bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes in microglia in the mouse hippocampus during administration and withdrawal of the CSF1R inhibitor PLX3397
Authors: Wang Qirun , Wang Yi‐Yan , Pu Wen‐Jun , Ma Xiaohong , Ni Rong‐Jun 
Published: April 2023

AbstractPexidartinib (PLX3397), a colony‐stimulating factor‐1 receptor (CSF1R) inhibitor, is currently in phase 1–3 clinical trials as a treatment for a variety of tumours. CSF1R signalling regulates the development, survival and maintenance of microglia, the resident brain innate immune cells. In this study, we examined the effects of PLX3397 in the drinking water of mice on microglia in the hippocampus using ionized calcium‐binding adapter molecule 1 (Iba1, a microglial marker) immunocytochemistry. A high concentration of PLX3397 (1 mg/mL) significantly decreased the density of Iba1‐immunoreactive cells after 7 days of exposure, but a low concentration of PLX3397 (0.5 mg/mL) did not. In addition, both low and high concentrations of PLX3397 significantly increased the intersection number, total length and maximum length of microglial processes in male mice. PLX3397 administered for 21 days eliminated microglia with 78% efficiency in males and 84% efficiency in females. Significant increases in microglial processes were found after both seven and 21 days of PLX3397 exposure in males, whereas decreases in microglial processes were observed after both 14 and 21 days of exposure in females. After PLX3397 withdrawal following its administration for 14 days in males, the soma size quickly returned to normal levels within a week. However, the microglial density, intersection number and total length of microglial processes after 3 days of recovery stabilized to untreated levels. In summary, these findings provide detailed insight into the dynamic changes in microglial number and morphology in the hippocampus in a dose‐ and time‐dependent manner after PLX3397 treatment and withdrawal.
Immune checkpoint inhibitor–associated capillary leak syndrome: A systematic review and a worldwide pharmacovigilance study
Authors: Wong So Jonathan , Bouibede Fatma , Jonville‐Béra Annie‐Pierre , Maillot François , Barbier François , Largeau Bérenger 
Published: April 2023

AbstractBackgroundAlthough a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI‐induced CLS through a systematic review and to assess a potential safety signal.MethodsMedline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0.ResultsA total of 47 cases of ICI‐associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8–49, n = 24). A total of 57% (8/14) of patients experienced an immune‐related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8).ConclusionThis study showed a significant signal of disproportionality reporting for ICI‐induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.
Diagnostic predictivity of transtubular potassium gradient for primary hypoadrenocorticism in hyperkalemic dogs: a cross‐sectional study
Authors: Petini M. , Drigo M. , Caldin M. , Zoia A. 
Published: April 2023

ObjectivesTranstubular potassium gradient has never been evaluated in the diagnosis of primary hypoadrenocorticism in dogs. The objective of this study is to evaluate the diagnostic utility of transtubular potassium gradient for the diagnosis of primary hypoadrenocorticism in dogs with serum K+ > 5.5 mol/L.Materials and MethodsCross‐sectional study including dogs with primary hypoadrenocorticism and dogs with other disease. Differences in signalment and laboratory parameters between groups were assessed by binary logistic regression modelling. Variables significantly associated with primary hypoadrenocorticism were evaluated for their diagnostic accuracy of this condition by receiver operator characteristic curve analysis and by multivariable logistic regression analysis, respectively.ResultsDogs with primary hypoadrenocorticism (n=39) were significantly younger than hyperkalemic dogs without primary hypoadrenocorticism (n=41). Moreover they had higher serum and urinary concentrations of Na+and Na+:K+, but lower transtubular potassium gradient than hyperkalemic dogs without hypoadrenocorticism. Serum Na+(sNa+) had the highest diagnostic accuracy (area under the curve [AUC]: 0.87, 95% confidence interval, 0.78 to 0.96), followed by the transtubular potassium gradient (AUC: 0.81, 0.72 to 0.91), however the accuracy of the two AUCs was not statistically different. The transtubular potassium gradient‐sNa+additive index (i.e.transtubular potassium gradient+sNa+/10) had a greater accuracy (AUC: 0.88, 0.79 to 0.94) than transtubular potassium gradient or sNa+, although it was not statistically superior to the latter. The multivariable logistic regression model showed that transtubular potassium gradient (adjusted odds ratio [aOR]: 0.51, 0.3 to 0.84), sNa+(aOR: 0.86, 0.78 to 0.95) and spayed female (aOR: 24.96, 2.32 to 267.66) were associated with primary hypoadrenocorticism.Clinical SignificanceTranstubular potassium gradient‐sNa+additive index can contribute to decision‐making on diagnosis of primary hypoadrenocorticism in dogs presenting with hyperkalaemia.
Effect of sample volume and time on rumen juice analysis in cattle
Authors: Clergue Suzanne A. C. , Depenbrock Sarah M. , Chigerwe Munashe 
Published: April 2023

