syedzayyan/paper_mill_benchmark huggingface dataset:
Opicapone as an Add-on to Levodopa in Patients with Parkinson's Disease Without Motor Fluctuations: Rationale and Design of the Phase III, Double-Blind, Randomised, Placebo-Controlled EPSILON Trial.

Introduction levodopa remains the cornerstone treatment for parkinson's disease (pd) but its use is associated with the development of 'wearing-off' fluctuations and other motor and non-motor complications over time.Adding a catechol-o-methyltransferase (comt) inhibitor to levodopa/dopa decarboxylase (ddc) inhibitor therapy reduces fluctuations in the profile of plasma levodopa levels following oral dosing, and can therefore be beneficial for the management of motor complications.The objective of the epsilon study is to investigate the efficacy of opicapone (opc; a third-generation, once-daily comt inhibitor) in enhancing the clinical benefit of levodopa in patients in earlier stages of pd, without end-of-dose motor fluctuations.Methods epsilon is a phase iii, double-blind, randomised, placebo-controlled and parallel-group study, designed to evaluate the efficacy and safety of opc as add-on to levodopa/ddc inhibitor therapy in patients with early pd who do not exhibit signs of motor complications.Eligible patients will be randomised (1:1) to receive opc 50 mg or placebo, in addition to their existing levodopa/ddc inhibitor therapy, over a 24-week, double-blind treatment period, after which they will have the option of entering an additional 1-year, open-label extension period, during which all patients will receive opc 50 mg.Planned outcomes the primary efficacy endpoints are change in movement disorders society unified parkinson's disease rating scale (mds-updrs) part iii total score from baseline to the end of the double-blind period (double-blind phase) and change in mds-updrs part iv total score from open-label baseline to the end of the open-label period (open-label phase).Secondary outcomes during the double-blind phase will include other measures of pd symptoms, including quality of life, non-motor symptoms, and development of motor fluctuations.Safety assessments will include evaluation of treatment-emergent adverse events, laboratory safety parameters, suicidality and impulse control disorders.Trial registration european union drug regulating authorities clinical trials database (number 2020-005011-52).

Journal: Neurology and therapy (2022)
Publication types: Journal Article
Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response.

Tyrosine kinase inhibitors (tkis) as first-line therapy for chronic myeloid leukemia (cml) show a high success rate.However, a low number of patients with long-term treatment-free remission (tfr) were observed.Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months.One of the reasons for relapse is untimely tkis discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for cml.Methods next generation sequencing (ngs) was used to identify micro rnas (mi rnas) at the molecular response in cml adult patients receiving tkis treatment.A total of 86 samples were collected, 30 from cml patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors.Ngs was conducted whereby 18 mi rnas were selected and validated by real-time rt-q pcr in triplicate.Results hsa-mi r-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-mi r-182-5p and hsa-mi r-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation.The down-regulation was consistent with decreased amounts of bcr-abl1 in patients taking tkis regardless of molecular responses.The up-regulation was consistent with the substantial presence of bcr-abl1 in cml patients treated with tkis at the molecular response.Conclusions therefore, these mi rnas have potential as new therapeutic biomarkers for bcr-abl1 status in adult cml patients treated with tkis at molecular responses.These could improve current approaches and require further analysis to look for targets of these mi rnas in cml.

Journal: BMC cancer (2022)
Publication types: Journal Article
Prediction of White Matter Hyperintensity in Brain MRI Using Fundus Photographs via Deep Learning.

We investigated whether a deep learning algorithm applied to retinal fundoscopic images could predict cerebral white matter hyperintensity (wmh), as represented by a modified fazekas scale (fs), on brain magnetic resonance imaging (mri).Methods participants who had undergone brain mri and health-screening fundus photography at hallym university sacred heart hospital between 2010 and 2020 were consecutively included.The subjects were divided based on the presence of wmh, then classified into three groups according to the fs grade (0 vs.1 vs.2+) using age matching.Two pre-trained convolutional neural networks were fine-tuned and evaluated for prediction performance using 10-fold cross-validation.Results a total of 3726 fundus photographs from 1892 subjects were included, of which 905 fundus photographs from 462 subjects were included in the age-matched balanced dataset.In predicting the presence of wmh, the mean area under the receiver operating characteristic curve was 0.736 ± 0.030 for dense net-201 and 0.724 ± 0.026 for efficient net-b7.For the prediction of fs grade, the mean accuracies reached 41.4 ± 5.7% with dense net-201 and 39.6 ± 5.6% with efficient net-b7.The deep learning models focused on the macula and retinal vasculature to detect an fs of 2+.Conclusions cerebral wmh might be partially predicted by non-invasive fundus photography via deep learning, which may suggest an eye-brain association.

