bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismo-Stratigraphic Model for the Urban Area of Milan (Italy) by Ambient-Vibration Monitoring and Implications for Seismic Site Effects Assessment
Authors: Massa M. , Lovati S. , Puglia R. , Brunelli G. , Lorenzetti A. , Mascandola C. , Felicetta C. , Pacor F. , Luzi L.
Published: June 2022

In this paper, we present the work carried out to characterize the spatial variability of seismic site response related to local soil conditions in the city of Milan and its surroundings, an area with ∼3 million inhabitants and a high density of industrial facilities. The area is located at the northwestern end of the Po Plain, a large and deep sedimentary basin in northern Italy. An urban-scale seismo-stratigraphic model is developed based on new passive and active seismic data, supported by the available geological data and stratigraphic information from shallow and deep vertical wells. In particular, 33 single-station and 4 ambient-vibration array measurements are acquired, together with 4 active multichannel analyses of surface waves (MAWS). To estimate the resonant frequencies of the sediments, the horizontal to vertical spectral ratio technique (HVSR) is applied to the ambient-vibration recordings, whereas to determine the Rayleigh-wave dispersion curves from the passive array, the data are analysed using the conventional frequency-wavenumber, the modified spatial autocorrelation and the extended spatial autocorrelation (ESAC) techniques. The array data are used to determine the local shear wave velocity profiles, VS, via joint inversion of the Rayleigh-wave dispersion and ellipticity curves deduced from the HVSR. The results from HVSR show three main bands of amplified frequencies, the first in the range 0.17–0.23 Hz, the second from 0.45 to 0.65 Hz and the third from 3 to 8 Hz. A decreasing trend of the main peaks is observed from the northern to the southern part of the city, allowing us to hypothesize a progressive deepening of the relative regional chrono-stratigraphic unconformities. The passive ambient noise array and MASW highlight the dispersion of the fundamental mode of the Rayleigh-wave in the range 0.4–30 Hz, enabling to obtain detailed Vs. profiles with depth down to about 1.8 km. The seismo-stratigraphic model is used as input for 1D numerical modelling assuming linear soil conditions. The theoretical 1D transfer functions are compared to the HVSR curves evaluated from both ambient noise signals and earthquake waveforms recorded by the IV. MILN station in the last 10 years.
Effects of Rainfall on Mechanical Behaviors of Residual-Soil Landslide
Authors: He Yong , Yu Zhi-Peng , Zhang Zhao , Chen Bin , Zhang Ke-Neng
Published: June 2022

Rainfall-induced landslides commonly occur in residual-soil layers of Chenzhou city, China. Slope failure induced by rainfall is intimately related to changes in the mechanical property and microstructures of residual soils. In this study, series of direct shear tests were respectively conducted on four typical residual soils from the area of Chenzhou to study influences of rainwater on their mechanical behaviors. Meanwhile, X-ray diffraction (XRD) tests and scanning electron microscope (SEM) tests were also performed to investigate microstructure characteristic of several types of soils. Experimental results revealed that the shear strength of soils decreased with increasing water content and its development trends were obviously influenced by the types of residual soils. Meanwhile, the shear strength of soils increased with the increase of vertical loads, and the relationship between them could be well expressed by a linear function. As water content increased, the calculated cohesions and internal friction angles both decreased. XRD observations implied that several residual soils showed rich clay minerals, including pyrophyllite, illite, kaolinite and montmorillonite, etc. Microstructures of these soils presented a sheet-structure system which was composed of various-sized clay particles. During hydration, these clay minerals gradually transferred from a face-face arrangement to face-edge or even edge-edge one, leading to the softening of clay particles and the reduction of the contact force between soil particles.
Association Between the Growth Hormone/Insulin-Like Growth Factor-1 Axis and Muscle Density in Children and Adolescents of Short Stature
Authors: Yang Guangzhi , Yang Qing , Li Yanying , Zhang Yanhong , Chen Shuxiong , He Dongye , Zhang Mei , Ban Bo , Liu Fupeng
Published: June 2022

Objective

To evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature.

Methods

Participants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition.

Results

A total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2 = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (β = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (β = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (β = 0.180, P < .01 and β = 0.222, P < .01).

