bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Magnesia Blended Cement Studies for Geotechnical Well Construction—A Review
Authors: Chen Weiqing , Elkatatny Salaheldin , Murtaza Mobeen , Mahmoud Ahmed Abdulhamid
Published: October 2021

The current paper presents a literature review on the studies of incorporation of magnesia (magnesium oxide) into Portland cement material from the geotechnical well construction perspective. Starting with a comparison of application conditions between civil construction and geotechnical well cementing, this work reviewed the Portland cement categorizations, magnesia manufacturing routes at first. Then, the physical-chemical-mechanical properties were investigated which includes the reactivity of magnesia, expansion influence from its hydration, and carbonation/dehydroxylation of magnesia blended Portland cement. The development of cement material hydration modeling methods is also summarized. Moreover, the experimental characterization methods have also been elucidated including composition determination, particle size analysis, volumetric variation measurement, compressive strength testing, shear-bond strength testing, transition state analysis, etc. Meanwhile, the results and conclusions were extracted from the literature. Through this route, a comprehensive understanding of the scientific research progress on magnesia blended Portland cement development for geotechnical well construction is derived. Additionally, it is concluded that incorporating magnesia into Portland cement can provide benefits for this material utilization in geotechnical well constructions provided the reasonable tuning among the characteristics of magnesia, the downhole surrounding conditions, and the formulation of the cement slurry. Satisfying these pre-conditions, the effective expansion not only mitigates the micro-annulus issues but also increases the shear bonding strength at the cementing interfaces. Moreover, the caustic magnesia introduction into Portland cement has the potential advantage on carbon dioxide geological sequestration well integrity compared with the Portland cement sheath without it because of the denser in-situ porous matrix evolvement and more stable carbon fixation features of magnesium carbonate. However, since the impact of magnesia on Portland cement strongly depended on its properties (calcination conditions, particle size, reactivity) and the aging conditions (downhole temperature, pressure, contacting medium), it should be noted that some extended research is worth conducting in the future such as the synchronized hydration between magnesia and Portland cement, the dosage limit of caustic magnesia in Portland cement in terms of CO2 sequestration and the corresponding mechanical properties analysis, and the hybrid method (caustic magnesia, Portland cement, and other supplementary cementitious materials) targeting the co-existence of the geothermal environment and the corrosive medium scenario.
Adhesive Boundary Element Method Using Virtual Crack Closure Technique
Authors: Xu Yang , Zhou Rongxin
Published: October 2021

In this study, a new adhesive contact model is built upon a boundary element method (BEM) model developed by Pohrt and Popov (2015). The strain energy release rate (SERR) on the edge of the bonding interface is evaluated using Virtual Crack Closure Technique (VCCT) which is shown to have better accuracy and weaker mesh-size dependency than the closed-form SERR formula derived by Pohrt and Popov. A composite delamination criterion is proposed for crack nucleation and propagation. Numerical results predicted by the present model are in good agreement with the analytical solutions of two classic problems, namely, the axisymmetric parabolic contact and the sinusoidal waviness contact in the plane strain condition. The model of Pohrt and Popov can achieve a similar accuracy for the axisymmetric parabolic contact where the mesh grid is non-conforming to the crack front. Once the conforming mesh grid is used, the accuracy of their model is significantly deteriorated, especially at high work of adhesion and high mesh density. In both BEM models, however, the crack nucleation is found to be mesh-dependent which may be solved by introducing an upper limit for the tensile normal traction.
Epidemiological Characteristics of Sporadic Nosocomial COVID-19 Infections From June 2020 to June 2021 in China: An Overview of Vaccine Breakthrough Infection Events
Authors: He Zhigang , Xiang Hongbing , Manyande Anne , Xu Weiguo , Fan Li , Xiang Boqi
Published: October 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has wreaked havoc on millions of people around the world. Although China quickly brought the Coronavirus disease (COVID-19) under control, there have been several sporadic outbreaks in different regions of China since June 2020. This article described the chronological nosocomial COVID-19 infection events related to several sporadic outbreaks of SARS-CoV-2 in different regions of China. We have reported epidemiological characteristics and management measures of sporadic nosocomial COVID-19 infections from June 2020 to June 2021 and specially focused on the domestic COVID-19 breakthrough infection in China, such as domestic COVID-19 breakthrough infection—a vaccinated healthcare professional working in the isolation ward of a designated COVID-19 hospital.
Associations of ADL Disability With Trunk Muscle Mass and Muscle Quality Indicators Measured by Opportunistic Chest Computed Tomography Imaging Among Older Inpatients
Authors: Jing Xiaofan , Tan Lingling , Fu Hongbo , Yang Ling , Yang Ming
Published: October 2021

Objectives: Sarcopenia is an important predictor of dependence in activities of daily living (ADL disability); however, the association between muscle quality and ADL disability has not been established. We aimed (1) to assess the feasibility of measuring trunk muscle mass and muscle quality by chest CT images; and (2) to explore the possible associations of ADL disability with these muscle mass and muscle quality indicators among older inpatients.

