Miracle-dz/UniFAR-FTUs huggingface dataset:
Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD‐sodium era

The impact of hyponatremia on waitlist and post‐transplant outcomes following the implementation of MELD‐Na‐based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD‐Na‐based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre‐MELD‐Na and post‐MELD‐Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety‐day waitlist outcomes and post‐LT survival were compared using Fine‐Gray proportional hazard and mixed‐effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre‐MELD‐Na; n = 53 547: post‐MELD‐Na). In the pre‐MELD‐Na era, extreme hyponatremia at listing was associated with an increased risk of 90‐day waitlist mortality ([ref: 135–145] HR: 3.80; 95% CI: 2.97–4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38–2.01; P < 0.001). In the post‐MELD‐Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60–3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76–2.55; P < 0.001) as patients with normal serum sodium levels (135–145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365‐day post‐LT survival compared to patients with normal serum sodium levels. With the introduction of MELD‐Na‐based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short‐term post‐LT survival.
On the lexical representation(s) of compounds: A continuous picture naming study.

The lexical representation of compound words in speech production is still under debate. While most studies with healthy adult speakers suggest that a single lemma representation is active during compound production, data from neuropsychological studies point toward multiple representations, with activation of the compound's constituent lemmas in addition to the compound's lemma. This study exploits the cumulative semantic interference effect to investigate the lexical representation of compounds in speech production. In a continuous picture naming experiment, category membership was established through the compounds' first constituents (category animals: zebra crossing, pony tail, cat litter …), while the compounds themselves were not semantically related. Moreover, pictures depicting the compounds' first constituents (zebra, pony, cat …) were presented as a control condition. As expected, naming latencies within categories increased linearly with each additionally named category member when producing monomorphemic words, which is interpreted as increasing interference during lexical selection. Importantly, this cumulative semantic interference effect was also observed for compounds. This indicates that the lemmas of the compounds' first constituents were activated during compound production, causing interference due to their semantic relationship and thereby hampering the production of the whole compound. The results are thus in line with the multiple-lemma representation account (Marelli et al., 2012). We argue that the apparent contradiction between results of previous studies with healthy adult speakers and our current study can be explained by the different experimental paradigms used. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
False discovery rate control in genome-wide association studies with population structure

Significance Genome-wide association studies compare a phenotype to thousands of genetic variants, searching for associations of potential biological interest. Standard analyses rely on linear models of the phenotype given one variable at a time. However, their assumptions are difficult to verify and their univariate approaches make it hard to recognize interesting associations from spurious ones. Our work takes a different path: We analyze all variants simultaneously, modelling the randomness in the genotypes, which is better understood, instead of the phenotype. Our solution accounts for linkage disequilibrium and population structure, controls the false discovery rate, and leverages powerful machine-learning tools. Applications to the UK Biobank data indicate increased power compared to state-of-the-art alternatives and high replicability. We present a comprehensive statistical framework to analyze data from genome-wide association studies of polygenic traits, producing interpretable findings while controlling the false discovery rate. In contrast with standard approaches, our method can leverage sophisticated multivariate algorithms but makes no parametric assumptions about the unknown relation between genotypes and phenotype. Instead, we recognize that genotypes can be considered as a random sample from an appropriate model, encapsulating our knowledge of genetic inheritance and human populations. This allows the generation of imperfect copies (knockoffs) of these variables that serve as ideal negative controls, correcting for linkage disequilibrium and accounting for unknown population structure, which may be due to diverse ancestries or familial relatedness. The validity and effectiveness of our method are demonstrated by extensive simulations and by applications to the UK Biobank data. These analyses confirm our method is powerful relative to state-of-the-art alternatives, while comparisons with other studies validate most of our discoveries. Finally, fast software is made available for researchers to analyze Biobank-scale datasets.
Dynamic investigation of microbial activity in microbial enhanced oil recovery (MEOR)

ABSTRACT The activity of reservoir microorganism is essential to Microbial enhanced oil recovery (MEOR). This present paper investigates the relationship between the microbial activity and production performance by means of long-scale & long-term experiments. The six rounds of nutritional injection was carried out in 135 days. During the microbial flooding experiment was performed recovering additional oil (10.44% Original Oil in Place, OOIP) after first water flooding. There is a positive correlation between water content and shannon index. And the fourth round of nutritional injection causes a considerable reduction in water content, while the concentration of Methyl-coenzyme reductase subunit alpha (mcrA) reaches peak value. In microbial flooding and reference water flooding, the concentration of mcrA maintained higher level with the low concentration of acetic acid. There are intimate correlation between water content and mcrA concentration & bacterial diversity (shannon index), which can be consider the symbol to guide the MEOR filed test.
Outcome and prognostication after cardiac arrest