Conclusions

A chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.
Effects of Heterogeneity of Financialization on Firm Innovation: Evidence in Context of Energy Transition in Lens of Research and Development
Authors: Yu Wenjing , Zhan Qilin , Ameer Waqar , Li Lianwei , Tarczyński Waldemar , Mentel Urszula
Published: June 2022

Innovation is essential to promote energy transition, reduce CO2 emissions and break resources and environmental constraints. Financialization has become an important part of firm asset portfolio. Different forms of financialization have great differences in liquidity, profitability, risk and purpose. This paper focus on the effect of heterogeneity of financialization on firm innovation to provide evidence for energy transition from the perspective of R&D with annual data of non-financial listed firms in Shanghai and Shenzhen A shares from 2009 to 2018. The Pooled Ordinary Least Square, fixed effect regression, Heckman two-stage model and instrumental variable regression are implied. The study also examines the impact of agency conflict on the relationship between the heterogeneity of financialization and firm innovation. The results show that: first, there is heterogeneity in financialization, with different motives and influences on firm innovation. Second, transaction-oriented financialization can significantly improve firm innovation, while there is a negative correlation between investment-oriented financialization and firm innovation. Finally, the existence of two types of agency conflict not only weakens the role of transaction-oriented financialization in promoting firm innovation, but also intensifies the ‘crowding-out’ effect of investment-oriented financialization. Firms should allocate financialization types rationally under effective supervision and incentives to achieve innovation and energy transition goals.
Sewage Sludge-Induced Effect on Growth, Enzyme Inhibition, and Genotoxicity can be Ameliorated Using Wheat Straw and Biochar in Pheretima posthuma Earthworms
Authors: Khalid Hira , Kashif Zahoor Muhammad , Riaz Danish , Arshad Madeeha , Yaqoob Rabia , Ranian Kanwal
Published: June 2022

Sewage sludge, rich in organic matter and nutrients, is widely used as a fertilizer to increase the fertility of soil. The direct application of sewage sludge without any treatment causes soil contamination as well as significantly affects the earthworm population. In the present study, the effect of sewage sludge-amended soil on growth, enzyme activities, and the DNA damage inPheretima posthumaearthworms was studied under wheat straw and biochar treatment of 30-day laboratory incubation. Wheat straw, biochar, and sewage sludge were applied at 0 (control), 5, 10, and 25% w/w along with combined treatment of sewage sludge with biochar and wheat straw, respectively at 25% each. After the incubation period, the percentage change in mean weight and length was measured and esterase and phosphatase enzyme activities were quantitatively determined. RAPD-PCR and the comet assay were performed to assess the genotoxicity. A significant weight loss was observed (26%) at a 25% rate of sewage sludge and biochar (11%). Similarly, a maximum decrease in length was observed with sewage sludge (2.5%) followed by biochar (0.80%) at a 25% application rate. Mean weight and length both decreased by increasing the rate of sewage sludge and biochar. In addition, no change was observed in the weight and length ofP.posthumain the treatment consisting of sewage sludge and wheat straw. Moreover, sewage sludge caused inhibition of esterase and phosphatase activities as well as induced DNA damage. The comet parameters showed that wheat straw and biochar ameliorated the toxic effects of sewage sludge. It is, therefore, concluded that sewage sludge has a tangible impact on earthworms which ultimately disrupts ecosystem functions and wheat straw and biochar can thus be utilized to reduce the toxicity of sewage sludge inPheretima posthumaearthworms.
Exploring the Fundamental Factors Behind Algal-Bacterial Symbiosis and Their Impact on Ecological Interactions
Authors: Sun Li , Lei Yongjia , Li Hui
Published: June 2022

This study focused on important factors including light intensity, light/dark cycles, and the biomass of algae/bacteria to explore the relationship between algae and bacteria, aiming to obtain the optimal performance in the algae–sludge membrane bioreactor (AS-MBR). It was found that 3000 lux was considered to be the appropriate light intensity that could improve algal biomass and nitrogen removal among the chosen light intensities. Further analysis of results indicated that a higher or lower light intensity could not simultaneously promote algal energy absorption and nitrifying bacterial activity. Moreover, the highest average growth rate of algae (0.16 mg/L d−1) and the removal efficiency of NH4+-N (96.4 ± 1.5%) were both observed during the 12-h light/12-h dark cycle, respectively. Meantime, the appropriate algal proportion would mitigate membrane fouling compared with the conventional MBR. The investigation of the mechanism suggested that light intensity, light–dark cycle, and algal proportion were significantly associated with algal photosynthesis (key proteins, chromophores, and nucleic acids), the characteristics of functional bacteria, and the underlying cognition of cell-to-cell signaling between algae and bacteria, which would further influence the reactor performance.
Determinants of Carbon Dioxide Emissions and Their Peaking Prospect: Evidence From China
Authors: Zhao Huiqing , Hu Jian , Hao Feng , Zhang Hongyuan
Published: June 2022

