syedzayyan/paper_mill_benchmark huggingface dataset:
Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions.

Although the accessory proteins are considered non-essential for coronavirus replication, accumulating evidences demonstrate they are critical to virus-host interaction and pathogenesis.Orf9b is a unique accessory protein of sars-co v-2 and sars-co v.It is implicated in immune evasion by targeting mitochondria, where it associates with the versatile adapter tom70.Here, we determined the crystal structure of sars-co v-2 orf9b in complex with the cytosolic segment of human tom70 to 2.2 å.A central portion of orf9b occupies the deep pocket in the tom70 c-terminal domain (ctd) and adopts a helical conformation strikingly different from the β-sheet-rich structure of the orf9b homodimer.Interactions between orf9b and tom70 ctd are primarily hydrophobic and distinct from the electrostatic interaction between the heat shock protein 90 (hsp90) eevd motif and the tom70 n-terminal domain (ntd).Using isothermal titration calorimetry (itc), we demonstrated that the orf9b dimer does not bind tom70, but a synthetic peptide harboring a segment of orf9b (denoted c-peptide) binds tom70 with nanomolar kd.While the interaction between c-peptide and tom70 ctd is an endothermic process, the interaction between hsp90 eevd and tom70 ntd is exothermic, which underscores the distinct binding mechanisms at ntd and ctd pockets.Strikingly, the binding affinity of hsp90 eevd motif to tom70 ntd is reduced by ~29-fold when orf9b occupies the pocket of tom70 ctd, supporting the hypothesis that orf9b allosterically inhibits the hsp90/tom70 interaction.Our findings shed light on the mechanism underlying sars-co v-2 orf9b mediated suppression of interferon responses.

Journal: Nature communications (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Pitfalls and Common Findings in68Ga-FAPI PET: A Pictorial Analysis.

Fibroblast activation protein inhibitor (fapi) pet/ct is a new tool in the diagnostic workup of cancer.With a growing volume of applications, pitfalls and common findings need to be considered for68ga-fapi pet/ct image interpretation.The aim of this study was to summarize common findings and report pitfalls in68ga-fapi pet/ct.methods:ninety-one patients underwent whole-body pet/ct with either fapi-04 (n= 25) or fapi-46 (n= 66).Findings were rated in a consensus session of 2 experienced readers.Pitfalls and common findings were defined as focal or localized uptake above the background level and categorized as unspecific or nonmalignant and grouped into degenerative, muscular, scarring/wound-healing, uterine, mammary gland, and head-and-neck findings.The frequency of findings was reported on a per-patient and per-group basis, and suvmax, suvmean, and suvpeakwere measured.results:non-tumor-specific uptake was found in 81.3% of patients.The most frequent finding was uptake in degenerative lesions (51.6%), with a mean suvmaxof 7.7 ± 2.9, and head-and-neck findings (45.1%).Except for the salivary glands, the uptake values did not differ between 10 and 60 min after injection in most findings.Uterine uptake was found in most women (66.7%), with a mean suvmaxof 12.2 ± 7.3, and uptake correlated negatively with age (suvmax,r= -0.6,p< 0.01; suvpeak,r= -0.57,p< 0.01; suvmean,r= -0.58,p< 0.01).conclusion:pitfalls include non-tumor-specific68ga-fapi uptake in degenerative lesions, muscle, the head and neck, scarring, the mammary glands, or the uterus.Here, we summarize the findings to help readers avoid common mistakes at centers introducing68ga-fapi pet/ct.

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2022)
Publication types: Journal Article
Orthodontic force and extracorporeal shock wave therapy: Assessment of orthodontic tooth movement and bone morphometry in a rat model.

The objective was to investigate the effect of extracorporeal shock wave therapy (eswt) on the magnitude of orthodontic tooth movement, in a rat model, based on a previously established treatment protocol.Design in conjunction with orthodontic force commencement, rats underwent eswt.The amount of tooth movement along with different microarchitectural parameters were measured after three weeks by means of microcomputed tomography.In addition, the percentage of cells expressing vascular endothelial growth factor, the number of tartrate-resistant acid phosphatase (trap) positive cells/area and blood vessel density were evaluated both for the pressure and tension sides.Results the addition of eswt to the orthodontic force after three weeks more than doubled the average tooth movement.The addition of eswt on the pressure side induced a significant decrease in volumetric bone mineral density.Blood vessel density and the number of trap positive cells were higher after the application of eswt.Conclusion the induction of eswt during orthodontic tooth movement in a rat model increases the rate of tooth movement by accelerating bone resorption on the pressure side and possibly enhances bone formation on the tension side.

Journal: Archives of oral biology (2022)
Publication types: Journal Article
What vaccination rate(s) minimize total societal costs after 'opening up' to COVID-19? Age-structured SIRM results for the Delta variant in Australia (New South Wales, Victoria and Western Australia).

Using three age-structured, stochastic sirm models, calibrated to australian data post july 2021 with community transmission of the delta variant, we projected possible public health outcomes (daily cases, hospitalisations, icu beds, ventilators and fatalities) and economy costs for three states: new south wales (nsw), victoria (vic) and western australia (wa).Nsw and vic have had on-going community transmission from july 2021 and were in 'lockdown' to suppress transmission.Wa did not have on-going community transmission nor was it in lockdown at the model start date (october 11th 2021) but did maintain strict state border controls.We projected the public health outcomes and the economic costs of 'opening up' (relaxation of lockdowns in nsw and vic or fully opening the state border for wa) at alternative vaccination rates (70%, 80% and 90%), compared peak patient demand for icu beds and ventilators to staffed state-level bed capacity, and calculated a 'preferred' vaccination rate that minimizes societal costs and that varies by state.We found that the preferred vaccination rate for all states is at least 80% and that the preferred population vaccination rate is increasing with: (1) the effectiveness (infection, hospitalization and fatality) of the vaccine; (2) the lower is the daily lockdown cost; (3) the larger are the public health costs from covid-19; (4) the higher is the rate of community transmission before opening up; and (5) the less effective are the public health measures after opening up.

Journal: PLOS global public health (2022)
Publication types: Journal Article
Local structure-function relationships in human brain networks across the lifespan.

A growing number of studies have used stylized network models of communication to predict brain function from structure.Most have focused on a small set of models applied globally.Here, we compare a large number of models at both global and regional levels.We find that globally most predictors perform poorly.At the regional level, performance improves but heterogeneously, both in terms of variance explained and the optimal model.Next, we expose synergies among predictors by using pairs to jointly predict fc.Finally, we assess age-related differences in global and regional coupling across the human lifespan.We find global decreases in the magnitude of structure-function coupling with age.We find that these decreases are driven by reduced coupling in sensorimotor regions, while higher-order cognitive systems preserve local coupling with age.Our results describe patterns of structure-function coupling across the cortex and how this may change with age.

Journal: Nature communications (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Inspiratory Airway Resistance in Respiratory Failure Due to COVID-19.

To measure inspiratory airflow resistance in patients with acute respiratory distress syndrome (ards) due to covid-19.Design observational cohort of a convenience sample.Setting three community icus.Subjects fifty-five mechanically ventilated patients with covid-19.Interventions measurements of ventilatory mechanics during volume control ventilation.Measurements flow-time and pressure-time scalars were used to measure inspiratory airways resistance.Results the median inspiratory airflow resistance was 12 cm h2o/l/s (interquartile range, 10-16).Inspiratory resistance was not significantly different among patients with asthma or chronic obstructive pulmonary disease compared with those without a history of obstructive airways disease (median 12.5 vs 12 cm h2o/l/s, respectively;p= 0.66).Survival to 90 days among patients with inspiratory resistance above 12 cm h2o/l/s was 68% compared with 60% for patients below 12 cm h2o/l/s (p= 0.58).Inspiratory resistance did not correlate with c-reactive protein, ferritin, pao2/fio2ratio, or static compliance.Conclusions inspiratory airflow resistance was normal to slightly elevated among mechanically ventilated patients with ards due to covid-19.Airways resistance was independent of a history of obstructive airways disease, did not correlate with biomarkers of disease severity, and did not predict mortality.

Journal: Critical care explorations (2022)
Publication types: Journal Article
Biology of Cardiac Troponins: Emphasis on Metabolism.

Understanding of the biology of endo- and exogenous molecules, in particular their metabolism, is not only of great theoretical importance, but also of high practical significance, since many molecules serve as drug targets or markers for the laboratory diagnostics of many human diseases.Thus, cardiac troponin (c tns) molecules have long been used as key markers for the confirmation of diagnosis of myocardial infarction (mi), and with the introduction of contemporary (high sensitivity) test methods, many of our concepts related to the biology of these cardiac markers have changed significantly.In current clinical practice, there are opening new promising diagnostic capabilities of c tns, the understanding and justification of which is closely connected with the theoretical principles of the metabolism of these molecules.However, today, the biology and metabolism of c tns have not been properly investigated; in particular, we do not know the precise mechanisms of release of these molecules from the myocardial cells (mcs) of healthy people and the mechanisms of circulation, and the elimination of c tns from the bloodstream.The main purpose of this manuscript is to systematize information about the biology of c tns, with an emphasis on the metabolism of c tns.The format of this paper, starting with the release of c tns in the blood and concluding with the metabolism/filtration of troponins, provides a comprehensive yet logically easy way for the readers to approach our current knowledge in the framework of understanding the basic mechanisms by which c tns are produced and processed.Conclusions.Based on the analysis of the current literature, the important role of biology and all stages of metabolism (release, circulation, removal) of c tns in laboratory diagnostics should be noted.It is necessary to continue studying the biology and metabolism of c tns, because this will improve the differential diagnosis of mi and i a new application of c tns immunoassays in current clinical practice.

