syedzayyan/paper_mill_benchmark huggingface dataset:
Evaluation of the representativeness of data in the COVID-19 Registry Japan during the first six waves of the epidemic.

The covid-19 registry japan (coviregi-jp), a registry of patients hospitalized with coronavirus disease (covid-19), contains the largest national covid-19 inpatient population.Since coviregi-jp invites voluntary participation by facilities, selection bias is inevitable.The current study examined the representativeness of coviregi-jp data in comparison to open-source national data.The number of infections and deaths among hospitalized covid-19 patients in coviregi-jp were compared to those in national data recorded during the six waves of the covid-19 epidemic until march 6, 2022.During the period studied, patients in coviregi-jp represented 1% of the total covid-19 cases according to national data; the proportion was high during the first wave (32.7%) and tended to decrease, especially after the fourth wave.The overall proportion of patients from each region varied from 0.8% to 2.5%, but case fatality rates in coviregi-jp tended to be higher than those in the national data, with the exception of a few waves, in several regions.The difference was smallest during the first wave.Although coviregi-jp consistently registered cases from all regions of the country, the proportion tended to decline after the beginning of the epidemic.Given the epidemiological persistence and the ever-changing epidemiology of covid-19, continued case registration and data utilization in coviregi-jp is desirable, although selection bias in coviregi-jp registration of cases should be carefully interpreted.

Journal: Global health & medicine (2022)
Publication types: Journal Article;Review
Rapamycin Modulates the Proinflammatory Memory-Like Response of Microglia Induced by BAFF.

Recently trained immunity of microglia provided an opportunity to study the chronic effect of microglial activation and its metabolic rewiring in neuroimmunological diseases.Since elevated levels of b cell-activating factor (baff) have been proved to be associated with some chronic neuroimmunological disorders.Here, we used the trained innate immunity model to analyze the effect of baff, a vital regulator of the adaptive immune system, on long-term microglial activation and metabolic reprogrammingin vitroandin vivo.Methods and results in vitro, bv2 cells and mouse primary microglial cells were incubated with baff for 24 h (baff priming).After 5 days of resting, microglia were restimulated with lps (lps restimulation) or baff (baff restimulation).Baff priming induced a pro-inflammatory trained immunity-phenotype of both bv2 cells and primary microglial cells, which was indicated by morphological change, secretion of pro-inflammatory cytokine and chemokine upon lps restimulation or baff restimulation.The production of lactate and nad+/nadh ratio were elevated 5 days after baff priming.The activation of the akt/m tor/hif-1α pathway was induced by baff priming and lasted for 5 days.Pretreating the bv2 cells or mouse primary microglial cells with rapamycin blocked m tor/hif-1α activation and cellular metabolic reprogramming induced by baff training.Consistently, rapamycin efficiently suppressed the trained immunity-like responses of microglia triggered by baff.In vivo, adult male mice were treated with baff by intracerebroventricular injection for priming and 7 days later with baff for restimulation.Baff training activated microglia in the cortex and hippocampus.The production of proinflammatory cytokines and chemokines was elevated after baff training.Conclusion our current data, for the first time, demonstrate that baff priming induces a proinflammatory memory-like response of microglia not only to lps but also to baff itself.Rapamycin inhibits microglial priming triggered by baff through targeting the m tor/hif-1α signaling pathway.Our data reveal a novel role of baff in trained immunity and that rapamycin may be a potential therapeutic target of neuroimmunological diseases.

Journal: Frontiers in immunology (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Extracellular matrix-inspired inhalable aerogels for rapid clearance of pulmonary tuberculosis.

Tuberculosis (tb) remains a leading cause of death from a single infectious agent, and limiting the spread of multidrug-resistant tb (mdr-tb) is now an urgent global health priority.Essential to the persistence of this disease is the ability of mycobacterium tuberculosis (mtb) to circumvent host defenses by infecting lung macrophages to create a cellular niche for its survival and proliferation.This has urged the development of new therapeutic strategies that act through mechanisms distinct from conventional antibiotics, and thus are effective against mdr bacteria, while being able to efficiently kill persister mtb cells in infected host macrophages.Here, we report a new class of gel-like microparticle aerosols, or 'aerogels', designed to exploit metabolic vulnerabilities of mtb pathogens and tb-infected macrophages to enable preferential delivery of synergistic peptide-antibiotic combinations for potent and rapid antitubercular therapy.This is achieved by formulating aerogels through the supramolecular assembly of a de novo designed anti-tb peptide and the extracellular matrix (ecm)-derived polysaccharide, hyaluronic acid (ha).Importantly, ha serves as a nutrient source for mtb cells during tissue invasion and proliferation, and is recognized by cd44 receptors highly expressed on lung macrophages during tb infection.By exploiting this metabolic substrate for pathogen targeting, ha aerogels are shown to avidly bind and kill both drug-sensitive and drug-resistant mycobacteria, while being efficiently internalized into macrophage host cells in vitro and in vivo to clear mtb persisters.This multifaceted bioactivity suggests aerogels may serve as a versatile inhalable platform upon which novel biomaterials-enabled therapeutics can be developed to rapidly clear pulmonary mdr-tb.