Methods: We included older patients in an acute care ward. ADL disability was defined as the Barthel Index (BI) score ≤ 60 points. Unenhanced chest CT images at the 12th thorax (T12) vertebral level were used to segment skeletal muscle area (SMA) and intermuscular adipose tissue (IMAT) and to measure the mean skeletal muscle radiodensity (SMD). Skeletal muscle index (SMI), the muscle mass indicator, was calculated by SMA (cm2)/body height squared (m2). The percentage of IMAT (IMAT%) was calculated using the equation: IMAT% = IMAT/(SMA+ IMAT) ×100%. Skeletal muscle radiodensity, IMAT, and IMAT% were the muscle quality indicators. Kendall's tau rank correlation coefficients (τ) were calculated to explore the correlations. Univariate and multivariate logistic regression models were performed to calculate odds ratios (OR) and 95% confidence interval (CI).

Results: We included 212 participants. Skeletal muscle index and SMD were positively and significantly associated with the BI score (τ = 0.14 and 0.31, respectively, both P < 0.001); whereas IMAT and IMAT% were negatively and significantly associated with the BI score (τ = −0.21, P < 0.001; τ = −0.21, P < 0.012). After adjusting for confounders, SMI (adjusted OR 1.03, 95% CI 0.97–1.09) was not independently associated with ADL disability; however, SMD (adjusted OR 0.94, 95% CI 0.88–0.99), IMAT (adjusted OR 1.11, 95% CI 1.03–1.20), and IMAT% (adjusted OR 1.09, 95% CI 1.02–1.16) were independently associated with ADL disability. Subgroup analysis found similar results in men; however, none of these indicators were independently associated with ADL disability in women.

Conclusion: Trunk muscle quality indicators (SMD, IMAT, and IMAT%) measured by chest CT images, but not SMI, are independently associated with ADL disability in a single-center study population of older inpatients, especially in men. Further research is necessary to validate our findings.
Clinical Outcomes of Unrelated Umbilical Cord Blood Graft vs. Haploidentical Donor Transplantation: Critical Issues for an Adequate Comparison
Authors: Vanegas Diana , Niño-Quiroga Laura , Chaparro Mauricio , Camacho-Rodríguez Bernardo , Estupiñán Marcela , Perdomo-Arciniegas Ana-María
Published: October 2021

Unrelated umbilical cord blood (UCB) and haploidentical grafts have been used for allogeneic hematopoietic stem and progenitor cell (HSPC) transplantation in patients without a related or non-related human leukocyte antigen (HLA)-matched donor. The less stringent HLA-matching requirement in both sources raises an important possibility for patients in need of urgent transplantation to treat any hematological disease. Selection of the best alternative donor is a difficult task that will depend on donor criteria, center experience, patient disease conditions, and risk, among others. Most comparisons available in scientific publications between both graft sources are obtained from retrospective analysis in wide time windows and a heterogeneous number of patients, types of disease, disease stages, previous treatments, graft source, conditioning regimen, graft vs. host disease (GVHD) approach, and evaluable endpoints. There is also an evident impact of the economic traits since low-income countries must consider less expensive treatments to satisfy the needs of the patients in the most effective possible path. Therefore, haploidentical transplantation could be an appealing option, even though it has not been completely established if any chronic treatment derived from the procedure could become a higher cost. In Colombia, there is a huge experience in UCB transplantation especially in units of pediatric transplantation where benign indications are more common than in adults. Due to the availability of a public UCB bank and HLA high-resolution typing in Colombia, there is a wider inventory of cord blood donors. Unfortunately, we do not have an unrelated bone marrow donor registry, so UCB is an important source along with haploidentical transplantation to consider in decision-making. This minireview focuses on comparing the main issues associated with the use of both HSCP sources and provides tools for physicians who face the difficult decision between these alternative donor sources.
Trends in Corneal Transplantation and Characteristics of Donors in the Chongqing Eye Bank, China: A Retrospective Study, 1999–2018
Authors: Tan Handan , Lin Meng , Gou Qingqing , Li Aijia , Gu Fengjuan , Liu Quan , Zhang Qi , Xu Mei , Kijlstra Aize , Yang Peizeng , Li Hong
Published: October 2021

Aim: This study aimed to analyze corneal transplantation trends and voluntary donor characteristics at the Chongqing Eye Bank in China.

Methods: We retrospectively reviewed and analyzed data from January 1, 1999, to December 31, 2018, covering 5,397 preregistered voluntary donors, 1,955 actual donors, 3,910 donated tissues, and 2,374 corneal transplantations.

Results: The 5,397 preregistered donors included 13 ethnic groups, with an overall mean age of 39.6 years (SD 21.5) and 3,010 were women (55.8%). The most prevalent education level was college and above (2,546, 47.2%), and the most common ethnic group was Han (5,335, 98.85%). Of the 1,955 actual donors, the male-to-female ratio was 3.3, and the mean age was 57.1 (SD 23.0 years). Based on population size in 2018, Jiangbei county was the most active in donation willingness, with ~60 × 10−6 per capita, and the Yuzhong county was the most active in cornea donations, with ~451 × 0−6 per capita. Of the 3,910 donated corneas, 2,540 (65.0%) were clinically used. Of those not used, 978 (71.4%) were rejected for poor corneal quality. The 2,374 (93.5%) corneal transplantation procedures were done at the Department of Ophthalmology of the First Affiliated Hospital of Chongqing Medical University and the rest (n = 166, 6.5%) were performed in other centers. Of those 2,374 corneal transplantations, there were 1,671 penetrating keratoplasty (70.39%), 700 anterior lamellar keratoplasty (29.49%), and three corneal endothelial transplantations in our center (0.13%). The number of annual corneal transplantations increased by nearly 10 times, from 35 cases in 1999 to 327 cases in 2018. Among them, cases of penetrating keratoplasty and anterior lamellar keratoplasty increased from 27, and eight cases in 1999 to 230 and 94 cases in 2018, respectively. Infectious keratitis (37.0%) was the leading indication for keratoplasty, followed by corneal scar (19.8%). Over the study period, corneal scars dropped from the first (41.1% in 1999–2003) to the second indication (20.5% in 2014–2018), while infectious keratitis advanced to take the lead, ranging from 12.2% in 1999–2003 to 26.3% in 2014–2018.

