bluuebunny/crossref_metadata_2025 huggingface dataset:
Land-dependent marine species face climate-driven impacts on land and at sea
Authors: Blondin HE , Armstrong KC , Hazen EL , Oestreich WK , Santos BS , Haulsee DE , Mikles CS , Knight CJ , Bennett AE , Crowder LB
Published: September 2022

Land-dependent marine species are a unique guild of species whose life histories rely on both land and sea. This group is exposed to climate change-related stressors 2-fold, as climate change impacts likely occur at different velocities across land and sea habitat, leading to a greater probability of evolutionary traps. Thus, it is difficult to assess vulnerability and subsequently manage these populations in response to climate change. Without consideration of the factors unique to land-dependent marine species, current vulnerability assessment frameworks may fall short when evaluating climate impacts on these species. We identified commonalities in climate-related threats across taxa and geographic regions, highlighting the specific life history strategies that may be better suited to adapt to the changing climate. Accordingly, we suggest 3 considerations for assessing the vulnerability of land-dependent marine species: (1) degree of specialization, (2) intraspecies population-level differences, and (3) non-climate stressors. Where possible, we suggest how the exclusion of this information in management and conservation planning may lead to less successful outcomes. Potential compounding impacts of multiple stressors puts this group at particular risk of population collapse when losing land and/or sea habitat and functionality. Each of these considerations should be included when assessing vulnerabilities to climate change, as well as in effective and proactive management responses.
Newspaper Endorsements, Candidate Quality, and Election Outcomes in the United States, 1950-2020
Authors: DeLuca Kevin
Published: September 2022

Spatial models of vote choice predict that valence factors like candidate quality matter less to voters as differences between policy platforms increase. However, this and related claims are hard to test because it is difficult to measure candidate quality. I construct a measure of candidate quality differences using over 23,000 endorsements from newspapers around the United States. I estimate candidate quality differences in elections between 1950-2020 to evaluate the effects of quality on election outcomes. I find that the higher quality candidate wins in a large majority of elections in the United States. A one-standard-deviation increase in relative quality increases two-party vote share by 4 percentage points. Contrary to popular beliefs, the effect of quality differences on vote shares has actually increased slightly over time. However, the decrease in competitive elections over the same period has reduced the share of elections where candidate quality can plausibly alter the election’s outcome.
Ethereum, IPFS and neural compression to decentralize and protect patient data in computational pathology
Authors: Cossio Manuel
Published: September 2022

The field of digital pathology produces a large number of images associated with patient metadata that are the raw material of computational pathology. The process of making images available with adequate privacy and data protection considerations takes a long time. Given that the Ethereum network associated with InterPlanetary File System (IPFS) promotes the exchange of information in a secure, private and decentralized manner, this association could be an important partner between digital and computational pathology. Therefore, here we propose and discuss a prototype with the aforementioned parts and the addition of neural compression, as an essential information preservation step. This prototype could constitute a link for the exchange of information in a secure way, providing transparency and reliability to the chain and empowering the field of manufacturing artificial vision solutions for the medical field
Economic and biological characteristics festulolium varieties Fest and features cultivation
Authors: Zolotarev Vladimir
Published: September 2022

One of the conditions for increasing the efficiency of feed production is the expansion of crops of perennial grasses and the permanent creation of their varieties. Festulolium ( Festulolium F. Aschers. et Graebn.) is a new crop with a complex of economically useful traits, the varieties of which are created by the method of hybridization of species in the system of genera Lolium and Festuca. Due to the use of combinations of different initial combinations of parents to create new varieties of festulolium, varieties of this culture have a number of distinctive features. The Fest variety was obtained as a result of intergenerational hybridization of ryegrass and fescue (Lolium multiflorum Lam.  Festuca arundinacea Schreb.). Tetraploid of the ryegrass morphotype. It was created by the method of experimental polyploidy with the selection of compatible fertile plants and subsequent multiple familial selection of elite plants in the population according to productive longevity, disease resistance, the level of yield of green mass and seeds, the intensity of regrowth and tolerance to repeated mowing. The variety is characterized by high seed productivity, the biological yield of its seeds can reach 1.7 t/ha. Under production conditions, the actual seed collections are usually 0.7–0.9 t/ha, and under favorable conditions and compliance with cultivation technology — up to 1.2 t/ha or more. The variety has high feed advantages, has an improved protein-carbohydrate complex. The content of carbohydrates in the tube exit phase is 22.2%, crude protein — 10.4–11.2%, crude fiber — 26%. The green mass, removed during the exit phase into the tube, is perfectly eaten by animals, since it contains a large amount of sugar in the dry matter. To increase the efficiency of the production use of the variety in different regions, it is necessary to develop zonal technologies for its cultivation for fodder purposes and seeds.
Treatment of hereditary angioedema—single or multiple pathways to the rescue
Authors: Valerieva Anna , Longhurst Hilary J.
Published: September 2022

