Miracle-dz/UniFAR-FTUs huggingface dataset:
Add-on sorafenib is beneficial for hepatocellular carcinoma patients with transarterial chemoembolization refractoriness: a real-world experience

Background and aims: Sorafenib is the first proved target therapy that shows significant survival benefit in advanced hepatocellular carcinoma. This study was aimed to investigate whether add-on sorafenib be beneficial for those experienced transarterial chemoembolization refractoriness. Methods: From 2005 to 2016, a total of 656 treatment-naive hepatocellular carcinoma patients receiving transarterial chemoembolization treatment were recruited. Transarterial chemoembolization refractoriness was defined as progressive disease after two consecutive of transarterial chemoembolization treatment within 6 months. Patient’s baseline characteristics, tumor burden, and parameters for liver function evaluation during treatment were analyzed. All the variables were compared between patients with and without transarterial chemoembolization refractoriness, as well as with and without add-on sorafenib. Results: Among the 656 patients, the median age was 62.5 (range 27.3–91.5) years old, and 74.5% were male. Transarterial chemoembolization refractoriness events were documented in 202 patients (30.8%). After multivariate logistic regression analysis, tumor size ≧5 cm, baseline alpha-fetoprotein level ≧200 mg/dl, elevation of alpha-fetoprotein ≧20%, and elevation of Child-Turcotte-Pugh score ≧2 points after first transarterial chemoembolization were the independent predictive factors for transarterial chemoembolization refractoriness. Twenty-two patients (10.9%) received add-on sorafenib treatment and 146 (72.3%) patients continued transarterial chemoembolization treatment alone. After 1:2 propensity score matching, patients with add-on sorafenib therapy had significantly longer median overall survival than transarterial chemoembolization treatment alone (23.1 vs. 11.0 months, log-rank P = 0.001). Conclusion: The tumor size, baseline alpha-fetoprotein, and elevation of alpha-fetoprotein and Child-Turcotte-Pugh score after first transarterial chemoembolization were the predictors for transarterial chemoembolization refractoriness. For patients with transarterial chemoembolization refractoriness, add-on sorafenib achieved better survival benefit than transarterial chemoembolization treatment alone.
Characteristics, Opportunities, and Challenges of Osteopathy (COCO) in the Perceptions of Osteopaths in Germany, Austria, and Switzerland: Protocol for a Comprehensive Mixed Methods Study

Background Currently, the importance of osteopathy within the health care system is controversial. The training structures and the acknowledgment of the occupational profile strongly differ in the German-speaking territory. Objective This study aims to examine the characteristics of the osteopathic profession as well as the possibilities and challenges for osteopaths in Germany, Austria, and Switzerland. Methods This study adopted a mixed methods design. The research topic will be examined based on qualitative and quantitative partial studies that will be conducted in parallel as well as sequentially. By applying different research methods and sample testing and by using standardized, validated measurement methods, we expect to be able to gain new insights into the work area of osteopathy. Results In November 2018, we started the research and data collection. Currently, we are conducting the first two partial studies. The planned duration of each of the partial study is 6-9 months. The project is scheduled to be completed in 2021. Conclusions This study will examine how osteopaths define themselves in comparison with professionals from other occupational profiles and how they describe the characteristics of their work. The identification of central issues is expected to help clarify the issues and define the profession. As such, the results might contribute to the conservation and improvement of the quality of osteopathic treatment. International Registered Report Identifier (IRRID) PRR1-10.2196/15399
Effects of Home Exercises on Shoulder Pain and Pathology in Chronic Spinal Cord Injury

