bluuebunny/crossref_metadata_2025_split huggingface dataset:
Periodic Discharges in Critically Ill Children: Predictors and Outcome
Authors: Fung France W. , Parikh Darshana S. , Massey Shavonne L. , Fitzgerald Mark P. , Vala Lisa , Donnelly Maureen , Jacobwitz Marin , Kessler Sudha K. , Xiao Rui , Topjian Alexis A. , Abend Nicholas S. 
Published: December 2023

Objectives:
We aimed to identify clinical and EEG monitoring characteristics associated with generalized, lateralized, and bilateral-independent periodic discharges (GPDs, LPDs, and BIPDs) and to determine which patterns were associated with outcomes in critically ill children.

Methods:
We performed a prospective observational study of consecutive critically ill children undergoing continuous EEG monitoring, including standardized scoring of GPDs, LPDs, and BIPDs. We identified variables associated with GPDs, LPDs, and BIPDs and assessed whether each pattern was associated with hospital discharge outcomes including the Glasgow Outcome Scale-Extended Pediatric version (GOS-E-Peds), Pediatric Cerebral Performance Category (PCPC), and mortality.

Results:
PDs occurred in 7% (91/1,399) of subjects. Multivariable logistic regression indicated that patients with coma (odds ratio [OR], 3.45; 95% confidence interval [CI]: 1.55, 7.68) and abnormal EEG background category (OR, 6.85; 95% CI: 3.37, 13.94) were at increased risk for GPDs. GPDs were associated with mortality (OR, 3.34; 95% CI: 1.24, 9.02) but not unfavorable GOS-E-Peds (OR, 1.93; 95% CI: 0.88, 4.23) or PCPC (OR, 1.64; 95% CI: 0.75, 3.58). Patients with acute nonstructural encephalopathy did not experience LPDs, and LPDs were not associated with mortality or unfavorable outcomes. BIPDs were associated with mortality (OR, 3.68; 95% CI: 1.14, 11.92), unfavorable GOS-E-Peds (OR, 5.00; 95% CI: 1.39, 18.00), and unfavorable PCPC (OR, 5.96; 95% CI: 1.65, 21.46).

Significance:
Patients with coma or more abnormal EEG background category had an increased risk for GPDs and BIPDs, and no patients with an acute nonstructural encephalopathy experienced LPDs. GPDs were associated with mortality and BIPDs were associated with mortality and unfavorable outcomes, but LPDs were not associated with unfavorable outcomes.
From Patients to Providers: Assessing Impact of Normothermic Machine Perfusion on Liver Transplant Practices in the US
Authors: Wang Benjamin K , Shubin Andrew D , Harvey Jalen A , MacConmara Malcolm M , Hwang Christine S , Patel Madhukar S , Vagefi Parsia A 
Published: December 2023

BACKGROUND:
Normothermic machine perfusion (NMP) of livers allows for the expansion of the donor pool and minimization of posttransplant complications. Results to date have focused on both donor and recipient outcomes, but there remains potential for NMP to also impact transplant providers.

STUDY DESIGN:
Using United Network for Organ Sharing Standard Transplant Analysis file data, adult deceased donors who underwent transplantation between January 1, 2016, and December 31, 2022, were identified. Transplanted livers were divided by preservation methods (static cold storage [SCS] and NMP) and case time (day-reperfusion 8 am to 6 pm). Patient factors, transplant characteristics, and short-term outcomes were analyzed between Mahalanobis-metric-matched groups.

RESULTS:
NMP livers represented 742 (1.4%) of 52,132 transplants. NMP donors were more marginal with higher Donor Risk Index scores (1.78 ± 0.50 NMP vs 1.49 ± 0.38 SCS, p < 0.001) and donation after cardiac death frequency (36.9% vs 8.4%, p < 0.001). NMP recipients more often had model for end-stage liver disease (MELD) exception status (29.9% vs 23.4%, p < 0.001), lower laboratory MELD scores (20.7 ± 9.7 vs 24.3 ± 10.9, p < 0.001), and had been waitlisted longer (111.5 [21.0 to 307.0] vs 60.0 [9.0 to 245.0] days, p < 0.001). One-year graft survival (90.2% vs 91.6%, p = 0.505) was similar between groups, whereas length of stay was lower for NMP recipients (8.0 [6.0 to 14.0] vs 10.0 [6.0 to 16.0], p = 0.017) after adjusting for confounders. Notably, peak case volume occurred at 11 am with NMP livers (vs 9 pm with SCS). Overall, a higher proportion of transplants was performed during daytime hours with NMP (51.5% vs 43.0%, p < 0.001).

