bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ecological Value of Typical Agricultural Products: An Emergy-Based Life-Cycle Assessment Framework
Authors: Wang Yongyang , Liu Gengyuan , Cai Yanpeng , Giannetti Biagio F. , Agostinho Feni , Almeida Cecilia M. V. B. , Casazza Marco
Published: February 2022

Agri-products have an impact on food security, ecology protection, and crucial strategic deployment. With this respect, the economic value of agri-products should be paralleled with a non-monetary assessment of ecological value for humans. This study set up an emergy-based life-cycle assessment (Em-LCA) framework to calculate the ecosystem service (ES) and ecosystem dis-services (EDS) that was applied to six typical crops, exploring the implementation path of the agricultural eco-product value. The results showed the agriculture system mainly depends on non-renewable resources. EDS generated by China’s agri-products is higher than the ES provided by them. Nevertheless, there is a low correlation between the current price of agri-products and their greenness, but, economic value presents a rising trend with agri-product greenness increasing. Further to discussing effective approaches to sustainable agriculture, it can be seen that 1) sustainable agriculture will lead to increased greenness, but it is impossible to improve greenness indefinitely. 2) Improving greenness is an effective way to implement ecological value, another way to preserve and raise ecological value is to reduce EDS generation. 3) Reducing energy consumption leads to a decrease in EDS but it is not an appropriate way to achieve sustainable development. These findings provide meaningful suggestions for decision-makers to realize the ecological value of agri-products.
mTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment
Authors: Mafi Sahar , Mansoori Behzad , Taeb Shahram , Sadeghi Hossein , Abbasi Reza , Cho William C. , Rostamzadeh Davoud
Published: February 2022

The mechanistic/mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways, which plays a pivotal role in regulating numerous cellular functions including cell growth, proliferation, survival, and metabolism by integrating a variety of extracellular and intracellular signals in the tumor microenvironment (TME). Dysregulation of the mTOR pathway is frequently reported in many types of human tumors, and targeting the PI3K/Akt/mTOR signaling pathway has been considered an attractive potential therapeutic target in cancer. The PI3K/Akt/mTOR signaling transduction pathway is important not only in the development and progression of cancers but also for its critical regulatory role in the tumor microenvironment. Immunologically, mTOR is emerging as a key regulator of immune responses. The mTOR signaling pathway plays an essential regulatory role in the differentiation and function of both innate and adaptive immune cells. Considering the central role of mTOR in metabolic and translational reprogramming, it can affect tumor-associated immune cells to undergo phenotypic and functional reprogramming in TME. The mTOR-mediated inflammatory response can also promote the recruitment of immune cells to TME, resulting in exerting the anti-tumor functions or promoting cancer cell growth, progression, and metastasis. Thus, deregulated mTOR signaling in cancer can modulate the TME, thereby affecting the tumor immune microenvironment. Here, we review the current knowledge regarding the crucial role of the PI3K/Akt/mTOR pathway in controlling and shaping the immune responses in TME.
IgG Binds Escherichia coli Serine Protease EspP and Protects Mice From E. coli O157:H7 Infection
Authors: Tontanahal Ashmita , Sperandio Vanessa , Kovbasnjuk Olga , Loos Sebastian , Kristoffersson Ann-Charlotte , Karpman Diana , Arvidsson Ida
Published: February 2022

Shiga toxin-producing Escherichia coli O157:H7 is a virulent strain causing severe gastrointestinal infection, hemolytic uremic syndrome and death. To date there are no specific therapies to reduce progression of disease. Here we investigated the effect of pooled immunoglobulins (IgG) on the course of disease in a mouse model of intragastric E. coli O157:H7 inoculation. Intraperitoneal administration of murine IgG on day 3, or both on day 3 and 6, post-inoculation improved survival and decreased intestinal and renal pathology. When given on both day 3 and 6 post-inoculation IgG treatment also improved kidney function in infected mice. Murine and human commercially available IgG preparations bound to proteins in culture filtrates from E. coli O157:H7. Bound proteins were extracted from membranes and peptide sequences were identified by mass spectrometry. The findings showed that murine and human IgG bound to E. coli extracellular serine protease P (EspP) in the culture filtrate, via the IgG Fc domain. These results were confirmed using purified recombinant EspP and comparing culture filtrates from the wild-type E. coli O157:H7 strain to a deletion mutant lacking espP. Culture filtrates from wild-type E. coli O157:H7 exhibited enzymatic activity, specifically associated with the presence of EspP and demonstrated as pepsin cleavage, which was reduced in the presence of murine and human IgG. EspP is a virulence factor previously shown to promote colonic cell injury and the uptake of Shiga toxin by intestinal cells. The results presented here suggest that IgG binds to EspP, blocks its enzymatic activity, and protects the host from E. coli O157:H7 infection, even when given post-inoculation.
Variability in Donor-Derived Cell-Free DNA Scores to Predict Mortality in Heart Transplant Recipients – A Proof-of-Concept Study
Authors: Kamath Megan , Shekhtman Grigoriy , Grogan Tristan , Hickey Michelle J. , Silacheva Irina , Shah Karishma S. , Shah Kishan S. , Hairapetian Adrian , Gonzalez Diego , Godoy Giovanny , Reed Elaine F. , Elashoff David , Bondar Galyna , Deng Mario C.
Published: February 2022

