bluuebunny/crossref_metadata_2025 huggingface dataset:
A Real-Time PCR Assay for Detection of Low Pneumocystis jirovecii Levels
Authors: Ruiz-Ruiz Susana , Ponce Carolina A. , Pesantes Nicole , Bustamante Rebeca , Gatti Gianna , San Martin Viviana , Gutierrez Mireya , Bórquez Pamela , Vargas Sergio L. , Magne Fabien , Calderón Enrique J. , Pérez-Brocal Vicente , Moya Andrés
Published: January 2022

Here we report a new real-time PCR assay using SYBR Green which provides higher sensitivity for the specific detection of low levels of Pneumocystis jirovecii. To do so, two primer sets were designed, targeting the family of genes that code for the most abundant surface protein of Pneumocystis spp., namely the major surface glycoproteins (Msg), and the mitochondrial large subunit rRNA (mtLSUrRNA) multicopy gene, simultaneously detecting two regions. PCR methods are instrumental in detecting these low levels; however, current nested-PCR methods are time-consuming and complex. To validate our new real-time Msg-A/mtLSUrRNA PCR protocol, we compared it with nested-PCR based on the detection of Pneumocystis mitochondrial large subunit rRNA (mtLSUrRNA), one of the main targets used to detect this pathogen. All samples identified as positive by the nested-PCR method were found positive using our new real-time PCR protocol, which also detected P. jirovecii in three nasal aspirate samples that were negative for both rounds of nested-PCR. Furthermore, we read both rounds of the nested-PCR results for comparison and found that some samples with no PCR amplification, or with a feeble band in the first round, correlated with higher Ct values in our real-time Msg-A/mtLSUrRNA PCR. This finding demonstrates the ability of this new single-round protocol to detect low Pneumocystis levels. This new assay provides a valuable alternative for P. jirovecii detection, as it is both rapid and sensitive.
Recent Advances in Porcine Reproductive and Respiratory Syndrome Virus NADC30-Like Research in China: Molecular Characterization, Pathogenicity, and Control
Authors: Yu Ying , Zhang Qiaoya , Cao Zhi , Tang Yan-Dong , Xia Dasong , Wang Gang , Shan Hu
Published: January 2022

The name porcine reproductive and respiratory syndrome virus (PRRSV) NADC30-like was first coined in 2015. It originated from the NADC30 strain that was introduced into China by importing breeding pigs and has since undergone mutations or recombination, resulting in variant viruses. Following widespread outbreaks in China in recent years, these NADC30-like strains have presented major health challenges in swine production systems. Outcomes induced by PRRSV NADC30-like infection are highly variable, ranging from inapparent to severe, depending on the recombination between NADC30 and field PRRSV strains prevalent in swine farms. Vaccines and strict biosecurity measures have been explored to fight this disease; however, current PRRSV commercially modified-live virus vaccines (MLVs) have the potential to revert to virulence and only provide limited or no cross-protection efficacy against NADC30-like strains. PRRSVs will remain an ongoing challenge to the swine industry until safe and effective vaccines or antiviral reagents are developed.
Isolation, Characterization, and Antimicrobial Activity of Bacterial and Fungal Representatives Associated With Particulate Matter During Haze and Non-haze Days
Authors: Yan Dong , Zhang Tao , Bai Jing-Lin , Su Jing , Zhao Li-Li , Wang Hao , Fang Xiao-Mei , Zhang Yu-Qin , Liu Hong-Yu , Yu Li-Yan
Published: January 2022

Particulate matter (PM) has been a threat to the environment and public health in the metropolises of developing industrial countries such as Beijing. The microorganisms associated with PM have an impact on human health if they are exposed to the respiratory tract persistently. There are few reports on the microbial resources collected from PM and their antimicrobial activities. In this study, we greatly expanded the diversity of available commensal organisms by collecting 1,258 bacterial and 456 fungal isolates from 63 PM samples. A total of 77 bacterial genera and 35 fungal genera were included in our pure cultures, with Bacillus as the most prevalent cultured bacterial genus, Aspergillus, and Penicillium as the most prevalent fungal ones. During heavy-haze days, the numbers of colony-forming units (CFUs) and isolates of bacteria and fungi were decreased. Bacillus, Paenibacillus, and Chaetomium were found to be enriched during haze days, while Kocuria, Microbacterium, and Penicillium were found to be enriched during non-haze days. Antimicrobial activity against common pathogens have been found in 40 bacterial representatives and 1 fungal representative. The collection of airborne strains will provide a basis to greatly increase our understanding of the relationship between bacteria and fungi associated with PM and human health.
Chromium (VI) Inhibition of Low pH Bioleaching of Limonitic Nickel-Cobalt Ore
Authors: Santos Ana Laura , Dybowska Agnieszka , Schofield Paul F. , Herrington Richard J. , Cibin Giannantonio , Johnson D. Barrie
Published: January 2022