Journal: Biomaterials (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Flavonoids bridging the gut and the brain: Intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration.

In recent years, experimental evidence suggested a possible role of the gut microbiota in the onset and development of several neurodegenerative disorders, such as ad and pd, ms and pain.Flavonoids, including anthocyanins, egcg, the flavonol quercetin, and isoflavones, are plant polyphenolic secondary metabolites that have shown therapeutic potential for the treatment of various pathological conditions, including neurodegenerative diseases.This is due to their antioxidant and anti-inflammatory properties, despite their low bioavailability which often limits their use in clinical practice.In more recent years it has been demonstrated that flavonoids are metabolized by specific bacterial strains in the gut to produce their active metabolites.On the other way round, both naturally-occurring flavonoids and their metabolites promote or limit the proliferation of specific bacterial strains, thus profoundly affecting the composition of the gut microbiota which in turn modifies its ability to further metabolize flavonoids.Thus, understanding the best way of acting on this virtuous circle is of utmost importance to develop innovative approaches to many brain disorders.In this review, we summarize some of the most recent advances in preclinical and clinical research on the neuroinflammatory and neuroprotective effects of flavonoids on ad, pd, ms and pain, with a specific focus on their mechanisms of action including possible interactions with the gut microbiota, to emphasize the potential exploitation of dietary flavonoids as adjuvants in the treatment of these pathological conditions.

Journal: Biochemical pharmacology (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't
Intramuscular myxoma of the longus colli mistaken for a cervical rootlet schwannoma.

An 86-year-old woman was referred to the otolaryngology clinic for a 1-year history of a painless, slow-growing neck mass.Physical examination showed a fixed, immobile right level ii neck mass with normal vocal cord movement.Mri demonstrated a lobulated mass laterally displacing the carotid vessels, consistent with a schwannoma.Despite the pathognomonic radiographic findings for schwannoma, core needle biopsy of the mass was consistent with intramuscular myxoma (im), which rarely presents in the head and neck region.After multiple years of slow growth with bulging into the pharynx, the patient ultimately underwent surgery to reduce the risk of airway compromise.The location of this im together with its unusual imaging appearance is a unique finding in the head and neck and adds to the differential diagnoses for neck masses displacing the carotid sheath.

Journal: BMJ case reports (2021)
Publication types: Case Reports;Journal Article
Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers.The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites.Extracellular vesicles (evs) are emerging as promising clinical biomarkers in liquid biopsy.Here, we aimed to investigate robust liquid biopsy-based ev mi rna biomarkers for ovarian cancer diagnosis and metastasis regulation.Evs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases.Ev small rna sequencing identified a panel of eight mi rnas (mi r-1246, mi r-1290, mi r-483, mi r-429, mi r-34b-3p, mi r-34c-5p, mi r-145-5p, mi r-449a) based on dysregulated mi rnas overlapped in the ascites and plasma subset.The ovarian cancer ev mi rna (ocem) signature developed based on these eight mi rnas demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine).In addition, malignant ascites-derived evs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids.Notably, mi r-1246 and mi r-1290 shuttled in malignant ascites-derived evs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target rorα.

Journal: Cancer letters (2022)
Publication types: Journal Article
A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.

The α7 nicotinic acetylcholine receptor (n ach r) is present in neuronal and non-neuronal cells and has anti-inflammatory actions.Molecular dynamics simulations suggested that α7 n ach r interacts with a region of the sars-co v-2 spike protein (s), and a potential contribution of n ach rs to covid-19 pathophysiology has been proposed.We applied whole-cell and single-channel recordings to determine whether a peptide corresponding to the y674-r685 region of the s protein can directly affect α7 n ach r function.The s fragment exerts a dual effect on α7.It activates α7 n ach rs in the presence of positive allosteric modulators, in line with our previous molecular dynamics simulations showing favourable binding of this accessible region of the s protein to the n ach r agonist binding site.The s fragment also exerts a negative modulation of α7, which is evidenced by a profound concentration-dependent decrease in the durations of openings and activation episodes of potentiated channels and in the amplitude of macroscopic responses elicited by ach.Our study identifies a potential functional interaction between α7 n ach r and a region of the s protein, thus providing molecular foundations for further exploring the involvement of n ach rs in covid-19 pathophysiology.