Background

Over the last decade, expanding use of molecular diagnostics in heart transplantation has allowed implementation of non-invasive surveillance strategies for monitoring allograft health. The commercially available HeartCare platform combines the AlloMap gene expression profiling assay and the AlloSure donor-derived cell-free DNA test (dd-cfDNA). Beyond their established use for assessment of rejection, evidence is building for predictive utility, with the longitudinal AlloMap Variability score previously shown to correlate with the risk of future rejection, graft dysfunction, re-transplantation, or death. In this single-center, retrospective pilot study, we evaluated the performance of a novel AlloSure Variability metric in predicting mortality in a cohort of heart transplant recipients.

Methods

Seventy-two adult heart transplant recipients with at least 3 concurrent AlloMap/AlloSure results were included. Demographic, clinical, imaging, and laboratory parameters were captured. Variability was defined as the standard deviation of longitudinal AlloMap/AlloSure results. A Cox multivariable adjusted proportional hazards model was used to evaluate the variability metrics as predictors of mortality. Associations between AlloMap/AlloSure variability and donor specific antibody (DSA) status were also assessed.

Results

A total of 5 patients (6.9%) died during a median follow-up of 480 days. In a univariate Cox proportional hazards model, higher AlloSure variability (HR 1.66, 95%CI 1.14 – 2.41), but not AlloMap variability or the cross-sectional AlloSure/AlloMap results was associated with increased mortality risk. Longitudinal AlloSure variability was also higher among patients with both preformed DSA and those developing de novo DSA.

Conclusion

Our results suggest that increased variability of dd-cfDNA in heart transplant patients is associated with both mortality risk and the presence of donor specific antibodies. These findings highlight the added value of longitudinal data in the interpretation of AlloMap/AlloSure scores in this population and open the door to larger studies investigating the utility of these metrics in shaping post-transplant clinical care paradigms.
A Novel Prognostic Index Model for Adult Hemophagocytic Lymphohistiocytosis: A Multicenter Retrospective Analysis in China
Authors: Shen Ziyuan , Jin Yingliang , Sun Qian , Zhang Shuo , Chen Xi , Hu Lingling , He Chenlu , Wang Ying , Liu Qinhua , Zhang Hao , Liu Xin , Wang Ling , Jiao Jun , Miao Yuqing , Gu Weiying , Wang Fei , Wang Chunling , Shi Yuye , Ye Jingjing , Zhu Taigang , Sun Cai , Song Xuguang , Xu Linyan , Yan Dongmei , Sun Haiying , Cao Jiang , Li Depeng , Li Zhenyu , Wang Zhao , Huang Shuiping , Xu Kailin , Sang Wei
Published: February 2022

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from the Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cutoff points of continuous variables; univariate and multivariate Cox analyses were used for variable selection, and the Kaplan–Meier curve was used to analyze the value of variables on prognosis. The C-index, Brier Score, and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio, and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in the derivation and validation cohorts by using a bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH.
Case Report: Myxedema Coma Caused by Immunoglobulin A Vasculitis in a Patient With Severe Hypothyroidism
Authors: Ito Hiroshi , Fukuda Kenzo , Ashida Kenji , Nagayama Ayako , Sako Tomoki , Mizuochi Kouichiro , Kabashima Masaharu , Yoshinobu Satoko , Iwata Shimpei , Hasuzawa Nao , Hayashi Sumika , Akashi Tomoyuki , Nomura Masatoshi
Published: February 2022