Limonitic layers of the regolith, which are often stockpiled as waste materials at laterite mines, commonly contain significant concentrations of valuable base metals, such as nickel, cobalt, and manganese. There is currently considerable demand for these transition metals, and this is projected to continue to increase (alongside their commodity values) during the next few decades, due in the most part to their use in battery and renewable technologies. Limonite bioprocessing is an emerging technology that often uses acidophilic prokaryotes to catalyse the oxidation of zero-valent sulphur coupled to the reduction of Fe (III) and Mn (IV) minerals, resulting in the release of target metals. Chromium-bearing minerals, such as chromite, where the metal is present as Cr (III), are widespread in laterite deposits. However, there are also reports that the more oxidised and more biotoxic form of this metal [Cr (VI)] may be present in some limonites, formed by the oxidation of Cr (III) by manganese (IV) oxides. Bioleaching experiments carried out in laboratory-scale reactors using limonites from a laterite mine in New Caledonia found that solid densities of ∼10% w/v resulted in complete inhibition of iron reduction by acidophiles, which is a critical reaction in the reductive dissolution process. Further investigations found this to be due to the release of Cr (VI) in the acidic liquors. X-ray absorption near edge structure (XANES) spectroscopy analysis of the limonites used found that between 3.1 and 8.0% of the total chromium in the three limonite samples used in experiments was present in the raw materials as Cr (VI). Microbial inhibition due to Cr (VI) could be eliminated either by adding limonite incrementally or by the addition of ferrous iron, which reduces Cr (VI) to less toxic Cr (III), resulting in rates of extraction of cobalt (the main target metal in the experiments) of >90%.
Correlation Between Antimicrobial Resistance, Virulence Determinants and Biofilm Formation Ability Among Extraintestinal Pathogenic Escherichia coli Strains Isolated in Catalonia, Spain
Authors: Ballén Victoria , Gabasa Yaiza , Ratia Carlos , Sánchez Melany , Soto Sara
Published: January 2022

Escherichia coliis a well-characterized bacterium highly prevalent in the human intestinal tract and the cause of many important infections. The aim of this study was to characterize 376 extraintestinal pathogenicE. colistrains collected from four hospitals in Catalonia (Spain) between 2016 and 2017 in terms of antimicrobial resistance, siderophore production, phylogroup classification, and the presence of selected virulence and antimicrobial resistance genes. In addition, the association between these characteristics and the ability to form biofilms was also analyzed. The strains studied were classified into four groups according to their biofilm formation ability: non-biofilm formers (15.7%), weak (23.1%), moderate (35.6%), and strong biofilm formers (25.6%). The strains were highly resistant to ciprofloxacin (48.7%), trimethoprim-sulfamethoxazole (47.9%), and ampicillin (38%), showing a correlation between higher resistance to ciprofloxacin and lower biofilm production. Seventy-three strains (19.4%) were ESBL-producers. However, no relationship between the presence of ESBL and biofilm formation was found. The virulence factor genesfimH(92%),pgaA(84.6%), andirp1(77.1%) were the most prevalent in all the studied strains. A statistically significant correlation was found between biofilm formation and the presence ofiroN,papA,fimH,sfa,cnf,hlyA,iutA, and colibactin-encoding genesclbA,clbB, clbN, andclbQ. Interestingly, a high prevalence of colibactin-encoding genes (19.9%) was observed. Colibactin is a virulence factor, which interferes with the eukaryotic cell cycle and has been associated with colorectal cancer in humans. Most colibactin-encodingE. coliisolates belonged to phylogroup B2, exhibited low antimicrobial resistance but moderate or high biofilm-forming ability, and were significantly associated with most of the virulence factor genes tested. Additionally, the analysis of their clonal relatedness by PFGE showed 48 different clusters, indicating a high clonal diversity among the colibactin-positive strains. Several studies have correlated the pathogenicity ofE. coliand the presence of virulence factor genes; however, colibactin and its relationship to biofilm formation have been scarcely investigated. The increasing prevalence of colibactin inE. coliand other Enterobacteriaceae and the recently described correlation with biofilm formation, makes colibactin a promising therapeutic target to prevent biofilm formation and its associated adverse effects.
Dynamics of the Fermentation Products, Residual Non-structural Carbohydrates, and Bacterial Communities of Wilted and Non-wilted Alfalfa Silage With and Without Lactobacillus plantarum Inoculation
Authors: Yang Fengyuan , Wang Yanping , Zhao Shanshan , Feng Changsong , Fan Xiaomiao
Published: January 2022