Supplemental digital content is available in the text. Objective The aims of this study were to replicate findings that a home exercise program intervention improved shoulder pain and function and to assess changes in supraspinatus tendon pathology associated with the home exercise program in persons with chronic spinal cord injury. Design The study is a single-blind randomized controlled trial. Individuals with spinal cord injury of at least 1 yr and chronic shoulder pain of moderate or greater average intensity were enrolled. Participants were randomized to a 12-wk home exercise program consisting of strengthening and stretching exercises or to an education-only control group, with immediate postintervention and 4-wk postintervention (16 wks) follow-ups. The main outcome measures were self-report measures of shoulder pain and impairment, the Physical Examination of the Shoulder Scale, quantitative ultrasound metrics of the supraspinatus tendon, and the Ultrasound Shoulder Pathology Rating Scale. Results Thirty-two participants were randomized to home exercise program or education-only control condition. The mean ± SD age was 44.8 ± 12.5; 81.3% were male; 65.6% had motor complete paraplegia. Using a per-protocol, within-group analysis method, significant differences were observed between baseline and postintervention for the home exercise program group for the least pain intensity (P = 0.02), number of days with shoulder pain (P = 0.042), Physical Examination of the Shoulder Scale scores (dominant side, P = 0.036; nondominant side, P = 0.008), the Disabilities of the Arm, Shoulder, and Hand (P = 0.028), and the Patient Global Impression of Change (P = 0.015). The education-only control condition group demonstrated significant changes in average unpleasantness of shoulder pain after the intervention period (P = 0.049). Comparisons in changes from baseline between groups showed that the home exercise program group had greater improvements in nondominant-side Physical Examination of the Shoulder Scale scores and global impression of change, whereas the education-only control condition group had greater improvements in depressive symptoms. For quantitative ultrasound measures, no significant changes were found with within-group analyses for the home exercise program group, although the education-only control condition group demonstrated a decrease in tendon width in the nondominant-side supraspinatus tendon (P = 0.036). Comparison of changes between groups suggests that the education-only control condition group had a greater increase in dominant shoulder supraspinatus tendon ultrasound contrast at the end of the study. Conclusions Changes in several measures of shoulder pain and function occurred after the home exercise program intervention, although the magnitude of changes was only significantly greater than those of the education-only control condition group for two measures. Significant changes in supraspinatus pathology were not detected with quantitative ultrasound metrics.
Self-Esteem and Depression as Mediators of the Effects of Gratitude on Suicidal Ideation Among Taiwanese College Students

This study aimed at examining the roles of self-esteem and depression in the relationship between gratitude and suicidal ideation. A total of 814 Taiwanese college students ranging in age from 18 to 22 years completed measures of gratitude, self-esteem, depression, and suicidal ideation. Structural equation modeling showed partial mediation effects of self-esteem and depression between gratitude and suicidal ideation. Moreover, a multigroup analysis found that males with higher levels of self-esteem could protect themselves from depression more easily than their female counterparts. Implications for future research and limitations of the present findings are discussed.
Optimization of Flat Ends in Pressure Vessels

The application of flat ends in pressure boilers is inevitably associated with the presence of stress concentration, which is observed in the vicinity of the junction of the cylinder and the closing flat plate. The analyzed flat end plates with stress relief grooves fall into the group of solutions recognized by the respective Standards of Calculations of Pressure Vessels. Unfortunately, no clear evidence is given in the Standards on how to choose the best groove parameters. This opens up the problem of the optimal choice of the groove parameters providing a minimum stress level. Even for the optimal values defining the stress relief groove geometry, certain plastic deformations are observed in the groove area for materials which exhibit elastic-plastic properties. Such a situation is completely unacceptable during exploitation, and a suitable reduction of the operating pressure is necessary. This paper discusses the effectiveness of other designs for flat ends used in pressure vessels. The proposed modifications took the form of external ribs applied around the top of the endplate circumference. The dimensions of these ribs were set using parametric optimization. The results of the study encouraged the authors to perform a more general analysis with the use of topology optimization. The results of all performed studies proved that the reduction of stress concentration and the full elimination of plastic deformation are possible. All numerical calculations were made using the finite element code (FEM), Ansys.
NOx-, IL-1β-, TNF-α-, and IL-6-Inhibiting Effects and Trypanocidal Activity of Banana (Musa acuminata) Bracts and Flowers: UPLC-HRESI-MS Detection of Phenylpropanoid Sucrose Esters