Myxedema coma is a critical disorder with high mortality rates. Disruption of the compensatory mechanism for severe and long-term hypothyroidism by various causes leads to critical conditions, including hypothermia, respiratory failure, circulatory failure, and central nervous system dysfunction. Infectious diseases, stroke, myocardial infarction, sedative drugs, and cold exposure are considered the main triggers for myxedema coma. A 59-year-old Japanese woman presented with bilateral painful purpura on her lower legs. She was diagnosed with coexisting immunoglobulin A (IgA) vasculitis and severe IgA vasculitis with nephritis and was consequently treated with intravenous methylprednisolone (125 mg/day). However, she rapidly developed multiple organ failure due to the exacerbation of severe hypothyroidism, i.e., myxedema. Her condition improved significantly following oral administration of prednisolone along with thyroxine. There was a delayed increase in the serum free triiodothyronine level, while the serum free thyroxine level was quickly restored to normal. Rapid deterioration of the patient’s condition after admission led us to diagnose her as having myxedema coma triggered by IgA vasculitis. Hence, clinicians should be aware of the risks of dynamic exacerbations in patients with hypothyroidism. Furthermore, our study suggested that combination therapy with thyroxine and liothyronine might prove effective for patients with myxedema coma, especially for those who require high-dose glucocorticoid administration.
Translating From Egg- to Antigen-Based Indicators for Schistosoma mansoni Elimination Targets: A Bayesian Latent Class Analysis Study
Authors: Clark Jessica , Moses Arinaitwe , Nankasi Andrina , Faust Christina L. , Adriko Moses , Ajambo Diana , Besigye Fred , Atuhaire Arron , Wamboko Aidah , Rowel Candia , Carruthers Lauren V. , Francoeur Rachel , Tukahebwa Edridah M. , Lamberton Poppy H. L. , Prada Joaquin M.
Published: February 2022

Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations.
Spray-Dried Porcine Plasma Promotes the Association Between Metabolic and Immunological Processes at Transcriptional Level in Gilthead Sea Bream (Sparus aurata) Gut
Authors: Vallejos-Vidal Eva , Reyes-Cerpa Sebastián , Tort Lluis , Polo Javier , Reyes-López Felipe E. , Gisbert Enric
Published: February 2022

The spray-dried porcine plasma (SDPP) is an abattoir by-product used in animal nutrition with beneficial effects reported in livestock and commercial aquatic species. Previous results have found that the dietary inclusion of SDPP in gilthead sea bream (Sparus aurata) increased the density of intestinal goblet cells, and it did not result in significant changes in the autochthonous microbiota. However, there is no comprehensive data on the mechanisms that could take place on the intestine of gilthead sea bream fed with an SDPP-supplemented diet. For this reason, this study aimed to unveil the biological mechanisms modulated in response to the dietary administration of SDPP in the gilthead sea bream gut. To achieve this goal, we made a microarrays-based transcriptomic approach in gut samples from gilthead sea bream fed with an SDPP-supplemented diet for 95 days. As control diet, we used a protein-rich commercial feed (51% crude protein, 17% crude fat, and 20.6 MJ/kg gross energy) which was supplemented with 3% SDPP at the expense of LT70 fishmeal. The microarray analyses showed a total of 803 (468 up- and 335 down-regulated) differential expressed genes (DEGs). The functional network analysis revealed that dietary inclusion of SDPP induced sustained changes in 120 biological processes, grouped in 12-clusters. Among them, the metabolic-related process (cellular catabolic process, organic substance catabolic process, protein metabolism process), protein transport, and leukocyte mediated immunity interacted in the leading interactome network. This evidence confirms the previous evidence of the enhancement of the mucosal health status in response to the dietary administration of SDPP and provides further understanding of the mode of action of this ingredient in aquafeeds.
Lagrangian Observation of 234Th and Its Application in Constraining the Sinking of Particulate Organic Carbon on the Slope of the Northeastern South China Sea
Authors: Yang Weifeng , Zhao Xiufeng , Chen Min , Qiu Yusheng , Zheng Minfang
Published: February 2022