Journal: Biology (2022)
Publication types: Journal Article;Review
Host gut microbiome and potential therapeutics in Gulf War Illness: A short review.

S since our troops had returned from the first persian gulf war in 1990-91, the veterans have reported chronic multisymptomatic illness widely referred to as gulf war illness (gwi).We aim to review the current directions of gwi pathology research in the context of chronic multisymptomatic illness and its possible gut microbiome targeted therapies.The veterans of gulf war show symptoms of chronic fatigue, cognitive deficits, and a subsection report of gastrointestinal complications.Method efforts of finding a suitable treatment regimen and clinical management remain a challenge.More recently, we have shown that the pathology is connected to alterations in the gut microbiome, and efforts of finding a suitable regimen for gut-directed therapeutics are underway.We discuss the various clinical interventions and summarize the possible effectiveness of gut-directed therapies such as the use of short-chain fatty acids (scfa), phenolic compounds, and their metabolites, use of probiotics, and fecal microbiota transfer.Significance the short review will be helpful to gwi researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.

Journal: Life sciences (2021)
Publication types: Journal Article;Review
Examining the Educational Gap for Children with ADHD and Subthreshold ADHD.

The present study examined the impact of attention deficit hyperactivity disorder (adhd) on core educational outcomes in two large community cohorts of australian school children.Method academic (reading and numeracy) and non-academic (school engagement, attendance, peer victimization, and parental expectations) outcomes were compared between children with adhd, subthreshold adhd, and controls when children were in grade 5 (m age = 10.5).Data were drawn from the longitudinal study of australian children birth cohort (lsac;n= 3,540) and the children's attention project (cap;n= 356).Results both subthreshold adhd and adhd groups had poorer outcomes on all measures, with medium effects sizes.Differences were not evident between subthreshold adhd and adhd groups.Conclusions educational outcomes examined in this study highlight the educational risk for upperprimary school children with adhd or subthreshold adhd, in comparison to their peers.Monitoring these outcomes is necessary to inform policy, practice, and intervention.

Journal: Journal of attention disorders (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in theDrosophilaembryo.

The evolutionarily conserved toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects.In the drosophilaembryo, toll is required to establish gene expression domains along the dorsal-ventral axis.Pathway activation induces degradation of the iκb inhibitor cactus, resulting in a ventral-to-dorsal nuclear gradient of the nfκb effector dorsal.Here, we investigate howcactusmodulates toll signals through its effects on the dorsal gradient and on dorsal target genes.Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the dorsal gradient can behave differently with respect to cactus fluctuations.In lateral and dorsal embryo domains, loss of cactus allows more dorsal to translocate to the nucleus.Unexpectedly,cactusloss-of-function alleles decrease dorsal nuclear localization ventrally, where toll signals are high.Overexpression analysis suggests that this ability of cactus to enhance toll stems from the mobilization of a free cactus pool induced by the calpain a protease.These results indicate that cactus acts to bolster dorsal activation, in addition to its role as a nfκb inhibitor, ensuring a correct response to toll signals.

Journal: Development (Cambridge, England) (2017)
Publication types: Journal Article
Adhesion molecule cross-linking and cytokine exposure modulate IgE- and non-IgE-dependent basophil activation.

Basophils are known for their role in allergic inflammation, which makes them suitable targets in allergy diagnostics such as the basophil activation test (bat) and the microfluidic immunoaffinity basophil activation test (mi bat).Beside their role in allergy, basophils have an immune modulatory role in both innate immunity and adaptive immunity.To accomplish this mission, basophils depend on the capability to migrate from blood to extravascular tissues, which includes interactions with endothelial cells, extracellular matrix and soluble mediators.Their receptor repertoire is well known, but less is known how these receptor-ligand interactions impact the degranulation process and the responsiveness to subsequent activation.As the consequences of these interactions are crucial to fully appreciate the role of basophils in immune modulation and to enable optimization of the mi bat, we explored how basophil activation status is regulated by cytokines and cross-linking of adhesion molecules.The expression of adhesion molecules and activation markers on basophils from healthy blood donors was analysed by flow cytometry.Cross-linking of cd203c, cd62l, cd11b and cd49d induced a significant upregulation of cd63 and cd203c.To mimic in vivo conditions, valid also for mi bat, cd62l and cd49d were cross-linked followed by ig e-dependent activation (anti-ig e), which caused a reduced cd63 expression compared with anti-ig e activation only.Il-3 and il-33 priming caused increased cd63 expression after ig e-independent activation (f mlp).Together, our data suggest that mechanisms operational both in the microfluidic chip and in vivo during basophil adhesion may impact basophil anaphylactic and piecemeal degranulation procedures and hence their immune regulatory function.

