Miracle-dz/UniFAR-FTUs huggingface dataset:
Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02)

Objective Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Methods Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m2 day 1) and paclitaxel (135 mg/m2 day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. Results The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. Conclusion Rikkunshito provided additive effect for the prevention of CINV and anorexia.
IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14)

Objective— IL-35 (interleukin-35) is an anti-inflammatory cytokine, which inhibits immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. It remains unknown whether atherogenic stimuli induce IL-35 and whether IL-35 inhibits atherogenic lipid-induced endothelial cell (EC) activation and atherosclerosis. EC activation induced by hyperlipidemia stimuli, including lysophosphatidylcholine is considered as an initiation step for monocyte recruitment and atherosclerosis. In this study, we examined the expression of IL-35 during early atherosclerosis and the roles and mechanisms of IL-35 in suppressing lysophosphatidylcholine-induced EC activation. Approach and Results— Using microarray and ELISA, we found that IL-35 and its receptor are significantly induced during early atherosclerosis in the aortas and plasma of ApoE (apolipoprotein E) knockout mice—an atherosclerotic mouse model—and in the plasma of hypercholesterolemic patients. In addition, we found that IL-35 suppresses lysophosphatidylcholine-induced monocyte adhesion to human aortic ECs. Furthermore, our RNA-sequencing analysis shows that IL-35 selectively inhibits lysophosphatidylcholine-induced EC activation-related genes, such as ICAM-1 (intercellular adhesion molecule-1). Mechanistically, using flow cytometry, mass spectrometry, electron spin resonance analyses, and chromatin immunoprecipitation-sequencing analyses, we found that IL-35 blocks lysophosphatidylcholine-induced mitochondrial reactive oxygen species, which are required for the induction of site-specific H3K14 (histone 3 lysine 14) acetylation, increased binding of proinflammatory transcription factor AP-1 in the promoter of ICAM-1, and induction of ICAM-1 transcription in human aortic EC. Finally, IL-35 cytokine therapy suppresses atherosclerotic lesion development in ApoE knockout mice. Conclusions— IL-35 is induced during atherosclerosis development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation-AP-1–mediated EC activation.
Colchicine for Prevention of Perioperative Atrial Fibrillation in patients undergoing lung resection surgery: a pilot randomized controlled study

OBJECTIVES We carried out a pilot randomized controlled study to determine the feasibility of a large trial evaluating the impact of colchicine versus placebo on postoperative atrial fibrillation or atrial flutter (POAF) among patients undergoing lung resection surgery. METHODS Patients ≥55 years of age undergoing lung resection surgery were randomly assigned to receive colchicine 0.6 mg or placebo starting a few hours before surgery. Postoperatively, patients received colchicine 0.6 mg or placebo twice daily for an additional 9 days. Our feasibility outcomes included the period of time required to recruit 100 patients, the completeness of follow-up and compliance with the study drug. The primary efficacy outcome was POAF within 30 days of randomization. RESULTS One hundred patients were randomized (49 to colchicine and 51 to placebo) over a period of 12 months at 2 centres in Canada. All patients completed the 30-day follow-up. The mean staff time required to recruit and to follow-up each patient was 165 min. In all, 71% of patients completed the study drug course without interruption. Patient refusal to continuing taking the study drug was the main reason for permanent drug discontinuation. New POAF occurred in 5 (10.2%) patients in the colchicine group and 7 (13.7%) patients in the placebo group (adjusted hazard ratio 0.69, 95% confidence interval 0.20-2.34). CONCLUSIONS These results show the feasibility of a trial evaluating Colchicine for the prevention of perioperative Atrial Fibrillation in patients undergoing lung resection surgery. This pilot study will serve as the foundation for the large multicentre COP-AF trial.
Wildtype motoneurons, ALS‐Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling

The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non‐cell‐autonomous effects of astrocytes. However, mechanisms underlying astrocyte‐mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS‐associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS‐causing mutated superoxide dismutase‐1 (SOD1) when co‐cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra‐ and intra‐cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592–605
A learning approach for email conversation thread reconstruction

