bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Contrast Agent Dosage on Contrast-Enhanced T2 Fluid-Attenuated Inversion Recovery: An In Vitro and In Vivo Study
Authors: Rui Wenting , Jin Teng , Zhang Hua , Wang Jing , Ren Yan , Wu Shiman , Bai Jing , Zhang Junhai , Yao Zhenwei
Published: September 2020

Objective

This study aimed to ascertain the minimum gadolinium dosage on contrast-enhanced (CE) T2 fluid-attenuated inversion recovery (FLAIR) at appropriate imaging time.

Methods

Different dosages of gadodiamide were imaged with a 3.0-T magnetic resonance scanner for T2-FLAIR and T1WI. Twenty glioma-induced rat models were randomly assigned into 4 groups (1/2, 1/4, 1/6, 1/8 of routine dosage) and imaged for T2-FLAIR and T1WI preinjection and postinjection of gadodiamide. Contrast-enhanced T2-FLAIR was acquired for 8 repetitions postinjection. Enhancement effects were assessed by calculating contrast-noise ratio and contrast ratio using Kruskal-Wallis and Mann-Whitney rank sum test.

Results

The in vitro experiment showed that gadodiamide at 1/4 of the T1WI dosage presented the best contrast on CE-T2-FLAIR. For in vivo study, the best enhancement effect on CE-T2-FLAIR was achieved at 1/2 of the routine dosage at 8 to 12 minutes of delayed scanning. Compared with CE-T1WI at routine dosage, CE-T2-FLAIR at 1/2 gadodiamide dosage presented similar enhancement effects with no statistical difference (P = 0.244 and 0.090 for contrast-noise ratio and contrast ratio, respectively).

Conclusions

Contrast-enhanced T2-FLAIR imaging with half of T1WI routine gadodiamide dosage can produce similar enhancement effects to CE-T1WI when characterizing brain gliomas. The cut-down of contrast agent dosage may help reduce gadolinium accumulation in certain tissues.
Texture Analysis of Hepatocellular Carcinoma on Magnetic Resonance Imaging: Assessment for Performance in Predicting Histopathologic Grade
Authors: Choi Jeong Min , Yu Jeong-Sik , Cho Eun-Suk , Kim Joo Hee , Chung Jae-Joon
Published: September 2020

Objective

The aim of the study was to evaluate the performance of texture analysis for discriminating the histopathological grade of hepatocellular carcinoma (HCC) on magnetic resonance imaging.

Methods

Preoperative magnetic resonance imaging data from 101 patients with HCC, including T2-weighted imaging, arterial phase, and apparent diffusion coefficient mapping, were analyzed using texture analysis software (TexRAD). Differences among the histological groups were analyzed using the Mann-Whitney U test. The performance of texture features was evaluated using receiver operating characteristic analysis.

Results

Entropy was the most significantly relevant texture feature for distinguishing each histological grade group of HCC (P < 0.05). In ROC analysis, entropy with spatial scale filter 3 (area under curve the receiver operating characteristic curve [AUC], 0.778), mean with coarse filter (spatial scale filter 5; AUC, 0.670), and skewness without filtration (AUC, 0.760) had the highest AUC value on T2-weighted imaging, arterial phase, and apparent diffusion coefficient maps, respectively.

Conclusions

Magnetic resonance imaging texture analysis demonstrated potential for predicting the histopathological grade of HCCs.
Fat-Water Swaps in Iterative Decomposition of Water and Fat With Echo Asymmetry and Least-Squares Estimation Magnetic Resonance Imaging for Postinstrumentation Spine
Authors: Chiang I-Chan , Lu Chia-Hsin , Chung Wei-Shiuan , Huang Yu-Fang , Hsieh Tsyh-Jyi
Published: September 2020

Objective

To determine the frequencies of fat-water swaps in iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-only images of the postinstrumentation spine and discuss the efficiency of in-phase imaging in improving visibility of the thecal sac.

Materials and Methods

A total of 276 patients (167 women; mean age, 62.3 years; range, 23–89 years) with metallic devices on the lumbar spine who received complete routine 1.5 T MR imaging, including axial and sagittal images of T1-weighted, T2-weighted, and T2-weighted IDEAL sequences, were included. The exclusion criteria were significant motion artifacts and severe metallic artifacts in any one of the sequences. The images were reviewed by two radiologists to identify fat-water swaps that were divided into 3 groups: extraspinal swaps, intraspinal swaps in sagittal images, and intraspinal swaps in axial images. The qualitative evaluations for the spinal canal in axial images were performed by rating on a five-point scale. Side-by-side comparisons of T2-weighted images and IDEAL in-phase images were also performed.

Results

In patient-based data of 276 patients, extraspinal fat-water swaps were noted in 10 patients (3.6%) and intraspinal swaps were noted in 160 patients (58.0%). The intraspinal swaps had a higher incidence in the patients with more levels of metallic devices with screws and the trend was not noted in the extraspinal swaps. A total of 928 axial levels were evaluated in the level-based data of axial images. T1-weighted, T2-weighted, and IDEAL in-phase images had significantly better imaging quality than the IDEAL water-only images (3.9 ± 0.4, 3.9 ± 0.3, 3.8 ± 0.4 vs 3.0 ± 1.3, allP< 0.001). Compared with T2-weighted images, most of the IDEAL in-phase images (reader 1, 90.9%; reader 2, 86.7%) present similar quality.