In order to examine the key determinants of carbon dioxide emissions and judge whether China’s carbon dioxide emissions can reach their peak value before 2030, this study first uses the extended STIRPAT model to analyze the determinants of China’s carbon dioxide emissions from 1995 to 2019 and then uses the model regression result to forecast the carbon dioxide emissions from 2020 to 2040 under six scenarios to investigate their prospect. It is found that population size, GDP per capita, energy intensity, the share of coal consumption, urbanization level, the share of secondary industry, and investment have significant positive effects on carbon dioxide emissions. Among them, the influence of population size is the biggest and energy intensity is the weakest. China’s carbon dioxide emissions can reach their peak in 2029 under the baseline scenario. Increasing the rate of population growth, energy intensity, and share of coal consumption will push back the peak year. A lower rate of economic growth and share of the secondary industry will bring the peak year forward. Therefore, it is necessary to optimize the industrial structure and energy consumption structure, reduce the energy intensity, and control the population size in order to achieve the goal of peaking carbon dioxide emissions as soon as possible.
Subterranean Life-Style Does Not Limit Long Distance Dispersal in African Mole-Rats
Authors: Finn Kyle T. , Thorley Jack , Bensch Hanna M. , Zöttl Markus
Published: June 2022

Dispersal from the natal site to breeding sites is a crucial phase in the life history of animals and can have profound effects on the reproductive ecology and the structure of animal societies. However, few studies have assessed dispersal dynamics in subterranean mammals and it is unknown whether dispersal distances are constrained by living underground. Here we show, in social, subterranean Damaraland mole-rats (Fukomys damarensis), that a subterranean lifestyle does not preclude long distance dispersal and that both sexes are capable of successfully dispersing long distances (>4 km). Body condition did not predict dispersal distance, but dispersers from larger groups traveled farther than individuals from smaller groups. Subsequently we show in a phylogenetically controlled comparative analysis of dispersal distances in subterranean and surface-dwelling rodents that living underground does not constrain dispersal distances and that dispersal capacity is mainly a consequence of body size in both lifestyles.
RhythmicDB: A Database of Predicted Multi-Frequency Rhythmic Transcripts
Authors: Castellana Stefano , Biagini Tommaso , Petrizzelli Francesco , Cabibbo Andrea , Mazzoccoli Gianluigi , Mazza Tommaso
Published: June 2022

The physiology and behavior of living organisms are featured by time-related variations driven by molecular clockworks that arose during evolution stochastically and heterogeneously. Over the years, several high-throughput experiments were performed to evaluate time-dependent gene expression in different cell types across several species and experimental conditions. Here, these were retrieved, manually curated, and analyzed by two software packages, BioCycle and MetaCycle, to infer circadian or ultradian transcripts across different species. These transcripts were stored in RhythmicDB and made publically available.
A Bioinformatics Approach to Investigate Structural and Non-Structural Proteins in Human Coronaviruses
Authors: Cicaloni Vittoria , Costanti Filippo , Pasqui Arianna , Bianchini Monica , Niccolai Neri , Bongini Pietro
Published: June 2022

Recent studies confirmed that people unexposed to SARS-CoV-2 have preexisting reactivity, probably due to previous exposure to widely circulating common cold coronaviruses. Such preexistent reactivity against SARS-CoV-2 comes from memory T cells that can specifically recognize a SARS-CoV-2 epitope of structural and non-structural proteins and the homologous epitopes from common cold coronaviruses. Therefore, it is important to understand the SARS-CoV-2 cross-reactivity by investigating these protein sequence similarities with those of different circulating coronaviruses. In addition, the emerging SARS-CoV-2 variants lead to an intense interest in whether mutations in proteins (especially in the spike) could potentially compromise vaccine effectiveness. Since it is not clear that the differences in clinical outcomes are caused by common cold coronaviruses, a deeper investigation on cross-reactive T-cell immunity to SARS-CoV-2 is crucial to examine the differential COVID-19 symptoms and vaccine performance. Therefore, the present study can be a starting point for further research on cross-reactive T cell recognition between circulating common cold coronaviruses and SARS-CoV-2, including the most recent variants Delta and Omicron. In the end, a deep learning approach, based on Siamese networks, is proposed to accurately and efficiently calculate a BLAST-like similarity score between protein sequences.
Quantifying the Contribution of Each Driving Force to the Lagrangian Residual Velocity in Xiangshan Bay
Authors: Deng Fangjing , Jiang Wensheng , Zong Xiaolong , Chen Zhaoyun
Published: June 2022

