Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver transplantation for intrahepatic cholangiocarcinoma

Although hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma–cholangiocarcinoma (cHCC‐CCA) are historically contraindicated due to their aggressive behavior. On the basis of recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early cholangiocarcinoma (CCA), defined as a single lesion ≤ 2 cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC‐CCA on explant. Patients with the diagnosis of primary liver cancer (PLC) after LT from a single center were retrospectively reviewed. Outcomes for patients with early CCA were compared with patients with HCC within Milan criteria (MC). Out of 618 patients transplanted with PLC, 44 patients were found to have CCA on explant. On the basis of preoperative imaging, 12 patients met criteria for early CCA and were compared with 319 patients who had HCC within MC. The 1‐ and 5‐year overall survival for early CCA versus HCC was 63.6% versus 90.0% and 63.6% versus 70.3% (log‐rank, P = 0.25), respectively. Overall recurrence was 33.3% for early CCA versus 11% for HCC. On explant the patients with CCA were more likely understaged with higher tumor grade and vascular invasion. In conclusion, patients with CCA present a diagnostic challenge, which often leads to the finding of more aggressive lesions on explant after LT, higher recurrence rates, and worse post‐LT survival. Careful consideration of this diagnostic conundrum needs to be made before a clinical trial is undertaken. Liver Transplantation 24 634–644 2018 AASLD.
Efficacy of Mirogabalin (DS-5565) on Patient-Reported Pain and Sleep Interference in Patients with Diabetic Neuropathic Pain: Secondary Outcomes of a Phase II Proof-of-Concept Study

Objective To evaluate the effects of mirogabalin on patient-reported pain and sleep interference in diabetic peripheral neuropathic pain (DPNP). Subjects Adults (≥18 years) with type 1 or 2 diabetes, glycosylated hemoglobin of 10% or less at screening, and DPNP for six months or more were eligible for participation. Methods Subjects (N = 452) were randomly assigned (2:1:1:1:1:1:1) to receive placebo, dose-ranging mirogabalin (5, 10, 15, 20, 30 mg/day), or pregabalin (300 mg/day) for five weeks. Secondary efficacy end points studied here included patient global impression of change (PGIC), modified brief pain inventory (BPI), and average daily sleep interference score (ADSIS). Correlation plots were generated to examine the relationship between ADSIS and average daily pain score (ADPS). Results At week 5, significant reductions in ADSIS were observed in the mirogabalin 15, 20, and 30 mg/day groups, compared with placebo (P < 0.05). Baseline ADSIS and ADPS were strongly correlated (R2 = 0.4407), as were mean changes from baseline in ADSIS and ADPS at week 5 (R2 = 0.6694). The mirogabalin 30 mg/day group showed significant improvement compared with placebo in four of six BPI subscales at end point; the mirogabalin 15 mg/day group showed significant improvement in three of six BPI subscales (P < 0.05). At end of treatment, the percentage of subject with PGIC status of "much improved or better" was greater in all mirogabalin dose groups than in the placebo group (P < 0.05). A low incidence of treatment-related adverse events was reported for mirogabalin. Conclusions Results support the effectiveness of mirogabalin in improving patient-reported pain and sleep interference in DPNP.
Do predictors of smoking relapse change as a function of duration of abstinence? Findings from the United States, Canada, United Kingdom and Australia

AIMS To estimate predictors of time to smoking relapse and test if prediction varied by quit duration. DESIGN Longitudinal cohort data from the International Tobacco Control Four-Country survey with annual follow up collected between 2002 and 2015. SETTING Canada, United States, United Kingdom and Australia. PARTICIPANTS A total of 9171 eligible adult smokers who had made at least one quit attempt during the study period. MEASUREMENTS Time to relapse was the main outcome. Predictor variables included pre-quit baseline measures of nicotine dependence, smoking and quitting-related motivations, quitting capacity and social influence, and also two post-quit measures, use of stop-smoking medications and quit duration (1-7 days, 8-14 days, 15-31 days, 1-3 months, 3-6 months, 6-12 months, 1-2 years and 2+ years), along with socio-demographics. FINDINGS All factors were predictive of relapse within the first 6 months of quitting but only wanting to quit, quit intentions and number of friends who smoke were still predictive of relapse in the 6-12-month period of quitting [hazard ratios (HR) = 1.20, P < 0.05; 1.13, P < 0.05; and 1.21, P < 0.001, respectively]. Number of friends smoking was the only remaining predictor of relapse in the 1-2 years quit period (HR = 1.19, P = 0.001) with none predictive beyond the 2-year quit period. Use of stop-smoking medications during quit attempts was related negatively to relapse during the first 2 weeks of quitting (HR = 0.71-0.84), but related positively to relapse in the 1-6-month quit period (HR = 1.29-1.54). Predictive effects of all factors showed significant interaction with quit duration except for perceiving smoking as an important part of life, prematurely stubbing out a cigarette and wanting to quit. CONCLUSIONS Among adult smokers in the United States, Canada, United Kingdom and Australia, factors associated with smoking relapse differ between the early and later stages of a quit attempt, suggesting that the determinants of relapse change as a function of abstinence duration.
The conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis factor initiation