Banana inflorescences are a byproduct of banana cultivation consumed in various regions of Brazil as a non-conventional food. This byproduct represents an alternative food supply that can contribute to the resolution of nutritional problems and hunger. This product is also used in Asia as a traditional remedy for the treatment of various illnesses such as bronchitis and dysentery. However, there is a lack of chemical and pharmacological data to support its consumption as a functional food. Therefore, this work aimed to study the anti-inflammatory action of Musa acuminata blossom by quantifying the cytokine levels (NOx, IL-1β, TNF-α, and IL-6) in peritoneal neutrophils, and to study its antiparasitic activities using the intracellular forms of T. cruzi, L. amazonensis, and L. infantum. This work also aimed to establish the chemical profile of the inflorescence using UPLC-ESI-MS analysis. Flowers and the crude bract extracts were partitioned in dichloromethane and n-butanol to afford four fractions (FDCM, FNBU, BDCM, and BNBU). FDCM showed moderate trypanocidal activity and promising anti-inflammatory properties by inhibiting IL-1β, TNF-α, and IL-6. BDCM significantly inhibited the secretion of TNF-α, while BNBU was active against IL-6 and NOx. LCMS data of these fractions revealed an unprecedented presence of arylpropanoid sucroses alongside flavonoids, triterpenes, benzofurans, stilbenes, and iridoids. The obtained results revealed that banana inflorescences could be used as an anti-inflammatory food ingredient to control inflammatory diseases.
Adenosine A1-A2A Receptor-Receptor Interaction: Contribution to Guanosine-Mediated Effects

Guanosine, a guanine-based purine nucleoside, has been described as a neuromodulator that exerts neuroprotective effects in animal and cellular ischemia models. However, guanosine’s exact mechanism of action and molecular targets have not yet been identified. Here, we aimed to elucidate a role of adenosine receptors (ARs) in mediating guanosine effects. We investigated the neuroprotective effects of guanosine in hippocampal slices from A2AR-deficient mice (A2AR−/−) subjected to oxygen/glucose deprivation (OGD). Next, we assessed guanosine binding at ARs taking advantage of a fluorescent-selective A2AR antagonist (MRS7396) which could engage in a bioluminescence resonance energy transfer (BRET) process with NanoLuc-tagged A2AR. Next, we evaluated functional AR activation by determining cAMP and calcium accumulation. Finally, we assessed the impact of A1R and A2AR co-expression in guanosine-mediated impedance responses in living cells. Guanosine prevented the reduction of cellular viability and increased reactive oxygen species generation induced by OGD in hippocampal slices from wild-type, but not from A2AR−/− mice. Notably, while guanosine was not able to modify MRS7396 binding to A2AR-expressing cells, a partial blockade was observed in cells co-expressing A1R and A2AR. The relevance of the A1R and A2AR interaction in guanosine effects was further substantiated by means of functional assays (i.e., cAMP and calcium determinations), since guanosine only blocked A2AR agonist-mediated effects in doubly expressing A1R and A2AR cells. Interestingly, while guanosine did not affect A1R/A2AR heteromer formation, it reduced A2AR agonist-mediated cell impedance responses. Our results indicate that guanosine-induced effects may require both A1R and A2AR co-expression, thus identifying a molecular substrate that may allow fine tuning of guanosine-mediated responses.
Body Image and Disturbed Eating Attitudes and Behaviors in Sport-Involved Adolescents: The Role of Gender and Sport Characteristics