The outcome after out‐of‐hospital cardiac arrest has historically been grim at best. The current overall survival rate of patients admitted to a hospital is approximately 10%, making cardiac arrest one of the leading causes of death in the United States. The situation is improving with the incorporation of therapeutic temperature modulation, aggressive prevention of secondary brain injury, and improved access to advanced cardiovascular support, all of which have decreased mortality and allowed for better outcomes. Mortality after cardiac arrest is often the direct result of active withdrawal of life‐sustaining therapy based on the perception that neurological recovery is not possible. This reality highlights the importance of providing accurate estimates of neurological prognosis to decision makers when discussing goals of care. The current standard of care for assessing neurological status in patients with hypoxic‐ischemic encephalopathy emphasizes a multimodal approach that includes five elements: (1) neurological examination off sedation, (2) continuous electroencephalography, (3) serum neuron‐specific enolase levels, (4) magnetic resonance brain imaging, and (5) somatosensory‐evoked potential testing. Sophisticated decision support systems that can integrate these clinical, imaging, and biomarker and neurophysiologic data and translate it into meaningful projections of neurological outcome are urgently needed.
IP3R-driven increases in mitochondrial Ca2+ promote neuronal death in NPC disease

Significance NPC1 is a ubiquitously expressed lysosomal cholesterol transporter whose loss of function results in neurodegenerative NPC1 disease. Here, we report that loss-of-function, knockout, or mutation-causing NPC1 initiates a damaging signaling cascade that alters the expression and nanoscale distribution of IP3R type 1 that precipitates neuron death. Targeting IP3R1 or upstream elements of this signaling cascade rescues neuronal death and provides potential therapeutic targets to address IP3R dysfunction, a feature of NPC1 disease and other neurodegenerative disorders. Ca2+ is the most ubiquitous second messenger in neurons whose spatial and temporal elevations are tightly controlled to initiate and orchestrate diverse intracellular signaling cascades. Numerous neuropathologies result from mutations or alterations in Ca2+ handling proteins; thus, elucidating molecular pathways that shape Ca2+ signaling is imperative. Here, we report that loss-of-function, knockout, or neurodegenerative disease–causing mutations in the lysosomal cholesterol transporter, Niemann-Pick Type C1 (NPC1), initiate a damaging signaling cascade that alters the expression and nanoscale distribution of IP3R type 1 (IP3R1) in endoplasmic reticulum membranes. These alterations detrimentally increase Gq-protein coupled receptor–stimulated Ca2+ release and spontaneous IP3R1 Ca2+ activity, leading to mitochondrial Ca2+ cytotoxicity. Mechanistically, we find that SREBP-dependent increases in Presenilin 1 (PS1) underlie functional and expressional changes in IP3R1. Accordingly, expression of PS1 mutants recapitulate, while PS1 knockout abrogates Ca2+ phenotypes. These data present a signaling axis that links the NPC1 lysosomal cholesterol transporter to the damaging redistribution and activity of IP3R1 that precipitates cell death in NPC1 disease and suggests that NPC1 is a nanostructural disease.
Exploration of the longitudinal trend of DUI crashes in Pennsylvania, USA (2008 to 2019)

Abstract Objective This study aims to explore the longitudinal trends of DUI crashes in Pennsylvania, USA to provide insights for making the long-term DUI countermeasures. Methods Crash data of Pennsylvania from 2008 to 2019 are collected from the Pennsylvania Department of Transportation. DUI crashes are divided into alcohol-impaired, drug-impaired, and alcohol-drug-impaired ones in the analysis. The linear regression models are adopted to check whether traffic crashes had significantly changed over time. Results Alcohol-impaired crashes decreased but drug-impaired crashes increased in the study period. Drugged driving is increasingly more deadly compared to drunk driving, and alcohol-drug-impaired crashes are the deadliest. Besides, illicit drugs dominate drug-impaired crashes now, drugged driving is increasing in rural areas, and older drivers are overwhelmingly involved in DUI crashes. Conclusions The growth of drug-impaired crashes, especially illicit drug-impaired crashes, raises new concerns to the proposal of marijuana legalization in Pennsylvania, where recreational use of marijuana is currently prohibited. The decreasing trend of alcohol-impaired crashes is suggestive of the success of the long-term crackdown to drunk driving and implies the necessity of developing the uniform and handy roadside drug test devices. Besides, rural areas and older drivers should be paid special attention to deter DUI in the context of urbanization and population aging.
None of My Business? An Experiment Analyzing Willingness to Formally Report Incidents of Intimate Partner Violence Against Women

