bonnet Marc , Aquino Wilkins
Published: September 2021

The concept of adaptive eigenspace basis (AEB) has recently proved effective for solving medium imaging problems. In this article, we present an AEB strategy for design parameterization in topology optimization (TO) problems. We seek the density design field as a linear combination of eigenfunctions, computed for an elliptic operator defined over the structural domain, and solve for the associated eigenfunction coefficients. Restriction to this truncated eigenspace drastically reduces the design dimension and imposes implicit regularization upon the solution, removing the need for auxiliary filtering operations and design‐variable bound constraints. We furthermore develop the basis adaptation scheme inherent in the AEB, which iteratively recomputes the eigenfunction basis to conform to the evolving density field, enabling further dimension reduction and acceleration of the optimization process. The known aptitude of the adapted eigenfunctions to approximate piecewise constant fields is especially useful for TO as relevant design subspaces can be given low‐dimensional representations. We propose criteria for the selection of the basis dimension and demonstrate the use of basis function selection as means for length scale control. We compare performance of the AEB against conventional TO implementations in problems for static linear‐elasticity, showing comparable structural solutions, computational cost benefits, and consistent design dimension reduction.
Simultaneous topology and machine orientation optimization for multiaxis machining
Authors: Gasick Joshua , Qian Xiaoping
Published: September 2021

We present a density‐based topology optimization approach for multi‐axis machining where optimized designs can be machined by one or multiple axes. In our approach, density and machine axes can be simultaneously optimized. The fulcrum of our multi‐axis machinability based topology optimization approach is a formulation that characterizes machinability through inaccessible volume. This formulation is differentiable to both density and machining axes, and thus is amenable to gradient‐based optimization. We use an advection‐diffusion equation to facilitate the evaluation of inaccessible volume. Numerical examples on 2D and 3D linear elasticity problems are presented as a demonstration of the efficacy of this approach.
Untangling the complexities of micropapillary cancer†
Authors: Charles Campbell Frederick
Published: September 2021

Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology, Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three‐dimensional (3D) patient‐derived CRC tissue‐originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho–ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho–ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Reductant‐Free Synthesis of MnO2 Nanosheet‐Decorated Hybrid Nanoplatform for Magnetic Resonance Imaging‐Monitored Tumor Microenvironment‐Responsive Chemodynamic Therapy and Near‐Infrared‐Mediated Photodynamic Therapy
Authors: Yu Qili , Wei Zhenyang , Qin Xing , Qin Limei , Li Yongsheng , Shi Jianlin , Niu Dechao
Published: September 2021

Recently, the therapeutic efficacy of reactive oxygen species (ROS)‐mediated photodynamic therapy (PDT) involving laser irradiation or chemodynamic therapy (CDT) has been limited by low laser penetration depth and insufficient O2 supply in PDT and modest ROS production in CDT. To address these, a facile “reductant‐free reduction” strategy is developed to construct a smart tumor microenvironment (TME)/near‐infrared dual‐responsive hybrid nanoplatform, consisting of up‐conversion nanoparticles (UCNPs) and photosensitizer chlorin e6 (Ce6) in the micellar core and MnO2 nanosheets on the organosilica shell, via the self‐assembly of block copolymer and followed by a sol−gel process. The conversion capability of UCNPs improves laser penetration of visible light for initiating the photodynamic process. The degradation of MnO2 nanosheets in the TME rich in acid H2O2 achieves continuous O2 supply for enhanced PDT. Following degradation of MnO2, the endogenous antioxidant glutathione (GSH) is significantly depleted and hydroxyl radicals (•OH) are simultaneously produced though CDT, together inducing massive production of ROS. More importantly, Mn2+ released from MnO2 decomposition serves as a T1‐weighted MR contrast agent, providing an easy monitor for the CDT process. This hybrid MnO2/Ce6@UPOMs nanoplatform could be used for MRI‐monitored tumor therapy of TME‐responsive CDT and NIR‐mediated PDT.
pH‐Buffer Contained Electrolyte for Self‐Adjusted Cathode‐Free Zn–MnO2 Batteries with Coexistence of Dual Mechanisms
Authors: Liu Zhexuan , Yang Yongqiang , Liang Shuquan , Lu Bingan , Zhou Jiang
Published: September 2021