Conclusion

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation sequence can provide good fat suppression in most spine MRI with metallic devices but the loss of cerebrospinal fluid signal intensities due to fat-water swaps are noted in more than half of postinstrumentation spine. Routine reconstruction of in-phase images is recommended to improve evaluation of the thecal sac by avoiding pitfall caused by fat-water swaps.
The University of Pennsylvania Medical School Commencement of 1889
Authors: Kaiser Larry R. , Morris Jon B.
Published: September 2020

Academic commencements ceremonies usually do not result in memorable occasions and once ended usually are forgotten. Not so for the University of Pennsylvania's School of Medicine commencement on May 1,1889, which was marked by an address by William Osler, the retirement of the renowned Professor of Surgery, D. Hayes Agnew, and the presentation to the University of Thomas Eakins’ remarkable masterpiece, “The Agnew Clinic.” Osler had been on the faculty of the University for 5 years and in his keynote address, Aequanimitas, he laid out 2 elements, imperturbability and equanimity, that he stated would “make or mar” the lives of the students he was addressing. His words and message that day have continued to resonate for medical students and many others up to the present day. Osler ended his address on a more somber note, seemingly surprising the assembled, by announcing his imminent departure from the University. He would soon be one of the 4 founders of the Johns Hopkins Hospital along with fellow Penn faculty member, Howard Kelly. Osler was not the only one on the verge of leaving as this commencement also marked the end of the career of D. Hayes Agnew. To honor him on this occasion of his retirement the 3 classes of medical students had commissioned Eakins to paint a portrait of their revered professor, which was presented on this commencement day and accepted by Trustee Dr S. Weir Mitchell on behalf of the University. The day was indeed one to be remembered.
Combined Vascular Resection for Locally Advanced Perihilar Cholangiocarcinoma
Authors: Mizuno Takashi , Ebata Tomoki , Yokoyama Yukihiro , Igami Tsuyoshi , Yamaguchi Junpei , Onoe Shunsuke , Watanabe Nobuyuki , Kamei Yuzuru , Nagino Masato
Published: September 2020

Objective:

To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC).

Summary of Background Data:

Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated.

Methods:

Patients diagnosed with PHC during 2001–2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups.

Results:

Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P
= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P
= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517).

Conclusion:

VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.
A Preconditioning Strategy to Augment Retention and Engraftment Rate of Donor Cells During Hepatocyte Transplantation
Authors: Hsu Yu-Chen , Yu I-Shing , Tsai Yu-Fei , Wu Yao-Ming , Chen You-Tzung , Sheu Jin-Chuan , Lin Shu-Wha
Published: September 2020

Background.

Hepatocyte transplantation has been extensively investigated as an alternative to orthotopic liver transplantation. However, its application in routine clinical practice has been restricted because of low initial engraftment and subsequent repopulation.

Methods.

Using mice as a model, we have developed a minimally invasive and nontoxic preconditioning strategy based on preadministration of antibodies against hepsin to increase donor hepatocyte retention and engraftment rate.

Results.

Liver sinusoid diameters decreased significantly with antihepsin pretreatment, and graft cell numbers increased nearly 2-fold in the recipients’ liver parenchyma for 20 days after hepatocyte transplantation. Postoperative complications such as hepatic ischemia injury or apparent immune cell accumulation were not observed in recipients. In a hemophilia B mouse model, antihepsin preconditioning enhanced the expression and clotting activity of coagulation factor IX (FIX) to nearly 2-fold that of immunoglobulin G–treated controls and maintained higher plasma FIX clotting activity relative to the prophylactic range for 50 days after hepatocyte transplantation. Antihepsin pretreatment combined with adeno-associated virus−transduced donor hepatocytes expressing human FIX-Triple, a hyperfunctional FIX variant, resulted in plasma FIX levels similar to those associated with mild hemophilia, which protected hemophilia B mice from major bleeding episodes for 50 days after transplantation. Furthermore, antihepsin pretreatment and repeated transplantation resulted in extending the therapeutic period by 30 days relative to the immunoglobulin G control.

Conclusions.

Thus, this antihepsin strategy improved the therapeutic effect of hepatocyte transplantation in mice with tremendous safety and minimal invasion. Taken together, we suggest that preconditioning with antihepsin may have clinical applications for liver cell therapy.
A Report of 85 Cases of COVID-19 and Abdominal Transplantation From a Single Center: What Are the Associated Factors With Death Among Organ Transplantation Patients
Authors: Ali Malekhosseini Seyed , Nikoupour Hamed , Gholami Siavash , Shamsaeefar Alireza , Arasteh Peyman , Kazemi Kourosh , Dehghani Masood , Eghlimi Hesameddin , Raeisi Shahraki Hadi , Roozbeh Jamshid , Rezaianzadeh Abbas , Nikeghbalian Saman
Published: September 2020

Background.

In this study, we report the epidemiology of COVID-19 among recipients of organ transplantation and evaluate associated factors with death.

Methods.

We screened 6969 patients who had organ transplantations in our center for COVID-19. Specific data on presentation, clinical course, treatment, and prognosis were acquired.

