bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Biosensor Based on Angiotensin‐Converting Enzyme II for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Human Saliva
Authors: Moreira Geisianny , Casso-Hartmann Lisseth , Datta Shoumen Palit Austin , Dean Delphine , McLamore Eric , Vanegas Diana
Published: July 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for COVID-19. Infection in humans requires angiotensin-converting enzyme II (hACE2) as the point of entry for SARS-CoV-2. PCR testing is generally definitive but expensive, although it is highly sensitive and accurate. Biosensor-based monitoring could be a low-cost, accurate, and non-invasive approach to improve testing capacity. We develop a capacitive hACE2 biosensor for intact SARS-CoV-2 detection in saliva. Laser-induced graphene (LIG) electrodes were modified with platinum nanoparticles. The quality control of LIG electrodes was performed using cyclic voltammetry. Truncated hACE2 was used as a biorecognition element and attached to the electrode surface by streptavidin–biotin coupling. Biolayer interferometry was used for qualitative interaction screening of hACE2 with UV-attenuated virions. Electrochemical impedance spectroscopy (EIS) was used for signal transduction. Truncated hACE2 binds wild-type SARS-CoV-2 and its variants with greater avidity than human coronavirus (common cold virus). The limit of detection (LoD) is estimated to be 2,960 copies/ml. The detection process usually takes less than 30 min. The strength of these features makes the hACE2 biosensor a potentially low-cost approach for screening SARS-CoV-2 in non-clinical settings with high demand for rapid testing (for example, schools and airports).
Changes in Muscle Activation During and After a Shoulder-Fatiguing Task: A Comparison of Elite Female Swimmers and Water Polo Players
Authors: King Savannah , Dong Lily , Caron Michelle , Côté Julie N.
Published: July 2022

This study compared female athletes with different aquatic sports expertise in their neuromuscular activation before, during, and after a shoulder internal rotation fatigue protocol. Eleven water polo players, 12 swimmers, and 14 controls completed concentric maximal voluntary external and internal shoulder rotations before and after a fatigue protocol consisting of concentric internal rotations at 50% of maximal voluntary contraction for at least 3 min or until reporting a rating of perceived effort RPE of 8/10 or higher. Muscle activation was measured for the maximal voluntary contractions, as well as for the first (T1), middle (T2), and third (T3) minute of the fatigue protocol using surface electromyography (EMG) on pectoralis major, anterior and posterior deltoid, upper and middle trapezius, and latissimus dorsi. Intramuscular EMG was used for supraspinatus, infraspinatus, and subscapularis. Pre-fatigue internal rotation torque was significantly correlated with shorter task duration (r = −0.39, p = 0.02), with water polo players producing significantly greater torque than controls but having significantly lower endurance. Swimmers demonstrated decreased latissimus dorsi activation at T3 compared to T2 (p = 0.020, g = 0.44) and T1 (p = 0.029, g = 0.74), differing from water polo players and controls who exhibited increased agonist activation and decreased activation of stabilizers. Comparing the pre-fatigue to the post-fatigue maximal shoulder rotations, water polo players had decreased activation in subscapularis (p = 0.018, g = 0.67); all groups had decreased activation in latissimus dorsi (p < 0.001), though swimmers demonstrated a large effect (g = 0.97); and controls had decreased activation in supraspinatus (p = 0.005, g = 0.71). Together, these results suggest that sports expertise may be associated with different muscle activation both while and after fatigue is induced. Further research should continue to explore sports-specific patterns of muscle recruitment and fatigue adaptations, as well as if certain strategies are adaptive or maladaptive. This may have important consequences for injury prevention among athletes who perform repetitive overhead movements in their sports and who are susceptible to overuse injuries.
The Indirect Impact of Smallholder Vegetable Production on Children's Nutrition Outcomes in Rural Vietnam
Authors: Genova Christian , Umberger Wendy , Peralta Alexandra , Newman Suzie , Zeng Di
Published: July 2022

Childhood undernutrition, particularly stunting, wasting, and micronutrient deficiencies, remains a major health concern in rural Vietnam. While literature suggests leveraging agriculture to improve child nutrition via agricultural diversification, market engagement, and women's empowerment, very few studies have empirically explored how smallholder vegetable production can influence household nutrition. This paper examines the association of household-level vegetable diversity, market access, and market participation with nutrition outcome measures of children in smallholder households. We use a cross-sectional household dataset, collected in 2016 in northwest Vietnam, covering 234 children aged 6–60 months. We estimate and compare the results of regression models using three-stage least squares (3SLS), ordinary least squares (OLS), logistic regression, and seemingly unrelated regression (SUR), to explore variations in six nutrition outcome measures: height-for-age z-score (HAZ), weight-for-height z-score (WHZ), weight-for-age z-score (WAZ), stunting, wasting, and underweight. Our results suggest smallholder vegetable production has a significant indirect association with children's nutrition status via market participation. Market participation is an important factor in improving girls' HAZ and WHZ, and in reducing the probability of boys being stunted and underweight. The additional income from selling vegetables allows households to purchase nutritious food, which is likely to have a positive impact on children's nutrition outcomes.
The European Hernia Society Prehabilitation Project: A Systematic Review of Intra-Operative Prevention Strategies for Surgical Site Occurrences in Ventral Hernia Surgery
Authors: Wouters D. , Cavallaro G. , Jensen Kristian K. , East B. , Jíšová B. , Jorgensen L. N. , López-Cano M. , Rodrigues-Gonçalves V. , Stabilini C. , Berrevoet F.
Published: July 2022

Background

Ventral hernia repair is one of the most commonly performed surgical procedures worldwide. To reduce the risk of complications, pre- and intra-operative strategies have received increasing focus in recent years. To assess possible preventive surgical strategies, this European Hernia Society endorsed project was launched. The aim of this review was to evaluate the current literature focusing on pre- and intra-operative strategies for surgical site occurrences (SSO) and specifically surgical site infection (SSI) in ventral hernia repair.