The aim of this study was to investigate effects of wilting and Lactobacillus plantarum inoculation on the dynamics of the fermentation products, residual non-structural carbohydrates, and bacterial communities in alfalfa silage. Fresh and wilted alfalfa were ensiled with and without L. plantarum for 10, 30, 60, and 90 days. A high-throughput sequencing method for absolute quantification of 16S rRNA was adopted to determine the bacterial community composition at different ensiling periods. For the wilted silage, the bacterial community, pH value, and ammonia nitrogen concentration remained stable in the silage at 30 days. L. plantarum inoculation accelerated lactic acid fermentation and altered the predominant genus in the wilted silage as compared with the non-inoculated group. For the non-wilted group, fast consumption of water-soluble carbohydrates (WSCs) was observed at 10 days in the non-inoculated silage along with rapid growth of undesirable Hafnia. L. plantarum inoculation inhibited growth of Hafnia at 10 days in the non-wilted silage. Clostridia fermentation occurred in the non-wilted silage at 90 days, as indicated by an increased pH, formation of butyric acid (BA), and apparent abundance of genera belonging to Clostridia. L. plantarum inoculation inhibited BA accumulation and growth of Garciella in the non-wilted silage at 90 days as compared with the non-wilted silage without inoculation, but had little effect on the growth of Clostridium sensu stricto. Overall, the high moisture content of the non-wilted alfalfa silage led to rapid consumption of WSCs and growth of harmful microorganisms at the early stage of ensiling, resulting in poor fermentation quality. Wilting and L. plantarum inoculation both improved fermentation quality and inhibited the growth of spoilage microorganisms in alfalfa silage, while L. plantarum inoculation alone failed to achieve optimum fermentation quality of non-wilted alfalfa silage.
Exercise-Induced Extracellular Vesicles Delay the Progression of Prostate Cancer
Authors: Sadovska Lilite , Auders Jānis , Keiša Laura , Romanchikova Nadezhda , Silamiķele Laila , Kreišmane Madara , Zayakin Pawel , Takahashi Satoru , Kalniņa Zane , Linē Aija
Published: January 2022

Increasing evidence suggests that regular physical exercise not only reduces the risk of cancer but also improves functional capacity, treatment efficacy and disease outcome in cancer patients. At least partially, these effects are mediated by the secretome of the tissues responding to exercise. The secreted molecules can be released in a carrier-free form or enclosed into extracellular vesicles (EVs). Several recent studies have shown that EVs are actively released into circulation during physical exercise. Here, we for the first time investigated the effects of exercise-induced EVs on the progression of cancer in an F344 rat model of metastatic prostate cancer. Although we did not observe a consistent increase in the circulating EV levels, RNA sequencing analysis demonstrated substantial changes in the RNA content of EVs collected before and immediately after forced wheel running exercise as well as differences between EVs from runners at resting state and sedentary rats. The major RNA biotype in EVs was mRNA, followed by miRNA and rRNA. Molecular functions of differentially expressed RNAs reflected various physiological processes including protein folding, metabolism and regulation of immune responses triggered by the exercise in the parental cells. Intravenous administration of exercise-induced EVs into F344 rats with orthotopically injected syngeneic prostate cancer cells PLS10, demonstrated reduction of the primary tumor volume by 35% and possibly—attenuation of lung metastases. Hence, our data provide the first evidence that exercise-induced EVs may modulate tumor physiology and delay the progression of cancer.
GDP-Mannose 3,5-Epimerase: A View on Structure, Mechanism, and Industrial Potential
Authors: Beerens Koen , Gevaert Ophelia , Desmet Tom
Published: January 2022

GDP-mannose 3,5-epimerase (GM35E, GME) belongs to the short-chain dehydrogenase/reductase (SDR) protein superfamily and catalyses the conversion of GDP-d-mannose towards GDP-l-galactose. Although the overall reaction seems relatively simple (a double epimerization), the enzyme needs to orchestrate a complex set of chemical reactions, with no less than 6 catalysis steps (oxidation, 2x deprotonation, 2x protonation and reduction), to perform the double epimerization of GDP-mannose to GDP-l-galactose. The enzyme is involved in the biosynthesis of vitamin C in plants and lipopolysaccharide synthesis in bacteria. In this review, we provide a clear overview of these interesting epimerases, including the latest findings such as the recently characterized bacterial and thermostable GM35E representative and its mechanism revision but also focus on their industrial potential in rare sugar synthesis and glycorandomization.
eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions
Authors: Stanciu Andrei , Luo Juncheng , Funes Lucy , Galbokke Hewage Shanya , Kulkarni Shardul D. , Aitken Colin Echeverría
Published: January 2022

Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment. More recently, eIF3 has been implicated in driving the selective translation of specific classes of mRNAs. However, unraveling the mechanism of these diverse contributions—and disentangling the roles of the individual subunits of the eIF3 complex—remains challenging. We employed ribosome profiling of budding yeast cells expressing two distinct mutations targeting the eIF3 complex. These mutations either disrupt the entire complex or subunits positioned near the mRNA-entry channel of the ribosome and which appear to relocate during or in response to mRNA binding and start-codon recognition. Disruption of either the entire eIF3 complex or specific targeting of these subunits affects mRNAs with long 5′-untranslated regions and whose translation is more dependent on eIF4A, eIF4B, and Ded1 but less dependent on eIF4G, eIF4E, and PABP. Disruption of the entire eIF3 complex further affects mRNAs involved in mitochondrial processes and with structured 5′-untranslated regions. Comparison of the suite of mRNAs most sensitive to both mutations with those uniquely sensitive to disruption of the entire complex sheds new light on the specific roles of individual subunits of the eIF3 complex.
Nanotechnology in Drug Delivery for Liver Fibrosis
Authors: Gu Lihong , Zhang Feng , Wu Jinhui , Zhuge Yuzheng
Published: January 2022