Although data show that intimate partner violence against women (IPVAW) is a concealed phenomenon that is severely underreported, studies examining willingness to report episodes of IPVAW are limited. To contribute to this field of research, a factorial survey experiment was implemented in which each respondent (N = 1,007) received a unique vignette describing a hypothetical case of IPVAW. Slightly over one in four respondents (28.1%) indicated that they would report the aggression. It was also found that willingness to report was influenced by both the characteristics of the vignettes and certain personal ones of the respondents. Practical implications are proposed that may contribute to preventing IPVAW.
Elimination of Radiation-Induced Senescence in the Brain Tumor Microenvironment Attenuates Glioblastoma Recurrence

This study uncovers mechanisms by which radiotherapy can promote GBM recurrence by inducing senescence in non-neoplastic brain cells, suggesting that senolytic therapy can blunt recurrent GBM growth and aggressiveness. Glioblastomas (GBM) are routinely treated with ionizing radiation (IR) but inevitably recur and develop therapy resistance. During treatment, the tissue surrounding tumors is also irradiated. IR potently induces senescence, and senescent stromal cells can promote the growth of neighboring tumor cells by secreting factors that create a senescence-associated secretory phenotype (SASP). Here, we carried out transcriptomic and tumorigenicity analyses in irradiated mouse brains to elucidate how radiotherapy-induced senescence of non-neoplastic brain cells promotes tumor growth. Following cranial irradiation, widespread senescence in the brain occurred, with the astrocytic population being particularly susceptible. Irradiated brains showed an altered transcriptomic profile characterized by upregulation of CDKN1A (p21), a key enforcer of senescence, and several SASP factors, including HGF, the ligand of the receptor tyrosine kinase (RTK) Met. Preirradiation of mouse brains increased Met-driven growth and invasiveness of orthotopically implanted glioma cells. Importantly, irradiated p21−/− mouse brains did not exhibit senescence and consequently failed to promote tumor growth. Senescent astrocytes secreted HGF to activate Met in glioma cells and to promote their migration and invasion in vitro, which could be blocked by HGF-neutralizing antibodies or the Met inhibitor crizotinib. Crizotinib also slowed the growth of glioma cells implanted in preirradiated brains. Treatment with the senolytic drug ABT-263 (navitoclax) selectively killed senescent astrocytes in vivo, significantly attenuating growth of glioma cells implanted in preirradiated brains. These results indicate that SASP factors in the irradiated tumor microenvironment drive GBM growth via RTK activation, underscoring the potential utility of adjuvant senolytic therapy for preventing GBM recurrence after radiotherapy. Significance: This study uncovers mechanisms by which radiotherapy can promote GBM recurrence by inducing senescence in non-neoplastic brain cells, suggesting that senolytic therapy can blunt recurrent GBM growth and aggressiveness. Graphical Abstract
Ammonium nutrition interacts with iron homeostasis in Brachypodium distachyon.

Most plants species develop stress symptoms when exposed to high ammonium (NH4 +) concentrations. Root is the first organ in contact with high NH4 + and therefore the first barrier to cope with ammonium stress. In this work, we focused on root adaptation to ammonium nutrition in the model plant Brachypodium distachyon. Proteome analysis evidenced changes associated to primary metabolism, cell wall remodelling and redox homeostasis. In addition, it revealed a strong induction of proteins related to methionine (Met) metabolism and phytosiderophore (PS) synthesis in ammonium-fed plants. In agreement, we show how the nitrogen source impacts Met/S-adenosyl-Met and PS metabolic pathways together with increasing root iron (Fe) content. Nevertheless, ammonium-fed plants displayed higher sensitivity to Fe deficiency, suggesting ammonium nutrition triggers impaired Fe utilization and root-to-shoot transport, which entailed an induction in Fe-related responses. Overall, this work evidences the importance of Fe homeostasis during ammonium nutrition and paves a new route to better understand and improve plants ammonium use efficiency and tolerance.
The effect of dydrogesterone on sexual function in endometriosis