Methods

A systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases used were Pubmed and Web of Science. Original retrospective or prospective human adult studies describing at least one intra-operative intervention to reduce SSO after ventral hernia repair were considered eligible.

Results

From a total of 4775 results, a total of 18 papers were considered suitable after full text reading. Prehospital chlorhexidine gluconate (CHG) scrub appears to increase the risk of SSO in patients undergoing ventral hernia repair, while there is no association between any type of surgical hat worn and the incidence of postoperative wound events. Intraoperative measures as prophylactic negative pressure therapy, surgical drain placement and the use of quilt sutures seem beneficial for decreasing the incidence of SSO and/or SSI. No positive effect has been shown for antibiotic soaking of a synthetic mesh, nor for the use of fibrin sealants.

Conclusion

This review identified a limited amount of literature describing specific preventive measures and techniques during ventral hernia repair. An advantage of prophylactic negative pressure therapy in prevention of SSI was observed, but different tools to decrease SSIs and SSOs continuously further need our full attention to improve patient outcomes and to lower overall costs.
Average Daily Gain and Energy and Nitrogen Requirements of 4-Month-Old Female Yak Calves
Authors: Bai Binqiang , Degen A. Allan , Han Xiaodong , Hao Lizhuang , Huang Yayu , Niu Jianzhang , Liu Shujie
Published: July 2022

There is little information available on milk intake and energy and nitrogen requirements of growing yak calves. This study aimed to fill this important gap, as this information could be beneficial in designing a system to wean yak calves earlier than in natural time. We determined the average daily gain and energy and nitrogen balances and requirements of 4-month-old female yak calves (48.8 ± 2.45 kg,n= 8). The calves were allowed to suck once a day and were fed anad libitumconcentrate: hay diet at a ratio of 60:40. Milk intake averaged 540 ± 26 g/d, yielding 2.28 ± 0.112 MJ/d, which was 13% of the gross energy intake (GEI). The digestible energy intake (DEI):GEI ratio was 0.681, metabolizable energy intake (MEI):DEI was 0.913, and MEI:GEI was 0.621. The average daily gain of the calves was 433 ± 153.1 g/d, which consisted of 78.0 ± 8.99 g protein, 52.7 ± 23.74 g fat, and 302.3 ± 95.1 g water, that is, 18.0% protein, 13.0% fat and 69.8% water. There were 130.7 g of body solids and 9.06 MJ of energy in every kg of body mass gain. Of the MEI, 25.17 kJ were required for 1 g of body mass, 83.40 kJ for 1 g of body solids, and 2.62 kJ for 1 kJ of retained energy (RE), and RE was 36.6% of MEI. The maintenance energy requirement was 5.35 MJ/d, the efficiency of utilization of energy for growth (kg) was 0.72, and the heat increment of feeding for growth was 0.28 (1.55 MJ/d). Digestible nitrogen (N) was 0.685 while retained N (RN) was 0.489 of N intake. The N requirement for maintenance was 11.73 g/d or 0.61 g N/kg0.75per day, while the biological value (BV) of N was 91.1%. The energy and N requirements for yak calves were relatively low, which could be explained, at least in part, by the high efficiency of utilization of energy and high BV of N when compared to other livestock. These findings could be beneficial in designing early weaning systems for the many Himalayan households depending on yak production for their livelihoods.
Plasma Cytokines and Birth Weight as Biomarkers of Vaccine-Induced Humoral Responses in Piglets
Authors: Lipsit Sean , Facciuolo Antonio , Scruten Erin , Griebel Philip , Napper Scott
Published: July 2022

Failure to mount an effective immune response to vaccination leaves individuals at risk for infection and can compromise herd immunity. Vaccine unresponsiveness can range from poor responses “low responders” to a failure to seroconvert “non-responders.” Biomarkers of vaccine unresponsiveness, particularly those measured at the time of vaccination, could facilitate more strategic vaccination programs. We previously reported that pro-inflammatory cytokine signaling within peripheral blood mononuclear cells, elevated plasma interferon-gamma (IFNγ), and low birth weight correlated with vaccine-induced serum IgG titers in piglets that were below the threshold of detectable seroconversion (vaccine non-responders). These observations suggested that plasma IFNγ concentration and birth weight might serve as pre-vaccination biomarkers of vaccine unresponsiveness. To test this hypothesis, piglets (n = 67) from a different production facility were vaccinated with the same commercial Mycoplasma hyopneumoniae bacterin (RespiSure-One) to determine if there was a consistent and significant association between vaccine-induced serum IgG titers and either plasma cytokine concentrations or birth weight. All piglets seroconverted following vaccination with significantly less variability in vaccine-induced serum IgG titers than observed in the previous vaccine trial. Piglets exhibited highly variable birth weights and plasma cytokine concentrations prior to vaccination, but there were no significant associations (p > 0.05) between these variables and vaccine-induced serum IgG titers. There were significant (p < 0.001) differences in plasma IFNγ concentrations among individual litters (n = 6), and plasma IFNγ concentrations decreased in all pigs from birth to 63-days of age. One of the six litters (n = 11 piglets) exhibited significantly elevated plasma IFNγ concentrations during the first 3 weeks of life (p < 0.001) and at the time of vaccination (p < 0.01). This litter, however, had similar vaccine-induced serum IgG titers when compared to the other piglets in this study. Collectively the two studies indicate that while plasma cytokines and birth weight can be associated with vaccine non-responsiveness, their temporal and individual variation, as well as the complexity of the vaccine responsiveness phenotype, make them inconsistent biomarkers for predicting the less extreme phenotype of vaccine low responders.
SV40T/E6E7-Induced Proliferation Is Involved in the Activity of E2F3 in Bovine Mammary Epithelial Cells
Authors: Zhang Yihui , Zhan Kang , Hu Zixuan , Zhao Guoqi
Published: July 2022