The 234Th–238U disequilibrium has been widely used to quantify the sinking flux of particulate organic carbon (POC) out of the upper ocean. However, the influence of the advection on the quantification is poorly understood due to the lack of in situ measured physical parameters. Here, a Lagrangian observation was deployed for 39 h to track the variability of 234Th along with the current on the slope of the northeastern South China Sea (SCS). Contrasting to the general ocean interior, 234Th showed deficits relative to 238U in the mesopelagic waters, indicating an enhanced removal of 234Th. Concurrently, elevated total particulate matter (TPM) and POC contents were observed in the mesopelagic waters, supporting the driving force of the cross-shelf dispersion of re-suspended shelf/slope sediments for the 234Th removal. The widely used 234Th-model (ignoring physical processes) produced a much lower sinking flux of POC than the sediment trap-derived POC flux during the same observation, indicating an unneglectable influence of advection and diffusion. By considering the main horizontal advection and vertical diffusion, the 234Th–238U method gave rise to comparable results to sediment trap. 234Th-derived POC fluxes showed an increased pattern from 300 to 1,000 m, consistent with the more abundant POC where. These results indicated that advection represents an unneglectable process during the quantification of the sinking flux of 234Th over the slope of the SCS.
Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: An Evidence-Based Analysis
Authors: Cao Dehong , Li Jinze , Lu You , Huang Yin , Chen Bo , Chen Zeyu , Shen Yinzhi , Liu Liangren , Wei Qiang
Published: February 2022

Background

Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic.

Methods

We searched the Web of Science, PubMed, Embase, and ClinicalTrials.gov for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity.

Results

Four articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: −318.77, p < 0.001) and PDSB (WMD: −1.20, p < 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: −0.64, P = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, p < 0.001].

Conclusions

The current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.
Novel Application of 18F-NaF PET/CT Imaging for Evaluation of Active Bone Remodeling in Diabetic Patients With Charcot Neuropathy: A Proof-of-Concept Report
Authors: Tram Nguyen K. , Chou Ting-Heng , Patel Surina , Ettefagh Laila N. , Go Michael R. , Atway Said A. , Stacy Mitchel R.
Published: February 2022

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide 18F-sodium fluoride (NaF) has historically been used as a bone imaging probe due to its high sensitivity for targeting hydroxyapatite and bone turnover, but has not been applied in the context of CN. Therefore, the present study focused on novel application of 18F-NaF PET/computed tomography (CT) imaging to three clinical cases of CN to evaluate active bone remodeling at various time courses of CN. PET/CT imaging in all 3 cases demonstrated focal uptake of 18F-NaF in the bones of the feet afflicted with CN, with bone retention of 18F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot (p = 0.039). 18F-NaF PET/CT imaging may provide a non-invasive tool for monitoring active bone remodeling in the setting of CN, thereby offering novel opportunities for tracking disease progression and improving treatment and surgical intervention.
Antitumor Anesthetic Strategy in the Perioperatory Period of the Oncological Patient: A Review
Authors: Santander Ballestín Sonia , Lanuza Bardaji Andrea , Marco Continente Cristina , Luesma Bartolomé María José
Published: February 2022

The stress response triggered by the surgical aggression and the transient immunosuppression produced by anesthetic agents stimulate the inadvertent dispersion of neoplastic cells and, paradoxically, tumor progression during the perioperative period. Anesthetic agents and techniques, in relation to metastatic development, are investigated for their impact on long-term survival. Scientific evidence indicates that inhaled anesthetics and opioids benefit immunosuppression, cell proliferation, and angiogenesis, providing the ideal microenvironment for tumor progression. The likely benefit of reducing their use, or even replacing them as much as possible with anesthetic techniques that protect patients from the metastatic process, is still being investigated. The possibility of using “immunoprotective” or “antitumor” anesthetic techniques would represent a turning point in clinical practice. Through understanding of pharmacological mechanisms of anesthetics and their effects on tumor cells, new perioperative approaches emerge with the aim of halting and controlling metastatic development. Epidural anesthesia and propofol have been shown to maintain immune activity and reduce catecholaminergic and inflammatory responses, considering the protective techniques against tumor spread. The current data generate hypotheses about the influence of anesthesia on metastatic development, although prospective trials that determinate causality are necessary to make changes in clinical practice.
A Nomogram for Predicting Portal Hypertensive Gastropathy in Patients With Liver Cirrhosis: A Retrospective Analysis
Authors: Wang WenSheng , Mu ZhiYong , Zhu GuangXi , Wang Tao , Lai ShuJie , Guo Yan , Yin XinRu , Wen LiangZhi , Chen DongFeng
Published: February 2022

Background

There is an urgent need for non-invasive methods for predicting portal hypertensive gastropathy (PHG). This study aims to develop and validate a non-invasive method based on clinical parameters for predicting PHG in patients with liver cirrhosis (LC).

