bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating incidence and attributable length of stay of healthcare-associated infections—Modeling the Swiss point-prevalence survey
Authors: Doerken Sam , Metsini Aliki , Buyet Sabina , Wolfensberger Aline , Zingg Walter , Wolkewitz Martin 
Published: August 2021

AbstractObjectives:In 2017, a point-prevalence survey was conducted with 12,931 patients in 96 hospitals across Switzerland as part of the national strategy to prevent healthcare-associated infections (HAIs). We present novel statistical methods to assess incidence proportions of HAI and attributable length-of-stay (LOS) in point-prevalence surveys.Methods:Follow-up data were collected for a subsample of patients and were used to impute follow-up data for all remaining patients. We used weights to correct length bias in logistic regression and multistate analyses. Methods were also tested in simulation studies.Results:The estimated incidence proportion of HAIs during hospital stay and not present at admission was 2.3% (95% confidence intervals [CI], 2.1–2.6), the most common type being lower respiratory tract infections (0.8%; 95% CI, 0.6–1.0). Incidence proportion was highest in patients with a rapidly fatal McCabe score (7.8%; 95% CI, 5.7–10.4). The attributable LOS for all HAI was 6.4 days (95% CI, 5.6–7.3) and highest for surgical site infections (7.1 days, 95% CI, 5.2–9.0). It was longest in the age group of 18–44 years (9.0 days; 95% CI, 5.4–12.6). Risk-factor analysis revealed that McCabe score had no effect on the discharge hazard after infection (hazard ratio [HR], 1.21; 95% CI, 0.89–1.63). Instead, it only influenced the infection hazard (HR, 1.84; 95% CI, 1.39–2.43) and the discharge hazard prior to infection (HR, 0.73; 95% CI, 0.66–0.82).Conclusions:In point-prevalence surveys with limited follow-up data, imputation and weighting can be used to estimate incidence proportions and attributable LOS that would otherwise require complete follow-up data.
Socioeconomic correlates of sedentary time during pregnancy among women at risk of gestational diabetes in the UK
Authors: Wagnild Janelle M. , Pollard Tessa M. 
Published: August 2021

AbstractLittle is known about the relationship between socioeconomic position (SEP) and duration and patterning of objectively measured sedentary time (ST) among adults, especially adults at high risk of diabetes. The aim of this study was to examine cross-sectional associations of SEP with ST (total, prolonged ST, breaks in ST) and self-reported TV time among pregnant women at risk of gestational diabetes in the UK. At 20 weeks’ gestation, pregnant women (n=174) wore an activPAL accelerometer and reported their usual TV time. Generalized linear mixed models were used to test associations of education, household income and area-level deprivation (separately and with mutual adjustment) with total ST, prolonged ST and breaks in ST. Logistic regression models were used to test associations between SEP indicators and high (≥2h/day) TV time. Those with the lowest education, lowest household income and highest area-level deprivation had the lowest ST and lowest prolonged ST. After mutual adjustment, area-level deprivation remained associated with total ST (β=0.10 [0.01, 0.20]). There was an inverse association between area-level deprivation and breaks in sedentary time (exp(b)=1.11 [1.01, 1.22]). Education was the only SEP correlate of high TV time, with more of those with least education reporting high TV time; this association persisted after adjustment for household income and area-level deprivation. The association between SEP and total and prolonged ST (positive) was the opposite of the association between education and high TV time (negative) in this sample of high-risk pregnant women. These findings should inform interventions to reduce sedentary time.
Outcome of two-week head and neck cancer pathway for the otolaryngology department in a tertiary centre
Authors: Mettias B , Charlton A , Ashokkumar S 
Published: August 2021

