bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Where You Live Matter? An Analysis of Intergenerational Transmission of Education Among Hispanic Americans
Authors: Wang Sharron Xuanren , Sakamoto Arthur
Published: August 2021

The intergenerational transmission of education from parents to children is an important indicator of societal inclusiveness and educational inequality. The present study uses restricted-access data from the National Longitudinal Survey of Youth 1997 (NLSY97) to investigate whether intergenerational educational transmission varies by county-level demographic and socioeconomic characteristics for Hispanic Americans. Based on parental birthplace, Hispanic Americans are grouped into 3 + generation (i.e., children of native-born Hispanic parents) and 2nd generation (i.e., children of foreign-born Hispanic parents). Men and women are analyzed separately. The results indicate that intergenerational educational mobility is higher if 3 + generation Hispanic men reside in areas with a larger Hispanic population, and if 2nd generation Hispanic men reside in areas with a larger college-educated population, during their adolescent years. County-level socioeconomic characteristics do not seem to affect intergenerational educational mobility of Hispanic women, non-Hispanic white men, or non-Hispanic white women. Theoretical and empirical implications of the findings are discussed.
Porcine Parvovirus 2 Is Predominantly Associated With Macrophages in Porcine Respiratory Disease Complex
Authors: Nelsen April , Lin Chun-Ming , Hause Ben M.
Published: August 2021

Porcine respiratory disease complex (PRDC) is a significant source of morbidity and mortality, manifested by pneumonia of multiple etiologies, where a variety of pathogens and environment and management practices play a role in the disease. Porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus (IAV), and porcine circovirus 2 (PCV2) are well-established pathogens in PRDC. Porcine parvovirus 2 (PPV2) has been identified in both healthy and clinically diseased pigs at a high prevalence worldwide. Despite widespread circulation, the significance of PPV2 infection in PRDC and its association with other co-infections are unclear. Here, PPV2 was detected in the lung tissue in 39 of 100 (39%) PRDC-affected pigs by quantitative polymerase chain reaction (qPCR). Using in situ hybridization (ISH) in conjunction with tissue microarrays (TMA), PPV2 infection was localized in alveolar macrophages and other cells in the lungs with interstitial pneumonia in 28 of 99 (28.2%) samples. Viral load tended to correlate with the number of macrophages in the lungs. Assessment of the frequency, viral titers, and tissue distributions showed no association between infection of PPV2 and other major viral respiratory pathogens. In one-third of the PPV2-positive samples by qPCR, no other known viruses were identified by metagenomic sequencing. The genome sequences of PPV2 were 99.7% identical to the reference genomes. Although intensive intranuclear and intracytoplasmic signals of PPV2 were mainly detected in alveolar macrophages by ISH, no obvious virus replication was noted in in vitro cell culture. Together, these results suggest that PPV2 is associated, but may not be the sole causative agent, with PRDC, warranting the control and prevention of this underdiagnosed virus.
Pilot-Scale H2S and Swine Odor Removal System Using Commercially Available Biochar
Authors: Ro Kyoung S. , Woodbury Bryan , Spiehs Mindy , Szogi Ariel A. , Silva Philip J. , Hwang Okhwa , Cho Sungback
Published: August 2021

Although biochars made in laboratory seem to remove H2S and odorous compounds effectively, very few studies are available for commercial biochars. This study evaluated the efficacy of a commercial biochar (CBC) for removing H2S and odorous volatile organic compounds (VOCs). We found that the well-known Ergun equation may not be adequate in predicting pressure drop for properly sizing a ventilation system. The H2S breakthrough adsorption capacity of the CBC was 2.51 mg/g under humid conditions, which was much higher than that for dry conditions. The breakthrough capacity increased with the influent concentration of H2S. The efficacy of a pilot-scale biochar odor removal system (PSBORS) for removing 15 odorous VOCs was evaluated by placing it in a swine gestation stall continually treating the inside air for 21 days. All VOCs in the PSBORS effluent were below detection limit except for acetic acid. However, due to the very high odor threshold of acetic acid, its contribution to the odor would be minimal. It appeared that the CBC could be used to reduce both H2S and odorous VOCs with the potential of recycling the spent CBC for soil health improvement after using it for H2S and odor removal.
Biostimulant Application under Different Nitrogen Fertilization Levels: Assessment of Yield, Leaf Quality, and Nitrogen Metabolism of Tunnel-Grown Lettuce
Authors: Ottaiano Lucia , Di Mola Ida , Cozzolino Eugenio , El-Nakhel Christophe , Rouphael Youssef , Mori Mauro
Published: August 2021