CONCLUSIONS:
NMP results in increased use of marginal allografts, which facilitated transplantation in lower laboratory MELD recipients who have been waitlisted longer and often have exception points. Importantly, NMP also appeared to shift peak caseloads from nighttime to daytime, which may have significant effects on the quality of life for the entire liver transplant team.
Signalling-state dependent drug-tolerance in head and neck squamous cell carcinoma
Authors: Karjosukarso Dyah W. , Dini Alice , Wingens Laura J.A. , Liu Ruiqi , Joosten Leo A.B. , Bussink Johan , Mulder Klaas W. 
Published: December 2023

AbstractIntratumor heterogeneity negatively impacts therapeutic response and patient prognosis. Besides the established role of genetic heterogeneity, non-genetic mechanisms of persistence to drug treatment are emerging. Here, we characterise cells selected for their persistence to control, epidermal growth factor inhibition (EGFRi), radiation and combined treatment from low passage head and neck squamous cell carcinoma (HNSCC) cultures. Using a panel of 70 (phospho-)specific DNA-conjugated antibodies we measured activities of 8 signalling pathways, self-renewal, differentiation, DNA damage and cell-cycle, in conjunction with the transcriptional output in single cells, using our RNA and Immuno-Detection (RAID) technology. Six recurrent transcriptional programs reflecting processes including proliferation, differentiation and metabolic activity, as well as protein-based signalling-states, were associated with drug persistence, while copy number variation inference indicated involvement of non-genetic tolerance mechanisms. Projecting RNA velocity onto the antibody-derived signalling-states suggested a key role for integrin-mediated focal-adhesion signalling in drug-persistence in our cell system. Using machine-learning we derived a core transcriptional signature connected to adhesion-based drug-persistence, which was predictive of poor prognosis in a TGCA HNSCC cohort (hazard-ratio 1.87, p<10-5). Furthermore, functional analyses confirmed that cells expressing high levels of integrin alpha-6 (ITGA6) were tolerant to EGFRi treatment, and that forcing cells out of this cell-state through transient targeted inhibition of Focal Adhesion Kinase activity re-instated EGFRi sensitivity in drug persistent cells. Taken together, our single-cell multi-omics analysis identified an actionable adhesion-signalling mediated cell-state driving drug tolerance in HNSCC.
The two key substitutions in the chromophore environment of mKate2 to produce an enhanced FusionRed-like red fluorescent protein
Authors: Ruchkin Dmitry A. , Gavrikov Alexey S. , Kolesov Danila V. , Gorokhovatsky Andrey Yu. , Chepurnykh Tatiana V. , Mishin Alexander S. , Maksimov Eugene G. , Pletneva Nadya V. , Pletnev Vladimir Z. , Pavlova Anastasiia M. , Nikitin Vladimir A. , Lukyanov Konstantin A. , Bogdanov Alexey M. 
Published: December 2023

AbstractRed fluorescent proteins (RFPs) are often probes of choice for living tissue microscopy and whole-body imaging. When choosing a specific RFP variant, the priority may be focused on fluorescence brightness, maturation rate, monomericity, excitation/emission wavelengths, and low toxicity, which are rarely combined in optimal way in a single protein. If the additional requirements such as prolonged fluorescence lifetime and/or blinking ability are applied, the available probe’s repertoire could become surprisingly narrow. Since the whole diversity of the conventional single-component RFPs belongs to just a few phylogenetic lines (with DsRed-, eqFP578- and eqFP611-derived being the major ones), it is not unexpected that their advantageous properties are split between close homologs. In such cases, a systematic mutagenetic analysis focused on variant-specific amino acid residues can shed light on the origins of sibling RFPs’ distinctness and might be beneficial for consolidation of their strengths in new RFP variants. For instance, the protein FusionRed, although being efficient in the fluorescence labeling due its good monomericity and low cytotoxicity, has undergone a considerable loss in fluorescence brightness/lifetime compared to the parental mKate2. In this contribution, we describe a fast-maturing monomeric RFP designed semi-rationally based on the mKate2 and FusionRed templates, outperforming both its parents in molecular brightness, having extended fluorescence lifetime, and showing spontaneous blinking pattern promising for nanoscopy use.
TML1ANDTML2SYNERGISTICALLY REGULATE NODULATION AND AFFECT ARBUSCULAR MYCORRHIZA INMEDICAGO TRUNCATULA
Authors: Chaulagain Diptee , Schnabel Elise , Kappes Mikayla , Lin Erica Xinlei , Müller Lena Maria , Frugoli Julia A. 
Published: December 2023