Results.

We found 85 patients (66 liver, 16 kidney, 2 kidney-pancreas, and 1 liver-kidney recipient) who acquired COVID-19. Most common symptoms included fever (48.2%), cough (41.2%), myalgia (41.2%), and fatigue (40%). Dyspnea developed in 33% of patients. Overall, one-third of patients had an oxygen saturation of below 90% on admission. Patients were hospitalized for a median (interquartile range) of 9 (5, 13.7) days and had a 33.9% intensive care unit admission rate. Overall, 17 patients (20%) died, which included 31.3% of patients with kidney transplantations and 18.2% of patients with liver transplantations. All 4 pediatric patients in our series died. In our univariate analysis among adults, rates of leukopenia (38.4% versus 13.2%;P = 0.04), low albumin levels (53.8% versus 10.2%;P = 0.001), and shorter duration between transplantation and COVID-19 (P = 0.02), were higher among patients who died. In our least absolute shrinkage and selection operator regression model, low albumin levels (OR, 4.48; 95% confidence interval, 1.16-17.27) were associated with higher risk of death.

Conclusions.

This is the largest single-center report on abdominal transplantations and COVID-19. Liver and kidney transplant recipients have an increased risk of mortality compared with the general population due to COVID-19. More specifically, pediatric patients and those with low albumin levels are at higher risks of death due COVID-19.
Neuroimaging of EEG Rhythms at Resting State in Normal Elderly Adults: A Standard Low-Resolution Electromagnetic Tomography Study
Authors: Lu Guilin , Hou Yuxin , Chen Yu , Guo Feng
Published: September 2020

Purpose:

Brain source mechanisms of the cortical EEG brainwave at the resting state in the elderly during normal aging are rarely known. To solve the problem, we use a standard low-resolution electromagnetic tomography to explore the brain source mechanisms on the effects of healthy aging on brain function at the resting state.

Methods:

Eye-closed EEG signals at resting state were sampled in 13 normal elderly adults and 17 normal young adults. The EEG rhythms by frequency band, delta, theta, alpha 1, alpha 2, beta 1, and beta 2 were of interest for this analysis. Brain sources of these rhythms were estimated by standard low-resolution electromagnetic tomography.

Results:

Statistical results demonstrated that central, parietal, occipital, and temporal alpha 1 and theta brain sources presented the pattern normal young adults > normal elderly adults (P < 0.05), whereas the global beta 1 and beta 2 brain sources presented the pattern normal elderly adults > normal young adults (P < 0.05). Moreover, the same is true that amplitude of central, parietal, occipital, and temporal alpha 2 brain sources were lower in normal elderly adults compared with those in normal young adults (P < 0.05).

Conclusions:

These results imply that normal aging is linked to cortical neural desynchronization of alpha and delta rhythms and synchronization of beta rhythm in central, parietal, and frontal cortices at resting state.
Expanded roles of pyruvate-sensing PdhR in transcription regulation of the Escherichia coli K-12 genome: fatty acid catabolism and cell motility
Authors: Anzai Takumi , Imamura Sousuke , Ishihama Akira , Shimada Tomohiro
Published: September 2020

The transcription factor PdhR has been recognized as the master regulator of the pyruvate catabolism pathway in

Escherichia coli

, including both NAD-linked oxidative decarboxylation of pyruvate to acetyl-CoA by PDHc (pyruvate dehydrogenase complex) and respiratory electron transport of NADH to oxygen by Ndh-CyoABCD enzymes. To identify the whole set of regulatory targets under the control of pyruvate-sensing PdhR, we performed genomic SELEX (gSELEX) screening in vitro. A total of 35 PdhR-binding sites were identified along the

E. coli

K-12 genome, including previously identified targets. Possible involvement of PdhR in regulation of the newly identified target genes was analysed in detail by gel shift assay, RT-qPCR and Northern blot analysis. The results indicated the participation of PdhR in positive regulation of fatty acid degradation genes and negative regulation of cell mobility genes. In fact, GC analysis indicated an increase in free fatty acids in the mutant lacking PdhR. We propose that PdhR is a bifunctional global regulator for control of a total of 16–23 targets, including not only the genes involved in central carbon metabolism but also some genes for the surrounding pyruvate-sensing cellular pathways such as fatty acid degradation and flagella formation. The activity of PdhR is controlled by pyruvate, the key node between a wide variety of metabolic pathways, including generation of metabolic energy and cell building blocks.
Diagnosis of SARS-CoV-2 infection with LamPORE, a high-throughput platform combining loop-mediated isothermal amplification and nanopore sequencing
Authors: Peto Leon , Rodger Gillian , Carter Daniel P , Osman Karen L , Yavuz Mehmet , Johnson Katie , Raza Mohammad , Parker Matthew D , Wyles Matthew D , Andersson Monique , Justice Anita , Vaughan Alison , Hoosdally Sarah , Stoesser Nicole , Matthews Philippa C , Eyre David W , Peto Timothy EA , Carroll Miles W , de Silva Thushan I , Crook Derrick W , Evans Cariad M , Pullan Steven T
Published: September 2020

