bluuebunny/crossref_metadata_2025 huggingface dataset:
0947 Parent-Perceived Sleep Problems and Sleep Goals in Infants and Toddlers: A Global Sample
Authors: Mindell J A , Goh D , Collins M , Bartle A , Kohyama J , Sekartini R , Veeravigrom M , Leichman E S
Published: May 2020

Introduction

The aim of this study was to assess parent perceptions of sleep problems in young children and parent-identified areas of change in a global sample.

Methods

Caregivers (95.6% mothers) of 1555 infants/toddlers (birth-37 mos; M=12.2 mos; 49.5% male) completed an online survey, representing Indonesia (n=187), Japan (n=718), New Zealand (n=231), Singapore (n=199), and Thailand (n=221). The survey included an abbreviated version of the Brief Infant Sleep Questionnaire, and a list of potential sleep-related areas of change.

Results

36.9% reported a perceived sleep-problem, whereas 92.9% indicated an area of desired change related to their child’s sleep. In terms of areas of change, 82.5% endorsed bedtime/how child falls asleep, 70.0% nighttime sleep, and 57.8% related to the morning. As expected, 99.7% of parents who endorsed a problem indicated a desired change compared to 88.9% who did not perceive a problem, p < .001. Those who noted a problem were more likely to endorse a change at bedtime (92.5%) and during the night (90.1%), compared to the morning (68.8%). There were country-based differences, with caregivers in New Zealand (47.0%) and Singapore (44.2%) more likely to report a child sleep problem compared to Thailand (35.3%), Japan (34.1%) and Indonesia (29.4%), p < .001. No differences were noted in parent-report of desired change across Japan, New Zealand, Singapore, and Thailand (94-96%) but were significantly higher than Indonesia (83.4%).

Conclusion

Although one-third of parents of young children in a global sample indicate a perceived sleep problem, almost all parents wish to change something about their child’s sleep, primarily relate to bedtime and during the night. Sleep education and assessment delivered by health care providers should focus not only on what families consider to be “problematic,” but also what families would like to modify, or improve, about their child’s sleep within a developmentally appropriate framework.

Support

Johnson & Johnson Consumer Inc., Skillman, NJ, USA.
0959 Associations Between Sleep and Academic Performance in Typically Developing Adolescent Girls
Authors: Gruber R , Lin L , Santisteban J , Boursier J , Somerville G
Published: May 2020

Introduction

Healthy sleep promotes cognitive functioning and is associated with better academic performance, whereas insufficient, poor, and inconsistent sleep schedules are associated with poor school performance. Several studies have identified gender differences in the timing, duration, and quality of sleep in adolescence, with adolescent girls having poorer sleep compared to adolescent boys, yet research shows that girls outperform boys academically. This could be because sleep might not affect all subjects similarly and previous studies regarding sleep and academic performance combined both genders. The goal of the present study was to determine which aspects of academic performance are specifically associated with short or poor sleep in typically developing adolescents girls.

Methods

80 adolescent girls aged 12-17 years participated in the study. Sleep was assessed in the home environment for five consecutive weeknights using actigraphy. Academic performance was assessed using report card grades.

Results

Hierarchical regression analyses adjusted for age, pubertal status, and socioeconomic status revealed that longer average sleep time was significantly associated with higher grades in mathematics. No significant associations were found between sleep variables and grades in other subjects.

Conclusion

Longer average weekday sleep duration is associated with better mathematics grades in typically developing adolescent girls.

Support

NSERC grant to Reut Gruber
0972 Persistence, Remission, Acquisition Of Sleep Disturbances Contributes To The Transition Of Emotional/behavioral Problems In Preschool Children
Authors: Deng Y , Wang G , Li W , Zhang Y , Zhao J , Zhang Z , Jiang F
Published: May 2020

Introduction

Cross-sectional and longitudinal studies have consistently reported associations between sleep disturbances and emotional/behavioral problems in children. However, few studies have examined whether the remission, acquisition of sleep disturbances contribute to the transition of emotional and behavioral problems during preschool years.

