bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfect Timing: Associations Between Dietary Timing, Eating Intervals and Metabolic Health
Authors: Ali Marriam , Knutson Kristen , Reutrakul Sirimon 
Published: May 2021

Abstract
Background: Metabolic disorders are on the rise resulting in an increased need for novel interventions to combat this growing concern. One such intervention is time-restricted eating, which consolidates caloric intake to a shortened eating duration, and has consistently demonstrated improvement in metabolic health. Additional interventions could harness circadian clocks, which help regulate daily rhythms of hormone release and maintain metabolic homeostasis. Circadian rhythms are influenced by timing of food intake and therefore meal timing may also impact metabolic health.
Objective: To examine whether timing of eating was associated with metabolic health independently of eating duration.
Methods: Data are from the National Health and Nutrition Examination Survey (NHANES), a nationally representative U.S. survey and physical exam. We analyzed two non-consecutive dietary recalls, fasting glucose and insulin from 10,575 adults (&gt;18) over four cycles (2005–2012). We calculated eating interval duration as the time between first and last eating occasion (&gt;10kcal) and formulated three groups: &lt;10h, 10-13h, &gt;13h. We then created 6 subgroups based on eating duration start time (before or after 0830 h) to analyze associations of eating interval timing. Linear regression analyses controlling for demographics were computed to determine whether eating interval duration and eating interval timing were associated with fasting glucose and estimated insulin resistance using HOMA-IR.
Results: Fasting glucose did not differ significantly among eating interval groups. Adjusted mean HOMA-IR increased with shorter eating interval duration (2.23, 2.20, 1.97 for &lt;10h, 10-13h, &gt;13h; p&lt;0.05). When eating start time occurred before 0830 h compared to start time after 0830 h, mean adjusted HOMA-IR decreased across all eating interval subgroups (1.96 vs 2.28 for &lt;10h, 2.13 vs 2.28 for 10-13h, 1.94 vs 2.13 for &gt;13h; p &lt;0.05). Adjusted mean fasting glucose had a similar pattern (96.3 mg/dL vs 98.7 mg/dL for &lt;10h, 97.3 mg/dL vs 98.4 mg/dL for 10-13h, and 97.3 mg/dL vs 99.3 mg/dL for &gt;13h; p &lt; 0.05). In regression models where eating duration and timing were both entered as continuous variables, only timing was significantly associated with fasting glucose and HOMA-IR. Later time was associated with higher glucose and HOMA values (p&lt;.001)
Conclusion: Shorter eating durations, i.e. time-restricted eating, was associated with worse metabolic outcomes, except when paired with an earlier start time. All subgroups with an early eating start time had better metabolic outcomes regardless of eating duration. These findings suggest that timing is more strongly associated with metabolic measures than duration and supports early eating strategies.
Psychological Impact of Diabetes Technology on Type 1 Diabetes Pregnancy
Authors: Less Jacob , Basina Marina 
Published: May 2021