AbstractBackgroundThe two-week-wait head and neck cancer referral pathway was introduced by the Department of Health, and refined through National Institute for Health and Care Excellence guidelines which were updated in 2015.MethodsA retrospective study was conducted of two-week-wait referrals to out-patient ENT from January to June 2018. The analysis included demographics, referral symptoms according to National Institute for Health and Care Excellence 2015 guidelines, cancer pick-up rates and positive predictive values.ResultsA total of 1107 patients were referred for suspected head and neck cancer over six months, with 6 per cent diagnosed with cancer. Neck lump, persistent hoarseness and throat pain were the most common presenting symptoms. Neck lump had the highest positive predictive value, followed by oral swelling. Oral bleeding and persistent unilateral sore throat showed significant positive predictive values. Investigation for metastatic head and neck cancer of an unknown primary or the involvement of other multidisciplinary teams could hinder the achievement of a 62-day treatment target.ConclusionThe cancer pick-up rate from two-week-wait referrals is only 1.5 times higher than routine referrals. The ‘red flag’ symptoms given in the 2015 National Institute for Health and Care Excellence update would benefit from further review.
The accuracy of dry surgical field sublabial biopsy in the diagnosis of sicca syndrome
Authors: O’ Byrne L , Ramli R , Khoo S G 
Published: August 2021

AbstractBackgroundSublabial gland biopsy is the ‘gold standard’ in establishing the diagnosis of primary Sjögren's syndrome. Bleeding and nerve damage are complications. Our centre has adopted the use of the chalazion clamp to provide a dry surgical field to address these challenges. This study aimed to assess the accuracy of minor salivary gland harvest rate using this technique.MethodA retrospective review of all minor salivary gland biopsies was carried out in a single tertiary referral centre over a five-year period.ResultsForty-one biopsy patients were identified, with a mean age of 56.1 years. There was 100 per cent accuracy in harvest rate in our series. Twelve patients (29 per cent) were positive for primary Sjögren's syndrome. No patients had a complication immediately or at one month follow up.ConclusionDry surgical field sublabial gland biopsy is a safe and highly effective technique in the diagnosis of primary Sjögren's syndrome. Initial results indicate it may provide a higher harvest rate with fewer complications than traditional non-ischaemic techniques.
Acute kidney injury after the arterial switch operation: incidence, risk factors, and outcomes
Authors: Schoenmaker Nikki J. , Weeda Jesse A. , van der Palen Roel L.F. , Hazekamp Mark G. , Bunker-Wiersma Heleen E. 
Published: August 2021

AbstractBackground:The aim of this retrospective cohort study was to determine the incidence, potential risk factors, characteristics, and outcomes of acute kidney injury in children following the arterial switch operation for transposition of the great arteries.Methods:Retrospective review of children who underwent ASO between 2000 and 2020 in our tertiary children’s hospital in the Netherlands. Pre-and post-ASO serum creatinine levels were collected. Severe AKI was defined as 100% serum creatinine rise or estimated creatinine clearance <35 ml/min/1.73 m2according to pRIFLE criteria. Logistic regression was used to adjust for confounders.Results:A total of 242 children were included. Fifty-seven (24%) children developed severe AKI after ASO. Four patients with severe AKI were treated with renal replacement therapy. Children with severe AKI had a longer duration of mechanical ventilation 4.5 (1.0–29) versus 3 (1.0–12) days (p = 0.001), longer PICU stay 7 (2–76) versus 5 (1–70) days, (p = 0.001), higher rate of myocardial infarction 5% versus 0.5% (p = 0.001), sepsis 24% versus 9% (p = 0.002), post-operative pulmonary hypertension 19% versus 6% (p = 0.002), post-operative bleeding 9% versus 3% (p = 0.044), longer time to sternal closure 3 (1–19) versus 2 (1–6) days, (p = 0.009), and a higher mortality rate 9.0% versus 0.5% (p = 0.001) compared to children without severe AKI. Sepsis was a risk factor for developing severe AKI.Conclusions:In this single-centre cohort, 24% of our patients developed severe AKI after ASO, which is associated with increased morbidity, longer PICU stay, and higher mortality.
Lower Thermospheric Material Transport via Lagrangian Coherent Structures
Authors: Datta‐Barua Seebany , Pedatella Nicholas , Greer Katelynn , Wang Ningchao , Nutter Leanne , Harvey V. Lynn 
Published: August 2021