Methods

This study used data from the Shanghai Children’s Health, Education and Lifestyle Evaluation-Preschool (SCHEDULEA-P), a prospective, population-based cohort study of newly enrolled preschoolers in Shanghai kindergartens in Nov. 2016. In total, 17182 children with complete data on parent-reported Strength and Difficulties Questionnaire (SDQ) both at school enrollment(wave 1) and the third year(wave 2) were included in the study. Children’s sleep disturbances were measured using Children Sleep Habit Questionnaire (CSHQ) at both waves.

Results

The 17182 participants included 8935(52.0%) males, with a mean (SD) age of 3.73(0.29) years at wave 1. 66.9%, 7.2%, 17.4% and 8.5% of these children were divided into persistent sleep disturbance, acquired, remitted group and persistent normal sleep group, respectively. The proportion of persistent, acquired, remitted emotional/behavioral problems and normal group was 13.7%, 9.4%, 21.1%, 55.8%. SDQ scores of acquired sleep disturbances group stayed high at wave 3, while SDQ scores of remitted sleep disturbances group decreased sharply during the preschool years. After adjusted for confounding factors, the odds of remission from emotional/behavioral problems among children who experienced remission of sleep disturbances, who had persistent normal sleep were both much higher compared to those who had persistent sleep disturbances (OR=2.53(2.12-3.01), p<0.001; OR=2.74(2.01-3.75), p<0.001). Meanwhile, the odds of acquisition of emotional/behavioral problems at wave 2 among subjects who newly acquired sleep disturbances at wave 2 and who had persistent sleep disturbances was similarly higher than those who never have sleep disturbances(OR= 2.75, P<0.001 VS OR=2.77, P<0.001). Besides, those who experience remission of sleep disturbances still have 1.48 times the odds of acquisition of emotional / behavioral problems(P=0.006).

Conclusion

The remission of sleep disturbances contributed to the remission of emotional/behavioral problems, while the emergence of sleep disturbances throughout preschool years increased the risk of the acquisition of emotional/behavioral problems.

Support

Supported by the Chinese National Natural Science Foundation of China (81773443, 81728017, 81602870, 81601162, 81602868)
0973 Maternal Depression And Infant Sleep Duration Trajectory In The First 3 Years: A Prospective Cohort Study
Authors: Gui Y , Wang G , Deng Y , Li W , Jiang F
Published: May 2020

Introduction

The study was to investigate trajectories of infant sleep duration and associations with trajectories of maternal depression status during 3 years post-partum.

Methods

Data were from the Child Health Promotion Project in Shanghai (CHPPS). Mothers were recruited at the third trimester of pregnancy and followed up together with the infants until 36 months postpartum. Between 2012 and 2013, 262 women (Mage=29.5, SDage=3.2, range: 22-39 years old) were recruited and were followed from June 2012 to August 2015. Sleep duration of the children was assessed using Brief Infant Sleep Questionnaire (BISQ) at 42 days, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, and 36 months postpartum. Center for Epidemiological Survey-Depression Scale (CESD), Edinburgh Postnatal Depression Scale (EPDS), and the Profile of Mood States (POMS) were used to measure the mother’s depression status at late pregnancy, 42 days postpartum, and 12-36 months postpartum, respectively. The group-based trajectory models (GBTM) were used to estimate patterns of infant sleep duration development and maternal depression status.

Results

Two trajectories of infant day sleep duration were identified, defined as “initial short sleepers” (54.8%) and “initial long sleepers” (45.2%). Three trajectories of infant night sleep duration were identified, labeled as “increasing” (8.5%), “stable” (61.7%), and “mild declining” (29.8%). Two trajectories infant total sleep duration were identified, defined as “initial short sleepers” (51.5%) and “initial long sleepers” (48.5%). Two trajectories of maternal depression status were identified, labeled as “low” (74.2%) and “high” (25.8%). After controlling for covariates, women who have higher depression status had infants of shorter day sleep duration. There was no significant association with infant night sleep duration.

Conclusion

Our study suggests that maternal postpartum depression is associated with short infant day sleep duration, but not with infant night sleep duration.

Support

Supported by the Chinese National Natural Science Foundation of China (81773443, 81728017, 81602870, 81601162, 81602868)
0990 Evaluating Components Of Sleep Quality And The Sleep-Quality Of Life Relationship For Children With Acute Lymphoblastic Leukemia
Authors: Gross Y , Barakat L , Daniel L C
Published: May 2020

Introduction

Poor sleep quality is associated with reduced health-related quality of life (HRQL) for children with Acute Lymphoblastic Leukemia (ALL). Research has yet to evaluate how components of child sleep quality uniquely contribute to HRQL beyond demographic characteristics. This study evaluates features of sleep and the relationship between sleep and HRQL for children in the maintenance phase of ALL treatment.

Methods

89 caregivers (ages 20-52, M=35.95, SD=7.10) of children with ALL (ages 3-12, M=5.73, SD=2.21; 13.76 months from diagnosis) completed demographic questionnaires and reports of child sleep quality (Child Sleep Habits Questionnaire; CSHQ), and 64 caregivers reported on child HRQL (Pediatric Quality of Life Inventory). Descriptive statistics were calculated. T-tests compared CSHQ subscales to ratings of healthy normative values. Pearson correlations evaluated associations between sleep and overall HRQL. Hierarchical regression assessed whether CSHQ subscales uniquely predicted HRQL beyond demographic characteristics.

Results

This sample reported greater bedtime resistance [t(88)=6.413, p<.001], sleep onset delay [t(88)=3.180, p=.002], sleep anxiety [t(88)=4.271, p<.001], night awakenings [t(88)=6.031, p<.001], parasomnias [t(88)=3.900, p<.001], and daytime sleepiness [t(87)=1.781, p=.078] than normative values, although sleep duration [t(88)=1.781, p=.078] and sleep disordered breathing (SDB) [t(88)=-.061, p=.951] did not differ. HRQL was related to SDB (r=-.289, p=.021), bedtime resistance (r=-.263, p=.036), and total sleep score (r=-.34, p=.006). The regression model with SDB and bedtime resistance explained 24.2% of variance but was not significant [F(6,31)=1.651, p=.167].

Conclusion

Caregiver ratings showed greater sleep impairments for children in this sample than of norms. Sleep subscales were associated with HRQL, but did not predict HRQL beyond demographic factors. Caregiver reports of child sleep and HRQL may vary depending on when during the monthly chemotherapy cycle questionnaires were completed. SDB did not differ from normative values but was related to HRQL, suggesting the need to screen for SDB symptoms to potentially improve child outcomes.

Support

This study was supported by funding from the American Cancer Society PF-13-238-01-PCSM (PI: Daniel).
0996 School Start Times Are Associated With Youth And Parent Sleep Duration
Authors: Gunn H E , Eberhardt K R
Published: May 2020

Introduction

Early school start times contribute to insufficient sleep in adolescents; however, we know little about the impact of school start times at a family level. Moreover, even among similar school start times, sleep opportunity varies depending on mode of transportation and travel time. Thus, the purpose of this study was to determine whether AM school departure time is associated with sleep duration in parents and young adolescents.

Methods

Parent-adolescent dyads (n=31) completed 10 days of actigraphy and sleep diaries. Adolescents were 10-14 year olds (58% male). Parents were predominately mothers (87%) and their mean age was 44 yrs (SD = 5.9). Dyads were 77% White, 11% Black, and 12% Biracial or Other. Youth leave for school time was assessed with the School Sleep Habits Survey. Actigraphy- and diary-assessed total sleep time (TST) was averaged across 10 days and on weekdays. Separate regressions models for parents and adolescents determined associations between school leave time (predictor) and two outcomes: 10-day TST and weekday TST.

Results

For adolescents, later leave for school time was associated with longer 10-day actigraphy-assessed TST (β = .504, p = .012) and diary-assessed TST (β =.683, p <.001). Later leave for school time was also associated with more weekday actigraphy and diary-assessed TST (β = .661 and .426, respectively, p’s < .05). For parents, later leave for school time predicted more diary-assessed sleep across 10 days (β = .481, p = .013) and on weekdays, but this finding did not reach significance (β = .373, p = .061). Leave for school time was not associated with parents’ actigraphy-assessed TST across the 10-day period or on weekdays (p’s > .10).

Conclusion

The time that youth need to leave for school may more closely approximate sleep opportunity regardless of actual school start time. This is particularly relevant for urban and rural youth with long commutes. Findings add to the strong support that delayed school start times or flexible scheduling will benefit adolescent sleep and also suggest positive impacts at the family level.

Support

This material is based upon work supported by the Sleep Research Society Foundation.
Prevalence of COVID-19-like symptoms in Italy and Lombardy, March–April 2020, and their implications on cancer prevention, diagnosis and management
Authors: Negri Eva , Scarpino Vilma , La Vecchia Carlo
Published: May 2020

Two population-based surveys on coronavirus disease-2019 (Covid-19)-like symptoms were conducted by BVA-Doxa on representative samples of the general population from Italy and its largest region, Lombardy, with over 10 million inhabitants and heavily struck by Covid-19, on 27–30 March and 3–7 April, on a total of 2000 individuals – 353 from Lombardy. Overall, 14.2% of Italians – and 19.6% in Lombardy – reported Covid-19-like symptoms. The estimated prevalence was higher in the young, in smokers, and in Lombardy over the period 20 March to 7 April. Although the influenza season was ended by mid-March, at least part of the symptoms may be not Covid-19 related. Even assuming that only half are, at least 7% of Italians and 10% in Lombardy had been affected by Covid-19. To these, asymptomatic or paucisymptomatic cases have to be added. These estimates are at least one or two orders of magnitude larger than official registered cases. This has major implications for cancer prevention, management and treatment.
Efficacy and Safety in Combining Primary Palatoplasty and Myringotomy in Patients with Cleft Palate
Authors: Mantilla-Rivas Esperanza , Mamidi Ishwarya , Rokni Alex , Brennan Ashleigh , Rana Md Sohel , Goldrich Agnes , Manrique Monica , Shah Monica , Reilly Brian K. , Rogers Gary F. , Oh Albert K.
Published: May 2020

Background:

Patients born with a cleft lip and palate undergo multiple surgical procedures, increasing the infants’ exposure to anesthesia and potential risk of neurocognitive delays. In addition, these numerous procedures lead to greater use of hospital resources. This study analyzes the differences in anesthetic exposure and perioperative characteristics between performing combined versus separate primary palatoplasty (PP) and placement of bilateral myringotomy tubes (BMT).

Methods:

We reviewed patients younger than 2 years who underwent PP and BMT at our institution from June 2014 to January 2019. Patients who underwent PP and BMT during the same admission (combined group = 74) and during separate admissions (separate group = 26) were studied. Due to the small sample size in the separate group, additional data for this group were gathered by propensity score matching by gender, race, and American Society of Anesthesiology class. Statistical analyses were carried out to identify significant differences between the 2 groups. Linear regression was performed to compare perioperative variables.

Results:

One hundred patients met the inclusion criteria. There were no significant differences in demographic characteristics or American Society of Anesthesiology class, surgery and anesthesia duration, dosage of intraoperative dexmedetomidine, hospital length of stay, and perioperative complications (P > 0.05). Per contra, combined group had significantly lower intraoperative dosages of fentanyl (P = 0.01) and shorter postoperative care unit stay (P = 0.047).

Conclusions:

This study documents decreased postoperative care unit time and anesthesia drug exposure without increased length of stay or perioperative complications in patients undergoing combined PP and BMT. These results support combining PP and BMT to reduce exposure to potentially neurotoxic medications and to increase efficient utilization of hospital resources.
Autologous Fat Transfer for Scar Prevention and Remodeling: A Randomized, Blinded, Placebo-controlled Trial
Authors: Brown J. Christian , Shang Hulan , Yang Ning , Pierson Justine , Ratliff Catherine R. , Prince Noah , Roney Nicholas , Chan Rodney , Hatem Victoria , Gittleman Haley , Barnholtz-Sloan Jill S. , Vincek Vladimir , Katz Adam J.
Published: May 2020

Background:

Autologous fat transfer—also referred to as fat grafting—has been reported to provide beneficial effects to overlying scar and skin. Despite procedural frequency, there is a paucity of high-level evidence guiding the surgeon in technique, patient selection, and efficacy.

Methods:

A multicenter, double-blinded, randomized, internally placebo-controlled trial was performed with an aim to qualitatively and quantitatively evaluate the impact of autologous fat transfer on the quality of overlying scar tissue. Fat-grafted scars were evaluated and compared with paired, saline-injected “control” scars. Subjective and objective metrics were evaluated in treated sites for 12 months after treatment.

Results:

Blinded qualitative results demonstrated a statistically significant improvement in scar quality over time in fat-grafted scars. However, these improvements were not found to be statistically different from changes noted in scars treated with saline. In addition, objective metrics did not statistically differ between saline-injected and autologous fat-grafted scars.

Conclusions:

Our results demonstrate that autologous fat grafting can improve the qualitative profile of a scar from both the patient and observer perspectives. However, there was no difference in improvement when compared with scars that were treated with saline in a randomized and blinded fashion. These results demonstrate that any improvements in scar quality related to fat grafting are also achieved using saline and suggest that mechanisms other than cell activity may be at play. Additional randomized, blinded, placebo-controlled trials are required to either corroborate or contest the putative beneficial effect(s) of adipose tissue on scar remodeling.
Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide in Wiskott-Aldrich Syndrome With Myeloablative Conditioning
Authors: Sharma Anil , Rastogi Neha , Kapoor Rohit , Chatterjee Goutomi , Yadav Satya P.
Published: May 2020

Hematopoietic stem cell transplant (HSCT) is the only curative treatment modality for Wiskott-Aldrich syndrome. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an upcoming option in children with nonmalignant conditions. However, only few cases have been reported for Wiskott-Aldrich syndrome HSCT with PTCy approach. Here we report a 4-year-old boy, treated successfully by haploidentical HSCT with myeloablative conditioning (busulfan, fludarabine, and thiotepa) and PTCy. Posttransplant chimerism was fully donor. Of 13 cases (current case and other 12 published cases) 10 are alive and disease free after haploidentical HSCT with PTCy. Haploidentical HSCT with PTCy using myeloablative conditioning is feasible and safe.
Treatment of Hepatoblastoma With Drug-eluting Bead Transarterial Chemoembolization in a 13-Month-Old Infant: A Case Report and Review of the Literature
Authors: Hoyer Matthew , Goli Rakesh , Barnett Katherine K. , Raabe Eric H. , Hong Kelvin
Published: May 2020

Background:

Prior reports have shown the utility of conventional lipiodol-based transarterial chemoembolization in hepatoblastoma. The authors describe the first reported case of hepatoblastoma treated with drug-eluting bead transarterial chemoembolization (DEB-TACE).

Observations:

An 11-month-old infant presented with hepatoblastoma measuring 14.3 cm. A trial of cisplatin chemotherapy followed by sequential DEB-TACE to the tumor’s feeding vasculature reduced the mass to 5.3 cm. The patient tolerated both sessions of DEB-TACE without any major complication. Having demonstrated adequate disease control, the patient then underwent successful liver transplantation.