Hereditary angioedema (HAE) is a rare disease caused by mutations in the SERPING1 gene. This results in deficient or dysfunctional C1 esterase inhibitor (C1-INH) and affects multiple proteases involved in the complement, contact-system, coagulation, and fibrinolytic pathways. Current options for the treatment and prevention of HAE attacks include treating all affected pathways via direct C1-INH replacement therapy; or specifically targeting components of the contact activation system, in particular by blocking the bradykinin B2 receptor (B2R) or inhibiting plasma kallikrein, to prevent bradykinin generation. Intravenously administered plasma-derived C1-INH (pdC1-INH) and recombinant human C1-INH have demonstrated efficacy and safety for treatment of HAE attacks, although time to onset of symptom relief varied among trials, specific agents, and dosing regimens. Data from retrospective and observational analyses support that short-term prophylaxis with intravenous C1-INH products can help prevent HAE attacks in patients undergoing medical or dental procedures. Long-term prophylaxis with intravenous or subcutaneous pdC1-INH significantly decreased the HAE attack rate vs. placebo, although breakthrough attacks were observed. Pathway-specific therapies for the management of HAE include the B2R antagonist icatibant and plasma kallikrein inhibitors ecallantide, lanadelumab, and berotralstat. Icatibant, administered for treatment of angioedema attacks, reduced B2R-mediated vascular permeability and, compared with placebo, reduced the time to initial symptom improvement. Plasma kallikrein inhibitors, such as ecallantide, block the binding site of kallikrein to prevent cleavage of high molecular weight kininogen and subsequent bradykinin generation. Ecallantide was shown to be efficacious for HAE attacks and is licensed for this indication in the United States, but the labeling recommends that only health care providers administer treatment because of the risk of anaphylaxis. In addition to C1-INH replacement therapy, the plasma kallikrein inhibitors lanadelumab and berotralstat are recommended as first-line options for long-term prophylaxis and have demonstrated marked reductions in HAE attack rates. Investigational therapies, including the activated factor XII inhibitor garadacimab and an antisense oligonucleotide targeting plasma prekallikrein messenger RNA (donidalorsen), have shown promise as long-term prophylaxis. Given the requirement of lifelong management for HAE, further research is needed to determine how best to individualize optimal treatments for each patient.
The effects of process parameters on polydopamine coatings employed in tissue engineering applications
Authors: Sarkari Soulmaz , Khajehmohammadi Mehran , Davari Niyousha , Li Dejian , Yu Baoqing
Published: September 2022

The biomaterials’ success within the tissue engineering field is hinged on the capability to regulate tissue and cell responses, comprising cellular adhesion, as well as repair and immune processes’ induction. In an attempt to enhance and fulfill these biomaterials’ functions, scholars have been inspired by nature; in this regard, surface modification via coating the biomaterials with polydopamine is one of the most successful inspirations endowing the biomaterials with surface adhesive properties. By employing this approach, favorable results have been achieved in various tissue engineering-related experiments, a significant one of which is the more rapid cellular growth observed on the polydopamine-coated substrates compared to the untreated ones; nonetheless, some considerations regarding polydopamine-coated surfaces should be taken into account to control the ultimate outcomes. In this mini-review, the importance of coatings in the tissue engineering field, the different types of surfaces requiring coatings, the significance of polydopamine coatings, critical factors affecting the result of the coating procedure, and recent investigations concerning applications of polydopamine-coated biomaterials in tissue engineering are thoroughly discussed.
The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery
Authors: Marotta Ludovica , Rossi Sara , Ibba Roberta , Brogi Simone , Calderone Vincenzo , Butini Stefania , Campiani Giuseppe , Gemma Sandra
Published: September 2022

The sustainable use of resources is essential in all production areas, including pharmaceuticals. However, the aspect of sustainability needs to be taken into consideration not only in the production phase, but during the whole medicinal chemistry drug discovery trajectory. The continuous progress in the fields of green chemistry and the use of artificial intelligence are contributing to the speed and effectiveness of a more sustainable drug discovery pipeline. In this light, here we review the most recent sustainable and green synthetic approaches used for the preparation and derivatization of chalcones, an important class of privileged structures and building blocks used for the preparation of new biologically active compounds with a broad spectrum of potential therapeutic applications. The literature here reported has been retrieved from the SciFinder database using the term “chalcone” as a keyword and filtering the results applying the concept: “green chemistry”, and from the Reaxys database using the keywords “chalcone” and “green”. For both databases the time-frame was 2017–2022. References were manually selected based on relevance.
Bi-ventricular assessment with cardiovascular magnetic resonance at 5 Tesla: A pilot study
Authors: Lin Lu , Liu Peijun , Sun Gan , Wang Jian , Liang Dong , Zheng Hairong , Jin Zhengyu , Wang Yining
Published: September 2022

Background

Cardiovascular magnetic resonance (CMR) imaging at ultra-high fields (UHF) such as 7T has encountered many challenges such as faster T2* relaxation, stronger B0 and B1+ field inhomogeneities and additional safety concerns due to increased specific absorption rate (SAR) and peripheral nervous stimulation (PNS). Recently, a new line of 5T whole body MRI system has become available, and this study aims at evaluating the performance and benefits of this new UHF system for CMR imaging.