The E2F family of transcription factor is divided into activators and repressors that control cell proliferation. Bovine mammary epithelial cells (BMECs) can be immortalized using human papillomavirus 16 E6E7 (HPV16 E6E7) and simian vacuolating virus 40 large T antigen (SV40T). In addition, SV40T does not require E2F1, E2F2, and E2F3 activators to induce proliferation in mouse embryo fibroblasts (MEFs). However, we report that E2F3 activator is required to induce the proliferation of BMECs. Our results showed that, at an early stage, primary BMECs lacking the E2F1 expression have the capacity to proliferate and show E2F2 and E2F3 slight protein levels. At a late stage, primary BMECs deficient for E2F3 completely abolish any proliferative ability and exhibit a severe cell senescence signal, although the E2F2 can be expressed at a late stage of primary BMECs. Compared with the late stage of primary BMECs, the BMECs immortalized by SV40T and E6E7 restored the protein level of E2F3 and enhanced the CDK4, CDK6, cyclin D3, and CDK2 protein level, leading to proliferating robustly. Surprisingly, it was found that p53, p21Cip1, and p27Kip1 were upregulated in SV40T and E6E7-immortalized BMECs, relatively to primary BMECs. Notably, Cdc2 was almost expressed in primary BMECs. However, Cdc2 was elevated in BMECs immortalized by SV40T and E6E7. In conclusion, this study revealed a molecular mechanism where E2F3 controls the BMECs’ proliferation and senescence.
Assessment of Negative Gingival Recession: A Critical Component of Periodontal Diagnosis
Authors: Wang I-Ching , Chan Hsun-Liang , Johnson Georgia K. , Elangovan Satheesh
Published: July 2022

Accurate measurement of negative gingival recession (GR) is essential to accurately determine the clinical attachment loss, which leads to an accurate diagnosis and optimal therapy of periodontal disease. However, the accuracy of measuring the negative GR has been shown to be low and highly variable between examiners. The position of the gingiva margin in relation to the cemento-enamel junction (CEJ) varies among different stages of passive eruption. The amount of negative GR is about 2 mm on average at the mid-facial sites and ranges from 2 to 3.5 mm at interproximal sites in periodontally healthy patients. Some other clinical conditions may change the gingival dimension coronal to the CEJ, such as altered passive eruption and gingival enlargement. In addition to the traditional approach using a periodontal probe to assess the negative GR, nowadays dental ultrasound imaging may be able to assist in accurately measuring the amount of negative GR. This narrative review will discuss the existing evidence of the dimension of dentogingival tissue and the clinical assessment of negative GR using different clinical tools.
Transport, Persistence, and Toxicity of Pollutants in the Sea
Authors: Marini Mauro , Annibaldi Anna
Published: July 2022

Eight research articles and two reviews are included in this Special Issue focused on the transport, persistence, and toxicity of pollutants in different seas: the Western and Central Mediterranean Sea, the Adriatic Sea, the Tyrrhenian Sea, the Baltic Sea, and the South China Sea [...]
A Binary Decision Model and Fat Tails in Financial Market
Authors: Sano Kazuo
Published: July 2022

Binary decision models have been the subject of renewed research in recent years. In these models, agents follow a stochastic evolution where they must choose between two possible choices by taking into account the choices of their peers. Kirman explained the process of ant social herding using a simple model, and he conducted an interesting simulation. The fat-tail distribution in the security market is well known, but its causes have not been sufficiently clarified. The aim of this article is to clarify them by a very simple model. In this article, by establishing a simple security market model and by applying the model of Kirman, the fat tail observed for price fluctuations is reproduced. Recent research in neuroscience has shown that noise plays a positive roll and enables us to have a deeper understanding of a natural commonality between ants and traders. The beauty competition of Keynes is kept in mind, and it is shown that a cause of the fat tail is the balance between independence and interdependence of the economic agents. Using a natural computing algorithm called Kirman’s ant model, I conducted a time series analysis of finance that appears when simplifying the human “behavior of imitating others”. The results show that natural fat tails appear.
The Synergy of Metadata and Metamodel through Algorithm Modeling—Case Study of the Roof Tiles in Yangxindian Palace (Beijing, China)
Authors: Wang Xi , Wu Cong , Lu Yutian , Tian Miao
Published: July 2022