An email conversation thread is defined as a topic-centric discussion unit that is composed of exchanged emails among the same group of people by reply or forwarding. Detecting conversation threads contained in email corpora can be beneficial for both humans to digest the content of discussions and automatic methods to extract useful information from the conversations. This research explores two new feature-enriched learning approaches, LExLinC and LExTreC, to reconstruct linear structure and tree structure of conversation threads in email data. In this work, some simplifying assumptions considered in previous methods for extracting conversation threads are relaxed, which makes the proposed methods more powerful in detecting real conversations. Additionally, the supervised nature of the proposed methods makes them adaptable to new environments by automatically adjusting the features and their weights. Experimental results show that the proposed methods are highly effective in detecting conversation threads and outperform the existing methods.
Predicting category intuitiveness with the rational model, the simplicity model, and the generalized context model.

Naïve observers typically perceive some groupings for a set of stimuli as more intuitive than others. The problem of predicting category intuitiveness has been historically considered the remit of models of unsupervised categorization. In contrast, this article develops a measure of category intuitiveness from one of the most widely supported models of supervised categorization, the generalized context model (GCM). Considering different category assignments for a set of instances, the authors asked how well the GCM can predict the classification of each instance on the basis of all the other instances. The category assignment that results in the smallest prediction error is interpreted as the most intuitive for the GCM-the authors refer to this way of applying the GCM as "unsupervised GCM. " The authors systematically compared predictions of category intuitiveness from the unsupervised GCM and two models of unsupervised categorization: the simplicity model and the rational model. The unsupervised GCM compared favorably with the simplicity model and the rational model. This success of the unsupervised GCM illustrates that the distinction between supervised and unsupervised categorization may need to be reconsidered. However, no model emerged as clearly superior, indicating that there is more work to be done in understanding and modeling category intuitiveness.
Abstraction, Refinement, Enrichment

In the no longer existing South African journal Quaestiones Informaticae, An Approach to Defining Abstractions, Refinements and Enrichments was published by Derrick Kourie more than twenty years ago. At some occasion, about two years ago, Derrick Kourie had asked and encouraged me to review his original topics, such as to re- construct and re-present them from a dierent perspective. In this festschrift chapter, in honour of Derrick Kourie's 65 th birthday, I outline the results of my attempt at fulfilling Derrick Kourie's collegial request. For this purpose I shall first recapitulate the key concepts of Kourie's original paper, since that paper has more or less fallen into oblivion and cannot be easily retrieved from the public domain any more. Thereafter Kourie's notions of abstraction, refinement and enrichment are re-defined in a dierent (more classical) theoretical framework. Finally those notions are contextualised with respect to the related notion of retrenchment developed since the mid-1990s by Banach, Poppleton, et al.
Antibiotic prescribing frequency amongst patients in primary care: a cohort study using electronic health records

Background: Reducing inappropriate antibiotic prescribing in primary care is a public health priority. Objectives: We hypothesized that a subset of patients account for the majority of antibiotic prescriptions in primary care. We investigated the relationship between the total amount of antibiotics prescribed, individual-level antibiotic use and comorbidity. Methods: This was a cohort study using electronic health records from 1 948 390 adults registered with 385 primary care practices in the UK in 2011–13. We estimated the average number of antibiotic prescriptions per patient and the association between prescribing and comorbidity. We modelled the impact on total prescribing of reducing antibiotic use in those prescribed antibiotics most frequently. Results: On average 30.1% (586 194/1 948 390) of patients were prescribed at least one antibiotic per year. Nine percent (174 602/1 948 390) of patients were prescribed 53% (2 091 496/3 922 732) of the total amount of antibiotics, each of whom received at least five antibiotic prescriptions over 3 years. The presence of any comorbidity increased the prescribing rate by 44% [adjusted incidence rate ratio (IRR) 1.44, 95% CI 1.43–1.45]; rates of prescribing to women exceeded those in men by 62% (adjusted IRR 1.62, 95% CI 1.62–1.63). Conclusions: Half of antibiotics prescribed to adults in primary care were for <10% of patients. Efforts to tackle antimicrobial resistance should consider the impact of this on total prescribing.
Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK

ABSTRACT The two-component response regulator RisA, encoded by open reading frame BP3554 in the Bordetella pertussis Tohama I genomic sequence, is a known activator of vrg genes, a set of genes whose expression is increased under the same environmental conditions (known as modulation) that result in repression of the bvgAS virulence regulon. Here we demonstrate that RisA is phosphorylated in vivo and that RisA phosphorylation is required for activation of vrg genes. An adjacent histidine kinase gene, risS, is truncated by frameshift mutation in B. pertussis but not in Bordetella bronchiseptica or Bordetella parapertussis. Neither deletion of risS′ or bvgAS nor phenotypic modulation with MgSO4 affected levels of phosphorylated RisA (RisA∼P) in B. pertussis. However, RisA phosphorylation did require the histidine kinase encoded by BP3223, here named RisK (cognate histidine kinase of RisA). RisK was also required for expression of the vrg genes. This requirement could be obviated by the introduction of the phosphorylation-mimicking RisAD60E mutant, indicating that an active conformation of RisA, but not phosphorylation per se, is crucial for vrg activation. Interestingly, expression of vrg genes is still modulated by MgSO4 in cells harboring the RisAD60E mutation, suggesting that the activated RisA senses additional signals to control vrg expression in response to environmental stimuli. IMPORTANCE In B. pertussis, the BvgAS two-component system activates the expression of virulence genes by binding of BvgA∼P to their promoters. Expression of the reciprocally regulated vrg genes requires RisA and is also repressed by the Bvg-activated BvgR. RisA is an OmpR-like response regulator, but RisA phosphorylation was not expected because the gene for its presumed, cooperonic, histidine kinase is inactivated by mutation. In this study, we demonstrate phosphorylation of RisA in vivo by a noncooperonic histidine kinase. We also show that RisA phosphorylation is necessary but not sufficient for vrg activation but, importantly, is not affected by BvgAS status. Instead, we propose that vrg expression is controlled by BvgAS through its regulation of BvgR, a cyclic di-GMP (c-di-GMP) phosphodiesterase.
A global research synthesis of HIV and STI biobehavioural risks in female-to-male transgender adults

ABSTRACT There is a growing interest in HIV infection and sexually transmitted infection (STI) disease burden and risk among transgender people globally; however, the majority of work has been conducted with male-to-female transgender populations. This research synthesis comprehensively reviews HIV and STI research in female-to-male (FTM) transgender adults. A paucity of research exists about HIV and STIs in FTMs. Only 25 peer-reviewed papers (18 quantitative, 7 qualitative) and 11 ‘grey literature’ reports were identified, most in the US or Canada, that include data identifying HIV and STI risks in FTMs (five with fully laboratory-confirmed HIV and/or STIs, and five with partial laboratory confirmation). Little is known about the sexual and drug use risk behaviours contributing to HIV and STIs in FTMs. Future directions are suggested, including the need for routine surveillance and monitoring of HIV and STIs globally by transgender identity, more standardised sexual risk assessment measures, targeted data collection in lower- and middle-income countries, and explicit consideration of the rationale for inclusion/exclusion of FTMs in category-based prevention approaches with MSM and transgender people. Implications for research, policy, programming, and interventions are discussed, including the need to address diverse sexual identities, attractions, and behaviours and engage local FTM communities.
Impact of Ménière’s Disease on Significant Others’ Health and Lives