Methods

Gradient echo (GRE) CINE imaging was performed on healthy volunteers at both 5 and 3T, and was compared to balanced steady-state-free-procession (bSSFP) CINE imaging at 3T as reference. Higher spatial resolution GRE CINE scans were additionally performed at 5T. All scans at both fields were performed with ECG-gating and breath-holding. Image quality was blindly evaluated by two radiologists, and the cardiac functional parameters (e.g., EDV/ESV/mass/EF) of the left and right ventricles were measured for statistical analyses using the Wilcoxon signed-rank test and Bland-Altman analysis.

Results

Compared to 3T GRE CINE imaging, 5T GRE CINE imaging achieved comparable or improved image quality with significantly superior SNR and CNR, and it has also demonstrated excellent capability for high resolution (1.0 × 1.0 × 6.0 mm3) imaging. Functional assessments from 5T GRE CINE images were highly similar with the 3T bSSFP CINE reference.

Conclusions

This pilot study has presented the initial evaluation of CMR CINE imaging at 5T UHF, which yielded superior image quality and accurate functional quantification when compared to 3T counterparts. Along with reliable ECG gating, the new 5T UHF system has the potential to achieve well-balanced performance for CMR applications.
Fitter Fontans for future—Impact of physical exercise on cardiopulmonary function in Fontan patients
Authors: Weigelt Annika , Fritsch Regina , Rottermann Kathrin , Wällisch Wolfgang , Moosmann Julia , Dittrich Sven , Purbojo Ariawan , Schöffl Isabelle
Published: September 2022

Background

In Fontans, exercise tolerance is poorer compared to their healthy peers. Higher V˙O2peak represents a strong predictor for mortality and morbidity in these patients. Cardiac rehabilitation programs have been shown to improve cardiopulmonary function in Fontans. More habitual physical activity should therefore lead to a better exercise tolerance.

Methods

We performed cardiopulmonary exercise testing in 24 Fontan patients who had engaged in physical activity for a minimum of 3 h per week over their lifetime. As a control we performed cardiopulmonary exercise testing in 20 Fontan patients who had undertaken no physical activity or <3 h per week in the past.

Results

A total of 44 Fontan patients was included (mean age 18.1 years). The mean parameters measured at peak exercise differed significantly between the active and inactive group (peak oxygen uptake [V˙O2peak] of 34.0 vs. 25.0 ml/min/kg, peak heart rate (HR) of 169.8/min vs. 139.8/min). Even though the O2pulse and the EF did not differ significantly between both groups, N-Terminal-Pro-B-Type Natriuretic Peptide (NT-pro BNP) was significantly higher in the inactive group. The two groups did not differ with respect to their cardiac function determined by magnetic resonance imaging (MRI). V˙O2peak was positively correlated with hours of sports performed by Fontans.

Conclusions

V˙O2peak and maximum HR were significantly higher in Fontans who had been physically active compared to those who had been inactive. The values reported in this study were higher than in other studies and reached normal values for V˙O2peak for most Fontans in the physically active group. The positive correlation between V˙O2peak and physical activity is an indicator of the importance of incorporating physical exercise programs into the treatment of Fontan patients.
The comparative ethics of artificial-intelligence methods for military applications
Authors: Rowe Neil C.
Published: September 2022

Concerns about the ethics of the use of artificial intelligence by militaries have insufficiently addressed the differences between the methods (algorithms) that such software provides. These methods are discussed and key differences are identified that affect their ethical military use, most notably for lethal autonomous systems. Possible mitigations of ethical problems are discussed such as sharing decision-making with humans, better testing of the software, providing explanations of what is being done, looking for biases, and putting explicit ethics into the software. The best mitigation in many cases is explaining reasoning and calculations to aid transparency.
Mechanical mechanism of in situ stress ratio limit and its evolution simulation
Authors: Chen Yifei , Wang Yongjian , Huang Fuqiong , Ma Long , Yang Changyi , Shi Haoyu
Published: September 2022