Journal: Molecular neurobiology (2022)
Publication types: Journal Article
Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report.

Epidermal growth factor receptor (egfr) triple mutations with exon 19 deletion (del19), t790m, and cis-c797s (del19/t790m/cis-c797s mutations) frequently occur in patients with non-small cell lung cancer (nsclc), while progression to frontline egfr-tyrosine kinase inhibitors (tkis) and osimertinib was resistant to all clinically available egfr-tkis.Brigatinib monotherapy may be a potential treatment for nsclc harboring del19/t790m/cis-c797s mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on egfrdel19/t790m/cis-c797s mutations.Herein, we present a case of a female patient with egfrdel19-mutated nsclc treated with afatinib followed by osimertinib due to acquired t790m mutation.The egfrdel19/t790m/cis-c797s mutations were detected following osimertinib treatment.Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily).Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage.This report provides the first reported evidence for the use of brigatinib monotherapy in patients with nsclc harboring egfrdel19/t790m/cis-c797s mutations after progression to previous egfr-tkis.

Journal: International journal of molecular sciences (2022)
Publication types: Case Reports;Journal Article
Functional specificity and neural integration in the aesthetic appreciation of artworks with implied motion.

Although there is growing interest in the neural foundations of aesthetic experience, it remains unclear how particular mental subsystems (e.g.Perceptual, affective and cognitive) are involved in different types of aesthetic judgements.Here, we use f mri to investigate the involvement of different neural networks during aesthetic judgements of visual artworks with implied motion cues.First, a behavioural experiment (n = 45) confirmed a preference for paintings with implied motion over static cues.Subsequently, in a preregistered f mri experiment (n = 27), participants made aesthetic and motion judgements towards paintings representing human bodies in dynamic and static postures.Using functional region-of-interest and bayesian multilevel modelling approaches, we provide no compelling evidence for unique sensitivity within or between neural systems associated with body perception, motion and affective processing during the aesthetic evaluation of paintings with implied motion.However, we show suggestive evidence that motion and body-selective systems may integrate signals via functional connections with a separate neural network in dorsal parietal cortex, which may act as a relay or integration site.Our findings clarify the roles of basic visual and affective brain circuitry in evaluating a central aesthetic feature-implied motion-while also pointing towards promising future research directions, which involve modelling aesthetic preferences as hierarchical interplay between visual and affective circuits and integration processes in frontoparietal cortex.

Journal: The European journal of neuroscience (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Effect of Functionalized Benzene Derivatives as Potential Hole Scavengers for BiVO4and rGO-BiVO4Photoelectrocatalytic Hydrogen Evolution.

Sustainable hydrogen production is one of the main challenges today in the transition to a green and sustainable economy.Photocatalytic hydrogen production is one of the most promising technologies, amongst which bi vo4-based processes are highly attractive due to their suitable band gap for solar-driven processes.However, the performance of bi vo4alone in this role is often unsatisfactory.Herein we report the improvement of bi vo4performance with reduced graphene oxide (r go) as a co-catalyst for the photoelectrochemical water splitting (pec-ws) in the presence of simple functionalized benzene derivatives (sfbds), i.e., phenol (ph), benzoic acid (ba), salicylic acid (sa), and 5-aminosalicylic acid (5-asa) as potential photogenerated hole scavengers from contaminated wastewaters.Linear sweep voltammetry and chronoamperometry, along with electrochemical impedance spectroscopy were utilized to elucidate pec-ws performance under illumination.R go has remarkably improved the performance of bi vo4in this role by decreasing photogenerated charge recombination.In addition, 5-asa greatly improved current densities.After 120 min under led illumination, 0.53 μmol of h2was produced.The type and concentration of sfbds can have significant and at times opposite effects on the pec-ws performance of both bi vo4and r go-bi vo4.

Journal: Molecules (Basel, Switzerland) (2022)
Publication types: Journal Article
Effect of salinity stress on respiratory metabolism, glycolysis, lipolysis, and apoptosis in Pacific oyster (Crassostrea gigas) during depuration stage.