Abstract
Pregnant women with Type 1 Diabetes (T1D) experience challenges with glycemic management, planning for and transitioning into motherhood. Diabetes technology (DT) has been shown to improve glycemic control and pregnancy outcomes. The data on psychological aspects for the use of DT among women and their families during different stages of pregnancy is very sparse. This study characterized the perceived benefits and burdens of DT during T1D pre-, ongoing, and past-pregnancy journey. We surveyed 119 women with T1D from 12 countries (mean age 33.33 ± 5.26 years) as “Planning” (PP), “Attempting” (AP), “Previously” (PrP), or “Currently” (CP) pregnant. We explored the top three perceived “benefits” and “burdens” of DT (and their partners if relevant). Survey questions included: type of CGM device and insulin pump, use of hybrid closed-loop (Medtronic 670 G or Tandem X2 w/ Dexcom G6) or DIY system, insurance coverage, monthly out of pocket costs, breastfeeding. Results: 67 women in PrP group, 38 in CP group, and 7 in both PP and AP groups. A majority used CGM or insulin pump prior to pregnancy (n = 90 for CGM, n = 100 for pump). 11 women did not use any DT prior to pregnancy (n = 1 in CP group, n = 10 in PrP group). Five initiated DT during the first trimester, one during the second trimester, and five did not use any DT. Three women in CP group initiated CGM during the first trimester. Out of 12 women not using CGM in PP group, 7/12 initiated during pregnancy (n = 1 for 14-day Libre, n = 5 for Dexcom G5/6, n = 1 for Guardian 3). Overall these women, and their partners, perceived more benefits than burdens. Top three benefits of DT were “overall improved BS control,” improved confidence in DM control,” and “improved ease of administering insulin” (n = 86, 56, 55 respectively). Top three burdens were “alarms,” “problems with infusion sets,” and “glitches with sensors” (n = 52, 45, 43 respectively). Perceived benefits of DT for partners were the same except for a differing top-ranked benefit of “less worry about overnight hypoglycemia.” Burdens for partners were the same except for a differing top-ranked burden of “obsessiveness (more time thinking about BS).” CGM device usage showed: 68% for Dexcom (G4/5/6), 14.9% for Guardian 3, 9.9% for Libre (10 and 14 -day), and 7% reported no usage. Insulin pump usage showed: 52.2% for Medtronic, 15.7% for Tandem T:slim, 13% for Omnipod, 6% indicated other systems not listed, and 13% reported no usage. 26% of women have used a hybrid closed-loop system and 23% have used a DIY system. Our study is the first one to identify specific psychological benefits and stressors with the use of DT in women and their significant others internationally at various stages around pregnancy. It provides insight to clinicians on how to best counsel women and their families. Having the right expectations will help the with adaptability of DT and increase its use in order to improve pregnancy outcomes.
Liver-Specific Kisspeptin Deletion Impairs Energy Metabolism in Mice
Authors: Aloqaily Bahaa , Kwon Hyokjoon , Al-Samerria Sarmed , Negron Ariel L , Wondisford Fredric Edward , Radovick Sally 
Published: May 2021

Abstract
Kisspeptin, a neuroendocrine protein critical for the control of pubertal development and fertility has been shown to be modulated by nutritional signals. While the secretion of kisspeptin from specific hypothalamic nuclei is well-known to regulate GnRH-mediated pubertal maturation and reproduction, it remains unclear what role peripheral kisspeptin, specifically of hepatic origin, plays in regulating metabolism and glucose homeostasis. To define the role of kisspeptin in the liver, we developed a novel Kiss1f/f mouse line and targeted liver-specific Kiss1 ablation by injecting a AAV8-TBG-iCre virus via the tail vein (LKiss1KO). Control mice included Kiss1f/f male and female mice injected with AAV-GFP (LKiss1WT). We previously showed that deletion of hepatic kisspeptin did not affect body weight, but resulted in decreased insulin secretion and glucose intolerance in both sexes. To clarify the effects of liver-specific Kiss1 knockout on insulin action and glucose homeostasis in vivo, we conducted hyperinsulinemic-euglycemic clamp studies three weeks after tail injections. We noted a sexual dimorphism in the glucose infusion rate (GIR), female mice have a higher GIR to maintain euglycemia associated with an elevated glucose consumption rate, suggesting that female mice are more insulin sensitive than male mice. However, the deletion of liver kisspeptin had no effect on the glucose production rate in either sex. Indirect calorimetry assessment was conducted 4 weeks post-injection. Both male and female LKiss1KO mice showed significantly higher oxygen consumption, carbon dioxide production, and increased energy expenditure as compared to the LKiss1WT groups. However, there were no differences in either the respiratory exchange ratio or total ambulatory activity among treatments. These findings clearly define a pivotal role for hepatic Kiss1 in the modulation of insulin secretion to maintain glucose homeostasis without modulating glucose production as well as in maintaining energy homeostasis in both male or female mice.
Bisphenols effects on Granulosa Cell-Cell Communication
Authors: Sabry Reem , Apps Charlotte , Diepstraten Cassidy Van Den , Favetta Laura A 
Published: May 2021