A three-dimensional numerical model is used to quantitatively evaluate the contribution of each driving force to the Lagrangian residual velocity (LRV) in Xiangshan Bay under conditions of constant buoyancy gradient in time and multi-frequency tide. Each component of the LRV from various processes is derived by tracking each driving force in a tidal period along the particle trajectory. For a comparison of the results, the driving force in the momentum equations is averaged at the fixed points to obtain six components of the Eulerian residual velocity (ERV). A quantitative evaluation of the contribution of each component to the total ERV and total LRV is performed. The sum of the acceleration component, nonlinear advection component, and barotropic pressure gradient component of ERV determines the structure of the total ERV. The LRV is influenced by different dynamic mechanisms. The barotropic pressure gradient component of LRV determines the outflow pattern of the total longitudinal LRV at the surface of the inner Xiangshan Bay, and the density gradient component of LRV is the main determinant of the structure of the total longitudinal LRV at the bottom of the inner Xiangshan Bay. The eddy viscosity component causes the total longitudinal LRV to flow seaward in the Niubi Channel. The sum of the acceleration component and nonlinear advection component of LRV is the main contributor to the inward total longitudinal LRV in the Fodu Channel. The barotropic pressure gradient component leads to total lateral flow in the outer Xiangshan Bay. The collective effect of the components induced by all of the forces determines the structure of the lateral LRV in the inner Xiangshan Bay.
The Welfare of Nile Tilapia (Oreochromis niloticus, GIFT Strain) Juveniles Cultured in Different Light Spectra
Authors: Yi Mengmeng , Zhai Wanting , Wang Miao , Wang He , Liu Zhigang , Gao Fengying , Ke Xiaoli , Song Changbin , Cao Jianmeng , Lu Maixin
Published: June 2022

The light spectrum is a vital environmental factor for the culture of fish, and the welfare of farmed fish is a crucial issue in aquaculture. In this study, Nile tilapia (Oreochromis niloticus, GIFT strain) juveniles were exposed to full-spectrum (LW), red (LR), yellow (LY), or blue (LB) light. After the 45-day experiment, growth performance, stress responses, and aggressive behaviors were evaluated, and transcriptomic analysis was carried out. The results revealed that LW and LR positively affected growth performance. At the same time, LY and LB had a negative effect. Light spectrum induced stress responses of juvenile fish exposed to LY, under which the total antioxidant capacity (T-AOC) and cortisol (COR) contents were the highest. The activities of α-amylase (AMS), protease (PES), and lipase (LPS) in the digestive tract showed a similar tendency, indicating that the light spectra altered the digestive enzyme activities and then affected growth. Behavioral analyses showed increased chase and bite activities of tilapia juveniles exposed to LW and LY. The affected functions included the nervous system, muscle morphogenesis, and immune system-related regulation. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways include the tryptophan metabolism signaling pathway, protein digestion and absorption signaling pathway, Jak-STAT signaling pathway, arachidonic acid metabolism signaling pathway, and alpha-linolenic acid metabolism signaling pathway. Overall, light spectra influenced the welfare of farmed tilapia juveniles in terms of growth, stress, and behavior. Our results suggested that LR should be used in juvenile tilapia culture.
Effects of Diet on the Gut Microbial Communities of Nile Tilapia (Oreochromis niloticus) Across Their Different Life Stages
Authors: Wang Miao , Fan Zijian , Zhang Ziyue , Yi Mengmeng , Liu Zhigang , Ke Xiaoli , Gao Fengying , Cao Jianmeng , Lu Maixin
Published: June 2022

Nile tilapia (Oreochromis niloticus) is one of the most important commercial freshwater fish in China, and dietary transition occurs in their different life stages. The gut microbiota is important to host health. The relationships among the diet, gut microbiota, and development of tilapia are not well known. In the present study, we attempted to understand how diet is associated with microbiota community dynamics during the development of tilapia. The first experiment was performed under standard laboratory feeding operation to determine the effect of diet transition on intestinal microbiota. In the second experiment, tilapia were fed with Artemia or plant-based dry (PBD) food from the fish started feeding to their late juvenile stage (90 days post-fertilization). The results in the first experiment showed that feeding habit transition in juvenile fish had a low effect on the microbiota of the tilapia intestine. In the second experiment, plant-based food negatively affected the survival rate and intestinal development of tilapia. The phylum Planctomycetes was dominant in juvenile fish fed PBD food. The phylum Fusobacteria was dominant in the juvenile fish fed Artemia. At the genus level, Gemmobacter, Pirellula, and Planctomyces, belonging to the phylum Planctomycetes, were significantly abundant in the guts of fish fed the PBD food diet. Cetobacterium of the phylum Fusobacteria was dominant in juvenile fish fed Artemia. Thus, we can conclude that diet types have a great effect on the microbiota of tilapia intestine in their early life stages. The intestinal microflora of tilapia was established in juvenile tilapia, approximately 2 months after hatching. Our results provide useful information for the experimental design of studies on the microbial community of the tilapia gut. We suggest that modulation of gut microbiota of tilapia could be performed in their early life.
Grain Size and Heterophase Effects on Mechanical Properties of Mg-Cu Nanoglasses
Authors: Chen Yu , Ding Jun , Sha Zhen-Dong
Published: June 2022

