Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved National Results With Simultaneous Liver‐Kidney Transplantation Using Donation After Circulatory Death Donors

Previous large registry studies have demonstrated inferior outcomes for simultaneous liver‐kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD‐SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000‐2010) and era 2 (2011‐2018). Improvement in DCD‐SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD‐SLKT. When DCD‐SLKT in era 2 was compared with a propensity‐matched cohort of DBD‐SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow‐up were not different between the DCD‐SLKT and DBD‐SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD‐SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD‐SLKT. DCD‐SLKT represents a viable option for appropriately selected recipients.
Targeted Forward Genetics: Population-Scale Analyses of Allele Replacements Spanning Thousands of Base Pairs in Fission Yeast

Precise allele replacement (genome editing), without unwanted changes to the genome, provides a powerful tool to define the functions of DNA elements and encoded factors in their normal biological context. While CRISPR is now used extensively for gene targeting, its utility for precise allele replacement at population scale is limited because: (A) there is a strict requirement for a correctly positioned PAM motif to introduce recombinogenic dsDNA breaks (DSBs); (B) efficient replacements only occur very close to the DSBs; and (C) indels and off-target changes are frequently generated. Here we show, using a saturated mutation library with about 15,000 alleles of the ade6 gene of Schizosaccharomyces pombe, that pop-in, pop-out allele replacement circumvents these problems. Two rounds of selection ensure that clones arise by homologous recombination with the target locus. Moreover, the exceptionally high efficiency allows one to carry out the process in bulk, then screen individual clones for phenotypes and genotypes. Alleles were introduced successfully throughout the region targeted, up to 1,956 base pairs from the DSB. About 11% of mutant alleles were hypomorphic, demonstrating utility for analyses of essential genes and genetic elements. This process of “targeted forward genetics” can be used to analyze comprehensively, across thousands of base pairs within a specific target region, a variety of allelic changes, such as scanning amino acid substitutions, deletions, and epitope tags. The overall approach and optimized workflow are extensible to other organisms that support gene targeting.
Structural and functional contributions of lipids to the stability and activity of the photosynthetic cytochrome b6f lipoprotein complex

The photosynthetic cytochrome b6f complex, a homodimer containing eight distinct subunits and 26 transmembrane helices per monomer, catalyzes proton-coupled electron transfer across the thylakoid membrane. The 2.5-Å-resolution structure of the complex from the cyanobacterium Nostoc sp. revealed the presence of 23 lipid-binding sites per monomer. Although the crystal structure of the cytochrome b6f from a plant source has not yet been solved, the identities of the lipids present in a plant b6f complex have previously been determined, indicating that the predominant lipid species are monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), phosphatidylglycerol (PG), and sulfoquinovosyldiacylglycerol (SQDG). Despite the extensive structural analyses of b6f–lipid interactions, the basis of the stabilization by lipids remains poorly understood. In the present study, we report on the effect of individual lipids on the structural and functional integrity of the b6f complex, purified from Spinacea oleracea. It was found that (i) galactolipids (MGDG, DGDG, and SQDG) and phospholipids dilinolenoyl-phosphatidylglycerol (DLPG), 1,2-dioleoylphosphatidylglycerol (DOPG), and 1,2-dioleoyl-sn-glycerol-3-phosphatidylcholine (DOPC) structurally stabilize the complex to varying degrees; (ii) SQDG has a major role in stabilizing the dimeric complex; (iii) the b6f complex is stabilized by incorporation into nanodiscs or bicelles; (iv) removal of bound phospholipid by phospholipase A2 inactivates the cytochrome complex; and (v) activity can be restored significantly by the addition of the anionic lipid PG, which is attributed to stabilization of the quinone portal and the hinge region of the iron–sulfur protein.
Population pharmacokinetic‐pharmacodynamic modelling of liquid and controlled‐release formulations of oxycodone in healthy volunteers