In situ stress is a natural phenomenon. According to the Mohr–Coulomb criterion, it is found that when the ratio of principal stress (the ratio of maximum principal stress to minimum principal stress) of crustal rock mass in a certain environment exceeds the critical value, the rock mass will change from an elastic state to a plastic state. This critical value is the extreme limit of the principal stress ratio, which is related to the cohesion and internal friction angle of rock mass, and the limit of the principal stress ratio in the shallow part is discrete. Although the principal stress of deep rock mass is large, the ratio limit is mainly related to the internal friction angle. The calculation results show that the principal stress ratio of deep rock mass is stable in a small range. By comparing and analyzing 574 groups of measured data, it is found that all the measured principal stress ratios are within the limit range of the theoretical ratio, which also shows the characteristics of shallow dispersion and deep stability, indicating that the theoretical analysis and the measured results are consistent with each other. In order to show the change process of in situ stress, a numerical model fitting plate motion is established, and the limits of the principal stress ratio in five periods in the past 500,000 years are compared. The results show that the maximum principal stress at measuring points at different depths shows a change law of “first increasing and then stabilizing.” In areas close to or exceeding the principal stress ratio, high shear strain zones appear in the rock mass, and the stress is released in the form of plastic failure or shear dislocation, making the main stress ratio finally stable between 6.0 and 8.0. Therefore, it is easy to judge the stability of regional strata by using the ratio of principal stress; the area with a small ratio of principal stress belongs to the area with good stability, and when the ratio of principal stress is close to the limit of the ratio, it is an unstable area. The measured data show that the area with a high ratio of principal stress is often the recent seismic activity area; therefore, the ratio of in situ stress may become a possible index for earthquake prediction.
Modeling energy governance index for the adequacy of policy, legal, and institutional response measures for climate compatible development
Authors: Iqbal Kanwar Muhammad Javed , Waheed Farah , Azhar Urooj , Akhtar Nadia , Khan Muhammad Irfan
Published: September 2022

Climate compatible and sustainable expansion of energy resources is a major global challenge. Developing countries, with inadequate resources and incoherent policies, and legal and institutional frameworks must strive hard to achieve targets set by the Sustainable Development Goals (SDGs) while keeping track of Nationally Determined Contributions for Greenhouse Gas (GHG) emissions abatement. Inclusive governance is quite complex due to the interplay of informal and formal systems, rules-based to rights-based approaches, and arrangements in national to local scenarios vis-à-vis methodological limitations. In this context, this study aims at developing a governance index for assessing climate compatible development (CCD) by taking case of the energy sector in Pakistan. The study adopted a two-step approach to develop and validate a methodological framework for assessing the adequacy of governance. In the first step, a multivariate analysis model was developed using principle (CP-1), criteria (09), and 43 indicators (PCIs) through stakeholder involvement. In the second step, the model was deployed by combining the Multi Criteria Decision Analysis method with statistical analysis of the dataset. Data were collected from federal and provincial capitals as well as ten districts through a structured scoring matrix consisting of all 43 indicators. The sample population was based on key informant interviews (340), and experts (17) who were engaged through focus group discussion at federal, provincial, and district levels. Respondents were asked to score against each indicator on a ratio scale, which was then aggregated to develop a governance index score. The findings reveal the dearth of a preemptive and comprehensive governance to address climate compatible development in the energy sector in all tiers of constituencies in Pakistan. There is a need for coherent and inclusive policy, and a legal and institutional framework. This study’s outcome authenticates the findings of United Nations SDGs Report 2020 that efforts to achieve sustainable energy targets are not up to scale and stresses the need to speed up the efforts and development of the associated governance framework for renewable energy to achieve climate compatible and SDGs.
Factors influencing the photodegradation of acid orange 8 by nitrocellulose membranes
Authors: Wu Li , Fu Jiwei , Song Baihui , Zhao Tongqian , Liu Hong , Li Xiaolin
Published: September 2022

Nitrocellulose membranes (NCM) have broad application prospects in the field of organic wastewater treatment. In this research, acid orange 8 was used as the target pollutant, and the effects of factors, such as concentration, light intensity, anions, and cations, on the photodegradation of acid orange 8 were investigated under simulated sunlight by NCM. The results showed that the degradation rate constant of acid orange 8 in the NCM system was 1.94 × 10−3 min−1, which was 27.3 times that in the pure water. The photodegradation rate increases with decreasing concentration in the range of 20–120 μmol/L for acid orange 8. The photodegradation rate increased with increasing NCM area. The degradation effect of acid orange 8 increased with the increase of light intensity. Acidic conditions were favorable for the degradation of acid orange 8. The optimal conditions for photodegradation of acid orange 8 were the solution concentration of 20 μmol/L, membrane area of 17.35 cm2, light intensity of 481 μmol/(m2s), and pH value of 3.0. The effect of different components in water on the photodegradation of acid orange 8 was different. Ca2+, Mg2+, and NO3− could promote the photodegradation of acid orange 8, while CO32- could inhibit the photodegradation. The effect of degrading acid orange 8 by NCM under light conditions is obvious, which can provide a new method for the removal of acid orange 8 in wastewater.
Identification of protein–protein interaction associated functions based on gene ontology and KEGG pathway
Authors: Yang Lili , Zhang Yu-Hang , Huang FeiMing , Li ZhanDong , Huang Tao , Cai Yu-Dong
Published: September 2022