The investigation of cultural heritage is a continuous process, in which a large scale of metadata is gradually accumulated, i.e., condition data, intervention data, and the comprehension of building techniques. We take the roof tile of Yangxindian Palace as an example. The total number of roof tiles is 17,154. Their positions are various, as they are equally distributed on double-curved irregular surfaces. Their metadata are multisource and heterogeneous. Therefore, the integration between the model and the data can be complex. This paper aims to generate the M1 (metalevel) model with its graph database based on the M3 (metalevel) model through algorithm modeling. This synergy approach consists of three parts. First is the data collection. The unique identifier is used as the index while investigating onsite, which eventually forms the metadata repository. Second is the algorithm modeling. All the roof tiles are rebuilt in Grasshopper with identifiers. Their metadata are merged through Cypher syntax, which can generate the graph database in Neo4j. Third is the delivery. The IFC model and knowledge graph are connected in real time during the whole process. The significance of this paper is to provide a synergy approach and discuss its efficiency for the integration between a model and data of very large quantities. The results show that it is efficient to express the semantic relationships of both conditions and interventions. It is practicable to lightweight the IFC model and to associate metadata into the graph database, enabling online browsing and querying.
The Effect of Forklift Type, Pallet Design, Entry Speed, and Top Load on the Horizontal Shock Impacts Exerted during the Interactions between Pallet and Forklift
Authors: Masis Jorge , Horvath Laszlo , Böröcz Péter
Published: July 2022

Forklift handling of palletized loads produces shock impacts that cause significant damage, affecting the durability and life cycle of pallets and unit loads. Laboratory testing processes using an incline impact tester have been developed to assess the resistance of pallets and unit loads to shock impact damage. A key element of the pallet durability test using the incline impact tester is the intensity of the impact. However, there is a lack of information on the intensity of the shock impacts during forklift handling. The objective of this research was to investigate the effects of forklift type, pallet design, entry speed, and top load on the horizontal shock responses measured during the interactions between pallets and forklifts. Two data loggers, SAVER 3X90 and 3D15, were used to measure the horizontal shock impacts experienced during the same event on both the pallet and the forklift. The results showed that the average peak acceleration of the forklift was 2.98 G; the same event resulted in a 4.4 times greater peak acceleration in the pallet. The average duration of these impacts was 10–12 ms. Pallet design and entry speed had the greatest effect on the response measured for the forklift, while the pallet was most heavily influenced by entry speed and forklift type. The paper mainly focused on measuring the severity of the impacts and did not attempt to correlate the measured impacts to damage experienced by unit loads.
China’s Water Intensity Factor Decomposition and Water Usage Decoupling Analysis
Authors: Du Boyu , Guo Xiaoqian , Liu Guwang , Wang Anjian , Duan Hongmei , Guo Shaobo
Published: July 2022

As the most populous country in the world, China has a great shortage pressure of water resources. With the acceleration of urbanization, China’s water usage in different sectors will change significantly in next few years. In order to investigate the main reasons behind water usage change in China, the Logarithmic Mean Divisia Index (LMDI) model was adopted in this paper from 2000 to 2020 with provincial data. Three effects, including that of technology, industrial structure, and regional scale, were analyzed. In addition, the decoupling effect between water usage and economic growth was also considered. The results show that: (1) from 2000 to 2020, the technological effect, industrial structure effect, and regional scale effect are −376.54, −89.85 and 20.66, respectively; (2) the technical effect and industrial structure effect have the greatest impact on primary industry, followed by secondary industry; (3) the technical effect is greater than the industrial structure effect in most provinces; and (4) the decoupling state gradually changes from weak decoupling to strong decoupling. In the future, the key policy recommendations for water saving are the following: (1) technological innovation has the most efficient effect on the reduction of water usage in China, and (2) the optimization of industrial structure can be helpful in water-saving in the future.
Investigation of Nonlinear Forced Vibrations of the “Rotor-Movable Foundation” System on Rolling Bearings by the Jacobi Elliptic Functions Method
Authors: Kydyrbekuly Almatbek , Zhauyt Algazy , Ibrayev Gulama-Garip Alisher
Published: July 2022

The paper considers a rotor system with a nonlinear characteristic. Its equations of motion are a kind of Duffing class equations with multiple degrees of freedom. The paper shows the advantage of using the method of elliptic functions for solving problems of this type. This method enables us to take into account not only vibrations of the rotor installed in elastic nonlinear supports, but also vibrations of the foundation. A comparative analysis of application of the method of elliptic functions proposed by the authors is carried out by comparing the derived equations of motion of the system, as well as by comparing the obtained amplitude-frequency characteristics with the results obtained by the numerical Runge–Kutta–Fehlberg’s 4-order method and the approximate analytical Van der Pol method. The regions of resonant frequencies for superharmonic oscillations and bifurcation regimes are determined. It is concluded that the method proposed by the authors is a more accurate and general case than the previously used approximate methods.
Analysis of Dental Implant Rehabilitation in the Reconstructed Jaw by Deep Circumflex Iliac Artery Flap, a Retrospective Study
Authors: Choi Jun-Seok , Jo Ye-Joon , Bang Jin-Ah , Kim Jin , Oh Ji-Su , Moon Seong-Yong
Published: July 2022

The purpose of this study is to analyze the clinical results of the implant rehabilitation for a jaw reconstructed by the deep circumflex iliac artery (DCIA) flap. A total of 13 patients were included in this study from 2010 to 2020. Medical records were collected retrospectively and analyzed. The mandible was involved in 10 cases and the maxilla was in 3 cases. The average width of the DCIA flap was 8.6 mm, and the height was 20.65 mm. A total of 41 dental implants with a diameter of 3.9–5.0 mm and a length of 10.0–11.5 mm were placed at an average of 12.3 months after the reconstruction. The average follow-up period after delivering a permanent prosthesis was 15 months (range, 2 to 51 months) and the overall mean follow-up period was 48 months. In all, 3 implants of the total 41 implants were removed. The DCIA flap is the most suitable for reproducing the original contour of the original jawbone compared with the fibular flap. In addition, the height and width of the reconstructed bone is appropriate for implant placement, which is advantageous for the rehabilitation of oral function and aesthetics using the implant.
Spatial-Temporal Distribution and Variation of NO2 and Its Sources and Chemical Sinks in Shanxi Province, China
Authors: Li Hongyan , Zhang Jin , Wen Biao , Huang Shidan , Gao Shuqin , Li Hongyu , Zhao Zhixin , Zhang Yanru , Fu Guo , Bai Jingai , Cui Yang , He Qiusheng , Wang Zhentao
Published: July 2022