Conclusion:

This report provides promising evidence for the treatment of hepatoblastoma with DEB-TACE.
The association between polymorphism of norepinephrine transporter G1287A and major depressive disorder, antidepressant response: a meta-analysis
Authors: Zhao Xiaofeng , Song Chuanfu , Wang Na , He Jin , Yang Xueping , Zhang Huijie , Deng Yajie , He Yi , Liu Yujia , Li Hengfen , Cao Suxia
Published: May 2020

Objectives

Massive research has examined the cause of major depressive disorder (MDD) and accumulating evidence has revealed that the gene for the norepinephrine transporter (NET) is involved in MDDs etiology as well as the antidepressant response. The G1287A (rs5569, GRCh38, Chromosome 16, 55697923) is located in the exon 9 region of the SLC6A2 gene. It was found to be connected with MDD and antidepressant response in people of different genetic ancestries. However, the results are still inconsistent.

Methods

A meta-analysis was conducted to evaluate the overall association of rs5569 polymorphisms with MDD and the antidepressant response.

Results

Sixteen articles that studied the connection between the G1287A polymorphism and MDD or antidepressant response were identified, and their outcomes revealed there was a significant connection between the polymorphisms and MDD and antidepressant response. Our study indicated that the GG genotype may be a protection factor against the development of MDD [odds ratio (OR = 0.78, 95% confidence interval (CI) = 0.64–0.96, P = 0.02 for Asian population; OR = 0.79, 95% CI = 0.63–0.98, P = 0.03 for Han Chinese population] while the GG genotype had a worse antidepressant response (OR = 0.49, 95% CI = 0.25–0.94, P = 0.03).

Conclusions:

NET G1287A polymorphisms are involved in the etiology of MDD and antidepressant response.
Turkey adenovirus 3, a siadenovirus, uses sialic acid on N-linked glycoproteins as a cellular receptor
Authors: Mahsoub Hassan M. , Yuan Lijuan , Pierson F. William
Published: May 2020

Turkey adenovirus 3 (TAdV-3) is the causative agent of an immune-mediated disease in turkeys, haemorrhagic enteritis, through targeting B lymphocytes. In the present study, we investigated the role of sialic acid in TAdV-3 entry and characterized the structural components of TAdV-3 receptor(s) on RP19, B lymphoblastoid cells. Removal of the cell-surface sialic acids by neuraminidases or blocking of sialic acids by wheat germ agglutinin lectin reduced virus infection. Pre-incubation of cells with Maackia amurensis lectin or Sambucus nigra agglutinin resulted in virus reduction, suggesting that TAdV-3 uses both α2,3-linked and α2,6-linked sialic acids as attachment receptor. Virus infectivity data from RP19 cells treated with sodium periodate, proteases (trypsin or bromelain) or metabolic inhibitors (dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, tunicamycin, or benzyl N-acetyl-α-d-galactosaminide) indicated that N-linked, but not O-linked, carbohydrates are part of the sialylated receptor and they are likely based on a membrane glycoprotein, rather than a glycolipid. Furthermore, our data, in conjunction with previous findings, implies that the secondary receptor for TAdV-3 is a protein molecule since the inhibition of glycolipid biosynthesis did not affect the virus infection, which was rather reduced by protease treatment. We can conclude that terminal sialic acids attached to N-linked membrane glycoproteins on B cells are used for virus attachment and are essential for successful virus infection.
Mathematical framework for place coding in the auditory system
Authors: Reyes Alex D.
Published: May 2020

In the auditory system, tonotopy is postulated to be the substrate for a place code, where sound frequency is encoded by the location of the neurons that fire during the stimulus. Though conceptually simple, the computations that allow for the representation of intensity and complex sounds are poorly understood. Here, a mathematical framework is developed in order to define clearly the conditions that support a place code. To accommodate both frequency and intensity information, the neural network is described as a topological space with elements that represent individual neurons and clusters of neurons. A bijective mapping is then constructed from acoustic space to neural space so that frequency and intensity are encoded, respectively, by the location and size of the clusters. Algebraic operations -addition and multiplication- are derived to elucidate the rules for representing, assembling, and modulating multi-frequency sound in networks. The predicted outcomes of these operations are consistent with network simulations as well as with electrophysiological and psychophysical data. The analyses show how both frequency and intensity can be encoded with a purely place code, without the need for rate or temporal coding schemes. The algebraic operations are used to describe loudness summation and suggest a mechanism for the critical band. The mathematical approach complements experimental and computational approaches and provides a foundation for interpreting data and constructing models.