AbstractWe show that inter‐model variation due to under‐constraint by observations impacts the ability to predict material transport in the lower thermosphere. Lagrangian coherent structures (LCSs), indicating regions of maximal separation (or convergence) in a time‐varying flow, are derived in the lower thermosphere from models for several space shuttle water vapor plume events. We find that inter‐model differences in thermospheric transport manifest in LCSs in a way that is more stringent than mean wind analyses. LCSs defined using horizontal flow fields from the Specified Dynamics version of the Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (SD‐WACCMX) at 109 km altitude are compared to Global Ultraviolet Imager (GUVI) observations of the space shuttle main engine plume. In one case, SD‐WACCMX predicts an LCS ridge to produce spreading not found in the observations. LCSs and tracer transport from SD‐WACCMX and from data assimilative WACCMX (WACCMX + DART) are compared to each other and to GUVI observations. Differences in the modeled LCSs and tracer positions appear between SD‐WACCMX and WACCMX + DART despite the similarity of mean winds. WACCMX + DART produces better tracer transport results for a July 2006 event, but it is unclear which model performs better in terms of LCS ridges. For a February 2010 event, when mean winds differ by up to 50 m/s between the models, differences in LCSs and tracer trajectories are even more severe. Low‐pass filtering the winds up to zonal wavenumber 6 reduces but does not eliminate inter‐model LCS differences. Inter‐model alignment of LCSs improves at a lower 60 km altitude.
The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(6;11)
Authors: Kundu Arpita , Kowarz Eric , Marschalek Rolf 
Published: August 2021

AbstractLeukemia patients bearing t(6;11)(q27;q23) translocations can be divided in two subgroups: those with breakpoints in the major breakpoint cluster region of MLL (introns 9–10; associated mainly with AML M1/4/5), and others with breakpoints in the minor breakpoint cluster region (introns 21–23), associated with T-ALL. We cloned all four of the resulting fusion genes (MLL-AF6, AF6-MLL, exMLL-AF6, AF6-shMLL) and subsequently transfected them to generate stable cell culture models. Their molecular function was tested by inducing gene expression for 48 h in a Doxycycline-dependent fashion. Here, we present our results upon differential gene expression (DGE) that were obtained by the “Massive Analyses of cDNA Ends” (MACE-Seq) technology, an established 3′-end based RNA-Seq method. Our results indicate that the PHD/BD domain, present in the AF6-MLL and the exMLL-AF6 fusion protein, is responsible for chromatin activation in a genome-wide fashion. This led to strong deregulation of transcriptional processes involving protein-coding genes, pseudogenes, non-annotated genes, and RNA genes, e.g., LincRNAs and microRNAs, respectively. While cooperation between the MLL-AF6 and AF6-MLL fusion proteins appears to be required for the above-mentioned effects, exMLL-AF6 is able to cause similar effects on its own. The exMLL-AF6/AF6-shMLL co-expressing cell line displayed the induction of a myeloid-specific and a T-cell specific gene signature, which may explain the T-ALL disease phenotype observed in patients with such breakpoints. This again demonstrated that MLL fusion proteins are instructive and allow to study their pathomolecular mechanisms.
BRUCE silencing leads to axonal dystrophy by repressing autophagosome-lysosome fusion in Alzheimer’s disease
Authors: Zhang Lu , Fang Yu , Zhao Xinyu , Zheng Yake , Ma Yunqing , Li Shuang , Huang Zhi , Li Lihao 
Published: August 2021