AbstractBackgroundRumen juice analysis (RJA) involves analysis of a 10mL sample within minutes after sampling. However, it can be challenging to collect 10 mL of rumen juice (RJ) from some ruminants, and clinical circumstances can delay RJA.ObjectivesQuantify the effect of sample volume (2, 5, 10, 50, and 100 mL), and time‐to‐analysis (0, 30, and 60 minutes) on RJA.AnimalsCannulated cow.MethodsObservational experimental study. Two liters of RJ were collected at 26 separate times. The samples were subdivided into 2 duplicates of each sample volume at each sampling time; and analyzed at 0, 30, and 60 minutes after collection. Rumen juice analysis included pH measurement, methylene blue reduction time (MBRT), and protozoal motility.ResultsThe pH of 2 and 5 mL samples was significantly (P = .01) higher than the pH of 50 and 100 mL samples at all time points. The MBRT was significantly lower (faster bacterial reduction) for 100 mL samples compared to all other samples at 0 minute and to 2, 5, and 50 mL samples at 30 min. The pH and MBRT at 60 minutes were significantly higher than at 0 minute for all volumes (P < .05 and P < .01, respectively). For large protozoa, small sample volumes (2 and 5 mL) had significantly lower protozoal motility (scores of 5 and 4.5, respectively) compared to 100 mL samples at 60 minutes (score of 4; P < .05).Conclusions and Clinical ImportanceInterpretation of RJA could be affected by small sample volumes and delays to analysis. Sample volumes of ≥10 mL analyzed within 30 minutes after collection are recommended.
Apoptosis‐inducing factor‐like protein‐mediated stress and metronidazole‐responsive programmed cell death pathway in Entamoeba histolytica
Authors: Bandyopadhyay Anwesha , Ghosh Sudip Kumar 
Published: April 2023

AbstractApoptosis‐inducing factor (AIF) is the major component of the caspase‐independent cell death pathway that is considered to be evolutionarily ancient. Apoptosis is generally evolved with multicellularity as a prerequisite for the elimination of aged, stressed, or infected cells promoting the survival of the organism. Our study reports the presence of a putative AIF‐like protein in Entamoeba histolytica, a caspase‐deficient primitive protozoan, strengthening the concept of occurrence of apoptosis in unicellular organisms as well. The putative cytoplasmic EhAIF migrates to the nucleus on receiving stresses that precede its binding with DNA, following chromatin degradation and chromatin condensation as evident from both in vitro and in vivo experiments. Down‐regulating the EhAIF expression attenuates the apoptotic features of insulted cells and increases the survival potency in terms of cell viability and vitality of the trophozoites, whereas over‐expression of the EhAIF effectively enhances the phenomena. Interestingly, metronidazole, the most widely used drug for amoebiasis treatment, is also potent to elicit similar AIF‐mediated cell death responses like other stresses indicating the AIF‐mediated cell death could be the probable mechanism of trophozoite‐death by metronidazole treatment. The occurrence of apoptosis in a unicellular organism is an interesting phenomenon that might signify the altruistic death that overall improves the population health.
The broad host range pathogen Sclerotinia sclerotiorum produces multiple effector proteins that induce host cell death intracellularly
Authors: Newman Toby E. , Kim Haseong , Khentry Yuphin , Sohn Kee Hoon , Derbyshire Mark C. , Kamphuis Lars G. 
Published: April 2023