Promising strategies that could aid a shift from N-intensive agriculture to an eco-friendlier approach include the integrated use of plant-based biostimulants. To date, results about the accumulation of nitrate in green leafy vegetables due to biostimulant application are conflicting. Therefore, the current study aimed at assessing the effect of a new plant-based biostimulant, containing triacontanol (TRIA), that is claimed to reduce nitrate accumulation in leaves, based on the yield and leaf quality of lettuce grown in a plastic tunnel under different N conditions. The experimental design was a factorial combination of three nitrogen fertilization levels (N0, N30, and N60, corresponding to 0, 30, and 60 kg N ha−1) and two biostimulant applications (treated with ‘ILSASTIM+’ = YB and untreated control = NB). Nitrogen fertilization resulted in a 40% yield increase over N0. Biostimulant application increased the yield 21% over NB, and both improved all growth parameters. In addition, the biostimulant had a positive effect on color and Soil Plant Analysis development (SPAD) index, thus enhancing the qualitative aspect. Interestingly, biostimulant application boosted nitrogen use efficiency with a 23% increase over untreated plants. The use of biostimulant proved to be suitable to be applied in a sustainable strategy of production and quality improvement.
Blend of Essential Oils Supplemented Alone or Combined with Exogenous Amylase Compared with Virginiamycin Supplementation on Finishing Lambs: Performance, Dietary Energetics, Carcass Traits, and Nutrient Digestion
Authors: Estrada-Angulo Alfredo , Arteaga-Wences Yesica J. , Castro-Pérez Beatriz I. , Urías-Estrada Jesús D. , Gaxiola-Camacho Soila , Angulo-Montoya Claudio , Ponce-Barraza Elizama , Barreras Alberto , Corona Luis , Zinn Richard A. , Leyva-Morales José B. , Perea-Domínguez Xiomara P. , Plascencia Alejandro
Published: August 2021

Two experiments were conducted to compare a supplemental blend of essential oils alone (EO) or combined with enzymes (EO + ENZ) versus virginiamycin (VM), on characteristics of growth performance (Exp. 1) and digestion (Exp. 2) in finishing lambs. Lambs were fed a high-energy finishing diet supplemented with: (1) no supplement (control); (2) 150 mg supplemental EO; (3) 150 mg supplemental EO plus 560 mg alpha-amylase (EO + ENZ); and 4) 25 mg VM. Compared with the control, growth performance response to EO and VM were similar, enhancing (5.7%, p < 0.05) feed efficiency and observed dietary net energy. Compared with control, supplementation with EO + ENZ tended (p = 0.09) to increase dry matter intake (6.8%), improving (p < 0.05) weight gain and feed efficiency (10.4 and 4.4%, respectively). Dietary energy utilization was greater (2.7%, p < 0.05) for EO and VM than EO + ENZ. Treatment effects on the carcass and visceral mass were small, but additive supplementation decreased (p ≤ 0.03) the relative weight of the intestines. There were no treatment effects on measures of digestion nor digestible energy of the diet. Supplemental EO may be an effective alternative to VM in high-energy finishing diets for feedlot lambs. Combination EO + ENZ may further enhance dry matter intake, promoting increased weight gain.
Application of the Resazurin Cell Viability Assay to Monitor Escherichia coli and Salmonella Typhimurium Inactivation Mediated by Phages
Authors: Costa Pedro , Gomes Ana T. P. C. , Braz Márcia , Pereira Carla , Almeida Adelaide
Published: August 2021

Bacterial inactivation using bacteriophages (or phages) has emerged as an effective solution for bacterial infections, but the screening methods used to evaluate the effectiveness of the phages to inactivate bacteria are not fast, reliable or precise enough. The efficiency of bacterial inactivation by phages has been evaluated by monitoring bacterial concentration either by counting colony-forming units (CFU), a laborious and time-consuming method, or by monitoring the optical density (OD), a less sensitive method. In this study, the resazurin cell viability assay was used to monitor the viability of bacteria from different genera during the inactivation by different phages, and the results were compared with the standard methods used to assess bacterial inactivation. The results showed that the resazurin colorimetric cell viability assay produces similar results to the standard method of colony-counting and giving, and also more sensitive results than the OD method. The resazurin assay can be used to quickly obtain the results of the cell viability effect profile using two different bacterial strains and several different phages at the same time, which is extremely valuable in screening studies. Moreover, this methodology is established as an effective, accurate and rapid method when compared to the ones widely used to monitor bacterial inactivation mediated by phages.
Comparative Effectiveness of Treatments for Bacterial Vaginosis: A Network Meta-Analysis
Authors: Muñoz-Barreno Alison , Cabezas-Mera Fausto , Tejera Eduardo , Machado António
Published: August 2021

Bacterial vaginosis (BV) is a common vaginal dysbiosis in women of reproductive age. However, the cure rate for BV varies considerably and many women experience a relapse after the initial treatment. The present meta-analysis aimed to evaluate the clinical cure rates (CCRs) in randomized controlled trials (RCTs) through different therapies and administration routes. This meta-analysis included a final set of 25 eligible studies with a total of 57 RCTs and compared the effectiveness of BV treatments among non-pregnant and pregnant women. The initial range of CCRs varied greatly from 46.75% to 96.20% and the final pooled CCR was 75.5% (CI: 69.4–80.8) using the random model. The heterogeneity indices were Q = 418.91, I2 = 94.27%, and τ = 0.7498 (p < 0.0001). No publication bias was observed according to Funnel plot symmetry and Egger’s linear regression test (p = 0.1097). To evaluate different variables, sub-group analysis, meta-regressions, and network meta-analysis were also realized. The highest P-scores in CCR were obtained by: (1) a combined therapy with local probiotic treatment and application of antibiotics by both administration route (oral clindamycin and local 5-nitroimidazole; P-score = 0.92); (2) a combined therapy with oral administration of 5-nitroimidazole and probiotic treatment (P-score = 0.82); (3) and a combined therapy with local administration of 5-nitroimidazole and oral probiotic treatment (P-score = 0.68). A clear-cut decision of the best BV treatment was not possible due to the heterogeneity of outcomes reported in the trials, indicating the necessity for a better characterization of RCTs. Finally, combined therapies suggested the reduction of the optimal concentration of antibiotics, and double phase treatments of antibiotics indicated an increment of CCRs in BV.
Mycobacterium tuberculosis H2S Functions as a Sink to Modulate Central Metabolism, Bioenergetics, and Drug Susceptibility
Authors: Kunota Tafara T. R. , Rahman Md. Aejazur , Truebody Barry E. , Mackenzie Jared S. , Saini Vikram , Lamprecht Dirk A. , Adamson John H. , Sevalkar Ritesh R. , Lancaster Jack R. , Berney Michael , Glasgow Joel N. , Steyn Adrie J. C.
Published: August 2021

