Machine-learning model selection and parameter estimation from kinetic data of complex first-order reaction systems

Dealing with a system of first-order reactions is a recurrent issue in chemometrics, especially in the analysis of data obtained by spectroscopic methods applied on complex biological systems. We argue that global multiexponential fitting, the still common way to solve such problems, has serious weaknesses compared to contemporary methods of sparse modeling. Combining the advantages of group lasso and elastic net—the statistical methods proven to be very powerful in other areas—we created an optimization problem tunable from very sparse to very dense distribution over a large pre-defined grid of time constants, fitting both simulated and experimental multiwavelength spectroscopic data with high computational efficiency. We found that the optimal values of the tuning hyperparameters can be selected by a machine-learning algorithm based on a Bayesian optimization procedure, utilizing widely used or novel versions of cross-validation. The derived algorithm accurately recovered the true sparse kinetic parameters of an extremely complex simulated model of the bacteriorhodopsin photocycle, as well as the wide peak of hypothetical distributed kinetics in the presence of different noise levels. It also performed well in the analysis of the ultrafast experimental fluorescence kinetics data detected on the coenzyme FAD in a very wide logarithmic time window. We conclude that the primary application of the presented algorithms—implemented in available software—covers a wide area of studies on light-induced physical, chemical, and biological processes carried out with different spectroscopic methods. The demand for this kind of analysis is expected to soar due to the emerging ultrafast multidimensional infrared and electronic spectroscopic techniques that provide very large and complex datasets. In addition, simulations based on our methods could help in designing the technical parameters of future experiments for the verification of particular hypothetical models

Ultragyors lineáris és nemlineáris optikai folyamatok makromolekulákon = Ultrafast linear and nonlinear optical processes on macromolecules

Mérőrendszerünkhöz új tükörkészletet és diszperzió szabályozó egységet fejlesztettünk ki, széles hullámhossz tartományban lehetővé téve (akár 40 fs-nál rövidebb) stabil fényimpulzusok keltését. Félvezető alapú telítődő abszorbens (SESAM) mintákon meghatároztuk a a fs-ps időtartományba eső tranziens abszorpció időállandóit. A kinetikai adatok kiértékelésére kidolgoztunk egy modellfüggetlen, nemparametrikus dekonvolúciós eljárást. Fotoszinetikus fénybegyűjtő komplexeken jellemeztük a fénykárosodást kivédő hődisszipáció ps-os kinetikáját. A fényenergia hasznosító bakteriorodopszin (bR) fehérjéből készített natív és módosított szárított mintákon megállapítottuk a gerjesztett állapot valamint az ultragyors intermedierek abszorpciókinetikai paramétereit. 10 fs időfelbontású koherens infravörös emissziós kísérletek alapján jellemeztük a bR retinál kromofórjának gerjesztése során létrejövő dipólmomentum változást, és az azt követő koherens vibrációs folyamatokat. Elsőként mutattuk ki és jellemeztük a bR mintából származó terahertzes emisszó jelenségét, megállapítva, hogy az részben a retinál molekula gerjesztett állapotú elektronmozgásából, részben pedig - a feltehetően ez által keltett - kezdeti funkcionális protonmozgásból származik. Kidolgoztunk egy kvantumelektrodinamikai leírást, melynek keretében a retinál gerjesztése során fellépő másodrendű optikai folyamatok egységesen tárgyalhatók. | A new mirror set and a dispersion control unit was developed for our measuring system, making possible to generate stable light pulses (of even shorter than 40 fs) in a wide range of wavelength. The fs-ps transient absorption time-constants of semiconductor saturable absorber mirror (SESAM) samples were determined. A model-independent nonparametric deconvolution procedure was elaborated for the analysis of the kinetic data. Photosynthetic light-harvesting complexes were characterized by their ps kinetics of heat dissipation process, protecting them from light-induced damages. The absorption kinetic parameters describing the excited state and the ultrafast intermediers in native and modified dried samples of bacteriorhodopsin (bR) protein - utilizing light energy - were determined. By coherent infrared emission experiments the dipole moment change upon the excitation of the retinal chromophore of bR, as well as the subsequent coherent vibration processes were characterized. The phenomenon of terahertz emission from a bR sample was demonstrated and characterized for the first time, showing that it originates both from the excited-state electron motion of the retinal molecule and the functional early proton movement, probably generated by the former process. A theoretical description was derived from quantum electrodynamics for a unified description of the second order optical processes occurring on the excitation of retinal

Self-reported efficacy and safety of infliximab and adalimumab biosimilars after non-medical switch in patients with inflammatory bowel disease: results of a multicenter survey

Few data are available on subjective disease control and perception of adverse events (AEs) during switching from original anti-TNF agents to biosimilars.Hungarian patients with inflammatory bowel disease were interviewed after a mandatory non-medical switch from an infliximab (IFX) originator to a biosimilar GP1111 or from an adalimumab (ADA) originator to a biosimilar GP2017. Drug choice was based on patient's and physician's decision. Subjective efficacy was measured using a 10-point scale, and AEs were assessed. Difference in efficacy before and after the switch was compared within and between the drugs.Seventy-three ADA and 106 IFX switching patients were interviewed. Subjective efficacy of IFX biosimilar was rated lower compared to IFX originator (8.72 ± 1.68 vs. 7.77 ± 2.34; p = 0.001). The ADA biosimilar was rated higher than its originator (9.02 ± 1.61 vs. 8.42 ± 1.93; p = 0.017). Patients receiving ADA biosimilar were more satisfied with the new treatment compared to IFX (p = 0.032). The incidence of new AEs was 85% in the ADA and 55% in the IFX group (1.79 vs. 0.93 AEs per patient, respectively, p < 0.001).Subjective efficacy of switching to a biosimilar was proven in case of ADA, while reduced efficacy was experienced with IFX biosimilar. Perception of AEs was high and varied between biosimilars

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis

Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases.We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease.No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease.No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided

Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease - A nationwide Hungarian cohort study

Background: GEMINI trials demonstrated the therapeutic efficacy of vedolizumab (VDZ) in Crohn's disease (CD) and ulcerative colitis (UC).Research design and methods: Aim of this study was to determine the real-life effectiveness of VDZ on endoscopic healing in the Hungarian nationwide cohort of inflammatory bowel disease (IBD) patients based on changes on clinical and endoscopic scores. Every adult IBD patient in the country (121 UC and 83 CD) who completed short-term VDZ therapy were enrolled, of which 72 UC and 52 CD patients could complete the long-term therapy.Results: Rates of endoscopic healing were substantially higher in UC compared with CD patients during short- and long-term therapy (52.9% vs. 21.7%, p<0.0001, and 51.4% vs. 21.2%, p=0.015, respectively). In CD, the rate of endoscopic healing was lower at week 14 compared with week 22 (14.5% vs. 37.0%, p=0.026). Prior anti-TNF-alpha therapy (88.73%) was not associated with a significant decrease in therapeutic response. Average disease duration was significantly lower in CD patients achieving endoscopic healing at week 52 (11.75 vs. 5.27 years, p=0.007).Conclusions: VDZ therapy is an effective therapeutic option in anti-TNF-alpha refractory IBD. However, endoscopic healing rate was substantially lower and showed a significant delay in CD compared with UC

Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease: a nationwide Hungarian cohort study

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Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.Peer reviewe

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis

Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases.We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease.No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease.No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided