bluuebunny/crossref_metadata_2025_split huggingface dataset:
MURIN: Multimodal Retinal Imaging and Navigated-laser-delivery for dynamic and longitudinal tracking of photodamage in murine models
Authors: Rico-Jimenez Jose J. , Jovanovic Joel , Nolen Stephanie L. , Malone Joseph D. , Rao Gopikrishna M. , Levine Edward M. , Tao Yuankai K. 
Published: April 2023

IntroductionLaser-induced photodamage is a robust method for investigating retinal pathologies in small animals. However, aiming of the photocoagulation laser is often limited by manual alignment and lacks real-time feedback on lesion location and severity. Here, we demonstrate MURIN: MUltimodal Retinal Imaging and Navigated-laser-delivery, a multimodality OCT and SLO ophthalmic imaging system with an image-guided scanning laser lesioning module optimized for the murine retina. The proposed system enables targeting of focal and extended area lesions under OCT guidance to benefit visualization of photodamage response and the precision and repeatability of laser lesion models of retinal injury.MethodsMURIN optics were optimized for simultaneous near-infrared and visible wavelength imaging/laser lesioning. Custom LabView control software was developed to steer the photocoagulation laser and automatically deliver laser pulses to targets-of-interest. In vivo retinal imaging was performed in transgenic Müller glia-tdTomato reporter mice (Rlbp1:CreER; Rosaai14, 5 animals, 10 eyes) and microglia-GFP/Müller glia-tdTomato reporter mice (Cx3cr1GFP; Rlbp1:CreER; Rosaai14, 9 animals, 15 eyes) to visualize cellular changes in the retina after laser lesion delivery.ResultsReal-time MURIN imaging concurrent with laser lesioning allowed us to visualize lesion formation dynamics and any corresponding changes in retinal morphology. We observe increasing fluorescence photoconversion on SLO and scattering contrast on OCT. Significant morphological changes are visible on MURIN after high-severity photodamage. OCT cross-sections show the spatial extent of the lesions contract over time from diffusion areas of increased scattering to granular scatterers and corresponding SLO images show a radial pattern surrounding severe focal lesions, which may be a result of a change in Müller cell shape or orientation in response to injury. The inner plexiform layer is distorted and increased RPE thickness and scattering are observed, all of which are confirmed on corresponding hematoxylin and eosin (H&amp;E) histology and differential interference contrast (DIC) microscopy.DiscussionMURIN as a unique imaging platform that enables combined SLO and OCT imaging with an integrated image-guided laser lesioning module. This technology has clear benefits over existing multimodal imaging and laser lesioning systems by enabling simultaneous multimodal imaging, independent and precise control of Iridex laser pulse parameters and patterns, and real-time OCT and SLO visualization of lesion formation.
Chinese Herbal Medicine Combined With Antiepileptic Drugs for Intractable Epilepsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhao Ying , Zhou Hufang , Liu Qingxuan , Liu Jialin , Wu Mengwei , Yuan Siyuan , Xu Weiwei , Wang Ying , Wang Kaiyue , Li Lili , Liu Jinmin 
Published: April 2023

Background: Intractable epilepsy (IE) is still a major concern in neurology, and existing therapies do not adequately control symptoms. Chinese Herbal Medicine (CHM) has been widely used as an adjunct to antiepileptic drugs (AEDs) for IE. However, because of the contradictory findings reported in previous studies, it is uncertain if the present evidence is robust enough to warrant its usage. The purpose of this meta-analysis was to systematically evaluate the efficacy of the combination of CHM and AEDs for IE.Methods: From inception to September 2021, Medline, Ovid, Embase, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database were searched. Only randomized controlled trials (RCTs) that assessed the efficacy of the combination of CHM and AEDs for IE were included. We defined monthly seizure frequency as the primary outcome. The secondary outcomes included the abnormal rate of electroencephalogram (EEG), seizure duration, quality of life (QoL), and adverse events (AEs).Results: Twenty studies with 1,830 patients were enrolled. Most trials had poor methodological quality. The meta-analysis showed that the combination of CHM and AEDs was more efficient than AEDs alone in reducing monthly seizure frequency [MD = −1.26%, 95% CI (−1.62, −0.91); p &lt; 0.00001], the abnormal rate of EEG [RR = 0.66%, 95% CI (0.53, 0.82); p = 0.0002], and improving the QoL [MD = 6.96%, 95% CI (3.44, 10.49); p = 0.0001]. There was no significant difference in seizure duration between groups. Moreover, the combination of CHM and AEDs significantly reduced the AEs [RR = 0.45%, 95% CI (0.32, 0.64); p &lt; 0.00001].Conclusion: The combination of CHM and AEDs could improve seizure control by reducing monthly seizure frequency and abnormal rate of EEG with a decreased risk of adverse events in patients with IE. However, these findings must be interpreted carefully due to the high or uncertain risk of bias in the included trials. To provide stronger evidence for the use of CHM combined with AEDs in IE, high-quality RCTs will be urgently warranted in the future.
Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections
Authors: Rivara-Espasandín Martin , Palumbo Miranda Clara , Sosa Ezequiel J. , Radío Santiago , Turjanski Adrián G. , Sotelo-Silveira José , Fernandez Do Porto Dario , Smircich Pablo 
Published: April 2023

