bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender-specific clinical risk scores incorporating blood pressure variability for predicting incident dementia
Authors: Zhou Jiandong , Lee Sharen , Wong Wing Tak , Waleed Khalid Bin , Leung Keith Sai Kit , Lee Teddy Tai Loy , Wai Abraham Ka Chung , Liu Tong , Chang Carlin , Cheung Bernard Man Yung , Zhang Qingpeng , Tse Gary
Published: August 2021

Introduction

The present study examined the gender-specific prognostic value of blood pressure (BP) and its variability in the prediction of dementia risk and developed a score system for risk stratification.

Materials and Methods

This was a retrospective, observational population-based cohort study of patients admitted to government-funded family medicine clinics in Hong Kong between January 1, 2000 and March 31, 2002 with at least 3 blood pressure measurements. Gender-specific risk scores for dementia were developed and tested.

Results

The study consisted of 74 855 patients, of whom 3550 patients (incidence rate: 4.74%) developed dementia over a median follow-up of 112 months (IQR= [59.8–168]). Nonlinear associations between diastolic/systolic BP measurements and the time to dementia presentation were identified. Gender-specific dichotomized clinical scores were developed for males (age, hypertension, diastolic and systolic BP and their measures of variability) and females (age, prior cardiovascular, respiratory, gastrointestinal diseases, diabetes mellitus, hypertension, stroke, mean corpuscular volume, monocyte, neutrophil, urea, creatinine, diastolic and systolic BP and their measures of variability). They showed high predictive strengths for both male (hazard ratio [HR]: 12.83, 95% confidence interval [CI]: 11.15–14.33, P value < .0001) and female patients (HR: 26.56, 95% CI: 14.44–32.86, P value < .0001). The constructed gender-specific scores outperformed the simplified systems without considering BP variability (C-statistic: 0.91 vs 0.82), demonstrating the importance of BP variability in dementia development.

Conclusion

Gender-specific clinical risk scores incorporating BP variability can accurately predict incident dementia and can be applied clinically for early disease detection and optimized patient management.
Spectrophotometric Determination of Aspirin and Omeprazole in the Presence of Salicylic Acid as a Degradation Product: A Comparative Evaluation of Different Univariate/Multivariate Post Processing Algorithms
Authors: Elmasry Manal S , Serag Ahmed , Hassan Wafaa S , El-Mammli Magda Y , Badrawy Mohamed
Published: August 2021

Background

A recent combination of aspirin (ASP) and omeprazole (OMP) has been presented in a fixed dosage form for the treatment of many cardiovascular diseases, particularly in patients with gastric diseases. However, ASP is very sensitive to degradation into salicylic acid (SAL) as its main degradation product. Hence, it is very important to develop methods for the determination of ASP and OMP in the presence of SAL.

Objective

In this study, UV spectrophotometry assisted by different univariate/multivariate post processing algorithms is presented for quantitative determination of ASP, OMP, and SAL without any prior separation.

Methods

The univariate/multivariate algorithms include double divisor ratio difference and double divisor mean centering as the univariate approaches while the multivariate methods include principal component regression (PCR) and partial least squares (PLS) models. Validation of the univariate methods was done according to International Conference on Harmonization guidelines, while the multivariate models were validated using an external validation set.

Results

The univariate algorithms displayed excellent regression and validation capabilities in terms of linearity, accuracy, precision, and selectivity. Regarding PCR and PLS, the number of latent variables were carefully optimized, and the model’s validation criteria displayed excellent recoveries and lower errors of prediction.

Conclusion

Our findings indicate that the developed methods were comparable to the reported chromatographic methods, but are simpler and have much shorter analysis times.

Highlights

Overall, this report presents the first spectrophotometric methods applied for determination of possible combinations of ASP, OMP, and SAL, and poses these methods as valuable analytical tools for in-process testing and quality control analysis.
A Multimetric Evaluation of Online Patient Educational Materials for Breast Implant–associated Anaplastic Large Cell Lymphoma
Authors: Miles Randy C , Lourenco Ana P , Baird Grayson L , Roy Ishita T , Choi Paul H S , Lehman Constance , Lamb Leslie R
Published: August 2021

Objective

To assess understandability, actionability, and readability of online patient educational materials (OPEM) related to breast implant–associated anaplastic large cell lymphoma (BIA-ALCL).

Methods

Search volumes for query terms related to BIA-ALCL including “breast implant associated lymphoma,” “breast implant associated anaplastic large cell lymphoma,” and “BIA-ALCL” were analyzed in one-week increments and normalized to total Google search volume. The same terms were then queried using an online search engine to identify commonly accessed OPEM on this topic. Understandability and actionability of OPEM were evaluated using the Patient Education Materials Assessment Tool. Grade-level readability was determined using generalized estimating equations, with observations nested within readability metrics from each website. All interval estimates were calculated for 95% confidence.

Results

Overall, 24 websites were identified based on search parameters. Of these websites, 11 (45.8%) met criteria for understandability, and 1 (4.2%) met criteria for actionability. Overall, readability ranged from 10.2 to 17.3 for all websites with an average grade level readability of 12.4; 0 websites were written at or below a sixth-grade reading level. Government websites had the highest average grade reading level at 14.0, followed by commercial websites at 13.2, nonprofit websites at 12.0, and then academic/hospital-based websites at 11.5.