Protein–protein interactions (PPIs) are extremely important for gaining mechanistic insights into the functional organization of the proteome. The resolution of PPI functions can help in the identification of novel diagnostic and therapeutic targets with medical utility, thus facilitating the development of new medications. However, the traditional methods for resolving PPI functions are mainly experimental methods, such as co-immunoprecipitation, pull-down assays, cross-linking, label transfer, and far-Western blot analysis, that are not only expensive but also time-consuming. In this study, we constructed an integrated feature selection scheme for the large-scale selection of the relevant functions of PPIs by using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations of PPI participants. First, we encoded the proteins in each PPI with their gene ontologies and KEGG pathways. Then, the encoded protein features were refined as features of both positive and negative PPIs. Subsequently, Boruta was used for the initial filtering of features to obtain 5684 features. Three feature ranking algorithms, namely, least absolute shrinkage and selection operator, light gradient boosting machine, and max-relevance and min-redundancy, were applied to evaluate feature importance. Finally, the top-ranked features derived from multiple datasets were comprehensively evaluated, and the intersection of results mined by three feature ranking algorithms was taken to identify the features with high correlation with PPIs. Some functional terms were identified in our study, including cytokine–cytokine receptor interaction (hsa04060), intrinsic component of membrane (GO:0031224), and protein-binding biological process (GO:0005515). Our newly proposed integrated computational approach offers a novel perspective of the large-scale mining of biological functions linked to PPI.
Discovery and Validation of Grain Shape Loci in U.S. Rice Germplasm Through Haplotype Characterization
Authors: Angira Brijesh , Cerioli Tommaso , Famoso Adam N.
Published: September 2022

Rice grain shape is a major determinant of rice market value and the end-use. We mapped quantitative trait loci (QTL) for grain shape traits in a bi-parental recombinant inbred line population (Trenasse/Jupiter) and discovered two major grain length QTLs—qGL3.1 and qGL7.1. Previously, a major grain shape gene GS3 was reported in the qGL3.1 region and grain length gene GL7 was reported to be encompassing qGL7.1 locus. The re-sequencing SNP data on the International Rice Research Institute (IRRI) 3K Rice Genome Project (RGP) panel were obtained from the IRRI SNP-Seek database for both genes and haplotype diversity was characterized for each gene in this diverse panel. United States rice germplasm was not well represented in the IRRI 3K RGP database. Therefore, a minimum SNP set was identified for each gene that could differentiate all the characterized haplotypes. These haplotypes in the 3K RGP panel were screened across 323 elite U.S. genotypes using the minimum SNP set. The screening of haplotypes and phenotype association confirmed the role of GS3 under qGL3.1. However, screening of the GL7 haplotypes in the U.S. germplasm panel showed that GL7 did not play a role in qGL7.1, and in addition, GL7.1 did not segregate in the Trenasse/Jupiter RIL population. This concluded that qGL7.1 is a novel QTL discovered on chr7 for grain shape in the Trenasse/Jupiter RIL population. A high-throughput KASP-based SNP marker for each locus (GS3 and qGL7.1) was identified and validated in elite U.S. rice germplasm to be used in an applied rice breeding program.
The regulatory network of potential transcription factors and MiRNAs of mitochondria-related genes for sarcopenia
Authors: Fu Wanrui , Kadeer Guzailinuer , He Yaqi , Feng Ying
Published: September 2022

Background: Mitochondrial dysfunction is a significant contributor to sarcopenia, but the mechanism remains unclear.

Methods: In the present study, we downloaded GSE117525 and GSE8479 datasets from Gene Expression Omnibus (GEO), then the weighted correlation network analysis (WGCNA) was used to construct scale-free co-expression networks respectively. The key genes of aging muscle were obtained by overlapping key modules of two networks. Receiver operating characteristic (ROC) curve was drawn to explore the diagnostic efficacy of key genes. Finally, a transcription factor-key gene network was constructed based on ChEA3 platform and hTFtarget database, and a miRNA-key gene network was constructed using starBase and the multimiR R package.

Results: The most positively or negatively correlated modules of the two datasets were identified, and genes related to oxidative phosphorylation and mitochondrial ribosomal proteins were identified as key genes. The diagnostic values were confirmed with ROC curves by self-verification (GSE117525 and GSE8479) and external verification (GSE47881). Then, Yin Yang 1 (YY1) was identified as the most important transcription factor of the transcription factor-key gene network. In addition, miRNAs related to key genes were also predicted.

Conclusion: The findings of the present study provide a novel insight into the pathological mechanism of sarcopenia.
Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy
Authors: Luo Jianquan , Chen Huiqing , Ma Fang , Xiao Chenlin , Sun Bao , Liu Yiping , Tang Haoneng , Yang Yue , Liu Wenhui , Luo Zhiying
Published: September 2022

Aim

Vitamin D (VitD) signaling has been increasingly investigated for its role in stimulating the innate and adaptive immune systems and suppressing inflammatory responses. Therefore, we examined the associations between VitD-related genetic polymorphisms, plasma 25-hydroxyvitamin D (25(OH)D), and the efficacy and safety of immune checkpoint inhibitors (ICIs).

