bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Genome Sequence of Bisphenol A-Degrading Bacterium
Sphingobium
sp. Strain A3, Isolated from Contaminated Soil
Authors: Jung Ji Young , Kang Hye Kyeoung , Jeong Dae Won , Jin Hyun Mi , Ryu Byung-Gon , Jo Bok Yeon , Chung Eu Jin , Han Sang-Soo
Published: January 2021

This study reports the complete genome sequence of bisphenol A-degrading bacterium
Sphingobium
sp. strain A3, which was isolated from a contaminated soil sample from the site of a factory fire in South Korea. The genome consists of a 6.53-Mbp chromosome and eight plasmid contigs (532,947 bp), with 6,406 protein-coding sequences and a GC content of 63.82%.
Complete Genome Sequence of Nisin-Producing Lactococcus lactis subsp.
lactis
N8
Authors: Wan Xing , Takala Timo M. , Qiao Mingqiang , Saris Per E. J.
Published: January 2021

We report here the genome sequence of
Lactococcus lactis
N8, a nisin producer isolated in the 1960s from a dairy product in Finland. The genome consists of a 2.42-Mb chromosome and two plasmids of 80.3 and 71.3 kb.
Draft Genome Sequence of NYR20, a Red Pigment-Secreting Mutant of Saccharomyces cerevisiae
Authors: Takahashi Hiro , Iwaguchi Shin-ichi , Kondo Hisashi , Motomura Taichiro , Murase Masataka , Takahashi Anna , Fukuyoshi Shuichi , Machida Chiyoko , Kanamasa Shin , Yamamoto Satoru , Yoshizaki Takayuki
Published: January 2021

A
Saccharomyces cerevisiae
mutant strain, NYR20, produces a red pigment owing to adenine auxotrophy. Unlike other yeast adenine biosynthetic mutants, this strain not only produces but also secretes this pigment. Here, we report the NYR20 draft genome sequence, thereby advancing our understanding of pigment secretion mechanisms.
Genome Sequence of the Fungus Nannizziopsis barbatae, an Emerging Reptile Pathogen
Authors: Powell Daniel , Jones Ashley , Jackson Nicola , Kaur Parwinder , Bar Ido , Schwessinger Benjamin , Frère Céline H.
Published: January 2021

Nannizziopsis barbata
is an emerging fungal pathogen capable of causing contagious dermatomycosis in reptiles. Here, we report a 31.54-Mb draft genome sequence of an isolate originating from an infected eastern water dragon in Brisbane, Australia.
Supplemental Material: Organic biomorphs may be better preserved than microorganisms in early Earth sediments
Authors: Nims Christine , Cosmidis Julie , al. et
Published: January 2021

Detailed materials and methods, supplemental text, and Figures S1–S4.
A child with Henoch-Schonlein purpura secondary to a COVID-19 infection
Authors: AlGhoozi Dalal Anwar , AlKhayyat Haya Mohammed
Published: January 2021

Henoch-Schonlein purpura (HSP) is a common IgA-mediated small vessel vasculitis of childhood that affects several systems. It is characterised by a tetrad of dermatological, abdominal, joint and renal manifestations. HSP can occur secondary to upper respiratory tract infections, medications, vaccinations and malignancies. COVID-19 is caused by SARS-CoV-2, a single-stranded RNA virus from the Beta-Coronaviridae family, and often presents as a respiratory infection with symptoms ranging from a mild common cold-like illness to severe pneumonia. It has also been reported to exhibit extrapulmonary manifestations, including but not limited to cardiac, thrombotic, hepatocellular and dermatological complications. We report a case of a 4-year-old boy who presented with clinical features of HSP, with detailed history that revealed a recent recovery from a COVID-19 upper respiratory tract infection, indicating a possible correlation between the two.
Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals
Authors: Izzi-Engbeaya Chioma , Distaso Walter , Amin Anjali , Yang Wei , Idowu Oluwagbemiga , Kenkre Julia S , Shah Ronak J , Woin Evelina , Shi Christine , Alavi Nael , Bedri Hala , Brady Niamh , Blackburn Sophie , Leczycka Martina , Patel Sanya , Sokol Elizaveta , Toke-Bjolgerud Edward , Qayum Ambreen , Abdel-Malek Mariana , Hope David C D , Oliver Nick S , Bravis Vasiliki , Misra Shivani , Tan Tricia M , Hill Neil E , Salem Victoria
Published: January 2021

Introduction

Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes.

