syedzayyan/paper_mill_benchmark huggingface dataset:
A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer.

Mammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts.We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (cmt), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors.We established the long-term culture of 24 organoid lines from 16 dogs, including organoids derived from normal mammary epithelium or benign lesions.Cmt organoids recapitulated key morphological and immunohistological features of the primary tissue from which they were derived, including hormone receptor status.Furthermore, genetic characteristics (driver gene mutations, dna copy number variations, and single-nucleotide variants) were conserved within tumor-organoid pairs.We show how cmt organoids are a suitable model for in vitro drug assays and can be used to investigate whether specific mutations predict therapy outcomes.Specifically, certain cmt subtypes, such as pik3ca mutated, estrogen receptor-positive simple carcinomas, can be valuable in setting up a preclinical model highly relevant to human breast cancer research.In addition, we could genetically modify the cmt organoids and use them to perform pooled crispr/cas9 screening, where library representation was accurately maintained.In summary, we present a robust 3d in vitro preclinical model that can be used in translational research, where organoids from normal, benign as well as malignant mammary tissues can be propagated from the same animal to study tumorigenesis.

Journal: Scientific reports (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Therapeutic Potential of Standardized Extract ofMelilotus indicus(L.) All. and Its Phytochemicals against Skin Cancer in Animal Model:In Vitro,In Vivo, andIn SilicoStudies.

Melilotus indicus(l.) all.Is known to have anti-inflammatory and anticancer properties.The present study explored thein vivoskin carcinogenesis attenuating potential of ethanolic extract of m.Indicus(l.) all.(miet) in a 7,12-dimethylbenz[a]anthracene (dmba)-induced skin cancer model.The ethanolic extract of the plant was prepared by a maceration method.Hplc analysis indicated the presence of quercetin in abundance and also various other phytoconstituents.Dpph radical scavenging assay results showed moderate antioxidant potential (ic50= 93.55 ± 5.59 μg/m l).A topical acute skin irritation study showed the nonirritant nature of miet.Data for the skin carcinogenic model showed marked improvement in skin architecture in miet and its primary phytochemicals (quercetin and coumarin) treated groups.Miet 50% showed comparable effects with 5-fluorouracil.Significant (p< 0.05) anticancerous effects were seen in coumarin-quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals.Chorioallantoic membrane (cam) assay results showed the antiangiogenic potential of miet.Treatment with miet significantly down-regulated the serum levels of cea (carcinoembryonic antigen) and tnf-α (tumor necrosis factor-α).Data for the docking study indicated the binding potential of quercetin and coumarin with tnf-α, egfr, vegf, and bcl2 proteins.Thus, it is concluded that miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules.Further studies to explore the effects of miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.

Journal: ACS omega (2022)
Publication types: Journal Article
Quantitative Measurement of Spinal Cerebrospinal Fluid by Cascade Artificial Intelligence Models in Patients with Spontaneous Intracranial Hypotension.

Cerebrospinal fluid (csf) hypovolemia is the core of spontaneous intracranial hypotension (sih).More than 1000 magnetic resonance myelography (mrm) images are required to evaluate each subject.An effective spinal csf quantification method is needed.In this study, we proposed a cascade artificial intelligence (ai) model to automatically segment spinal csf.From january 2014 to december 2019, patients with sih and 12 healthy volunteers (hvs) were recruited.We evaluated the performance of ai models which combined object detection (yolo v3) and semantic segmentation (u-net or u-net++).The network of performance was evaluated using intersection over union (io u).The best ai model was used to quantify spinal csf in patients.We obtained 25,603 slices of mrm images from 13 patients and 12 hvs.We divided the images into training, validation, and test datasets with a ratio of 4:1:5.The io u of cascade yolo v3 plus u-net++ (0.9374) was the highest.Applying yolo v3 plus u-net++ to another 13 sih patients showed a significant decrease in the volume of spinal csf measured (59.32 ± 10.94 m l) at disease onset compared to during their recovery stage (70.61 ± 15.31 m l).The cascade ai model provided a satisfactory performance with regard to the fully automatic segmentation of spinal csf from mrm images.The spinal csf volume obtained through its measurements could reflect a patient's clinical status.

Journal: Biomedicines (2022)
Publication types: Journal Article
Astragalus species: Phytochemistry, biological actions and molecular mechanisms underlying their potential neuroprotective effects on neurological diseases.