Background Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. Methods We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications. Results We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, P<0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population. Conclusion We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.
What Is Stress? Dose-Response Effects in Commonly Used in Vitro Stress Assays1[OPEN]

Responses to abiotic stress strongly depend on the stress level, and novel parameters, such as shoot growth inhibition and marker genes, are needed to accurately study and quantify mild stress responses. In vitro stress assays are commonly used to study the responses of plants to abiotic stress and to assess stress tolerance. A literature review reveals that most studies use very high stress levels and measure criteria such as germination, plant survival, or the development of visual symptoms such as bleaching. However, we show that these parameters are indicators of very severe stress, and such studies thus only provide incomplete information about stress sensitivity in Arabidopsis (Arabidopsis thaliana). Similarly, transcript analysis revealed that typical stress markers are only induced at high stress levels in young seedlings. Therefore, tools are needed to study the effects of mild stress. We found that the commonly used stress-inducing agents mannitol, sorbitol, NaCl, and hydrogen peroxide impact shoot growth in a highly specific and dose-dependent way. Therefore, shoot growth is a sensitive, relevant, and easily measured phenotype to assess stress tolerance over a wide range of stress levels. Finally, our data suggest that care should be taken when using mannitol as an osmoticum.
Alternative Models for Small Samples in Psychological Research

Unavoidable sample size issues beset psychological research that involves scarce populations or costly laboratory procedures. When incorporating longitudinal designs these samples are further reduced by traditional modeling techniques, which perform listwise deletion for any instance of missing data. Moreover, these techniques are limited in their capacity to accommodate alternative correlation structures that are common in repeated measures studies. Researchers require sound quantitative methods to work with limited but valuable measures without degrading their data sets. This article provides a brief tutorial and exploration of two alternative longitudinal modeling techniques, linear mixed effects models and generalized estimating equations, as applied to a repeated measures study (n = 12) of pairmate attachment and social stress in primates. Both techniques provide comparable results, but each model offers unique information that can be helpful when deciding the right analytic tool.
Effect of Phosphorylated Chitosan on Dentin Erosion: An in vitro Study

The aim of this study was to evaluate the antierosive effect of phosphorylated chitosan in dentin. Bovine dentin specimens were randomly distributed into the following groups: (1) no treatment (NoTx/negative control), (2) phosphate-buffered saline solution (PBS), (3) AmF/NaF/SnCl2 (positive control), (4) 0.5% chitosan solution (Chi), (5) 0.5% neutral phosphorylated (NP)-Chi, and (6) 0.5% alkaline phosphorylated (AP)-Chi. The specimens were submitted to de-remineralization treatment cycles for 5 days: 0.5% citric acid (2 min), remineralizing solution (30 min), and surface treatment according to assigned groups (2 min, 6×/day). The loss of dentin surface was measured by profilometry. Hardness and modulus of elasticity were measured using a nanoindenter equipped with a Berkovich diamond tip. The dentin surface was analyzed by scanning electron microscopy (SEM). The largest loss of dentin was observed in the No Tx and PBS groups (approx. 25 µm). The group treated with AmF/NaF/SnCl2 showed less loss of dentin (67% reduction vs. NoTx and PBS), followed by the groups treated with NP-Chi and AP-Chi (33% reduction), and Chi (18% reduction). Nanohardness and modulus of elasticity were similar in the NoTx and PBS groups, with a small increase in stiffness in all other groups. SEM revealed that the experimental solution of AP-Chi had a favorable effect on maintaining the integrity of collagen fibrils. AmF/NaF/SnCl2 showed a preserved mineralized collagen surface. Further studies are warranted to explore this nontoxic phosphorylated chitosan polymer as an effective agent in the prevention and treatment of dental erosion.
Demographics and Genetic Variability of the New World Bollworm (Helicoverpa zea) and the Old World Bollworm (Helicoverpa armigera) in Brazil