Aqueous Zn–MnO2 batteries have received much attentions for large‐scale applications because of high safety and low cost. However, the energy storage mechanisms of Zn–MnO2 system are still in dispute. Herein, a cathode‐free Zn–MnO2 battery is provided with the coexistence of dual mechanisms in mild acidic environment, in which the decisive guiding effect of the pH value in electrolyte on the mechanism is deeply investigated. On this basis, acetic acid (HAc) is used as a buffering additive to effectively suppress the “fluctuation” phenomenon during the operation, hence achieving the “self‐adjust” mechanism. The assembled soft package battery possesses a long lifetime of 2000 cycles with the Coulombic efficiency of 99.6%, improved high‐loading performance and rate capability. A new idea is provided for the exploration of energy storage mechanism of Zn–MnO2 battery as well as a guidance on the optimization strategies especially the battery construction.
Effect of topical antimicrobial therapy and household cleaning on meticillin‐resistant Staphylococcus pseudintermedius carriage in dogs
Authors: Frosini Siân‐Marie , Bond Ross , King Ruth , Feudi Claudia , Schwarz Stefan , Loeffler Anette
Published: September 2021

Background: Meticillin‐resistant Staphylococcus pseudintermedius (MRSP) is a multidrug‐resistant canine pathogen with a low zoonotic potential. This study investigated MRSP carriage and clearance through topical antimicrobial therapy and household cleaning in dogs recovered from MRSP infection.

Methods: Dogs were swabbed for MRSP carriage; household contamination was assessed using contact plates. Carrier dogs were allocated randomly to receive topical fusidic acid and chlorhexidine/miconazole treatment combined with owners implementing a household hygiene protocol (H&T) or implementation of hygiene alone (H) over three weeks. Carriage‐negative dogs were monitored monthly. The relatedness of isolates over time was investigated by pulsed‐field gel electrophoresis (PFGE).

Results: At inclusion, MRSP carriage was confirmed in 31/46 (67.4%) index dogs and 16/24 (66.7%) contact dogs, and contamination was found in 18/40 (45%) environments. In dogs completing all cycles, interventions cleared carriage in 5/9 (55.6%) dogs in group H&T and 2/6 (33.3%) in group H. Environmental contamination was infrequent but associated with carrier dogs (p = 0.047). Monthly monitoring of initially negative dogs showed intermittent carriage in 9/14 dogs. PFGE‐concordance was found among all 34 MRSP isolated from eight index dogs over time.

Conclusion: MRSP carriage was common in dogs after recovery from infection. Topical antimicrobial therapy temporarily eliminated carriage but recurrence was frequent. Management efforts must include the prevention of recurrent infections and hygiene.
Study on the impact of the Beijing–Shanghai high-speed railway on regional economic equity based on economic performance
Authors: Yang Heng , Tong Qiong , Zhao Pan
Published: September 2021

According to the panel data of stations along the Beijing–Shanghai high-speed railway (BSHR) from 2008 to 2018, the influence of BSHR on regional economy of cities along the line is analyzed, and the influence of the opening of the BSHR on regional economic equity of cities along the line, through constructing the difference-in-differences model. The research result shows that the opening of the BSHR greatly promotes the growth of the GDP per capita of the site cities along the line and the optimal allocation of resources, such as labor, information and technology, and accelerates the two-way flow of factors of production between big cities and small and medium-sized cities at stations along the high-speed railway, makes high-quality resources from small and medium-sized cities flow to big cities along the line, while some backward resources from big cities gradually tilt toward small- and medium-sized cities along the line. In short, the opening of BSHR promotes the economic growth of the cities along the line, shortens the economic gap between the cities, is conducive to realizing regional economic equity.
Research progress on selective laser melting (SLM) of bulk metallic glasses (BMGs): a review
Authors: Zhang Peilei , Tan Jie , Tian Yingtao , Yan Hua , Yu Zhishui
Published: September 2021