Abstract Background: Ménière’s disease (MD) is a chronic and, in part, intermittent illness that poses multiple challenges for both the physical and psychological well-being of patients, as well as on those around them. The patients face psychosocial consequences, which include disruptions to life goals, employment, income, relationships, leisure activities, and daily living activities that also influence their family members and friends. However, there is a limited understanding of the impact of MD on significant others (SOs). Purpose: The current study was aimed at identifying how the SOs of patients with MD respond to different aspects of the impact of the disorder on health and life (i.e., psychological aspects, activities, participation, and positive aspects). Research Design: The study employed a cross-sectional survey design. Study Sample: The study sample was 186 SOs of patients with MD who were recruited through Finnish Ménière’s Federation. Data Collection and Analysis: Participants completed a 25-item structured questionnaire focusing on different aspects of the impact of the disorder on health and life, and also provided some demographic information. Data were analyzed using Kruskal–Wallis test, Pearson’s correlation, and K-means cluster analysis techniques. Results: Examination of response patterns suggests that the disorder had, on average, a marginal effect on SOs’ psychological aspects, activities, and participation as the SOs generally focused on complaints. Interestingly, SOs reported some positive consequences as a result of their partners’ condition. The results show a limited association between SOs’ demographic variables and response patterns. The Pearson’s correlation suggested a strong association between the subscales psychological aspects, activity limitations, and participation restrictions. Also, a weak negative correlation was observed among positive aspects and participation restrictions. The cluster analysis resulted in three clusters, namely, (1) “nonengaged,” (2) “supportive,” and (3) “concerned. ” Conclusions: The current study results identify that the SOs’ reaction to patients’ condition varies and this may be from coping with victimization. Although the impact of MD on SOs is limited, some of the SOs may have more severe consequences and may require rehabilitation. The information gathered about SOs’ coping and adjustment in this study can also help while developing management and/or rehabilitation plan for people with MD.
miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR‐322‐5p (the rodent orthologue of miR‐424‐5p) expression is decreased in the right ventricle of monocrotaline‐treated rats, a model of PAH, whereas a putative target insulin‐like growth factor 1 (IGF‐1) is increased. IGF‐1 mRNA was enriched 16‐fold in RNA immunoprecipitated with Ago2, indicating binding to miR‐322‐5p. In cell transfection experiments, miR‐322‐5p suppressed the activity of a luciferase reporter containing a section of the IGF‐1 3′ untranslated region (UTR) as well as IGF‐1 mRNA and protein levels. Taken together, these data suggest that miR‐322 targets IGF‐1, a process downregulated in PAH‐related RV hypertrophy.
Barriers and facilitators to the implementation of mentalization-based treatment (MBT) for borderline personality disorder.

There are several evidence-based treatments for borderline personality disorder, but very little is known about the success or failure of implementation in daily practice. This study aims to investigate the success or failure of newly started mentalization-based treatment programs, and to explore the barriers and facilitators. The implementation trajectories of seven different mentalization-based treatment programs in six mental health clinics in the Netherlands were included in a multiple case study combining a qualitative and quantitative design. Semi-structured interview data were collected from several stakeholders of each program. Narrative reconstructions of each interview were assessed by 12 independent experts. Results showed that several programs struggled to implement their program successfully, leading to discontinuation in three programs. According to the experts, particularly elements at the organizational level (i.e. organizational support) and team level (i.e. leadership) contributed to implementation outcome. These findings have important implications for the translation of guidelines and research findings in daily practice. Copyright © 2017 John Wiley & Sons, Ltd.
Finnish Dentists Find Smoking Cessation Important but Seldom Offer Practical Support for Their Patients.

OBJECTIVES To investigate Finnish dentists' smoking cessation related attitudes, consultation practices and familiarity with the local treatment guideline on smoking cessation. BASIC RESEARCH DESIGN An online questionnaire was sent to 1740 dentists, which corresponds to 39% of dentists in Finland. A total of 456 dentists responded (response rate 26%), of whom 435 (95%) were clinicians. The dentists' smoking cessation practices were also compared to ones reported in a previous study in Finnish physicians. RESULTS Dentists found smoking cessation important and often discussed and recommended quitting to the patients, but concrete withdrawal actions were seldom provided. The local treatment guideline on smoking cessation was actively utilized by 36% of the dentists. Adherence to the guideline was associated with higher rates of smoking cessation activities and success in them. Smoking cessation activity among dentists was significantly lower than in Finnish physicians. In accordance with the literature, among dentists, the most common barriers for smoking cessation were lack of time (44%) and education (42%). CONCLUSION Although smoking cessation is discussed with patients, dentists are less active in taking concrete actions to support the patient on withdrawal. Adherence to the local treatment guideline was associated with better capabilities in dealing with tobacco withdrawal and a more active role in smoking cessation. The results suggest that more education on the local smoking cessation treatment guideline and cessation intervention is needed in order to overcome the remaining barriers to promoting effective smoking cessation in dental practice.