Conclusion

The quality of available OPEM on BIA-ALCL is limited. Future development of OPEM should be designed with the goal of improving both comprehension and actionability to help reduce patient anxiety and unnecessary clinical appointments related to this disease.
Characterization of cross-species transcription and splicing from Penicillium to Saccharomyces cerevisiae
Authors: Lin Zhenquan , Xu Kang , Cai Guang , Liu Yangqingxue , Li Yi , Zhang Zhihao , Nielsen Jens , Shi Shuobo , Liu Zihe
Published: August 2021

Heterologous expression of eukaryotic gene clusters in yeast has been widely used for producing high-value chemicals and bioactive secondary metabolites. However, eukaryotic transcription cis-elements are still undercharacterized, and the cross-species expression mechanism remains poorly understood. Here we used the whole expression unit (including original promoter, terminator, and open reading frame with introns) of orotidine 5′-monophosphate decarboxylases from 14 Penicillium species as a showcase, and analyzed their cross-species expression in Saccharomyces cerevisiae. We found that pyrG promoters from the Penicillium species could drive URA3 expression in yeast, and that inefficient cross-species splicing of Penicillium introns might result in weak cross-species expression. Thus, this study demonstrates cross-species expression from Penicillium to yeast, and sheds light on the opportunities and challenges of cross-species expression of fungi expression units and gene clusters in yeast without refactoring for novel natural product discovery.
Demystifying Schrems II for the cross-border transfer of clinical research data
Authors: Liss Joseph , Peloquin David , Barnes Mark , Bierer Barbara E
Published: August 2021

The Courts of Justice of the European Union (CJEU) held in its July 2020 Schrems II decision that, in order for entities in other countries to import personal data from the European Economic Area (EEA), the importer must be able to provide data protections ‘essentially equivalent’ to those the EEA offers under its General Data Protection Regulation. The CJEU expressed particular concern that United States’ national security intelligence gathering laws prevent U.S.-based entities from providing such protections. This decision has sharply limited the sharing of clinical research data from the EEA to the United States. After describing the pertinent aspects of the Schrems II decision, this article evaluates U.S. national security intelligence gathering frameworks, including Section 702 of the Foreign Intelligence Surveillance Act and Executive Order 12333. The article then leverages recent draft guidance from the European Data Protection Board to explain how entities may be able to adopt widely used contractual and technical measures, such as data pseudonymization, to provide ‘essentially equivalent’ protections in the clinical research context.
Loss of Lysosomal Proteins Progranulin and Prosaposin Associated with Increased Neurofibrillary Tangle Development in Alzheimer Disease
Authors: Mendsaikhan Anarmaa , Tooyama Ikuo , Serrano Geidy E , Beach Thomas G , Walker Douglas G
Published: August 2021

Alzheimer disease (AD) is a progressive neurodegenerative disease causing cognitive decline in the aging population. To develop disease-modifying treatments, understanding the mechanisms behind the pathology is important, which should include observations using human brain samples. We reported previously on the association of lysosomal proteins progranulin (PGRN) and prosaposin (PSAP) with amyloid plaques in non-demented aged control and AD brains. In this study, we investigated the possible involvement of PGRN and PSAP in tangle formation using human brain tissue sections of non-demented aged control subjects and AD cases and compared with cases of frontotemporal dementia with granulin (GRN) mutations. The study revealed that decreased amounts of PGRN and PSAP proteins were detected even in immature neurofibrillary tangles, while colocalization was still evident in adjacent neurons in all cases. Results suggest that neuronal loss of PGRN preceded loss of PSAP as tangles developed and matured. The GRN mutation cases exhibited almost complete absence of PGRN in most neurons, while PSAP signal was preserved. Although based on correlative data, we suggest that reduced levels of PGRN and PSAP and their interaction in neurons might predispose to accumulation of p-Tau protein.
USING THE STATISTICAL CONCEPT OF “SEVERITY” TO ASSESS THE COMPATIBILITY OF SEEMINGLY CONTRADICTORY STATISTICAL EVIDENCE (WITH A PARTICULAR APPLICATION TO DAMAGE ESTIMATION)
Authors: Bönisch Peter , Inderst Roman
Published: August 2021

When parties present divergent econometric evidence, the court might either combine such evidence in an ad hoc way or view such evidence as contradictory and thus ignore it completely, without conducting closer analysis of the possible sources of the contradiction. We believe that the reasons for this development are (i) that the statistical evidence is often interpretated in a simplistic manner and (ii) that the fact is ignored that any statistical test tests within the boundary of a prespecified model which might be wrong. Contradictory evidence might therefore either occur by chance or because the underlying assumptions contradict each other. Based on the concept of severity, we propose a method to avoid common fallacies in the interpretation of empirical evidence. We further set out a simple method for distinguishing between actual and merely apparent contradiction based on the statistical concept of the “severity” of the furnished evidence. Our chosen application is that of damage estimation in follow-on cases.
Cryopreserved allogenic vascular graft in free-flap reconstructive microsurgery: case report
Authors: Lin Chih-Hsun , Hsia Kai , Lu Jen-Her , Ma Hsu
Published: August 2021