Journal: Journal of clinical medicine (2022)
Publication types: Journal Article
Homogeneity assessment of the SuperCam calibration targets onboard rover perseverance.

The super cam instrument, onboard the perseverance rover (mars 2020 mission) is designed to perform remote analysis on the martian surface employing several spectroscopic techniques such as laser induced breakdown spectroscopy (libs), time-resolved raman (trr), time-resolved fluorescence (trf) and visible and infrared (visir) reflectance.In addition, super cam also acquires high-resolution images using a color remote micro-imager (rmi) as well as sounds with its microphone.Super cam has three main subsystems, the mast unit (mu) where the laser for chemical analysis and collection optics are housed, the body unit (bu) where the different spectrometers are located inside the rover, and the super cam calibration target (scct) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples.To perform adequate calibrations on mars, the 22 mineral samples included in the complex scct assembly must have a very homogeneous distribution of major and minor elements.The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the scct has been the aim of this work.To verify the physic-chemical homogeneity of the calibration targets, micro energy dispersive x-ray fluorescence (edxrf) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 μm.For those targets showing a positive raman response, micro-raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 μm.The %rsd values (percent of relative standard deviation of mean values) for the major elements measured with edxrf were compared with similar values obtained by two independent libs set-ups at spot sizes of 300 μm in diameter.The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the scct, providing their uncertainty values for further calibration.Moreover, nine of the 22 targets showed a good raman response and their mineral distributions were also studied.Those targets can be also used for calibration purposes of the raman part of super cam using the wavenumbers of their main raman bands proposed in this work.

Journal: Analytica chimica acta (2022)
Publication types: Journal Article
Hypothalamic microinflammation.

Over the past decade, hypothalamic microinflammation has been studied and appreciated as a core mechanism involved in the advancement of metabolic syndrome and aging.Accumulating evidence suggests that atypical microinflammatory insults disturb hypothalamic regulation resulting in metabolic imbalance and aging progression, establishing a common causality for these two pathophysiologic statuses.Studies have causally linked these changes to activation of key proinflammatory pathways, especially nf-κb signaling within the hypothalamus, which leads to hypothalamic neuronal dysregulation, astrogliosis, microgliosis, and loss of adult hypothalamic neural stem/progenitor cells.While hypothalamic microinflammation is a complex, multifaceted process, initial work has been done to reveal how it contributes to the pathogenesis of metabolic syndrome and aging, and studies inhibiting hypothalamic microinflammation through targeting proinflammatory signaling pathways have shown to be beneficial against these disorders and diseases.In this chapter, we provide a broad overview on hypothalamic microinflammation, focusing on its features, inducers, and shared pathogenic roles in metabolic syndrome and aging.

Journal: Handbook of clinical neurology (2021)
Publication types: Journal Article;Review
Nuclear Magnetic Resonance Dipolar Cross-Relaxation Interaction between Nanoconfined Fluids and Matrix Solids.

Many different methods have been developed to investigate fluid-solid interactions in nanoporous systems.These methods either only work in the liquid phase or provide an indirect measurement by probing the fluid-solid interaction based on a measured property change of the fluid or solid under different sample conditions.Here, we report a direct measurement technique using nmr dipolar cross-relaxation between the nanoconfined fluids and the matrix solids.The method was tested using a methyl-functionalized mesostructured silica saturated with methanol as a model sample.A formal theory was established to describe the enhanced dipolar cross-relaxation interaction between the nanoconfined fluids and the matrix solids.Both the experiment and theory showed that nanoconfinement of the fluids enhances the dipolar cross-relaxation interaction between the fluid and the matrix solids, which can be applied to investigate the fluid-solid interaction for various materials of a similar nanostructure.

Journal: ACS omega (2022)
Publication types: Journal Article
A conceptual model of risk and protective factors for autistic burnout.