In present China, continuing to control PM2.5 (particulate matter < 2.5 μm) and preventing the rise of O3 are the most urgent environmental tasks in its air clean actions. Considering that NO2 is an important precursor of PM2.5 and O3, a comprehensive analysis around this pollutant was conducted based on the real-time-monitoring data from Jan 2018 to Mar 2019 in 11 prefecture-level cities in Shanxi Province of China. The results showed that the annual average concentration of NO2 in Shanxi prefecture-level cities is mainly distributed in the range of 28.84–48.93 μg/m3 with the values in five cities exceeding the Chinese Grade Ⅱ standard limit (40 μg/m3). The over-standard days were all concentrated in the heating season with a large pollution peak occurring in winter except in Lvliang, while four cities also had a small pollution peak in summer. High NO2 polluted areas were mainly concentrated in the central part of Shanxi, and trended on the whole from the southwest to the northeast (Lvliang/Linfen—Taiyuan/Jinzhong—Yangquan/Jinzhong), which was different from the spatial distribution of PM2.5 and O3. Lvliang was the hot spot of NO2 pollution in summer, while Taiyuan was the hot spot in winter. Concentration Weighted Trajectory (CWT) analysis indicated that central-north Shaanxi, central-south Shanxi, northern Henan, the south of Shijiazhuang and areas around Erdos in Inner Mongolia were important source areas of NO2 in Shanxi besides local emissions. Our findings are expected to provide valuable implications to policymakers in Shanxi of China to effectively abate the air pollution.
The Contribution of Efflux Systems to Levofloxacin Resistance in Stenotrophomonas maltophilia Clinical Strains Isolated in Warsaw, Poland
Authors: Zając Olga M. , Tyski Stefan , Laudy Agnieszka E.
Published: July 2022

Levofloxacin is considered an alternative treatment option of Stenotrophomonas maltophilia infections to trimethoprim/sulfamethoxazole. The fluoroquinolone resistance in S. maltophilia is usually caused by an overproduction of efflux pumps. In this study, the contribution of efflux systems to levofloxacin resistance in S. maltophilia clinical isolates was demonstrated using phenotypic (minimal inhibitory concentrations, MICs, of antibiotics determination ± efflux pump inhibitors, EPIs) and molecular (real-time polymerase-chain-reaction and sequencing) methods. Previously, the occurrence of genes encoding ten efflux pumps was shown in 94 studied isolates. Additionally, 44/94 isolates demonstrated reduction in susceptibility to levofloxacin. Only 5 of 13 isolates (with ≥4-fold reduction in levofloxacin MIC) in the presence of EPIs showed an increased susceptibility to levofloxacin and other antibiotics. The overexpression of smeD and smeV genes (in five and one isolate, respectively) of 5 tested efflux pump operons was demonstrated. Sequencing analysis revealed 20–35 nucleotide mutations in local regulatory genes such as smeT and smeRv. However, mutations leading to an amino acid change were shown only in smeT (Arg123Lys, Asp182Glu, Asp204Glu) for one isolate and in smeRv (Gly266Ser) for the other isolate. Our data indicate that the overproduction of the SmeVWX efflux system, unlike SmeDEF, plays a significant role in the levofloxacin resistance.
Effect of Gum Acacia on the Intestinal Bioavailability of n-3 Polyunsaturated Fatty Acids in Rats
Authors: Couëdelo Leslie , Joseph Cécile , Abrous Hélène , Chamekh-Coelho Ikram , Vaysse Carole , Baury Aurore , Guillemet Damien
Published: July 2022

Lipid emulsification is a technique that is being explored for improving the bioavailability of omega 3 (n-3) long chain (LC) fatty acid (FA). The nature of the emulsifiers can differently impact the lipid bioavailability via a modification of the lipolysis step. Among natural emulsifiers, gum acacia (GA), an indigestible polysaccharide, provides protective encapsulation of n-3 by forming a specifically crown-like shape around lipid drops, which could also impact the digestion step. Despite the interest in lipolysis rate, the impact of GA on lipid bioavailability has never been explored in a complete physiological context. Thus, we followed in a kinetics study the n-3 bioavailability in rat lymph, orally administered DHA-rich oil, formulated based on GA compared to the bulk phase form of the oil. The AUC values were significantly improved by +121% for total TG and by 321% for n-3 PUFA, specifically for EPA (+244%) and for DHA (+345%). Benefits of GA have also been related to the transport of FA in lymph, which was 2 h earlier (Tmax = 4 h), compared to the Tmax (6 h) obtained with the bulk phase oil. All the data showed that GA is one of the most favorable candidates of natural emulsifiers to improve n-3 bioavailability and their rate of absorption for health targets.
A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis
Authors: Chng Wei Seng , Li Aaron Wei Liang , Lim Jasmine Jia Min , Leong Esther Jia En , Amran Fathiah S. , Kini R. Manjunatha , Chan Mark Yan Yee , Koh Cho Yeow
Published: July 2022