Patients and methods

A total of 13 single-nucleotide polymorphisms (SNPs) in VitD metabolic pathway genes were genotyped in 343 cancer patients receiving ICI treatment using the MassARRAY platform. In 65 patients, the associations between plasma 25(OH)D levels and ICI treatment outcomes were investigated further.

Results

We found that the CYP24A1 rs6068816TT and rs2296241AA genotypes were significantly higher in patients who responded to ICIs. Furthermore, patients with higher plasma 25(OH)D levels had a better treatment response. The distribution of allele and genotype frequencies showed that three SNPs (rs10877012, rs2762934, and rs8018720) differed significantly between patients who had immune-related adverse events (irAEs) and those who did not. There was no statistically significant relationship between plasma 25(OH)D levels and the risk of irAEs.

Conclusion

In summary, our findings showed that genetic variations in the VitD metabolism pathway were associated with ICI treatment outcomes, and VitD supplementation may be useful in improving ICI treatment efficacy.
Cytokines as an important player in the context of CAR-T cell therapy for cancer: Their role in tumor immunomodulation, manufacture, and clinical implications
Authors: Silveira Caio Raony Farina , Corveloni Amanda Cristina , Caruso Sâmia Rigotto , Macêdo Nathália Araújo , Brussolo Natália Moscheta , Haddad Felipe , Fernandes Taisa Risque , de Andrade Pamela Viani , Orellana Maristela Delgado , Guerino-Cunha Renato Luiz
Published: September 2022

CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy.
Green gravel as a vector of dispersal for kelp restoration
Authors: Alsuwaiyan Nahlah A. , Filbee-Dexter Karen , Vranken Sofie , Burkholz Celina , Cambridge Marion , Coleman Melinda A. , Wernberg Thomas
Published: September 2022

Kelp forests are experiencing substantial declines due to climate change, particularly ocean warming and marine heatwaves, and active interventions are necessary to halt this decline. A new restoration approach termed “green gravel” has shown promise as a tool to combat kelp forest loss. In this approach, substrata (i.e. small gravel) are seeded with kelp propagules, reared in controlled conditions in the laboratory before out-planting to degraded reefs. Here, we tested the feasibility of cultivating Australia’s dominant kelp, Ecklonia radiata on green gravel with the aim of optimising the seeding conditions for E.radiata. We seeded substrata (i.e. gravel), that had different surface texture and size, with E. radiata gametophytes at two average seeding densities: high density of ~230 fragments mL-1 and low density of ~115 fragments mL-1. The tested substrata were small basalt, large basalt, crushed laterite and limestone. Gametophytes successfully adhered to all four tested substrata, however, gametophytes that adhered to the limestone gravel (the natural reef type off Western Australia) suffered extreme tissue bleaching likely due to dissolution and decrease in seawater pH. Gametophytes that adhered to the three other test substrata were healthy, fertilised following seeding and microscopic sporophytes were observed attaching to the gravel. Substrata and seeding density did not affect sporophyte growth (i.e. length) at the time of transferring into aquarium tanks (after three months of rearing in incubators) but over time substrata showed a significant effect on maximum lengths. After 12 months in aquarium tanks, sporophytes on both small and large basalt gravel were significantly larger than those on the crushed laterite. Gametophytes were also found to not only survive on the gravel itself but also detach from the gravel, settle successfully, fertilise and develop into healthy sporophytes ex situ on the surrounding substratum through lateral transfer. Substrata had a significant effect on density of detached gametophytes with rougher and larger gravel showing higher densities of detachment. Our results show the potential for green gravel to be a vector of dispersal for restoration in Western Australia where natural recovery of kelp forests has failed.
Association of ventilator-free days with respiratory physiotherapy in critically ill patients with Coronavirus Disease 2019 (COVID-19) during the first pandemic wave. A propensity score-weighted analysis
Authors: Privitera Emilia , Gambazza Simone , Rossi Veronica , Santambrogio Martina , Binda Filippo , Tarello Davide , Caiffa Salvatore , Turrin Valentina , Casagrande Carolina , Battaglini Denise , Panigada Mauro , Fumagalli Roberto , Pelosi Paolo , Grasselli Giacomo
Published: September 2022

Background

Respiratory physiotherapy is reported as safe and feasible in mechanically ventilated patients with severe Coronavirus Disease (COVID-19) admitted to Intensive Care Unit (ICU), but the short-term benefits remain unclear.

Methods

We performed a retrospective observational study in four ICUs in Northern Italy. All patients with COVID-19 admitted to ICU and under invasive mechanical ventilation (MV) between March 1st and May 30th, 2020, were enrolled into the study. Overlap weighting based on the propensity score was used to adjust for confounding in the comparison of patients who had or had not been treated by physiotherapists. The primary outcome was the number of days alive and ventilator-free (VFDs). The secondary outcomes were arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F) at ICU discharge, ICU length of stay, ICU and hospital mortality, and survival at 90 days. The trial protocol was registered on clinicaltrials.gov (NCT 05067907).