Conclusion: Our study reports corneal donation and transplantation trends in Chongqing over 20 years, showing that infectious keratitis is a leading indication for keratoplasty and that penetrating keratoplasty and anterior lamellar keratoplasty show upward trends. The analysis further suggests that a potential preregistered cornea donor is a female Han, with a higher education level.
Improving Access to Refractive Services in Adults: A Health Examination Center-Based Model
Authors: Lin Haishuang , Sun Jing , Congdon Nathan , Xu Meiping , Liu Shanshan , Liang Yuanbo , Wang Hailin , Zhang Shaodan
Published: October 2021

Purpose: To assess the potential of a health examination center-based screening model in improving service for uncorrected refractive error.

Methods: Individuals aged ≥18 years undergoing the routine physical examinations at a tertiary hospital in the northeast China were invited. Presenting visual acuity, noncycloplegic autorefraction, noncontact tonometry, fundus photography, and slit-lamp examination were performed. Refractive error was defined as having spherical equivalent ≤ -0.75 D or ≥ +1 D and uncorrected refractive error was considered as refractive error combined with presenting visual acuity < 6/12 in the better eye. Costs for the screening were assessed.

Results: A total of 5,284 participants (61 ± 14 years) were included. The overall prevalence of myopia and hyperopia was 38.7% (95% CI, 37.4–40.0%) and 23.5% (95% CI, 22.3–24.6%), respectively. The prevalence of uncorrected refractive error was 7.85% (95% CI, 7.13–8.58%). Women (p < 0.001 and p = 0.003), those with age ≥ 70 years (p < 0.001 and p = 0.003), and myopia (p < 0.001 and p < 0.001) were at higher risk of uncorrected refractive error and uncorrected refractive error-related visual impairment. Spectacle coverage rate was 70.6% (95% CI, 68.2–73.0%). The cost to identify a single case of refractive error and uncorrected refractive error was US$3.2 and US$25.2, respectively.

Conclusion: The prevalence of uncorrected refractive error is high in the urban Chinese adults. Health examination center-based refractive error screening is able to provide an efficient and low-cost model to improve the refractive services in China.
Factors Determining Retreatment Time Interval of Rituximab in Korean Patients With Rheumatoid Arthritis
Authors: Kim Ji-Won , Jung Ju-Yang , Shin Kichul , Suh Chang-Hee , Kim Hyoun-Ah
Published: October 2021

Unlike other biologic agents for rheumatoid arthritis (RA) that are administered at regular intervals even without flare, rituximab can be administered according to the timing of retreatment determined by the physician. Recently, there has been a tendency to prefer on-demand administration for disease flares rather than regular retreatment. We aimed to investigate the retreatment patterns of rituximab in patients with RA and to identify factors associated with extension of the time interval between retreatment courses. This study included RA patients on rituximab treatment who were enrolled in the Korean Rheumatology Biologics registry (KOBIO) or treated at Ajou University Hospital. Previous or current concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), corticosteroids, number of previous biologic agents, withdrawal, and time intervals of rituximab retreatment were collected. In case of treatment failure, the reasons such as lack of efficacy, adverse events, and others, were also identified. A total of 82 patients were enrolled. The mean follow-up period from the first cycle of rituximab was 46.1 months, and the mean interval between the retreatment courses was 16.3 months. The persistent rates of rituximab after 5 years was 72.4%. Concomitant use of at least two csDMARDs (β = 4.672; 95% CI: 0.089–9.255, p = 0.046) and concomitant use of corticosteroids (β = 7.602; 95% CI: 0.924–14.28, p = 0.026) were independent factors for extending the time interval between the retreatment courses. In conclusion, RA patients treated with rituximab in Korea show high persistence rates. Concomitant use of two or more csDMARDs and concomitant use of corticosteroids with rituximab are associating factors of extending the retreatment time interval. These findings should be considered when selecting rituximab as a treatment for patients with RA.
Case Report: Nintedaninb May Accelerate Lung Recovery in Critical Coronavirus Disease 2019
Authors: Bussolari Cecilia , Palumbo Diego , Fominsky Evgeni , Nardelli Pasquale , De Lorenzo Rebecca , Vitali Giordano , De Cobelli Francesco , Rovere-Querini Patrizia , Scandroglio Anna Mara
Published: October 2021