AbstractSclerotinia sclerotiorum is a broad host range necrotrophic fungal pathogen, which causes disease on many economically important crop species. S. sclerotiorum has been shown to secrete small effector proteins to kill host cells and acquire nutrients. We set out to discover novel necrosis‐inducing effectors and characterize their activity using transient expression in Nicotiana benthamiana leaves. Five intracellular necrosis‐inducing effectors were identified with differing host subcellular localization patterns, which were named intracellular necrosis‐inducing effector 1–5 (SsINE1–5). We show for the first time a broad host range pathogen effector, SsINE1, that uses an RxLR‐like motif to enter host cells. Furthermore, we provide preliminary evidence that SsINE5 induces necrosis via an NLR protein. All five of the identified effectors are highly conserved in globally sourced S. sclerotiorum isolates. Taken together, these results advance our understanding of the virulence mechanisms employed by S. sclerotiorum and reveal potential avenues for enhancing genetic resistance to this damaging fungal pathogen.
Cotton leafroll dwarf disease: An enigmatic viral disease in cotton
Authors: Edula Surendra R. , Bag Sudeep , Milner Hayley , Kumar Manish , Suassuna Nelson D. , Chee Peng W. , Kemerait Robert C. , Hand Lavesta C. , Snider John L. , Srinivasan Rajagopalbabu , Roberts Phillip M. 
Published: April 2023

AbstractTaxonomy: Cotton leafroll dwarf virus (CLRDV) is a member of the genus Polerovirus, family Solemoviridae.Geographical Distribution: CLRDV is present in most cotton‐producing regions worldwide, prominently in North and South America.Physical Properties: The virion is a nonenveloped icosahedron with T = 3 icosahedral lattice symmetry that has a diameter of 26–34 nm and comprises 180 molecules of the capsid protein. The CsCl buoyant density of the virion is 1.39–1.42 g/cm3 and S20w is 115–127S.Genome: CLRDV shares genomic features with other poleroviruses; its genome consists of monopartite, single‐stranded, positive‐sense RNA, is approximately 5.7–5.8 kb in length, and is composed of seven open reading frames (ORFs) with an intergenic region between ORF2 and ORF3a.Transmission: CLRDV is transmitted efficiently by the cotton aphid (Aphis gossypii Glover) in a circulative and nonpropagative manner.Host: CLRDV has a limited host range. Cotton is the primary host, and it has also been detected in different weeds in and around commercial cotton fields in Georgia, USA.Symptoms: Cotton plants infected early in the growth stage exhibit reddening or bronzing of foliage, maroon stems and petioles, and drooping. Plants infected in later growth stages exhibit intense green foliage with leaf rugosity, moderate to severe stunting, shortened internodes, and increased boll shedding/abortion, resulting in poor boll retention. These symptoms are variable and are probably influenced by the time of infection, plant growth stage, varieties, soil health, and geographical location. CLRDV is also often detected in symptomless plants.Control: Vector management with the application of chemical insecticides is ineffective. Some host plant varieties grown in South America are resistant, but all varieties grown in the United States are susceptible. Integrated disease management strategies, including weed management and removal of volunteer stalks, could reduce the abundance of virus inoculum in the field.
Risk assessment of infectious disease epidemic based on fuzzy Bayesian network
Authors: Fu Lingmei , Yang Qing , Liu Xingxing , He Ling 
Published: April 2023

AbstractThe prevention and control of infectious disease epidemic (IDE) is an important task for every country and region. Risk assessment is significant for the prevention and control of IDE. Fuzzy Bayesian networks (FBN) can capture complex causality and uncertainty. The study developed a novel FBN model, integrating grounded theory, interpretive structural model, and expert weight determination algorithm for the risk assessment of IDE. The algorithm is proposed by the authors for expert weighting in fuzzy environment. The proposed FBN model comprehensively takes into account the risk factors and the interaction among them, and quantifies the uncertainty of IDE risk assessment, so as to make the assessment results more reliable. Taking the epidemic situation of COVID‐19 in Wuhan as a case, the application of the proposed model is illustrated. And sensitivity analysis is performed to identify the important risk factors of IDE. Moreover, the effectiveness of the model is checked by the three‐criterion‐based quantitative validation method including variation connection, consistent effect, and cumulative limitation. Results show that the probability of the outbreak of COVID‐19 in Wuhan is as high as 82.26%, which is well‐matched with the actual situation. “Information transfer mechanism,” “coordination and cooperation among various personnel,” “population flow,” and “ability of quarantine” are key risk factors. The constructed model meets the above three criteria. The application potential and effectiveness of the developed FBN model are demonstrated. The study provides decision support for preventing and controlling IDE.
Comments on Divergence vs. Decision P‐values: A Distinction Worth Making in Theory and Keeping in Practice – or, How Divergence P‐values Measure Evidence Even When Decision P‐values Do Not by Greenland in Scandinavian Journal of Statistics, 2023
Authors: Lavine Michael 
Published: April 2023