Early qualitative research indicates that autistic burnout is commonly experienced by autistic people and is associated with significant, negative consequences for their mental health, wellbeing, and quality of life, including suicidality.Findings to date suggest that factors associated with being autistic and the widespread lack of autism awareness and acceptance within society contribute to the onset and recurrence of autistic burnout.Based on autistic adults' descriptions of their lived experiences, a conceptual model of autistic burnout (cmab) is proposed, which describes a series of hypothesized relationships between identified risk and protective factors that may contribute to, or buffer against, autistic burnout.The theoretical framework for the cmab is based on the social-relational model of disability and neurodiversity paradigm, and the job demands-resources model of burnout, and conservation of resources theory.The cmab offers a holistic perspective for understanding individual, social, and environmental factors that can influence autistic burnout via various direct and indirect pathways.Autistic burnout research is in its infancy and the cmab provides a foundation for future investigations about this condition.Lay summary: although many autistic people describe experiencing autistic burnout, there has been little research on this topic.Based on descriptions of autistic peoples' lived experiences, we developed a conceptual model to explore how various risk and protective factors may interact to contribute to, or prevent, autistic burnout.

Journal: Autism research : official journal of the International Society for Autism Research (2022)
Publication types: Journal Article
A Need to Revise Human Exposure Limits for Ultraviolet UV-C Radiation†.

The covid-19 pandemic has greatly heightened interest in ultraviolet germicidal irradiation (uvgi) as an important intervention strategy to disinfect air in medical treatment facilities and public indoor spaces.However, a major drawback of uvgi is the challenge posed by assuring safe installation of potentially hazardous short-wavelength (uv-c) ultraviolet lamps.Questions have arisen regarding what appear to be unusually conservative exposure limit values in the uv-c spectral band between 180 and 280 nm.We review the bases for the current limits and proposes some adjustments that would provide separate limits for the eye and the skin at wavelengths less than 300 nm and to increase both skin and eye limits in the uv-c below 250 nm.

Journal: Photochemistry and photobiology (2021)
Publication types: Journal Article;Review
Childhood stroke.

Stroke is an important cause of neurological morbidity in children; most survivors have permanent neurological deficits that affect the remainder of their life.Stroke in childhood, the focus of this primer, is distinguished from perinatal stroke, defined as stroke before 29 days of age, because of its unique pathogenesis reflecting the maternal-fetal unit.Although approximately 15% of strokes in adults are haemorrhagic, half of incident strokes in children are haemorrhagic and half are ischaemic.The causes of childhood stroke are distinct from those in adults.Urgent brain imaging is essential to confirm the stroke diagnosis and guide decisions about hyperacute therapies.Secondary stroke prevention strongly depends on the underlying aetiology.While the past decade has seen substantial advances in paediatric stroke research, the quality of evidence for interventions, such as the rapid reperfusion therapies that have revolutionized arterial ischaemic stroke care in adults, remains low.Substantial time delays in diagnosis and treatment continue to challenge best possible care.Effective primary stroke prevention strategies in children with sickle cell disease represent a major success, yet barriers to implementation persist.The multidisciplinary members of the international pediatric stroke organization are coordinating global efforts to tackle these challenges and improve the outcomes in children with cerebrovascular disease.

Journal: Nature reviews. Disease primers (2022)
Publication types: Journal Article;Review
Toward a Framework for Environmental Fate and Exposure Assessment of Polymers.

Development of risk-assessment methodologies for polymers is an emerging regulatory priority to prevent negative environmental impacts; however, the diversity and complexity of polymers require adaptation of existing environmental risk-assessment approaches.The present review discusses the challenges and opportunities for the fate and exposure assessment of polymers in the context of regulatory environmental risk assessment of chemicals.The review discusses the applicability and adequacy for polymers of existing fate parameters used for nonpolymeric compounds and proposes additional parameters that could inform the fate of polymers.The significance of these parameters in various stages of an exposure-assessment framework is highlighted, with classification of polymers as solid or dissolved being key for identification of those parameters most relevant to environmental fate.Considerations to address the key limitations and knowledge gaps are then identified and discussed, specifically the complexity of polymer identification, with the need for characterization of the most significant parameters for polymer grouping and prioritization; the complexity of polymer degradation in the environment, with the need to incorporate the fate and hazards of degradation products into risk assessment; the requirement for development and standardization of analytical methods for characterization of polymer fate properties and degradation products; and the need to develop exposure modeling approaches for polymers.Environ toxicol chem 2022;41:515-540.© 2021 the authors.Environmental toxicology and chemistry published by wiley periodicals llc on behalf of setac.

Journal: Environmental toxicology and chemistry (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Co-expression of CMTM6 and PD-L1: a novel prognostic indicator of gastric cancer.