Abstract Endometriosis is an oestrogen-dependent chronic disease, which is commonly regarded as a disease of reproductive-aged women. We aimed to evaluate the sexual function with Female Sexual Function Index (FSFI) in women with endometriosis who received dydrogesterone for 6 months. A total of 79 women with endometriomas were recruited in the study group and received 10 mg dydrogesterone tablets orally for 6 months. FSFI and visual analog scale (VAS) scores for each patient before and after treatment were recorded. When before treatment VAS scores and after treatment VAS scores (5.7 ± 1.27, 3.97 ± 1.01, respectively) were compared, a significant decrease was observed (p = .001). A significant increase in mean orgasm scores (3.23 ± 0.6 vs. 3.57 ± 0.65, p = .01) and means satisfaction scores (3.85 ± 0.48 vs. 4.10 ± 0.38, p < .001) were observed. In addition, means desire scores were also significantly higher following treatment (p = .01). In conclusion, this study showed that FSFI scores were increased after 6 months of dydrogesterone treatment in patients with endometriosis. Desire, satisfaction, orgasm and pain scores improved significantly, and sexual dysfunction decreased after treatment. Impact statement What is already known on this subject? Endometriosis is a chronic inflammatory disease associated with severe dysmenorrhoea, pelvic pain, dyspareunia, painful gastrointestinal symptoms and sub-fertility are among the symptoms. These symptoms can be responsible for a significant decrease in the quality of life scores of the patients. Dydrogesterone is a synthetic progesterone derivative, which suppresses oestrogen levels and ovulation. Dydrogesterone’s effect on pain relief in endometriosis patients has already been shown, but it’s role on the sexual dysfunction observed in women with endometriosis has not yet been questioned. What do the results of this study add? To the best of our knowledge this is the first study showing the effects of dydrogesterone on sexual function in patients with endometriosis. What are the implications of these findings for clinical practice and/or further research? Dydrogesterone can safely be used in medical treatment of endometriosis not only for pain relief but also patients with additional complaints such as sexual dysfunction can benefit from this treatment. Future studies with larger cohorts and long-term follow-ups are needed to validate our results.
Hypertriglyceridemia Is Associated with More Severe Histological Glomerulosclerosis in IgA Nephropathy

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.
Urbanization extends flight phenology and leads to local adaptation of seasonal plasticity in Lepidoptera

Significance Cities represent novel environments with altered seasonality; they are warmer, which may accelerate growth, but light pollution can also lengthen days, misleading organisms that use daylength to predict seasonal change. Using long-term observational data, we show that urban populations of a butterfly and a moth have longer flight seasons than neighboring rural populations for six Nordic city regions. Next, using laboratory experiments, we show that the induction of diapause by daylength has evolved in urban populations in the direction predicted by urban warming. We thus show that the altered seasonality of urban environments can lead to corresponding evolutionary changes in the seasonal responses of urban populations, a pattern that may be repeated in other species. Urbanization is gaining force globally, which challenges biodiversity, and it has recently also emerged as an agent of evolutionary change. Seasonal phenology and life cycle regulation are essential processes that urbanization is likely to alter through both the urban heat island effect (UHI) and artificial light at night (ALAN). However, how UHI and ALAN affect the evolution of seasonal adaptations has received little attention. Here, we test for the urban evolution of seasonal life-history plasticity, specifically changes in the photoperiodic induction of diapause in two lepidopterans, Pieris napi (Pieridae) and Chiasmia clathrata (Geometridae). We used long-term data from standardized monitoring and citizen science observation schemes to compare yearly phenological flight curves in six cities in Finland and Sweden to those of adjacent rural populations. This analysis showed for both species that flight seasons are longer and end later in most cities, suggesting a difference in the timing of diapause induction. Then, we used common garden experiments to test whether the evolution of the photoperiodic reaction norm for diapause could explain these phenological changes for a subset of these cities. These experiments demonstrated a genetic shift for both species in urban areas toward a lower daylength threshold for direct development, consistent with predictions based on the UHI but not ALAN. The correspondence of this genetic change to the results of our larger-scale observational analysis of in situ flight phenology indicates that it may be widespread. These findings suggest that seasonal life cycle regulation evolves in urban ectotherms and may contribute to ecoevolutionary dynamics in cities.