Severe Coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) which may lead to long-lasting pulmonary sequelae in the survivors. COVID-19 shares common molecular signatures with interstitial lung diseases (ILDs), including pro-angiogenic and tissue-remodeling mechanisms mediated by vascular endothelial growth factor receptor (VEGF-R), fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R). Nintedanib mainly targets these factors and is approved for ILDs. Therefore, we administered nintedanib through compassionate use to three patients with COVID-19 pneumonia requiring extra-corporeal membrane-oxygenation (ECMO). Here, we describe our experience in an attempt to explore the role of nintedanib in lung recovery in COVID-19. Three obese patients aged between 42 and 52 years were started on nintedanib due to difficulty in obtaining lung function restoration and weaning from ECMO support following the removal of orotracheal intubation (OTI). Soon after the start of the treatment, systemic inflammation and respiratory function rapidly improved and ECMO support was withdrawn. Serial chest CT scans confirmed the progressive lung amelioration, also reflected by functional tests during follow-up. Nintedanib was well-tolerated by all the three patients at the dosage used for ILDs and continued for 2–3 months based on drug availability. Although caution in interpreting events is required; it is tempting to speculate that nintedanib may have contributed to modulate lung inflammation and remodeling and to sustain lung repair. Altogether, nintedanib appears as a promising agent in patients with severe COVID-19 and delayed respiratory function recovery, for whom molecularly targeted therapies are still lacking. Clinical trials are necessary to confirm our observations.
The 5′ and 3′ Untranslated Regions of the Japanese Encephalitis Virus (JEV): Molecular Genetics and Higher Order Structures
Authors: Liu Hong , Zhang Jun , Niu Yuzhen , Liang Guodong
Published: October 2021

The untranslated region (UTRs) of viral genome are important for viral replication and immune modulation. Japanese encephalitis virus (JEV) is the most significant cause of epidemic encephalitis worldwide. However, little is known regarding the characterization of the JEV UTRs. Here, systematic analyses of the UTRs of JEVs isolated from a variety of hosts worldwide spanning about 80 years were made. All the important cis-acting elements and structures were compared with other mosquito-borne Flaviviruses [West Nile virus (WNV), Yellow fever virus (YFV), Zika virus (ZIKV), Dengue virus (DENV)] and annotated in detail in the UTRs of different JEV genotypes. Our findings identified the JEV-specific structure and the sequence motif with unique JEV feature. (i) The 3’ dbsHP was identified as a small hairpin located in the DB region in the 3′ UTR of JEV, with the structure highly conserved among the JEV genotypes. (ii) The spacer sequence UARs of JEV consist of four discrete spacer sequences, whereas the UARs of other mosquito-borne Flaviviruses are continuous sequences. In addition, repetitive elements have been discovered in the UTRs of mosquito-borne Flaviviruses. The lengths, locations, and numbers of the repetitive elements of JEV also differed from other Flaviviruses (WNV, YFV, ZIKV, DENV). A 300 nt-length region located at the beginning of the 3′ UTR exhibited significant genotypic specificity. This study lays the basis for future research on the relationships between the JEV specific structures and elements in the UTRs, and their important biological function.
Non-invasive Biofouling Monitoring to Assess Drinking Water Distribution System Performance
Authors: Pick Frances C. , Fish Katherine E. , Husband Stewart , Boxall Joby B.
Published: October 2021

Biofilms are endemic in drinking water distribution systems (DWDS), forming on all water and infrastructure interfaces. They can pose risks to water quality and hence consumers. Our understanding of these biofilms is limited, in a large part due to difficulties in sampling them without unacceptable disruption. A novel, non-destructive and non-disruptive biofilm monitoring device (BMD), which includes use of flow cytometry analysis, was developed to assess biofouling rates. Laboratory based experiments established optimal configurations and verified reliable cell enumeration. Deployment at three operational field sites validated assessment of different biofouling rates. These differences in fouling rates were not obvious from bulk water sampling and analysis, but did have a strong correlation with long-term performance data of the associated networks. The device offers the potential to assess DWDS performance in a few months, compared to the number of years required to infer findings from historical customer contact data. Such information is vital to improve the management of our vast, complex and uncertain drinking water supply systems; for example rapidly quantifying the benefits of improvements in water treatment works or changes to maintenance of the network.
Deep Learning Driven Drug Discovery: Tackling Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Zhang Yang , Ye Taoyu , Xi Hui , Juhas Mario , Li Junyi
Published: October 2021

Deep learning significantly accelerates the drug discovery process, and contributes to global efforts to stop the spread of infectious diseases. Besides enhancing the efficiency of screening of antimicrobial compounds against a broad spectrum of pathogens, deep learning has also the potential to efficiently and reliably identify drug candidates against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Consequently, deep learning has been successfully used for the identification of a number of potential drugs against SARS-CoV-2, including Atazanavir, Remdesivir, Kaletra, Enalaprilat, Venetoclax, Posaconazole, Daclatasvir, Ombitasvir, Toremifene, Niclosamide, Dexamethasone, Indomethacin, Pralatrexate, Azithromycin, Palmatine, and Sauchinone. This mini-review discusses recent advances and future perspectives of deep learning-based SARS-CoV-2 drug discovery.
Mitochondrial Genomics of Six Cacao Pathogens From the Basidiomycete Family Marasmiaceae
Authors: Ali Shahin S. , Amoako-Attah Ishmael , Shao Jonathan , Kumi-Asare Eric , Meinhardt Lyndel W. , Bailey Bryan A.
Published: October 2021