Abstract
Bisphenols are Endocrine Disrupting Compounds (EDCs) linked to negative fertility outcomes in humans. The most common one, bisphenol A (BPA) is a plasticizer that acts as an estrogen agonist. Alternatives such as BPS and BPF are becoming widespread and possess similar activities. The oocyte and nearby granulosa cells are particularly vulnerable to EDCs as they are dependent on hormone signaling. Granulosa-Granulosa cell communications are pivotal for proper development and are mediated by gap junction molecules, called connexins (Cxs). Cx37, Cx26, and Cx43 are crucial in follicular communication and are the focus of this study. Bisphenols can alter these genes which directly affects cell-cell communication and in turn proper development. This study uses an in vitro cell culture model of bovine granulosa cells as the bovine species is an excellent translational model for human reproductive toxicology. To determine optimal doses and exposure times, we performed a cytotoxic assay (CCK8) and treated cells with a low dose (0.5 μg/mL), a medium dose (5 μg/mL), the current reported LOAEL (50 μg/mL), and a high dose (0.5 mg/mL) of bisphenols for 1, 6, 12, 24, 48, and 72 hrs. The high dose was lethal at all time points for BPA/BPF, while BPS was toxic from 1 hrs (P=0.0016; n=4). The LOAEL dose was toxic for BPA at 6, 12, 24 hrs (P=0.018, 0.0021, 0.0042 respectively; n=7) and was lethal at 48/72 hrs. BPF at the LOAEL dose showed an increase in cell viability at 6 hrs which was significant at 12hrs (P=0.0119; n=5). This trend declined at 48/72 hrs but was not significant. BPS did not affect cell viability at any other dose and the medium dose did not affect viability for all bisphenols; however, the low dose of BPA/BPF showed a trend towards decreased viability at 48 hrs of treatment. Therefore, we looked at the effects of BPA/S/F at the low and LOAEL doses for 12/48 hrs. We used qPCR and western blotting to quantify transcripts and proteins of the three connexins. Our data show that Cx43 mRNA was significantly increased at the LOAEL dose for BPA/BPF at 12 hrs (p=0.02; n=6). Preliminary data on proteins indicate a decrease and increase in expression at 12hrs for BPA/BPF treatment, respectively, at the LOAEL dose. BPS shows no effect on Cx43. BPS low dose and BPA/BPF LOAEL doses at 12 and 48 hrs increase Cx37 mRNA. Preliminary data on the protein levels show a significant decrease of Cx37 protein at BPA low dose, but no changes after exposure to the other bisphenols. Lastly, Cx26 mRNA is significantly increased after BPA treatment at the LOAEL dose at 12 hrs (P&lt;0.0001; n=5). This novel study investigates the effects of low/high doses and short-term/chronic exposure of bisphenols on cell-cell communication in granulosa cells and provides the basis for future studies on bisphenol toxicity in early development.
Prediction of Prolonged Opioid Use After Surgery in Adolescents: Insights From Machine Learning
Authors: Ward Andrew , Jani Trisha , De Souza Elizabeth , Scheinker David , Bambos Nicholas , Anderson T. Anthony 
Published: May 2021

BACKGROUND:
Long-term opioid use has negative health care consequences. Patients who undergo surgery are at risk for prolonged opioid use after surgery (POUS). While risk factors have been previously identified, no methods currently exist to determine higher-risk patients. We assessed the ability of a variety of machine-learning algorithms to predict adolescents at risk of POUS and to identify factors associated with this risk.

METHODS:
A retrospective cohort study was conducted using a national insurance claims database of adolescents aged 12–21 years who underwent 1 of 1297 surgeries, with general anesthesia, from January 1, 2011 to December 30, 2017. Logistic regression with an L2 penalty and with a logistic regression with an L1 lasso (Lasso) penalty, random forests, gradient boosting machines, and extreme gradient boosted models were trained using patient and provider characteristics to predict POUS (≥1 opioid prescription fill within 90–180 days after surgery) risk. Predictive capabilities were assessed using the area under the receiver-operating characteristic curve (AUC)/C-statistic, mean average precision (MAP); individual decision thresholds were compared using sensitivity, specificity, Youden Index, F1 score, and number needed to evaluate. The variables most strongly associated with POUS risk were identified using permutation importance.

RESULTS:
Of 186,493 eligible patient surgical visits, 8410 (4.51%) had POUS. The top-performing algorithm achieved an overall AUC of 0.711 (95% confidence interval [CI], 0.699-0.723) and significantly higher AUCs for certain surgeries (eg, 0.823 for spinal fusion surgery and 0.812 for dental surgery). The variables with the strongest association with POUS were the days’ supply of opioids and oral morphine milligram equivalents of opioids in the year before surgery.