Activated factor XI (FXIa) is an important antithrombotic drug target. Clinical and pre-clinical data have demonstrated that its inhibition attenuates thrombosis with minimal risk of excessive bleeding. We isolated Fasxiator from the venom of banded krait Bungarus fasciatus and subsequently engineered FasxiatorN17R,L19E, with improved affinity (Ki = 0.9 nM) and selectivity towards FXIa. Here, we assess the in vivo efficacy and bleeding risk of rFasxiatorN17R, L19E in pre-clinical animal models. Rats injected intravenously (i.v.) with bolus rFasxiatorN17R, L19E showed the specific in vivo attenuation of the intrinsic coagulation pathway, lasting for at least 60 min. We performed the in vivo dose-ranging experiments for rFasxiatorN17R, L19E as follows: FeCl3-induced carotid artery occlusion in rats (arterial thrombosis); inferior vena cava ligation in mice (venous thrombosis); tail bleeding time in both rats and mice (bleeding risk). Head-to-head comparisons were made using therapeutic dosages of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for arterial and venous thrombosis, respectively. In the arterial thrombosis model, 2 mg/kg i.v. rFasxiatorN17R,L19E achieved a similar antithrombotic efficacy to that of UFH, with >3-fold lower bleeding time. In the venous thrombosis model, the 10 mg/kg subcutaneous (s.c.) injection of rFasxiatorN17R,L19E achieved similar efficacy and bleeding levels to those of LMWH enoxaparin. Overall, rFasxiatorN17R,L19E represents a promising molecule for the development of FXIa-targeting anticoagulants.
“CAPA in Progress”: A New Real-Life Approach for the Management of Critically Ill COVID-19 Patients
Authors: Carbonell Nieves , Alcaráz María Jesús , Serrano-Lázaro Ainhoa , Rodríguez-Gimillo María , Sánchez Ramos David , Ros Francisco , Ferrer Josep , Blasco María Luisa , Navarro David , Clari María Ángeles
Published: July 2022

(1) Background: COVID-19-associated pulmonary aspergillosis (CAPA) has worsened the prognosis of patients with pneumonia and acute respiratory distress syndrome admitted to the intensive care unit (ICU). The lack of specific diagnosis criteria is an obstacle to the timely initiation of appropriate antifungal therapy. Tracheal aspirate (TA) has been employed under special pandemic conditions. Galactomannan (GM) antigens are released during active fungal growth. (2) Methods: We proposed the term “CAPA in progress” (CAPA-IP) for diagnosis at an earlier stage by GM testing on TA in a specific population admitted to ICU presenting with clinical deterioration. A GM threshold ≥0.5 was set as the mycological inclusion criterion. This was followed by a pre-emptive short-course antifungal. (3) Results: We prospectively enrolled 200 ICU patients with COVID-19. Of these, 164 patients (82%) initially required invasive mechanical ventilation and GM was tested in TA in 93 patients. A subset of 19 patients (11.5%) fulfilled the CAPA-IP criteria at a median of 9 days after ICU admittance. The median GM value was 3.25 ± 2.82. CAPA-IP cases showed significantly higher ICU mortality [52.6% (10/19) vs. 34.5% (50/145), p = 0.036], as well as a much longer median ICU stay than those with a normal GM index [27 (7–64) vs. 11 (9–81) days, p = 0.008]. All cases were treated with a pre-emptive systemic antifungal for a median time of 19 (3–39) days. (4) Conclusions: CAPA-IP highlights a new real-life early approach in the field of fungal stewardship in ICU programs.
Supramolecular Enzymatic Labeling for Aptamer Switch-Based Electrochemical Biosensor
Authors: Villalonga Anabel , Parrado Concepción , Díaz Raúl , Sánchez Alfredo , Mayol Beatriz , Martínez-Ruíz Paloma , Vilela Diana , Villalonga Reynaldo
Published: July 2022

Here we report a novel labeling strategy for electrochemical aptasensors based on enzymatic marking via supramolecular host–guest interactions. This approach relies on the use of an adamantane-modified target-responsive hairpin DNA aptamer as an affinity bioreceptor, and a neoglycoconjugate of β-cyclodextin (CD) covalently attached to a redox enzyme as a labeling element. As a proof of concept, an amperometric aptasensor for a carcinoembryonic antigen was assembled on screen-printed carbon electrodes modified with electrodeposited fern-like gold nanoparticles/graphene oxide and, by using a horseradish peroxidase-CD neoglycoenzyme as a biocatalytic redox label. This aptasensor was able to detect the biomarker in the concentration range from 10 pg/mL to 1 ng/mL with a high selectivity and a low detection limit of 3.1 pg/mL in human serum samples.
Effects of Various Pseudomonas Bacteria Concentrations on the Strength and Durability Characteristics of Concrete
Authors: Shukla Ashish , Gupta Nakul , Dixit Saurav , Ivanovich Vatin Nikolai , Gupta Manish , Saxena Kuldeep Kumar , Prakash Chander
Published: July 2022

