Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C Virus Stability: The Issue!

One of the major challenges concerning the implementation of nucleic acid testing (NAT) as a blood donor screening method is the question of how to store blood samples in order to get reliable results. Many reports have been published which quote the hepatitis C virus (HCV) as very unstable in serum; one of them even condemned the storage of clotted blood for longer than 2 h [1–3]. These findings suggest that for the appropriate NAT screening of blood donations the current sampling and storage conditions of blood samples have to be completely changed. However, sophisticated storage conditions might not always be practicable for the blood transfusion services with mobile blood collection units. Observations made in the German Red Cross Blood Transfusion Service of Baden-Württemberg (DRK-BSD BaWü) have always suggested that HCV is stable in serum samples which are kept at 4°C, even without separation of serum from the clot [4]. The study reported here was designed to evaluate variables such as HCV stability in serum versus plasma, individual stability of different sera and HCV-RNA titer in different blood components. Moreover, the current sampling, transport and storage conditions of blood samples collected by mobile units of the DRKBSD BaWü were taken into account when investigating these parameters. Rapid Communication
The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST)*

Aim of the study was to analyze the outcome of treatment and factors predicting results of sorafenib therapy in inoperable/metastatic CD117-positive GIST patients after failure on imatinib and sunitinib. Material and methods We identified 60 consecutive patients (40 men, 20 women) with advanced inoperable/metastatic GIST after failure on at least imatinib and sunitinib treated in one sarcoma center with sorafenib at initial dose 2 × 400 mg daily in 2007–2015 (in 56 cases it was 3rd line therapy). Median follow-up time was 39 months. Results One year progression-free survival (PFS; calculated from the date of the start of sorafenib to disease progression) rate was 23% and median PFS = 7.7 months. The median overall survival (OS) was 13.5 months calculated from sorafenib start (1-year OS rate = 57%) and 7 years from imatinib start. Three patients (5%) had objective partial responses to therapy, 31 patients (52%) had stabilization of disease > 4 months. Primary tumor mutational status was known in 43 cases (73%), but we have not identified the differences in PFS between tumors carrying different KIT/PDGFRA mutations. The most common adverse events were: diarrhoea, hand and foot syndrome, fatigue, loss of weight and skin reactions; grade 3–5 toxicity occurred in 35% of patients. 23 patients required sorafenib dose reductions due to AEs. Conclusions We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.
Reduced order model using modified cauer form for multi-input and multi-output LTI systems

In this paper, the modified Cauer form (MCF) discussed to reduce a high order system. This method is based on the continued fraction method. Reduced order model analysis is much easier as compared to original high order model. The coefficients of denominator and numerator of desired reduced order model are evaluated by inversion of modified Routh array. The modified Cauer form is used to reduce multi-input multioutput (MIMO) linear time invariant system. The proposed reduced order model is compared with other model order reduction techniques.
On optical mass estimation methods for galaxy groups

We examine the performance of a variety of different estimators for the mass of galaxy groups, based on their galaxy distribution alone. We draw galaxies from the Sloan Digital Sky Survey for a set of groups and clusters for which hydrostatic mass estimates based on high-quality Chandra X-ray data are available. These are used to calibrate the galaxy-based mass proxies, and to test their performance. Richness, luminosity, galaxy overdensity, rms radius and dynamical mass proxies are all explored. These different mass indicators all have their merits, and we argue that using them in combination can provide protection against being misled by the effects of dynamical disturbance or variations in star formation efficiency. Using them in this way leads us to infer the presence of significant non-statistical scatter in the X-ray based mass estimates we employ. We apply a similar analysis to a set of mock groups derived from applying a semi-analytic galaxy formation code to the Millennium dark matter simulation. The relations between halo mass and the mass proxies differ significantly in some cases from those seen in the observational groups, and we discuss possible reasons for this.
Monoamine oxidase inhibitors potentiate the effects of deep brain stimulation.