LamPORE is a novel diagnostic platform for the detection of SARS-CoV-2 RNA that combines loop-mediated isothermal amplification with nanopore sequencing, which could potentially be used to analyse thousands of samples per day on a single instrument. We evaluated the performance of LamPORE against RT-PCR using RNA extracted from spiked respiratory samples and from stored nose and throat swabs collected at two UK hospitals. The limit of detection of LamPORE was 7-10 genome copies/µl of extracted RNA. This is above the limit achievable by RT-PCR but was not associated with a significant reduction of sensitivity in clinical samples. Positive clinical specimens came mostly from patients with acute symptomatic infection, and among these LamPORE had a diagnostic sensitivity of 99.1% (226/228 [95% CI 96.9–99.9%]). Among negative clinical specimens, including 153 with other respiratory pathogens detected, LamPORE had a diagnostic specificity of 99.6% (278/279 [98.0–100.0%]). Overall, 1.4% (7/514 [0.5–2.9]) of samples produced an indeterminate result on first testing, and repeat LamPORE testing on the same RNA extract had a reproducibility of 96.8% (478/494 [94.8–98.1]). This indicates that LamPORE has a similar performance to RT-PCR for the diagnosis of SARS-CoV-2 infection in symptomatic patients, and offers a promising approach to high-throughput testing.
FeverIQ - A Privacy-Preserving COVID-19 Symptom Tracker with 3.6 Million Reports
Authors: Ranjan Ankit , Li Serena , Chen Boyuan , Jagadeesh Karthik A. , Chiu Alan , Liphardt Jan
Published: September 2020

Population-scale COVID-19 management benefits from timely and honest information from billions of people. Here, we provide a first report on the FeverIQ symptom tracker, a global effort to collect symptom and test data which has received more than 3.6 million submissions. Unlike other trackers, FeverIQ uses secure multiparty computation (SMC) to cryptographically guarantee user privacy while providing insights to scientists and public health efforts. We performed basic integrity checks of the FeverIQ dataset, such as by comparing it to other publicly released data. We then trained a linear classifier on diagnosis scores which were computed securely, without unprotected symptom data ever leaving a user’s phone or computer. FeverIQ is currently the world’s largest application of SMC in a health context, demonstrating the practicality of privacy-preserving analytics for population-scale digital health interventions.
Iterative Development of a Mobile Phone Application to Support Community Health Volunteers during Cervical Cancer Screening in Western Kenya
Authors: Stocks Jacob , Choi Yujung , Saduma Ibrahim , Huchko Megan
Published: September 2020

Background

To achieve the World Health Organization targets for cervical cancer elimination, low- and middle income countries must develop innovative strategies to provide human papillomavirus (HPV) -based screening at a population level. Mobile health may help fill gaps in electronic specimen tracking and patient education. We sought to develop a mobile health application (“mSaada”) to support HPV-based screening in partnership with community health volunteers and program planners in western Kenya.

Methods

A team of student programmers developed a prototype to meet previously identified gaps in screening patient education, protocol support, data capture and specimen tracking. The protoype was iteratively developed through three waves of in-person working sessions with quantitative and qualitative feedback, with planned improvements in mSaada functionality after each wave of in-person data collection. Results: Twelve Community Health Volunteers (CHVs) and clinicians took part in the in-person sessions. Participants found mSaada useful and easy to use. Key feedback was used to alter the appearance of the mainframes, add translation in additional local languages and change potentially embarrassing figures. Participants also suggested workflow design and technology needs necessary for sustainability.

Conclusion

Using a process of iterative feedback with key stakeholders and rapid response from developers, we have developed a mobile application ready for pilot testing in HPV-based screening programs led by CHVs.
Electrostatic filters to reduce COVID-19 spread in bubble CPAP: an in vitro study of safety and efficacy
Authors: Davis Jonathan W , Pillow J Jane , Cooper Matt N , Dahl Mar Janna
Published: September 2020

Background

Bubble CPAP may be used in infants with suspected or confirmed COVID-19. Electrostatic filters may reduce cross-infection. This study aims to determine if including a filter in the bubble CPAP circuit impacts stability of pressure delivery.

Methods

A new electrostatic filter was placed before (pre) or after (post) the bubble CPAP generator, or with no filter (control) in an in vitro study. Pressure was recorded at the nasal interface for 18 h (6 L/min; 7 cmH2O) on three occasions for each configuration. Filter failure was defined as pressure >9 cmH20 for 60 continuous minutes. The filter was weighed before and after each experiment.

Results

Mean (SD) time to reach the fail-point was 257 (116) min and 525 (566) min for filter placement pre- and post-CPAP generator, respectively. Mean pressure was higher throughout in the pre-generator position compared to control. The filter weight was heavier at study end in the pre-compared to the post-generator position.

Conclusions

Placement of the filter at the pre-generator position in a bubble CPAP circuit should be avoided due to unstable mean pressure. Filters are likely to become saturated with water over time. The post-generator position may accommodate a filter, but regular pressure monitoring and early replacement are required.
STUDY TO ASSESS ASSOCIATION OF C-REACTIVE PROTEIN WITH NEPHROPATHY IN PEOPLE LIVING WITH TYPE 2 DIABETES MELLITUS
Authors: Mondal Kaushik , Mukherjee Dattatreya
Published: September 2020

Introduction

Diabetes mellitus (DM) is a metabolic disorder with inappropriate hyperglycemia either due to an absolute or relative deficiency of insulin secretion or reduction in the biologic effectiveness of insulin or both. An inflammatory basis for Diabetes & its complications has attracted interest. Among several markers of inflammation, C reactive protein (CRP) is found to be significant in people with diabetes. Diabetic nephropathy may be associated with abnormally high levels of CRP.