Research design and methods

This is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis.

Results

62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count.

Conclusions

In this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups.
Taking prevention to the next step: implementation of a brief, sustainable frailty assessment in a cardiology clinic
Authors: Orkaby Ariela R , James Kirstyn , Leuchtenburg Jessica , Solooki Esther , Gaziano J Michael , Driver Jane A
Published: January 2021

Background

Frailty measurement is recommended when assessing older adults with cardiovascular disease to individualise prevention and treatment. We sought to address this by incorporating routine gait speed measurement by clinicians into an outpatient preventive cardiology clinic.

Methods

Quality improvement (QI) project initiated at VA Boston in January 2015 to measure usual gait speed in m/s over a 4 m distance for patients aged 70 and older. The primary outcome was completion and documentation of 4 m usual gait speed. Data were manually extracted from the electronic health record. Frequency distributions and descriptive statistics are presented.

Interventions

Several change interventions were implemented over a 5-year period (January 2015–December 2019) addressing (1) stakeholder engagement and project champions, (2) staff education, (3) assessment space, (4) electronic health record template update and (5) sustaining the initiative. Statistical process control charts were used to monitor proportion of gait speed measurement and to detect shifts resulting from 5 phase change interventions.

Results

During this QI project, 178 patients aged 70 and older attended the clinic, accounting for 1042 individual clinic visits. Gait speed was measured at least once for 157 patients; 21 were never assessed. At the end of the first month (January 2015), gait speed was measured during 40% of clinic visits and rose to a median measurement rate of 78% at clinic visits during the 2018–2019 study period. An unanticipated result was the spread of the initiative to other cardiology clinics.

Conclusions

Gait speed measurement was successfully embedded into clinic assessments for older adults at a cardiology clinic following targeted interventions. This project highlights the feasibility of incorporating a brief frailty assessment such as gait speed, into non-geriatric medicine clinics.
Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment
Authors: Liu Chen-Hua , Chen Chi-Yi , Su Wei-Wen , Tseng Kuo-Chih , Lo Ching-Chu , Liu Chun-Jen , Chen Jyh-Jou , Peng Cheng-Yuan , Shih Yu-Lueng , Yang Sheng-Shun , Huang Chia-Sheng , Huang Ke-Jhang , Chang Chi-Yang , Tsai Ming-Chang , Kao Wei-Yu , Fang Yo-Jen , Chen Po-Yueh , Su Pei-Yuan , Tseng Chih-Wei , Huang Jow-Jyh , Lee Pei-Lun , Lai Hsueh-Chou , Hsieh Tsai-Yuan , Chang Chung-Hsin , Huang Yi-Jie , Lee Fu-Jen , Chang Chun-Chao , Kao Jia-Horng
Published: January 2021

Objective

Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.

Design

191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed.

Results

The SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations.

Conclusion

SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.
Improvement in left ventricular mechanics following medical treatment of constrictive pericarditis
Authors: Sato Kimi , Ayache Ayman , Kumar Arnav , Cremer Paul C , Griffin Brian , Popovic Zoran B , Jellis Christine , Kwon Deborah H , Bolen Michael , Ramchand Jay , Chetrit Michael , Furqan Muhammad M , Johnston Douglas , Klein Allan L
Published: January 2021

Objective

Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP.

Methods

We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e’) at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e’) or the ratio of the left ventricular lateral and septal wall longitudinal strain (LSlateral/LSseptal) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model.

Results

During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LSlateral/LSseptaland lateral/septal e’. During follow-up, only transient CP showed improvement in lateral/septal e’ (p<0.001) and LSlateral/LSseptal(p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e’ and LSlateral/LSseptalwere associated with clinical resolution of CP using anti-inflammatory therapy.

