Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC‐UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty‐seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min−1 completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L−1. Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL−1 in all samples and of 8 μg mL−1 in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB.
Bacterial virulence against an oceanic bloom-forming phytoplankter is mediated by algal DMSP

A new alga-bacterium model system sheds light on mortality factors affecting phytoplankton bloom demise and sulfur cycling. Emiliania huxleyi is a bloom-forming microalga that affects the global sulfur cycle by producing large amounts of dimethylsulfoniopropionate (DMSP) and its volatile metabolic product dimethyl sulfide. Top-down regulation of E. huxleyi blooms has been attributed to viruses and grazers; however, the possible involvement of algicidal bacteria in bloom demise has remained elusive. We demonstrate that a Roseobacter strain, Sulfitobacter D7, that we isolated from a North Atlantic E. huxleyi bloom, exhibited algicidal effects against E. huxleyi upon coculturing. Both the alga and the bacterium were found to co-occur during a natural E. huxleyi bloom, therefore establishing this host-pathogen system as an attractive, ecologically relevant model for studying algal-bacterial interactions in the oceans. During interaction, Sulfitobacter D7 consumed and metabolized algal DMSP to produce high amounts of methanethiol, an alternative product of DMSP catabolism. We revealed a unique strain-specific response, in which E. huxleyi strains that exuded higher amounts of DMSP were more susceptible to Sulfitobacter D7 infection. Intriguingly, exogenous application of DMSP enhanced bacterial virulence and induced susceptibility in an algal strain typically resistant to the bacterial pathogen. This enhanced virulence was highly specific to DMSP compared to addition of propionate and glycerol which had no effect on bacterial virulence. We propose a novel function for DMSP, in addition to its central role in mutualistic interactions among marine organisms, as a mediator of bacterial virulence that may regulate E. huxleyi blooms.
Modeling of Protein Structural Flexibility and Large-Scale Dynamics: Coarse-Grained Simulations and Elastic Network Models

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function of proteins and their complexes. Experimental studies of such phenomena remain very challenging and therefore molecular modeling can be a good alternative or a valuable supporting tool for the investigation of large molecular systems and long-time events. In this minireview, we present two alternative approaches to the coarse-grained (CG) modeling of dynamic properties of protein systems. We discuss two CG representations of polypeptide chains used for Monte Carlo dynamics simulations of protein local dynamics and conformational transitions, and highly simplified structure-based elastic network models of protein flexibility. In contrast to classical all-atom molecular dynamics, the modeling strategies discussed here allow the quite accurate modeling of much larger systems and longer-time dynamic phenomena. We briefly describe the main features of these models and outline some of their applications, including modeling of near-native structure fluctuations, sampling of large regions of the protein conformational space, or possible support for the structure prediction of large proteins and their complexes.
A Mobile Cough Strength Evaluation Device Using Cough Sounds

Although cough peak flow (CPF) is an important measurement for evaluating the risk of cough dysfunction, some patients cannot use conventional measurement instruments, such as spirometers, because of the configurational burden of the instruments. Therefore, we previously developed a cough strength estimation method using cough sounds based on a simple acoustic and aerodynamic model. However, the previous model did not consider age or have a user interface for practical application. This study clarifies the cough strength prediction accuracy using an improved model in young and elderly participants. Additionally, a user interface for mobile devices was developed to record cough sounds and estimate cough strength using the proposed method. We then performed experiments on 33 young participants (21.3 ± 0.4 years) and 25 elderly participants (80.4 ± 6.1 years) to test the effect of age on the CPF estimation accuracy. The percentage error between the measured and estimated CPFs was approximately 6.19%. In addition, among the elderly participants, the current model improved the estimation accuracy of the previous model by a percentage error of approximately 6.5% (p < 0.001). Furthermore, Bland-Altman analysis demonstrated no systematic error between the measured and estimated CPFs. These results suggest that the developed device can be applied for daily CPF measurements in clinical practice.
Deep Learning Based Real-Time Driver Emotion Monitoring