Methods

The overall survival (OS) and hepatocellular carcinoma (HCC)-free survival were evaluated in LC patients, both with and without PHG. A prediction model for PHG was then constructed based on a training dataset that contained data on 492 LC patients. The discrimination, calibration, and clinical utility of the predicting nomogram were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was conducted using a bootstrapping method, and further external validation using data on the 208 other patients.

Results

LC patients with PHG had a worse prognosis compared with those without PHG. A nomogram was constructed using clinical parameters, such as age, hemoglobin content, platelet count and Child-Pugh class. The C-index was 0.773 (95% CI: 0.730–0.816) in the training cohort, 0.761 after bootstrapping and 0.745 (95% CI: 0.673–0.817) in the validation cohort. The AUC values were 0.767, 0.724, and 0.756 in the training, validation and total cohorts, respectively. Well-fitted calibration curves were observed in the training and validation cohorts. Decision curve analysis demonstrated that the nomogram was clinically useful at a threshold of 15%.

Conclusion

The nomogram constructed to predict the risk of developing PHG was found to be clinically viable. Furthermore, PHG is an independent risk factor for OS of LC, but not for the occurrence of HCC.
Serum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study
Authors: Hahn Robert G. , Yanase Fumitaka , Zdolsek Joachim H. , Tosif Shervin H. , Bellomo Rinaldo , Weinberg Laurence
Published: February 2022

Background

The Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery.

Methods

We performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed.

Results

The median perioperative change in serum creatinine in the two groups was −19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th−75th percentiles, 0.09–1.98) to 0.35 (0.19–0.57) (mg/L)2 in the first group and rose from 0.57 (0.22–1.53) to 0.85 (0.67–2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2–11.7) μg2/mmol2 before surgery vs.6.9 (5.3–11.0) μg2/mmol2 after the surgery (P = 0.69).

Conclusion

In the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.
Methanogen Productivity and Microbial Community Composition Varies With Iron Oxide Mineralogy
Authors: Gadol Hayley J. , Elsherbini Joseph , Kocar Benjamin D.
Published: February 2022

Quantifying the flux of methane from terrestrial environments remains challenging, owing to considerable spatial and temporal variability in emissions. Amongst a myriad of factors, variation in the composition of electron acceptors, including metal (oxyhydr)oxides, may impart controls on methane emission. The purpose of this research is to understand how iron (oxyhydr)oxide minerals with varied physicochemical properties influence microbial methane production and subsequent microbial community development. Incubation experiments, using lake sediment as an inoculum and acetate as a carbon source, were used to understand the influence of one poorly crystalline iron oxide mineral, ferrihydrite, and two well-crystalline minerals, hematite and goethite, on methane production. Iron speciation, headspace methane, and 16S-rRNA sequencing microbial community data were measured over time. Substantial iron reduction only occurred in the presence of ferrihydrite while hematite and goethite had little effect on methane production throughout the incubations. In ferrihydrite experiments the time taken to reach the maximum methane production rate was slower than under other conditions, but methane production, eventually occurred in the presence of ferrihydrite. We suggest that this is due to ferrihydrite transformation into more stable minerals like magnetite and goethite or surface passivation by Fe(II). While all experimental conditions enriched for Methanosarcina, only the presence of ferrihydrite enriched for iron reducing bacteria Geobacter. Additionally, the presence of ferrihydrite continued to influence microbial community development after the onset of methanogenesis, with the dissimilarity between communities growing in ferrihydrite compared to no-Fe-added controls increasing over time. This work improves our understanding of how the presence of different iron oxides influences microbial community composition and methane production in soils and sediments.
Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
Authors: Hou Shitong , Wang Xiangwei , Ren Shanhui , Meng Xuelian , Yin Xiangping , Zhang Jie , Tarasiuk Kazimierz , Pejsak Zygmunt , Jiang Tao , Mao Ruoqing , Zhang Yongguang , Sun Yuefeng
Published: February 2022

Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. However, only a few cell lines are sensitive to FMDV, and there is still a lot of room for improvement. Acetylation is an important post-translational modification, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). However, the study of the relationship between FMDV and HDACs is still unclear. HDAC9 belongs to the class II of HDACs family; in this study, HDAC9 knockout (KO) BHK-21 cells were successfully established using CRISPR/cas9 technology. The results of karyotype analysis, growth curve analysis, and morphological observation showed that the HDAC9 knockout cell line was stable in growth and morphological characteristics. After infection with FMDV, the expression of viral RNA and protein, viral titers, and the copies of viral RNA in HDAC9-KO cells were significantly higher than those in NC cells. Meanwhile, RNA-seq technology was used to sequence HDAC9-KO cells and NC cells infected and uninfected with FMDV. It was found that the differentially expressed innate immune factors containing NFKBIA, SOD2, IL2RG, BCL2L1, CXCL1/2/3, and IL1RAP have significantly enriched in the Jak-STAT, NOD-like receptor, Toll-like receptor, NF-κB, and MAPK signaling pathway. RT-qPCR was performed to detect the expression level of differentially expressed genes and showed consistency with the RNA-seq data. These results preliminarily reveal the role of HDAC9 in host antiviral innate immune response, and the HDAC9-KO cell line could also serve as a useful tool for FMDV research.
Biogenesis and Biological Functions of Extracellular Vesicles in Cellular and Organismal Communication With Microbes
Authors: Fang Yuan , Wang Zhiwen , Liu Xili , Tyler Brett M.
Published: February 2022

Extracellular vesicles (EVs) represent a prominent mechanism of transport and interaction between cells, especially microbes. Increasing evidence indicates that EVs play a key role in the physiological and pathological processes of pathogens and other symbionts. Recent research has focused on the specific functions of these vesicles during pathogen-host interactions, including trans-kingdom delivery of small RNAs, proteins and metabolites. Much current research on the function of EVs is focused on immunity and the interactions of microbes with human cells, while the roles of EVs during plant-microbe interactions have recently emerged in importance. In this review, we summarize recent research on the biogenesis of these vesicles and their functions in biology and pathology. Many key questions remain unclear, including the full structural and functional diversity of EVs, the roles of EVs in communication among microbes within microbiomes, how specific cargoes are targeted to EVs, whether EVs are targeted to specific destinations, and the full scope of EVs’ transport of virulence effectors and of RNA and DNA molecules.
Antibacterial Activity of Small Molecules Which Eradicate Methicillin-Resistant Staphylococcus aureus Persisters
Authors: Hamad Mohamad , Al-Marzooq Farah , Srinivasulu Vunnam , Omar Hany A. , Sulaiman Ashna , Zaher Dana M. , Orive Gorka , Al-Tel Taleb H.
Published: February 2022

Graphical Abstract

Antibacterial activity of small molecules which eradicate methicillin-resistant Staphylococcus aureus (MRSA) persisters.
Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer
Authors: Moens Ugo , Prezioso Carla , Pietropaolo Valeria
Published: February 2022

As their name indicates, polyomaviruses (PyVs) can induce tumors. Mouse PyV, hamster PyV and raccoon PyV have been shown to cause tumors in their natural host. During the last 30 years, 15 PyVs have been isolated from humans. From these, Merkel cell PyV is classified as a Group 2A carcinogenic pathogen (probably carcinogenic to humans), whereas BKPyV and JCPyV are class 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer. Although the other PyVs recently detected in humans (referred to here as novel HPyV; nHPyV) share many common features with PyVs, including the viral oncoproteins large tumor antigen and small tumor antigen, as their role in cancer is questioned. This review discusses whether the nHPyVs may play a role in cancer based on predicted and experimentally proven functions of their early proteins in oncogenic processes. The functional domains that mediate the oncogenic properties of early proteins of known PyVs, that can cause cancer in their natural host or animal models, have been well characterized and we examined whether these functional domains are conserved in the early proteins of the nHPyVs and presented experimental evidence that these conserved domains are functional. Furthermore, we reviewed the literature describing the detection of nHPyV in human tumors.
Identification of Gyromitra infula: A Rapid and Visual Method Based on Loop-Mediated Isothermal Amplification
Authors: Xie Xiaomei , Li Bu , Fan Yuguang , Duan Renhe , Gao Chonghua , Zheng Yuan , Tian Enjing
Published: February 2022

With mushroom poisoning emerging as one of the most serious food safety problems worldwide, a rapid identification method of poisonous mushrooms is urgently required to investigate the source of poisoning. Gyromitra infula, a kind of poisonous mushroom, contains gyromitrin toxin, which causes epileptogenic neurotoxicity and hemolytic disease. This study aimed to establish a rapid and visual method of G. infula identification based on loop-mediated isothermal amplification (LAMP). A set of specific LAMP primers was designed, and its specificity in G. infula was confirmed against various mushroom species, including its closely related species and other macrofungi. The sensitivity assay showed that the minimum concentration of genomic DNA detected by LAMP was 1 ng/μl. The method’s applicability was conducted by preparing mushroom samples that were boiled and digested in artificial gastric juice. The results showed that the content as low as 1% G. infula can be successfully detected. This method can be completed within 90 min, and the reaction results can be directly observed by the naked eyes. Hence, the identification method of G. infula established based on LAMP in this study is accurate, rapid, sensitive, and low-cost, which is required for clinical treatment or forensic analysis when mushroom poisoning occurs.
A Multi-Purpose Approach to the Mechanisms of Action of Two Biocides (Benzalkonium Chloride and Dibromonitrilopropionamide): Discussion of Pseudomonas fluorescens’ Viability and Death
Authors: Barros Ana C. , Melo Luis F. , Pereira Ana
Published: February 2022