H2S is a potent gasotransmitter in eukaryotes and bacteria. Host-derived H2S has been shown to profoundly alter M. tuberculosis (Mtb) energy metabolism and growth. However, compelling evidence for endogenous production of H2S and its role in Mtb physiology is lacking. We show that multidrug-resistant and drug-susceptible clinical Mtb strains produce H2S, whereas H2S production in non-pathogenic M. smegmatis is barely detectable. We identified Rv3684 (Cds1) as an H2S-producing enzyme in Mtb and show that cds1 disruption reduces, but does not eliminate, H2S production, suggesting the involvement of multiple genes in H2S production. We identified endogenous H2S to be an effector molecule that maintains bioenergetic homeostasis by stimulating respiration primarily via cytochrome bd. Importantly, H2S plays a key role in central metabolism by modulating the balance between oxidative phosphorylation and glycolysis, and it functions as a sink to recycle sulfur atoms back to cysteine to maintain sulfur homeostasis. Lastly, Mtb-generated H2S regulates redox homeostasis and susceptibility to anti-TB drugs clofazimine and rifampicin. These findings reveal previously unknown facets of Mtb physiology and have implications for routine laboratory culturing, understanding drug susceptibility, and improved diagnostics.
Effect of Sunflower, Almond, and Rapeseed Oils as Additives on Thermal Properties of a Machinery Oil
Authors: Flores Cuautle José de Jesús Agustín , Sandoval González Oscar Osvaldo , González Morán Carlos Omar , Rodríguez Jarquin José Pastor , Trujillo Romero Citlalli Jessica , Lara Hernandez Gemima
Published: August 2021

Vegetable oils are considered to be eco-friendly and to offer good lubricant properties; however, their low thermo-oxidative stability makes their use as a lubricant base challenging. In this research, sunflower, almond, and rapeseed vegetable oils were added in volumes of 5, 10, 15, and 20% to a machinery oil, and the thermal properties of the resulting fluids were studied. Sunflower, almond, and rapeseed oils were chosen considering their fatty acid composition and the tocopherol content. During this investigation, thermal diffusivity was measured by using the thermal wave resonance cavity technique, while thermal effusivity was determined by the inverse photopyroelectric method, and the obtained values ranged from 4.63 to 5.75 Ws1/2m−2K−1 × 102. The thermal conductivity was calculated by obtaining a complete thermal characterization. The results showed a linear relationship between the percentage of vegetable oil and the thermal diffusivity. It was also noted that the thermal properties of diffusivity and effusivity could be tuned when using almond, sunflower, and rapeseed oils in the appropriate percentages. Hence, the influence of vegetable oils on the thermal properties of lubricating oil were closely related to the number of fatty acids.
The Helical Resonator: A Scheme for Radio Frequency Plasma Generation
Authors: Martines Emilio , Cavazzana Roberto , Cordaro Luigi , Zuin Matteo
Published: August 2021

The helical resonator is a scheme for the production of high voltage at radio frequency, useful for gas breakdown and plasma sustainment, which, through a proper design, enables avoiding the use of a matching network. In this work, we consider the treatment of the helical resonator, including a grounded shield, as a transmission line with a shorted end and an open one, the latter possibly connected to a capacitive load. The input voltage is applied to a tap point located near the shorted end. After deriving an expression for the velocity factor of the perturbations propagating along the line, and in the special case of the shield at infinity also of the characteristic impedance, we calculate the input impedance and the voltage amplification factor of the resonator as a function of the wave number. Focusing on the resonance condition, which maximizes the voltage amplification, we then discuss the effect of the tap point position, dissipation and the optional capacitive load, in terms of resonator performance and matching to the power supply.
Comparison of the Kinematics Following Gait Perturbation in Individuals Who Did or Did Not Undergo Total Knee Replacement
Authors: Elkarif Vicktoria , Kandel Leonid , Rand Debbie , Schwartz Isabella , Greenberg Alexander , Gurion Rivkin , Portnoy Sigal
Published: August 2021