Approximately 50%–60% of patients with treatment-resistant depression respond to deep brain stimulation (DBS) to the subcallosal cingulate gyrus (1). The therapeutic strategies for patients who are considered nonresponders are still unclear. We provide clinical and preclinical evidence suggesting that the effects of DBS may be potentiated by the co-administration of monoamine oxidase inhibitors (MAOIs).
Influence of past and future climate changes on the distribution of three Southeast Asian murine rodents

We tested the influence of Pleistocene climatic fluctuations and the potential effect of future climate change on Southeast Asian small mammal distributions using two forest‐dwelling (Leopoldamys herberti and Leopoldamys sabanus) and one karst (Leopoldamys neilli) endemic rodent species as models.
Effect of Voice Quality on Perceived Height of English Vowels

Abstract Across a variety of languages, phonation type and vocal-tract shape systematically covary in vowel production. Breathy phonation tends to accompany vowels produced with a raised tongue body and/or advanced tongue root. A potential explanation for this regularity, based on a hypothesized interaction between the acoustic effects of vocal-tract shape and phonation type, is evaluated. It is suggested that increased spectral tilt and first-harmonic amplitude resulting from breathy phonation interact with the lower-frequency first formant resulting from a raised tongue body to produce a perceptually ‘higher’ vowel. To test this hypothesis, breathy and modal versions of vowel series modelled after male and female productions of English vowel pairs /i/ and /i/, /u/ and /ω/, and /λ/ and /a/ were synthesized. Results indicate that for most cases, breathy voice quality led to more tokens being identified as the higher vowel (i.e. /i/, /u/, /ÊŒ/). In addition, the effect of voice quality is greater for vowels modelled after female productions. These results are consistent with a hypothesized perceptual explanation for the covariation of phonation type and tongue-root advancement in West African languages. The findings may also be relevant to gender differences in phonation type.
Endocannabinoid and Mood Responses to Exercise in Adults with Varying Activity Levels

Acute aerobic exercise improves mood and activates the endocannabinoid (eCB) system in physically active individuals; however, both mood and eCB responses to exercise may vary based on habitual levels of physical activity. Purpose This study aimed to examine eCB and mood responses to prescribed and preferred exercises among individuals with low, moderate, and high levels of physical activity. Methods Thirty-six healthy adults (21 ± 4 yr) were recruited from low (⩽60 min moderate–vigorous physical activity [MVPA] per week), moderate (150–299 min MVPA per week), and high (≥300 MVPA per week) physical activity groups. Participants performed both prescribed (approximately 70%–75% max) and preferred (i.e., self-selected) aerobic exercise on separate days. Mood states and eCB concentrations were assessed before and after exercise conditions. Results Both preferred and prescribed exercise resulted in significant increases (P < 0.01) in circulating eCB (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol); however, increases in AEA (P < 0.05) were larger in the prescribed condition. Likewise, both preferred and prescribed exercise elicited positive mood improvements compared with preexercise values, but changes in state anxiety, total mood disturbance, and confusion were greater in the preferred condition (P < 0.05). Changes in 2-arachidonoylglycerol concentrations were found to negatively correlate with changes in depression, tension, and total mood disturbance in the preferred condition (P < 0.05), and changes in AEA were positively associated with changes in vigor in the prescribed condition (P < 0.05). There were no significant group differences for mood or eCB outcomes. Conclusion These results indicate that eCB and mood responses to exercise do not differ significantly between samples with varying physical activity levels. This study also demonstrates that in addition to prescribed exercise, preferred exercise activates the eCB system, and this activation may contribute to positive mood outcomes with exercise.
Improving Health Care Providers' Capacity for Self-Regulated Learning in Online Continuing Pharmacy Education: The Role of Internet Self-Efficacy

Introduction: Although Internet-based learning is widely used to improve health professionals' knowledge and skills, the self-regulated learning (SRL) activities of online continuing education in pharmacy are seldom discussed. The main purpose of this study was to explore the relationships between pharmacists' Internet self-efficacy (ISE) and their SRL in online continuing education. Methods: A total of 164 in-service pharmacists in Taiwan were surveyed with the Internet Self-Efficacy Survey, including basic ISE (B-ISE), advanced ISE (A-ISE) and professional ISE (P-ISE), as well as the Self-Regulated Learning Questionnaire consisting of preparatory SRL (P-SRL) and enactment SRL (E-SRL). Results: Results of a 1-by-3 (educational levels: junior college versus bachelor versus master) analysis of variance and a 1-by-4 (institutions: community-based versus hospital versus clinic versus company) analysis of variance revealed that there were differences in ISE and SRL among different education levels and working institutions. The hierarchical regression analyses indicated that B-ISE and P-ISE were significant predictors of P-SRL, whereas P-ISE was a critical predictor of E-SRL. Moreover, the interaction of P-ISE × age was linked to E-SRL, implying that P-ISE has a stronger influence on E-SRL for older pharmacists than for younger pharmacists. However, the interactions between age and ISE (A-ISE, B-ISE, and P-ISE) were not related to P-SRL. Discussion: This study highlighted the importance of ISE and age for increasing pharmacists' SRL in online continuing education.
Patterns of methadone maintenance treatment provision in Ontario: Policy success or pendulum excess?