Conclusions

Improvement of constrictive physiology detected by lateral/septal e’ and LSlateral/LSseptalwas associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP.
Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women
Authors: Martikainen Pekka , Korhonen Kaarina , Jelenkovic Aline , Lahtinen Hannu , Havulinna Aki , Ripatti Samuli , Borodulin Katja , Salomaa Veikko , Davey Smith George , Silventoinen Karri
Published: January 2021

Background

Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.

Methods

The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.

Results

Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.

Conclusions

PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.
Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors
Authors: Hao Xingxing , Falo III Louis D , Chen Guo , Zhang Jiying , Carey Cara D , Storkus Walter J , Falo Jr Louis D , You Zhaoyang
Published: January 2021

Background

Despite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need.

Methods

Mice developing induced/spontaneous BrafV600E/Pten−/−melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4+and CD8+T cells, and the development of TRP2-specific CD8+T cells were then monitored over time.

Results

Vaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1. The therapeutic efficacy of the vaccine was associated with host skin-resident cells, the induction of a systemic, broadly reactive IFNγ+CD8+T cell repertoire, increased frequencies of CD8+TIL and reduced levels of PD1hi/intCD8+T cells. Extended survival was associated with improved TIL functionality, exemplified by the presence of enhanced levels of IFNγ+CD8+TIL and IL2+CD4+TIL.

Conclusions

These data support the use of a novel genetic vaccine for the effective treatment of localized or multifocal melanoma refractory to conventional αPD1-based and/or Brafi-based (immune)therapy.
Rationing, racism and justice: advancing the debate around ‘colourblind’ COVID-19 ventilator allocation
Authors: Schmidt Harald , Roberts Dorothy E , Eneanya Nwamaka D
Published: January 2021

Withholding or withdrawing life-saving ventilators can become necessary when resources are insufficient. In the USA, such rationing has unique social justice dimensions. Structural elements of dominant allocation frameworks simultaneously advantage white communities, and disadvantage Black communities—who already experience a disproportionate burden of COVID-19-related job losses, hospitalisations and mortality. Using the example of New Jersey’s Crisis Standard of Care policy, we describe how dominant rationing guidance compounds for many Black patients prior unfair structural disadvantage, chiefly due to the way creatinine and life expectancy are typically considered.

We outline six possible policy options towards a more just approach: improving diversity in decision processes, adjusting creatinine scores, replacing creatinine, dropping creatinine, finding alternative measures, adding equity weights and rejecting the dominant model altogether. We also contrast these options with making no changes, which is not a neutral default, but in separate need of justification, despite a prominent claim that it is simply based on ‘objective medical knowledge’. In the regrettable absence of fair federal guidance, hospital and state-level policymakers should reflect on which of these, or further options, seem feasible and justifiable.

Irrespective of which approach is taken, all guidance should be supplemented with a monitoring and reporting requirement on possible disparate impacts. The hope that we will be able to continue to avoid rationing ventilators must not stand in the way of revising guidance in a way that better promotes health equity and racial justice, both to be prepared, and given the significant expressive value of ventilator guidance.
Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people
Authors: Hopkinson Nicholas S , Rossi Niccolo , El-Sayed_Moustafa Julia , Laverty Anthony A , Quint Jennifer K , Freidin Maxim , Visconti Alessia , Murray Ben , Modat Marc , Ourselin Sebastien , Small Kerrin , Davies Richard , Wolf Jonathan , Spector Tim D , Steves Claire J , Falchi Mario
Published: January 2021

Background

The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.

Methods

UK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of ‘classic’ symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers.

Results

Between 24 March 2020 and 23 April 2020, data were available on 2 401 982 participants, mean (SD) age 43.6 (15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834 437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR (95% CI) 1.14 (1.10 to 1.18); >5 symptoms 1.29 (1.26 to 1.31); >10 symptoms 1.50 (1.42 to 1.58). The pattern of association between reported symptoms did not vary between smokers and non-smokers.

