syedzayyan/paper_mill_benchmark huggingface dataset:
Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.

The anti-cd20 monoclonal antibodies rituximab and obinutuzumab differ in their mechanisms of action, with obinutuzumab evoking greater direct b cell death.To characterize the signaling processes responsible for improved b cell killing by obinutuzumab, we undertook a phosphoproteomics approach and demonstrate that rituximab and obinutuzumab differentially activate pathways downstream of the b cell receptor.Although both antibodies induce strong erk and myc activation sufficient to promote cell-cycle arrest and b cell death, obinutuzumab exceeds rituximab in supporting apoptosis induction by means of aberrant syk phosphorylation.In contrast, rituximab elicits stronger anti-apoptotic signals by activating akt, by impairing pro-apoptotic bad, and by releasing membrane-bound notch1 to up-regulate pro-survival target genes.As a consequence, rituximab appears to reinforce bcl2-mediated apoptosis resistance.The unexpected complexity and differences by which rituximab and obinutuzumab interfere with signaling pathways essential for lymphoma pathogenesis and treatment provide important impetus to optimize and personalize the application of different anti-cd20 treatments.

Journal: iScience (2021)
Publication types: Journal Article
Single cell analysis of docosahexaenoic acid suppression of sequential LPS-induced proinflammatory and interferon-regulated gene expression in the macrophage.

Preclinical and clinical studies suggest that consumption of long chain omega-3 polyunsaturated fatty acids (pufas) reduces severity of chronic inflammatory and autoimmune diseases.While these ameliorative effects are conventionally associated with downregulated expression of proinflammatory cytokine and chemokine genes, our laboratory has recently identified type 1 interferon (ifn1)-regulated gene expression to be another key target of omega-3 pufas.Here we used single cell rna sequencing (sc rnaseq) to gain new mechanistic perspectives on how the omega-3 pufa docosahexaenoic acid (dha) influences tlr4-driven proinflammatory and ifn1-regulated gene expression in a novel self-renewing murine fetal liver-derived macrophage (flm) model.Flms were cultured with 25 μm dha or vehicle for 24 h, treated with modest concentration of lps (20 ng/ml) for 1 and 4 h, and then subjected to sc rnaseq using the 10x chromium system.At 0 h (i.e., in the absence of lps), dha increased expression of genes associated with the nrf2 antioxidant response (e.g.sqstm1,hmox1, chchd10) and metal homeostasis (e.g.mt1,mt2, ftl1, fth1), both of which are consistent with dha-induced polarization of flms to a more anti-inflammatory phenotype.At 1 h post-lps treatment, dha inhibited lps-induced cholesterol synthesis genes (e.g.scd1, scd2,pmvk, cyp51, hmgcs1, and fdps)which potentially could contribute to interference with tlr4-mediated inflammatory signaling.At 4 h post-lps treatment, lps-treated flms reflected a more robust inflammatory response including upregulation of proinflammatory cytokine (e.g.il1a, il1b, tnf) and chemokine (e.g.ccl2, ccl3, ccl4, ccl7) genes as well as ifn1-regulated genes (e.g.irf7, mx1, oasl1, ifit1), many of which were suppressed by dha.Using single-cell regulatory network inference and clustering (scenic) to identify gene expression networks, we found dha modestly downregulated lps-induced expression of nf-κb-target genes.Importantly, lps induced a subset of flms simultaneously expressing nf-κb- and irf7/stat1/stat2-target genes that were conspicuously absent in dha-pretreated flms.Thus, dha potently targeted both the nf-κb and the ifn1 responses.Altogether, sc rnaseq generated a valuable dataset that provides new insights into multiple overlapping mechanisms by which dha may transcriptionally or post-transcriptionally regulate lps-induced proinflammatory and ifn1-driven responses in macrophages.

Journal: Frontiers in immunology (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Characterization of influenza A virus pseudotyped with the spike protein of porcine epidemic diarrhea virus.