Thread blight disease has recently been described as an emerging disease on cacao (Theobroma cacao) in Ghana. In Ghana, thread blight disease is caused by multiple species of theMarasmiaceaefamily:Marasmius tenuissimus, M. crinis-equi,M. palmivorus, andMarasmiellus scandens. Interestingly, two additional members of theMarasmiaceae;Moniliophthora roreri(frosty pod rot) andMoniliophthora perniciosa(witches’ broom disease), are major pathogens of cacao in the Western hemisphere. It is important to accurately characterize the genetic relationships among these economically important species in support of their disease management. We used data from Illumina NGS-based genome sequencing efforts to study the mitochondrial genomes (mitogenomes) of the four cacao thread blight associated pathogens from Ghana and compared them with published mitogenomes ofMon. roreriandMon. perniciosa. There is a remarkable interspecies variation in mitogenome size within the six cacao-associatedMarasmiaceaespecies, ranging from 43,121 to 109,103 bp. The differences in genome lengths are primarily due to the number and lengths of introns, differences in intergenic space, and differences in the size and numbers of unidentified ORFs (uORF). Among sevenM. tenuissimusmitogenomes sequenced, there is variation in size and sequence pointing to divergent evolution patterns within the species. The intronic regions show a high degree of sequence variation compared to the conserved sequences of the 14 core genes. The intronic ORFs identified, regardless of species, encode GIY-YIG or LAGLIDADG domain-containing homing endonuclease genes. Phylogenetic relationships using the 14 core proteins largely mimic the phylogenetic relationships observed in gene order patterns, groupingM. tenuissimuswithM. crinis-equi, andM. palmivoruswithMon. roreriandMon. perniciosa, leavingMar. scandensas an outlier. The results from this study provide evidence of independent expansion/contraction events and sequence diversification in each species and establish a foundation for further exploration of the evolutionary trajectory of the fungi inMarasmiaceaefamily.
An Stomatin, Prohibitin, Flotillin, and HflK/C-Domain Protein Required to Link the Phage-Shock Protein to the Membrane in Bacillus subtilis
Authors: Scholz Abigail Savietto , Baur Sarah S. M. , Wolf Diana , Bramkamp Marc
Published: October 2021

Membrane surveillance and repair is of utmost importance to maintain cellular integrity and allow cellular life. Several systems detect cell envelope stress caused by antimicrobial compounds and abiotic stresses such as solvents, pH-changes and temperature in bacteria. Proteins containing an Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH)-domain, including bacterial flotillins have been shown to be involved in membrane protection and membrane fluidity regulation. Here, we characterize a bacterial SPFH-domain protein, YdjI that is part of a stress induced complex inBacillus subtilis. We show that YdjI is required to localize the ESCRT-III homolog PspA to the membrane with the help of two membrane integral proteins, YdjG/H. In contrast to classical flotillins, YdjI resides in fluid membrane regions and does not enrich in detergent resistant membrane fractions. However, similarly to FloA and FloT fromB. subtilis, deletion of YdjI decreases membrane fluidity. Our data reveal a hardwired connection between phage shock response and SPFH proteins.
Characterization of Leader Processing Shows That Partially Processed Mersacidin Is Activated by AprE After Export
Authors: Viel Jakob H. , van Tilburg Amanda Y. , Kuipers Oscar P.
Published: October 2021

The ribosomally synthesized and post-translationally modified peptide mersacidin is a class II lanthipeptide with good activity against Gram-positive bacteria. The intramolecular lanthionine rings, that give mersacidin its stability and antimicrobial activity, are specific structures with potential applications in synthetic biology. To add the mersacidin modification enzymes to the synthetic biology toolbox, a heterologous expression system for mersacidin in Escherichia coli has recently been developed. While this system was able to produce fully modified mersacidin precursor peptide that could be activated by Bacillus amyloliquefaciens supernatant and showed that mersacidin was activated in an additional proteolytic step after transportation out of the cell, it lacked a mechanism for clean and straightforward leader processing. Here, the protease responsible for activating mersacidin was identified and heterologously produced in E. coli, improving the previously reported heterologous expression system. By screening multiple proteases, the stringency of proteolytic activity directly next to a very small lanthionine ring is demonstrated, and the full two-step proteolytic activation of mersacidin was elucidated. Additionally, the effect of partial leader processing on diffusion and antimicrobial activity is assessed, shedding light on the function of two-step leader processing.
Effects of Dietary Zinc Sources on Growth Performance and Gut Health of Weaned Piglets
Authors: Diao Hui , Yan Jiayou , Li Shuwei , Kuang Shengyao , Wei Xiaolan , Zhou Mengjia , Zhang Jinxiu , Huang Chongbo , He Peng , Tang Wenjie
Published: October 2021