We aimed to compare the spatiotemporal parameters and joint kinematics during unperturbed and perturbed gait between individuals with osteoarthritis (OA) who did or did not undergo total knee replacement (TKR) one year post a baseline evaluation. OA subjects scheduled for TKR (TKR group; n = 14) and not scheduled for TKR (NTKR group; n = 17) were age-matched. Outcome measures included: joint range of motion, timed up and go, joint pain levels, Oxford score, and the Activities-specific Balance Confidence Scale. In addition, spatiotemporal gait parameters and joint kinematics were recorded during perturbed and unperturbed gait. After one year, most of the TKR group (71%), but only 41% of the NTKR group, increased their gait velocity by more than 0.1m/sec, which is the meaningful clinical important difference for gait velocity. After perturbation of the contralateral limb, the TKR group showed a greater decrease in the maximal extension of the OA hip compared to the NTKR group (p = 0.031). After perturbation of the OA limb, more subjects decreased their OA knee flexion–extension range in the NTKR group compared to the TKR group (p = 0.011) and more subjects decreased their maximal ankle plantar flexion in the TKR group (p = 0.049). Although the surgery was successful in terms of pain reduction and increased functionality, individuals following TKR exhibited unique compensatory strategies in response to the perturbation of both limbs. These findings might suggest that balance deficits remain in individuals following TKR and therefore are associated with a risk of falls.
On IoT-Friendly Skewness Monitoring for Skewness-Aware Online Edge Learning
Authors: Li Zheng , Galdames-Retamal Jhon
Published: August 2021

Machine learning techniques generally require or assume balanced datasets. Skewed data can make machine learning systems never function properly, no matter how carefully the parameter tuning is conducted. Thus, a common solution to the problem of high skewness is to pre-process data (e.g., log transformation) before applying machine learning to deal with real-world problems. Nevertheless, this pre-processing strategy cannot be employed for online machine learning, especially in the context of edge computing, because it is barely possible to foresee and store the continuous data flow on IoT devices on the edge. Thus, it will be crucial and valuable to enable skewness monitoring in real time. Unfortunately, there exists a surprising gap between practitioners’ needs and scientific research in running statistics for monitoring real-time skewness, not to mention the lack of suitable remedies for skewed data at runtime. Inspired by Welford’s algorithm, which is the most efficient approach to calculating running variance, this research developed efficient calculation methods for three versions of running skewness. These methods can conveniently be implemented as skewness monitoring modules that are affordable for IoT devices in different edge learning scenarios. Such an IoT-friendly skewness monitoring eventually acts a cornerstone for developing the research field of skewness-aware online edge learning. By initially validating the usefulness and significance of skewness awareness in edge learning implementations, we also argue that conjoint research efforts from relevant communities are needed to boost this promising research field.
An Observational Study of Aerosols and Tropical Cyclones over the Eastern Atlantic Ocean Basin for Recent Hurricane Seasons
Authors: Patel Mohin , Chiao Sen , Tan Qian
Published: August 2021

The aerosol vertical distribution in the tropical cyclone (TC) main development region (MDR) during the recent active hurricane seasons (2015–2018) was investigated using observations from NASA’s Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) Satellite. The Total Attenuated Backscatter (TAB) at 532 nm was measured by the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP Lidar) onboard CALIPSO which is a polar orbiting satellite that evaluates the role clouds and atmospheric aerosols play in Earth’s weather, climate and air quality. The TAB was used to illustrate the dispersion and magnitude of the aerosol vertical distribution in the TC-genesis region. A combination of extinction quality flag, cloud fraction, and cloud-aerosol discrimination (CAD) scores were used to filter out the impact of clouds. To better describe the qualitative and quantitative difference of aerosol along the paths of African Easterly Waves (AEWs), the MDR was further divided into two domains from 18° W to 30° W (Domain 1) and 30° W to 45° W (Domain 2), respectively. The distribution of average aerosol concentration from the time of active cyclogenesis was compared and quantified between each case. The resulting observations suggest that there are two distinct layers of aerosols in the vertical profile, a near surface layer from 0.5–1.75 km and an upper layer at 1.75–5 km in altitude. A quantification of the total aerosol concentration values indicate domain 2 cases were associated with higher aerosol concentrations than domain 1 cases. The environmental variables such as sea surface temperature (SST), vertical windshear (VWS), and relative humidity (RH) tended to be favorable for genesis to occur. Among all cases in this study, the results suggested tropical cyclone genesis and further development occurred under dust-loaded conditions while the environmental variables were favorable, indicating that dust aerosols may not play a significant role in inhibiting the genesis process of TCs.
Clinical Trial for Cartilage Conduction Hearing Aid in Indonesia
Authors: Suwento Ronny , Widodo Dini Widiarni , Airlangga Tri Juda , Alviandi Widayat , Watanuki Keisuke , Nakanowatari Naoko , Hosoi Hiroshi , Nishimura Tadashi
Published: August 2021

Hearing improvement represents one of the may valuable outcomes in microtia and aural atresia reconstruction surgery. Most patients with poor development in their hearing function have had a severe microtia. Conventional methods to improve hearing function are bone conduction and bone anchored hearing aids. Cartilage conduction hearing aids (CCHA) represents a new amplification method. This study assessed the outcomes and evaluated the impact and its safety in the patients with microtia and aural atresia whose hearing dysfunction did not improve after surgery for ear reconstruction in our hospital. Hearing functions were evaluated with pure tone audiometry or sound field testing by behavioral audiometry and speech audiometry before and after CCHA fitting. As a result, there was a significant difference between unaided and aided thresholds (p < 0.001). Speech recognition threshold and speech discrimination level also significantly improved with CCHA. The average functional gains of 14 ears were 26.9 ± 2.3 dB. Almost all parents of the patients reported satisfaction with the performance of CCHA, and daily communication in children with hearing loss also became better than usual.
Deep Neural Network and Boosting Based Hybrid Quality Ranking for e-Commerce Product Search
Authors: Jbene Mourad , Tigani Smail , Saadane Rachid , Chehri Abdellah
Published: August 2021