Interpretation

These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.
A New Fuzzy Knowledge-based Optimisation System for Management of Container Yard Operations
Authors: Al Bazi Ammar , Palade Vasile , Abbas Ali
Published: January 2021

Managing the container yard operations can be challenging as a result of various uncertainties associated with storing and retrieving containers from the yard. These associated uncertainties occur because the arrival of a truck to pick up the container is random, so the departure time of the container is unknown. The problem investigated in this paper emerges when newly arrived containers of different sizes, types and weights require storage operation in the same yard where other containers have already been stored. This situation becomes more challenging when the time of departure of existing container is not known. This study develops a new Fuzzy Knowledge-Based optimisation system named ‘FKB_GA’ for optimal storage and retrieval of containers in a yard that contains long stay pre-existing containers. The containers’ duration of stay factor is considered along with two other factors such as the similarity (containers with same customer) and the quantity of containers per stack. A new Multi-Layered Genetic Algorithm module is proposed which identifies the optimal fuzzy rules required for each set of fired rules to achieve a minimum number of container re-handlings when selecting a stack. An industrial case study is used to demonstrate the applicability and practicability of the developed system.
On Some Construction Method and Orness Measure of Bi-Capacities
Authors: Jin LeSheng , Mesiar Radko , Stupnanov Andrea , Yager Ronald R. , Kalina Martin
Published: January 2021

Bi-Choquet Integrals based on bi-capacities are very powerful aggregation operators introduced by Grabisch and Labreuche, and they can generalize Choquet Integrals. Bi-capacities can model a lager range of preferences than capacities. However, there are few existent knowledge about constructing bi-capacities, and there lacks the practical and reasonable orness/andness definitions for bi-capacities to present an effective optimism/pessimism indicator. We present a convenient way to generate bi-capacities. As the main proposal of this study, we propose an orness/andness definition for bi-capacities. Although structurally complex in defining, with the help of one interesting proposition related to bi-Choquet Integral, its reasonability in the way of constructing further proves it can indeed serve as a perfect generalization of orness/andness for capacities.
The α, β-Cut Intervals and Weakest t-Norm Based Importance Measure for Criticality Analysis in Intuitionisitic Fuzzy Fault Tree Analysis of LNG-ESD System
Authors: Kumar Mohit , Sharma Swati
Published: January 2021

Different importance measures have been developed and widely utilized in system reliability analysis to measure the importance of system components. During operation period of a complex system, it becomes more difficult to collect exact failure data of system components i.e. the collected failure data may have some sort of uncertainties due to various reasons. Generally, triangular shaped fuzzy numbers or intuitionistic fuzzy numbers (IFNs) are used to quantify the various types of uncertainty in failure data of the system’s components and fuzzy arithmetic operations are utilized which computes each reliability index with wide range of prediction due to accumulating phenomenon of fuzziness. In this paper, different types of intuitionistic fuzzy number (IFN) are used to quantify the failure data uncertainty of the system’s components while α, β-cut intervals and weakest t-norm (Tw)-based arithmetic operations are employed to reduce the range of prediction for each reliability index. The objective of the present study is to develop Tw-based importance measure for criticality analysis in intuitionistic fuzzy fault tree analysis (IF-FTA) of a system, when different types of uncertainties in crisp failure data of basic events are quantified by different types of membership and non-membership functions. The developed importance measure applies system fault tree, α-cut and β-cut intervals, different types of intuitionistic fuzzy number (IFN) and weakest t-norm (Tw) based intuitionistic fuzzy arithmetic operations. To demonstrate the applicability of the proposed measure, a case study of liquefied natural gas terminal emergency shutdown system (LNG-ESD system) is performed. The IF-FTA of LNG-ESD system is presented to evaluate the fault intervals of the system at different levels using Tw-based arithmetic operations on different types of IFNs. The developed importance measure is applied to identify and rank the critical basic events in IF-FTA of LNG-ESD system. The proposed measure is also compared with some existing importance measures.
A Conversational Agent Framework with Multi-modal Personality Expression
Authors: Sonlu Sinan , Güdükbay Uğur , Durupinar Funda
Published: January 2021