The present study aimed to investigate the effects of dietary zinc sources on the growth performance and gut health of weaned piglets. In total, 96 Duroc × Landrace × Yorkshire (DLY) weaned piglets with an initial average body weight of 8.81±0.42kg were divided into four groups, with six replicates per treatment and four pigs per replicate. The dietary treatment groups were as follows: (1) control group, basal diet; (2) zinc sulphate (ZnSO4) group, basal diet +100mg/kg ZnSO4; (3) glycine zinc (Gly-Zn) group, basal diet +100mg/kg Gly-Zn and (4) zinc lactate group, and basal diet +100mg/kg zinc lactate. The whole trial lasted for 28days. Decreased F/G was noted in the Gly-Zn and zinc lactate groups (p<0.05). The zinc lactate group had a lower diarrhea rate than the control group (p<0.05). Moreover, the ZnSO4, Gly-Zn, and zinc lactate groups had significantly higher apparent total tract digestibility of dry matter (DM), crude protein (CP), ether extract (EE), crude ash, and zinc than the control group (p<0.05). The Gly-Zn and zinc lactate groups had higher jejunal villus height and a higher villus height:crypt depth ratio than the control group (p<0.05). In addition, the ZnSO4, Gly-Zn and zinc lactate groups had a significantly lower mRNA expression level of jejunal ZRT/IRT-like protein 4 (ZIP4) and higher mRNA expression level of jejunal interleukin-1β (IL-1β) than the control group (p<0.05). The mRNA expression level of jejunal zinc transporter 2 (ZNT2) was higher and that of jejunal Bcl-2-associated X protein (Bax) was lower in the Gly-Zn and zinc lactate groups than in the control group (p<0.05). Moreover, the zinc lactate group had a higher count of Lactobacillus spp. in the cecal digesta and higher mRNA expression levels of jejunal occludin and mucin 2 (MUC2) than the control group (p<0.05). In conclusion, dietary supplementation with 100mg/kg ZnSO4, Gly-Zn, or zinc lactate could improve the growth performance and gut barrier function of weaned piglets. Dietary supplementation with organic zinc, particularly zinc lactate, had the best effect.
The Effects of 5-Fluorouracil/Leucovorin Chemotherapy on Cognitive Function in Male Mice
Authors: Groves Thomas , Corley Christa , Byrum Stephanie D. , Allen Antiño R.
Published: October 2021

5-Fluorouracil (5-Fu) and leucovorin (LV) are often given in combination to treat colorectal cancer. 5-Fu/LV prevents cell proliferation by inhibiting thymidylate synthase, which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. While 5-Fu has been shown to cause cognitive impairment, the synergistic effect of 5-Fu with LV has not been fully explored. The present investigation was designed to assess how the combination of 5-Fu and LV affect cognition in a murine model. Six-month-old male mice were used in this study; 15 mice received saline injections and 15 mice received 5-Fu/LV injections. One month after treatment, the elevated plus maze, Y-maze, and Morris water maze behavioral tasks were performed. Brains were then extracted, cryosectioned, and stained for CD68 to assay microglial activation and with tomato lectin to assay the vasculature. All animals were able to locate the visible and hidden platform locations in the water maze. However, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden-platform training (first probe trial) in animals that received 5-Fu/LV, but these animals showed spatial memory retention by day 5. There were no significant increases in inflammation as measured by CD68, but 5-Fu/LV treatment did modulate blood vessel morphology. Tandem mass tag proteomics analysis identified 6,049 proteins, 7 of which were differentially expressed with a p-value of <0.05 and a fold change of >1.5. The present data demonstrate that 5-Fu/LV increases anxiety and significantly impairs spatial memory retention.
Aging Effect on Visuomotor Adaptation: Mediated by Cognitive Decline
Authors: Li Na , Chen Guopeng , Xie Yong , Chen Zhongting
Published: October 2021

The question of whether and how aging affects humans’ visuomotor adaptation remains controversial. This study investigates how the effect of aging on visuomotor adaptation is related to age-related cognitive declines. We compared the performance of 100 older people (age: 55–82 years) and 20 young adults (age: 18–27 years) on a visuomotor adaptation task and three cognition tasks. A decline in visuomotor adaptation of older people was well observed. However, this decline was not strongly correlated with chronological age increase but was associated to the age-related declines of cognitive functions and speed of motor planning. We then constructed a structural mediation model in which the declined cognitive resources mediated the effect of age increase on the decline in visuomotor adaptation. The data from the present study was well-explained by the mediation model. These findings indicate that the aging effect on visuomotor adaptation mainly reflects the age-related decline of cognitive functions, which results in insufficient explicit processing on visual perturbation during visuomotor control.
Differential Effects of a Nap on Motor Sequence Learning-Related Functional Connectivity Between Young and Older Adults
Authors: Fang Zhuo , Smith Dylan M. , Albouy Genevieve , King Bradley R. , Vien Catherine , Benali Habib , Carrier Julie , Doyon Julien , Fogel Stuart
Published: October 2021

In older adults, motor sequence learning (MSL) is largely intact. However, consolidation of newly learned motor sequences is impaired compared to younger adults, and there is evidence that brain areas supporting enhanced consolidation via sleep degrade with age. It is known that brain activity in hippocampal–cortical–striatal areas is important for sleep-dependent, off-line consolidation of motor-sequences. Yet, the intricacies of how both age and sleep alter communication within this network of brain areas, which facilitate consolidation, are not known. In this study, 37 young (age 20–35) and 49 older individuals (age 55–75) underwent resting state functional magnetic resonance imaging (fMRI) before and after training on a MSL task as well as after either a nap or a period of awake rest. Young participants who napped showed strengthening of functional connectivity (FC) between motor, striatal, and hippocampal areas, compared to older subjects regardless of sleep condition. Follow-up analyses revealed this effect was driven by younger participants who showed an increase in FC between striatum and motor cortices, as well as older participants who showed decreased FC between the hippocampus, striatum, and precuneus. Therefore, different effects of sleep were observed in younger vs. older participants, where young participants primarily showed increased communication in the striatal-motor areas, while older participants showed decreases in key nodes of the default mode network and striatum. Performance gains correlated with FC changes in young adults, and this association was much greater in participants who napped compared to those who stayed awake. Performance gains also correlated with FC changes in older adults, but only in those who napped. This study reveals that, while there is no evidence of time-dependent forgetting/deterioration of performance, older adults exhibit a completely different pattern of FC changes during consolidation compared to younger adults, and lose the benefit that sleep affords to memory consolidation.
Histological Correlates of Neuroanatomical Changes in a Rat Model of Levodopa-Induced Dyskinesia Based on Voxel-Based Morphometry
Authors: Zhang Xiaoqian , Chen Wei , Wu Yi , Zeng Weiqi , Yuan Yuhao , Cheng Chi , Yang Xiaoman , Wang Jialing , Yang Xiaomei , Xu Yu , Lei Hao , Cao Xuebing , Xu Yan
Published: October 2021