CONCLUSIONS:
Machine-learning models to predict POUS risk among adolescents show modest to strong results for different surgeries and reveal variables associated with higher risk. These results may inform health care system–specific identification of patients at higher risk for POUS and drive development of preventative measures.
Urokinase-type plasminogen activator-mediated crosstalk between N-cadherin and β-catenin promotes wound healing
Authors: Diaz Ariel , Martin-Jimenez Cynthia , Xu Yang , Merino Paola , Woo Yena , Torre Enrique , Yepes Manuel 
Published: April 2021

ABSTRACT
Urokinase-type plasminogen activator (uPA; encoded by Plau) is a serine proteinase that, in the central nervous system, induces astrocytic activation. β-Catenin is a protein that links the cytoplasmic tail of cadherins to the actin cytoskeleton, thus securing the formation of cadherin-mediated cell adhesion complexes. Disruption of cell–cell contacts leads to the detachment of β-catenin from cadherins, and β-catenin is then degraded by the proteasome following its phosphorylation by GSK3β. Here, we show that astrocytes release uPA following a scratch injury, and that this uPA promotes wound healing via a plasminogen-independent mechanism. We found that uPA induces the detachment of β-catenin from the cytoplasmic tail of N-cadherin (NCAD; also known as CDH2) by triggering its phosphorylation at Tyr654. Surprisingly, this is not followed by degradation of β-catenin because uPA also induces the phosphorylation of the low density lipoprotein receptor-related protein 6 (LRP6) at Ser1490, which then blocks the kinase activity of GSK3β. Our work indicates that the ensuing cytoplasmic accumulation of β-catenin is followed by its nuclear translocation and β-catenin-triggered transcription of the receptor for uPA (Plaur), which in turn is required for uPA to induce astrocytic wound healing.
Automated morphometric analysis with SMorph software reveals plasticity induced by antidepressant therapy in hippocampal astrocytes
Authors: Sethi Parul , Virmani Garima , Gupta Kushaan , Thumu Surya Chandra Rao , Ramanan Narendrakumar , Marathe Swananda 
Published: April 2021

ABSTRACT
Nervous system development and plasticity involve changes in cellular morphology, making morphological analysis a valuable exercise in the study of nervous system development, function and disease. Morphological analysis is a time-consuming exercise requiring meticulous manual tracing of cellular contours and extensions. We have developed a software tool, called SMorph, to rapidly analyze the morphology of cells of the nervous system. SMorph performs completely automated Sholl analysis. It extracts 23 morphometric features based on cell images and Sholl analysis parameters, followed by principal component analysis (PCA). SMorph was tested on neurons, astrocytes and microglia and reveals subtle changes in cell morphology. Using SMorph, we found that chronic 21-day treatment with the antidepressant desipramine results in a significant structural remodeling in hippocampal astrocytes in mice. Given the proposed involvement of astroglial structural changes and atrophy in major depression in humans, our results reveal a novel kind of structural plasticity induced by chronic antidepressant administration.
Wolbachia manipulate fitness benefits of olfactory associative learning in a parasitoid wasp
Authors: Farahani Hossein Kishani , Ashouri Ahmad , Abroon Pouria , Pierre Jean-Sebastien , van Baaren Joan 
Published: April 2021

ABSTRACT
Upon encountering a host, a female parasitoid wasp has to decide whether to learn positive or negative cues related to the host. The optimal female decision will depend on the fitness costs and benefits of learned stimuli. Reward quality is positively related to the rate of behavioral acquisition in processes such as associative learning. Wolbachia, an endosymbiotic bacterium, often plays an impressive role in the manipulation of its arthropod host's biology. Here, we studied the responses of two natural Wolbachia infected/uninfected Trichogramma brassicae wasp populations to theoretically high- and low-reward values during a conditioning process and the consequences of their responses in terms of memory duration. According to our results, uninfected wasps showed an attraction response to high-value rewards, but showed aversive learning in response to low-value rewards. The memory span of uninfected wasps after conditioning by low-value rewards was significantly shorter than that for high-value rewards. As our results revealed, responses to high-quality hosts will bring more benefits (bigger size, increased fecundity and enhanced survival) than those to low-quality hosts for uninfected wasps. Infected wasps were attracted to conditioned stimuli with the same memory duration after conditioning by both types of hosts. This was linked to the fact that parasitoids emerging from both types of hosts present the same life-history traits. Therefore, these hosts represent the same quality reward for infected wasps. According to the obtained results, it can be concluded that Wolbachia manipulates the learning ability of its host, resulting in the wasp responding to all reward values similarly.
Low repeatability of aversive learning in zebrafish (Danio rerio)
Authors: Mason Dominic , Zajitschek Susanne , Anwer Hamza , O'Dea Rose E. , Hesselson Daniel , Nakagawa Shinichi 
Published: April 2021