Neurodegenerative and neuropsychiatric illnesses are prevalent and life-threatening disorders characterized by a wide range of clinical syndromes and comorbidities, all of which have complex origins and share common molecular pathomechanisms.Although the pathophysiology of neurological illnesses is not completely understood, researchers have discovered that several ion channels and signalling pathways may have played a role in disease pathogenesis.Active substances from astragalus sp.Are being employed for nutrition, and their usefulness in the treatment of neurological illnesses is receiving more attention.Because their extracts and active components exert different pharmacological effects on a variety of ailments, they have a long history of usage as a cure for various diseases.This review summarizes the research work on astragalus and their biologically active constituents as potential candidates for the protection against and treatment of neurodegenerative and neuropsychiatric disorders to show the potential efficacy of astragalus sp.And its active ingredients in treating some neurological diseases.Simultaneously, the chemical structures of these active compounds, their sources, biological properties, and mechanisms are also listed.In ethnopharmacological applications, astragalus membranaceus and spinosus have been studied as traditional medicines worldwide.The chemical constituents of astragalus species mainly comprise terpenoids, flavonoids, and polysaccharides.The extracts and phytochemical compounds of astragalus species exhibit various pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antitumor, anticonvulsive, immunomodulatory, and other activities.Based on the current literature, we conclude that astragalus is a promising dietary herb with multiple potential signal modulating applications that mainly include the modulation of neurotransmitters and receptors, anti-inflammatory activities, inhibition of amyloid aggregation, induction of myelin sheath repair and neurogenesis, as well as activation of the signalling pathways relevant to neurological diseases.

Journal: Phytochemistry (2022)
Publication types: Journal Article;Review
Fecal1H-NMR Metabolomics: A Comparison of Sample Preparation Methods for NMR and Novel in Silico Baseline Correction.

Analysis of enteric microbiota function indirectly through the fecal metabolome has the potential to be an informative diagnostic tool.However, metabolomic analysis of feces is hampered by high concentrations of macromolecules such as proteins, fats, and fiber in samples.Three methods-ultrafiltration (uf), bligh-dyer (bd), and no extraction (samples added directly to buffer, vortexed, and centrifuged)-were tested on multiple rat (n= 10) and chicken (n= 8) fecal samples to ascertain whether the methods worked equally well across species and individuals.An in silico baseline correction method was evaluated to determine if an algorithm could produce spectra similar to those obtained via uf.For both rat and chicken feces, uf removed all macromolecules and produced no baseline distortion among samples.By contrast, the bd and no extraction methods did not remove all the macromolecules and produced baseline distortions.The application of in silico baseline correction produced spectra comparable to uf spectra.In the case of no extraction, more intense peaks were produced.This suggests that baseline correction may be a cost-effective method for metabolomic analyses of fecal samples and an alternative to uf.Uf was the most versatile and efficient extraction method; however, bd and no extraction followed by baseline correction can produce comparable results.

Journal: Metabolites (2022)
Publication types: Journal Article
When the infectious environment meets the AD brain.

The amyloid theory of alzheimer's disease (ad) suggests that the deposition of amyloid β (aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors.The infectious theory linked various infectious agents with the development of ad, raising the possibility that they serve as etiological causes of the disease.Are these theories mutually exclusive, or do they coincide?Main body in this review, we will discuss how the two theories converge.We present a model by which (1) the systemic infectious burden accelerates the development of ad brain pathology via bacterial amyloids and other pathogen-associated molecular patterns (pamps), and (2) the developing ad brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived pamps, which drive neurodegeneration via activated microglia.Conclusions the reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling alzheimer's disease pathogenesis.

Journal: Molecular neurodegeneration (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't
Accuracy checking of dispensed medications by a pharmacy technician: a hospital case study.

Medication order accuracy checking is an integral and time-consuming component of the current australian pharmacist's role.However, the pharmacy profession internationally has moved towards separating the checking task into two parts: a clinical check performed by the registered pharmacist and a technical accuracy check delegated to an appropriately trained pharmacy technician.This case study demonstrates that in an australian hospital pharmacy context, appropriately trained pharmacy technicians have the potential to be more proficient and time efficient than pharmacists when undertaking accuracy checking of dispensed medications.

Journal: Australian health review : a publication of the Australian Hospital Association (2020)
Publication types: Journal Article
Bullying and Substance Use in Early Adolescence: Investigating the Longitudinal and Reciprocal Effects Over 3 Years Using the Random Intercept Cross-Lagged Panel Model.