SummaryTwo symbiotic processes, nodulation and arbuscular mycorrhiza, are primarily controlled by the plant’s need for nitrogen (N) and phosphorus (P), respectively. Autoregulation of Nodulation (AON) and Autoregulation of Mycorrhization (AOM) both negatively regulate their respective processes and share multiple components - plants that make too many nodules usually have higher AM fungal root colonization. The protein TML (TOO MUCH LOVE) was shown to function in roots to maintain susceptibly to rhizobial infection under low N conditions and control nodule number through AON inLotus japonicus.M. truncatulahas two sequence homologs:MtTML1 andMtTML2. We report the generation of stable single and double mutants harboring multiple allelic variations inMtTML1andMtTML2using CRISPR-Cas9 targeted mutagenesis and screening of a transposon mutagenesis library. Plants containing single mutations inMtTML1 orMtTML2 produced 2-3 times the nodules of wild-type plants whereas plants containing mutations in both genes displayed a synergistic effect, forming 20x more nodules compared to wild type plants. Examination of expression and heterozygote effects suggest genetic compensation may play a role in the observed synergy. Plants with mutations in bothTMLsonly showed mild increases in AM fungal root colonization at later timepoints in our experiments, suggesting these genes may also play a minor role in AM symbiosis regulation. The mutants created will be useful tools to dissect the mechanism of synergistic action ofMtTML1 andMtTML2 inM. truncatulasymbiosis with beneficial microbes.
The socioeconomic gap in life expectancy in Germany: a decomposition of age- and cause-specific mortality contributions, 2003–2021
Authors: Tetzlaff F , Sauerberg M , Grigoriev P , Tetzlaff J , Mühlichen M , Baumert J , Michalski N , Wengler A , Nowossadeck E , Hoebel J 
Published: December 2023

SummaryBackgroundEarlier death among people in socioeconomically deprived circumstances has been found internationally and for various causes of death, resulting in a considerable life expectancy gap between socioeconomic groups. This study examines how age- and cause-specific mortality contributions to the socioeconomic gap in life expectancy have changed in Germany over time.MethodsOfficial German population and cause-of-death statistics from 2003 to 2021 were linked to the district-level German Index of Socioeconomic Deprivation. Life-table and decomposition methods were applied to calculate life expectancy by deprivation quintile and decompose the life expectancy gap (ΔLE) between the most and least deprived quintiles into age- and cause-specific mortality contributions.FindingsFrom 2003 to 2019, the ΔLE between the most and least deprived quintiles of districts increased from 1.1 to 1.8 years among women and from 3.0 to 3.1 years among men. Thereafter, in the COVID-19 pandemic, it increased more rapidly to 2.2 and 3.5 years respectively in 2021. The causes of death contributing most to the ΔLE were cardiovascular diseases (CVD) and cancer, with declining contributions of CVD deaths at age 70 and above and increasing contributions of cancer deaths at ages 40–74 over time. COVID-19 mortality at ages 45+ was the strongest contributor to the increase in ΔLE after 2019.InterpretationTo reduce the socioeconomic gap in life expectancy, effective efforts are needed to prevent early deaths from CVD and cancer in deprived populations, with cancer prevention and control becoming an increasingly important field of action in this respect.
HIV and viremia prevalence in non-migrating members of migrant households in Rakai region, Uganda: A cross-sectional population-based study
Authors: Young Ruth , Ssekasanvu Joseph , Kagaayi Joseph , Ssekubugu Robert , Kigozi Godfrey , Reynolds Steven J. , Wawer Maria J. , Nonyane Bareng A.S. , Chang Larry W. , Kennedy Caitlin E. , Paina Ligia , Anglewicz Philip A. , Quinn Thomas C. , Serwadda David , Nalugoda Fred , Grabowski M. Kate 
Published: December 2023

