syedzayyan/paper_mill_benchmark huggingface dataset:
Conceptual clarifications regarding Chilean Act 20850 on public funding of high-cost diseases.

In 2015, chile enacted the 20850 law, providing public funds for rare and costly diseases that demanded high diagnostic and therapeutic expenditures.The law modifies the chilean sanitary code regulation of research with human beings, aiming at the protection of subjects by securing post-investigational medical benefits and insurance coverage for damage imputable to the research they participated in.Due to ambiguous phrasing, a polemic rose for fear that these protective measures applied to all clinical research, although a careful reading of the law in its context clearly suggests that it refers to phase i therapeutic trials.This paper stresses the distinction between compassionate use and genuine phase i/ii therapeutic trials aimed at both pharmacodynamics and an intended therapeutic effect for severe and progressive diseases that are therapeutically orphaned, emphasizing the ethical and medical duty of providing post-trial beneficial medication.

Journal: Medwave (2016)
Publication types: Journal Article
The Role of Intraventricular Antibiotics in the Treatment of Nosocomial Ventriculitis/Meningitis from Gram-Negative Pathogens: A Systematic Review and Meta-Analysis.

The emergence of multidrug-resistant pathogens has resulted in difficult-to-treat ventriculitis/meningitis (vm).We used a meta-analysis to study the role of intraventricular (ivt) antibiotic administration as an adjunct (ivt plus intravenous [iv]) to the classic intravenous antimicrobial therapy (iv-only) in the management of vm in terms of infection control, functional outcome, microbial eradication, complications, cost-benefit analysis, infectious mortality, and overall mortality.Methods the electronic search focused on adult neurosurgical cases complicated by gram-negative vm and was limited to studies comparing ivt plus iv and iv-only.The quality of the overall body of evidence was assessed according to grade (grading of recommendations assessment, development, and evaluation).The pooled estimates for each question were summarized as odds ratios (ors) and visualized using forest plots.Every outcome was stratified according to carbapenem resistance.Results eleven studies with 348 patients fulfilled the eligibility criteria.No evidence was found for infection control, functional outcome, or complications.For the remaining items evaluated, the overall quality of the best available evidence was low.Ivt plus iv treatment was statistically superior to iv-only therapy in eradication (or, 10.06; 95% confidence interval [ci], 2.62-38.65), infectious mortality (or, 0.1; 95% ci, 0.03-0.36), and overall mortality (or, 0.22; 95% ci, 0.08-0.60) in the management of carbapenem-resistant pathogens only.Conclusions combined ivt plus iv treatment did not prove superior to standard iv-only treatment in the management of vm.Nevertheless, weak evidence showed that ivt treatment might serve as an adjunct in the management of carbapenem-resistant pathogens.

Journal: World neurosurgery (2018)
Publication types: Journal Article;Meta-Analysis;Systematic Review
Molecularly imprinted Monolithic column-based SERS sensor for selective detection of cortisol in dog saliva.

Molecularly imprinted monolithic column embedded with silver nanoparticles (mimc@ag) was synthesized by in-situ polymerization with template and porogen inside capillary tube followed by silver precursor reduction and template/porogen removal for realizing raman detection of cortisol.Dense silver nanoparticles generated within the monolith makes this kind of column suitable for surface enhanced raman scattering (sers) detection, designated as sers-mimc.Scanning electron microscopy and bet profiler confirmed larger pore structure in the column after template removal.The corresponding increased mass transfer/binding rate, selective adsorption and adsorptive mechanism of the mimc were well studied with a series of adsorption experiments.The minimum raman detectable concentration of cortisol is 1 × 10-7mol l-1by using mimc@ag with a good linear relationship in the concentration range from 1 × 10-3to 1 × 10-7mol l-1.Sers sigmal of cortisol can be clearly distinguished from its analogs (estradiol, cholesterol and dexamethasone), proving the selective recognition of cortisol for sers detection by mimc@ag.This ease-to-prepare sers-mimc sensor also shows good stability and reusability.The sers-mimc has been successfully applied for the easy, sensitive and selective detection of cortisol in dog saliva.

Journal: Talanta (2022)
Publication types: Journal Article
Genomic mapping of copy number variations influencing immune response in breast cancer.