The coronavirus spike protein and the influenza virus hemagglutinin are class i viral membrane fusion proteins.While the two proteins display strong structural conservation and the mechanisms underlying membrane fusion are similar, they share no sequence similarity.Whether they are functionally interchangeable is currently unknown.In this study, we constructed sc iav-s, a single-cycle influenza a virus pseudotyped with the spike protein of porcine epidemic diarrhea virus (pedv), and demonstrated that this virus could infect cultured cells and trigger massive syncytium formation.Treatment with endocytosis inhibitors did not affect syncytium formation by infected cells.Moreover, the infectivity of sc iav-s was associated with the degree of cell adaptation of pedv-s.Intriguingly, sc iav-s lacking functional neuraminidase (na) exhibited substantially higher infectivity, suggesting a pivotal role of the sialic acid in the binding/entry of pedv.Together, sc iav-s offers a robust platform for the investigation of the entry mechanism of pedv or, possibly, of other coronaviruses.

Journal: Archives of virology (2018)
Publication types: Journal Article
Engineering a Reliable and Convenient SARS-CoV-2 Replicon System for Analysis of Viral RNA Synthesis and Screening of Antiviral Inhibitors.

The etiologic agent of covid-19 is highly contagious and has caused a severe global pandemic.Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for sars-co v-2 virologic research and inhibitor screening.In this study, we reported a replicon system which consists of four plasmids expressing the required segments of sars-co v-2.Our study revealed that the features for viral rna synthesis and responses to antivirus drugs of the replicon are similar to those of wild-type viruses.Further analysis indicated that orf6 provided potent intransstimulation of the viral replication.Some viral variations, such as 5'utr-c241t and orf8-(t28144c) l84s mutation, also exhibit their different impact upon viral replication.Besides, the screening of clinically used drugs identified that several tyrosine kinase inhibitors and dna-top ii inhibitors potently inhibit the replicon, as well as authentic sars-co v-2 viruses.Collectively, this replicon system provides a biosafety-worry-free platform for studying sars-co v-2 virology, monitoring the functional impact of viral mutations, and developing viral inhibitors.importancecovid-19 has caused a severe global pandemic.Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for sars-co v-2 virologic research and inhibitor screening.We reported a replicon system which consists of four ordinary plasmids expressing the required segments of sars-co v-2.Using the replicon system, we developed three application scenarios: (i) to identify the effects of viral proteins on virus replication, (ii) to identify the effects of mutations on viral replication during viral epidemics, and (iii) to perform high-throughput screening of antiviral drugs.Collectively, this replicon system would be useful for virologists to study sars-co v-2 virology, for epidemiologists to monitor virus mutations, and for industry to develop antiviral drugs.

Journal: mBio (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Study protocol for pragmatic trials of Internet-delivered guided and unguided cognitive behavior therapy for treating depression and anxiety in university students of two Latin American countries: the Yo Puedo Sentirme Bien study.

Major depressive disorder (mdd) and generalized anxiety disorder (gad) are highly prevalent among university students and predict impaired college performance and later life role functioning.Yet most students do not receive treatment, especially in low-middle-income countries (lmics).We aim to evaluate the effects of expanding treatment using scalable and inexpensive internet-delivered transdiagnostic cognitive behavioral therapy (i cbt) among college students with symptoms of mdd and/or gad in two lmics in latin america (colombia and mexico) and to investigate the feasibility of creating a precision treatment rule (ptr) to predict for whom i cbt is most effective.Methods we will first carry out a multi-site randomized pragmatic clinical trial (n = 1500) of students seeking treatment at student mental health clinics in participating universities or responding to an email offering services.Students on wait lists for clinic services will be randomized to unguided i cbt (33%), guided i cbt (33%), and treatment as usual (tau) (33%).I cbt will be provided immediately whereas tau will be whenever a clinic appointment is available.Short-term aggregate effects will be assessed at 90 days and longer-term effects 12 months after randomization.We will use ensemble machine learning to predict heterogeneity of treatment effects of unguided versus guided i cbt versus tau and develop a precision treatment rule (ptr) to optimize individual student outcome.We will then conduct a second and third trial with separate samples (n = 500 per arm), but with unequal allocation across two arms: 25% will be assigned to the treatment determined to yield optimal outcomes based on the ptr developed in the first trial (ptr for optimal short-term outcomes for trial 2 and 12-month outcomes for trial 3), whereas the remaining 75% will be assigned with equal allocation across all three treatment arms.Discussion by collecting comprehensive baseline characteristics to evaluate heterogeneity of treatment effects, we will provide valuable and innovative information to optimize treatment effects and guide university mental health treatment planning.Such an effort could have enormous public-health implications for the region by increasing the reach of treatment, decreasing unmet need and clinic wait times, and serving as a model of evidence-based intervention planning and implementation.Trial status irb approval of protocol version 1.0; june 3, 2020.Recruitment began on march 1, 2021.Recruitment is tentatively scheduled to be completed on may 30, 2024.Trial registration clinical trials.gov nct04780542 .First submission date: february 28, 2021.