Bulk metallic glasses (BMGs) are a subject of interest due to their superior specific properties such as low coefficient of friction, high strength, large ductility in bending, high elastic modulus, high microhardness, and high resistance to corrosion, oxidation, wear, and so on. However, BMGs are difficult to apply in industry due to their difficulty in manufacturing and secondary operation. In the past few decades, many efforts have been carried out to overcome the defects in the manufacturing of BMGs. It is difficult to fabricate complex structures with the whole amorphous alloy owing to the limit of crystallization and critical cooling rate. Additive manufacturing (AM), such as selective laser melting (SLM), can obtain relatively high cooling rates during the “layer-by-layer” process, which makes it possible to surpass the dimensional limitation of metallic glass. In the SLM process, the high-speed cooling of molten pool and the avoidance of secondary processing are very beneficial to the production and application of amorphous alloys. In this paper, based on the research of SLM additive manufacturing BMGs in recent years, the factors affecting crystallization and forming ability are discussed from many aspects according to different material systems. The status and challenges of SLM manufacturing BMGs including Fe-based, Zr-based, Al-based, and some composite-based BMGs will be presented. Mechanical properties and physicochemical properties were introduced. This review aims to introduce the latest developments in SLM additive manufacturing BMGs, especially on the development of process parameters, structure formation, simulation calculation, fracture mechanism, and crystallization behavior. With the traditional fabricating methods, BMGs were mainly used as a structure material. It will provide another alternative to use BMGs as a functional material by introducing SLM technology in amorphous preparation with complex geometry. This review summarizes the technical difficulty and application prospects of BMGs preparation by SLM and discusses the challenges and unresolved problems. This review identifies key issues that need to be addressed in this important field in the future. These problems are related to the application of BMGs as high-strength structural materials and new functional materials in the future.
Correction to: Determination of organically bound fluorine sum parameters in river water samples—comparison of combustion ion chromatography (CIC) and high resolution-continuum source-graphite furnace molecular absorption spectrometry (HR-CS-GFMAS)
Authors: Gehrenkemper Lennart , Simon Fabian , Roesch Philipp , Fischer Emily , von der Au Marcus , Pfeifer Jens , Cossmer Antje , Wittwer Philipp , Vogel Christian , Simon Franz-Georg , Meermann Björn
Published: September 2021

A Correction to this paper has been published: 10.1007/s00216-021-03675-z
Effect of lacto-fermentation and freeze-drying on the quality of beetroot evaluated using machine vision and sensory analysis
Authors: Ropelewska Ewa , Wrzodak Anna , Sabanci Kadir , Aslan Muhammet Fatih
Published: September 2021

This study was aimed at evaluating the effect of freeze-drying and lacto-fermentation on the texture parameters of images and sensory attributes of beetroots. The samples were imaged using a flatbed scanner, and textures from images converted to color channels L, a, b, R, G, B, X, Y, Z were computed. The discrimination of raw and processed beetroots was performed using models based on textures selected for each color channel. The sensory quality of processed samples was determined using the attributes related to smell, color, texture and taste. The highest discrimination accuracy of 97.25% was obtained for the model built for color channel b. The accuracies for other channels were equal to 96.25% for channel a, 95.25% for channel R, 95% for channel Y, 94.75% for channel B, 94.5% for channel X, 94% for channel L, 92.5% for channel G, 88.25% for channel Z. In the case of some models, the raw and lacto-fermented beetroots were discriminated with 100% correctness. The freeze-dried and freeze-dried lacto-fermented samples were also the most similar in terms of sensory attributes, such as off-odor, attractiveness color, beetroot color, crunchiness, hardness, bitter taste, overall quality. The results indicated that the image parameters and sensory attributes may be related.
Correction to: Post‐traumatic Splenic Injury Outcomes for Nonoperative and Operative Management: A Systematic Review
Authors: Gill Sabrina , Hoff John , Mila Ashley , Sanchez Carol , McKenney Mark , Elkbuli Adel
Published: September 2021

Sabrina Gill's, John Hoff's and Ashley Mila's affiliation is correct as reflected here.
Increased β-adrenergic stimulation augments vascular smooth muscle cell calcification via PKA/CREB signalling
Authors: Moser Barbara , Poetsch Florian , Estepa Misael , Luong Trang T. D. , Pieske Burkert , Lang Florian , Alesutan Ioana , Voelkl Jakob
Published: September 2021

In chronic kidney disease (CKD), hyperphosphatemia promotes medial vascular calcification, a process augmented by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). VSMC function is regulated by sympathetic innervation, and these cells express α- and β-adrenergic receptors. The present study explored the effects of β2-adrenergic stimulation by isoproterenol on VSMC calcification. Experiments were performed in primary human aortic VSMCs treated with isoproterenol during control or high phosphate conditions. As a result, isoproterenol dose dependently up-regulated the expression of osteogenic markers core-binding factor α-1 (CBFA1) and tissue-nonspecific alkaline phosphatase (ALPL) in VSMCs. Furthermore, prolonged isoproterenol exposure augmented phosphate-induced calcification of VSMCs. Isoproterenol increased the activation of PKA and CREB, while knockdown of the PKA catalytic subunit α (PRKACA) or of CREB1 genes was able to suppress the pro-calcific effects of isoproterenol in VSMCs. β2-adrenergic receptor silencing or inhibition with the selective antagonist ICI 118,551 blocked isoproterenol-induced osteogenic signalling in VSMCs. The present observations imply a pro-calcific effect of β2-adrenergic overstimulation in VSMCs, which is mediated, at least partly, by PKA/CREB signalling. These observations may support a link between sympathetic overactivity in CKD and vascular calcification.