Liver fibrosis is a reversible disease course caused by various liver injury etiologies, and it can lead to severe complications, such as liver cirrhosis, liver failure, and even liver cancer. Traditional pharmacotherapy has several limitations, such as inadequate therapeutic effect and side effects. Nanotechnology in drug delivery for liver fibrosis has exhibited great potential. Nanomedicine improves the internalization and penetration, which facilitates targeted drug delivery, combination therapy, and theranostics. Here, we focus on new targets and new mechanisms in liver fibrosis, as well as recent designs and development work of nanotechnology in delivery systems for liver fibrosis treatment.
The Effect of Training Sample Size on the Prediction of White Matter Hyperintensity Volume in a Healthy Population Using BIANCA
Authors: Wulms Niklas , Redmann Lea , Herpertz Christine , Bonberg Nadine , Berger Klaus , Sundermann Benedikt , Minnerup Heike
Published: January 2022

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are an important magnetic resonance imaging marker of cerebral small vessel disease and are associated with cognitive decline, stroke, and mortality. Their relevance in healthy individuals, however, is less clear. This is partly due to the methodological challenge of accurately measuring rare and small WMH with automated segmentation programs. In this study, we tested whether WMH volumetry with FMRIB software library v6.0 (FSL; https://fsl.fmrib.ox.ac.uk/fsl/fslwiki) Brain Intensity AbNormality Classification Algorithm (BIANCA), a customizable and trainable algorithm that quantifies WMH volume based on individual data training sets, can be optimized for a normal aging population.

Methods: We evaluated the effect of varying training sample sizes on the accuracy and the robustness of the predicted white matter hyperintensity volume in a population (n = 201) with a low prevalence of confluent WMH and a substantial proportion of participants without WMH. BIANCA was trained with seven different sample sizes between 10 and 40 with increments of 5. For each sample size, 100 random samples of T1w and FLAIR images were drawn and trained with manually delineated masks. For validation, we defined an internal and external validation set and compared the mean absolute error, resulting from the difference between manually delineated and predicted WMH volumes for each set. For spatial overlap, we calculated the Dice similarity index (SI) for the external validation cohort.

Results: The study population had a median WMH volume of 0.34 ml (IQR of 1.6 ml) and included n = 28 (18%) participants without any WMH. The mean absolute error of the difference between BIANCA prediction and manually delineated masks was minimized and became more robust with an increasing number of training participants. The lowest mean absolute error of 0.05 ml (SD of 0.24 ml) was identified in the external validation set with a training sample size of 35. Compared to the volumetric overlap, the spatial overlap was poor with an average Dice similarity index of 0.14 (SD 0.16) in the external cohort, driven by subjects with very low lesion volumes.

Discussion: We found that the performance of BIANCA, particularly the robustness of predictions, could be optimized for use in populations with a low WMH load by enlargement of the training sample size. Further work is needed to evaluate and potentially improve the prediction accuracy for low lesion volumes. These findings are important for current and future population-based studies with the majority of participants being normal aging people.
The Specificity of Cognitive-Motor Dual-Task Interference on Balance in Young and Older Adults
Authors: Ward Nathan , Menta Alekya , Ulichney Virginia , Raileanu Cristiana , Wooten Thomas , Hussey Erika K. , Marfeo Elizabeth
Published: January 2022

Standing upright on stable and unstable surfaces requires postural control. Postural control declines as humans age, presenting greater risk of fall-related injury and other negative health outcomes. Secondary cognitive tasks can further impact balance, which highlights the importance of coordination between cognitive and motor processes. Past research indicates that this coordination relies on executive function (EF; the ability to control, maintain, and flexibly direct attention to achieve goals), which coincidentally declines as humans age. This suggests that secondary cognitive tasks requiring EF may exert a greater influence on balance compared to non-EF secondary tasks, and this interaction could be exaggerated among older adults. In the current study, we had younger and older adults complete two Surface Stability conditions (standing upright on stable vs. unstable surfaces) under varying Cognitive Load; participants completed EF (Shifting, Inhibiting, Updating) and non-EF (Processing Speed) secondary cognitive tasks on tablets, as well as a single task control scenario with no secondary cognitive task. Our primary balance measure of interest was sway area, which was measured with an array of wearable inertial measurement unit sensors. Replicating prior work, we found a main effect of Surface Stability with less sway on stable surfaces compared to unstable surfaces, and we found an interaction between Age and Surface Stability with older adults exhibiting significantly greater sway selectively on unstable surfaces compared to younger adults. New findings revealed a main effect of Cognitive Load on sway, with the single task condition having significantly less sway than two of the EF conditions (Updating and Shifting) and the non-EF condition (Processing Speed). We also found an interaction of Cognitive Load and Surface Stability on postural control, where Surface Stability impacted sway the most for the single task and two of the executive function conditions (Inhibition and Shifting). Interestingly, Age did not interact with Cognitive Load, suggesting that both age groups were equally impacted by secondary cognitive tasks, regardless the presence or type of secondary cognitive task. Taken together, these patterns suggest that cognitive demands vary in their impact on posture control across stable vs. unstable surfaces, and that EF involvement may not be the driving mechanism explaining cognitive-motor dual-task interference on balance.
Type 2 Diabetes Increases Risk of Unfavorable Survival Outcome for Postoperative Ischemic Stroke in Patients Who Underwent Non-cardiac Surgery: A Retrospective Cohort Study
Authors: Zhang Faqiang , Ma Yulong , Yu Yao , Sun Miao , Li Hao , Lou Jingsheng , Cao Jiangbei , Liu Yanhong , Niu Mu , Wang Long , Mi Weidong
Published: January 2022

Objective: Diabetes mellitus (DM) has been critically associated with unfavorable outcomes in the general population. We aimed to investigate the association between type 2 DM and long-term survival outcomes for postoperative ischemic stroke in patients who underwent non-cardiac surgery.