Bullying and substance use among adolescents have been increasingly studied in the field of developmental psychology, but research to date has primarily investigated the cross-sectional relationship and, to a lesser extent, the long-term impact of bullying on substance use.Grounded in the general theory of crime, this study focused on the longitudinal reciprocal relationships between bullying and substance use (i.e., smoking and alcohol consumption) during early to mid-adolescence, which is a critical developmental phase.We aimed to investigate the hypothesis of a reinforcing downward spiral at the within-person level.Moreover, we intended to examine gender differences in the expected longitudinal relationships.Our analyses are based on self-report data for bullying and substance use collected from 1,495 adolescents (746 males;mage at t1= 12.42,sd= 0.58) at three waves between 2017 and 2019.We applied the random intercept cross-lagged panel model to separate within-person from between-person effects.At the between-person level, the mutual association between bullying and substance use, previously demonstrated in cross-sectional studies, was confirmed.At the within-person level, results provide evidence of a significant age-dependent change in bullying and substance use from 13 to 14 years old, where the significant increase in bullying could be attributed to females but not to males.We also found a gender-independent significant positive effect of bullying at 12 years old on substance use at 13 years, but not vice versa.Thus, the hypothesis of a reinforcing downward spiral, shown by significant positive reciprocal effects, did not find support.According to the general theory of crime, our findings underline that bullying can be considered a context-related factor inasmuch as it pushes adolescents to smoke and drink, which are both expressions of low levels of self-control, which need to be considered in intervention programs to effectively prevent unhealthy and risky behaviors in adolescence.

Journal: Frontiers in psychology (2020)
Publication types: Journal Article
Patterns of Perceived Indoor Environment in Danish Homes.

The indoor environment is composed of several exposures existing simultaneously.Therefore, it might be useful to combine exposures into common combined measures when used to assess the association with health.The aim of our study was to identify patterns of the perceived indoor environment.Data from the danish health and morbidity survey in the year 2000 were used.The perceived indoor environment was assessed using a questionnaire (e.g., annoyances from noise, draught, and stuffy air; 13 items in total).Factor analysis was used to explore the structure of relationships between these 13 items.Furthermore, groups of individuals with similar perceived indoor environment were identified using latent class analysis.A total of 16,688 individuals ≥16 years participated.Their median age was 46 years.Four factors were extracted from the factor analysis.The factors were characterized by: (1) a mixture of items, (2) temperature, (3) traffic, and (4) neighbor noise.Moreover, three groups of individuals sharing the same perception of their indoor environment were identified.They were characterized by: a low (n = 14,829), moderate (n = 980), and large number of annoyances (n = 879).Observational studies need to take this correlation and clustering of perceived annoyances into account when studying associations between the indoor environment and health.

Journal: International journal of environmental research and public health (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Simvastatin preparations promote PDGF-BB secretion to repair LPS-induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway.

Endothelial barrier dysfunction is a critical pathophysiological process of sepsis.Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction.Statins may have a protective effect on endothelial barrier function.However, the effect and mechanism of statins on lipopolysaccharide (lps)-induced endothelial barrier dysfunction remain unclear.Simvastatin (sv) was loaded in nanostructured lipid carriers to produce sv nanoparticles (sv-nps).Normal sv and sv-nps were used to treat human umbilical vein vascular endothelial cells (huvecs) injured by lps.Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay.Ly294002 and imatinib were used to inhibit the activity of pi3k/akt and platelet-derived growth factor receptor (pdgfr) β.Iq-gtpase-activating protein 1 (iqgap1) si rna was used to knockdown endogenous iqgap1, which was used to verify the role of the pdgfrβ/pi3k/akt/iqgap1 pathway in sv/sv-nps-mediated barrier protection in huvecs injured by lps.The results show that sv/sv-nps promoted the migration and decreased the permeability of huvecs treated with lps, and the efficacy of the sv-nps exceeded that of sv significantly.Ly294002, imatinib and iqgap1 si rna all suppressed the barrier protection of sv/sv-nps.Sv/sv-nps promoted the secretion of platelet-derived growth factor-bb (pdgf-bb) and activated the pdgfrβ/pi3k/akt/iqgap1 pathway.Sv preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the pdgfrβ/pi3k/akt/iqgap1 pathway and pdgf-bb secretion.As an appropriate formulation for restoring endothelial dysfunction, sv-nps may be more effective than sv.

Journal: Journal of cellular and molecular medicine (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review.