Long-term therapy with levodopa (L-DOPA) in patients with Parkinson’s disease (PD) often triggers motor complications termed as L-DOPA-induced dyskinesia (LID). However, few studies have explored the pathogenesis of LID from the perspective of neuroanatomy. This study aimed to investigate macroscopic structural changes in a rat model of LID and the underlying histological mechanisms. First, we established the hemiparkinsonism rat model through stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, followed by administration of saline (PD) or L-DOPA to induce LID. Magnetic resonance imaging (MRI) and behavioral evaluations were performed at different time points. Histological analysis was conducted to assess the correlations between MRI signal changes and cellular contributors. Voxel-based morphometry (VBM) analysis revealed progressive bilateral volume reduction in the cortical and subcortical areas in PD rats compared with the sham rats. These changes were partially reversed by chronic L-DOPA administration; moreover, there was a significant volume increase mainly in the dorsolateral striatum, substantia nigra, and piriform cortex of the lesioned side compared with that of PD rats. At the striatal cellular level, glial fibrillary acidic protein-positive (GFAP+) astrocytes were significantly increased in the lesioned dorsolateral striatum of PD rats compared with the intact side and the sham group. Prolonged L-DOPA treatment further increased GFAP levels. Neither 6-OHDA damage nor L-DOPA treatment influenced the striatal expression of vascular endothelial growth factor (VEGF). Additionally, there was a considerable increase in synapse-associated proteins (SYP, PSD95, and SAP97) in the lesioned striatum of LID rats relative to the PD rats. Golgi-Cox staining analysis of the dendritic spine morphology revealed an increased density of dendritic spines after chronic L-DOPA treatment. Taken together, our findings suggest that striatal volume changes in LID rats involve astrocyte activation, enrichment of synaptic ultrastructure and signaling proteins in the ipsilateral striatum. Meanwhile, the data highlight the enormous potential of structural MRI, especially VBM analysis, in determining the morphological phenotype of rodent models of LID.
Middle Meningeal Artery Embolization for the Treatment of Bilateral Chronic Subdural Hematoma
Authors: Wei Qi , Fan Gangxian , Li Zhenzhu , Wang Qingbo , Li Ke , Wang Chao , Li Zefu
Published: October 2021

Background: Bilateral chronic subdural hematoma (bCSDH) is a frequent condition commonly linked to the need for retreatment; however, the reason for this high retreatment rate remains unclear. The middle meningeal artery (MMA) was found to have a relationship with the occurrence and development of chronic subdural hematomas. This study examines a possible method to reduce bCSDH recurrence using bilateral MMA embolization combined with bilateral burr-hole drainage.

Materials and Methods: Ten patients with bCSDH who underwent bilateral MMA embolization combined with bilateral burr-hole drainage at our hospital between June 2018 and May 2020, were retrospectively analyzed. Patients' clinical information, prognoses, imaging results, as well as surgical results were documented and analyzed.

Results: Ten patients were diagnosed with bCSDH with no comorbid brain diseases. They underwent bilateral MMA embolization combined with bilateral burr-hole drainage. We embolized the MMA immediately before burr hole drainage successfully and employed angiography to validate these results. All the patients attained relief of symptoms without adverse events, and no re-expansion or relapse was reported in the follow-up computed tomography.

Conclusion: Bilateral MMA embolization combined with bilateral burr-hole drainage is an available treatment for patients with bCSDH and may have the potential for preventing recurrence.
Neurosurgical Admission Later Than 4 h After the Emergency Call Does Not Result in Worse Long-Term Outcome in Subarachnoid Haemorrhage
Authors: Sonne Asger , Andersen Jesper B. , Eskesen Vagn , Lippert Freddy , Waldorff Frans B. , Siersma Volkert , Lohse Nicolai , Rasmussen Lars S.
Published: October 2021

Background: Few studies have investigated the importance of the time interval between contact to the emergency medical service and neurosurgical admission in patients with spontaneous subarachnoid haemorrhage. We hypothesised that longer time to treatment would be associated with an increased risk of death or early retirement.

Methods: This was a retrospective observational study with 4 years follow-up. Those who reached a neurosurgical department in fewer than 4 h were compared with those who reached it in more than 4 h. Individual level data were merged from the Danish National Patient Register, medical records, the Copenhagen Emergency Medical Dispatch Centre, the Civil Registration System, and the Ministry of Employment and Statistics Denmark. Patients were ≥18 years and had a verified diagnosis of spontaneous subarachnoid haemorrhage. The primary outcome was death or early retirement after 4 years.