Journal: Trials (2022)
Publication types: Clinical Trial Protocol;Journal Article
Amyloid deposition at the carotid artery in an ATTRwt amyloidosis patient: a case report.

Systemic amyloidosis is a diseased condition where misfolded proteins deposit in various organs in the form of amyloids, and transthyretin deposition, termed attr amyloidosis, can be either an age-related amyloid formation from misfolded wild-type ttr (attrwt) or by hereditary ttr malfunction due to mutation in the ttr gene (attrv).Although attrwt amyloidosis can cause various diseases, such as cardiac failure, conduction disturbances, arrhythmias and carpal tunnel syndrome, it is still under-recognised considering its clinical significance.Here the authors report a case of attrwt amyloidosis leading to carotid stenosis requiring surgical intervention.To the best of our knowledge, the current report is the first that described histopathological evidence of amyloid deposition in the carotid artery due to attrwt amyloidosis.

Journal: Journal of surgical case reports (2022)
Publication types: Case Reports;Journal Article
Targeting the Opening of Mitochondrial Permeability Transition Pores Potentiates Nanoparticle Drug Delivery and Mitigates Cancer Metastasis.

Mitochondria are highly involved in the metastasis of cancer cells.However, low permeability of mitochondria impedes the entry of anti-cancer drugs.Here, a self-assembled nanoparticle platform is designed that not only targets the dna-intercalating agent doxorubicin to mitochondria but also enhances the specific penetration by opening the mitochondrial permeability transition pores (mptps).With drastic improvement in mitochondrial uptake, the drug delivery system results in substantial mitochondrial impairment leading to amplified induction of apoptosis, depletion of energy supply, and inhibition of numerous metastasis-associated proteins.As a consequence, the drug delivery system significantly inhibits the orthotopic tumor growth, and suppressed the metastasis of cancer cells detached from primary tumors.Additionally, the nanoparticle exhibits a potent effect on eradicating the metastasis of disseminated tumor cell from blood to lung.The results show that strategies of targeting mitochondria and unlocking mptp are feasible and beneficial to mitigate both tumorigenesis and metastasis.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
Publication types: Journal Article
Decreased number of days of fever detection and duration of fever with continuous intake of a fermented milk drink: a randomized, double-blind, placebo-controlled study of elderly nursing home residents.

We conducted a randomized, double-blind, placebo-controlled parallel study to investigate the effects of a fermented milk on elderly nursing home residents.Eighty-eight participants each drank one bottle of fermented milk containing lactobacillus caseistrain shirota, or a placebo, on a daily basis for 6 months in winter.Peripheral blood, saliva, fecal samples, and clinical data were analyzed to assess the milk's efficacy.Fermented milk consumption was associated with a significant decrease in the number of days on which fever was detected and the mean duration of fever compared with these values in the placebo group.No significant differences were observed in other biological parameters.Continuous intake of this fermented milk could be beneficial for the elderly in terms of suppressing the number of days of detection of fever and the duration of fever, which usually increase in winter.

Journal: Bioscience of microbiota, food and health (2019)
Publication types: Journal Article
UNILATERAL ACUTE IDIOPATHIC MACULOPATHY IN A PATIENT WITH HAND-FOOT-MOUTH DISEASE: A CASE REPORT.