Disordered eating in adolescents who participate in sports is an issue of great concern. However, very few studies have examined the prevalence of sport-related determinants of disturbed eating attitudes and behaviours (DEABs) in sport-involved adolescents. The present study aims to assess body image and DEABs in the sample of adolescents involved in a sport of different characteristics (competitive sport, leisure sport; weight-sensitive and less-weight-sensitive sport) and to compare the results with those of the controls. A total sample of 732 adolescents (437 (59.4%) were female) participated in the study. The participants ranged in age from 16 to 19 years (mean = 17.2, SD = 0.6). Study participants completed a questionnaire assessing sports characteristics, body image, disordered eating, and health-compromising eating behaviours. Analysis of covariance was used to test the differences of major study variables between controls and weight-sensitive and less-weight-sensitive leisure and competitive sports groups. There was no significant difference observed in DEABs between the sports groups. Competitive athletes reported more satisfaction with body image than controls. The girls participating in weight-sensitive leisure sports reported higher overweight preoccupation and greater DEABs compared to those participating in less-weight-sensitive leisure sports. Boys participating in weight-sensitive leisure sports reported a greater drive for muscularity-related behaviour compared to those participating in less-weight-sensitive leisure sports. There was no observed interaction between gender and weight sensitivity in the competitive sports group. Adolescents involved in a competitive sport demonstrated greater body image satisfaction and did not seem to present a greater risk for DEABs than controls. Special prevention attempts for lowering body image concerns and DEABs should be addressed for adolescents participating in a weight-sensitive leisure sports.
Detection of Copy Number Alterations by Shallow Whole-Genome Sequencing of Formalin-Fixed, Paraffin-Embedded Tumor Tissue.

CONTEXT. — In routine clinical practice, tumor tissue is stored in formalin-fixed, paraffin-embedded blocks. However, the use of formalin-fixed, paraffin-embedded tissue for genome analysis is challenged by poorer DNA quality and quantity. Although several studies have reported genome-wide massive parallel sequencing applied on formalin-fixed, paraffin-embedded samples for mutation analysis, copy number analysis is not yet commonly performed. OBJECTIVE. — To evaluate the use of formalin-fixed, paraffin-embedded tissue for copy number alteration detection using shallow whole-genome sequencing, more generally referred to as copy number variation sequencing. DESIGN. — We selected samples from 21 patients, covering a range of different tumor entities. The performance of copy number detection was compared across 3 setups: array comparative genomic hybridization in combination with fresh material; copy number variation sequencing on fresh material; and copy number variation sequencing on formalin-fixed, paraffin-embedded material. RESULTS. — Very similar copy number profiles between paired samples were obtained. Although formalin-fixed, paraffin-embedded profiles often displayed more noise, detected copy numbers seemed equally reliable if the tumor fraction was at least 20%. CONCLUSIONS. — Copy number variation sequencing of formalin-fixed, paraffin-embedded material represents a trustworthy method. It is very likely that copy number variation sequencing of routinely obtained biopsy material will become important for individual patient care and research. Moreover, the basic technology needed for copy number variation sequencing is present in most molecular diagnostics laboratories.
Accessibility of children with special health needs to the health care network.

OBJECTIVE To know how children with special health needs access the health care network. METHOD This is a qualitative research of descriptive-exploratory type, developed using semi-structured interviews mediated by the Talking Map design. Participants were 19 family caregivers of these children in two Brazilian municipalities. Data were submitted to inductive thematic analysis. RESULTS Difficulties were mentioned from the diagnosis moment to the specialized follow-up, something represented by the itinerary of the c hild and his/her family in the search for the definition of the medical diagnosis and the access to a specialized professional; a gap between the children's needs and the care offered was observed in primary health care. CONCLUSION The access of children with special health needs is filled with obstacles such as slowness in the process of defining the child's diagnosis and referral to a specialist. Primary health care services were replaced by care in emergency care units.
Primary Epstein-Barr virus infection with and without infectious mononucleosis