In the age of information overload, customers are overwhelmed with the number of products available for sale. Search engines try to overcome this issue by filtering relevant items to the users’ queries. Traditional search engines rely on the exact match of terms in the query and product meta-data. Recently, deep learning-based approaches grabbed more attention by outperforming traditional methods in many circumstances. In this work, we involve the power of embeddings to solve the challenging task of optimizing product search engines in e-commerce. This work proposes an e-commerce product search engine based on a similarity metric that works on top of query and product embeddings. Two pre-trained word embedding models were tested, the first representing a category of models that generate fixed embeddings and a second representing a newer category of models that generate context-aware embeddings. Furthermore, a re-ranking step was performed by incorporating a list of quality indicators that reflects the utility of the product to the customer as inputs to well-known ranking methods. To prove the reliability of the approach, the Amazon reviews dataset was used for experimentation. The results demonstrated the effectiveness of context-aware embeddings in retrieving relevant products and the quality indicators in ranking high-quality products.
Comparing Swarm Intelligence Algorithms for Dimension Reduction in Machine Learning
Authors: Kicska Gabriella , Kiss Attila
Published: August 2021

Nowadays, the high-dimensionality of data causes a variety of problems in machine learning. It is necessary to reduce the feature number by selecting only the most relevant of them. Different approaches called Feature Selection are used for this task. In this paper, we propose a Feature Selection method that uses Swarm Intelligence techniques. Swarm Intelligence algorithms perform optimization by searching for optimal points in the search space. We show the usability of these techniques for solving Feature Selection and compare the performance of five major swarm algorithms: Particle Swarm Optimization, Artificial Bee Colony, Invasive Weed Optimization, Bat Algorithm, and Grey Wolf Optimizer. The accuracy of a decision tree classifier was used to evaluate the algorithms. It turned out that the dimension of the data can be reduced about two times without a loss in accuracy. Moreover, the accuracy increased when abandoning redundant features. Based on our experiments GWO turned out to be the best. It has the highest ranking on different datasets, and its average iteration number to find the best solution is 30.8. ABC obtained the lowest ranking on high-dimensional datasets.
Transcriptomic Properties of HER2+ Ductal Carcinoma In Situ of the Breast Associate with Absence of Immune Cells
Authors: Agahozo Marie Colombe , Smid Marcel , van Marion Ronald , Hammerl Dora , van den Bosch Thierry P. P. , Timmermans Mieke A. M. , Heijerman Chayenne J. , Westenend Pieter J. , Debets Reno , Martens John W. M. , van Deurzen Carolien H. M.
Published: August 2021

The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor-infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL-poor HER2+ DCIS to that of TIL-rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL-poor DCIS cases were micro-dissected for RNA isolation. The Ion AmpliSeq Transcriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann–Whitney rank sum test was used to analyze differentially expressed genes between TIL-poor and TIL-rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein expression. We identified a 29-gene expression profile that differentiated TIL-rich from TIL-poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously described in breast cancer and cancer immunity and were more highly expressed in TIL-rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL-rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy.
Bcl-xL Is Required by Primary Hippocampal Neurons during Development to Support Local Energy Metabolism at Neurites
Authors: Jansen Joseph , Scott Madison , Amjad Emma , Stumpf Allison , Lackey Kimberly , Caldwell Kim , Park Han-A
Published: August 2021

B-cell lymphoma-extra large (Bcl-xL) is a mitochondrial protein known to inhibit mitochondria-dependent intrinsic apoptotic pathways. An increasing number of studies have demonstrated that Bcl-xL is critical in regulating neuronal energy metabolism and has a protective role in pathologies associated with an energy deficit. However, it is less known how Bcl-xL regulates physiological processes of the brain. In this study, we hypothesize that Bcl-xL is required for neurite branching and maturation during neuronal development by improving local energy metabolism. We found that the absence of Bcl-xL in rat primary hippocampal neurons resulted in mitochondrial dysfunction. Specifically, the ATP/ADP ratio was significantly decreased in the neurites of Bcl-xL depleted neurons. We further found that neurons transduced with Bcl-xL shRNA or neurons treated with ABT-263, a pharmacological inhibitor of Bcl-xL, showed impaired mitochondrial motility. Neurons lacking Bcl-xL had significantly decreased anterograde and retrograde movement of mitochondria and an increased stationary mitochondrial population when Bcl-xL was depleted by either means. These mitochondrial defects, including loss of ATP, impaired normal neurite development. Neurons lacking Bcl-xL showed significantly decreased neurite arborization, growth and complexity. Bcl-xL depleted neurons also showed impaired synapse formation. These neurons showed increased intracellular calcium concentration and were more susceptible to excitotoxic challenge. Bcl-xL may support positioning of mitochondria at metabolically demanding regions of neurites like branching points. Our findings suggest a role for Bcl-xL in physiological regulation of neuronal growth and development.
Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies
Authors: Passardi Alessandro , Rapposelli Ilario Giovanni , Scarpi Emanuela , Sullo Francesco Giulio , Bartolini Giulia , Neri Elisa , Ghigi Giulia , Tontini Luca , Ercolani Giorgio , Monti Manlio , Ruscelli Silvia , Matteucci Laura , Valgiusti Martina , Frassineti Giovanni Luca , Romeo Antonino
Published: August 2021