Cklf like marvel transmembrane domain containing 6 (cmtm6) is involved in the epigenetic regulation of genes and tumorigenesis.Programmed cell death ligand 1 (pd-l1) is closely related to the prognosis of some human cancers.Cmtm6 is a key regulator of pd-l1 in many cancers.The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival.Methods the expression levels of cmtm6 and pd-l1 were examined in 185 gastric cancer specimens using immunohistochemistry, quantitative real-time pcr and western blot.Immunofluorescence was used to examine the localizations of cmtm6 and pd-l1.Chi-square test was used to analyze the relationship between cmtm6 and pd-l1 expressions and clinicopathological characteristics.Kaplan-meier method and log-rank test were used to analyze the survival data of patients.Results the positive expression rates of cmtm6 and pd-l1 in gastric cancers were 78.38% (145/185) and 75.68% (140/185), respectively.Cmtm6 and pd-l1 were both mainly expressed in the cell membrane and nucleus of gastric cancer tumor cells.High expression of cmtm6 and pd-l1 was correlated with borrmann type (p < 0.001), n stage (p = 0.002), peritoneal metastasis (p = 0.007) and tnm stage (p = 0.038).Cmtm6 and pd-l1 expression in gastric cancer tissues showed a positive correlation (pearson's coefficient test, r = 0.260; p < 0.001).Cmtm6 may positively regulate pd-l1 expression.High expression of cmtm6 was correlated with poor prognosis of gastric cancer patients (hr = 1.668; 95% ci = 1.032-2.695; p = 0.037).High expression of both cmtm6 and pd-l1 may be an independent factor for overall survival (hr = 1.554; 95% ci = 1.011-2.389; p = 0.044).Conclusion the combined detection of cmtm6 and pd-l1 may be used as an indicator for judging the prognosis of gastric cancer patients.

Journal: Cancer cell international (2021)
Publication types: Journal Article
Chubby, Hairy and Fearless. Subcultural Identities and Predictors of Self-Esteem in a Sample of Polish Members of Bear Community.

Bear subculture exists within a larger gay community, which has been recognized by public health experts as disproportionately burdened with stigma and related health adversities.Bears are distinguished by a particular body look-body hirsuteness and heavy-set physique.Previous research documented the various health risks, and the exposure to both sexual minority and weight stigma, of this population.In this study we focused on the determinants of self-esteem in bears.We explored the significance of such predictors as: perceived sexual minority and weight stigma, age, resilience, and physique as reflected by the bmi.Our sample consisted of 60 men from the polish bear community (i.e., bears, cubs, otters, wolves).Linear regression models were performed for the entire sample (n = 60) and for bear-identified men (n = 31).Perceived sexual minority stigma negatively, and resilience positively, predicted self-esteem.In the case of bear-identified men, age, perceived exposure to weight discrimination, and bmi were also significant predictors of self-esteem.Higher bmi in the case of bear-identified men predicted higher self-esteem.Our results suggest that although bear-identified men are characterized by their similarities to other gay men, subcultural identities create unique social contexts that are important for health and health interventions in this population.

Journal: International journal of environmental research and public health (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
Site-specific nanobody-oligonucleotide conjugation for super-resolution imaging.

Camelid single-domain antibody fragments, also called nanobodies, constitute a class of binders that are small in size (~15 k da) and possess antigen-binding properties similar to their antibody counterparts.Facile production of recombinant nanobodies in several microorganisms has made this class of binders attractive within the field of molecular imaging.Particularly, their use in super-resolution microscopy has improved the spatial resolution of molecular targets due to a smaller linkage error.In single-molecule localization microscopy techniques, the effective spatial resolution can be further enhanced by site-specific fluorescent labeling of nanobodies owing to a more homogeneous protein-to-fluorophore stoichiometry, reduced background staining and a known distance between dye and epitope.Here, we present a protocol for site-specific bioconjugation of dna oligonucleotides to three distinct nanobodies expressed with an n- or c-terminal unnatural amino acid, 4-azido-l-phenylalanine (p az f).Using copper-free click chemistry, the nanobody-oligonucleotide conjugation reactions were efficient and yielded highly pure bioconjugates.Target binding was retained in the bioconjugates, as demonstrated by bio-layer interferometry binding assays and the super-resolution microscopy technique, dna points accumulation for imaging in nanoscale topography (paint).This method for site-specific protein-oligonucleotide conjugation can be further extended for applications within drug delivery and molecular targeting where site-specificity and stoichiometric control are required.

Journal: Journal of biological methods (2022)
Publication types: Journal Article