Journal: Immunology (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Review and analysis of biologic therapies currently in phase II and phase III clinical trials for atopic dermatitis.

Biologic medications are recent advances that have clinical significance in the treatment of moderate-to-severe ad.A systemic literature review was performed to examine the efficacy and safety of biologic therapies currently in phase ii and phase iii of clinical trials for moderate-to-severe ad.Our team searched the databases, pub med, google scholar, and clinical trials.gov, on september 2019 for studies pertaining to the use of biologic drugs in ad.Key words included each drug (lebrikizumab, tralokinumab, fezakinumab, etokimab, nemolizumab, tezepelumab, and gbr 830) or 'biologic drugs' or 'immunotherapies' combined with 'atopic dermatitis.' references within retrieved articles were also reviewed to identify potentially missed studies.A total of 19 articles were included in this review.Lebrikizumab, tralokinumab, fezakinumab, nemolizumab, and gbr 830 lead to statistically significant improvements in disease severity and multiple endpoint outcome scores.Tezepelumab and etokimab, however, did not demonstrate statistically significant changes in primary outcome endpoints.Further assessment of tezepelumab and etokimab are needed to assess their safety and efficacy in patients with moderate-to-severe ad.Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and gbr 830 are effective treatment options for adults with moderate-to-severe ad, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe ad.

Journal: The Journal of dermatological treatment (2022)
Publication types: Journal Article;Review
Abuse detection in healthcare insurance with disease-treatment network embedding.

Abuse in healthcare insurance refers to a medical service or practice inconsistent with the generally accepted sound fiscal practices, such as overtreatment or overcharging.These types of abuses may lead to prescriptions that do not meet the criteria for medical stability.On the other hand, abuse may incur unnecessary costs by deliberately executing gratuitous treatments.In efforts to detect and prevent abuse, insurance companies hire medical professionals to manually examine the legitimacy of claim filings.It is, however, very costly in terms of labor and time to review all of the claims given the exploding amount of filings.In this light, there are growing interests for employing data mining techniques to automatically detect abusive claims or providers showing an abnormal billing pattern.Unfortunately, most of these models do not consider the disease-treatment information explicitly.In order for detection models to properly address the issues rising from individual drugs with similar efficacy, it is absolutely essential to account for the relationship between diseases and treatments during the learning process.In this paper, we propose a network-based approach which assesses the relationship between the diseases and treatments when detecting abuse from claim filings.Our proposed model consists of three stages.During the first stage, a disease-treatment network is constructed based on information extracted from the claim filings.Since the association between diseases and treatments is not explicitly expressed on these filings, we infer the disease-treatment relationship by computing the relative risk (rr).Second stage involves selecting the best graph embedding method from several candidates.We select the best method by comparing performances on link prediction.At the final stage, we solve a link prediction problem as a vehicle to detecting overtreatments.If our link prediction model predicts links to be nonexistent for all of the diseases and treatments listed in a given claim, then the claim is classified as an overtreatment case.We test the proposed model using the real-world claim data and showed that the proposed method classifies the treatment well which does not explicitly exist in the training network.

Journal: Journal of biomedical informatics (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Characterization of multiple enolase genes from Trichomonas vaginalis. Potential novel targets for drug and vaccine design.

Trichomonas vaginalis is the protist parasite that causes the most common, non-viral sexually transmitted infection called trichomonosis.Enolase is a moonlighting protein that apart from its canonical function as a glycolytic enzyme, serves as a plasminogen receptor on the cell surface of t.Vaginalis and, in consequence, it has been stablished as a virulence factor in this parasite.In the trichomonas vaginalis sequence database there are nine genes annotated as enolase.In this work, we analyzed these genes as well as their products.We found that seven out of nine genes might indeed perform enolase activity, whereas two genes might have been equivocally identified, or they might be pseudogenes.Furthermore, a combination of q rt-pcr and proteomic approaches was used to assess, for the first time, the expression of these genes in the highly virulent mexican isolate of t.Vaginalis cncd-147 at different iron concentrations.We could find peptides corresponding to enolases encoded by genes tvag_464170, tvag_043500 and tvag_329460.Moreover, we identified two distinctive characteristics within enolases from trichomonas vaginalis.One of them corresponds to three key substitutions within one of the loops of the active site, compared to host enolase.The other, is a unique n-terminal motif, composed of 15 to 18 residues, on all the potentially active enolases, whose function still has to be stablished.Both differential features merit further studies as potential drug and vaccine targets as well as diagnosis markers.These findings offer new possibilities to fight trichomonosis.

Journal: Parasitology international (2018)
Publication types: Journal Article