Consistently exhibited personalities are crucial elements of realistic, engaging, and behavior-rich conversational virtual agents. Both nonverbal and verbal cues help convey these agents’ unseen psychological states, contributing to our effective communication with them. We introduce a comprehensive framework to design conversational agents that express personality through non-verbal behaviors like body movement and facial expressions, as well as verbal behaviors like dialogue selection and voice transformation. We use the OCEAN personality model, which defines personality as a combination of five orthogonal factors of openness, conscientiousness, extraversion, agreeableness, and neuroticism. The framework combines existing personality expression methods with novel ones such as new algorithms to convey Laban Shape and Effort qualities. We perform Amazon Mechanical Turk studies to analyze how different communication modalities influence our perception of virtual agent personalities and compare their individual and combined effects on each personality dimension. The results indicate that our personality-based modifications are perceived as natural, and each additional modality improves perception accuracy, with the best performance achieved when all the modalities are present. We also report some correlations for the perception of conscientiousness with neuroticism and openness with extraversion.
Bernoulli Factories and Black-box Reductions in Mechanism Design
Authors: Dughmi Shaddin , Hartline Jason , Kleinberg Robert D. , Niazadeh Rad
Published: January 2021

We provide a polynomial time reduction from Bayesian incentive compatible mechanism design to Bayesian algorithm design for welfare maximization problems. Unlike prior results, our reduction achieves exact incentive compatibility for problems with multi-dimensional and continuous type spaces. The key technical barrier preventing exact incentive compatibility in prior black-box reductions is that repairing violations of incentive constraints requires understanding the distribution of the mechanism’s output, which is typically #P-hard to compute. Reductions that instead estimate the output distribution by sampling inevitably suffer from sampling error, which typically precludes exact incentive compatibility. We overcome this barrier by employing and generalizing the computational model in the literature on
Bernoulli Factories
. In a Bernoulli factory problem, one is given a function mapping the bias of an “input coin” to that of an “output coin,” and the challenge is to efficiently simulate the output coin given only sample access to the input coin. This is the key ingredient in designing an incentive compatible mechanism for bipartite matching, which can be used to make the approximately incentive compatible reduction of Hartline et al. [18] exactly incentive compatible.
Short-term metformin ingestion by healthy older adults improves myoblast function
Authors: Mahmassani Ziad S. , McKenzie Alec I. , Petrocelli Jonathan J. , de Hart Naomi M. , Reidy Paul T. , Fix Dennis K. , Ferrara Patrick J. , Funai Katsuhiko , Drummond Micah J.
Published: January 2021

Muscle progenitor cells (MPCs) in aged muscle exhibit impaired activation into proliferating myoblasts, thereby impairing fusion and changes in secreted factors. The antihyperglycemic drug metformin, currently studied as a candidate antiaging therapy, may have potential to promote function of aged MPCs. We evaluated the impact of 2 wk of metformin ingestion on primary myoblast function measured in vitro after being extracted from muscle biopsies of older adult participants. MPCs were isolated from muscle biopsies of community-dwelling older (4 male/4 female, ∼69 yr) adult participants before (pre) and after (post) the metformin ingestion period and studied in vitro. Cells were extracted from Young participants (4 male/4 female, ∼27 yr) to serve as a “youthful” comparator. MPCs from Old subjects had lower fusion index and myoblast-endothelial cell homing compared with Young, while Old MPCs, extracted after short-term metformin ingestion, performed better at both tasks. Transcriptomic analyses of Old MPCs (vs. Young) revealed decreased histone expression and increased myogenic pathway activity, yet this phenotype was partially restored by metformin. However, metformin ingestion exacerbated pathways related to inflammation signaling. Together, this study demonstrated that 2 wk of metformin ingestion induced persistent effects on Old MPCs that improved function in vitro and altered their transcriptional signature including histone and chromatin remodeling.
Cellular clocks in hyperoxia effects on [Ca2+]i regulation in developing human airway smooth muscle
Authors: Bartman Colleen M. , Matveyenko Aleksey , Pabelick Christina , Prakash Y. S.
Published: January 2021