Materials & Methods

This study was performed for 1 year over 100 type 2 diabetic patients (n=100) aged 30-70 years in Calcutta National Medical College & Hospital. Necessary clinical & Diabetes related laboratory investigations were done as the routine procedure.

Results

Among 100 study population, all macro-albuminuria patients were found to have high CRP. 63% of Stage 3 chronic kidney disease (CKD) patients were having high CRP in our study. High CRP values were also found among patients with higher spot urine ACR (329.50±259.40 mg/gram).(P<0.05)

Conclusion

CRP is a marker which increased in inflammatory reactions. Low grade inflammation as indicated by high CRP was an important predictor of diabetic nephropathy.
Outcomes of NAFLD and MAFLD: Results from a community-based, prospective cohort study
Authors: Niriella Madunil Anuk , Ediriweera Dileepa Senajith , Kasturiratne Anuradhani , Silva Shamila Thivanshi De , Dassanayaka Anuradha Supun , Silva Arjuna Priyadarshin De , Kato Norihiro , Pathmeswaran Arunasalam , Wickramasinghe Ananda Rajitha , Silva Hithanadura Janaka de
Published: September 2020

Introduction

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is a recently suggested alternative to Non-alcoholic fatty liver disease (NAFLD). We compared baseline metabolic traits and outcomes of NAFLD and MAFLD.

Methods

In an ongoing, community-based, cohort study, participants were first screened in 2007 by structured-interview, anthropometry, liver ultrasonography, and biochemical/serological tests and reassessed after 7-years. Baseline characteristics and outcomes after 7-years were compared in NAFLD and MAFLD, in those excluded by the NAFLD definition but captured by the MAFLD definition and those excluded by the MAFLD definition but captured by the NAFLD definition, versus controls.

Results

Of 2985 recruited in 2007, 940 (31.5%) had NAFLD, 990 (33.1%) had MAFLD and 362 (12.1%) were controls. Compared to NAFLD, MAFLD captured an additional 2.9% of individuals from the cohort and lost 1.3%. At baseline, anthropometric and metabolic traits were similar in NAFLD and MAFLD. At follow-up after 7 years, the odds of having new-onset metabolic traits and fatal/non-fatal CVEs were similar in the two groups, but were significantly higher in both the groups compared to controls. However, those excluded by the NAFLD definition but captured by the MAFLD definition, showed higher baseline metabolic derangements compared to those excluded by the MAFLD definition but captured by the NAFLD definition and had higher odds for having new onset metabolic traits and CVEs compared to controls.

Conclusion

Even though it was able to increase the index population by only a small proportion, redefining NAFLD as MAFLD seemed to improve clinical utility.

Lay Summary

The term “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” has recently been suggested as an alternative to “non-alcoholic fatty liver disease (NAFLD)”.

In our study, the diagnostic criteria for MAFLD detected a slightly higher number of individuals than NAFLD from the community.

The proportions of anthropometric and metabolic abnormalities in NAFLD and MAFLD were similar. The adverse outcomes of NAFLD and MAFLD were also similar, but were worse than in a population without NAFLD or MAFLD.

Those who were excluded by the NAFLD definition and captured by the MAFLD definition seem to be at higher risk of adverse outcomes than those excluded by the MAFLD definition but captured by the NAFLD definition.

Although it was able to increase the index population by only a small proportion, redefining NAFLD as MAFLD seems useful.
Adipocyte REVERBα dictates adipose tissue expansion during obesity
Authors: Louise Hunter A. , Pelekanou Charlotte E. , Barron Nichola J. , Northeast Rebecca C. , Adamson Antony , Downton Polly , Cornfield Thomas , Cunningham Peter S. , Hodson Leanne , Loudon Andrew S.I. , Unwin Richard D. , Iqbal Mudassar , Ray David W. , Bechtold David A.
Published: September 2020

The circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with globalReverbαdeletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbαFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERBα regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding,ReverbαFlox2-6AdipoCremice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERBα cistrome with differential gene expression reveals broad control of metabolic processes by REVERBα which is unmasked in the obese state. Adipocyte REVERBα does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERBα action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
Working nights and lower leisure-time physical activity associate with chronic pain in Southern African truck drivers: a cross-sectional study
Authors: Wadley Antonia L , Iacovides Stella , Roche Johanna , Scheuermaier Karine , Venter WD Francois , Vos Alinda G , Lalla-Edward Samanta T
Published: September 2020

Background

Globally the trucking industry employs millions of people. Recently the prevalence of chronic pain in Southern African truck drivers was reported at 10%. We investigated factors associated with chronic pain in truck drivers including mental health, physical activity, and sleep, as no study has done so.