In this paper, we propose a novel, real-time driver emotion monitoring system “in the wild” based on face detection and racial expression analysis. A camera is placed inside the vehicle that continuously looks at the driver's face and monitors the driver's emotional state at regular time intervals. Camera based monitoring of the driver's attentiveness based on the driver's emotional state in naturalistic driving environments is a non-intrusive approach and an important part of an automated driver assistance system (ADAS). Our work employs a face detection model based on mixture of trees with shared pool of parts to robustly detect the drivers face in varied environmental conditions. We also extract racial landmark points, and use them to enhance our emotion recognition system. In our proposed work, we use convolution neural networks. In the first, we use VGG16 to extract appearance features from the detected face image and in the second VGG16 network, to extract geometrical features from the racial landmark points. We then combine these two features using an integration method to accurately recognize the emotions. Based on the recognized emotional state of the driver, the driver can be made aware of his emotional state in case necessary. Experimental results on publicly available driver and face expression datasets show that our system is robust and accurate for driver emotion detection.
Executive Dysfunction in Patients With Korsakoff’s Syndrome: A Theory-Driven Approach

Aims In addition to amnesia, executive deficits are prominent in Korsakoff's syndrome (KS), yet poorly studied. This study investigates the degree of executive dysfunction in patients with KS for the three main executive subcomponents shifting, updating and inhibition using novel, theory-driven paradigms. Short summary Compared to healthy controls, patients with KS show impairments on the executive subcomponents shifting and updating, but not on inhibition. Methods Executive functions were measured with six carefully designed tasks in 36 abstinent patients with KS (mean age 62.3; 28% woman) and compared with 30 healthy non-alcoholic controls (mean age 61.8; 40% woman). ANOVAs were conducted to examine group differences and effect sizes were calculated. Results Compared to healthy controls, patients with KS were impaired on the executive subcomponents shifting and updating. No statistically significant group difference was found on the factor inhibition. Conclusions Executive dysfunction in long-abstinent patients with alcoholic KS shows a profile in which shifting and updating ability are affected most. It also highlights that executive dysfunction is an important feature of KS and requires more attention in scientific and clinical practice, as these deficits may also affect daily functioning.
Nocturnal blood pressure measured by home devices: evidence and perspective for clinical application

&NA; Studies using ambulatory blood pressure (BP) monitoring have shown that BP during night-time sleep is a stronger predictor of cardiovascular outcomes than daytime ambulatory or conventional office BP. However, night-time ambulatory BP recordings may interfere with sleep quality because of the device cuff inflation and frequency of measurements. Hence, there is an unmet need for obtaining high quality BP values during sleep. In the last two decades, technological development of home BP devices enabled automated BP measurements during night-time. Preliminary data suggest that nocturnal home BP measurements yield similar BP values and show good agreement in detecting nondippers when compared with ambulatory BP monitoring. Thus, nocturnal home BP measurements might be a reliable and practical alternative to ambulatory BP monitoring to evaluate BP during sleep. As the use of home BP devices is widespread, well accepted by users and has relatively low cost, it may prove to be more feasible and widely available for routine clinical assessment of nocturnal BP. At present, however, data on the prognostic relevance of nocturnal BP measured by home devices, the optimal measurement schedule, and other methodological issues are lacking and await further investigation. This article offers a systematic review of the current evidence on nocturnal home BP, highlights the remaining research questions, and provides preliminary recommendations for application of this novel approach in BP management.
Seasonal variations in cellular and humoral immunity in male striped hamsters (Cricetulus barabensis)

ABSTRACT Animals in the non-tropical zone usually demonstrate seasonal variations in immune function, which is important for their survival. In the present study, seasonal changes in immunity in striped hamsters (Cricetulus barabensis) were investigated to test the winter immunoenhancement hypothesis. Male hamsters were captured from the wild in the fall and winter of 2014 and in the spring and summer of 2015. Body mass, body fat mass and blood glucose levels of the hamsters were all highest in the summer, whereas relative fatness and thymus mass had no seasonal changes. Spleen mass was highest in the fall and white blood cells and phytohaemagglutinin (PHA) response indicative of cellular immunity were lowest in the summer among the four seasons, which supports the winter immunoenhancement hypothesis. IgG and IgM titers were lowest in the fall, which was against this hypothesis. Body fat mass had no correlations with cellular and humoral immunity, suggesting it was not the reason for seasonal changes in cellular and humoral immunity in males. Leptin titers were higher in spring and summer than in fall and winter. No correlation between leptin and cellular and humoral immunity suggested that leptin did not mediate their seasonal changes. Similarly, corticosterone levels were also higher in spring and summer than in fall and winter, which correlated negatively with cellular immunity but positively with IgG levels. This result implied that corticosterone has a suppressive effect on cellular immunity and an enhancing effect on humoral immunity. In summary, distinct components of immune systems exhibited different seasonal patterns. This article has an associated First Person interview with the first author of the paper. Summary: Seasonal changes in immunity, body fat, blood glucose, leptin and corticosterone and their correlations in striped hamsters.
Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines

Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly‐chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B‐cell lymphoma and follicular lymphoma undergoing first‐line immunochemotherapy from 2000–2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline‐containing chemotherapy [R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R‐CHOEP (R‐CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3–5 cycles of R‐CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5‐year risk of CHF with all‐cause mortality as competing risk was 4·6% after 3–5 cycles of R‐CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5‐year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first‐line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R‐CHOP/CHOEP is associated with a significant increase in CHF rate.
Inhibition of calpain delays early muscle atrophy after rotator cuff tendon release in sheep

Chronic rotator cuff (RC) tears are characterized by retraction, fat accumulation, and atrophy of the affected muscle. These features pose an intractable problem for surgical repair and subsequent recovery, and their prevention may be easier than reversal. Using an established ovine model, we tested the hypothesis that inhibition of the protease calpain mitigates m. infraspinatus atrophy by preservation of the myofibers’ structural anchors in the sarcolemma (the costameres). Already 2 weeks of distal tendon release led to a reduction in muscle volume (−11.6 ± 9.1 cm3, P = 0.038) and a 8.3% slow‐to‐fast shift of the fiber area (P = 0.046), which were both entirely abolished by chronic local administration of the calpain inhibitor calpeptin alone, and in combination with sildenafil. Calpain inhibition blunted the retraction of the muscle‐tendon unit by 0.8–1.0 cm (P = 0.020) compared with the control group, and prevented cleavage of the costameric protein talin. Calpain 1 and 2 protein levels increased in the medicated groups after 4 weeks, counteracting the efficacy of calpeptin. Hence atrophic changes emerged after 4 weeks despite ongoing treatment. These findings suggest that the early muscular adaptations in the specific case of RC tear in the ovine model are indistinguishable from the atrophy and slow‐to‐fast fiber transformation observed with conventional unloading and can be prevented for 2 weeks. Concluding, calpain is a potential target to extend the temporal window for reconstruction of the ruptured RC tendon before recovery turns impossible.
Expression of somatostatin and its receptor 1–5 in endometriotic tissues and cells

The present study aimed to detect the expression of somatostatin (SS) and SS receptor (SSTR)1-5 in tissues from patients with endometriosis (EMS). Reverse transcription-quantitative polymerase chain reaction analysis was applied to examine the expression of somatostatin gene in ectopic endometrial cells (EECs). The expression of somatostatin receptor 1–5 in the ectopic endometrium (EE), eutopic endometrium and normal endometrium and their association with EMS staging were determined by immunohistochemistry. The results indicated that the expression of SS in EECs was significantly higher compared with that in the control group. SSTR1-5 were expressed in the EE tissues from 30 patients with EMS, and the positive rates were 43.3, 70.0, 53.3, 50.0 and 96.7%, respectively, which were closely associated with EMS staging of the patients. The positive rates of SSTR1-5 expression in the eutopic endometrium from 12 patients with EMS were 33.3, 41.7, 58.3, 58.3 and 83.3%, respectively, while the positive rates of SSTR1-5 expression in the normal endometrium from 14 women without EMS were 7.1, 7.1, 21.4, 28.6 and 64.3%, which were lower than the positive rates of SSTR1-5 in the EE (43.3, 70, 53.3, 50 and 96.7%) and eutopic endometrial cells (33.3, 41.7, 58.3, 58.3 and 83.3%). In conclusion, SS was highly expressed in EECs. SSTR1-5 were expressed in the ectopic as well as eutopic endometrium, and low or moderate expression of SSTR1-4 and high expression of SSTR5 were detected in the ectopic and eutopic endometrial tissues, while low expression of SSTR1-4 and partial expression of SSTR5 were detected in normal endometrium. The positive rates of expression of SSTR1-5 in the EE cells and eutopic endometrium were higher than those in the normal endometrium. The expression of all the subtypes of SSTR in the EE tissues was closely associated with EMS staging.
pH and redox dual-responsive copolymer micelles with surface charge reversal for co-delivery of all-trans-retinoic acid and paclitaxel for cancer combination chemotherapy