AbstractGreenland (2023) distinguishes between P‐values used for data description and P‐values used for declaring significance. That's a useful distinction and Greenland has advanced our field by making it. That distinction comes with the idea that describing data with statistical models is often a useful task for statisticians. Again, we agree. Along the way, Greenland also says (i) there is such a thing as a “measure …of evidence [from data] against a statistical hypothesis or model” without regard to alternatives; (ii) “a discrepancy P‐value is an ordinal description …”; (iii) descriptive “P‐values can be derived to provide coherent measures of refutational evidence”; and a few other things that deserve comment and discussion.
A modular equality for m$m$‐ovoids of elliptic quadrics
Authors: Gavrilyuk Alexander L. , Metsch Klaus , Pavese Francesco 
Published: April 2023

AbstractAn ‐ovoid of a finite polar space is a set of points such that every maximal subspace of contains exactly points of . In the case when is an elliptic quadric of rank in , we prove that an ‐ovoid exists only if satisfies a certain modular equality, which depends on and . This condition rules out many of the possible values of . Previously, only a lower bound on was known, which we slightly improve as a byproduct of our method. We also obtain a characterization of the ‐ovoids of for and .
Compost Waste Heat to Power Organic Rankine Cycle Design and Analysis
Authors: Mitri Frederick B. , Ponce Genesis , Anderson Kevin R. 
Published: April 2023

Abstract
This paper presents a feasibility study of a hybrid compost waste heat to power/Concentrating Solar Panel (CSP) green energy Organic Rankine Cycle (ORC). The power plant is baselined to operate with a duty of 24/7 on compost waste heat and utilize solar thermal energy to boost power output during the day. This paper discusses the design of the power plant, the design of a compost driven heat exchanger/boiler, compost pile thermal analysis, CSP analysis, and simulated power plant output analysis The selection of isobutane as ORC working fluid is justified herein. A Levelized Cost of Energy (LCOE) analysis was performed to ensure that the energy produced by this hybrid power plant would come at a reasonable and competitive cost. The results herein show that the hybrid power plant affords an LCOE of 4 ¢/kWh for compost operation alone and an LCOE of 10.7 ¢/kWh for compost and CSP solar energy operation. The hybrid compost/ORC power plant presented herein affords an average energy conversion efficiency of 4.3%. Centric to the operation of the compost waste heat to power plant presented herein is the correct design and selection of the heat exchanger which interfaces the compost waste heat stream to the isobutane ORC. The design and analysis of this heat exchanger as well as commercially off-the-shelf hardware to meet the specifications is given in detail herein
Novel intervention to promote COVID-19 protective behaviours among Black and South Asian communities in the UK: protocol for a mixed-methods pilot evaluation
Authors: Forbes Lindsay , Armes Jo , Shafi Shuja , Mohamed Amran , Mustafa Reham , Dar Osman , Vandrevala Tushna , Amlôt Richard , Hayward Andrew , Asaria Miqdad , Pirani Tasneem , Weston Dale , Shah Sunayana , Zumla Alimuddin , Ala Aftab 
Published: April 2023

