Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative effectiveness research and patients with multiple chronic conditions.

The aim of comparative effectiveness research (CER) is to improve the quality, effectiveness, and efficiency of health care and to help patients, health care professionals, and purchasers make informed decisions. CER is moving forward, with recently defined priorities and a newly funded Patient-Centered Outcomes Research Institute, which we hope will survive congressional cost cutting. To achieve its goals, CER must address the population that consumes the most health care: patients with multiple chronic conditions, especially those with combinations of behavioral and physical conditions such as dementia, mental illness, end-stage renal disease, and heart failure. Such patients account for more than .
Influence of auditory attention on sentence recognition captured by the neural phase

The aim of this study was to investigate whether attentional influences on speech recognition are reflected in the neural phase entrained by an external modulator. Sentences were presented in 7 Hz sinusoidally modulated noise while the neural response to that modulation frequency was monitored by electroencephalogram (EEG) recordings in 21 participants. We implemented a selective attention paradigm including three different attention conditions while keeping physical stimulus parameters constant. The participants’ task was either to repeat the sentence as accurately as possible (speech recognition task), to count the number of decrements implemented in modulated noise (decrement detection task), or to do both (dual task), while the EEG was recorded. Behavioural analysis revealed reduced performance in the dual task condition for decrement detection, possibly reflecting limited cognitive resources. EEG analysis revealed no significant differences in power for the 7 Hz modulation frequency, but an attention‐dependent phase difference between tasks. Further phase analysis revealed a significant difference 500 ms after sentence onset between trials with correct and incorrect responses for speech recognition, indicating that speech recognition performance and the neural phase are linked via selective attention mechanisms, at least shortly after sentence onset. However, the neural phase effects identified were small and await further investigation.
An investigation of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay.

BACKGROUND The aims of this study were to establish whether individual differences exist in the frequency and size of vacuoles found in human sperm and to ascertain whether such vacuoles are involved in causing DNA damage. METHODS Morphologically normal sperm were obtained from 15 IVF and 2 ICSI patients and 3 fertile donors. (i) Sperm heads were analyzed for the presence of vacuoles under a 1000× differential interference contrast microscope. (ii) In three patients and two donor samples, structural chromosomal damage was evaluated in normal sperm containing large vacuoles and selected at 1000× magnification for injection into mouse oocytes. (iii) In 10 patients and two donor samples, confocal laser microscopy detected DNA damage in sperm-exhibiting large vacuoles and stained with an in situ cell death detection kit. RESULTS (i) Vacuoles were observed in almost all normal sperm from patient and donor ejaculates and were mainly located at the tip or middle area of the sperm heads. However, average incidence of normal sperm exhibiting large vacuoles was 4.6 and 4.2% in the patient and donor groups, respectively. (ii) Sperm chromosome assays did not reveal any differences in the incidence of structural chromosome aberrations between sperm exhibiting large vacuoles and those without them (9.1 versus 4.1%). (iii) No significant difference in frequency of TUNEL-positive cells was found between normal sperm with large vacuoles and those without them in the samples examined. Among 227 sperm exhibiting large vacuoles, only 7 cells were TUNEL positive. CONCLUSION The results showed that large vacuoles were not responsible for DNA damage, suggesting that intra-cytoplasmic injection of morphologically selected sperm may not be required for patients who produce high-quality semen.
Activity restriction and the mechanistic basis for extinctions under climate warming

*Correspondence: E-mail: mrke@unimelb.edu. au Abstract Correlative analyses predict that anthropogenic climate warming will cause widespread extinction but the nature and generality of the underlying mechanisms is unclear. Warming-induced activity restriction has been proposed as a general explanatory mechanism for recent population extinctions in lizards, and has been used to forecast future extinction. Here, I test this hypothesis using globally applied biophysical calculations of the effects of warming and shade reduction on potential activity time and whole-life-cycle energy budgets. These ‘thermodynamic niche’ analyses show that activity restriction from climate warming is unlikely to provide a general explanation of recent extinctions, and that loss of shade is viable alternative explanation. Climate warming could cause population declines, even under increased activity potential, through joint impacts on fecundity and mortality rates. However, such responses depend strongly on behaviour, habitat (shade, food) and life history, all of which should be explicitly incorporated in mechanistic forecasts of extinction risk under climate change.
The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh‐TNF‐α, IL‐1β and IFN‐γ