Tailoring heterogeneities in amorphous alloys is a promising strategy for promoting the strength-ductility synergy. Here, molecular dynamics simulations are performed to investigate the effects of grains size and heterogeneous chemical composition on the mechanical properties of Mg-Cu nanoglasses (NGs). The reduced grain size in single-phase NGs improves the plasticity but at the expense of strength. In addition, the mechanical properties of dual-phase NGs composed of two chemical compositions depend critically upon the fraction of softer phase. In particular, the plasticity is improved for the low fraction of the softer phase, but is deteriorated for the high fraction of the softer phase, which is in striking contrast to the observations of the plasticity improvement reported in the traditional nanostructured metals/alloys. This is because that heterogeneities at the glass-glass interfaces intentionally introduce more stress concentration sites which are easier to accelerate the shear band formation. For an appropriate fraction of heterogeneous composition, a balance among strength and plasticity can be realized, which is useful for the design of novel NGs with high strength and superior ductility.
Recent Progress in Contact Probing Methods of Two-Dimensional Materials and Van Der Waals Heterostructures
Authors: Zhang Jiazhen , Chen Peijian , Peng Juan , Zhang Yingying
Published: June 2022

Due to the unique properties, two-dimensional materials and van der Waals heterostructures play an important part in microelectronics, condensed matter physics, stretchable electronics and quantum sciences. But probing properties of two-dimensional materials and van der Waals heterostructures is hard as a result of their nanoscale structures, which hinders their development and applications. Therefore, the progress of contact probing measurement in recent years including mechanical properties, interfacial properties, tribological properties, as well as electrical properties are summarized in this paper. It is found that useful properties such as Young’s modulus, adhesive energy, friction coefficient and so on can be well estimated from contact probing methods. We believe that the contact probing methods will be more advanced to promote the blooming applications of two-dimensional materials and van der Waals heterostructures.
Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study
Authors: Yang Qilin , Gao Jun , Zeng Xiaomei , Chen Junyu , Wen Deliang
Published: June 2022

Background

The coronavirus disease 2019 (COVID-19) has become a global pandemic. Systemic inflammation in COVID-19 patients has been associated with poor clinical outcome. This study aims to determine the relationship between platelet count and in-hospital mortality.

Methods

The original data of this study were from article development and validation of a predictive model of in-hospital mortality in COVID-19 patients. In this secondary analysis, we adopted multi-variable logistic regression analyses and smooth curve fitting to assess the independent association between platelet count and in-hospital mortality. We further applied a two-piecewise linear regression model to examine the nonlinear association between platelet count and in-hospital mortality.

Results

Of the 2006 patients, the average age of the participants was 65.9 ± 16.5 years and 42.6% were women. We observed a U-shaped relationship between platelet count and in-hospital mortality. We found two different slopes, the correlations between platelet count and in-hospital mortality of COVID-19 patients were totally different below and above the inflection point which was around 370 × 109/L. On the left side of the inflection point, the OR was 0.996 (OR: 0.996, 95%CI: 0.994–0.998, p < 0.001). On the right side of the inflection point, the OR was 1.011 (OR: 1.011, 95%CI: 1.001–1.021, p = 0.029).

Conclusions

A U-shaped association between platelet count and in-hospital mortality was found in the patients with COVID-19. The optimal of platelet count associated with the lowest risk of in-hospital mortality was around 370 × 109/L.
“Endothelium-Out” and “Endothelium-In” Descemet Membrane Endothelial Keratoplasty (DMEK) Graft Insertion Techniques: A Systematic Review With Meta-Analysis
Authors: Ong Hon Shing , Htoon Hla M. , Ang Marcus , Mehta Jodhbir S.
Published: June 2022

Background

We evaluated the visual outcomes and complications of “endothelium-out” and “endothelium-in” Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques.

Materials and Methods

Electronic searches were conducted in CENTRAL, Cochrane databases, PubMed, EMBASE, ClinicalTrials.gov. Study designs included clinical trials, comparative observational studies, and large case series (≥25 eyes). PRISMA guidelines were used for abstracting data and synthesis. Random-effects models were employed for meta-analyses.

Results

21,323 eyes (95 studies) were included. Eighty-six studies reported on “endothelium-out” techniques; eight studies reported on “endothelium-in” techniques. One study compared “endothelium-out” to “endothelium-in” techniques. Eighteen “endothelium-out” studies reported that 42.5–85% of eyes achieved best-corrected visual acuity (BCVA) ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 58.7% (95% CI 49.4–67.7%,15 studies). Three “endothelium-in” studies reported that 44.7–87.5% of eyes achieved BCVA of ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 62.4% (95% CI 33.9–86.9%). Pooled mean endothelial cell loss was lower in the “endothelium-in” studies (28.1 ± 1.3%, 7 studies) compared to “endothelium-out” studies (36.3 ± 6.9%,10 studies) at 6 months (p = 0.018). Graft re-bubbling rates were higher in the “endothelium-out” studies (26.2%, 95% CI 21.9–30.9%, 74 studies) compared to “endothelium-in” studies (16.5%, 95% CI 8.5–26.4%, 6 studies), although statistical significance was not reached (p = 0.440). Primary graft failure rates were comparable between the two groups (p = 0.552). Quality of evidence was considered low and significant heterogeneity existed amongst the studies.