Helicoverpa armigera is one of the primary agricultural pests in the Old World, whereas H. zea is predominant in the New World. However, H. armigera was first documented in Brazil in 2013. Therefore, the geographical distribution, range of hosts, invasion source, and dispersal routes for H. armigera are poorly understood or unknown in Brazil. In this study, we used a phylogeographic analysis of natural H. armigera and H. zea populations to (1) assess the occurrence of both species on different hosts; (2) infer the demographic parameters and genetic structure; (3) determine the potential invasion and dispersal routes for H. armigera within the Brazilian territory; and (4) infer the geographical origin of H. armigera. We analyzed partial sequence data from the cytochrome c oxidase subunit I (COI) gene. We determined that H. armigera individuals were most prevalent on dicotyledonous hosts and that H. zea were most prevalent on maize crops, based on the samples collected between May 2012 and April 2013. The populations of both species showed signs of demographic expansion, and no genetic structure. The high genetic diversity and wide distribution of H. armigera in mid-2012 are consistent with an invasion period prior to the first reports of this species in the literature and/or multiple invasion events within the Brazilian territory. It was not possible to infer the invasion and dispersal routes of H. armigera with this dataset. However, joint analyses using sequences from the Old World indicated the presence of Chinese, Indian, and European lineages within the Brazilian populations of H. armigera. These results suggest that sustainable management plans for the control of H. armigera will be challenging considering the high genetic diversity, polyphagous feeding habits, and great potential mobility of this pest on numerous hosts, which favor the adaptation of this insect to diverse environments and control strategies.
Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

Abstract OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.
Knowledge on self-management and levels of asthma control among adult patients in Ho Chi Minh City, Vietnam

Background Most asthma patients in Vietnam have poorly controlled asthma. Besides reasons related to the health care system and health care providers, knowledge on the self-management of patients has also contributed to this situation. Purpose To assess knowledge on asthma self-management among adult asthma patients in Ho Chi Minh City. Patients and methods A cross-sectional study with convenience sampling was conducted among 322 ambulatory patients using questionnaires filled in via a face-to-face interview. The questionnaires enquired about: 1) sociodemographic details, 2) the Global Initiative for Asthma 2017 criteria of asthma control, 3) the Asthma Control Test, and 4) the Asthma Self-Management Questionnaire (ASMQ). Knowledge on asthma self-management was determined by the ASMQ score. The relationship between this knowledge and demographic factors and asthma control levels was determined. Results The knowledge on asthma self-management was low, with a mean raw ASMQ score of 4.3 (maximum 14); this is equivalent to 30 in a transformed score (maximum 100). Only 0.3% of these patients had good knowledge, 16.2% had adequate knowledge, and 83.5% had poor knowledge. Of all participants, 52% stated erroneously that asthma can be cured, 30% were confused about control and rescue medications, 68% failed to correctly describe the inhalation technique, and only 15.5% could answer correctly about the management of an exacerbation. Although most participants had poor asthma control, the higher the patient’s level of control, the better the ASMQ score. Conversely, patients with better knowledge of asthma self-management (ASMQ score ≥50) had better asthma control based on the Asthma Control Test score. Also, a higher education level was associated with more knowledge on asthma self-management. Conclusion In these patients, the level of knowledge on asthma self-management was low and significantly correlated with the level of asthma control. There is a clear need to improve knowledge in order to improve asthma control in Vietnam.
The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for Viability of Thermococcus kodakarensis