Oral controlled‐release formulations are playing an ever‐increasing role in opioid therapy; however, little is known about their influence on the relationship between pharmacokinetics and pharmacodynamics. The study aim was to characterize the pharmacokinetic‐pharmacodynamics of two controlled‐release tablet formulations and a liquid formulation of oxycodone in healthy, opioid‐naïve volunteers, which can serve as a reference for future patient studies. A semi‐double‐blinded, three‐way crossover study was conducted, with fifteen healthy volunteers receiving two differently designed 20 mg monophasic controlled‐release oxycodone tablets and 10 mg oral solution oxycodone in a randomized order. Venous plasma concentrations and pupil diameter were determined pre‐dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.33, 2.66, 3, 3.33, 3.66, 4, 5, 6, 8, 12 and 24 hour post‐dose. Oxycodone pharmacokinetics was best described by a two‐compartment model with first‐order absorption. The controlled‐release formulations had an absorption lag of 0.23 hour and a slower absorption rate constant (kaCR = 0.19 hour‐1) compared to the oral solution (kaSOL = 0.94 hour‐1). Effects on pupil diameter were delayed relative to plasma (14 minutes half‐life) for all formulations and were best described by a proportional Emax model. The plasma concentration of oxycodone at half‐maximum effect was lower in males (31.1 μg/L) compared to females (52.8 μg/L; P < .001). The absorption profile of controlled‐release oxycodone formulations provided a prolonged onset and offset of action compared to oral solution oxycodone. The controlled‐release formulations showed no differences in pharmacokinetic and pharmacodynamic parameters suggesting that both may be used interchangeably in human beings with normal gastrointestinal function.
Gestational Weight Gain and Adverse Birth Outcomes in Twin Pregnancies.

OBJECTIVE To evaluate the association between gestational weight gain in twin pregnancies and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth, preterm birth before 32 weeks of gestation, cesarean delivery, and infant death within each prepregnancy body mass index (BMI) category. METHODS Data in this population-based study came from Pennsylvania-linked infant birth and death records (2003-2013). We studied 54,836 twins born alive before 39 weeks of gestation. Total pregnancy weight gain (kg) was converted to gestational age-standardized z scores. Multivariable modified Poisson regression models stratified by prepregnancy BMI were used to estimate associations between z scores and outcomes. A probabilistic bias analysis, informed by an internal validation study, evaluated the effect of BMI and weight gain misclassification. RESULTS Gestational weight gain z score was negatively associated with SGA and positively associated with LGA and cesarean delivery in all BMI groups. The relation between weight gain and preterm birth was U-shaped in nonobese women. An increased risk of infant death was observed for very low weight gain among normal-weight women and for high weight gain among women without obesity. Most excess risks of these outcomes were observed at weight gains at 37 weeks of gestation that are equivalent to less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity. The bias analysis supported the validity of the conventional analysis. CONCLUSION Very low or very high weight gains were associated with the adverse outcomes we studied. If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes.
Improving Attitudes to Volunteering Among Older Adults: A Randomized Trial Approach

Promoting engagement in formal volunteering represents a potential means of facilitating healthy aging. Given reluctance to participate in volunteering has been partially attributed to negative perceptions of various aspects of this activity, this study assessed whether trialing volunteering can improve perceptions among older people. Using a parallel-group design, Australians aged 60+ years (n = 445) were randomly assigned to one of two conditions, one in which they were encouraged to trial volunteering and one in which they were asked to continue their usual activities. Perceptions and attitudes among those in the volunteering condition became significantly more favorable over 6 months relative to those in the control condition, with this change predicted by several aspects of the volunteering experience (e.g., acquisition of skills, increased social connectedness). Providing access to roles that cater to the learning and social needs of older adults appears to be important for improving attitudes toward engaging in volunteer work.
Validation of Semantic Analyses of Unstructured Medical Data for Research

Affliations 1 Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz 2 Studienzentrale, Nationales Centrum für Tumorerkrankungen Heidelberg, Heidelberg 3 Averbis GmbH, Freiburg 4 Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, University Medical Center of the Johannes Gutenberg University Mainz, Mainz 5 Leibniz-Institut für Präventionsforschung und Epidemiologie (BIPS), Prevention and Evaluation, Bremen 6 Institut fur Medizinische Biometrie Epidemiologie und Informatik, Johannes-Gutenberg Universität Mainz, Mainz
Interferon-Inducible Protein 10 and Disease Activity in Systemic Lupus Erythematosus and Lupus Nephritis: A Systematic Review and Meta-Analysis

There is increasing evidence of a correlation between interferon-inducible protein 10 (IP-10) and disease activity of systemic lupus erythematosus (SLE) and lupus nephritis (LN). We conducted a comprehensive search on IP-10 using MEDLINE, Scopus, and Cochrane electronic databases from the beginning to the end of December 2017. All studies that compared serum and/or urine IP-10 between active SLE/LN patients and any control groups were identified and included in this systematic review and meta-analysis. The mean difference (MD) of IP-10 level among active SLE and LN patients, as well as the correlation of IP-10 with disease activity, were meta-analyzed using a random-effects model. From 23 eligible studies, 15 provided adequate data for meta-analysis. Serum IP-10 was significantly elevated in patients with active SLE compared to non-active SLE patients (MD 356.5 pg/mL, 95% CI 59.6 to 653.4, p = 0.019). On the other hand, the levels of serum IP-10 was not different between active LN and non-active LN. However, serum IP-10 was positively correlated with disease activity like SLE disease activity index (SLEDAI) (pooled r = 0.29, 95% CI 0.22 to 0.35, p < 0.001). Furthermore, urine IP-10 tended to be higher in patients with active LN compared to non-active LN patients but this did not reach statistical significance (MD 3.47 pg/mgCr × 100, 95% CI −0.18 to 7.12, p = 0.06). Nevertheless, urine IP-10 was positively correlated with renal SLEDAI (pooled r = 0.29, 95% CI 0.05 to 0.50, p = 0.019). In conclusion, serum and urine IP-10 levels may be useful in monitoring the disease activity of SLE and LN. Serum IP-10 was correlated with systemic disease whereas urine IP-10 was a useful biomarker for detecting active LN.
Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies: Translatable Microbubble Targeting Murine and Human VCAM (Vascular Cell Adhesion Molecule) 1.