In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1–65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8–13.2) and 14.3 (95% CI 12.0–18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6–33.0), and the R0 resection rate was 13.7% (95% CI 5.8–21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19–9 were associated with improved OS and PFS. Concerning OS, log(CA19–9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02–1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46–4.96); for PS 2, HR was 4.18 (95% CI 0.90–19.46); p = 0.003. Low CA19–9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52–0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.
Biological Functions of the Intrinsically Disordered N-Terminal Domain of the Prion Protein: A Possible Role of Liquid–Liquid Phase Separation
Authors: Polido Stella A. , Kamps Janine , Tatzelt Jörg
Published: August 2021

The mammalian prion protein (PrPC) is composed of a large intrinsically disordered N-terminal and a structured C-terminal domain, containing three alpha-helical regions and a short, two-stranded beta-sheet. Traditionally, the activity of a protein was linked to the ability of the polypeptide chain to adopt a stable secondary/tertiary structure. This concept has been extended when it became evident that intrinsically disordered domains (IDDs) can participate in a broad range of defined physiological activities and play a major functional role in several protein classes including transcription factors, scaffold proteins, and signaling molecules. This ability of IDDs to engage in a variety of supramolecular complexes may explain the large number of PrPC-interacting proteins described. Here, we summarize diverse physiological and pathophysiological activities that have been described for the unstructured N-terminal domain of PrPC. In particular, we focus on subdomains that have been conserved in evolution.
Cytokine Storms in the Course of COVID-19 and Haemophagocytic Lymphohistiocytosis in Pregnant and Postpartum Women
Authors: Obuchowska Aleksandra , Standyło Arkadiusz , Obuchowska Karolina , Kimber-Trojnar Żaneta , Leszczyńska-Gorzelak Bożena
Published: August 2021

The term ‘cytokine storm’ (CS) applies to a pathological autoimmune reaction when the interactions that lead to cytokine production are destabilised and may even lead to death. CS may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we present our analysis of certain pathological processes that induce a CS in pregnant and postpartum women. We draw our attention to the similarities between the severe course of Coronavirus Disease 2019 (COVID-19) and haemophagocytic lymphohistiocytosis (HLH). It is noteworthy that many of the criteria used to diagnose HLH are described as COVID-19 mortality predictors. Cytokine storms are considered to be an important cause of death in patients with the severe course of SARS-CoV-2 infection. Due to the fact that pregnant women are in an immunosuppressive state, viral pulmonary infections are more perilous for them—possible risks include miscarriage, intrauterine growth restriction or birth before the term; sometimes ventilation support is needed. HLH should be considered in pregnant and puerperal women suffering from moderately severe to severe COVID-19 and presenting with: fever unresponsive to antibiotic therapy, cytopenia, hepatitis and hyperferritinaemia. The HLH disorder is rare and difficult to diagnose; however, its early detection could reduce patient mortality.
Enthalpy–Entropy Compensation in the Promiscuous Interaction of an Intrinsically Disordered Protein with Homologous Protein Partners
Authors: Kragelj Jaka , Orand Thibault , Delaforge Elise , Tengo Laura , Blackledge Martin , Palencia Andrés , Jensen Malene Ringkjøbing
Published: August 2021

Intrinsically disordered proteins (IDPs) can engage in promiscuous interactions with their protein targets; however, it is not clear how this feature is encoded in the primary sequence of the IDPs and to what extent the surface properties and the shape of the binding cavity dictate the binding mode and the final bound conformation. Here we show, using a combination of nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), that the promiscuous interaction of the intrinsically disordered regulatory domain of the mitogen-activated protein kinase kinase MKK4 with p38α and JNK1 is facilitated by folding-upon-binding into two different conformations, despite the high sequence conservation and structural homology between p38α and JNK1. Our results support a model whereby the specific surface properties of JNK1 and p38α dictate the bound conformation of MKK4 and that enthalpy–entropy compensation plays a major role in maintaining comparable binding affinities for MKK4 towards the two kinases.
Clinical Relevance of the Sympathetic–Vascular Interactions in Health and Disease
Authors: Quarti-Trevano Fosca , Seravalle Gino , Grassi Guido
Published: August 2021

The sympathetic nervous system is known to play a pivotal role in the short- and long-term regulation of different cardiovascular functions. In recent decades, increasing evidence has demonstrated that sympathetic neural influences are involved not only in the vasomotor modulation of small resistance arteries but also in the control of large arteries. Sympathetic activity and vascular function, which are key factors in the pathophysiology and prognosis of cardiovascular disease, are linked by a close relationship. Evidence from experimental studies indicates that the sympathetic nervous system is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, namely nitric oxide, reactive oxygen species and endothelin. Additionally, there is evidence of a reciprocal influence between endothelial function and sympathetic mechanisms. This paper will provide an overview of the relationships between endothelial function and the sympathetic nervous system characterizing physiological states. It will also briefly mention the alterations described in cardiovascular disease, with particular emphasis on essential hypertension and congestive heart failure, i.e., the two pathological states in which endothelial dysfunction and neuroadrenergic activation appear to be relevant factors for determining cardiovascular prognosis.
RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets
Authors: Bastin Guillaume , Luu Lemieux , Batchuluun Battsetseg , Mighiu Alexandra , Beadman Stephanie , Zhang Hangjung , He Changhao , Al Rijjal Dana , Wheeler Michael B. , Heximer Scott P.
Published: August 2021