AbstractIntroductionIn sub-Saharan Africa, migrants are more likely to be HIV seropositive and viremic than non-migrants. However, little is known about HIV prevalence and viremia in non-migrants living in households with in- or out-migration events. We compared HIV outcomes in non-migrating persons in households with and without migration events using data from the Rakai Community Cohort Study (RCCS), an open population-based cohort in UgandaMethodsWe analyzed RCCS survey data from one survey round collected between August 2016 and May 2018 from non-migrating participants aged 15–49. Migrant households were classified as those reporting ≥1 member moving into or out of the household since the prior survey. A validated rapid test algorithm determined HIV serostatus. HIV viremia was defined as >1,000 copies/mL. Modified Poisson regression was used to estimate associations between household migration and HIV outcomes, with results reported as adjusted prevalence ratios (adjPR) with 95% confidence intervals (95%CI). Analyses were stratified by gender, direction of migration (into/out of the household), and relationship between non-migrants and migrants (e.g., spouse).ResultsThere were 14,599 non-migrants (7,654, 52% women) identified in 9,299 households. 4,415 (30%) lived in a household with ≥1 recent migrant; of these, 972(22%) had migrant spouses, 1,102(25%) migrant children, and 875(20%) migrant siblings. Overall, HIV prevalence and viremia did not differ between non-migrants in migrant and non-migrant households. However, in stratified analyses, non-migrant women with migrant spouses were significantly more likely to be HIV seropositive compared to non-migrant women with non-migrant spouses (adjPR:1.44, 95%CI:1.21-1.71). Conversely, non-migrant mothers living with HIV who had migrant children were less likely to be viremic (adjPR:0.34, 95%CI:0.13-0.86). Among non-migrant men living with HIV, spousal migration was associated with a non-significant increased risk of viremia (adjPR:1.37, 95%CI:0.94-1.99). Associations did not typically differ for migration into or out of the household.ConclusionsHousehold migration was associated with HIV outcomes for certain non-migrants, suggesting that the context of household migration influences the observed association with HIV outcomes. In particular, non-migrating women with migrating spouses were more likely to have substantially higher HIV burden. Non-migrants with migrant spouses may benefit from additional support when accessing HIV services.
A pilot study of the comparison using a standard and individual altitude exposure protocol in elite gymnasts
Authors: Grushin A.A. , Zelenkova I.E. , Ilin D. , Zotkin S.V. , Korneev P.V. , Koprov S.V. , Almyashev D.Kh. , Badtieva V.A. , Glazachev O.S 
Published: December 2023

AbstractAimEvaluate the effectiveness of the use of altitude training in elite gymnasts and compare two approaches of the altitude exposure protocols.Materials and methodsThe study involved 6 athletes of high qualification specializing in gymnastics (22 (20.5-22.5 years, 166.5 (162.5-169) cm, 63.5 (60-65 kg)). Athletes underwent hypoxic exposure using “Live high - train low” method using standard (18 days) and individual protocol (18 days). The biochemical parameters of blood, total hemoglobin mass, blood volume, hypoxic index, and oxygen saturation of arterial blood were determined.ResultsThe tHb-mass values before the standard protocol were 678.5 (664-712.5) g, immediately after 696 (679-752.7) g. Before the start of the individual protocol, the tHb-mass values were 687 (622.7-752) g, immediately after 751.5 (750.2-827) g, (p < 0.05). The tHb-mass shifts after exposure to the unified protocol were 24 (4.8-31) g, and after personified 73.5 (55.5-132.7) g, (p < 0.05). At the same time, ALT, AST, and CPK values did not differ from the baseline, and testosterone values increased after a personalized hypoxic exposure program.ConclusionsThe application of personalized protocol of additional hypoxic impact seems to be more effective than standard protocol in terms of change of hematological parameters.
Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity
Authors: Russell Jamie , Chen Luming , Liu Aijie , Wang Jianhui , Ghosh Subarna , Zhong Xue , Shi Hexin , Beutler Bruce , Nair-Gill Evan 
Published: December 2023