Results

A total of 317 patients were included in the analysis. The median VFDs was 18 days [interquartile range (IQR) 10; 24] in patients performing physiotherapy and 21 days (IQR 0; 26) in the group without physiotherapy [incidence rate ratio (IRR) 0.86, 95% confidence interval (CI): 0.78; 0.95]. The chance of 0 VFDs was lower for patients treated by physiotherapists compared to those who were not [odds ratio (OR) = 0.36, 95% CI: 0.18–0.71]. Survival at 90 days was 96.0% in the physiotherapy group and 70.6% in patients not performing physiotherapy [hazard ratio (HR) = 0.14, 95% CI: 0.03–0.71]. Number of VFDs was not associated with body mass index (BMI), sex, or P/F at ICU admission for individuals with at least 1 day off the ventilator.

Conclusion

In patients with COVID-19 admitted to ICU during the first pandemic wave and treated by physiotherapists, the number of days alive and free from MV was lower compared to patients who did not perform respiratory physiotherapy. Survival at 90 days in the physiotherapy group was greater compared to no physiotherapy. These findings may be the starting point for further investigation in this setting.
Toll-like receptor 2 signaling pathway activation contributes to a highly efficient inflammatory response in Japanese encephalitis virus-infected mouse microglial cells by proteomics
Authors: Zhao Guanyu , Gao Yan , Zhang Jiaqi , Zhang He , Xie Changzhan , Nan Fulong , Feng Sheng , Ha Zhuo , Li Chenghui , Zhu Xiangyu , Li Zhuoxin , Zhang Ping , Zhang Ying , Lu Huijun , Jin Ningyi
Published: September 2022

Thousands of people die each year from Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV), probably due to exacerbation of the inflammatory response that impairs the course of the disease. Microglia are mononuclear phagocytic cells located within the parenchyma of the central nervous system; these play a key role in the innate immune response against JEV infections. However, the involvement of toll-like receptor 2 (TLR2) in the inflammatory response during the early stages of JEV infection in BV2 cells remains. Here, we evaluated protein profiles and determined the role of TLR2 in the inflammatory response of JEV-infected BV2 cells. High-depth tandem mass tags labeling for quantitative proteomics was used to assess JEV infected-BV2 cells and compare immune response profiles at 6, 12, and 24 h post-infection (hpi). In total, 212 upregulated proteins were detected at 6 hpi, 754 at 12 h, and 191 at 24 h. According to GO and KEGG enrichment analysis, the upregulated proteins showed enrichment for proteins related to the immune response. Parallel reaction monitoring tests, western blotting, and qPCR results showed that the adaptor protein MyD88 was not activated. The expression levels of key proteins downstream of MyD88, such as IRAK1, IRAK4, and TRAF6 did not increase; however, the expression levels of PI3K-AKT did increase. By inhibiting key proteins (TLR2, PI3K, and AKT) we confirmed that JEV activated TLR2, thus resulting in a robust inflammatory response. Consequently, the TLR2-PI3K-AKT signaling axis was proven to play a critical in the early stages of the JEV infection-induced inflammatory response in microglia.
Isolation, characterization, and genome sequencing of a novel chitin deacetylase producing Bacillus aryabhattai TCI-16
Authors: Liang Ying-yin , Yan Lu-qi , Tan Ming-hui , Li Gang-hui , Fang Jian-hao , Peng Jie-ying , Li Kun-tai
Published: September 2022

Chitin deacetylase (CDA) is a chitin degradation enzyme that catalyzes the conversion of chitin to chitosan by the deacetylation of N-acetyl-D-glucosamine residues, playing an important role in the high-value utilization of waste chitin. The shells of shrimp and crab are rich in chitin, and mangroves are usually recognized as an active habitat to shrimp and crab. In the present study, a CDA-producing bacterium, strain TCI-16, was isolated and screened from the mangrove soil. Strain TCI-16 was identified and named as Bacillus aryabhattai TCI-16, and the maximum CDA activity in fermentation broth reached 120.35 ± 2.40 U/mL at 36 h of cultivation. Furthermore, the complete genome analysis of B. aryabhattai TCI-16 revealed the chitin-degrading enzyme system at genetic level, in which a total of 13 putative genes were associated with carbohydrate esterase 4 (CE4) family enzymes, including one gene coding CDA, seven genes encoding polysaccharide deacetylases, and five genes encoding peptidoglycan-N-acetyl glucosamine deacetylases. Amino acid sequence analysis showed that the predicted CDA of B. aryabhattai TCI-16 was composed of 236 amino acid residues with a molecular weight of 27.3 kDa, which possessed a conserved CDA active like the known CDAs. However, the CDA of B. aryabhattai TCI-16 showed low homology (approximately 30%) with other microbial CDAs, and its phylogenetic tree belonged to a separate clade in bacteria, suggesting a high probability in structural novelty. In conclusion, the present study indicated that the novel CDA produced by B. aryabhattai TCI-16 might be a promising option for bioconversion of chitin to the value-added chitosan.
Prevalence of lower urinary tract symptoms, urinary incontinence and retention in Parkinson's disease: A systematic review and meta-analysis
Authors: Li Fang-Fei , Cui Yu-Sha , Yan Rui , Cao Shuang-Shuang , Feng Tao
Published: September 2022

Background

Lower urinary tract symptoms (LUTS) are common non-motor symptoms but are often overlooked in Parkinson's disease (PD). The prevalence of LUTS in PD is inconsistent among different studies.