Research Design and Methods: This was a retrospective cohort study of patients with non-cardiac surgery who had suffered from postoperative ischemic stroke between January 2008 and August 2019. Diabetic individuals were included in postoperative ischemic stroke patients with the DM group. The outcome of interest was long-term overall survival (OS). We conducted propensity score matching (PSM) and inverse probability treatment weighting (IPTW) to adjust for baseline characteristic differences between groups. Multivariate Cox regression analysis with stepwise selection was used to calculate the adjusted hazard ratio (HR) of OS and type 2 DM.

Results: During a median follow-up of 46.2 month [interquartile range (IQR), 21.1, 84.2], 200 of 408 patients (49.0%) died. The OS rates at 3, 5, and 10 years were significantly lower for postoperative ischemic stroke patients with DM than those without DM (3 years OS: 52.2 vs. 69.5%, p < 0.001; 5 years OS: 41.6 vs. 62.4%, p < 0.001; 10 years OS: 37.2 vs. 56.6%, p < 0.001). All covariates were between-group balanced after using PSM or IPTW. The postoperative ischemic stroke patients with type 2 DM had a shortened OS in primary analysis (HR: 1.947; 95% CI: 1.397–2.713; p < 0.001), PSM analysis (HR: 2.190; 95% CI: 1.354–3.540; p = 0.001), and IPTW analysis (HR: 2.551; 95% CI: 1.769–3.679; p < 0.001).

Conclusion: Type 2 DM was associated with an unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery. When postoperative ischemic stroke co-occurred with type 2 DM, the potential synergies would have multiplicative mortality risk. Further research to assess the adverse effects of type 2 DM on long-term survival may be warranted.
The Role of Individual Characteristics in Predicting Short- and Long-Term Cognitive and Psychological Benefits of Cognitive Stimulation Therapy for Mild-to-Moderate Dementia
Authors: Carbone Elena , Piras Federica , Pastore Massimiliano , Borella Erika
Published: January 2022

Introduction: This study examined the role of individual characteristics in predicting short- and long-term benefits of the Italian version of Cognitive Stimulation Therapy (CST-IT), an evidence-based intervention for people with mild-to-moderate dementia.

Materials and Methods: Data were drawn from a sample (N = 123) of people with dementia (PwD) who took part in a multicenter controlled clinical trial of CST-IT. Assessments at pre-test, immediately after completing the treatment, and 3 months later investigated the following outcomes: general cognitive functioning and language, mood and behavior, everyday functioning, and quality of life. Age, education and baseline (pre-test) cognitive functioning, mood (depression) and behavioral and neuropsychiatric symptoms were considered as predictors of any short- and long-term benefits.

Results: Linear mixed-effects models showed that different individual characteristics -particularly education and age- influenced the benefits of CST-IT, depending on the outcome measures considered. Higher education predicted larger gains in general cognitive functioning and, along with less severe depressive symptoms, in language (magnification effects). Older age was associated with positive changes in mood (compensation effects). Albeit very modestly, older age was also associated with larger gains in everyday functioning (compensation effects). Gains in quality of life were predicted by older age and lower education (compensation effects). Baseline cognitive functioning, mood and/or behavioral symptoms broadly influenced performance too, but their role again depended on the outcomes considered.

Discussion: These findings underscore the importance of considering and further exploring how psychosocial interventions like CST are affected by individual characteristics in order to maximize their efficacy for PwD.
Control Framework for Sloped Walking With a Powered Transfemoral Prosthesis
Authors: Anil Kumar Namita , Patrick Shawanee , Hong Woolim , Hur Pilwon
Published: January 2022

User customization of a lower-limb powered Prosthesis controller remains a challenge to this date. Controllers adopting impedance control strategies mandate tedious tuning for every joint, terrain condition, and user. Moreover, no relationship is known to exist between the joint control parameters and the slope condition. We present a control framework composed of impedance control and trajectory tracking, with the transitioning between the two strategies facilitated by Bezier curves. The impedance (stiffness and damping) functions vary as polynomials during the stance phase for both the knee and ankle. These functions were derived through least squares optimization with healthy human sloped walking data. The functions derived for each slope condition were simplified using principal component analysis. The weights of the resulting basis functions were found to obey monotonic trends within upslope and downslope walking, proving the existence of a relationship between the joint parameter functions and the slope angle. Using these trends, one can now design a controller for any given slope angle. Amputee and able-bodied walking trials with a powered transfemoral prosthesis revealed the controller to generate a healthy human gait. The observed kinematic and kinetic trends with the slope angle were similar to those found in healthy walking.
Clinical Characteristics, Outcomes, and Risk Factors of Disease Severity in Patients With COVID-19 and With a History of Cerebrovascular Disease in Wuhan, China: A Retrospective Study
Authors: Li Mengzhen , He Zehui , Yang Jiecong , Guo Qihua , Weng Heng , Luo Jielian , Gong Baoying , Cui Wanzhen , Ding Banghan , Guo Jianwen
Published: January 2022

Background and Purpose: Coronavirus disease 2019 (COVID-19) rapidly resulted in a pandemic. Information on patients with a history of cerebrovascular disease (CVD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. This study investigated the clinical features and the risk factors of developing adverse outcomes in patients with COVID-19 and with previous CVD.