A number of diverse G-protein signaling pathways have been shown to regulate insulin secretion from pancreatic β-cells. Accordingly, regulator of G-protein signaling (RGS) proteins have also been implicated in coordinating this process. One such protein, RGS4, is reported to show both positive and negative effects on insulin secretion from β-cells depending on the physiologic context under which it was studied. We here use an RGS4-deficient mouse model to characterize previously unknown G-protein signaling pathways that are regulated by RGS4 during glucose-stimulated insulin secretion from the pancreatic islets. Our data show that loss of RGS4 results in a marked deficiency in glucose-stimulated insulin secretion during both phase I and phase II of insulin release in intact mice and isolated islets. These deficiencies are associated with lower cAMP/PKA activity and a loss of normal calcium surge (phase I) and oscillatory (phase II) kinetics behavior in the RGS4-deficient β-cells, suggesting RGS4 may be important for regulation of both Gαi and Gαq signaling control during glucose-stimulated insulin secretion. Together, these studies add to the known list of G-protein coupled signaling events that are controlled by RGS4 during glucose-stimulated insulin secretion and highlight the importance of maintaining normal levels of RGS4 function in healthy pancreatic tissues.
Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain
Authors: Camelliti Simone , Le Noci Valentino , Bianchi Francesca , Storti Chiara , Arnaboldi Francesca , Cataldo Alessandra , Indino Serena , Jachetti Elena , Figini Mariangela , Colombo Mario Paolo , Balsari Andrea , Gagliano Nicoletta , Tagliabue Elda , Sfondrini Lucia , Sommariva Michele
Published: August 2021

Background. A combination of TLR9 agonists and an anti-PD-1 antibody has been reported to be effective in immunocompetent mice but the role of innate immunity has not yet been completely elucidated. Therefore, we investigated the contribution of the innate immune system to this combinatorial immunotherapeutic regimens using an immunodeficient mouse model in which the effector functions of innate immunity can clearly emerge without any interference from T lymphocytes. Methods. Athymic mice xenografted with IGROV-1 human ovarian cells, reported to be sensitive to TLR9 agonist therapy, were treated with cytosine–guanine (CpG)-oligodeoxynucleotides (ODNs), an anti-PD-1 antibody or their combination. Results. We found that PD-1 blockade dampened CpG-ODN antitumor activity. In vitro studies indicated that the interaction between the anti-PD-1 antibody fragment crystallizable (Fc) domain and macrophage Fc receptors caused these immune cells to acquire an immunoregulatory phenotype, contributing to a decrease in the efficacy of CpG-ODNs. Accordingly, in vivo macrophage depletion abrogated the detrimental effect exerted by the anti-PD-1 antibody. Conclusion. Our data suggest that if TLR signaling is active in macrophages, coadministration of an anti-PD-1 antibody can reprogram these immune cells towards a polarization state able to negatively affect the immune response and eventually promote tumor growth.
Efficacy and Safety of Auricular Acupuncture for the Treatment of Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial
Authors: Höxtermann Melanie D. , Buner Katja , Haller Heidemarie , Kohl Wiebke , Dobos Gustav , Reinisch Mattea , Kümmel Sherko , Cramer Holger , Voiss Petra
Published: August 2021

Among women, breast cancer is the most commonly diagnosed cancer worldwide. Sleep problems impair 40–70% of breast cancer survivors. This randomized controlled trial evaluates the effect of auricular acupuncture on sleep quality in breast cancer survivors suffering from insomnia. Fifty-two female breast cancer survivors with insomnia (mean age 55.73 ± 8.10 years) were randomized either to 10 treatments of auricular acupuncture within five weeks (n = 26), or to a single session of psychoeducation plus an insomnia advice booklet (n = 26). The primary outcome was sleep quality (measured by the Pittsburgh Sleep Quality Index) at week 5. Secondary outcomes were inflammation parameter (interleukin-6), stress, anxiety, depression, quality of life, and fatigue at week 5, and sleep quality, stress, anxiety, depression, quality of life, and fatigue 17 and 29 weeks after randomization. Intention-to-treat analysis showed a significantly stronger increase in sleep quality in the auricular acupuncture group compared to the psychoeducation group (p = 0.031; η2p = 0.094) at week 5. Furthermore, auricular acupuncture improved stress (p = 0.030; η2p = 0.094), anxiety (p = 0.001; η2p = 0.192), and fatigue (p = 0.006; η2p = 0.148) at week 5 compared to psychoeducation. No significant group difference was found concerning the other outcomes at week 5, or in any outcome at week 17 or week 29. No serious adverse events occurred during the study period. In conclusion, a semi-standardized group auricular acupuncture might be an effective and safe intervention in treating insomnia in breast cancer survivors in the short term, and may reduce stress, anxiety, and fatigue as well. Long-term effects remain questionable.
Naja atra Cardiotoxin 1 Induces the FasL/Fas Death Pathway in Human Leukemia Cells
Authors: Chiou Jing-Ting , Wang Liang-Jun , Lee Yuan-Chin , Chang Long-Sen
Published: August 2021