Methods

Southern African truck drivers were recruited at truck stops in Gauteng and Free State Provinces, South Africa (n=614). Chronic pain was defined as pain present for at least the last three months. Depressive symptoms were assessed with the Patient Health Questionnaire-9, post-traumatic stress disorder with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), exposure to traumatic events with the Life Events Checklist-5 (LEC-5) and daytime sleepiness with the Epworth Sleepiness Scale. Sleep quality was measured on a four-point Likert scale. Leisure-time physical activity was measured using the Godin-Shephard leisure-time physical activity questionnaire. Associations between these factors, demographic factors and chronic pain were investigated.

Results

Six hundred and fourteen male truck drivers were recruited. Multivariate analysis showed that working ≥ 2 nights/week (OR=2.68, 95% CI=1.55-4.68) was associated with chronic pain and physical activity was protective (OR=0.97, 95% CI 0.95-0.98). In an exploratory analysis, greater depressive symptoms (p=0.004), daytime sleepiness (p=0.01) and worse sleep quality (p=0.001) was associated with working ≥ 2 nights/week. Lower leisure-time physical activity was associated with worse sleep quality (p=0.006), but not daytime sleepiness or depressive symptoms (p>0.05).

Conclusions

There is a clear relationship between working nights and activity levels, and chronic pain, sleep quality, and depression in truck drivers.
Oncogenic Activation of AKT by MAPK6
Authors: Cai Qinbo , Wang Wei , Dong Bingning , Zhou Wolong , Shen Tao , Moore David D. , Creighton Chad J. , Yang Feng
Published: September 2020

Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK closely related to MAPK4. We recently reported that MAPK4 can promote cancer by activating the Protein Kinase B (PKB/AKT) pathway of cell growth and survival. Here we report that MAPK6 overexpression also activates AKT to induce oncogenic outcomes, including transforming “normal” human epithelial cells into anchorage-independent growth and enhancing cancer cell growth. Knockdown of MAPK6 inhibited cancer cell growth and xenograft growth, supporting the tumor-promoting activities of endogenous MAPK6. Unlike MAPK4, which binds AKT through its kinase domain and phosphorylates AKT at T308, MAPK6 interacts with AKT through its C34 region and the unique C-terminal tail and phosphorylates AKT at S473 independent of mTORC2, the major AKT S473 kinase. MAPK6 overexpression is associated with decreased overall survival and the survival of lung adenocarcinoma, mesothelioma, uveal melanoma, and breast cancer patients. We conclude that MAPK6 can promote cancer by activating AKT and that targeting MAPK6 may be effective in human cancers.
TopoStats – a program for automated tracing of biomolecules from AFM images
Authors: Beton Joseph G. , Moorehead Robert , Helfmann Luzie , Gray Robert , Hoogenboom Bart W. , Joseph Agnel Praveen , Topf Maya , Pyne Alice L. B.
Published: September 2020

We present TopoStats, a Python toolkit for automated editing and analysis of Atomic Force Microscopy images. The program automates identification and tracing of individual molecules in circular and linear conformations without user input. TopoStats was able to identify and trace a range of molecules within AFM images, finding, on average, 90% of all individual molecules and molecular assemblies within a wide field of view, and without the need for prior processing. DNA minicircles of varying size, DNA origami rings and pore forming proteins were identified and accurately traced with contour lengths of traces typically within 10 nm of the predicted contour length. TopoStats was also able to reliably identify and trace linear and enclosed circular molecules within a mixed population. The program is freely available via GitHub (https://github.com/afm-spm/TopoStats) and is intended to be modified and adapted for use if required.
Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death
Authors: Meyer Nina , Henkel Lisa , Linder Benedikt , Zielke Svenja , Tascher Georg , Trautmann Sandra , Geisslinger Gerd , Münch Christian , Fulda Simone , Tegeder Irmgard , Kögel Donat
Published: September 2020

Increasing evidence suggests that induction of lethal autophagy carries potential significance for the treatment of glioblastoma (GBM). In continuation of previous work, we demonstrate that pimozide and loperamide trigger an ATG5- and ATG7-dependent type of cell death that is significantly inhibited with the cathepsin inhibitors E64D/Pepstatin A and the lipid ROS scavenger α-tocopherol in MZ-54 GBM cells. Global proteomic analysis after treatment with both drugs also revealed an increase of proteins related to lipid and cholesterol metabolic processes. These changes were accompanied by AKT1 (AKT serine/threonine kinase 1) inhibition and a massive accumulation of cholesterol and other lipids in the lysosomal compartment, indicative of impaired lipid transport/degradation. In line with these observations, pimozide and loperamide treatment were associated with a pronounced increase of bioactive sphingolipids including ceramides, glucosylceramides and sphingoid bases measured by targeted lipidomic analysis. Furthermore, pimozide and loperamide inhibited the activity of acid sphingomyelinase (ASM), increased lipid-ROS levels and promoted induction of lysosomal membrane permeabilization (LMP), as well as release of cathepsin B into the cytosol in MZ-54 wt cells. While LMP and cell death were significantly attenuated in ATG5/7 KO cells, both events were enhanced by depletion of the lysophagy receptor VCP (valosin containing protein), supporting a pro-survival function of lysophagy under these conditions. Collectively, our data suggest that pimozide and loperamide-driven autophagy and lipotoxicity synergize to induce LMP and lysosomal cell death. The results also support the notion that simultaneous overactivation of autophagy and induction of LMP represents a promising approach for the treatment of GBM.
Nature-inspired Circular-economy Recycling (NaCRe) for Proteins: Proof of Concept
Authors: Giaveri Simone , Schmitt Adeline Marie , Roset Julià Laura , Scamarcio Vincenzo , Murello Anna , Cheng Shiyu , Menin Laure , Ortiz Daniel , Patiny Luc , Bolisetty Sreenath , Mezzenga Raffaele , Maerkl Sebastian Josef , Stellacci Francesco
Published: September 2020