Background Infectious mononucleosis (IM) is a common adverse presentation of primary infection with Epstein-Barr virus (EBV) in adolescence and later, but is rarely recognized in early childhood where primary EBV infection commonly occurs. It is not known what triggers IM, and also not why IM risk upon primary EBV infection (IM attack rate) seemingly varies between children and adolescents. IM symptoms may be severe and persist for a long time. IM also markedly elevates the risk of Hodgkin lymphoma and multiple sclerosis for unknown reasons. The way IM occurrence depends on age and sex is incompletely described and hard to interpret etiologically, because it depends on three quantities that are not readily observable: the prevalence of EBV-naϊve persons, the hazard rate of seroconverting and the attack rate, i.e. the fraction of primary EBV infections that is accompanied by IM. We therefore aimed to provide these quantities indirectly, to obtain epidemiologically interpretable measures of the dynamics of IM occurrence to provide etiological clues. Methods and findings We used joint modeling of EBV prevalence and IM occurrence data to provide detailed sex- and age-specific EBV infection rates and IM attack rates and derivatives thereof for a target population of all Danes age 0–29 years in 2006–2011. We demonstrate for the first time that IM attack rates increase dramatically rather precisely in conjunction to typical ages of puberty onset. The shape of the seroconversion hazard rate for children and teenagers confirmed a priori expectations and underlined the importance of what happens at age 0–2 years. The cumulative risk of IM before age 30 years was 13.3% for males and 22.4% for females. IM is likely to become more common through delaying EBV infection in years to come. Conclusions The change in attack rate at typical ages of puberty onset suggests that the immunologic response to EBV drastically changes over a relatively short age-span. We speculate that these changes are an integrated part of normal sexual maturation. Our findings may inform further etiologic research into EBV-related diseases and vaccine design. Our methodology is applicable to the epidemiological study of any infectious agent that establishes a persistent infection in the host and the sequelae thereof.
Substrate binding in the processive cellulase Cel7A: Transition state of complexation and roles of conserved tryptophan residues

Cellobiohydrolases effectively degrade cellulose and are of biotechnological interest because they can convert lignocellulosic biomass to fermentable sugars. Here, we implemented a fluorescence-based method for real-time measurements of complexation and decomplexation of the processive cellulase Cel7A and its insoluble substrate, cellulose. The method enabled detailed kinetic and thermodynamic analyses of ligand binding in a heterogeneous system. We studied WT Cel7A and several variants in which one or two of four highly conserved Trp residues in the binding tunnel had been replaced with Ala. WT Cel7A had on/off-rate constants of 1 × 105 m−1 s−1 and 5 × 10−3 s−1, respectively, reflecting the slow dynamics of a solid, polymeric ligand. Especially the off-rate constant was many orders of magnitude lower than typical values for small, soluble ligands. Binding rate and strength both were typically lower for the Trp variants, but effects of the substitutions were moderate and sometimes negligible. Hence, we propose that lowering the activation barrier for complexation is not a major driving force for the high conservation of the Trp residues. Using so-called Φ-factor analysis, we analyzed the kinetic and thermodynamic results for the variants. The results of this analysis suggested a transition state for complexation and decomplexation in which the reducing end of the ligand is close to the tunnel entrance (near Trp-40), whereas the rest of the binding tunnel is empty. We propose that this structure defines the highest free-energy barrier of the overall catalytic cycle and hence governs the turnover rate of this industrially important enzyme.
Polyphenols, Antioxidant, Antibacterial, and Biofilm Inhibitory Activities of Peel and Pulp of Citrus medica L., Citrus bergamia, and Citrus medica cv. Salò Cultivated in Southern Italy

The aim of this paper was to study the polyphenols of peel and pulp of three Citrus taxa—Citrus medica, Citrus bergamia, and Citrus medica cv. Salò—cultivated in the Cosenza province, Southern Italy, and to evaluate their antioxidant and antibacterial activity, performed against Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Staphylococcus aureus, and Pectobacterium carotovorum. Furthermore, we assessed the inhibitory effect of the extracts on bacterial capacity to form biofilm, and on the metabolic activity of the cells present therein. The results indicated that such extracts could find new potential applications in the field of natural antioxidant and anti-bacterial agents in pharmaceutics, agriculture, and food fields.