ABSTRACT Many aspects of and factors required for DNA replication are conserved across all three domains of life, but there are some significant differences surrounding lagging-strand synthesis. In Archaea, a 5′-to-3′ exonuclease, related to both bacterial RecJ and eukaryotic Cdc45, that associates with the replisome specifically through interactions with GINS was identified and designated GAN (for GINS-associated nuclease). Despite the presence of a well-characterized flap endonuclease (Fen1), it was hypothesized that GAN might participate in primer removal during Okazaki fragment maturation, and as a Cdc45 homologue, GAN might also be a structural component of an archaeal CMG (Cdc45, MCM, and GINS) replication complex. We demonstrate here that, individually, either Fen1 or GAN can be deleted, with no discernible effects on viability and growth. However, deletion of both Fen1 and GAN was not possible, consistent with both enzymes catalyzing the same step in primer removal from Okazaki fragments in vivo. RNase HII has also been proposed to participate in primer processing during Okazaki fragment maturation. Strains with both Fen1 and RNase HII deleted grew well. GAN activity is therefore sufficient for viability in the absence of both RNase HII and Fen1, but it was not possible to construct a strain with both RNase HII and GAN deleted. Fen1 alone is therefore insufficient for viability in the absence of both RNase HII and GAN. The ability to delete GAN demonstrates that GAN is not required for the activation or stability of the archaeal MCM replicative helicase. IMPORTANCE The mechanisms used to remove primer sequences from Okazaki fragments during lagging-strand DNA replication differ in the biological domains. Bacteria use the exonuclease activity of DNA polymerase I, whereas eukaryotes and archaea encode a flap endonuclease (Fen1) that cleaves displaced primer sequences. RNase HII and the GINS-associated exonuclease GAN have also been hypothesized to assist in primer removal in Archaea. Here we demonstrate that in Thermococcus kodakarensis, either Fen1 or GAN activity is sufficient for viability. Furthermore, GAN can support growth in the absence of both Fen1 and RNase HII, but Fen1 and RNase HII are required for viability in the absence of GAN.
Flow resistance and bed form geometry in a wide alluvial channel

This paper explores the underlying mechanism of flow resistance in a wide alluvial channel with bed forms. On the basis of published data, it is shown that the grain roughness can be taken as equal to 2 times the median diameter of the bed sediment. An empirical equation for the bed form roughness has been proposed, and it depends on the bed form height and bed form steepness. The influence of the bed form length and height on the total bed shear stress and energy slope is deliberated, and empirical expressions for the length of the separation zone behind the bed forms are also proposed. The study proposed an equation to compute the total bed shear stress as a function of the grain and bed form roughness as well as the important role of the bed form geometry in the overall flow resistance in alluvial channels. The model is tested and verified against 670 flume measurements and 1540 field observations. The computed and measured energy slopes are in good agreement with close to 71% of all data sets within the ±20% error band.
Evaluation of a Stereo Music Preprocessing Scheme for Cochlear Implant Users

Abstract Background: Although for most cochlear implant (CI) users good speech understanding is reached (at least in quiet environments), the perception and the appraisal of music are generally unsatisfactory. Purpose: The improvement in music appraisal was evaluated in CI participants by using a stereo music preprocessing scheme implemented on a take-home device, in a comfortable listening environment. The preprocessing allowed adjusting the balance among vocals/bass/drums and other instruments, and was evaluated for different genres of music. The correlation between the preferred settings and the participants’ speech and pitch detection performance was investigated. Research Design: During the initial visit preceding the take-home test, the participants’ speech-in-noise perception and pitch detection performance were measured, and a questionnaire about their music involvement was completed. The take-home device was provided, including the stereo music preprocessing scheme and seven playlists with six songs each. The participants were asked to adjust the balance by means of a turning wheel to make the music sound most enjoyable, and to repeat this three times for all songs. Study Sample: Twelve postlingually deafened CI users participated in the study. Data Collection and Analysis: The data were collected by means of a take-home device, which preserved all the preferred settings for the different songs. Statistical analysis was done with a Friedman test (with post hoc Wilcoxon signed-rank test) to check the effect of “Genre. ” The correlations were investigated with Pearson’s and Spearman’s correlation coefficients. Results: All participants preferred a balance significantly different from the original balance. Differences across participants were observed which could not be explained by perceptual abilities. An effect of “Genre” was found, showing significantly smaller preferred deviation from the original balance for Golden Oldies compared to the other genres. Conclusions: The stereo music preprocessing scheme showed an improvement in music appraisal with complex music and hence might be a good tool for music listening, training, or rehabilitation for CI users.