OBJECTIVE Contrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MBcAbVcam1-5) and microbubble with a control nanobody (MBVHH2E7) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MBcAbVcam1-5 and MBVHH2E7. Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×105 per microbubble. Compared with MBVHH2E7, MBcAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MBcAbVcam1-5 in early (P=0.0003 versus MBVHH2E7) and late atherosclerosis (P=0.007 versus MBVHH2E7); in wild-type mice, there were no differences between MBcAbVcam1-5 and MBVHH2E7. CEUMI in human endarterectomy specimens showed a 100% increase in signal for MBcAbVcam1-5versus MBVHH2E7 (20.6±27.7 versus 9.6±14.7, P=0.0156). CONCLUSIONS CEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.
Well-being measures for younger children.

Understanding variations in children's well-being is key to addressing inequalities. It is especially useful to understand children's own perspectives, although there is a lack of short questionnaires using simple language which can be administered to younger children (or in situations when testing-time is limited). Here we first present the VSWQ-C, a Very Short Well-Being Questionnaire for Children, which captures health-related quality-of-life in a brief questionnaire for both older and younger child responders. We provide preliminary validation evidence for this new measure from two English samples of children aged 6-7 and 9-10 years. Next, we also adapted an existing measure of children's emotional well-being (10-item Positive and Negative Effect Schedule for Children; Ebesutani et al., 2012), again to be suitable for a younger cohort. Our adaptation, the Definitional Positive and Negative Effect Schedule for Children (dPANAS-C), provides children as young as 6 with age-appropriate definitions of questionnaire vocabulary. We again present preliminary validation evidence from 9-10 year olds, as well as children 6-7 years (i.e., 1-2 years younger than the original version of this questionnaire had been psychometrically developed for). We looked too at demographic influences, and show that older children report greater well-being (in the VSWQ-C) as well as lower negative affect (in the dPANAS-C), but without gender differences. Our findings show that our tools eliciting self-reports of well-being are valuable and valid instruments for children as young as 6 years, with acceptable reliability and strong convergent validity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
OsATG8c-Mediated Increased Autophagy Regulates the Yield and Nitrogen Use Efficiency in Rice

Autophagy, a conserved pathway in eukaryotes, degrades and recycles cellular components, thus playing an important role in nitrogen (N) remobilization. N plays an important role in the growth and development of plants, which also affects plant yield and quality. In this research, it was found that the transcriptional level of a core autophagy gene of rice (Oryza sativa), OsATG8c, was increased during N starvation conditions. It was found that the overexpression of OsATG8c significantly enhanced the activity of autophagy and that the number of autophagosomes, dwarfed the plant height and increased the effective tillers’ number and yield. The nitrogen uptake efficiency (NUpE) and nitrogen use efficiency (NUE) significantly increased in the transgenic rice under both optimal and suboptimal N conditions. Based on our results, OsATG8c is considered to be a good candidate gene for increasing NUE, especially under suboptimal field conditions.
Psychiatric morbidity and suicidal behaviour in low- and middle-income countries: A systematic review and meta-analysis