Brca mutation carriers have an increased risk of developing breast or ovarian cancer.Oral contraception (oc) is known to increase breast cancer and reduce ovarian cancer risk in the general population.This review analyses the published data on oc and risk of cancer in brca mutation carriers.Methods we included all relevant articles published in english from 1995 to 2018.Literature was identified through a search on pub med and cochrane library.Results we included four meta-analyses, one review, one case-control study and one retrospective cohort study on the association between ovarian cancer and oc in brca mutation carriers.All report a risk reduction for the oc users and several also describe an inverse correlation with duration of use.Regarding breast cancer, we included four meta-analyses, one review, one case-control study, two case-only studies, one prospective and one retrospective cohort study.Some studies report a risk elevation, while others did not find an association between oc use and breast cancer in brca mutation carriers.In other studies, the association was limited to early-onset breast cancer and/or associated with young age at first start of oc.Conclusion oral contraception leads to a risk reduction of ovarian cancer also in brca mutation carriers.An increase in breast cancer risk due to oc cannot be excluded.Women with brca mutation who consider oc use have to be informed about possible increase in breast cancer risk and alternative contraceptive methods.Oc should not be used for the prevention of ovarian cancer in this population.

Journal: Archives of gynecology and obstetrics (2020)
Publication types: Journal Article;Review;Systematic Review
Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro.

Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as a consequence of a prolonged inflammatory phase during the healing process.They are extremely hard to heal and persist as a significant health care problem due to the absence of effective treatment and the uprising number of patients.Indeed, there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds.Development in skin engineering leads to a small catalogue of available substitutes manufactured in good manufacturing practices compliant (gmpc) conditions.Those substitutes are produced using primary cells that could limit their use due to restricted sourcing.Here, we propose gmpc protocols to produce functional populations of keratinocytes and fibroblasts derived from pluripotent stem cells to reconstruct the associated dermo-epidermal substitute with plasma-based fibrin matrix.In addition, this manufactured composite skin is biologically active and enhances in vitro wounding of keratinocytes.The proposed composite skin opens new perspectives for skin replacement using allogeneic substitute.

Journal: Cells (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes.

Chronic kidney disease (ckd) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (gfb).Gfb is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes.Ckd with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement.Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer.Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in ckd.Experiments were carried out on drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte.Furthermore, the survival rate of gelsolin-knocked down drosophilalarvae was extensively reduced after ag no3exposure.Secondly, the in vitro podocytes treated with puromycin aminonucleoside (pan) enhanced the gelsolin protein expression, as well as small gtpase rho a and rac1, which also regulated actin dynamic expression incrementally with the pan concentrations.Thirdly, we further demonstrated in vivo that gsn was highly expressed inside the glomeruli with mitochondrial dysfunction in a ckd mouse model.Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli.

Journal: International journal of molecular sciences (2021)
Publication types: Journal Article
Phospholipase Cγ2 Is Essential for Experimental Models of Epidermolysis Bullosa Acquisita.

Phospholipase cγ2 (plcγ2) mediates tyrosine kinase‒coupled receptor signaling in various hematopoietic lineages.Although plcγ2 has been implicated in certain human and mouse inflammatory disorders, its contribution to autoimmune and inflammatory skin diseases is poorly understood.In this study, we tested the role of plcγ2 in a mouse model of epidermolysis bullosa acquisita triggered by antibodies against type vii collagen (c7), a component of the dermo-epidermal junction.Plcγ2-deficient (plcg2-/-) mice and bone marrow chimeras with a plcg2-/-hematopoietic system were completely protected from signs of anti-c7-induced skin disease, including skin erosions, dermal‒epidermal separation, and inflammation, despite normal circulating levels and skin deposition of anti-c7 antibodies.Plcγ2 was required for the tissue infiltration of neutrophils, eosinophils, and monocytes/macrophages as well as for the accumulation of proinflammatory mediators (including il-1β, mip-2, and ltb4) and reactive oxygen species.Mechanistic experiments revealed a role for plcγ2 in the release of proinflammatory mediators and reactive oxygen species but not in the intrinsic migratory capacity of leukocytes.The phospholipase c inhibitor u73122 inhibited dermal-epidermal separation of human skin sections incubated with human neutrophils in the presence of anti-c7 antibodies.Taken together, our results suggest a critical role for plcγ2 in the pathogenesis of the inflammatory form of epidermolysis bullosa acquisita.

Journal: The Journal of investigative dermatology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't