Supplemental O2 (hyperoxia) is necessary for preterm infant survival but is associated with development of bronchial airway hyperreactivity and childhood asthma. Understanding early mechanisms that link hyperoxia to altered airway structure and function are key to developing advanced therapies. We previously showed that even moderate hyperoxia (50% O2) enhances intracellular calcium ([Ca2+]i) and proliferation of human fetal airway smooth muscle (fASM), thereby facilitating bronchoconstriction and remodeling. Here, we introduce cellular clock biology as a novel mechanism linking early oxygen exposure to airway biology. Peripheral, intracellular clocks are a network of transcription-translation feedback loops that produce circadian oscillations with downstream targets highly relevant to airway function and asthma. Premature infants suffer circadian disruption whereas entrainment strategies improve outcomes, highlighting the need to understand relationships between clocks and developing airways. We hypothesized that hyperoxia impacts clock function in fASM and that the clock can be leveraged to attenuate deleterious effects of O2 on the developing airway. We report that human fASM express core clock machinery ( PER1, PER2, CRY1, ARNTL/BMAL1 , CLOCK) that is responsive to dexamethasone (Dex) and altered by O2. Disruption of the clock via siRNA-mediated PER1 or ARNTL knockdown alters store-operated calcium entry (SOCE) and [Ca2+]i response to histamine in hyperoxia. Effects of O2 on [Ca2+]i are rescued by driving expression of clock proteins, via effects on the Ca2+ channels IP3R and Orai1. These data reveal a functional fASM clock that modulates [Ca2+]i regulation, particularly in hyperoxia. Harnessing clock biology may be a novel therapeutic consideration for neonatal airway diseases following prematurity.
The ethanol metabolite acetic acid activates mouse nucleus accumbens shell medium spiny neurons
Authors: Chapp Andrew D. , Mermelstein Paul G. , Thomas Mark J.
Published: January 2021

Ethanol consumption disrupts many neurophysiological processes leading to alterations in behavior and physiological function. The possible involvement of acetic acid, produced via ethanol metabolism, has been insufficiently explored. Here, we demonstrate that acetic acid contributes to rapid neurophysiological alterations in the accumbens shell. These findings raise the interesting possibility that ethanol may serve as a prodrug—generating acetic acid as a metabolite—that may influence ethanol consumption-associated behaviors and physiological responses by altering neurophysiological function.
Progress on Preparation of pH/Temperature-Sensitive Intelligent Hydrogels and Applications in Target Transport and Controlled Release of Drugs
Authors: Li Lixian , He Yongpeng , Zheng Xiaodong , Yi Lin , Nian Weiqi
Published: January 2021

Hydrogels with three-dimensional network structure, hydrophilic, and insoluble in water which are ideal carrier materials for intelligent drug delivery systems. Intelligent hydrogel has become a research frontier and hotspot because of its intelligence, high efficiency, safety, and convenience in drug controlled and prolonged release. It has a broad application prospect in the medicine and biomedicine fields and can lead the medicine fields into a new era of “precise treatment.” Based on the latest research progress, the main preparation methods of hydrogel and the development of the drug delivery system are briefly introduced. The most promising three intelligent hydrogels in the human physiological environment, namely, pH responsiveness, temperature responsiveness, and pH/temperature dual responsiveness, are emphatically reviewed. Their release mechanisms, targeting transport, and controlled-prolonged release of drug are also discussed. In addition, some suggestions for the main problems and future development were given.
Gait Recognition for Human-Exoskeleton System in Locomotion Based on Ensemble Empirical Mode Decomposition
Authors: Qiu Jing , Liu Huxian
Published: January 2021

As exoskeleton robots are more frequently applied to impaired people to regain mobility, detection and recognition of human gait motions is important to prepare suitable control modes for exoskeletons. This paper proposes to explore the potential of the ensemble empirical mode decomposition (EEMD) method to help analyze and recognize gait motions for human subjects who wear the exoskeleton to walk. The intrinsic mode functions (IMFs) extracted from the original gait signals by EEMD are utilized to act as inputs for classification algorithms. Evident correlations are found between some IMFs and original gait kinematic sequences. Experimental results on gait phase recognition performance on 14 able-bodied subjects are shown. The performance of the composing signals extracted from the original signals as