The use of cryopreserved allogenic vascular graft in reconstructive microsurgery has rarely been reported. Here, we report a case of lower extremity reconstruction using cryopreserved hepatic artery as the vein conduit. Postoperative flap perfusion was uneventful with satisfactory wound healing, and graft patency was observed on follow-up color Doppler. Thus, cryopreserved allogenic vascular graft could be a source of vascular conduit in microsurgery.
Red Blood Cell Transfusion Volumes According to AIMS65 Scores in Patients with Peptic Ulcer Bleeding
Authors: Lee Moon Won , Lee Hyun-Ji , Shin Kyung-Hwa , Kim Gwang Ha , Kim Hyung-Hoi
Published: August 2021

Objective

Fluid supplementation and red blood cell (RBC) transfusions form first-line management strategies to maintain circulating blood volumes in patients with upper gastrointestinal bleeding (UGIB). In this study, we aimed to analyze the utility of the AIMS65 score in predicting the volume of RBC transfusion required in patients with bleeding peptic ulcers.

Methods

In this single-center, retrospective study, the data of patients admitted between January 2019 and December 2019 with suspected UGIB were retrospectively reviewed. The RBC volume transfused during pre- and postendoscopic hemostasis was measured in relation to various patient factors including the AIMS65 scores.

Results

Transfusion rates, the mean number of transfused RBC units, and the duration of hospital stay differed significantly between patients with low AIMS65 scores and those with high AIMS65 scores. Patients with an AIMS65 score of 3 were transfused with more RBC units in the postendoscopic hemostasis period, compared with those with an AIMS65 score of 0, 1, or 2 (with a mean of 4.33 ± 2.07 and 2.67 ± 4.1 units transfused during the pre-endoscopic and postendoscopic hemostasis periods, respectively).

Conclusion

Patients with UGIB and with an AIMS65 score of 3 were more likely to require transfusions of RBCs.
Is the Genetic Code Optimized for Resource Conservation?
Authors: Xu Haiqing , Zhang Jianzhi
Published: August 2021

The causes and consequences of the nonrandom structure of the standard genetic code (SGC) have been of long-standing interest. A recent study reported that mutations in present-day protein-coding sequences are less likely to increase proteomic nitrogen and carbon uses under the SGC than under random genetic codes, concluding that the SGC has been selectively optimized for resource conservation. If true, this finding might offer important information on the environment in which the SGC and some of the earliest life forms evolved. However, we here show that the hypothesis of optimization of a genetic code for resource conservation is theoretically untenable. We discover that the aforementioned study estimated the expected mutational effect by inappropriately excluding mutations lowering resource consumptions and including mutations involving stop codons. After remedying these problems, we find no evidence that the SGC is optimized for nitrogen or carbon conservation.
Cross-reactive Antibody Response to mRNA SARS-CoV-2 Vaccine After Recent COVID-19-Specific Monoclonal Antibody Therapy
Authors: Schultz-Cherry Stacey , McGargill Maureen A , Thomas Paul G , Estepp Jeremie H , Gaur Aditya H , Allen E Kaitlynn , Allison Kim J , Tang Li , Webby Richard J , Cherry Sean D , Lin Chun-Yang , Fabrizio Thomas , Tuomanen Elaine I , Wolf Joshua ,   SJTRC Investigative Team, Kirkpatrick Roubidoux Ericka , Freiden Pamela , Mori Tomi , Hijano Diego R , Hakim Hana , Brice David C , Castellaw Ashley , Krammer Florian , Wittman David E , Hodges Jason , Dallas Ronald H , Cortez Valerie , Vazquez-Pagan Ana , Bajracharya Resha , Clark Brandi L , Van de Velde Lee-Ann , Awad Walid , Wilson Taylor L , Kirk Allison M , Hayden Randall T , Hoffman James , Russell-Bell Jamie , Sparks James
Published: August 2021

The efficacy of coronavirus disease 2019 (COVID-19) vaccines administered after COVID-19-specific monoclonal antibody is unknown, and “antibody interference” might hinder immune responses leading to vaccine failure. In an institutional review board–approved prospective study, we found that an individual who received mRNA COVID-19 vaccination <40 days after COVID-19-specific monoclonal antibody therapy for symptomatic COVID-19 had similar postvaccine antibody responses to SARS-CoV-2 receptor binding domain (RBD) for 4 important SARS-CoV-2 variants (B.1, B.1.1.7, B.1.351, and P.1) as other participants who were also vaccinated following COVID-19. Vaccination against COVID-19 shortly after COVID-19-specific monoclonal antibody can boost and expand antibody protection, questioning the need to delay vaccination in this setting.

Trial registration. 