Objective

To estimate the prevalence of LUTS, urinary incontinence, and urinary retention in PD patients, then, investigate potential sources of inconsistency in prevalence estimation.

Methods

We searched PubMed, EMBASE, and Web of Science databases from inception to May 2022. Studies reporting the prevalence of LUTS or LUTS subtypes in PD were included. Pooled prevalence of LUTS, LUTS subtypes, urinary incontinence, and urinary retention was calculated via random-effects models. Meta-regression and subgroup analyses were performed.

Results

Of 7,358 studies after duplicate removal, a total of 73 studies comprising 14,937 PD patients were included. The pooled prevalence of LUTS was 61% (95% CI 53–69; 27 studies; n = 5,179), while the pooled prevalence of storage symptoms and voiding symptoms was 59% (44–73; 9 studies; n = 798) and 24% (14–33; 11 studies; n = 886), respectively. The pooled prevalence of urinary incontinence, retention and post-void residual (PVR) volume ≥ 100 ml were 30% (95% CI 22–39; 21 studies; n = 6,054), 27% (17–37; 14 studies; n = 1,991), and 4% (1–7; 5 studies; n = 439), respectively. The prevalence of LUTS, urinary incontinence, or urinary retention was significantly associated with diagnostic methods.

Conclusion

LUTS and its subtypes present in a significant proportion of PD patients. It is necessary to use standardized and validated methods to detect and screen LUTS and its subtypes.

Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311233, Identifier: CRD42022311233.
Early life maternal separation induces sex-specific antidepressant-like responses but has minimal effects on adult stress susceptibility in mice
Authors: Baugher Brittany J. , Sachs Benjamin D.
Published: September 2022

Early life stress is known to increase the risk of depression and anxiety disorders, which are highly prevalent conditions that disproportionately affect women. However, the results of preclinical studies have been mixed, with some work suggesting that early life stress promotes anxiety-like behavior and/or increases susceptibility to subsequent stressors, and other research suggesting that early life stress reduces anxiety-like behavior and/or confers resilience to subsequent stress exposure. It is likely that factors such as sex and the timing and severity of early life and adult stress exposure dictate whether a particular early life experience promotes adaptive vs. maladaptive behavior later in life. Most work in this area has focused exclusively on males, but several sex differences in the effects of early life stress on subsequent stress susceptibility have been reported. The current study examined the impact of early life maternal separation on susceptibility to behavioral alterations induced by 3 days of variable stress in adulthood in male and female c57BL6 mice. Our results indicate that 3 days of adult stress is sufficient to increase anxiety-like behavior in several paradigms and to increase immobility in the forced swim test. In contrast, a history of maternal separation reduces anxiety-like behavior in several tests, particularly in males. These findings could contribute to our understanding of sex differences in mental illness by demonstrating that males are more likely than females to display adaptive responses to mild early life stressors.
Toward a unifying framework for the modeling and identification of motor primitives
Authors: Chiovetto Enrico , Salatiello Alessandro , d'Avella Andrea , Giese Martin A.
Published: September 2022

A large body of evidence suggests that human and animal movements, despite their apparent complexity and flexibility, are remarkably structured. Quantitative analyses of various classes of motor behaviors consistently identify spatial and temporal features that are invariant across movements. Such invariant features have been observed at different levels of organization in the motor system, including the electromyographic, kinematic, and kinetic levels, and are thought to reflect fixed modules—named motor primitives—that the brain uses to simplify the construction of movement. However, motor primitives across space, time, and organization levels are often described with ad-hoc mathematical models that tend to be domain-specific. This, in turn, generates the need to use model-specific algorithms for the identification of both the motor primitives and additional model parameters. The lack of a comprehensive framework complicates the comparison and interpretation of the results obtained across different domains and studies. In this work, we take the first steps toward addressing these issues, by introducing a unifying framework for the modeling and identification of qualitatively different classes of motor primitives. Specifically, we show that a single model, the anechoic mixture model, subsumes many popular classes of motor primitive models. Moreover, we exploit the flexibility of the anechoic mixture model to develop a new class of identification algorithms based on the Fourier-based Anechoic Demixing Algorithm (FADA). We validate our framework by identifying eight qualitatively different classes of motor primitives from both simulated and experimental data. We show that, compared to established model-specific algorithms for the identification of motor primitives, our flexible framework reaches overall comparable and sometimes superior reconstruction performance. The identification framework is publicly released as a MATLAB toolbox (FADA-T, https://tinyurl.com/compsens) to facilitate the identification and comparison of different motor primitive models.