Introduction:Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches.Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development.Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.
2D, 3D-QSAR study and docking of vascular endothelial growth factor receptor 3 (VEGFR3) inhibitors for potential treatment of retinoblastoma
Authors: Ren Rui , Gao Liyu , Li Guoqi , Wang Shuqiang , Zhao Yangzhong , Wang Haitong , Liu Jianwei 
Published: April 2023

Background: Retinoblastoma is currently the most common malignant tumor seen in newborns and children’s eyes worldwide, posing a life-threatening hazard. Chemotherapy is an integral part of retinoblastoma treatment. However, the chemotherapeutic agents used in clinics often lead to drug resistance. Thus there is a need to investigate new chemotherapy-targeted agents. VEGFR3 inhibitors are anti-tumour-growth and could be used to develop novel retinoblastoma-targeted agents.Objective: To predict drug activity, discover influencing factors and design new drugs by building 2D, 3D-QSAR models.Method: First, linear and non-linear QSAR models were built using heuristic methods and gene expression programming (GEP). The comparative molecular similarity indices analysis (COMISA) was then used to construct 3D-QSAR models through the SYBYL software. New drugs were designed by changing drug activity factors in both models, and molecular docking experiments were performed.Result: The best linear model created using HM had an R2, S2, and R2cv of 0.82, 0.02, and 0.77, respectively. For the training and test sets, the best non-linear model created using GEP had correlation coefficients of 0.83 and 0.72 with mean errors of 0.02 and 0.04. The 3D model designed using SYBYL passed external validation due to its high Q2 (0.503), R2 (0.805), and F-value (76.52), as well as its low standard error of SEE value (0.172). This demonstrates the model’s reliability and excellent predictive ability. Based on the molecular descriptors of the 2D model and the contour plots of the 3D model, we designed 100 new compounds using the best active compound 14 as a template. We performed activity prediction and molecular docking experiments on them, in which compound 14.d performed best regarding combined drug activity and docking ability.Conclusion: The non-linear model created using GEP was more stable and had a more substantial predictive power than the linear model built using the heuristic technique (HM). The compound 14.d designed in this experiment has the potential for anti-retinoblastoma treatment, which provides new design ideas and directions for retinoblastoma-targeted drugs.
Kinematic parameters and metabolic power in elite soccer players: A small sided a large sided games comparison
Authors: Zlojutro Nemanja , Eler Serdar , Joksimovic Marko , Eler Nebahat , Marković Saša , Kukrić Aleksandar , Goranovic Kosta 
Published: April 2023

Introduction: The goal of this paper is to determine what happens in one minute (on average) in kinematic parameters and metabolic power in small sided games (SSG) (3v3; 5v5) and large sided games (LSG) (10v10) and in which games kinematic parameters and metabolic power are best developed.Methods: The participants of this study were 22 professional football players, height 182.95±6.52 cm, mass 77.17±8.21 kg, body mass index (BMI) 22.97±1.47 kg/m2, body fat 9.85±2.55 %, aged 27.1±5.4 yrs, who played in the Premier League of Bosnia and Herzegovina. Data total distance (TD), maximum speed (MS), number of accelerations (nAcc), number of decelerations (nDec), number of sprints (nS), high intensity distance (Z4≥19.8 km/h), sprint distance (Z5≥25.2 km/h) and movements requiring a certain metabolic power (Pmet), were collected using a 20 Hz Global positioning system (GPS) system Pro2 (GPEXE, Exelio srl, Udine, Italy), on a total of 307 individual observations.Results: The results showed that the average total distance was significantly higher in the 5v5 (135.16±18.78 m) and 10v10 (133.43±20.06 m) games (F=64.26, p&lt;0.001) compared to the 3v3 (108.24±11.26 m). Furthermore, the values of the variables Z4 (8.32±3.38 m, F=97.59), Z5 (1.84±1.53 m, F=123.64), nS (0.13±0.10 n, F=96.14) as well as Maxspeed (27.06±1.90 km/h, F=139.33), are statistically significantly higher (p&lt;0.001) in the 10v10 game compared to the other two game formats. The average number of nAcc (0.40±0.32 n, F=9.86, p&lt;0.001) and nDec (0.62±0.36 n, F=6.42, p&lt;0.001) is statistically significantly higher in the 5v5 game. The results showed that the 5v5 game is significantly more metabolically demanding Pmet (2.76±0.67 W•kg−1, F=66.08, p&lt;0.001) compared to the other two game formats.Discussion: The data presented in this paper can be used as a basis for the construction of specific exercises based on kinematic and physiological requirements, and for planning and programming microcycles in football.
Attenuation of stretch-induced arrhythmias following chemical ablation of Purkinje fibres, in isolated rabbit hearts
Authors: Hurley Miriam , Walton Richard , Vigmond Edward J. , Haïssaguerre Michel , Bernus Olivier , White Ed 
Published: April 2023

Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether Purkinje fibres, play a role in these arrhythmias. Pseudo-ECGs were recorded in isolated, Langendorff-perfused, rabbit hearts in which the left ventricular endocardial surface was also irrigated with Tyrode, via an indwelling catheter placed in the left ventricular lumen. The number and period of ectopic activations was measured during left ventricular lumen inflation via an indwelling fluid-filled balloon (500 μL added over 2 s and maintained for 15 s in total). Mechanically-induced arrhythmias occurred in 70% of balloon inflations: they were maximal in the first 5 s and ceased within 15 s. Brief, (10 s) irrigation of the left ventricular lumen with Lugol solution (IK/I2), via the indwelling catheter, reduced inflation-induced ectopics by 98% (p &lt; 0.05). Ablation of endocardial PFs by Lugol was confirmed by Triphenyltetrazolium Chloride staining. Optical mapping revealed the left ventricular epicardial activation patterns of ectopics could have PF-mediated and focal sources. In silico modelling predicted ectopic sources originating in the endocardial region propagate to and through the Purkinje fibres network. Acute distention-induced ectopics are multi-focal, their attenuation by Lugol, their activation patterns and in silico modelling indicate a participation of Purkinje fibres in these arrhythmias.
Distinct metabolite classes in root exudates are indicative for field- or hydroponically-grown cover crops
Authors: Heuermann Diana , Döll Stefanie , Schweneker Dörte , Feuerstein Ulf , Gentsch Norman , von Wirén Nicolaus 
Published: April 2023

IntroductionPlants release a large variety of metabolites via their roots to shape physico-chemical soil properties and biological processes in the rhizosphere. While hydroponic growth conditions facilitate accessibility of the root system and recovery of root exudates, the natural soil environment can alter root metabolism and exudate secretion, raising the question to what extent the quantity and composition of root exudates released in hydroponic growth systems reflect those recovered from soil-grown roots.MethodsUsing a root washing method, we sampled root exudates from four field-grown cover crop species with wide taxonomic distance, namely white mustard, lacy phacelia, bristle oat, and Egyptian clover. A set of primary metabolites and secondary metabolites were analysed in a targeted and untargeted LC-MS-based approach, respectively, for comparison with exudates obtained from hydroponically cultured plants.Results and discussionWe found that hydroponically cultivated plants released a larger amount of total carbon, but that the recovery of total carbon was not indicative for the diversity of metabolites in root exudates. In the field, root exudates from phacelia and clover contained 2.4 to 3.8 times more secondary metabolites, whereas carbon exudation in hydroponics was 5- to 4-fold higher. The composition of the set of metabolites identified using the untargeted approach was much more distinct among all species and growth conditions than that of quantified primary metabolites. Among secondary metabolite classes, the presence of lipids and lipid-like molecules was highly indicative for field samples, while the release of a large amount of phenylpropanoids, organoheterocyclic compounds or benzenoids was characteristic for clover, mustard or oat, respectively, irrespective of the cultivation condition. However, at the compound level the bulk of released metabolites was specific for cultivation conditions in every species, which implies that hydroponically sampled root exudates poorly reflect the metabolic complexity of root exudates recovered from field-grown plants.
Group-based body psychotherapy improves appreciation of body awareness in post-treatment cancer patients: A non-randomized clinical trial
Authors: Grossert Astrid , Meffert Cornelia , Hess Viviane , Rochlitz Christoph , Pless Miklos , Hunziker Sabina , Wössmer Brigitta , Geuter Ulfried , Meinlschmidt Gunther , Schaefert Rainer 
Published: April 2023