Methods: This was a single-center retrospective clinical study including all the confirmed cases of COVID-19 at Wuhan Huoshenshan Hospital from February 4 to April 7, 2020. Differences in clinical characteristics were compared between patients with and without a history of CVD. The incidences of severe events comprising all-cause death, intensive care unit admission, shock, and mechanical ventilation usage during hospitalization in two groups were compared using propensity score matching analysis and multivariate logistic regression analyses. Besides, the risk factors of developing severe events in patients with COVID-19 who also have history of CVD were analyzed.

Results: A total of 2,554 consecutive patients were included in our study, of whom 109 (4.27%) had a medical history of CVD. Patients with CVD tend to be older and with more comorbidities, including hypertension, diabetes, coronary heart disease, and chronic obstructive pulmonary disease. The levels of white blood cell, neutrophil, C-reactive protein, creatine kinase isoenzymes, and lactate dehydrogenase were higher, whereas the levels of lymphocyte and albumin were lower in the CVD group. Compared to those without CVD, patients with CVD were more likely to have severe events after age matching (12.8 vs. 5.7%, P = 0.012). After adjusting for the confounding effects of age, sex, smoking, and comorbidities, the odds ratio for developing severe events with a history of CVD was 2.326 (95% CI, 1.168–4.630; P = 0.016). Besides, patients with CVD, either with decreased lymphocyte count (OR 9.192, 95% CI, 1.410–59.902, P = 0.020) or increased blood urea nitrogen (OR 5.916, 95% CI, 1.072–32.641, P = 0.041), had a higher risk of developing severe events during hospitalization.

Conclusions: Patients with CVD history tend to have adverse clinical outcomes after being infected with SARS-COV-2. Decreased lymphocyte counts and increased blood urea nitrogen levels may be risk factors for adverse outcomes in patients with COVID-19, and had CVD.
Visualization of Speech Perception Analysis via Phoneme Alignment: A Pilot Study
Authors: Ratnanather J. Tilak , Wang Lydia C. , Bae Seung-Ho , O'Neill Erin R. , Sagi Elad , Tward Daniel J.
Published: January 2022

Objective: Speech tests assess the ability of people with hearing loss to comprehend speech with a hearing aid or cochlear implant. The tests are usually at the word or sentence level. However, few tests analyze errors at the phoneme level. So, there is a need for an automated program to visualize in real time the accuracy of phonemes in these tests.

Method: The program reads in stimulus-response pairs and obtains their phonemic representations from an open-source digital pronouncing dictionary. The stimulus phonemes are aligned with the response phonemes via a modification of the Levenshtein Minimum Edit Distance algorithm. Alignment is achieved via dynamic programming with modified costs based on phonological features for insertion, deletions and substitutions. The accuracy for each phoneme is based on the F1-score. Accuracy is visualized with respect to place and manner (consonants) or height (vowels). Confusion matrices for the phonemes are used in an information transfer analysis of ten phonological features. A histogram of the information transfer for the features over a frequency-like range is presented as a phonemegram.

Results: The program was applied to two datasets. One consisted of test data at the sentence and word levels. Stimulus-response sentence pairs from six volunteers with different degrees of hearing loss and modes of amplification were analyzed. Four volunteers listened to sentences from a mobile auditory training app while two listened to sentences from a clinical speech test. Stimulus-response word pairs from three lists were also analyzed. The other dataset consisted of published stimulus-response pairs from experiments of 31 participants with cochlear implants listening to 400 Basic English Lexicon sentences via different talkers at four different SNR levels. In all cases, visualization was obtained in real time. Analysis of 12,400 actual and random pairs showed that the program was robust to the nature of the pairs.

Conclusion: It is possible to automate the alignment of phonemes extracted from stimulus-response pairs from speech tests in real time. The alignment then makes it possible to visualize the accuracy of responses via phonological features in two ways. Such visualization of phoneme alignment and accuracy could aid clinicians and scientists.
Characteristics of Cortical Atrophy and White Matter Lesions Between Dementia With Lewy Bodies and Alzheimer's Disease: A Case-Control Study
Authors: Zhu Han , Lu Hao , Wang Fei , Liu Shuai , Shi Zhihong , Gan Jinghuan , Du Xiaoshan , Yang Yaqi , Li Daibin , Wang Lichen , Ji Yong
Published: January 2022

Introduction: Currently, there is still clinical overlap between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients, which may affect the accuracy of the early diagnosis of DLB. For better diagnosis and prognosis, further exploration of local cortical atrophy patterns and white matter lesions is needed.

Methods: We reviewed the outpatient medical records of 97 DLB patients and 173 AD patients from January 2018 to September 2020 along with 30 matched outpatient clinic normal elderly people. MRI visual rating scales, including medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale (GCA-F), posterior atrophy (PA), Fazekas scale, Evans Index and cerebral microbleeds were evaluated and analyzed in DLB and AD patients with different severities and normal controls.