AbstractAxonal dystrophy is a swollen and tortuous neuronal process that contributes to synaptic alterations occurring in Alzheimer’s disease (AD). Previous study identified that brain-derived neurotrophic factor (BDNF) binds to tropomyosin-related kinase B (TrkB) at the axon terminal and then the signal is propagated along the axon to the cell body and affects neuronal function through retrograde transport. Therefore, this study was designed to identify a microRNA (miRNA) that alters related components of the transport machinery to affect BDNF retrograde signaling deficits in AD. Hippocampus tissues were isolated from APP/PS1 transgenic (AD-model) mice and C57BL/6J wild-type mice and subject to nicotinamide adenine dinucleotide phosphate and immunohistochemical staining. Autophagosome-lysosome fusion and nuclear translocation of BDNF was detected using immunofluorescence in HT22 cells. The interaction among miR-204, BIR repeat containing ubiquitin-conjugating enzyme (BRUCE) and Syntaxin 17 (STX17) was investigated using dual luciferase reporter gene assay and co-immunoprecipitation assay. The expression of relevant genes and proteins were determined by RT-qPCR and Western blot analysis. Knockdown of STX17 or BRUCE inhibited autophagosome–lysosome fusion and impacted axon growth in HT22 cells. STX17 immunoprecipitating with BRUCE and co-localization of them demonstrated BRUCE interacted with STX17. BRUCE was the target of miR-204, and partial loss of miR-204 by inhibitor promoted autophagosome–lysosome fusion to prevent axon dystrophy and accumulated BDNF nuclear translocation to rescue BDNF/TrkB signaling deficits in HT22 cells. The overall results demonstrated that inhibition of miR-204 prevents axonal dystrophy by blocking BRUCE interaction with STX17, which unraveled potential novel therapeutic targets for delaying AD.
Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder
Authors: Kantrowitz Joshua T. , Dong Zhengchao , Milak Matthew S. , Rashid Rain , Kegeles Lawrence S. , Javitt Daniel C. , Lieberman Jeffrey A. , John Mann J. 
Published: August 2021

AbstractGlutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal proton magnetic resonance spectroscopy (1H MRS) studies in MDD finds low Glx (combination of glutamate and glutamine) in medicated MDD. We hypothesize that elevated Glx or Glu may be a marker of more severe, untreated MDD. We examined ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC) Glx and glutamate levels using1H MRS in 34 medication-free, symptomatic, chronically ill MDD patients and 32 healthy volunteers, and GABA levels in a subsample. Elevated Glx and Glu were observed in MDD compared with healthy volunteers, with the highest levels seen in males with MDD. vmPFC/ACC GABA was low in MDD. Higher Glx levels correlated with more severe depression and lower GABA. MDD severity and diagnosis were both linked to higher Glx in vmPFC/ACC. Low GABA in a subset of these patients is consistent with our hypothesized model of low GABA leading to glutamate disinhibition in MDD. This finding and model are consistent with our previously reported findings that the NMDAR-antagonist antidepressant effect is proportional to the reduction of vmPFC/ACC Glx or Glu levels.
Tumor suppressor immune gene therapy to reverse immunotherapy resistance
Authors: Chada Sunil , Wiederhold Dora , Menander Kerstin B. , Sellman Beatha , Talbott Max , Nemunaitis John J. , Ahn Hyo Min , Jung Bo-Kyeong , Yun Chae-Ok , Sobol Robert E. 
Published: August 2021

Abstract
Background
While immune checkpoint inhibitors are becoming a standard of care for multiple types of cancer, the majority of patients do not respond to this form of immunotherapy. New approaches are required to overcome resistance to immunotherapies.

Methods
We investigated the effects of adenoviral p53 (Ad-p53) gene therapy in combination with immune checkpoint inhibitors and selective IL2 or IL15 CD122/132 agonists in the aggressive B16F10 tumor model resistant to immunotherapies. To assess potential mechanisms of action, pre- and post- Ad-p53 treatment biopsies were evaluated for changes in gene-expression profiles by Nanostring IO 360 assays.

Results
The substantial synergy of “triplet” Ad-p53 + CD122/132 + anti-PD-1 therapy resulted in potential curative effects associated with the complete tumor remissions of both the primary and contralateral tumors. Interestingly, contralateral tumors, which were not injected with Ad-p53 showed robust abscopal effects resulting in statistically significant decreases in tumor size and increased survival (p < 0.001). None of the monotherapies or doublet treatments induced the complete tumor regressions. Ad-p53 treatment increased interferon, CD8+ T cell, immuno-proteosome antigen presentation, and tumor inflammation gene signatures. Ad-p53 treatment also decreased immune-suppressive TGF-beta, beta-catenin, macrophage, and endothelium gene signatures, which may contribute to enhanced immune checkpoint inhibitor (CPI) efficacy. Unexpectedly, a number of previously unidentified, strongly p53 downregulated genes associated with stromal pathways and IL10 expression identified novel anticancer therapeutic applications.