The St. Jude Tracking of Viral and Host Factors Associated with COVID-19 study; NCT04362995; https://clinicaltrials.gov/ct2/show/NCT04362995.
The Timing, Duration and Conditions of UHT Metamorphism in Remnants of the Former Eastern Gondwana
Authors: Durgalakshmi   , Sajeev K , Williams Ian S , Reddy D Harinadha , Satish-Kumar M , Jöns Niels , Malaviarachchi Sanjeewa P K , Samuel Vinod O , George P M
Published: August 2021

Early Palaeozoic ultrahigh-temperature (UHT) metamorphism in eastern Gondwana was an event that started with Gondwana amalgamation at c. 580 Ma and lasted at least 50 Myr. Sapphirine + quartz, Mg–Al granulites preserve a record of the timing and duration of the event along the metamorphic belt. U–Th–Pb dating of zircon and monazite shows that metamorphism peaked almost simultaneously in Antarctica (554.0 ± 4.7 Ma), Sri Lanka (555.5 ± 4.6 Ma), southern India (548.1 ± 8.1 Ma) and Madagascar (550.6 ± 6.0 Ma), and ended in all locations at the same time, 530–520 Ma. Rare earth element (REE) compositions of the metamorphic zircon zones can be matched to the REE zoning in the associated garnet. Phase-diagram modelling indicates that the peak UHT P–T conditions in Antarctica, Sri Lanka, and India were very similar, 1020–1040 °C at 0.8 GPa. Peak conditions in Madagascar were at higher T and similar P: 1090 °C and 0.8 GPa. The East African Orogeny before 600 Ma preconditioned the crust of the eastern Gondwanan terranes by thickening it and harbouring heat-producing elements, heating the crust over c. 60 Myr; such that UHT conditions were reached when East and West Gondwana collided.
Reciprocal Influence of Mobility and Speech-Language: Advancing Physical Therapy and Speech Therapy Cotreatment and Collaboration for Adults With Neurological Conditions
Authors: Schwab Sarah M , Dugan Sarah , Riley Michael A
Published: August 2021

Mobility and speech-language impairments and limitations in adults with neurological conditions manifest not in isolated anatomical components but instead in the individual-environment system and are task-dependent. Optimization of function thus requires interprofessional care to promote participation in meaningful life areas within appropriate task and environmental contexts. Cotreatment guidelines (ie, the concurrent intervention of disciplines) were established by the physical therapy, occupational therapy, and speech-language and hearing professional organizations nearly 2 decades ago to facilitate seamless interprofessional care. Despite this, cotreatment between physical therapy and speech therapy remains limited. The purpose of this Perspective article is to encourage physical therapists and speech-language pathologists to increase interprofessional collaboration through cotreatment in the management of adults with neurological conditions. Evidence from pediatrics and basic motor control literature points toward reciprocal interactions between speech-language and mobility. We provide recommendations for clinical practice with an emphasis on the gains each discipline can provide the other. This Perspective is rooted in the International Classification of Functioning, Disability and Health model and ecological theory.

Impact

The goals of speech therapy and physical therapy are complementary and mutually supportive. Enhanced cotreatment, and collaboration more generally, between physical therapists and speech-language pathologists in the management of adults with neurological conditions can augment task-relevant conditions to improve function.
It takes two to tango: Examining productive interactions in urban research collaboration
Authors: Kalliomäki Helka , Ruoppila Sampo , Airaksinen Jenni
Published: August 2021

The science–society relations of social sciences and humanities have been increasingly discussed under the concept of productive interactions, which refers to the mutual learning processes between researchers and stakeholders for the benefit of societal development. While most studies have analysed the societal impact from the research performers’ perspective, in this article, we examine the practitioners’ side. We contribute to the evaluation theory by offering a new perspective to examine the emergence of productive interactions. Based on an empirical analysis of collaborative practices in two Finnish urban research programmes and how the practitioners reflected on them, we argue that practitioners’ competencies are essential in leveraging societal impact. The improvement of these ‘pracademic competencies’ need to be raised as an issue in research policy and evaluation promoting responsible research and innovation.
Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis
Authors: Clarke Sarah L N , Mageean Katie S , Maccora Ilaria , Harrison Sean , Simonini Gabriele , Sharp Gemma C , Relton Caroline L , Ramanan Athimalaipet V
Published: August 2021

Objectives

JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA.

Methods

Four databases (MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to January 2020. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form.

Results

This review includes 66 environmental factors from 39 studies (11 cohort and 28 case-control studies) over 45 years. Study sample sizes ranged from 41 to 1.9 million participants. Eight environmental factors from ten studies were meta-analysed. Caesarean section delivery was associated with increased JIA risk [pooled odds ratio (OR) 1.11, 95% CI: 1.01, 1.22]. Conversely, presence (vs absence) of siblings (pooled OR 0.60, 95% CI: 0.44, 0.81) and maternal prenatal smoking (pooled OR 0.70, 95% CI: 0.58, 0.84) were associated with decreased JIA risk.

Conclusion

This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research undertaken over five decades. We also highlight the challenges of combining data collected over this period due to limited between study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.
Neuromodulation by means of phase-locked auditory stimulation affects key marker of excitability and connectivity during sleep
Authors: Sousouri Georgia , Krugliakova Elena , Skorucak Jelena , Leach Sven , Snipes Sophia , Ferster Maria Laura , Da Poian Giulia , Karlen Walter , Huber Reto
Published: August 2021

The propagating pattern of sleep slow waves (high-amplitude oscillations < 4.5 Hz) serves as a blueprint of cortical excitability and brain connectivity. Phase-locked auditory stimulation is a promising tool for the modulation of ongoing brain activity during sleep; however, its underlying mechanisms remain unknown. Here, eighteen healthy young adults were measured with high-density electroencephalography in three experimental conditions; one with no stimulation, one with up- and one with down-phase stimulation; ten participants were included in the analysis. We show that up-phase auditory stimulation on a right prefrontal area locally enhances cortical involvement and promotes traveling by increasing the propagating distance and duration of targeted small-amplitude waves. On the contrary, down-phase stimulation proves more efficient at perturbing large-amplitude waves and interferes with ongoing traveling by disengaging cortical regions and interrupting high synchronicity in the target area as indicated by increased traveling speed. These results point out different underlying mechanisms mediating the effects of up- and down-phase stimulation and highlight the strength of traveling wave analysis as a sensitive and informative method for the study of connectivity and cortical excitability alterations.
The efficacy and safety of palbociclib combined with endocrine therapy in patients with hormone receptor-positive HER2-negative advanced breast cancer: a multi-center retrospective analysis
Authors: Zhang Linhui , Song Guohong , Shao Bin , Xu Ling , Xiao Yu , Wang Mopei , Sumou Ingrid Karmane , Zhang Yan , Liang Xu , Jiang Hanfang , Li Huiping
Published: August 2021

To explore the efficacy and safety of palbociclib combined with endocrine therapy (ET) in advanced breast cancer (ABC). We conducted a retrospective study involving patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) ABC who received palbociclib combined with ET in the first- to third-line at three centers in China between January 2018 and October 2020. A total of 151 patients were included in this study. The median age of the patients at palbociclib initiation was 56 years (range 30–86 years) with a median follow-up of 10.9 months (range 2.0–41.2 months). Among these patients, 88 patients received palbociclib combined with ET as first-line therapy, and achieved a median progression-free survival (mPFS) of 19.8 months and an objective response rate (ORR) of 40.9%, meanwhile, in the first-line setting, 62 patients received palbociclib at an initial dose of 125 mg, achieving a mPFS of 20.9 months and an ORR of 46.8%. There were 39 and 24 patients who received palbociclib combined with ET as second- and third-line therapy, the mPFS were 10.0 months and 6.1 months, respectively. The most common and serious adverse events (AEs) were leukopenia and neutropenia. A total of 64 patients (42.4%) underwent palbociclib dose reduction due to AEs. Palbociclib combined with ET is an effective therapeutic regimen for HR+/HER2− ABC, particularly in the first-line setting with palbociclib initial dose of 125 mg, and AEs were manageable.
A web-based fuzzy risk predictive-decision model of de novo stress urinary incontinence in women undergoing pelvic organ prolapse surgery
Authors: Moosavi Seyyde Yalda , Samad-Soltani Taha , Hajebrahimi Sakineh
Published: August 2021

Background:

Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are common conditions affecting women's health and quality of life. In 50% of cases, SUI occurs after POP surgery, which is called de novo SUI. Predicting the risk of de novo SUI is a complex multi-attribute decision-making process. The current study made available a Decision Support System in the form of a fuzzy calculator web-based application to help surgeons predict the risk of de novo SUI.

Materials and methods:

We first identified 12 risk factors and the diagnostic criteria for de novo SUI by means of a systematic review of the literature. Then based upon an expert panel, all risk factors were prioritized. A set of 232 fuzzy rules for the prediction of de novo SUI was determined. A fuzzy expert system was developed using MATLAB software and Mamdani Inference System. The risk prediction model was then evaluated using retrospective data extracted from 30 randomly selected medical records of female patients over the age of 50 without symptoms of urinary incontinence who had undergone POP surgery. Finally, the proposed results of the predictive system were compared with the results of retrospective medical record data review.

Results:

The results of this online calculator show that the accuracy of this risk prediction model, at more than 90%, compared favorably to other SUI risk prediction models.

Conclusions:

A fuzzy logic-based clinical Decision Support System in the form of an online calculator for calculating SUI prognosis after POP surgery in women can be helpful in predicting de novo SUI.
Comparison of Renal Responses Between Continuous Mycophenolate Mofetil and Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Lupus Nephritis
Authors: Liao Yu-Wan , Hung Wei-Ting , Chen Yi-Ming , Hsu Chiann-Yi , Lin Ching-Heng , Hsieh Tsu-Yi , Chen Hsin-Hua , Hsieh Chia-Wei , Lin Ching-Tsai , Lai Kuo-Lung , Tang Kuo-Tung , Tseng Chih-Wei , Chen Yi-Hsing , Huang Wen-Nan
Published: August 2021

Background

Mycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure.

Methods

In this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016–2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders.

Results

Baseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti–double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion.