Biocides are widely used in water treatment for microbiological control. The rise of antimicrobial resistance and the need to assure properly managed water systems require a better understanding of the mechanisms of action of biocides and of their impact on cell’s viability as a function of dosage concentrations. The present work addresses these two aspects regarding the biocides benzalkonium chloride (BAC) and dibromonitrilopropionamide (DBNPA)—two biocides commonly found in the water treatment industry. For that, the following parameters were studied: culturability, membrane integrity, metabolic activity, cellular energy, and the structure and morphology of cells. Also, to assess cell’s death, a reliable positive control, consisting of cells killed by autoclave (dead cells), was introduced. The results confirmed that BAC is a lytic biocide and DBNPA a moderate electrophilic one. Furthermore, the comparison between cells exposed to the biocides’ minimum bactericidal concentrations (MBCs) and autoclaved cells revealed that other viability parameters should be taken into consideration as “death indicators.” The present work also shows that only for the concentrations above the MBC the viability indicators reached values statistically similar to the ones observed for the autoclaved cells (considered to be definitively dead). Finally, the importance of considering the biocide mechanism of action in the definition of the viability parameter to use in the viable but non-culturable (VBNC) determination is discussed.
The Physical Basis for pH Sensitivity in Biomolecular Structure and Function, With Application to the Spike Protein of SARS-CoV-2
Authors: Warwicker Jim
Published: February 2022

Since pH sensitivity has a fundamental role in biology, much effort has been committed to establishing physical models to rationalize and predict pH dependence from molecular structures. Two of the key challenges are to accurately calculate ionizable group solvation and hydration and then to apply this modeling to all conformations relevant to the process in question. Explicit solvent methods coupled to molecular dynamics simulation are increasingly complementing lower resolution implicit solvent techniques, but equally, the scale of biological data acquisition leaves a role for high-throughput modeling. Additionally, determination of ranges of structures for a system allows sampling of key stages in solvation. In a review of the area, it is emphasized that pH sensors in biology beyond the most obvious candidate (histidine side chain, with an unshifted pKa near neutral pH) should be considered; that modeling can benefit from other concepts in bioinformatics, in particular modulation of interactions and function in families of homologs; and that it can also be beneficial to incorporate as many experimental structures as possible, to mitigate against small variations in conformation and to analyze larger, functional, conformational changes. These aspects are then demonstrated with new work on the spike protein of SARS-CoV-2, looking at the pH dependence of variants, including prediction of a change in the balance of locked, closed, and open forms at neutral pH for the Omicron variant spike protein.
Erythrocytes Are an Independent Protective Factor for Vascular Cognitive Impairment in Patients With Severe White Matter Hyperintensities
Authors: Tao Xi , Zhou Hang , Mo Danheng , Zhang Wenjie , Chang Zihan , Zeng Yiheng , Luo Yuqi , Wu Siyuan , Tang Wenjing , Yang Chen , Wang Qing
Published: February 2022

Background and Purpose: Hemoglobin is one of the main proteins in erythrocytes. There are significant correlations between low hemoglobin and white matter hyperintensities (WMH) and cognitive impairment. This study explored whether erythrocytopenia has predictive value for vascular cognitive impairment (VCI) in patients with WMH.

Method: We conducted a cross-sectional study of 302 patients, including 62 with cerebral small vessel disease and 240 with stroke. Basic demographic data and fasting blood were collected. First, all patients were divided into normal cognition (NC), mild VCI (mVCI), and severe VCI (sVCI) groups (subgroups later) based on cognitive behavior scores. Second, all patients were divided into mild WMH (mWMH) and severe WMH (sWMH) groups based on Fazekas scores. The differences in blood markers between different groups or subgroups with different cognitive levels were analyzed by univariate analysis. Then, binary logistic regression was used to analyze the diagnostic value of erythrocyte counts for VCI in the sWMH group, and ordinal logistic regression was used to analyze the predictive value of multiple variables for different cognitive levels.