To demonstrate a rare cause of acute, focal chorioretinitis.Methods review of slit-lamp fundoscopy, color fundus photography, spectral-domain optical coherence tomography, and fluorescein angiography.Results slit-lamp examination revealed parafoveal microaneurysms, parafoveal intraretinal hemorrhages, and outer segment irregularity in the left eye.Fundus photographs demonstrated retinal hemorrhages and a greyish-whitish sheen in the central parafoveal area.Optical coherence tomography was notable for a small pocket of outer segment and retinal pigment epithelium disruption and irregularity in the central foveal area of the left eye.Fluorescein angiography revealed increased focal macular leakage within a larger central area of leakage and staining.Conclusion unilateral acute idiopathic maculopathy and, specifically, coxsackievirus-related chorioretinitis should be considered in the differential diagnosis of atypical maculopathy.

Journal: Retinal cases & brief reports (2022)
Publication types: Case Reports;Journal Article
Bacterial Communities in the Rhizosphere at Different Growth Stages of Maize Cultivated in Soil Under Conventional and Conservation Agricultural Practices.

Farmers in mexico till soil intensively, remove crop residues for fodder and grow maize often in monoculture.Conservation agriculture (ca), including minimal tillage, crop residue retention and crop diversification, is proposed as a more sustainable alternative.In this study, we determined the effect of agricultural practices and the developing maize rhizosphere on soil bacterial communities.Bulk and maize (zea mays l.) rhizosphere soil under conventional practices (cp) and ca were sampled during the vegetative, flowering and grain filling stage, and 16s r rna metabarcoding was used to assess bacterial diversity and community structure.The functional diversity was inferred from the bacterial taxa using picrust.Conservation agriculture positively affected taxonomic and functional diversity compared to cp.The agricultural practice was the most important factor in defining the structure of bacterial communities, even more so than rhizosphere and plant growth stage.The rhizosphere enriched fast growing copiotrophic bacteria, such as rhizobiales, sphingomonadales, xanthomonadales, and burkholderiales, while in the bulk soil of cp other copiotrophs were enriched, e.g.,halomonasand bacillus.the bacterial community in the maize bulk soil resembled each other more than in the rhizosphere of ca and cp.The bacterial community structure, and taxonomic and functional diversity in the maize rhizosphere changed with maize development and the differences between the bulk soil and the rhizosphere were more accentuated when the plant aged.Although agricultural practices did not alter the effect of the rhizosphere on the soil bacterial communities in the flowering and grain filling stage, they did in the vegetative stage.importancewe studied the effect of sustainable conservation agricultural practices versus intensive conventional ones on the soil microbial diversity, potential functionality, and community assembly in rhizosphere of maize cultivated in a semiarid environment.We found that conservation agriculture practices increased the diversity of soil microbial species and functions and strongly affected how they were structured compared to conventional practices.Microbes affected by the roots of maize, the rhizobiome, were different and more diverse than in the surrounding soil and their diversity increased when the plant grew.The agricultural practices affected the maize rhizobiome only in the early stages of growth, but this might have an important impact on the development of maize plant.

Journal: Microbiology spectrum (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Copper-Catalyzed Trifluoromethylation of Ynones Coupled with Dearomatizing Spirocyclization of Indoles: Access to CF3-Containing Spiro[cyclopentane-1,3'-indole].

A one-pot protocol for the cu(i)-catalyzed difunctionalization of indolyl ynones has been achieved via trifluoromethylation of alkyne followed by dearomatizing spirocyclization of indoles.This cascade process enables constructing diverse cf3-containing spiro[cyclopentane-1,3'-indole] scaffolds in moderate to excellent yields which have challenging quaternary spirocyclic carbon and tetrasubstituted alkenes.

Journal: Organic letters (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Association of alcohol use and dietary lifestyle of commercial drivers during the COVID-19 pandemic in Nigeria.