Results: Overall, patients with DLB had higher scores on all visual rating scales than the normal controls. Meanwhile, compared with AD, DLB had lower MTA scores in the mild to moderate groups (both p ≤ 0.001), but the GCA-F and PA scores were similar (all p > 0.05). The Fazekas scores in the moderate to severe DLB group were lower than those in the AD group (p = 0.024 and p = 0.027, respectively). In addition, the diagnostic performance and sensitivity of multiple imaging indicators for DLB were better than that of MTA alone (the combination of MTA, GCA-F, PA, Fazekas visual rating scales, AUC = 0.756, 95%CI: 0.700–0.813, sensitivity = 0.647, specificity = 0.804 and MTA visual rating scale, AUC = 0.726, 95%CI: 0.667–0.785, sensitivity = 0.497, specificity = 0.876, respectively).

Conclusion: The medial temporal lobe of DLB patients was relatively preserved, the frontal and parietal lobes were similarly atrophied to AD patients, and the white matter hyperintensity was lighter than that in AD patients. Combined multiple visual rating scales may provide a novel idea for the diagnosis of early DLB.
Application of Multiplanar Volume Reconstruction Technique for the Assessment of Electrode Location and Analysis of the Correlation to Cochlear Programming and Performance in Common Cavity Deformity
Authors: Wei Xingmei , Zhang Huaiyu , Lu Simeng , Yang Mengge , Chen Biao , Chen Jingyuan , Zhang Lifang , Liu Sha , Xian Junfang , Li Yongxin , Kong Ying
Published: January 2022

Purpose: Owing to the characteristic anatomy, cochlear implantation (CI) for common cavity deformity (CCD) has resulted in varied outcomes and frequent facial and vestibular nerve stimulation. The current study analyzed the correlation among the distance between each electrode and cavity wall (abbreviation, D), programming parameters, and performances outcomes.

Materials and Methods: The current, retrospective study included 25 patients (27 ears) with CCD underwent CI. The multiplanar volume reconstruction (MPVR) techniques were employed to reconstruct and evaluate the postoperative temporal bone CT. The D and maximum comfortable level (MCL) 6 months after CI, facial and vestibular nerve stimulation, and outcomes 1, 2, and 3 years after CI pertaining to the questionnaires were documented and analyzed.

Results: The patients were divided into symptomatic (10, 37%) and asymptomatic (17, 63%) groups according to with or without facial and vestibular nerve stimulation. The MCL pertaining to the symptomatic group was significantly lower than asymptomatic group, but Categories of Auditory Performance (CAP) scores 1 year after surgery was better (p < 0.05). The subjects were divided into flat (12, 44.4%) and curved (15, 55.6%) groups based on the contour of MCL map. The MCL and D were lower and shorter in the curved group than the flat group, and CAP score 1 year after surgery and Speech Intelligibility Rating (SIR) 3 years after surgery were better (p < 0.05).

Conclusion: Although abnormal reactions such as facial and vestibular nerve stimulation were observed to be more frequent, lower MCL and better outcomes were observed in relation to the shorter D.
Changes of Cytokines in Children With Tic Disorder
Authors: Tao Yilin , Xu Peng , Zhu Weiyi , Chen Zhiyue , Tao Xiaohan , Liu Jiajing , Xue Ziru , Zhu Tao , Jiang Peifang
Published: January 2022

Tic disorder (TD) is a common childhood-onset disease associated with abnormal development of brain networks involved in the motor and sensory processing. The underlying pathophysiological mechanisms in TD are still unclear. An involvement of immune mechanisms in its pathophysiology has been proposed. This study investigates the association between the changes of cytokines and the etiology and development of TD. Different expressions of cytokines in a larger number of samples in our study may provide new insights to the field. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were evaluated in 1,724 patients who were clinically diagnosed with TD from 1 to 17.5 years old and 550 were from 6 months to 14.5 years old in the control group. We assessed the levels of cytokines according to the patient's medication status and the severity of the disease. Of the cytokines we investigated, the serum IL-6 concentration of children with TD was significantly higher than that of the control group, while the levels of other cytokines were lower in TD patients. In the patient group whose YTGSS score ranged from 1 to 9, the IL-4, IL-10, and IFN-γ levels increased in medication group compared to unmedication group. Our data suggested that the cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) may play an important role in the etiology and the severity in TD. Whether drug intervention in the early stage of tic disorder has a better effect on children needs further research.
Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury
Authors: Du Qing-Hua , Li Jian , Gan Yi-Xiu , Zhu Hui-Jun , Yue Hai-Ying , Li Xiang-De , Ou Xue , Zhong Qiu-Lu , Luo Dan-Jing , Xie Yi-Ting , Liang Qian-Fu , Wang Ren-Sheng , Liu Wen-Qi
Published: January 2022

Purpose

To study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements.

Methods and Materials

The brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; VD with different D for different distributions). Predictive ability of EUDVD (EUD of VD) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal DV and VD points were selected for a simple comparison.