ABSTRACT
Aversive learning – avoiding certain situations based on negative experiences – can profoundly increase fitness in animal species, yet no studies have systematically quantified its repeatability. Therefore, we assessed the repeatability of aversive learning by conditioning approximately 100 zebrafish (Danio rerio) to avoid a colour cue associated with a mild electric shock. Across eight different colour conditions, zebrafish did not show consistent individual differences in aversive learning (R=0.04). Within conditions, when zebrafish were conditioned to the same colour, blue conditioning was more repeatable than green conditioning (R=0.15 and R=0.02). Overall, aversive learning responses of zebrafish were weak and variable. We speculate that the effect of aversive learning might have been too weak to quantify consistent individual differences, or directional selection might have eroded additive genetic variance. We also discuss how confounded repeatability assays and publication bias could have inflated estimates of repeatability in the literature.
Effects of early-life conditions on innate immune function in adult zebra finches
Authors: Driessen Merijn M. G. , Versteegh Maaike A. , Gerritsma Yoran H. , Tieleman B. Irene , Pen Ido , Verhulst Simon 
Published: April 2021

ABSTRACTEarly life conditions can affect individuals for life, with harsh developmental conditions resulting in lower fitness, but the underlying mechanisms are not well understood. We hypothesized that immune function may be part of the underlying mechanism, when harsh developmental conditions result in less effective immune function. We tested this hypothesis by comparing innate immune function between zebra finches (Taeniopygia guttata) in adulthood (n=230; age 108–749 days) that were reared in either small or large broods. We used this experimental background to follow up our earlier finding that finches reared in large broods have a shorter lifespan. To render a broad overview of innate immune function, we used an array of six measures: bacterial killing capacity, hemagglutination, hemolysis, haptoglobin, nitric oxide and ovotransferrin. We found no convincing evidence for effects of natal brood size on any of the six measures of innate immune function. This raised the question whether the origin of variation in immune function was genetic, and we therefore estimated heritabilities using animal models. However, we found heritability estimates to be low (range 0.04–0.11) for all measured immune variables, suggesting variation in innate immune function can largely be attributed to environmental effects independent of early-life conditions as modified by natal brood size.
Disentangling the energetic costs of step time asymmetry and step length asymmetry in human walking
Authors: Stenum Jan , Choi Julia T. 
Published: April 2021

ABSTRACT
The metabolic cost of walking in healthy individuals increases with spatiotemporal gait asymmetries. Pathological gait, such as post-stroke, often has asymmetry in step length and step time which may contribute to an increased energy cost. But paradoxically, enforcing step length symmetry does not reduce metabolic cost of post-stroke walking. The isolated and interacting costs of asymmetry in step time and step length remain unclear, because previous studies did not simultaneously enforce spatial and temporal gait asymmetries. Here, we delineate the isolated costs of asymmetry in step time and step length in healthy human walking. We first show that the cost of step length asymmetry is predicted by the cost of taking two non-preferred step lengths (one short and one long), but that step time asymmetry adds an extra cost beyond the cost of non-preferred step times. The metabolic power of step time asymmetry is about 2.5 times greater than the cost of step length asymmetry. Furthermore, the costs are not additive when walking with asymmetric step time and asymmetric step length: the metabolic power of concurrent asymmetry in step length and step time is driven by the cost of step time asymmetry alone. The metabolic power of asymmetry is explained by positive mechanical power produced during single support phases to compensate for a net loss of center of mass power incurred during double support phases. These data may explain why metabolic cost remains invariant to step length asymmetry in post-stroke walking and suggest how effects of asymmetry on energy cost can be attenuated.