IMF
1
∼
IMF
8

is investigated, which indicates that

IMF
8

might be helpful when wearing exoskeleton and

IMF
5

might be helpful when walking without exoskeleton on gait recognition. And the similarity of joint synergy between wearing and without wearing exoskeleton is analyzed, and the result shows that the joint synergy might change between with and without wearing exoskeleton. The quantitative results show that based on some IMFs of the same orders, these machine learning algorithms can achieve promising performances.
Imaging Software-Based Sarcopenia Assessment in Gastroenterology: Evolution and Clinical Meaning
Authors: Marasco Giovanni , Sadalla Sinan , Vara Giulio , Golfieri Rita , Festi Davide , Colecchia Antonio , Renzulli Matteo
Published: January 2021

Sarcopenia is gaining attention as a negative prognostic factor in different fields of medicine, including chronic liver failure. However, the assessment of sarcopenia in patients with liver diseases is often neglected due to unawareness of reliable tools and methods and thus is limited to research studies. Cross-sectional imaging is a diffuse diagnostic tool and is commonly performed in patients with chronic liver failure. The last advancements in radiology image analysis using dedicated software allow an easy and standardized method to assess skeletal muscle volume. Several measures can be obtained from cross-sectional imaging analysis to evaluate sarcopenia in patients affected by chronic liver disease. We aimed to review the recent advances in imaging-based sarcopenia assessment, in particular in patients with chronic liver diseases. As a result, we found that the skeletal muscle index (SMI) seems to be a reliable method to assess sarcopenia in cirrhotic patients. Even if further studies are needed to validate proper cut-offs for each clinical endpoint, physicians are invited to consider the assessment of sarcopenia in the work-up of patients with chronic liver disease.
Homogenized ORB Algorithm Using Dynamic Threshold and Improved Quadtree
Authors: Ma Chaoqun , Hu Xiaoguang , Xiao Jin , Zhang Guofeng
Published: January 2021

The Oriented FAST and Rotated BRIEF (ORB) algorithm has the problem that the extracted feature points are overconcentrated or even overlapped, leading to information loss of local image features. A homogenized ORB algorithm using dynamic thresholds and improved quadtree method is proposed in this paper, named Quadtree ORB (QTORB). In the feature point extraction stage, a new dynamic local threshold calculation method is proposed to enhance the algorithm’s ability to extract feature points at homogeneous regions. Then, a quadtree method is improved and adopted to manage and optimize feature points to eliminate those excessively concentrated and overlapping feature points. Meanwhile, in the feature points optimization process, different quadtree depths are set at different image pyramid levels to prevent excessive splitting of the quadtree and increase calculation speed. In the feature point description stage, local gray difference value information is introduced to enhance the saliency of the feature description. Finally, the Hamming distance is used to match points and RANSAC is used to avoid mismatches. Two datasets, namely, the optical image dataset and SAR image dataset, are used in the experiment. The experimental result shows that, considering accuracy and real-time efficiency, the QTORB can effectively improve the distribution uniformity of feature points.
Some Integral Inequalities for
n
-Polynomial
ζ
-Preinvex Functions
Authors: Wu Shanhe , Awan Muhammad Uzair , Ullah Muhammad Ubaid , Talib Sadia , Kashuri Artion
Published: January 2021

In this paper, we study the properties of

n

-polynomial

ζ

-preinvex functions and establish some integral inequalities of Hermite-Hadamard type via this class of convex functions. Moreover, we discuss some special cases which provide a significant complement to the integral estimations of preinvex functions. Applications of the obtained results to the inequalities for special means are also considered.
Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet–Biedl Syndrome
Authors: Huang Li , Sun Limei , Wang Zhirong , Li Songshan , Chen Chonglin , Luo Xiaoling , Ding Xiaoyan
Published: January 2021

Background. Bardet–Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. Materials and Methods. Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. Results. Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. Conclusions. This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS.
An Update on the Potential of Mesenchymal Stem Cell Therapy for Cutaneous Diseases
Authors: Li Yanyun , Ye Ziyu , Yang Weiqin , Zhang Qunzhou , Zeng Jincheng
Published: January 2021