The billion tons of synthetic polymer-based materials (i.e.plastics) produced every year are one of the greatest challenges that humanity has to face. Nature produces even more natural polymers, yet they are sustainable. For example, proteins are sequence-defined natural polymers, that are constantly recycled when living systems feed. Indeed, digestion is the protein depolymerization into amino acids (i.e.the monomers) followed by their re-assembly into new proteins of arbitrarily different sequence and function. This process breaks a common recycling paradigm where a material is recycled into itself. Organisms feed of random protein mixtures that are ‘recycled’ into new proteins whose identity depends on the cell’s needs at the time of protein synthesis. Currently, advanced materials are increasingly made of proteins, but the abovementioned ideal recyclability of such materials has yet to be recognized and established. In this study mixtures of several (up to >30) peptides and/or proteins were depolymerized into their amino acid constituents, and these amino acids were used to synthesize new fluorescent, and bio-active proteins extra-cellularly by using an amino acid-free cell-free transcription-translation system. Proteins with high relevance in materials engineering (β-lactoglobulin films, used for water filtration, or silk fibroin solutions) were successfully recycled into biotechnologically relevant proteins (green, and red fluorescent proteins, catechol 2,3-dioxygenase). The potential long-term impact of this approach to recycling lies in its compatibility with circular-economy models where raw materials remain in use as long as possible, thus reducing the burden on the planet.
Etv5is not required for Schwann cell development but is required to regulate the Schwann cell response to peripheral nerve injury
Authors: Balakrishnan Anjali , Belfiore Lauren , Vasan Lakshmy , Touahri Yacine , Stykel Morgan , Fleming Taylor , Midha Rajiv , Biernaskie Jeff , Schuurmans Carol
Published: September 2020

Schwann cells are the principal glial cells of the peripheral nervous system, and their development into myelinating glia is critically dependent on MEK/ERK signaling. Ets-domain transcription factors (Etv1, Etv4, Etv5) are common downstream effectors of MEK/ERK signalling, but so far, onlyEtv1has been ascribed a role in Schwann cell development, and only in non-myelinating cells. Here, we examined the role ofEtv5, which is expressed in Schwann cell precursors, including neural crest cells and satellite glia, in Schwann cell lineage development. We analysedEtv5tm1Kmmmutants (designatedEtv5−/−) at embryonic days (E) 12.5, E15.5 and E18.5, focusing on dorsal root ganglia. At these embryonic stages, satellite glia (glutamine synthetase) and Schwann cell markers, including transcriptional regulators (Sox10, Sox9, Tfap2a, Pou3f1) and non-transcription factors (Ngfr, BFABP, GFAP), were expressed in the DRG of wild-type andEtv5−/−embryos. Furthermore, by E18.5, quantification of Sox10+Schwann cells and NeuN+neurons revealed that these cells were present in normal numbers in theEtv5−/−dorsal root ganglia. We next performed peripheral nerve injuries at postnatal day 21, revealing thatEtv5−/−mice had an enhanced injury response, generating more Sox10+Schwann cells compared to wild-type animals at five days post-injury. Thus, whileEtv5is not required for Schwann cell development, possibly due to genetic redundancy withEtv1and/orEtv4, Etv5is an essential negative regulator of the peripheral nerve injury repair response.

SIGNIFICANCE STATEMENT

Our study sought to determine whether the ets domain transcription factor,Etv5, plays a role in regulating Schwann cell development and nerve repair. By using an embryonically and postnatally viable hypomorphicEtv5mutant allele, we demonstrated thatEtv5is not required for the development of Schwann cells or other neural crest derivatives in the dorsal root ganglia, including satellite glia and neurons. Surprisingly, loss ofEtv5had a direct impact on the Schwann cell repair response post-injury, resulting in more Schwann cells populating the distal injured nerve site compared to wild-type animals. Thus, this work describes for the first time a role forEtv5in regulating the Schwann cell repair response after peripheral nerve injury.
Extraintestinal pathogenic Escherichia coli (ExPEC) are associated with prolonged carriage of extended-spectrum β-lactamase-producing E. coli acquired during travel
Authors: van der Putten Boas C.L. , van Hattem Jarne M. , Penders John ,   COMBAT Consortium, Mende Daniel R. , Schultsz Constance
Published: September 2020

Objectives

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveler cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage.

Methods

In a prospective cohort study of 2001 international travelers, we analysed 160 faecal ESBL-Ec isolates from all 38 travelers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travelers, we confirmed the persistence of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (≥12 months carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month carriage). Long-read sequencing was employed to investigate ESBL plasmid persistence.

Results

We show that in healthy travelers with very low antibiotic usage, extraintestinal pathogenic lineages of E. coli (ExPEC) are significantly more likely to persist than other E. coli lineages. The long-term carriage of E. coli from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D E. coli.