Conclusion

Switching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.
Spatial activation of ezrin by epidermal growth factor receptor and focal adhesion kinase co-ordinates epithelial cell migration
Authors: Chan Grace K. , McGrath John A. , Parsons Maddy
Published: August 2021

Epidermal growth factor receptor (EGFR) plays a critical role in the promotion of epithelial cell proliferation and migration. Previous studies have suggested a cooperative role between EGFR and integrin signalling pathways that enable efficient adhesion and migration but the mechanisms controlling this remain poorly defined. Here, we show that EGFR forms a complex with focal adhesion kinase in epithelial cells. Surprisingly, this complex enhances local Src activity at focal adhesions to promote phosphorylation of the cytoskeletal adaptor protein ezrin at Y478, leading to actomyosin contractility, suppression of focal adhesion dynamics and slower migration. We further demonstrate this regulation of Src is due to the suppression of PTP1B activity. Our data provide new insight into EGF-independent cooperation between EGFR and integrins and suggest transient interactions between these kinases at the leading edge of cells act to spatially control signalling to permit efficient motility.
Reservoir hosts experiencing food stress alter transmission dynamics for a zoonotic pathogen
Authors: Owen J. C. , Landwerlen H. R. , Dupuis A. P. , Belsare A. V. , Sharma D. B. , Wang S. , Ciota A. T. , Kramer L. D.
Published: August 2021

Food limitation is a universal stressor for wildlife populations and is increasingly exacerbated by human activities. Anthropogenic environmental change can significantly alter the availability and quality of food resources for reservoir hosts and impact host–pathogen interactions in the wild. The state of the host's nutritional reserves at the time of infection is a key factor influencing infection outcomes by altering host resistance. Combining experimental and model-based approaches, we investigate how an environmental stressor affects host resistance to West Nile virus (WNV). Using American robins (Turdus migratorius), a species considered a superspreader of WNV, we tested the effect of acute food deprivation immediately prior to infection on host viraemia. Here, we show that robins food deprived for 48 h prior to infection, developed higher virus titres and were infectious longer than robins fed normally. To gain an understanding about the epidemiological significance of food-stressed hosts, we developed an agent-based model that simulates transmission dynamics of WNV between an avian host and the mosquito vector. When simulating a nutritionally stressed host population, the mosquito infection rate rose significantly, reaching levels that represent an epidemiological risk. An understanding of the infection disease dynamics in wild populations is critical to predict and mitigate zoonotic disease outbreaks.
The three Ts of virulence evolution during zoonotic emergence
Authors: Visher Elisa , Evensen Claire , Guth Sarah , Lai Edith , Norfolk Marina , Rozins Carly , Sokolov Nina A. , Sui Melissa , Boots Michael
Published: August 2021

There is increasing interest in the role that evolution may play in current and future pandemics, but there is often also considerable confusion about the actual evolutionary predictions. This may be, in part, due to a historical separation of evolutionary and medical fields, but there is a large, somewhat nuanced body of evidence-supported theory on the evolution of infectious disease. In this review, we synthesize this evolutionary theory in order to provide a framework for clearer understanding of the key principles. Specifically, we discuss the selection acting on zoonotic pathogens' transmission rates and virulence at spillover and during emergence. We explain how the direction and strength of selection during epidemics of emerging zoonotic disease can be understood by a three Ts framework: trade-offs, transmission, and time scales. Virulence and transmission rate may trade-off, but transmission rate is likely to be favoured by selection early in emergence, particularly if maladapted zoonotic pathogens have ‘no-cost’ transmission rate improving mutations available to them. Additionally, the optimal virulence and transmission rates can shift with the time scale of the epidemic. Predicting pathogen evolution, therefore, depends on understanding both the trade-offs of transmission-improving mutations and the time scales of selection.
Growth acceleration results in faster telomere shortening later in life
Authors: Salmón Pablo , Millet Caroline , Selman Colin , Monaghan Pat
Published: August 2021

There is a wealth of evidence for a lifespan penalty when environmental conditions influence an individual's growth trajectory, such that growth rate is accelerated to attain a target size within a limited time period. Given this empirically demonstrated relationship between accelerated growth and lifespan, and the links between lifespan and telomere dynamics, increased telomere loss could underpin this growth–lifespan trade. We experimentally modified the growth trajectory of nestling zebra finches (Taeniopygia guttata), inducing a group of nestlings to accelerate their growth between 7 and 15 days of age, the main phase of body growth. We then sequentially measured their telomere length in red blood cells at various time points from 7 days to full adulthood (120 days). Accelerated growth between 7 and 15 days was not associated with a detectable increase in telomere shortening during this period compared with controls. However, only in the treatment group induced to show growth acceleration was the rate of growth during the experimental period positively related to the amount of telomere shortening between 15 and 120 days. Our findings provide evidence of a long-term influence of growth rate on later-life telomere shortening, but only when individuals have accelerated growth in response to environmental circumstances.
Quality and antioxidant properties of wheat cookies supplemented with
maqui berry powder
Authors: Jeon Hye Ju , Lee Jun Ho
Published: August 2021