Mesenchymal stem or stromal cells (MSCs) are nonhematopoietic postnatal stem cells with self-renewal, multipotent differentiation, and potent immunomodulatory and anti-inflammatory capabilities, thus playing an important role in tissue repair and regeneration. Numerous clinical and preclinical studies have demonstrated the potential application of MSCs in the treatment of tissue inflammation and immune diseases, including inflammatory skin diseases. Therefore, understanding the biological and immunological characteristics of MSCs is important to standardize and optimize MSC-based regenerative therapy. In this review, we highlight the mechanisms underlying MSC-mediated immunomodulation and tissue repair/regeneration and present the latest development of MSC-based clinical trials on cutaneous diseases.
Determination of Organophosphorus Esters in Fall Protection Equipment by Accelerated Solvent Extraction and Solid-Phase Extraction Coupled with LC-MS/MS Detection
Authors: Li Haihong , Ye Mingli , Wu Fangfang , Zhao Xuyang , Wang Lifeng , Wei Yili , Xie Shengyi , Cui Hairong
Published: January 2021

An analysis method was established to determine 14 organophosphorus ester (OPE) flame retardants in fall protection equipment by combining accelerated solvent extraction (ASE) and solid-phase extraction (SPE) with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The ASE parameters were optimized as follows: static extraction with acetonitrile at 80°C for 5 min for two cycles. The combined extract was purified with the ENVI-18 cartridge before further analysis. A HILIC column was used to separate the OPEs using an acetonitrile/water mixture as the mobile phase with the detection by the electrospray ionization mass spectrometry, which was operated under the positive mode. Under optimized conditions, the limit of detection for the target OPEs ranged in 0.015–1.33 ng/g, with a spike recovery of 71.6%–114% and a relative standard deviation of 0.8%–11.2%. The developed method was used to analyze OPEs in fall protection equipment (safety helmets and ropes), where OPEs were all detectable. Safety ropes displayed a higher concentration of OPEs than ones in safety helmets, with the pollutants being mainly triphenyl phosphate, 2-ethylhexyl diphenyl phosphate (EHDPP), tri(2-ethylhexyl) phosphate, and tri-n-butyl phosphate in the range of 11.07 ng/g‒815.53 ng/g. The EHDPP was the dominant compound in safety helmets with the concentration from 26.84 to 95.29 ng/g, while the other OPEs in safety helmets were lower than 5.136 ng/g. The potential health and environmental risks of these fall protection equipment during their use and disposal call for further attention.
Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
Authors: Lin Yan , Dong Yu , Gao Yanfeng , Shi Ranran , Li Yubing , Zhou Xiuman , Liu Wenwen , Li Guodong , Qi Yuanming , Wu Yahong
Published: January 2021

Tuberculosis is the world’s most deadly infectious disease, with 10 million people falling ill and 1.5 million people dying from the disease every year. With the increasing number of drug-resistant Mycobacterium tuberculosis (MTB) strains and prevalence of coinfection of MTB with human immunodeficiency virus, many challenges remain in the prevention and treatment of tuberculosis. Therefore, the development of safe and effective tuberculosis vaccines is an urgent issue. In this study, we identified cytotoxic T lymphocyte epitopes on drug resistance-associated membrane protein efflux pumps of MTB, the ATP-binding cassette and the major facilitator superfamilies. First, three online software were used to predict HLA-A2-restricted epitopes. Then, the candidate epitopes were confirmed with the T2A2 cell binding affinity and peptide/MHC (pMHC) complex stability assays and in vitro immune activity experiments. Two drug-resistant T lymphocyte epitopes, designated Rv1218c-p24 and Rv2477c-p182, were selected, and their immunogenic activities studied in vivo in genetically engineered mice. The immune activities of these two epitopes were improved with the help of complete Freund’s adjuvant (CFA). The epitopes identified here provide a foundation for the diagnosis and treatment of patients infected with drug resistant and the future development of a multiepitope vaccine.
Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps
Authors: Passarelli Michael N. , Thompson Bonne M. , McDonald Jeffrey G. , Snover Dale C. , Palys Thomas J. , Rees Judy R. , Barry Elizabeth L. , Baron John A.
Published: January 2021

The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05–1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17–3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66–1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50–2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps.

Prevention Relevance:

This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.