Background Psychiatric disorders are reported to be present in 80% to 90% of suicide deaths in high-income countries (HIC), but this association is less clear in low- and middle-income countries (LMIC). There has been no previous systematic review of this issue in LMIC. The current study aims to estimate the prevalence of psychiatric morbidity in individuals with suicidal behaviour in LMIC. Methods and findings PubMed, PsycINFO, and EMBASE searches were conducted to identify quantitative research papers (any language) between 1990 and 2018 from LMIC that reported on the prevalence of psychiatric morbidity in suicidal behaviour. We used meta-analytic techniques to generate pooled estimates for any psychiatric disorder and specific diagnosis based on International classification of disease (ICD-10) criteria. A total of 112 studies (154 papers) from 26 LMIC (India: 25%, China: 15%, and other LMIC: 60%) were identified, including 18 non-English articles. They included 30,030 individuals with nonfatal suicidal behaviour and 4,996 individuals who had died by suicide. Of the 15 studies (5 LMIC) that scored highly on our quality assessment, prevalence estimates for psychiatric disorders ranged between 30% and 80% in suicide deaths and between 3% and 86% in those who engaged in nonfatal suicidal behaviour. There was substantial heterogeneity between study estimates. Fifty-eight percent (95% CI 46%–71%) of those who died by suicide and 45% (95% CI 30%–61%) of those who engaged in nonfatal suicidal behaviour had a psychiatric disorder. The most prevalent disorder in both fatal and nonfatal suicidal behaviour was mood disorder (25% and 21%, respectively). Schizophrenia and related disorders were identified in 8% (4%–12%) of those who died by suicide and 7% (3%–11%) of those who engaged in nonfatal suicidal behaviour. In nonfatal suicidal behaviour, anxiety disorders, and substance misuse were identified in 19% (1%–36%) and 11% (7%–16%) of individuals, respectively. This systematic review was limited by the low number of high-quality studies and restricting our searches to databases that mainly indexed English language journals. Conclusions Our findings suggest a possible lower prevalence of psychiatric disorders in suicidal behaviour in LMIC. We found very few high-quality studies and high levels of heterogeneity in pooled estimates of psychiatric disorder, which could reflect differing study methods or real differences. There is a clear need for more robust evidence in order for LMIC to strike the right balance between community-based and mental health focussed interventions.
Phone Speech Recognition Improvement in Noisy Environment: Use of a Bluetooth Accessory

Objective: To evaluate speech understanding in noise and patient satisfaction using the new Cochlear Wireless Phone Clip device. Material and Methods: Twenty-nine experienced cochlear implant (CI) users (>6 months usage) were situated in a soundproof room where a 65 dB SPL Spanish cocktail noise was generated continuously from 4 loudspeakers. Lists of disyllabic words were presented through the clinic landline telephone to the patients. Patients were tested first holding the phone and then with the Cochlear Phone Clip© paired to the CP910 using various mixing ratios (2:1, 4:1, and Phone Clip© only). Results: Statistically significant (P < .001) improvement of speech recognition performance was found in cell phone usage by wireless transmission and also when using this new device. Kepler questionnaire results showed that before using Phone Clip in everyday life, 55.2% of patients described themselves highly or greatly affected by their deafness for telephone use and 80% moderately to greatly affected. Kim questionnaire results showed statistically significant differences (P < .001) in the subjective satisfaction of the Bluetooth-implemented CI compared to the conventional mode for sound quality, noise interference, and sound accuracy. Conclusions: The wireless Phone Clip© device helps implanted people to improve subjective and objective speech recognition performance through the phone in noisy environments.
Prefrontal GABA and glutamate levels correlate with impulsivity and cognitive function of prescription opioid addicts: A 1H‐magnetic resonance spectroscopy study

Prescription opioids are psychoactive substances that can elicit many neuropsychological effects. There are no studies that directly demonstrate the effects of prescription opioid addiction (POA) on the human brain. This study aimed to quantify γ‐aminobutyric acid (GABA) and glutamate (Glu) levels in the prefrontal cortex (PFC) of POA patients using proton magnetic resonance spectroscopy (1H‐MRS), and to explore their association with impulsive behavior and cognitive impairment.
Dysfunctional beliefs as mediators between illness-related intrusive thoughts and health anxiety symptoms

Abstract Background: Cognitive behavioural models of hypochondriasis assume that dysfunctional illness-related beliefs are involved in the genesis and maintenance of the disorder. The role that other more general dysfunctional beliefs about thoughts play in this disorder has also been highlighted. Internal triggers such as illness-related intrusive thoughts could activate these beliefs. Aim: The present paper examines whether general dysfunctional beliefs about distressing thoughts, such as intolerance of uncertainty, over-estimation of threat, and thought-action fusion-likelihood, mediate between illness-related intrusive thoughts and health anxiety symptoms. Method: A group of participants composed of individuals with hypochondriasis (n = 31; 51.5% women; mean age = 32.74 years, SD = 9.96) and community individuals (n = 219; 54.3% women; mean age = 39.56 years, SD = 15.20) completed a series of questionnaires to assess illness-related intrusive thoughts (INPIE), dysfunctional beliefs about thoughts (OBSI-R), and health anxiety symptoms (SHAI). Results: Results from a multiple parallel mediation analysis indicate that over-estimation of threat partially mediated the relationship between illness-related intrusive thoughts and health anxiety symptoms. Conclusions: The results support the importance of the tendency to over-estimate the threat in the relationship between intrusive thoughts related to illness contents and health anxiety. Conceptual and clinical implications of these results are discussed.