It is becoming widely accepted that the inflammatory response is involved in neurodegenerative disease. In this context, we have developed an animal model of dopaminergic system degeneration by the intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation. To address the importance of the inflammatory response in the LPS‐induced degeneration of nigral dopaminergic neurones, we carried out two different kinds of studies: (i) the possible protective effect of an anti‐inflammatory compound, and (ii) the effect of the intranigral injection of inflammatory cytokines (TNF‐α, IL‐1β and IFN‐γ) on dopaminergic neurones viability. Present results show that dexamethasone, a potent anti‐inflammatory drug that interferes with many of the features characterizing pro‐inflammatory glial activation, prevented the loss of catecholamine content, Tyrosine hydroxylase (TH) activity and TH immunostaining induced by LPS‐injection and also the bulk activation of microglia/macrophages. Surprisingly, injection of the pro‐inflammatory cytokines failed to reproduce the LPS effect. Taken together, our results suggest that inflammatory response is implicated in LPS‐induced neurodegeneration. This damage may be due, at least in part, to a cascade of events independent of that described for TNF‐α/IL‐1β/IFN‐γ.
The impact of irradiance on optimal and cellular nitrogen to phosphorus ratios in phytoplankton.

Phytoplankton acclimates to irradiance by regulating the cellular content of light-harvesting complexes, which are nitrogen (N) rich and phosphorus (P) poor. Irradiance is thus hypothesised to influence the cellular N : P ratio and the N : P defining the threshold between N and P limitation (the 'optimal' N : P). We tested this hypothesis by first addressing the response of the optimal N : P to irradiance in a controlled experiment with Chlamydomonas reinhardtii. Then, we did a meta-analysis of experimental data on optimal and cellular N : P ratios across light gradients to test the generality of an N : P to light response within species. In both the experiment and the meta-analysis, N : P ratios decreased with irradiance, indicating that factors affecting underwater irradiance, like depth and the composition of the water, may influence the relative N : P requirement. The effect of irradiance did not differ between optimal and cellular N : P ratios, but observations of optimal N : P were on average 2.8 times higher than observations of cellular N : P.
Influence of Quality of Relationship Between Patient With Melanoma and Partner on Partner-Assisted Skin Examination Education: A Randomized Clinical Trial.

IMPORTANCE Melanoma has a high survival rate if it is detected early. Training patients with early-stage melanoma who are at risk of developing new melanomas to perform skin self-examination (SSE) may improve survival. OBJECTIVE To examine for whom the intervention works best in a sample composed of dyads of patients with melanoma and skin-check partners who received an SSE intervention vs customary care. DESIGN, SETTING, AND PARTICIPANTS For 494 patients with stage 0 to IIB melanoma (mean age, 55 years; 253 [51.2%] females) and their skin-check partners (mean age, 55 years; 280 [56.7%] females), a randomized clinical trial was conducted in ambulatory care dermatologic offices from June 6, 2011, to April 14, 2014. Follow-up assessments were performed at 12 months. Analysis was performed between March 23 and June 25, 2015. METHODS Dyads of 494 patients and their partners were randomly assigned to receive the intervention (395 patients) or customary care (control) (99 patients). The main outcome was patient SSE self-efficacy. Partner motivation to assist with SSE and relationship quality (eg, agreeability, activities with partner, and happiness) were assessed for moderation of the influence of the intervention's effect on SSE self-efficacy. RESULTS Relationship quality, defined by activities with the partner (β = -0.892, SE = 0.432, t = -2.066; P = .001) and happiness (β = -4.586, SE = 2.044, t = -2.24; P = .001), significantly moderated the intervention effects on patients' SSE self-efficacy. In contrast, patient-partner agreeability (β = -0.262, SE = 0.148, t = -1.773; P = .09) and partner motivation (β = -0.328, SE = 1.024, t = -0.320; P = .10) did not significantly moderate the intervention effects on patients' SSE self-efficacy. Differences between the conditions were highest when activities performed with the partner were below average (mean difference, 6.652; P = .001) and when happiness was below average (mean difference, 7.000; P = .001). Although everyone receiving the intervention experienced some benefit, the findings indicate the greatest increases in self-efficacy were observed for those with below-average activities performed with the partner and happiness. CONCLUSIONS AND RELEVANCE The training of patients with melanoma and their partners in early-detection SSE benefited some more than others. Pairs who have low relationship quality, as determined by activities performed with the partner and happiness, may have received the greatest benefits from the training intervention because they were given an activity to perform together. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01432860.
Prenatal famine, birthweight, reproductive performance and age at menopause: the Dutch hunger winter families study.