IntroductionCancer-related impairments often co-occur with bodily disturbances. Body psychotherapy (BPT) can improve bodily wellbeing, yet evidence in cancer survivors is scarce. Hence, we aimed to evaluate whether blended group BPT alleviates bodily disturbances in post-treatment cancer patients.MethodsWe conducted a bi-center study (registered in ClinicalTrials.gov, under No. NCT03707548), applying a pre-post convergent parallel design of weekly group BPT interspersed with smartphone-based ambulatory interventions using a waiting-period comparator. We included patients with completed curatively intended treatment for malignant neoplasms, suffering from bodily disturbances. The primary outcome was body image disturbances. Secondary outcomes were experiencing and appreciating body awareness, mental wellbeing, and health-related quality of life.ResultsForty patients (mean age 51.7 years) attended group BPT. Mixed-effect linear regression models contrasting intervention with the waiting period did not show statistically significant differences regarding the primary outcome [Pre-post difference contrasts: 1.44, 95% confidence interval (CI): −1.51 to 4.93, p = 0.339]. However, patients showed greater improvements in appreciating body awareness, measured by the “Body Mindfulness Questionnaire” (BMQ), from pre- to post-intervention as compared to the waiting period (pre-post difference contrasts: 7.31 95% CI: 4.15–10.47, Bonferroni-Holm corrected q = 0.0002).DiscussionWe found no evidence that blended group BPT was effective in improving body image disturbances in post-treatment cancer patients, but found indications for an increase in body awareness appreciation.Clinical trial registrationClinicalTrials.gov, identifier NCT03707548.
Typical disease courses of patients with unipolar depressive disorder after in-patient treatments–results of a cluster analysis of the INDDEP project
Authors: Martinek Theresa , Jarczok Marc , Rottler Edit , Hartmann Armin , Zeeck Almut , Weiß Heinz , von Wietersheim Jörn 
Published: April 2023

IntroductionPreviously established categories for the classification of disease courses of unipolar depressive disorder (relapse, remission, recovery, recurrence) are helpful, but insufficient in describing the naturalistic disease courses over time. The intention of the present study was to identify frequent disease courses of depression by means of a cluster analysis.MethodsFor the longitudinal cluster analysis, 555 datasets of patients who participated in the INDDEP (INpatient and Day clinic treatment of DEPression) study, were used. The present study uses data of patients with at least moderate depressive symptoms (major depression) over a follow-up period of 1 year after their in-patient or day-care treatments using the LIFE (Longitudinal Interval Follow-Up Evaluation)-interview. Eight German psychosomatic hospitals participated in this naturalistic observational study.ResultsConsidering only the Calinski–Harabatz index, a 2-cluster solution gives the best statistical results. In combination with other indices and clinical interpretations, the 5-cluster solution seems to be the most interesting. The cluster sizes are large enough and numerically balanced. The KML-cluster analyses revealed five well interpretable disease course clusters over the follow-up period: “sustained treatment response” (N = 202, 36.4% of the patients), “recurrence” (N = 80, 14.4%), “persisting relapse” (N = 115, 20.7%), “temporary relapse” (N = 95, 17.1%), and remission (N = 63, 11.4%).ConclusionThe disease courses of many patients diagnosed with a unipolar depression do not match with the historically developed categories such as relapse, remission, and recovery. Given this context, the introduction of disease course trajectories seems helpful. These findings may promote the implementation of new therapy options, adapted to the disease courses.
Therapist perceptions of the implementation of a new screening procedure using the ItFits-toolkit in an iCBT routine care clinic: A mixed-methods study using the consolidated framework for implementation research
Authors: Tarp Kristine , Nielsen Søren Lange , Holmberg Trine Theresa , Dalsgaard Caroline Høier , Borkner Simone , Skaarnes Helene , Jensen Esben Kjems , Piera-Jiménez Jordi , Vis Christiaan , Mathiasen Kim 
Published: April 2023

IntroductionThis study investigates the implementation of a new, more automated screening procedure using the ItFits-toolkit in the online clinic, Internet Psychiatry (iPsych) (www.internetpsykiatrien.dk), delivering guided iCBT for mild to moderate anxiety and depressive disorders. The study focuses on how the therapists experienced the process.MethodsQualitative data were collected from semi-structured individual interviews with seven therapists from iPsych. The interviews were conducted using an interview guide with questions based on the Consolidated Framework for Implementation Research (CFIR). Quantitative data on the perceived level of normalization were collected from iPsych therapists, administrative staff, and off-site professionals in contact with the target demographic at 10-time points throughout the implementation.ResultsThe therapists experienced an improvement in the intake procedure. They reported having more relevant information about the patients to be used during the assessment and the treatment; they liked the new design better; there was a better alignment of expectations between patients and therapists; the patient group was generally a better fit for treatment after implementation; and more of the assessed patients were included in the program. The quantitative data support the interview data and describe a process of normalization that increases over time.DiscussionThe ItFits-toolkit appears to have been an effective mediator of the implementation process. The therapists were aided in the process of change, resulting in an enhanced ability to target the patients who can benefit from the treatment program, less expenditure of time on the wrong population, and more satisfied therapists.