Conclusion

Reported rates of endothelial cell loss were lower in “endothelium-in” DMEK studies at 6 months compared to “endothelium-out” studies. Outcomes of “endothelium-in” techniques were otherwise comparable to those reported in “endothelium-out” studies. Given the technical challenges encountered in “endothelium-out” procedures, surgeons may consider “endothelium-in” techniques designed for easier intra-operative DMEK graft unfolding. “Endothelium-in” studies evaluating outcomes at longer time points are required before conclusive comparisons between the two techniques can be drawn.
Challenges of Primary Care Medicine in a Tertiary Care Setting—The Case of Primary CMV Infection Compared to Primary EBV Infection: A Retrospective Cohort Study
Authors: Etienne Samuel , Leuzinger Karoline , Hirsch Hans H. , Osthoff Michael
Published: June 2022

Background

In the immunocompetent adult primary cytomegalovirus (CMV) infection may present as prolonged febrile illness or may resemble infectious mononucleosis. Hence, establishing a diagnosis of primary CMV infection may be challenging, in particular in the hospital setting.

Methods

We performed a retrospective analysis of all immunocompetent patients treated at a tertiary care center in Switzerland over a 5-year period in whom a diagnosis of primary CMV infection was established. We assessed their demographic, clinical, and laboratory characteristics and compared them to patients with a diagnosis of primary Epstein-Barr virus (EBV) infection during the same period.

Results

We identified 16 and 125 patients with primary CMV and EBV infection, respectively (rates of 3.1 and 23.8 cases/year, respectively). Patients in the CMV group were older (median 34 vs. 22 years), had a longer illness duration before presentation (median 14 vs. 7 days) and more frequently systemic symptoms compared to patients in the EBV group. Increased lymphocyte count and presence of atypical lymphocytes were observed in both groups, yet less frequently and less pronounced in the CMV group. The overall number of performed tests (including laboratory and radiology tests) was significantly higher in the CMV group (median 11.5 vs. 3.0) before arriving at the final diagnosis. Antibiotic treatment was more frequently prescribed in patients with primary EBV infections (40 vs. 25%).

Conclusions

Given its low incidence and non-specific symptoms, establishing a diagnosis of primary CMV infection can be challenging. Knowledge about clinical features of primary CMV infection in the immunocompetent host might help to adopt a stepwise approach to diagnosis avoiding over-testing.
Impact of Obstructive Sleep Apnea (OSA) in COVID-19 Survivors, Symptoms Changes Between 4-Months and 1 Year After the COVID-19 Infection
Authors: Labarca Gonzalo , Henríquez-Beltrán Mario , Lamperti Liliana , Nova-Lamperti Estefania , Sanhueza Sergio , Cabrera Camilo , Quiroga Romina , Antilef Barbara , Ormazábal Valeska , Zúñiga Felipe , Castillo Daniela , Horta Gloria , Enos Daniel , Lastra Jaime , Gonzalez Jessica , Targa Adriano , Barbe Ferran
Published: June 2022

Objective

To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection.

Methods

We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software.

Results

A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04–504) risk of neurocognitive impairment.

Discussion

Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.
Basal Cell Carcinoma and Hedgehog Pathway Inhibitors: Focus on Immune Response
Authors: Gambini Donatella , Passoni Emanuela , Nazzaro Gianluca , Beltramini Giada , Tomasello Gianluca , Ghidini Michele , Kuhn Elisabetta , Garrone Ornella
Published: June 2022

Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting more often elderly patients, but sometimes even younger ones, particularly if immunocompromised or genetically predisposed. Specifically, the Gorlin-Goltz syndrome, an autosomal dominant genodermatosis, also known as nevoid basal cell carcinoma syndrome, characterizes for multiple early onset BCCs. It is caused by a germline mutation in PTCH1, a tumor suppressor gene whose product is the key component of Hedgehog (Hh) signaling pathway, which also appears somatically mutated in more than 85% of sporadic BCCs. Hh pathway inhibitors vismodegib and sonidegib are currently indicated for BCC, in adults with advanced or recurred tumor following surgery or radiation therapy. The principal mechanism of action of these drugs is the inhibition of Smoothened (SMO), a transmembrane protein involved in Hh signal transduction, that plays a role in both cellular differentiation and cancer development. Some studies have reported effects of Hh pathway inhibitors at different levels of the immune response, from cytotoxic T cells to a modified local cytokines pattern. Given the specific relation between immune system and BCC development in some conditions, we will review BCC with focus on immune system changes mediated by Hh signaling pathway and induced by the inhibitors vismodegib and sonidegib in the treatment of BCC. Thus, we will give an overview of their effects on the local immune response, as well as a brief note on the supposed function of Hh pathway inhibition on the systemic one.
Heterotrophic Sulfur Oxidation of Halomonas titanicae SOB56 and Its Habitat Adaptation to the Hydrothermal Environment
Authors: Du Rui , Gao Di , Wang Yiting , Liu Lijun , Cheng Jingguang , Liu Jiwen , Zhang Xiao-Hua , Yu Min
Published: June 2022