OBJECTIVE To describe recent trends and patterns in methadone maintenance treatment (MMT) practice regionally and over time in the province of Ontario. DESIGN Population-based descriptive study using health administrative data between September 1, 2011, and December 31, 2014. SETTING Ontario. PARTICIPANTS All active MMT-prescribing physicians and patients receiving MMT in the study period. MAIN OUTCOME MEASURES Characteristics of MMT-prescribing physicians, including age, sex, specialty type, practice region, and practice volume; characteristics of patients receiving MMT, including age, sex, neighbourhood income, and region of residence. RESULTS Between September 1, 2011, and December 31, 2014, the number of MMT-prescribing physicians and patients who received MMT increased by 26% and 42%, respectively. In 2014, there was a total of 312 MMT-prescribing physicians and 49 703 patients receiving MMT. In 2014 and on a per capita basis, patients receiving MMT were more prevalent in rural regions; and within rural regions, there were disproportionately large numbers of young female MMT patients residing in low-income neighbourhoods. CONCLUSION The number of physicians prescribing MMT and patients receiving MMT has increased substantially between 2011 and 2014, with the largest per capita distribution occurring in rural regions and involving young adults. While availability of and access to MMT has improved considerably from before 2000 to levels of high use, these developments are likely influenced by recent trends in the proliferation of prescription opioid misuse across general populations.
Dose Volume Histogram Analysis of the Gamma Knife Radiosurgery Treating Twenty-Five Metastatic Intracranial Tumors

Treating multiple brain metastatic sites in Gamma Knife radiosurgery is not uncommon. Most metastases can be treated with few or even one single shot. Occasionally we have patients returning for retreatment for different intracranial metastatic sites at different times. Dose distribution for these metastases are prescribed locally without considering the previous dose contribution. We present a study which simultaneously calculates the dose distribution of 25 randomly placed shots distributed inside the intracranial region. The Dose Volume Histogram (DVH) is plotted to study the coverage of the tumor sites and normal tissues. We have calculated ten DVH studies and show that 50% of the brain volume receives less than 500 cGy for the maximum tumor dose of 40 Gy, and the dose gradient is extremely steep. This DVH analysis shows that the Gamma Knife radiosurgery is a good treatment modality to control the local tumors while maintaining normal brain function, even for the large number of brain metastasis treated at different times.
LRRK2 G2019S Induces Anxiety/Depression-like Behavior before the Onset of Motor Dysfunction with 5-HT1A Receptor Upregulation in Mice

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD). The neuropathology of LRRK2 mutation-related PD, including increased dopaminergic neurodegeneration and Lewy bodies, is indistinguishable from that of idiopathic PD. The subtle nonmotor phenotypes of LRRK2 mutation-related PD have not been fully evaluated. In the present study, we examined anxiety/depression-like behaviors and accompanying neurochemical changes in differently aged transgenic (Tg) mice expressing human mutant LRRK2 G2019S. Through multiple behavioral tests, including light–dark test, elevated plus maze, sucrose preference test, forced swimming test, and tail-suspension test, we found that anxiety/depression-like behavior appeared in middle-aged (43–52 weeks) Tg mice before the onset of PD-like motor dysfunction. These behavioral tests were performed using both male and female mice, and there were no sex-related differences in behavioral changes in the middle-aged Tg mice. Along with behavioral changes, serotonin levels also significantly declined in the hippocampus of Tg mice. Additionally, increases in the expression of the 5-HT1A receptor (5-HT1AR) grew more significant with aging and were detected in the hippocampus, amygdala, and dorsal raphe nucleus. In vitro study using the serotonergic RN46A and hippocampal HT22 cells showed that 5-HT1AR upregulation was related to enhanced expression of LRRK2 G2019S and was attenuated by the LRRK2 inhibitor LRRK2-IN-1. Wild-type LRRK2 had no significant effect on 5-HT1AR transcription. The present study provides the first in vivo and in vitro evidence demonstrating abnormal regulation of 5-HT1AR along with the manifestation of anxiety/depression-like, nonmotor symptom in PD related to LRRK2. SIGNIFICANCE STATEMENT Parkinson's disease (PD), the second most common neurodegenerative disorder, is clinically characterized by motor dysfunctions. In most cases, various nonmotor symptoms present several years before the onset of the classical motor features of PD and severely affect the quality of life of patients. Here, we demonstrate the causative role of leucine-rich repeat kinase 2 (LRRK2), a common PD-linked mutation, in the development of anxiety/depression-like behaviors. We found that age-dependent 5-HT1A receptor upregulation in the hippocampus, amygdala, and dorsal raphe nucleus is accompanied by the expression of the LRRK2 mutant phenotype. Our findings demonstrating a potential mechanism for nonmotor psychiatric symptoms produced by LRRK2 mutation suggest that directly targeting the 5-HT1A receptor can improve the therapeutic efficacy of drugs for PD-associated depression.
Predictive Value of Arterial Stiffness and Subclinical Carotid Atherosclerosis for Cardiovascular Disease in Patients with Rheumatoid Arthritis