The goal of this study is to improve concrete’s efficiency by using a microbiologically produced specific growth/filler. One such way of thinking has resulted in the invention of a highly unusual concrete known as microbial concrete, which uses bacteria to cure flaws in the concrete. Investigators working with various microorganisms suggested several microbial concretes. The bacterium “Pseudomonas” was used in this experiment. Pseudomonas bacteria, which can make calcite precipitates on a proper medium supplied with a calcium supply, is a typical science lab bacterium for calcite generation. Two different concentrations (106 cfu/mL and 107 cfu/mL) of bacteria were added to cement concrete and it was observed that the bacterial concrete with two different concentrations gives results as compared with normal concrete. According to the findings of this investigation, the inclusion of bacteria resulted in a considerable increase in compressive strength when the dilution factor was 106 cells per ml of mixed water. With the incorporation of the microorganisms, it was discovered that holes were partly filled up by material growth, as shown by scanning electron micrography inspection of the sample. Concrete cubes without and with the inclusion of bacteria were molded, and it was discovered that the compressive strength of the cubes with the injection of microorganisms increased significantly. In this study, concrete cylinders without and with the inclusion of microorganisms were molded, and it was discovered that the split tensile strength of the cylinders with the injection of microorganisms increased significantly above the control. When compared with regular concrete, the results showed a maximum increase of 16 percent in compressive strength and a maximum increase of 12 percent in split tensile strength. It was discovered via durability testing that bacterial concrete had less weight loss and stronger tensile strength than conventional concrete when treated with 5 percent H2SO4 or 5 percent MgSO4 compared with control concrete.
The Significance of MicroRNAs in the Molecular Pathology of Brain Metastases
Authors: Siegl Frantisek , Vecera Marek , Roskova Ivana , Smrcka Martin , Jancalek Radim , Kazda Tomas , Slaby Ondrej , Sana Jiri
Published: July 2022

Brain metastases are the most frequent intracranial tumors in adults and the cause of death in almost one-fourth of cases. The incidence of brain metastases is steadily increasing. The main reason for this increase could be the introduction of new and more efficient therapeutic strategies that lead to longer survival but, at the same time, cause a higher risk of brain parenchyma infiltration. In addition, the advances in imaging methodology, which provide earlier identification of brain metastases, may also be a reason for the higher recorded number of patients with these tumors. Metastasis is a complex biological process that is still largely unexplored, influenced by many factors and involving many molecules. A deeper understanding of the process will allow the discovery of more effective diagnostic and therapeutic approaches that could improve the quality and length of patient survival. Recent studies have shown that microRNAs (miRNAs) are essential molecules that are involved in specific steps of the metastatic cascade. MiRNAs are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression and thus regulate most cellular processes. The dysregulation of these molecules has been implicated in many cancers, including brain metastases. Therefore, miRNAs represent promising diagnostic molecules and therapeutic targets in brain metastases. This review summarizes the current knowledge on the importance of miRNAs in brain metastasis, focusing on their involvement in the metastatic cascade and their potential clinical implications.
Racial/Ethnic Disparities in Mortality Related to Access to Care for Major Cancers in the United States
Authors: Wang Fei , Shu Xiang , Pal Tuya , Berlin Jordan , Nguyen Sang M. , Zheng Wei , Bailey Christina E. , Shu Xiao-Ou
Published: July 2022

Importance: The reasons underlying racial/ethnic mortality disparities for cancer patients remain poorly understood, especially regarding the role of access to care. Participants: Over five million patients with a primary diagnosis of lung, breast, prostate, colon/rectum, pancreas, ovary, or liver cancer during 2004–2014, were identified from the National Cancer Database. Cox proportional hazards models were applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for total mortality associated with race/ethnicity, and access to care related factors (i.e., socioeconomic status [SES], insurance, treating facility, and residential type) for each cancer. Results: Racial/ethnic disparities in total mortality were observed across seven cancers. Compared with non-Hispanic (NH)-white patients, NH-black patients with breast (HR = 1.27, 95% CI: 1.26 to 1.29), ovarian (HR = 1.20, 95% CI: 1.17 to 1.23), prostate (HR = 1.31, 95% CI: 1.30 to 1.33), colorectal (HR = 1.11, 95% CI: 1.10 to 1.12) or pancreatic (HR = 1.03, 95% CI: 1.02 to 1.05) cancers had significantly elevated mortality, while Asians (13–31%) and Hispanics (13–19%) had lower mortality for all cancers. Racial/ethnic disparities were observed across all strata of access to care related factors and modified by those factors. NH-black and NH-white disparities were most evident among patients with high SES or those with private insurance, while Hispanic/Asian versus NH-white disparities were more evident among patients with low SES or those with no/poor insurance. Conclusions and Relevance: Racial/ethnic mortality disparities for major cancers exist across all patient groups with different access to care levels. The influence of SES or insurance on mortality disparity follows different patterns for racial/ethnic minorities versus NH-whites. Impact: Our study highlights the need for racial/ethnic-specific strategies to reduce the mortality disparities for major cancers.
One-Pot Synthesis of Fatty Amines: Rh-Catalyzed Hydroaminomethylation of 1-Decene in an Aqueous Microemulsion System—Influence of Reaction Conditions on the Reaction Performance
Authors: Weber Ariane , Porthun Linus , Schomäcker Reinhard
Published: July 2022

The hydroaminomethylation of the long-chain olefin 1-decene and diethylamine with a homogeneous Rh(acac)(cod)/SulfoXantphos catalyst complex as a one-pot synthesis was investigated. The influence of reaction conditions such as temperature and synthesis gas pressure was determined, as well as the effects of the initial concentrations of catalyst precursor, ligand, and reactants on the yield of fatty amine. Hydroaminomethylation was successfully carried out in an aqueous microemulsion system using a non-ionic surfactant with a reaction time of 2 h. A maximum yield of 34%, high regioselectivities >97%, and chemoselectivities >85% were achieved.
MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury
Authors: Silvestro Serena , Mazzon Emanuela
Published: July 2022