Halomonas bacteria are ubiquitous in global marine environments, however, their sulfur-oxidizing abilities and survival adaptations in hydrothermal environments are not well understood. In this study, we characterized the sulfur oxidation ability and metabolic mechanisms of Halomonas titanicae SOB56, which was isolated from the sediment of the Tangyin hydrothermal field in the Southern Okinawa Trough. Physiological characterizations showed that it is a heterotrophic sulfur-oxidizing bacterium that can oxidize thiosulfate to tetrathionate, with the Na2S2O3 degradation reaching 94.86%. Two potential thiosulfate dehydrogenase-related genes, tsdA and tsdB, were identified as encoding key catalytic enzymes, and their expression levels in strain SOB56 were significantly upregulated. Nine of fifteen examined Halomonas genomes possess TsdA- and TsdB-homologous proteins, whose amino acid sequences have two typical Cys-X2-Cys-His heme-binding regions. Moreover, the thiosulfate oxidation process in H. titanicae SOB56 might be regulated by quorum sensing, and autoinducer-2 synthesis protein LuxS was identified in its genome. Regarding the mechanisms underlying adaptation to hydrothermal environment, strain SOB56 was capable of forming biofilms and producing EPS. In addition, genes related to complete flagellum assembly system, various signal transduction histidine kinases, heavy metal transporters, anaerobic respiration, and variable osmotic stress regulation were also identified. Our results shed light on the potential functions of heterotrophic Halomonas bacteria in hydrothermal sulfur cycle and revealed possible adaptations for living at deep-sea hydrothermal fields by H. titanicae SOB56.
Akkermansia muciniphila Alters Gut Microbiota and Immune System to Improve Cardiovascular Diseases in Murine Model
Authors: He Xin , Bai Yang , Zhou Haiyang , Wu Kemin
Published: June 2022

The gut microbiota plays an important role in a variety of cardiovascular diseases. The probiotics screened based on microbiota can effectively improve metabolism and immune function of the body, which is of great value in the field of cardiovascular disease treatment. Abdominal aortic aneurysms (AAA) refer to the lesion or injury of the abdominal aortic wall resulting in a localized bulge, which is one of the cardiovascular diseases with pulsing mass as the main clinical symptom. Previous studies have confirmed that A. muciniphila was depleted in the guts of AAA patients or mice. A. muciniphila is a potential probiotic for the treatment of intestinal microbiome-related diseases. Therefore, this study aims to investigate the effects of A. muciniphila on gut microbiota and disease-related biomarkers in AAA mice. C57BL/6J mice were used to construct the AAA model and treated with A. muciniphila. Aortic aneurysm formation in the AAA group is associated with the increased diameter of the abdominal aorta and inflammatory infiltration. A. muciniphila inhibited the formation of AAA and repaired tissue damage. The number of gut microbiota and α diversity index were decreased in the model group. A. muciniphila increased the number of gut microbiota and α diversity in AAA mice. The abundance of uncultured bacterium and Lactobacillus were increased, while the abundance of the Lachnospiraceae NK4A136 group was reduced in the AAA group. Compared with the control group, the levels of MMP-1, MMP-9, IL-33, CTSB, and CTSL in tissue and the levels of IL-6, IFN-γ, and CRP in blood were significantly increased, and the levels of IL-4, IL-10, and IL-17A in blood were significantly decreased in the AAA group. The intervention of A. muciniphila reversed these changes. The gut microbiota function prediction showed changes in E. coli, Clostridium, and Lactobacillus metabolism-related functional pathways. Akkermansia was negatively correlated with Helicobacter and Lactobacillus and positively correlated with Clostridium_sensu_stricto_1 and Escherichia shigella at the genus level. In conclusion, A. muciniphila inhibited the formation of AAA by restoring gut microbiota diversity, altering the expression of peripheral immune factors, and the functions of E. coli, Clostridium, and Lactobacillus, which may provide a new theoretical basis for the application of probiotics in cardiovascular diseases.
Methionine and S-Adenosylmethionine Regulate Monascus Pigments Biosynthesis in Monascus purpureus
Authors: Yin Sheng , Yang Dongmei , Zhu Yiying , Huang Baozhu
Published: June 2022