Depuration is an important process performed to ensure the safety of oyster consumption, and the effect of salinity stress on physiological and ecological characteristics of oyster remains unknow.In this study, the simulated depuration of crassostrea gigas was performed with the salinities varying from ±10% to ±20% away from that of production area (26, 28, 32, 35, and 38 g l-1), as well as respiratory metabolism, glycolysis, lipolysis, and apoptosis were analyzed.Results (i) the oxygen consumption rate, ammonia discharge rate and enzyme activities related to respiratory metabolism were decreased significantly at salinities of 38 g l-1, indicating that salinity stress triggered the abnormal respiratory metabolism of c.Gigas, further, glycolysis was enhanced.(ii) glycogen decomposition, lactic acid increase, and fatty acid composition modifications were caused by adenosine monophosphate (amp)-activated protein kinase (ampk) -mediated during salinity stress.(iii) there was a clear decrease of the condition index and meat yield of c.Gigas after 72 h of depuration, especially in salinity 38 g l-1.(iv) salinity stress would lead to the increase of cytochrome c levels, then cause apoptosis of c.Gigas, while heat shock protein 70 (hsp70) would interfere with this process.Conclusion salinity stress had a significant effect on the physiological and ecological response of c.Gigas during the depuration process, including respiratory metabolism, glycolysis, lipolysis, and apoptosis.In general, the low depuration salinity fluctuation (±10%) is helpful to maintain quality of c.Gigas, as well as the optimal depuration time was 48 h.© 2021 society of chemical industry.

Journal: Journal of the science of food and agriculture (2022)
Publication types: Journal Article
Long-term objective and subjective outcomes following bilateral implantation of diffractive bifocal or trifocal intraocular lenses.

To evaluate and compare the objective and subjective outcomes after the bilateral implantation of a diffractive bifocal and trifocal intraocular lens.Methods this is a case-control, single-center observational study which included 27 patients; 16 patients were implanted bilaterally with the bifocal acry sof iq re stor+3.0d and 11 patients with the trifocal at lisa tri 839mp.Uncorrected visual acuity at distance, intermediate, and near under mesopic and photopic conditions using etdrs charts with 10% and 100% contrast, corrected distance visual acuity, and binocular defocus curve in photopic conditions; binocular contrast sensitivity under mesopic and photopic conditions for far and near distances were assessed.The visual function questionnaire-25 questionnaire was used to assess patients' satisfaction.All the measurements were performed 6-24 months after cataract surgery.Results the re stor group had better binocular uncorrected near visual acuity in photopic conditions with low and high contrast charts (p= 0.040 andp= 0.033, respectively), as well as in far contrast sensitivity measurement under mesopic conditions with a spatial frequency of 3 cycles per degree (p= 0.034).There was not a significant difference between the two study groups in uncorrected near, intermediate or distance vision under mesopic conditions.The at lisa tri study group had better subjective outcomes.Conclusion both intraocular lenses restore visual acuity after cataract surgery.The re stor intraocular lens provides better objective outcomes than the at lisa tri, although the latter provides better subjective outcomes.The relevance of this study is the evaluation of both objective and subjective outcomes.

Journal: European journal of ophthalmology (2021)
Publication types: Journal Article;Observational Study
Cascade π-Extended Decarboxylative Annulation Involving Cyclic Diaryliodonium Salts: Site-Selective Synthesis of Phenanthridines and Benzocarbazoles via a Traceless Directing Group Strategy.

A novel cascade π-extended decarboxylative annulation (peda) involved with cyclic diaryliodonium salts is described.Via fine-tuning of the reaction conditions, the pd(ii)-catalyzed site-selective n1/c2 or c2/c3 annulation of commercially available indole-2-carboxylic acids can be achieved, affording valuable phenanthridines or benzocarbazoles, respectively.The key strategy is the carboxylic acid functionality being employed as both a traceless directing group for theortho c-n or c-c coupling and a reactive group for the cascade π-extended decarboxylative annulation in a highly step economical manner.

Journal: Organic letters (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Simple yet effective methods to probe hydrogel stiffness for mechanobiology.

In spite of tremendous advances made in the comprehension of mechanotransduction, implementation of mechanobiology assays remains challenging for the broad community of cell biologists.Hydrogel substrates with tunable stiffness are essential tool in mechanobiology, allowing to investigate the effects of mechanical signals on cell behavior.A bottleneck that slows down the popularization of hydrogel formulations for mechanobiology is the assessment of their stiffness, typically requiring expensive and sophisticated methodologies in the domain of material science.Here we overcome such barriers offering the reader protocols to set-up and interpret two straightforward, low cost and high-throughput tools to measure hydrogel stiffness: static macroindentation and micropipette aspiration.We advanced on how to build up these tools and on the underlying theoretical modeling.Specifically, we validated our tools by comparing them with leading techniques used for measuring hydrogel stiffness (atomic force microscopy, uniaxial compression and rheometric analysis) with consistent results on paa hydrogels or their modification.In so doing, we also took advantage of yap/taz nuclear localization as biologically validated and sensitive readers of mechanosensing, all in all presenting a suite of biologically and theoretically proven protocols to be implemented in most biological laboratories to approach mechanobiology.

Journal: Scientific reports (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't