Alcohol intake, particularly to cope up with stress and depression experienced by commercial drivers during the peak of the covid-19 pandemic, is alarming as a rise in sales has been reported in certain countries during the quarantine.Alcoholism leads to malnutrition, either because those involved consume an insufficient amount of essential nutrients or because alcohol and its metabolism prevent the body from properly absorbing, digesting, and using those nutrients.This study was carried out to assess the association of alcohol use and dietary lifestyle of commercial motor drivers during the pandemic.Results the anthropometric studies revealed that 69.5% of the respondents fall within the range of 18.5-24.49 indicating that they have normal weights.63.5% reported daily consumption of alcohol, and 51% claimed that it does not affect their appetite, while 64.5% of the respondent stated that alcohol does not present them with any health problems.There was no significant association between the consumption of alcohol and nutritional status (p> 0.05), but a significant association between dietary lifestyle patterns and the nutritional status of participants was recorded (p< 0.05).Conclusion it is, therefore, essential that commercial drivers are given adequate information and guidance on improving their dietary lifestyle.

Journal: Bulletin of the National Research Centre (2022)
Publication types: Journal Article
Magnetically responsive polymer nanopillars with nickel cap.

Embedding magnetic particles within polymer matrix is a common and facile method to fabricate magnetically responsive micro-/nanoscale pillars.However, the balance between mechanical compliance and magnetic susceptibility cannot be decoupled and the particles are limited by the pillar feature size, which can limit the actuation performance.Here we demonstrate a new type of magnetically responsive nanostructure consisting of a polydimethylsiloxane (pdms) nanopillar array with deposited nickel caps, that has successfully achieved such decoupling with multiple cap-geometry designs for a better actuation control.The actuation result of nanopillars with 540 nm period and 1.3 μm height has been analyzed using image processing, leading to a maximum displacement of 180 nm with a ratio of 13.9% with respect to the pillar height.Magnetic and mechanical models based on magnetic force and torque have been developed and used to mitigate the weakening effect of the actuation by the residual magnetic layer.This structure demonstrates a feasible strategy for magnetic actuation at the sub-micrometer scale with freedom to design magnetic cap and polymeric pillar separately.This structure can also be utilized in multiple applications such as tunable optical elements, dynamic droplet manipulation, and responsive particle manipulation.

Journal: Nanotechnology (2021)
Publication types: Journal Article
Towards a better understanding of self-management interventions in type 2 diabetes: A concept analysis.

S diabetes self-management educational (dsme) interventions can vary considerably, and it is unclear what is the operational conceptualization of the ideal delivery to individuals with type 2 diabetes (t2d).Design from a search conducted concurrently we extracted and evaluated the 50 most recently published dsme intervention studies.Based on an analysis of these studies, we undertook a concept analysis using the walker and avant framework.Results five attributes describing the concept were recognized and organized into two groups.Group (a): skills related attributes that included (1) decision making, (2) problem solving and (3) taking action.Group (b): information related attributes that included (4) patient-provider interaction and (5) resource utilization.Conclusions the outcomes of this study make the operational conceptualization of the ideal dsme intervention measurable through its attributes and hence clarifies its delivery.This will improve the implementation of the key attributes in diabetes self-management intervention programs for t2d.

Journal: Primary care diabetes (2022)
Publication types: Journal Article
The E protein-TCF1 axis controls γδ T cell development and effector fate.

Tcf1 plays a critical role in t lineage commitment and the development of αβ lineage t cells, but its role in γδ t cell development remains poorly understood.Here, we reveal a regulatory axis where t cell receptor (tcr) signaling controls tcf1 expression through an e-protein-bound regulatory element in the tcf7 locus, and this axis regulates both γδ t lineage commitment and effector fate.Indeed, the level of tcf1 expression plays an important role in setting the threshold for γδ t lineage commitment and modulates the ability of tcr signaling to influence effector fate adoption by γδ t lineage progenitors.This finding provides mechanistic insight into how tcr-mediated repression of e proteins promotes the development of γδ t cells and their adoption of the interleukin (il)-17-producing effector fate.Il-17-producing γδ t cells have been implicated in cancer progression and in the pathogenesis of psoriasis and multiple sclerosis.

Journal: Cell reports (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't