Amino acid metabolism could exert regulatory effects on Monascus pigments (MPs) biosynthesis. In this work, MPs biosynthesis regulated by methionine and S-adenosylmethionine (SAM) was investigated in Monascus purpureus RP2. The results indicated that the addition of methionine in fermentation significantly reduced MPs production by 60–70%, and it induced a higher expression of SAM synthetase Mon2A2272 and consequently led to SAM accumulation. However, the addition of SAM in fermentation promoted MPs production by a maximum of 35%, while over-expression of the gene Mon2A2272 led to a decrease in MPs yield, suggesting that SAM synthetase and SAM were likely to play different regulatory roles in MPs biosynthesis. Furthermore, the gene transcription profile indicated that SAM synthetase expression led to a higher expression of the transcriptional regulatory protein of the MPs biosynthesis gene cluster, while the addition of SAM gave rise to a higher expression of MPs biosynthesis activator and the global regulator LaeA, which probably accounted for changes in MPs production and the mycelium colony morphology of M. purpureus RP2 triggered by methionine and SAM. This work proposed a possible regulation mechanism of MPs biosynthesis by SAM metabolism from methionine. The findings provided a new perspective for a deep understanding of MPs biosynthesis regulation in M. purpureus.
Spatial Organization of Osteoclastic Coupling Factors and Their Receptors at Human Bone Remodeling Sites
Authors: Borggaard Xenia G. , Nielsen Malene H. , Delaisse Jean-Marie , Andreasen Christina M. , Andersen Thomas L.
Published: June 2022

The strictly regulated bone remodeling process ensures that osteoblastic bone formation is coupled to osteoclastic bone resorption. This coupling is regulated by a panel of coupling factors, including clastokines promoting the recruitment, expansion, and differentiation of osteoprogenitor cells within the eroded cavity. The osteoprogenitor cells on eroded surfaces are called reversal cells. They are intermixed with osteoclasts and become bone-forming osteoblast when reaching a critical density and maturity. Several coupling factors have been proposed in the literature, but their effects and expression pattern vary between studies depending on species and experimental setup. In this study, we investigated the mRNA levels of proposed secreted and membrane-bound coupling factors and their receptors in cortical bone remodeling events within the femur of healthy adolescent human controls using high-sensitivity RNA in situ hybridization. Of the proposed coupling factors, human osteoclasts showed mRNA-presence of LIF, PDGFB, SEMA4D, but no presence of EFNB2, and OSM. On the other hand, the osteoblastic reversal cells proximate to osteoclasts presented with LIFR, PDGFRA and PLXNB1, but not PDGFRB, which are all known receptors of the proposed coupling factors. Although EFNB2 was not present in mature osteoclasts, the mRNA of the ligand-receptor pair EFNB2:EPHB4 were abundant near the central blood vessels within intracortical pores with active remodeling. EPHB4 and SEMA4D were also abundant in mature bone-forming osteoblasts. This study highlights that especially LIF:LIFR, PDGFB:PDGFRA, SEMA4D:PLXNB1 may play a critical role in the osteoclast-osteoblast coupling in human remodeling events, as they are expressed within the critical cells.
Acupuncture at GV20 and ST36 Improves the Recovery of Behavioral Activity in Rats Subjected to Cerebral Ischemia/Reperfusion Injury
Authors: Yang Yang , Deng Peiying , Si Yingkui , Xu Hong , Zhang Jianmin , Sun Hua
Published: June 2022

Traditional acupuncture and electroacupuncture (EA) have been widely performed to treat ischemic stroke. To provide experimental support for the clinical application of acupuncture to ameliorate post-stroke sequelae, in this study, we investigated the therapeutic effect of acupuncture and EA on CIRI following middle cerebral artery occlusion (MCAO) in rats. The animals were randomly divided into five groups: sham-operated (S), model (M), traditional acupuncture (A) treatment, electroacupuncture (EA) treatment, and drug (D; edaravone) therapies. Neurological behavioral characteristics (neurological deficit score, forelimb muscle strength, sensorimotor function, body symmetry, sucrose consumption, and mood) were examined in all the groups on days 1, 3, 5, and 7 after reperfusion. Expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were detected by immunohistochemistry. Both acupuncture and EA significantly reduced neurological deficits and improved forelimb muscle strength, sensorimotor function, body symmetry recovery, and neurovascular regeneration in the rats after ischemia/reperfusion injury. The efficacies of both acupuncture and EA were comparable to that of edaravone, a commonly used medicine for stroke in the clinic. Thus, our data suggest that acupuncture and EA therapy at acupoints GV20 and ST36 might represent alternative or complementary treatments to the conventional management of ischemic stroke, providing additional support for the experimental evidence for acupuncture therapy in clinical settings. In summary, EA might provide alternative or complementary treatment strategies for treating patients with apoplexy in the clinic. However, potential mechanisms underlying the role of acupuncture require further investigation.