Spinal cord injury (SCI) represents a devastating injury to the central nervous system (CNS) that is responsible for impaired mobility and sensory function in SCI patients. The hallmarks of SCI include neuroinflammation, axonal degeneration, neuronal loss, and reactive gliosis. Current strategies, including stem cell transplantation, have not led to successful clinical therapy. MiRNAs are crucial for the differentiation of neural cell types during CNS development, as well as for pathological processes after neural injury including SCI. This makes them ideal candidates for therapy in this condition. Indeed, several studies have demonstrated the involvement of miRNAs that are expressed differently in CNS injury. In this context, the purpose of the review is to provide an overview of the pre-clinical evidence evaluating the use of miRNA therapy in SCI. Specifically, we have focused our attention on miRNAs that are widely associated with neuronal and axon regeneration. “MiRNA replacement therapy” aims to transfer miRNAs to diseased cells and improve targeting efficacy in the cells, and this new therapeutic tool could provide a promising technique to promote SCI repair and reduce functional deficits.
The N-Terminal Domain of Bfa1 Coordinates Mitotic Exit Independent of GAP Activity in Saccharomyces cerevisiae
Authors: Li Yan , Song Kiwon
Published: July 2022

The spindle position checkpoint (SPOC) of budding yeast delays mitotic exit in response to misaligned spindles to ensure cell survival and the maintenance of genomic stability. The GTPase-activating protein (GAP) complex Bfa1–Bub2, a key SPOC component, inhibits the GTPase Tem1 to induce mitotic arrest in response to DNA and spindle damage, as well as spindle misorientation. However, previous results strongly suggest that Bfa1 exerts a GAP-independent function in blocking mitotic exit in response to misaligned spindles. Thus, the molecular mechanism by which Bfa1 controls mitotic exit in response to misaligned spindles remains unclear. Here, we observed that overexpression of the N-terminal domain of Bfa1 (Bfa1-D16), which lacks GAP activity and cannot localize to the spindle pole body (SPB), induced cell cycle arrest along with hyper-elongation of astral microtubules (aMTs) as Bfa1 overexpression in Δbub2. We found that Δbub2 cells overexpressing Bfa1 or Bfa1-D16 inhibited activation of Mob1, which is responsible for mitotic exit. In anaphase-arrested cells, Bfa1-D16 overexpression inhibited Tem1 binding to the SPB as well as Bfa1 overexpression. Additionally, endogenous levels of Bfa1-D16 showed minor SPOC activity that was not regulated by Kin4. These results suggested that Bfa1-D16 may block mitotic exit through inhibiting Tem1 activity outside of SPBs. Alternatively, Bfa1-D16 dispersed out of SPBs may block Tem1 binding to SPBs by physically interacting with Tem1 as previously reported. Moreover, we observed hyper-elongated aMTs in tem1-3, cdc15-2, and dbf2-2 mutants that induce anaphase arrest and cannot undergo mitotic exit at restrictive temperatures, suggesting that aMT dynamics are closely related to the regulation of mitotic exit. Altogether, these observations suggest that Bfa1 can control the SPOC independent of its GAP activity and SPB localization.
Modulation of MAPK- and PI3/AKT-Dependent Autophagy Signaling by Stavudine (D4T) in PBMC of Alzheimer’s Disease Patients
Authors: La Rosa Francesca , Zoia Chiara Paola , Bazzini Chiara , Bolognini Alessandra , Saresella Marina , Conti Elisa , Ferrarese Carlo , Piancone Federica , Marventano Ivana , Galimberti Daniela , Fenoglio Chiara , Scarpini Elio , Clerici Mario
Published: July 2022

Background: Aβ42 deposition plays a pivotal role in AD pathogenesis by inducing the activation of microglial cells and neuroinflammation. This process is antagonized by microglia-mediated clearance of Aβ plaques. Activation of the NLRP3 inflammasome is involved in neuroinflammation and in the impairments of Aβ-plaque clearance. On the other hand, stavudine (D4T) downregulates the NLRP3 inflammasome and stimulates autophagy-mediated Aβ-clearing in a THP-1-derived macrophages. Methods: We explored the effect of D4T on Aβ autophagy in PBMC from AD patients that were primed with LPS and stimulated with Aβ oligomers in the absence/presence of D4T. We analyzed the NLRP3 activity by measuring NLRP3-ASC complex formation by AMNIS FlowSight and pro-inflammatory cytokine (IL-1β, IL-18 and Caspase-1) production by ELISA. The phosphorylation status of p38, ERK, AKT, p70, and the protein expression of CREB, LAMP2A, beclin-1, Caspase-3 and Bcl2 were analyzed by Western blot. Results: Data showed that D4T: (1) downregulates NLRP3 inflammasome activation and the production of down-stream pro-inflammatory cytokines in PBMC; (2) stimulates the phosphorylation of AKT, ERK and p70 as well as LAMP2A, beclin-1 and Bcl2 expression and reduces Caspase-3 expression, suggesting an effect of this compound on autophagy; (3) increases phospho-CREB, which is a downstream target of p-ERK and p-AKT, inducing anti-inflammatory cytokine production and resulting in a possible decrease of Aβ-mediated cytotoxicity; and (4) reduces the phosphorylation of p38, a protein involved in the production of pro-inflammatory cytokines and tau hyperphosphorylation. Conclusions: D4T reduces the activation of the NLRP3 inflammasome, and it might stimulate autophagy as well as the molecular mechanism that modulates Aβ cytotoxicity, and D4T might reduce inflammation in the cells of AD patients. It could be very interesting to check the possible beneficial effects of D4T in the clinical scenario.