Wheat-based products have been supplemented with various health-promoting
ingredients to improve their overall qualities. Maqui berries are one of the
healthiest berries in nature; however, their use in cookie making has not been
reported. Herein, we aimed to develop functionally and nutritionally improved
wheat cookies by partially replacing white wheat flour with maqui berry powder
(MBP). We prepared cookies supplemented with different MBP concentrations (2.5%,
5%, 7.5%, and 10%) and compared their quality characteristics and antioxidant
activities with those of control cookies (100% wheat flour without MBP
addition). The incorporation of MBP significantly affected the physicochemical
parameters of cookie dough and cookies. Specifically, MBP supplementation
significantly decreased the pH, while slightly decreasing the density of cookie
dough (p<0.05). The cookie spread factor increased; however, the hardness
decreased significantly as the MBP concentration increased (p<0.05). No
significant changes in loss rates were observed upon MBP supplementation
(p>0.05). Regarding the color of the cookie surface, L* and b* values
significantly decreased, while the a* value increased with the addition of MBP
(p<0.05). The 2,2-Diphenyl-1-picrylhydrazyl and
2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid radical scavenging
activities were significantly increased (p<0.05) as the concentration of
MBP increased, and both activities were well correlated. Hedonic sensory results
indicated that cookies supplemented with 7.5% MBP generally received
satisfactory acceptance scores. Overall, the analysis indicated that cookies
with acceptable physical characteristics and improved antioxidant activities can
be produced by partially replacing wheat flour with MBP. Thus, the addition of
MBP to cookies may be a valuable strategy to increase the consumption of
health-promoting ingredients in a diet that includes convenience foods.
Evaluation of the physicochemical properties of starch isolated from
thinned young ‘Fuji’ apples compared to corn and potato
starches
Authors: Park Han-Sol , Chung Hun-Sik
Published: August 2021

Apple thinning is performed to enhance the mature fruit size and quality;
however, most thinned young fruits, which contain a high starch content compared
to that in mature fruits, are discarded. To increase the utilization of thinned
apples, it is necessary to analyze the various characteristics of the starch
isolated from these fruits. We investigated the chemical, morphological,
pasting, digestive, and syneresis properties of the starch from young
‘Fuji’ apples thinned 60 days after full bloom, and compared them
with those of corn and potato starches (controls). The apparent amylose content
was higher in apple starch (33.6%) than in corn starch (29.8%), and the
phosphorous contents of apple and potato starches were 13.0 and 49.2 mg/100 g,
respectively. Apple starch granules were mostly spherical, hemispherical, and
split in shape and had a C-type X-ray pattern. These granules were smaller than
those of corn and potato starches. The swelling power followed the order of
potato > apple > corn starch, with pasting temperatures of 65.8, 70.2, and
77.1°C, respectively. Potato starch had the highest peak viscosity, while
apple starch had the highest hold and final viscosities and in
vitro digestibility. Apple starch had lower syneresis than the
other two starches. These findings show that young ‘Fuji’ apple
starch displays unique properties that could be useful for industrial
applications.
Growth of Salmonella in napa cabbage kimchi during
fermentation
Authors: Choi Yukyung , Lee Soomin , Lee Heeyoung , Kim Jung Hyun , Kim Sejeong , Ha Jimyeong , Lee Jeeyeon , Oh Hyemin , Yoon Yohan
Published: August 2021

This study evaluated the growth of Salmonella in napa cabbage
kimchi during fermentation. The Baranyi model was fitted to the
Salmonella growth data to calculate lag phase duration
(LPD), maximum specific growth rate (μmax), initiation time of
decrease (ITD), shoulder period (SP), and death rate (DR). The effects of
temperature on kinetic parameters were analyzed using a polynomial model. In the
growth phase, LPD (180.00-4.81 h) decreased and μmax
(0.000-0.592 log CFU/g/h) increased (p<0.05). However, ITD (180-17 h)
decreased (p<0.05) as the temperature increased. In the death phase, SP
(14.95-1.04 h) decreased and DR (−0.018–−0.306 log CFU/g/h)
increased (p<0.05) as the temperature increased. Secondary models on the
kinetic parameters were proposed to describe the effect of temperature, with
R2=0.606−0.956, and the performance [root mean square
error (RMSE) values: 0.350 (growth phase) and 0.428 (death phase)] was
appropriate. The dynamic model demonstrated that Salmonella
growth in napa cabbage kimchi increased during the initiation of fermentation
and subsequently decreased at varying temperatures. Therefore, napa cabbage
kimchi should be sufficiently fermented to decrease the risk of
Salmonella infection.
Lesion Normalization and Supervised Learning in Post-Traumatic Seizure Classification with Diffusion MRI
Authors: Akbar Md Navid , Ruf Sebastian , Rocca Marianna La , Garner Rachael , Barisano Giuseppe , Cua Ruskin , Vespa Paul , Erdoğmuş Deniz , Duncan Dominique
Published: August 2021