This study aimed to investigate the mechanistic pathway of Naja atra (Taiwan cobra) cardiotoxin 1 (CTX1)–induced death of leukemia cell lines U937 and HL-60. CTX1 increased cytoplasmic Ca2+ and reactive oxygen species (ROS) production, leading to the death of U937 cells. It was found that Ca2+-induced NOX4 upregulation promoted ROS-mediated p38 MAPK phosphorylation, which consequently induced c-Jun and ATF-2 phosphorylation. Using siRNA knockdown, activated c-Jun and ATF-2 were demonstrated to regulate the expression of Fas and FasL, respectively. Suppression of Ca2+-mediated NOX4 expression or ROS-mediated p38 MAPK activation increased the survival of U937 cells exposed to CTX1. FADD depletion abolished CTX1-induced cell death, caspase-8 activation, and t-Bid production, supporting the correlation between the Fas death pathway and CTX1-mediated cytotoxicity. Among the tested N. atra CTX isotoxins, only CTX1 induced Fas and FasL expression. Chemical modification studies revealed that intact Met residues were essential for the activity of CTX1 to upregulate Fas and FasL expression. Taken together, the data in this study indicate that CTX1 induces c-Jun-mediated Fas and ATF-2-mediated FasL transcription by the Ca2+/NOX4/ROS/p38 MAPK axis, thereby activating the Fas death pathway in U937 cells. Furthermore, CTX1 activates Fas/FasL death signaling in the leukemia cell line HL-60.
Aptamer-Sensitized Nanoribbon Biosensor for Ovarian Cancer Marker Detection in Plasma
Authors: Ivanov Yuri D. , Malsagova Kristina A. , Pleshakova Tatyana O. , Galiullin Rafael A. , Kozlov Andrey F. , Shumov Ivan D. , Popov Vladimir P. , Kapustina Svetlana I. , Ivanova Irina A. , Isaeva Arina I. , Tikhonenko Fedor V. , Kushlinskii Nikolay E. , Alferov Alexander A. , Tatur Vadim Yu. , Ziborov Vadim S. , Petrov Oleg F. , Glukhov Alexander V. , Archakov Alexander I.
Published: August 2021

The detection of CA 125 protein in buffer solution with a silicon-on-insulator (SOI)-based nanoribbon (NR) biosensor was experimentally demonstrated. In the biosensor, sensor chips, bearing an array of 12 nanoribbons (NRs) with n-type conductance, were employed. In the course of the analysis with the NR biosensor, the target protein was biospecifically captured onto the surface of the NRs, which was sensitized with covalently immobilized aptamers against CA 125. Atomic force microscopy (AFM) and mass spectrometry (MS) were employed in order to confirm the formation of the probe–target complexes on the NR surface. Via AFM and MS, the formation of aptamer–antigen complexes on the surface of SOI substrates with covalently immobilized aptamers against CA 125 was revealed, thus confirming the efficient immobilization of the aptamers onto the SOI surface. The biosensor signal, resulting from the biospecific interaction between CA 125 and the NR-immobilized aptamer probes, was shown to increase with an increase in the target protein concentration. The minimum detectable CA 125 concentration was as low as 1.5 × 10−17 M. Moreover, with the biosensor proposed herein, the detection of CA 125 in the plasma of ovarian cancer patients was demonstrated.
Selective Enhancement of SERS Spectral Bands of Salicylic Acid Adsorbate on 2D Ti3C2Tx-Based MXene Film
Authors: Adomavičiūtė-Grabusovė Sonata , Ramanavičius Simonas , Popov Anton , Šablinskas Valdas , Gogotsi Oleksiy , Ramanavičius Arūnas
Published: August 2021

In this research, we have demonstrated that 2D Ti3C2Xn-based MXene (MXene) films are suitable for the design of surface-enhanced Raman spectroscopy (SERS)-based sensors. The enhanced SERS signal was observed for a salicylic acid molecule on Ti3C2Tx-based MXene film. Confirmation of the adsorption of the salicylic acid molecule and the formation of a salicylic acid–MXene complex were determined by experimental SERS-based spectral observations such as greatly enhanced out-of-plane bending modes of salicylic acid at 896 cm−1 and a band doublet at 681 cm−1 and 654 cm−1. Additionally, some other spectral features indicate the adsorption of salicylic acid on the MXene surface, namely, a redshift of vibrational modes and the disappearance of the carboxyl deformation spectral band at 771 cm−1. The determined enhancement factor indicates the value that can be expected for the chemical enhancement mechanism in SERS of 220 for out-of-plane vibrational modes. Theoretical modeling based on density functional theory (DFT) calculations using B3LYP/6311G++ functional were performed to assess the formation of the salicylic acid/MXene complex. Based on the calculations, salicylic acid displays affinity of forming a chemical bond with titanium atom of Ti3C2(OH)2 crystal via oxygen atom in hydroxyl group of salicylic acid. The electron density redistribution of the salicylic acid–MXene complex leads to a charge transfer effect with 2.2 eV (428 nm) and 2.9 eV (564 nm) excitations. The experimentally evaluated enhancement factor can vary from 220 to 60 when different excitation wavelengths are applied.