Results: Univariate analysis showed that erythrocytes, hemoglobin, high-sensitivity C-reactive protein, retinol binding protein and prealbumin were potential blood markers for different cognitive levels in sWMH patients. Among them, erythrocytopenia has good predictive value for the diagnosis of mVCI (AUC = 0.685, P = 0.008) or sVCI (AUC = 0.699, P = 0.003) in patients with sWMH. Multivariate joint analysis showed that erythrocytes were an independent protective factor reducing the occurrence of VCI in patients with sWMH (OR = 0.633, P = 0.045). Even after adjusting for age, there was still a significant difference (P = 0.047).

Conclusion: Erythrocytes are an independent protective factor for VCI in patients with sWMH. Promoting hematopoietic function may have potential value for prevention of cognitive decline in patients with cerebrovascular disease.
Designing Physical Human-Robot Interaction Interfaces: A Scalable Method for Simulation Based Design
Authors: John Varghese Rohit , Mukherjee Gaurav , Deshpande Ashish
Published: February 2022

Designing the physical coupling between the human body and the wearable robot is a challenging endeavor. The typical approach of tightening the wearable robot against the body, and softening the interface materials does not work well. It makes the task of simultaneously improving comfort, and anchoring the robot to the body at the physical human robot interaction interface (PHRII), difficult. Characterizing this behavior experimentally with sensors at the interface is challenging due to the soft-soft interactions between the PHRII materials and the human tissue. Therefore, modeling the interaction between the wearable robot and the hand is a necessary step to improve design. In this paper, we introduce a methodology to systematically improve the design of the PHRII by combining experimentally measured characteristics of the biological tissue with a novel dynamic modeling tool. Using a novel and scalable simulation framework, HuRoSim, we quantified the interaction between the human hand and an exoskeleton. In the first of our experiments, we use HuRoSim to predict complex interactions between the hand and the coupled exoskeleton. In our second experiment, we then demonstrate how HuRoSim can be coupled with experimental measurements of the stiffness of the dorsal surface of the hand to optimize the design of the PHRII. This approach of data-driven modeling of the interaction between the body and a wearable robot, such as a hand exoskeleton, can be generalized to other forms of wearable devices as well, demonstrating a scalable and systematic method for improving the design of the PHRII for future devices coupled to the body.
Association Between Carotid Artery Perivascular Fat Density and Embolic Stroke of Undetermined Source
Authors: Hu Xiaohong , Chen Jianhui , Fu Huajun , Chen Yinjuan , Fan Daofeng , Chen Yangui , Shen Chaoxiong
Published: February 2022

Aim

This study aims to retrospectively evaluate the association between pericarotid inflammation and the presence of embolic stroke of undetermined source (ESUS).

Methods

In total, 126 patients with ESUS and 118 patients with ischemic stroke from large artery atherosclerosis (LAA) were enrolled. All the patients underwent brain MRI and a neck CT angiography (CTA) examination. Reviewers were blinded to infarct location and stroke cause. Paired t-tests assessed within-subjects differences in mean Hounsfield units (HUs) in carotid perivascular fat between the cerebral infarction side and contralateral side for ESUS and LAA ischemic stroke cases. The unpaired Student's t-test was used to assess between-subjects differences in mean HUs between ESUS and LAA ischemic stroke cases.

Results

In both the ESUS cases and LAA ischemic stroke cases, the pericarotid fat density around the carotid artery ipsilateral to the stroke significantly increased compared with contralateral stroke position in both the groups (ESUS cases −56.31 ± 18.70 vs. −67.31 ± 20.01, p = 0.000; LAA ischemic stroke cases −51.62 ± 19.95 vs. −64.58 ± 22.68, p = 0.000). However, there was no significant difference in ipsilateral and contralateral positions to infarct between ESUS cases and LAA ischemic stroke cases (ipsilateral to infarct −56.31 ± 18.70 vs. −51.62 ± 19.95, p = 0.059; contralateral to infarct −67.31 ± 20.01 vs. −64.58 ± 22.68, p = 0.320).

Conclusion

We found increased density in the fat surrounding carotid artery ipsilateral to stroke compared with contralateral in ESUS, suggesting the presence of an inflammatory reaction that extends beyond the vessel lumen in patients with ESUS with a risk factor profile similar to LAA strokes.