Identification of genomic alterations that influence the immune response within the tumor microenvironment is mandatory in order to identify druggable vulnerabilities.In this article, by interrogating public genomic datasets we describe copy number variations (cnv) present in breast cancer (bc) tumors and corresponding subtypes, associated with different immune populations.We identified regulatory t-cells associated with the basal-like subtype, and type 2 t-helper cells with her2 positive and the luminal subtype.Using gene set enrichment analysis (gsea) for the type 2 t-helper cells, the most relevant processes included the erbb2 signaling pathway and the fibroblast growth factor receptor (fgfr) signaling pathway, and for cd8+ t-cells, cellular response to growth hormone stimulus or the jak-stat signaling pathway.Amplification of erbb2, grb2, grb7, and fgfreceptor genes strongly correlated with the presence of type 2 t helper cells.Finally, only 8 genes were highly upregulated and present in the cellular membrane:milr1, ace, dcstamp, slamf8, cd160, il2ra, icam2, and slamf6.in summary, we described immune populations associated with genomic alterations with different bc subtypes.We observed a clear presence of inhibitory cells, like tregs or th2 when specific chromosomic regions were amplified in basal-like or her2 and luminal groups.Our data support further evaluation of specific therapeutic strategies in specific bc subtypes, like those targeting tregs in the basal-like subtype.

Journal: Frontiers in oncology (2022)
Publication types: Journal Article
There Is a Clinical Need to Consider the Physical Activity: Sedentary Pattern in Children with Obesity - Position Paper of the European Childhood Obesity Group.

Introduction while international prevention guidelines recently advocated, in addition to moderate and vigorous physical activity (mvpa) guidelines, for a minimization of sedentary (sed) time, recommendations remain to be developed for youths with obesity.Methods a literature search was conducted in pub med, the cochrane library, plus the reference lists of selected articles for relevant publications in english, including original papers, systematic reviews, and meta-analyses, with search terms "sedentary behaviors" or "sedentary time" or "screen time" and "children" or "adolescents" and "obesity" or "adiposity" or "cardiometabolic risk" or "cardiometabolic disease." the results were summarized as a narrative review and presented to the scientific board of the european childhood obesity group (ecog), who then discussed their implication in clinical practice and proposed the position outlined in this paper.Results sed and screen times are associated with adiposity and cardiometabolic risks, independently of youths' physical activity (pa) level.Besides considering mvpa and sed times as separate variables, comprehensive studies have questioned the impact of different patterns of mvpa and sed levels.Although lower body adiposity and better cardiometabolic health are achieved among those with desirable movement behavior patterns (i.e., more mvpa/less sed or active/not sed), youths with intermediate patterns (i.e., high mvpa/high sed and low mvpa/low sed, or active/sed and inactive/not sed) have been found to be associated with intermediate risks.Conclusion there is a need to decrease sed behaviors irrespective of mvpa and to consider pa-sed patterns in youth with obesity.The ecog encourages anti-obesity strategies targeting both pa and sed behaviors to support the shift from long periods of sed time, especially screen time, to daily routines incorporating bouts of pa.Stepwise or sequential approaches to movement behavior counseling might start with targeting sed at first to decrease cardiometabolic risks when implementing mvpa is not yet possible.

Journal: Annals of nutrition & metabolism (2022)
Publication types: Journal Article;Review
Generation of Single-Chain Variable Fragment (scFv) Libraries for Use in Phage Display.

Phage display is a powerful platform for the discovery of novel biologics with high binding affinities to a specific target protein.Here, we describe methods to construct a phage display library containing diverse single-chain variable antibody fragments (sc fvs).Specifically, updated methods for polymerase chain reaction (pcr) amplification and fusion of human antibody genes, their ligation into the p comb3x vector for transformation into 5αf'iqcompetent bacterial cells, and their expression in m13ko7 helper phage are presented.Additionally, we describe how to amplify and quantify the phage library and to prepare it in various formats for short- and long-term storage.© 2021 wiley periodicals llc.Basic protocol 1: first-round polymerase chain reaction (pcr) for isolation of antibody fragments basic protocol 2: ethanol precipitation and pooling of fragment dna basic protocol 3: second-round polymerase chain reaction with splicing by overlap extension (soe) for antibody fragment fusion basic protocol 4: restriction digestion of individual sc fv constructs and p comb3xss vector basic protocol 5: directional ligation of the sc fv constructs and p comb3x backbone basic protocol 6: transformation of p comb-sc fv plasmids into 5αf'iqcompetent cells basic protocol 7: collection of bacteria containing the sc fv library basic protocol 8: preparation of bacterial glycerol stock basic protocol 9: preparation of phage library glycerol stock basic protocol 10: preparation of plasmid dna stock basic protocol 11: amplification of m13ko7 helper phage basic protocol 12: phage titer by plate assay alternate protocol: one-plate phage plaque assay.

Journal: Current protocols (2021)
Publication types: Journal Article
Noninvasive measurement of the 308 nm LED-based UVB protection factor of sunscreens.