Objective. We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD. Methods. In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses. Results. Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline. Conclusion. CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.
Multiple introductions, admixture and bridgehead invasion characterize the introduction history of Ambrosia artemisiifolia in Europe and Australia

Admixture between differentiated populations is considered to be a powerful mechanism stimulating the invasive success of some introduced species. It is generally facilitated through multiple introductions; however, the importance of admixture prior to introduction has rarely been considered. We assess the likelihood that the invasive Ambrosia artemisiifolia populations of Europe and Australia developed through multiple introductions or were sourced from a historical admixture zone within native North America. To do this, we combine large genomic and sampling data sets analysed with approximate Bayesian computation and random forest scenario evaluation to compare single and multiple invasion scenarios with pre‐ and postintroduction admixture simultaneously. We show the historical admixture zone within native North America originated before global invasion of this weed and could act as a potential source of introduced populations. We provide evidence supporting the hypothesis that the invasive populations established through multiple introductions from the native range into Europe and subsequent bridgehead invasion into Australia. We discuss the evolutionary mechanisms that could promote invasiveness and evolutionary potential of alien species from bridgehead invasions and admixed source populations.
Fibromyalgia Among Patients With Chronic Migraine and Chronic Tension‐Type Headache: A Multicenter Prospective Cross‐Sectional Study – A Response

In a comment regarding our article Fibromyalgia among patients with chronic migraine and chronic tension-type headache: A multicenter prospective cross-sectional study, Leiva-Calder on and MayorgaMoreno discussed the diagnostic process for chronic migraine (CM) and chronic tension-type headache (CTTH), and the statistical method for comparing frequency of localized pain between two conditions. For the diagnosis of CM and CTTH, we diagnosed CM and CTTH based on the headache history during the previous year according to ICHDIII beta. CM is a disease that is often delayed in diagnosis or treatment, so it is very common to see a history of headache for more than 1 year in firstvisit patients with headache. We tried to recruit all eligible CM or CTTH patients who firstly visited our clinics. Nevertheless, we did not collect data for total potential eligible patients and those who declined to participate in our study. Retainment of information on patients who declined to participate is somewhat complicated owing to privacy law in Korea. The ratio of CTTH to CM in the present study was similar to that recorded in previous studies. All participants who were initially selected completed the study. Finally, we used Fisher’s exact test in addition to chi-square test when the expected values in any of the cells of a contingency table were below 5. After the comments of Drs. Leiva-Calder on and MayorgaMoreno and a better understanding of the issues, we will include a comment on Fisher’s exact test in addition to a chi-square test in a correction statement to accompany the original article going forward.
Transcriptomic Studies of the Effect of nod Gene-Inducing Molecules in Rhizobia: Different Weapons, One Purpose

Simultaneous quantification of transcripts of the whole bacterial genome allows the analysis of the global transcriptional response under changing conditions. RNA-seq and microarrays are the most used techniques to measure these transcriptomic changes, and both complement each other in transcriptome profiling. In this review, we exhaustively compiled the symbiosis-related transcriptomic reports (microarrays and RNA sequencing) carried out hitherto in rhizobia. This review is specially focused on transcriptomic changes that takes place when five rhizobial species, Bradyrhizobium japonicum (=diazoefficiens) USDA 110, Rhizobium leguminosarum biovar viciae 3841, Rhizobium tropici CIAT 899, Sinorhizobium (=Ensifer) meliloti 1021 and S. fredii HH103, recognize inducing flavonoids, plant-exuded phenolic compounds that activate the biosynthesis and export of Nod factors (NF) in all analysed rhizobia. Interestingly, our global transcriptomic comparison also indicates that each rhizobial species possesses its own arsenal of molecular weapons accompanying the set of NF in order to establish a successful interaction with host legumes.