Background Co-delivery all-trans-retinoic acid (ATRA) and paclitaxel (PTX) is an effective strategy for cancer therapy. However, in many previous reported ATRA conjugated co-delivery systems, the ATRA was released slower than PTX, and the total drug release of ATRA far lower than that of PTX. Purpose We designed and prepared a pH and redox dual responsive drug delivery system (DA-ss-NPs) co-delivery ATRA and PTX for cancer therapy. The surface charge of DA-ss-NPs could change from negative to positive under tumor slightly acidic microenvironment, and both drugs could be quickly released from DA-ss-NPs under intracellular high concentration of glutathione (GSH). Methods The DA-ss-NPs were constructed by encapsulating PTX into the hydrophobic core of the polymer micelles, in which the polymer was synthesized by conjugating ATRA and 2,3-Dimethylmalefic anhydride (DMA) on side chains of Cystamine dihydrochloride (Cys) modified PEG-b-PAsp (named DA-ss-NPs). The surface charge of DA-ss-NPs under different pH conditions were detected. And the drug release was also measured under different concentration of GSH. The therapeutic effect of DA-ss-NPs were investigated in Human lung cancer A549 cells and A549 tumor-bearing mice. Results The zeta potential of DA-ss-NPs was -16.3 mV at pH 7.4, and which changed to 16 mV at pH 6.5. Cell uptake experiment showed that more DA-ss-NPs were internalized by A549 cells at pH 6.5 than that at pH 7.4. In addition, in presence of 10 mM GSH at pH 7.4, about 75%-85% ATRA was released from DA-ss-NPs within 48 h; but less than 20% ATRA was released without GSH. In vivo antitumor efficiency showed that the DA-ss-NPs could affectively inhibite the tumor in compared with control groups. Conclusion The charge-reversal and GSH-responsive DA-ss-NPs provide an excellent platform for potential tumor therapy.
Validity and the reliability of the Turkish version of the control of allergic rhinitis and asthma test for children (CARATKids)

Abstract Aim: Asthma occurs in association with allergic rhinitis. Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is a questionnaire to assess control of both diseases. The aim of this study was to assess the validity and reliability of the CARATKids in Turkish children aged 6–12 years. Methods: After a cultural adaptation process, children with asthma and allergic rhinitis were recruited. CARATKids, childhood Asthma Control Test, total nasal symptom score, visual analog scale scores for asthma and rhinitis, peak nasal inspiratory flow and peak expiratory flow values were obtained at baseline and after 4–6 weeks. The patients were classified according to the control level for asthma and rhinitis and stable/unstable groups. Discriminative properties, internal consistency, test–retest reliability, responsiveness, validity and minimal clinically important difference (MCID) were assessed. Receiver operating characteristic curve analysis was performed. Results: About 174 patients were included. The Cronbach’s alpha was 0.841. Correlation coefficients between CARATKids and external measures of control were 0.42–0.77, and between the score changes of CARATKids and external measures of control it was 0.56–0.78. Guyatt’s responsiveness index was −1.88, within-patient change of CARATKids score was significant. The intra-class correlation coefficient was 0.973. The MCID was 4. A cutoff score of ≤5 on the CARATKids had a sensitivity of 100% to distinguish the controlled groups according to both the GINA and ARIA. Conclusion: CARATKids is a reliable and valid tool to assess asthma and allergic rhinitis control in Turkish children. A score of ≤5 on CARATKids defines controlled disease for both diseases simultaneously.
N1 lateralization and dyslexia: An event‐related potential study in children with a familial risk of dyslexia

The rapid automatic specialized processing of printed words is signalled by the left‐lateralization of the N1 component in the visual event‐related potential (ERP). In the present study, we have investigated whether differences in N1 lateralization can be observed between Dutch children with and without (a familial risk of) dyslexia around the age of 12 years using a linguistic judgement task. Forty‐five participants were included in the ERP analysis, 18 in the low familial risk group without dyslexia, 15 in the high familial risk group without dyslexia, and 12 in the high familial risk group with dyslexia. The results showed that although the N1 peaked slightly earlier in the left hemisphere, the N1 amplitude was right‐lateralized in all groups. Moreover, there were no group differences in N1 amplitude or latency, and there was no relationship between reading (related) test scores and N1 characteristics. The results of the present study and our previous findings in adults suggest that print‐tuning lateralization is a process that is still developing in adolescence. Because other studies did find N1 lateralization in younger readers with a print versus nonprint contrast, the current results seem to indicate that differences in N1 lateralization also depend on the experimental paradigm.