The current method for determining the sun protection factor (spf) requires erythema formation.Noninvasive alternatives have recently been suggested by several groups.Our group previously developed a functional sensor based on diffuse reflectance measurements with one uvb led, which was previously evaluated on pig ear skin.Here we present the results of a systematic in vivo study using 12 sunscreens on 10 volunteers (skin types [st] i-iii).The relationship of the uvb-led reflectance of unprotected skin and melanin index was determined for each st.The spatial variation of the reflectance signal of different positions was analyzed and seems to be mainly influenced by sample inhomogeneity except for high-protection factors (pfs) where signal levels are close to detection noise.Despite the low-signal levels, a correlation of the measured led-based uvb pf with spf reference values from test institutes with r2= 0.57 is obtained, suggesting a strong relationship of spf and led-based uvb-pf.Measured pfs tend to be lower for increasing skin pigmentation.The sensor design seems to be suitable for investigations where a fast measurement of relative changes of pfs, such as due to inhomogeneous application, bathing and sweating, is of interest.

Journal: Journal of biophotonics (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1.

Bone marrow mesenchymal stem cell-derived exosomes (bmsc-exos) could mediate the malignancy of tumor cells by transmitting targeted cargo.Therein, this study intends to explore the function of bmsc-exos transmitting micro rna-425 (mi r-425)/cytoplasmic polyadenylation binding protein 1 (cpeb1) in lung cancer growth.Methods mi r-425 and cpeb1 levels in cancer tissues and cells were measured.Bmscs and their exosomes were collected and identified.After intervention with bmsc-exos, mi r-425 or cpeb1, invasion and migration of a549 and nci-h1299 cellsin vitro, and lung metastasis of a549 cellsin vivowere observed.The relationship between mi r-425 and cpeb1 was verified.Results mi r-425 was highly expressed while cpeb1 was lowly expressed in lung cancer tissues of patients.Cpeb1 was the direct target of mi r-425.Down-regulating mi r-425 or up-regulating cpeb1 decreased cell invasion and migration ability of a549 and nci-h1299 cells, as well as decreased the number of lung metastasis lesionsin vivo.After co-culture with bmsc-exos, a549 and nci-h1299 cells showed promoted migration and invasionin vitroand a549 cells demonstrated increased lung metastasisin vivo.Down-regulated mi r-425 or up-regulated cpeb1 reversed the promotion of bmsc-exos on lung cancer cell invasion, migration and lung metastasis.Conclusion bmsc-exos could deliver mi r-425 to inhibit cpeb1 expression in lung cancer cells, thereby promoting the malignant biological properties of lung cancer cells and their metastasisin vivo.

Journal: Regenerative therapy (2022)
Publication types: Journal Article
Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells.

The cerebral cortex is a structure that underlies various brain functions, including cognition and language.Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons.Newborn neurons migrate along progenitors' radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry.Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny.Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (mcds).They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex.Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder.The recent advancements of molecular and neuroimaging techniques, along with the development of appropriatein vitroandin vivomodel systems, have enabled the assessment of the genetic and environmental causes of mcds.Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to mcds.

Journal: Frontiers in neuroscience (2021)
Publication types: Journal Article;Review
A predictive dynamic yeast model based on component, energy, and electron carrier balances.

The present study describes a novel yeast model for the prediction of yeast fermentation.The proposed model considers the possible metabolic pathways of yeast.For each pathway, the time evolution of components, energy (atp/adp), and electron carriers (nad+/nadh) are expressed with limitation factors for all quantities consumed by each respective pathway.In this manner, the model can predict the partition of these pathways based on the growth conditions and their evolution over time.Several biological pathways and their stoichiometric coefficients are well known from literature.It is important to note that most of the kinetic parameters have no effect as the actual kinetics are controlled by the balance of limiting factors.The few remaining parameters were adjusted and compared with the literature when the data set was available.The model fits our experimental data from yeast fermentation on glucose in a nonaerated batch system.The predictive ability of the model and its capacity to represent the intensity of each pathway over time facilitate an improved understanding of the interactions between the pathways.The key role of energy (atp) and electron carrier (nad+) to trigger the different metabolic pathways during yeast growth is highlighted, whereas the involvement of mitochondrial respiration not being associated with the tca cycle is also shown.

Journal: Biotechnology and bioengineering (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Enhancing the health of NHS staff: eTHOS - protocol for a randomised controlled pilot trial of an employee health screening clinic for NHS staff to reduce absenteeism and presenteeism, compared with usual care.