Results: Two hundred sixty-two patients admitted within a three-and-a-half-year time period were identified. Data were available in 124 patients, and 61 of them were in their working age. Four-year all-cause mortality was 25.8%. No significant association was found between time to neurosurgical admission and risk of death or early retirement (OR = 0.35, 95% confidence interval [CI]: 0.10–1.23, p = 0.10).

Conclusion: We did not find an association between the time from emergency telephone call to neurosurgical admission and the risk of death or early retirement.
Physical Activity Levels of Adolescents and Adults With Cerebral Palsy in Urban South Africa
Authors: Salie Roshaan , Eken Maaike M. , Donald Kirsten A. , Fieggen A. Graham , Langerak Nelleke G.
Published: October 2021

Background: Research in high income countries shows that people with cerebral palsy (CP) are less physically active than typically developing (TD) peers, but less is known regarding physical activity (PA) in those with CP in low-to-middle income countries. The aim of this study was to determine daily step count and levels of PA in adolescents and adults with CP living in urban South Africa, compared to TD peers, and to determine associations with sex, Gross Motor Function Classification System (GMFCS) level, body mass index and socio-economic status.

Materials and Methods: This case–control study included 26 adolescents and 22 adults with CP (GMFCS Level I-V) and matched TD peers (25 and 30, respectively). Participants wore an ActiGraph GT3X for 7 consecutive days to determine step count and time (minutes per hour) spent in PA levels, including sedentary (SED), low physical activity (LPA) and moderate to vigorous physical activity (MVPA).

Results: The daily step count and PA levels for ambulant adolescents with CP (GMFCS level I-III) were similar to TD peers, while this was less for adolescents classified in GMFCS level IV-V. Daily step count, SED and MVPA were similar for adults classified in GMFCS level I-II compared to TD adults, while all parameters were lower for adults using assistive devices (GMFCS level III) and non-ambulant adults (GMFCS level IV-V) compared to TD peers. Daily step count and PA levels were inversely associated with GMFCS, while no other associations were found.

Conclusion: People with CP who were more mobile dependent (higher GMFCS level) were less active. However, adolescents and adults with CP classified as GMFCS levels I-II living in urban South Africa recorded similar step count and PA levels as their TD peers. This was also the case for adolescents using assistive devices, though not for those in the adult group (GMFCS level III). Furthermore, it was apparent that even the ambulant individuals with CP and TD cohorts were relatively inactive. Intervention programs for CP and TD adolescents should be aimed at finding strategies to keep adolescents physically active well into adulthood, in order to promote physical health, social and emotional well-being and independence.
Mood Disturbances, Anxiety, and Impact on Quality of Life in Patients Admitted to Epilepsy Monitoring Units
Authors: Rocamora Rodrigo , Chavarría Beatriz , Pérez Eva , Pérez-Enríquez Carmen , Barguilla Ainara , Panadés-de Oliveira Luisa , Principe Alessandro , Zucca Riccardo
Published: October 2021

Introduction: The overall combined prevalence of anxiety and depression in patients with epilepsy has been estimated at 20.2 and 22.9%, respectively, and is considered more severe in drug-refractory epilepsy. Patients admitted to epilepsy monitoring units constitute a particular group. Also, patients with psychogenic non-epileptic seizures can reach more than 20% of all admissions. This study aims to characterize these symptoms in a large cohort of patients admitted for evaluation in a tertiary epilepsy center.

Materials and Methods: The study was conducted among 493 consecutive patients (age: 38.78 ± 12.7, 57% females) admitted for long-term video EEG from January 2013 to February 2021. Demographic, clinical, and mood disorder patients' data were collected. Anxiety and depression symptoms were assessed through the Hospital Anxiety Depression Scale (HADS-A and HADS-D), the State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI-II). Quality of life was determined using the QOLIE-10. Patients were divided into three groups: patients with epilepsy (n = 395), psychogenic non-epileptic seizures (PNES) (n = 56), and combined (n = 33). A univariate and multivariate regression analysis was performed for variables associated with quality of life.

Results: Of 493 patients, 45.0% had structural etiology, and considering epilepsy classification, 43.6% were of temporal lobe origin. In addition, 32.45% of patients had a previous psychiatric history, 49.9% of patients had depressive symptoms in BDI, and 30.9% according to HADS-D; 56.42 and 52.63% of patients presented pathological anxiety scores in STAI-T and STAI-S, respectively; and 44.78% according to HADS-A. PNES and combined groups revealed a higher incidence of pathologic BDI scores (64.29 and 78.79%, p < 0.001) as well as pathologic HADS-A scores (p = 0.001). Anxiety and depression pathologic results are more prevalent in females, HADS-A (females = 50.7%, males = 36.8%; p = 0.0027) and BDI > 13 (females = 56.6%, males = 41.0%; p = 0.0006). QOLIE-10 showed that 71% of the patients had their quality of life affected with significantly higher scores in the combined group than in the epilepsy and PNES groups (p = 0.0015).

Conclusions: Subjective anxiety, depression, and reduced quality of life are highly prevalent in patients with refractory epilepsy. These symptoms are more evident when PNES are associated with epilepsy and more severe among female patients. Most of the cases were not previously diagnosed. These factors should be considered in everyday clinical practice, and specific approaches might be adapted depending on the patient's profile.