SUMMARYSignals emanating from the T cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T cell function. Through forward genetic screening in mice, we discovered that loss-of-function mutations inLDL receptor related protein 10(Lrp10) caused naïve and central memory CD8 T cells to accumulate in peripheral lymphoid organs.Lrp10encodes a conserved cell surface protein of unknown immunological function. Lrp10 was induced with T cell activation and its expression post-translationally suppressed IL7 receptor (IL7R) levels. Accordingly,Lrp10deletion enhanced T cell homeostatic expansion through IL7R signaling.Lrp10-deficient mice were also intrinsically resistant to syngeneic tumors. This phenotype depended on dense tumor infiltration of CD8 T cells that displayed increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.
Serotonin Reduces Belief Stickiness
Authors: Conceição Vasco A. , Petzschner Frederike H. , Cole David M. , Wellstein Katharina V. , Müller Daniel , Raman Sudhir , Maia Tiago V. 
Published: December 2023

ABSTRACTSerotonin fosters cognitive flexibility, but how, exactly, remains unclear. We show that serotonin reduces belief stickiness: the tendency to get “stuck” in a belief about the state of the world despite incoming contradicting evidence. Participants performed a task assessing belief stickiness in a randomized, double-blind, placebo-controlled study using a single dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram. In the escitalopram group, higher escitalopram plasma levels reduced belief stickiness more, resulting in better inference about the state of the world. Moreover, participants with sufficiently high escitalopram plasma levels had less belief stickiness, and therefore better state inference, than participants on placebo. Exaggerated belief stickiness is exemplified by obsessions: “sticky” thoughts that persist despite contradicting evidence. Indeed, participants with more obsessions had greater belief stickiness, and therefore worse state inference. The opposite relations of escitalopram and obsessions with belief stickiness may explain the therapeutic effect of SSRIs in obsessive-compulsive disorder.
Zika virus remodels and hijacks IGF2BP2 ribonucleoprotein complex to promote viral replication organelle biogenesis
Authors: Mazeaud Clément , Pfister Stefan , Owen Jonathan E. , Pereira Higor Sette , Charbonneau Flavie , Robinson Zachary E. , Anton Anaïs , Bemis Cheyanne L. , Sow Aïssatou Aïcha , Patel Trushar R. , Neufeldt Christopher J. , Scaturro Pietro , Chatel-Chaix Laurent 
Published: December 2023

SUMMARYZika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication and packaging into new virions, all within virus-induced replication organelles (vRO). In this study, with an RNAi mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis. In infected cells, IGF2BP2 associates with viral NS5 polymerase and redistributes to the perinuclear viral replication compartment. Combined fluorescencein situhybridization-based confocal imaging,in vitrobinding assays, and immunoprecipitation coupled to RT-qPCR, showed that IGF2BP2 directly interacts with ZIKV vRNA 3’-nontranslated region. Using ZIKV sub-genomic replicons and a replication-independent vRO induction system, we demonstrated that IGF2BP2 knockdown impairsde novoviral organelle biogenesis and, consistently, vRNA synthesis. Finally, the analysis of immunopurified IGF2BP2 complex using quantitative mass spectrometry and RT-qPCR, revealed that ZIKV infection alters the protein and RNA interactomes of IGF2BP2. Altogether, our data support that ZIKV hijacks and remodels the IGF2BP2 ribonucleoprotein complex to regulate vRO biogenesis and vRNA neosynthesis.
Quantitative description of six fish species’ gut contents and abundances of their prey in the benthic food web of the Baltic Sea (1968-1978)
Authors: Gauzens Benoit , Kalinkat Gregor , Antunes Ana Carolina , Boy Thomas , O’Gorman Eoin J. , Jacob Ute , Jochum Malte , Kortsch Susanne , Rosenbaum Benjamin , Figueiredo Ludmilla , Brose Ulrich 
Published: December 2023

AbstractThe dataset presents a compilation of stomach contents from six demersal fish species from two functional groups inhabiting the Baltic Sea. It includes detailed information on prey identities, body masses, and biomasses recovered from both the fish’s digestive systems and their surrounding environment. Environmental parameters, such as salinity and temperature levels, have been integrated to enrich this dataset. The juxtaposition of information on prey found in stomachs and in the environment provides an opportunity to quantify trophic interactions across different environmental contexts and investigate how fish foraging behaviour adapts to changes in their environment, such as an increase in temperature. The compilation of body mass and taxonomic information for all species allows approaching these new questions using either a taxonomic (based on species identity) or functional trait (based on body mass) approach.