IntroductionCulturally appropriate interventions to promote COVID-19 health protective measures among Black and South Asian communities in the UK are needed. We aim to carry out a preliminary evaluation of an intervention to reduce risk of COVID-19 comprising a short film and electronic leaflet.Methods and analysisThis mixed methods study comprises (1) a focus group to understand how people from the relevant communities interpret and understand the intervention’s messages, (2) a before-and-after questionnaire study examining the extent to which the intervention changes intentions and confidence to carry out COVID-19 protective behaviours and (3) a further qualitative study exploring the views of Black and South Asian people of the intervention and the experiences of health professionals offering the intervention. Participants will be recruited through general practices. Data collection will be carried out in the community.Ethics and disseminationThe study received Health Research Authority approval in June 2021 (Research Ethics Committee Reference 21/LO/0452). All participants provided informed consent. As well as publishing the findings in peer-reviewed journals, we will disseminate the findings through the UK Health Security Agency, NHS England and the Office for Health Improvement and Disparities and ensure culturally appropriate messaging for participants and other members of the target groups.
Associations between neighbourhood social cohesion and subjective well-being in two different informal settlement types in Delhi, India: a quantitative cross-sectional study
Authors: Humble Steve , Sharma Aditya , Rangaraju Baladevan , Dixon Pauline , Pennington Mark 
Published: April 2023

ObjectivesTo evaluate the relationships between neighbourhood cohesion and subjective well-being (SWB) in two different informal settlement types.DesignCross-sectional analysis of a community-based survey.SettingCommunities in two districts, Sanjay Colony, Okhla Phase II and Bhalswa in Delhi, India.Participants328 residents in Bhalswa and 311 from Sanjay Colony.MeasurementsNeighbourhood social cohesion scale measured on an 18-point scale and the SWB scale made up of four subjective measures—hedonic, eudaemonic, evaluative and freedom of choice. Sociodemographic characteristics and trust were used as covariates.ResultsIn both neighbourhood types there was a statistically significant positive bivariate correlation between neighbourhood cohesion and SWB (Sanjay: r=0.145, p<0.05; Bhalswa: r=0.264, p<0.01). Trust and neighbourhood cohesion were strongly correlated (Sanjay: r=0.618, p<0.01; Bhalswa: r=0.533, p<0.01) and the longer the resident had lived in the community the greater the feeling of neighbourhood cohesion (Sanjay: r=0.157, p<0.01; Bhalswa: r=0.171, p<0.05). Only in the resettlement colony (Bhalswa) was SWB negatively correlated with length of residency (r=−0.117, p<0.05). Residents who chose their settlement type (Sanjay residents) were 22.5 percentage points (pp) more likely to have a feeling of belonging to their neighbourhood than residents that had been resettled (Bhalswa) (Cohen’s d effect size 0.45). Sanjay residents had a greater likelihood to feel more satisfied with life (4.8 pp, p<0.01) and having greater perceived freedom of choice (4.8 pp, p<0.01).ConclusionsOur findings contribute to the general knowledge about neighbourhood cohesion and SWB within different informal settlement types in a mega-city such as New Delhi, India. Interventions that promote sense of belonging, satisfaction with life and freedom of choice have the potential to significantly improve people’s well-being.
Protective effects of methylsulfonylmethane (MSM) on barrier function injury of porcine intestinal epithelial cells (IPEC-J2) induced by lipopolysaccharide (LPS)
Authors: Jiao Yang , Li Hengjiang , Ren Ting , Kim In Ho 
Published: April 2023

Methylsulfonylmethane (MSM) is a natural organic sulfur component that has anti-inflammatory and antioxidant properties. In this study, injury of porcine intestinal epithelial cell (IPEC-J2) models were used to investigate the effect of MSM on lipopolysaccharide (LPS)-induced porcine intestinal epithelium barrier damage. The results of the cell cycle showed that the cells in the G2/M phase decreased significantly with the supplementation of 300 mmol/L MSM ( P < 0.05). The ELISA assay revealed that MSM could significantly inhibit the expression of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 ( P < 0.01). Meanwhile, MSM could significantly increase the value of cell monolayer transepithelial electrical resistance while reducing the FITC-dextran flux permeability and lactate dehydrogenase activity in IPEC-J2 cells ( P < 0.01). Additionally, 300 mmol/L MSM significantly increased both mRNA and protein expression of occludin, claudin-1, and ZO-1 ( P < 0.05). Furthermore, MSM prevented the downregulation of epidermal growth factor receptor (EGFR) by LPS, indicating that MSM might enhance tight junction function through mechanisms of activation of EGFR-mediated protein synthesis in IPEC-J2 cells. Therefore, our findings suggested that MSM has protective effects on inflammation and epithelial barrier injury in LPS-induced IPEC-J2 cells, indicating that MSM might be used as a potential therapeutic agent in the pig industry.