Traumatic brain injury (TBI) is a serious condition, potentially causing seizures and other lifelong disabilities. Patients who experience at least one seizure one week after TBI (late seizure) are at high risk for lifelong complications of TBI, such as post-traumatic epilepsy (PTE). Identifying which TBI patients are at risk of developing seizures remains a challenge. Although magnetic resonance imaging (MRI) methods that probe structural and functional alterations after TBI are promising for biomarker detection, physical deformations following moderate-severe TBI present problems for standard processing of neuroimaging data, complicating the search for biomarkers. In this work, we consider a prediction task to identify which TBI patients will develop late seizures, using fractional anisotropy (FA) features from white matter tracts in diffusion-weighted MRI (dMRI). To understand how best to account for brain lesions and deformations, four preprocessing strategies are applied to dMRI, including the novel application of a lesion normalization technique to dMRI. The pipeline involving the lesion normalization technique provides the best prediction performance, with a mean accuracy of 0.819 and a mean area under the curve of 0.785. Finally, following statistical analyses of selected features, we recommend the dMRI alterations of a certain white matter tract as a potential biomarker.
Prediction of therapy outcomes of CLL using gene expression intensity, clustering, and ANN classification of single cell transcriptomes
Authors: Lyu Minjie , Jin Huan , Bellotti Anthony , Lin Xin , Cao Zhiwei , Keskin Derin B. , Brusic Vladimir
Published: August 2021

Background

Single cell transcriptomics is a new technology that enables us to measure the expression levels of genes from an individual cell. The expression information reflects the activity of that individual cell which could be used to indicate the cell types. Chronic lymphocytic leukemia (CLL) is a malignancy of B cells, one of the peripheral blood mononuclear cells subtypes. We applied five analytical tools for the study of single cell gene expression in CLL course of therapy. These tools included the analysis of gene expression distributions – median, interquartile ranges, and percentage above quality control (QC) threshold; hierarchical clustering applied to all cells within individual single cell data sets; and artificial neural network (ANN) for classification of healthy peripheral blood mononuclear cell (PBMC) subtypes. These tools were applied to the analysis of CLL data representing states before and during the therapy.

Results

We identified patterns in gene expression that distinguished two patients that had complete remission (complete response), a patient that had a relapse, and a patient that had partial remission within three years of Ibrutinib therapy. Patients with complete remission showed a rapid decline of median gene expression counts, and the total number of gene counts below the QC threshold for healthy cells (670 counts) in 80% of more of the cells. These patients also showed the emergence of healthy-like PBMC cluster maps within 120 days of therapy and distinct changes in predicted proportions of PBMC cell types.

Conclusions

The combination of basic statistical analysis, hierarchical clustering, and supervised machine learning identified patterns from gene expression that distinguish four CLL patients treated with Ibrutinib that experienced complete remission, partial remission, or relapse. These preliminary results suggest that new bioinformatics tools for single cell transcriptomics, including ANN comparison to healthy PBMC, offer promise in prognostics of CLL.
Impacts of regional lockdown policies on COVID-19 transmission in India in 2020
Authors: Kalra Aarushi , Novosad Paul
Published: August 2021

Objective

To assess the impact of non-pharmaceutical interventions (NPIs) on the first wave of COVID transmission and fatalities in India.

Methods

We collected data on NPIs, using government notifications and news reports, in six major Indian states from March to August 2020, and we matched these with district-level data on COVID related deaths and Google Mobility reports. We used a district fixed effect regression approach to measure the extent to which district-level lockdowns and mobility restrictions helped reduce deaths in 2020.

Results

In most states, COVID deaths grew most rapidly only after the initial lockdown was lifted. District-level NPIs were associated with a statistically significantly lower COVID death count in three out of five sample states (district analysis was not possible in Delhi) and in the aggregate. Interventions that were most associated with slowing fatalities were temple closures, retail closures, and curfews.

Discussion

Outside of Maharashtra (the first state struck) the first fatality wave appears to have been delayed by the national lockdown. India’s NPIs, however incomplete, were successful in delaying or limiting COVID-19 deaths. Even with incomplete compliance, limiting mass gatherings in face of incipient viral waves may save lives.
Progress of the Delta variant and erosion of vaccine effectiveness, a warning from Utah
Authors: Keegan Lindsay T. , Truelove Shaun , Lessler Justin
Published: August 2021

Since the emergence of SARS-CoV-2, vaccines have been heralded as the best way to curtail the pandemic. Clinical trials have shown SARS-CoV-2 vaccines to be highly efficacious against both disease and infection. However, those currently in use were primarily tested against early lineages. Data on vaccine effectiveness (VE) against variants of concern (VOC), including the Delta variant (B.1.617.2), remain limited. To examine the effectiveness of vaccination in Utah we compared the proportion of cases reporting vaccination to that expected at different VEs, then estimated the combined daily vaccine effectiveness using a field evaluation approach. Delta has rapidly outcompeted all other variants and, as of June 20th, represents 70% of all SARS-CoV-2 viruses sequenced in Utah. If we attribute the entire change in VE to the Delta variant, the estimated vaccine effectiveness against Delta would be 82% (95% CI: 78%, 85%). We show a modest reduction in vaccine effectiveness against COVID-19 in Utah corresponding to the expansion of the Delta lineage in the state. This reduction in the effectiveness of available vaccines correlated with the arrival of novel VOCs, rather than waning immunity, is highly concerning.