Results

The mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDVD increased, while a decreased. The mAUC reached the maximum value when D was 50–55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857–0.830/0.845–0.830) was always larger than that of brain/half-brain EUD (0.681–0.819/0.691–0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDVD with a = 1) of high-dose volume (V50 Gy–V60 Gy) was superior to traditional EUD and dose/volume points.

Conclusion

Volume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.
Hsa_circ_0060927 Is a Novel Tumor Biomarker by Sponging miR-195-5p in the Malignant Transformation of OLK to OSCC
Authors: Xu Siming , Song Yuhan , Shao Yanxiong , Zhou Haiwen
Published: January 2022

Objective

To investigate the clinical significance of differentially expressed circRNAs and candidate circRNAs in the transformation of oral leukoplakia (OLK) to oral squamous cell carcinoma (OSCC).

Methods

We performed high-throughput circRNA sequencing in six cases of normal oral mucosal (NOM) tissues, six cases of OLK tissues, and six cases of OSCC tissues. Ten circRNAs with significant differential expression were verified by qRT-PCR. Enzyme tolerance assay and Sanger sequencing were performed on the screened target circRNA hsa_circ_0060927, and a qRT-PCR assay of hsa_circ_0060927 was performed in three tissues (24 cases in each group); this was followed by an ROC analysis. The ceRNA network was predicted using TargetScan and miRanda. MiR-195-5p and TRIM14 were selected as the downstream research objects of hsa_circ_0060927. The sponge mechanism of hsa_circ_0060927 was detected by AGO2 RIP. The interaction between hsa_circ_0060927 and miR-195-5p was verified by RNA pull-down assay and dual luciferase reporter gene assay. The expressions of hsa_circ_0060927, miR-195-5p, and TRIM14 were verified by normal oral epithelial primary cells and cell lines of LEUK1, SCC9, and SCC25. The hsa_circ_0060927 overexpressed plasmid and miR-195-5p mimics were constructed to transfection LEUK1 to detect the changes in cell proliferation, apoptosis, and migration.

Results

The results of qRT-PCR validation were consistent with the sequencing results. Hsa_circ_0060927 is a true circRNA with trans-splicing sites. The expression of hsa_circ_0060927 increased in NOM, OLK, and OSCC. Overexpression of hsa_circ_0060927 enhanced the ability of cell proliferation and migration, and decreased cell apoptosis capacity. The prediction of ceRNA network suggested that hsa_circ_0060927 could regulate the target gene TRIM14 through sponging miR-195-5p. AGO2 RIP indicated that hsa_circ_0060927 had a sponge mechanism. RNA pull-down and dual luciferase reporter gene assay suggested that hsa_circ_0060927 interacted with miR-195-5p. Hsa_circ_0060927 was positively correlated with the expression of TRIM14, and could relieve the inhibition of miR-195-5p on TRIM14 to regulate cell proliferation, apoptosis, and migration of LEUK1 cells.

Conclusion

Hsa_circ_0060927 acted as a potential key ceRNA to sponge downstream miR-195-5p and promote OLK carcinogenesis by upregulating TRIM14. Hsa_circ_0060927 was expected to be a molecular marker for the prevention and treatment of OLK carcinogenesis through the hsa_circ_0060927/miR-195-5p/TRIM14 axis.
Lipoxins and Resolvins in Patients With Pancreatic Cancer: A Preliminary Report
Authors: Blogowski Wojciech , Dolegowska Katarzyna , Deskur Anna , Dolegowska Barbara , Starzynska Teresa
Published: January 2022

Eicosanoids are bioactive lipids derived from arachidonic acid, which have emerged as key regulators of a wide variety of pathophysiological processes in recent times and are implicated as mediators of gastrointestinal cancer. In this study, we investigated the systemic levels of lipoxygenase (LOX)-derived lipoxin A4 and B4, together with resolvin D1 and D2 in patients with pancreatic adenocarcinoma (n = 68), as well as in healthy individuals (n = 32). Systemic concentrations of the aforementioned immunoresolvents were measured using an enzyme-linked immunosorbent assay (ELISA). In this study, we observed that compared with concentrations in healthy individuals, the peripheral concentrations of the aforementioned eicosanoids were significantly elevated (2- to 10-fold) in patients with pancreatic cancer (in all cases p<0.00001). No significant association was observed between eicosanoid levels and the TNM clinical staging. Furthermore, we observed no significant differences in concentrations of the analyzed bioactive lipids between patients diagnosed with early-stage (TNM stage I-II) and more advanced disease (TNM stage III-IV). Receiver operating characteristic (ROC) curve analysis of each aforementioned immunoresolvent showed area under the curve values ranging between 0.79 and 1.00. Sensitivity, specificity, as well as positive and negative predictive values of the eicosanoids involved in the detection/differentiation of pancreatic adenocarcinoma ranged between 56.8% and 100%. In summary, our research is the first study that provides clinical evidence to support a systemic imbalance in LOX-derived lipoxins and resolvins as the mechanism underlying the pathogenesis of pancreatic adenocarcinoma. This phenomenon occurs regardless of the clinical TNM stage of the disease. Furthermore, our study is the first to preliminarily highlight the role of peripheral levels of immunoresolvents, particularly resolvin D1, as potential novel biomarkers of pancreatic cancer in humans.