Conclusions
These results imply the ability of Ad-p53 to induce efficacious local and systemic antitumor immune responses with the potential to reverse resistance to immune checkpoint inhibitor therapy when combined with CD122/132 agonists and immune checkpoint blockade. Our findings further imply that Ad-p53 has multiple complementary immune mechanisms of action, which support future clinical evaluation of triplet Ad-p53, CD122/132 agonist, and immune checkpoint inhibitor combination treatment.
High-density linkage map construction and identification of loci regulating fruit quality traits in blueberry
Authors: Mengist Molla F. , Bostan Hamed , Young Elisheba , Kay Kristine L. , Gillitt Nicholas , Ballington James , Kay Colin D. , Ferruzzi Mario G. , Ashrafi Hamid , Lila Mary Ann , Iorizzo Massimo 
Published: August 2021

AbstractFruit quality traits play a significant role in consumer preferences and consumption in blueberry (Vaccinium corymbosumL). The objectives of this study were to construct a high-density linkage map and to identify the underlying genetic basis of fruit quality traits in blueberry. A total of 287 F1individuals derived from a cross between two southern highbush blueberry cultivars, ‘Reveille’ and ‘Arlen’, were phenotyped over three years (2016–2018) for fruit quality-related traits, including titratable acidity, pH, total soluble solids, and fruit weight. A high-density linkage map was constructed using 17k single nucleotide polymorphisms markers. The linkage map spanned a total of 1397 cM with an average inter-loci distance of 0.08 cM. The quantitative trait loci interval mapping based on the hidden Markov model identified 18 loci for fruit quality traits, including seven loci for fruit weight, three loci for titratable acidity, five loci for pH, and three loci for total soluble solids. Ten of these loci were detected in more than one year. These loci explained phenotypic variance ranging from 7 to 28% for titratable acidity and total soluble solid, and 8–13% for pH. However, the loci identified for fruit weight did not explain more than 10% of the phenotypic variance. We also reported the association between fruit quality traits and metabolites detected by Proton nuclear magnetic resonance analysis directly responsible for these fruit quality traits. Organic acids, citric acid, and quinic acid were significantly (P < 0.05) and positively correlated with titratable acidity. Sugar molecules showed a strong and positive correlation with total soluble solids. Overall, the study dissected the genetic basis of fruit quality traits and established an association between these fruit quality traits and metabolites.
Brown adipose tissue is the key depot for glucose clearance in microbiota depleted mice
Authors: Li Min , Li Li , Li Baoguo , Hambly Catherine , Wang Guanlin , Wu Yingga , Jin Zengguang , Wang Anyongqi , Niu Chaoqun , Wolfrum Christian , Speakman John R. 
Published: August 2021

AbstractGut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis.
Landscape heterogeneity buffers biodiversity of simulated meta-food-webs under global change through rescue and drainage effects
Authors: Ryser Remo , Hirt Myriam R. , Häussler Johanna , Gravel Dominique , Brose Ulrich 
Published: August 2021

AbstractHabitat fragmentation and eutrophication have strong impacts on biodiversity. Metacommunity research demonstrated that reduction in landscape connectivity may cause biodiversity loss in fragmented landscapes. Food-web research addressed how eutrophication can cause local biodiversity declines. However, there is very limited understanding of their cumulative impacts as they could amplify or cancel each other. Our simulations of meta-food-webs show that dispersal and trophic processes interact through two complementary mechanisms. First, the ‘rescue effect’ maintains local biodiversity by rapid recolonization after a local crash in population densities. Second, the ‘drainage effect’ stabilizes biodiversity by preventing overshooting of population densities on eutrophic patches. In complex food webs on large spatial networks of habitat patches, these effects yield systematically higher biodiversity in heterogeneous than in homogeneous landscapes. Our meta-food-web approach reveals a strong interaction between habitat fragmentation and eutrophication and provides a mechanistic explanation of how landscape heterogeneity promotes biodiversity.