Staff absenteeism and presenteeism incur high costs to the nhs and are associated with adverse health outcomes.The main causes are musculoskeletal complaints and mental ill-health, which are potentially modifiable, and cardiovascular risk factors are also common.We will test the feasibility of an rct to evaluate the clinical and cost-effectiveness of an employee health screening clinic on reducing sickness absenteeism and presenteeism.Methods this is an individually randomised controlled pilot trial aiming to recruit 480 participants.All previously unscreened employees from four hospitals within three uk nhs hospital trusts will be eligible.Those randomised to the intervention arm will be invited to attend an employee health screening clinic consisting of a screening assessment for musculoskeletal (star t msk and star t back), mental (phq-9 and gad-7) and cardiovascular (nhs health check if aged ≥ 40, lifestyle check if < 40 years) health.Screen positives will be given advice and/or referral to recommended services.Those randomised to the control arm will receive usual care.Participants will complete a questionnaire at baseline and 26 weeks; anonymised absenteeism and staff demographics will also be collected from personnel records.The co-primary outcomes are as follows: recruitment, referrals and uptake of recommended services in the intervention arm.Secondary outcomes include the following: results of screening assessments, uptake of individual referrals, reported changes in health behaviours, acceptability and feasibility of intervention, indication of contamination and costs.Outcomes related to the definitive trial include self-reported and employee records of absenteeism with reasons.Process evaluation to inform a future trial includes interviews with participants, intervention delivery staff and service providers receiving referrals.Analyses will include presentation of descriptive statistics, framework analysis for qualitative data and costs and consequences presented for health economics.Discussion the study will provide data to inform the design of a definitive rct which aims to find an effective and cost-effective method of reducing absenteeism and presenteeism amongst nhs staff.The feasibility study will test trial procedures, and process outcomes, including the success of strategies for including underserved groups, and provide information and data to help inform the design and sample size for a definitive trial.Trial registration isrctn reference number 10237475 .

Journal: Pilot and feasibility studies (2022)
Publication types: Journal Article
Draft genomes and descriptions of Urmitella timonensis gen. nov., sp. nov. and Marasmitruncus massiliensis gen. nov., sp. nov., isolated from severely malnourished African children using culturomics.

Two strains, designated as marseille-p2918tand marseille-p3646t, were isolated from a 14-week-old senegalese girl using culturomics: urmitella timonensis strain marseille-p2918t(= csur p2918, = dsm 103634) and marasmitruncus massiliensis strain marseille-p3646t(= csur p3646, = ccug72353).Both strains were rod-shaped, anaerobic, spore forming motile bacteria.The 16s r rna gene sequences of strains marseille-p2918t(lt598554) and marseille-p3646t(lt725660) shared 93.25% and 94.34% identity with tissierella praeacuta atcc 25539tand anaerotruncus colihominis cip 107754t, their respective phylogenetically closest species with standing in nomenclature.Therefore, strain marseille-p2918tis classified within the family tissierellaceae and order tissierellales whereas strain marseille-p3646tis classified within the family oscillospiraceae and order eubacteriales.The genome of strain marseille-p2918thad a size of 2.13 mb with a gc content of 50.52% and includes six scaffolds and six contigs, and that of strain marseille-p3646twas 3.76 mbp long consisting of five contigs with a 50.04% gc content.The genomes of both strains presented a high percentage of genes encoding enzymes involved in genetic information and processing, suggesting a high growth rate and adaptability.These new taxa are extensively described and characterised in this paper, using the concept of taxono-genomic description.

Journal: Antonie van Leeuwenhoek (2022)
Publication types: Journal Article
Radiological score of computed tomography scans predicts revision surgery for chronic rhinosinusitis.

Evaluate computed tomography (ct) signs that predict need for revision endoscopic sinus surgery (ess) of chronic rhinosinusitis (crs).Methods crs patients (n = 48) underwent routine sinus ct scans and baseline ess in 2006-2011.Lund-mackay (lm) scores and 43 other ct signs were analysed blinded from both sides.Patients filled in a questionnaire during the day of ct scanning.Follow-up data were collected from hospital records until january 2018.Associations were analysed by fisher's exact, mann whitney u, kaplan-meier method with logrank test and cox's proportional hazard model.Results total lm score was not significantly associated with the need for revision ess.The best predictive model was a sum of ct signs of non-detectable anatomy of inferior/middle turbinates, obstructed frontal recess, and previous sinus surgery.Using these ct findings, we formed a radiological score (rs) (min-max, 0-3 points).Having at least one rs point was significantly associated with the need for revision ess during the average follow-up of 10.7 years (p = 0.008, logrank test).Conclusion we identified a radiologic score that was able to predict the need for revision ess, which is probably useful in predicting crs outcomes.

Journal: Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale (2022)
Publication types: Journal Article
Highly Deep-Blue Luminescent Twisted Diphenylamino Terphenyl Emitters by Bromine-Lithium Exchange Borylation-Suzuki Sequence.

Four novel intensively blue luminescent chromophores were readily synthesized by bromine-lithium exchange borylation-suzuki (blebs) sequence in moderate to good yields.Their electronic properties were studied by absorption and emission spectroscopy and quantum chemical calculations revealing deep-blue emission in solution as well as in the solid state and upon embedding into a pmma (polymethylmethacrylate) matrix with small fwhm (full width at half maximum) values and cie y values smaller than 0.1.Moreover, high photoluminescence quantum yields (plqy), partially close to unity, are found.

Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (2022)
Publication types: Journal Article