STUDY QUESTION Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? SUMMARY ANSWER No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. WHAT IS KNOWN ALREADY Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. STUDY DESIGN, SIZE, DURATION This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. PARTICIPANTS/MATERIALS, SETTING, METHODS The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. MAIN RESULTS AND THE ROLE OF CHANCE Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. LIMITATIONS, REASON FOR CAUTION Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. WIDER IMPLICATIONS OF THE FINDINGS Our findings support previous results that prenatal famine exposure is not related to reproductive performance in adult life. However, natural menopause occurs earlier after prenatal famine exposure, suggesting that early life events can affect organ function even at the ovarian level. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the NHLBI/NIH (R01 HL-067914). TRIAL REGISTRATION NUMBER Not applicable.
Trans fatty acid intake is inversely related to total sperm count in young healthy men.

STUDY QUESTION Is intake of fatty acids related to semen quality among young men? SUMMARY ANSWER The intake of trans fatty acids is inversely related to total sperm count in healthy young men. WHAT IS KNOWN ALREADY Spain has seen an increase in the proportion of calories consumed as fat over the same period that a downward trend in semen quality has been observed. In addition, rodent models suggest that trans fat intake may severely affect testicular function. STUDY DESIGN, SIZE, DURATION Cross-sectional study of 209 men recruited between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS A group of 209 healthy young university students 18-23 years of age provided a semen sample and completed a previously validated food frequency questionnaire. The association between intake of fatty acids with semen quality parameters (sperm concentration, motility, morphology and total count) was assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF THE CHANCE Trans fatty acid intake was inversely related to total sperm count after adjusting for potential confounders (P, trend = 0.03). The multivariate adjusted mean (95% confidence interval) total sperm count in increasing quartiles of trans fat intake was 144 (110-190), 113 (87-148), 100 (18-130) and 89 (69-117). There also was an inverse association between cholesterol intake and ejaculate volume (P, trend = 0.04). No other statistically significant relations were observed. LIMITATIONS, REASONS FOR CAUTION The cross-sectional design of the study limits causal inference, we cannot exclude the possibility of unmeasured confounding and there was insufficient statistical power to identify modest associations. WIDER IMPLICATIONS OF THE FINDINGS The results of this study, together with previous experimental work in rodents and biomarker studies among infertility patients, suggest that intake of trans fatty acids may be related to lower semen quality. Although the data provide further evidence that diet is a modifiable factor that could impact male fertility, it is not known whether the observed differences in sperm count translate into differences in fertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by The Seneca Foundation, Regional Agency of Science and Technology, grant no 00694/PI/04, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (FIS), grant no PI10/00985, and grant P30 DK46200 from the National Institutes of Health. The authors have no competing interests to declare.
ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010.

STUDY QUESTION How do data in the 12th annual data collection (Data XII) of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis (PGD) Consortium compare with the cumulative data for collections I-XI? SUMMARY ANSWER Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. WHAT IS KNOWN ALREADY The PGD Consortium has collected, analysed and published 11 previous data sets since 1997. STUDY DESIGN, SIZE, DURATION Data were collected from each participating centre using a pre-designed FileMaker Pro database (versions 5-10). Separate FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2009 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2010). PARTICIPANTS/MATERIALS, SETTING, METHODS Data were submitted by 60 centres (full PGD Consortium members), and the blank files were distributed to each PGD Consortium member centre at the end of 2008. The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete data were excluded from the calculations. Corrections, tables and calculations were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE For data collection XII, 60 centres reported data for 6160 cycles with oocyte retrieval (OR), along with details of the follow-up on 1607 pregnancies and 1238 babies born. A total of 870 OR were reported for chromosomal abnormalities, 113 OR for sexing for X-linked diseases, 1597 OR for monogenic diseases, 3551 OR for preimplantation genetic screening and 29 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION These data cannot include every PGD cycle performed annually, and only indicate the trends in PGD worldwide. WIDER IMPLICATION OF THE FINDINGS The annual data collections provide an extremely valuable resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTEREST(S) None.
Ischaemic stroke at a young age is a serious event – final results of a population‐based long‐term follow‐up in Western Norway