Author Summary

One way of encoding sensory information in the brain is with a so-called place code. In the auditory system, tones of increasing frequencies activate sets of neurons at progressively different locations along an axis. The goal of this study is to elucidate the mathematical principles for representing tone frequency and intensity in neural networks. The rigorous, formal process ensures that the conditions for a place code and the associated computations are defined precisely. This mathematical approach offers new insights into experimental data and a framework for constructing network models.
A general model of population dynamics accounting for multiple kinds of interaction
Authors: Stucchi Luciano , Pastor Juan Manuel , García-Algarra Javier , Galeano Javier
Published: May 2020

Population dynamics has been modelled using differential equations almost since Malthus times, more than two centuries ago. Basic ingredients of population dynamics models are typically a growth rate, a saturation term in the form of Verhulst’slogistic brake, and a functional response accounting for interspecific interactions. However intraspecific interactions are not usually included in the equations. The simplest models use linear terms to represent a simple picture of the nature, meanwhile to represent more complex landscapes, it is necessary to include more terms with higher order or analytically more complex. The problem to use a simpler or more complex model depends on many factors: mathematical, ecological, or computational. To address it, here we discuss a new model based on a previous logistic-mutualistic model. We have generalised the interspecific terms (for antagonistic and competitive relationships) and we have also included new polynomial terms to explain any intraspecific interaction. We show that by adding simple intraspecific terms, new free-equilibrium solutions appear driving a much richer dynamics. These new solutions could represent more realistic ecological landscapes by including a new high order term.
State-space Modeling Clarifies Productivity Regime Shifts of Japanese Flying Squid
Authors: Nishijima Shota , Kubota Hiroshi , Kaga Toshiki , Okamoto Suguru , Miyahara Hisae , Okamura Hiroshi
Published: May 2020

Regime shifts of climatic and environmental conditions potentially affect productivity of fisheries resources, posing challenging issues to stock management. The stocks of the Japanese flying squid (Todarodes pacificus) are suspected to suffer from regime shifts, but their detection is difficult and possibly doubtful because the nature of short-lived species readily makes the effect of regime shifts confounded with observation errors. Here we developed a new state-space assessment model to evaluate the influence of regime shifts on spawner-recruitment relationship of the Japanese flying squid. The model simultaneously estimates the population dynamics of multiple stocks that could share some life history parameters, making parameter inference stable. We demonstrate that two-time regime shifts of productivity around 1991 and 2015 caused two-to three-fold changes of maximum sustinabile yields. The model with regime shifts clarifies the relationship between fishing pressure and spawner abudance that is difficult to detect in a model with no regime shift. The state-space approach will be a promising tool to accurately assess stock status by separating recruitment process from observation errors and contribute tothe management of marine biological resources sensitive to regime shifts.
BrphyBis critical for rapid recovery to darkness in matureBrassica rapaleaves
Authors: Arsovski Andrej A. , Zemke Joseph E. , Hamm Morgan , Houston Lauren , Romanowski Andrés , Halliday Karen J. , Nesi Nathalie , Nemhauser Jennifer L.
Published: May 2020