Conclusions

Although ExPEC frequently cause extra-intestinal infections such as bloodstream infections, our results imply that ExPEC are also efficient intestinal colonizers, which potentially contributes to their onward transmission.
The effects of luminal and trans-endothelial fluid flows on the extravasation and tissue invasion of tumor cells in a 3Din vitromicrovascular platform
Authors: Hajal Cynthia , Ibrahim Lina , Serrano Jean Carlos , Offeddu Giovanni S. , Kamm Roger D.
Published: September 2020

Throughout the process of metastatic dissemination, tumor cells are continuously subjected to mechanical forces resulting from complex fluid flows due to changes in pressures in their local microenvironments. While these forces have been associated with invasive phenotypes in 3D matrices, their role in key steps of the metastatic cascade, namely extravasation and subsequent interstitial migration, remains poorly understood. In this study, anin vitromodel of the human microvasculature was employed to subject tumor cells to physiological luminal, trans-endothelial, and interstitial flows to evaluate their effects on those key steps of metastasis. Luminal flow promoted the extravasation potential of tumor cells, possibly as a result of their increased intravascular migration speed. Trans-endothelial flow increased the speed with which tumor cells transmigrated across the endothelium as well as their migration speed in the matrix following extravasation. In addition, tumor cells possessed a greater propensity to migrate in close proximity to the endothelium when subjected to physiological flows, which may promote the successful formation of metastatic foci. These results show important roles of fluid flow during extravasation and invasion, which could determine the local metastatic potential of tumor cells.
A joint reaction coordinate for computing the free energy landscape of pore nucleation and pore expansion in lipid membranes
Authors: Hub Jochen S.
Published: September 2020

Topological transitions of membranes, such as pore formation or membrane fusion, play key roles in biology, biotechnology, and in medical applications. Calculating the related free energy landscapes has been complicated by the fact that such processes involve a sequence of transitions along highly distinct directions in conformational space, making it difficult to define good reaction coordinates (RCs) for the overall process. In this study, we present a new RC capable of driving both pore nucleation and pore expansion in lipid membranes. The potential of mean force (PMF) along the RC computed with molecular dynamics (MD) simulations provides a comprehensive view on the free-energy landscape of pore formation, including a barrier for pore nucleation, the size, free energy, and metastability of the open pore, and the energetic cost for further pore expansion against the line tension of the pore rim. We illustrate the RC by quantifying the effects (i) of simulation system size and (ii) of the addition of dimethyl sulfoxide (DMSO) on the free energy landscape of pore formation. PMF calculations along the RC provide mechanistic and energetic understanding of pore formation, hence they will be useful to rationalize the effects of membrane-active peptides, electric fields, and membrane composition on transmembrane pores.
lncRNA-RMST functioned as a SOX2 transcription co-regulator to regulate miR-1251 in the progression of Hirschsprung’s disease
Authors: Zhou Lingling , Zhi Zhengke , Chen Pingfa , Wei Zhonghong , Du Chunxia , Wang Binyu , Fang Xiang , Tang Weibing , Li Hongxing
Published: September 2020

Hirschsprung’s disease (HSCR) is a congenital disorder characterized by the absence of enteric neural crest cells (ENCCs). Non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been authenticated as important regulators of biological functions. We conducted a microarray analysis and found lncRNA Rhabdomyosarcoma 2-associated transcript (RMST) was down-regulated in the stenotic segment of HSCR patients. MiR-1251 is transcribed from the intron region of RMST and was also low-expressed. When the expression of RMST or miR-1251 was reduced, the cell proliferation and migration were attenuated. However, RMST didn’t affect the expression of miR-1251 directly found in this study. Through bioinformatic analysis, transcription factor SOX2 was predicted to bind to the promoter region of miR-1251 which was confirmed by CHIP assay. Herein, we demonstrated that RMST exerted as a co-regulator of SOX2 to regulate the expression of miR-1251. Furtherly, AHNAK was proved to be the target gene of miR-1251 in this study. Taken together, we revealed the role of RMST/SOX2/miR-1251/AHNAK pathway in the occurrence of Hirschsprung’s disease and provided a potential therapeutic target for this disease.

SUMMARY STATEMENT

Hirschsprung disease (HSCR) is characterized by a deficit in enteric neurons, however, the underlying mechanism remains unclear. This study revealed the role of lnc-RMST during the occurrence of HSCR.
Evenness-richness scatter plots: a graphical, intuitive approach to alpha diversity analysis
Authors: Gauthier Jeff , Derome Nicolas
Published: September 2020

Shannon’s diversity index is a popular alpha diversity metric because it estimates both richness and evenness in a single equation. However, since its value is dependent of both those parameters, there is theoretically an infinite number of richness / evenness value combinations translating into the same index score. By decoupling both components measured by Shannon’s index, two communities having identical indices can be differentiated by mapping richness and evenness coordinates on a scatter plot. In such graphs, confidence ellipses would allow testing significant differences between groups of samples. Multivariate statistical tests such as PERMANOVA can be performed on distance matrices calculated from richness and evenness coordinates and detect statistically significant differences that would have remained unforeseen otherwise.