Our population‐based long‐term follow‐up of young ischaemic stroke patients and controls showed 10‐fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive–dead survey.
Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis

Firategrast is an orally bioavailable alpha4 beta1/alpha4 beta7 integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS). This could decrease multiple sclerosis (MS) activity, but may compromise CNS immune surveillance. We aimed to quantitate the effect of firategrast treatment on cerebrospinal fluid (CSF) lymphocyte count and the extent/speed of recovery after its discontinuation.
Clinical and MRI predictors of response to interferon‐beta and glatiramer acetate in relapsing–remitting multiple sclerosis patients

It is still unclear which patients benefit more from available disease‐modifying treatments (DMTs) in multiple sclerosis (MS). Our objective is to identify the baseline clinical and magnetic resonance imaging (MRI) predictors of response to first‐line DMTs in a cohort of relapsing–remitting (RR) MS patients in a real‐world clinical setting.
Factors associated with post‐stroke anger proneness in ischaemic stroke patients

Factors related to post‐ stroke anger proneness (PSAP) are poorly studied. The aim of the present study was to determine the frequency of, and the factors related to, PSAP in the acute stage of stroke. Serotonin transporter protein genes and monoamine oxidase A (MAO‐A) gene polymorphisms were also examined.
Reply: Preimplantation genetic screening using comprehensive chromosome screening: evidence and remaining challenges.

Sir, We thank Dr Dahdouh and colleagues for their interest on our systematic review on the clinical effectiveness of preimplantation genetic diagnosis for aneuploidy (PGD-A) (Lee et al., 2015). We are pleased that in essence they concur with our conclusions, and that they also call for more robust evidence from randomized controlled trials (RCTs) before PGD-A is applied on a regular basis. We chose to use the terminology PGD for aneuploidy (PGD-A) instead of preimplantation genetic screening (PGS) as we believe it better reflects that this type of testing is diagnostic for the individual embryos and is not a screening test. Other key authors (Bisignano et al., 2011; Handyside, 2011; Munné 2012) in this field also recognize that either terminology can be used. We chose to include both intervention and observational studies in our systematic review to provide a synopsis of the quality of available evidence on the topic and to draw objective conclusions where possible on the effectiveness of PGD-A based on patient-centred outcomes. We also concur with Dahdouh et al.’s systematic review (Dahdouh et al., 2014) that current evidence based from published RCTs demonstrates improved implantation and pregnancy rates in young good-prognosis patients following PGD-A and that such an approach advances the adoption of single embryo transfer (Yang et al., 2012; Forman et al., 2013; Scott et al., 2013). However, good quality evidence is lacking in other patient groups. We did not claim that there were no reports on subsequent embryo transfer cycles following PGD-A, and in fact included the cumulative success rates following one thaw cycle reported in Forman’s RCT (Forman et al., 2014). However, we did not include the results of Yang et al.’s (Yang et al., 2013) follow-up thaw cycles because they were reported as a separate result of 15 patients and therefore did not fit our inclusion criteria of at least 20 patients. We can also only concur with Dr Dahdouh and colleagues that laboratory quality and experience are key aspects for a successful PGD-A program, and is why we dedicated some text to describing the minimal requirements for conducting high-quality studies in this area. Furthermore, it is also important that RCTs are correctly designed and analysed according to intention-to-treat principles that minimize bias and report success in terms of cumulative live birth rates from fresh and subsequent frozen cycles. References
Comparison of cortical thickness in patients with early‐stage versus late‐stage amnestic mild cognitive impairment

Disappointing outcomes from clinical trials involving amyloid‐modifying therapies for Alzheimer's disease (AD) have prompted more focus on the concept of early‐stage (E) amnestic mild cognitive impairment (E‐aMCI). However, limited evidence suggests that E‐aMCI may represent aMCI at a very early stage of AD. Furthermore, the nature of the progression of E‐aMCI to late‐stage aMCI (L‐aMCI) remains unclear. Therefore, the aim of the present study was to characterize patterns of cortical thinning in both E‐aMCI and L‐aMCI patients.