Crop biomass and yield are tightly linked to how the light signaling network translates information about the environment into allocation of resources, including photosynthates. Once activated, the phytochrome (phy) class of photoreceptors signal and re-deploy carbon resources to alter growth, plant architecture, and reproductive timing.Brassica rapahas been used as a crop model to test for conservation of the phytochrome–carbon network.B. rapa phyBmutants have significantly decreased or absent CO2-stimulated growth responses in seedlings, and adult plants have reduced chlorophyll levels, photosynthetic rate, stomatal index, and seed yield. Here, we examine the transcriptomic response of adult wild-type andBrphyBleaves to darkening and recovery in light. Three days of darkness was sufficient to elicit a response in wild type leaves suggesting a shift from carbon fixation and nutrient acquisition to active redistribution of cellular resources. Upon a return to light, wild-type leaves appeared to transcriptionally return to a pre-darkness state restoring a focus on nutrient acquisition. Overall,BrphyBmutant plants have a similar response with key differences in genes involved in photosynthesis and light response which deviate from the wild type transcriptional dynamics. Genes targeted to the chloroplast are especially affected. AdultBrphyBmutant plants had fewer, larger chloroplasts, further linking phytochromes, chloroplast development, photosynthetic deficiencies and optimal resource allocation.
Optimizing predictive models to prioritize viral discovery in zoonotic reservoirs
Authors: Becker Daniel J. , Albery Gregory F. , Sjodin Anna R. , Poisot Timothée , Bergner Laura M. , Dallas Tad A. , Eskew Evan A. , Farrell Maxwell J. , Guth Sarah , Han Barbara A. , Simmons Nancy B. , Stock Michiel , Teeling Emma C. , Carlson Colin J.
Published: May 2020

Despite global investment in One Health disease surveillance, it remains difficult—and often very costly—to identify and monitor the wildlife reservoirs of novel zoonotic viruses. Statistical models can be used to guide sampling prioritization, but predictions from any given model may be highly uncertain; moreover, systematic model validation is rare, and the drivers of model performance are consequently under-documented. Here, we use bat hosts of betacoronaviruses as a case study for the data-driven process of comparing and validating predictive models of likely reservoir hosts. In the first quarter of 2020, we generated an ensemble of eight statistical models that predict host-virus associations and developed priority sampling recommendations for potential bat reservoirs and potential bridge hosts for SARS-CoV-2. Over more than a year, we tracked the discovery of 40 new bat hosts of betacoronaviruses, validated initial predictions, and dynamically updated our analytic pipeline. We find that ecological trait-based models perform extremely well at predicting these novel hosts, whereas network methods consistently perform roughly as well or worse than expected at random. These findings illustrate the importance of ensembling as a buffer against variation in model quality and highlight the value of including host ecology in predictive models. Our revised models show improved performance and predict over 400 bat species globally that could be undetected hosts of betacoronaviruses. Although 20 species of horseshoe bats (Rhinolophusspp.) are known to be the primary reservoir of SARS-like viruses, we find at least three-fourths of plausible betacoronavirus reservoirs in this bat genus might still be undetected. Our study is the first to demonstrate through systematic validation that machine learning models can help optimize wildlife sampling for undiscovered viruses and illustrates how such approaches are best implemented through a dynamic process of prediction, data collection, validation, and updating.
Polymerase Theta Inhibition Kills Homologous Recombination Deficient Tumors
Authors: Zhou Jia , Gelot Camille , Pantelidou Constantia , Li Adam , Yücel Hatice , Davis Rachel E. , Farkkila Anniina , Kochupurakkal Bose , Syed Aleem , Shapiro Geoffrey I. , Tainer John A. , Blagg Brian S. J. , Ceccaldi Raphael , D’Andrea Alan D.
Published: May 2020

PARP inhibitors (PARPi) have become a new line of therapy for Homologous Recombination (HR)-deficient cancers. However, resistance to PARPi has emerged as a major clinical problem. DNA polymerase theta (POLθ) is synthetic lethal with HR and a druggable target in HR-deficient cancers. Here, we identified the antibiotic Novobiocin (NVB) as a specific POLθ inhibitor that selectively kills HR-deficient tumor cellsin vitroandin vivo. NVB directly binds to the POLθ ATPase domain, inhibits its ATPase activity, and phenocopies POLθ depletion. BRCA-deficient tumor cells and those with acquired PARPi resistance are sensitive to NVBin vitroandin vivo. Increased POLθ expression levels predict NVB sensitivity. The mechanism of NVB-mediated cell death in PARPi resistant cells is the accumulation of toxic RAD51 foci, which also provides a pharmacodynamic biomarker for NVB response. Our results demonstrate that NVB may be useful alone or in combination with PARPi in treating HR-deficient tumors, including those with acquired PARPi resistance.

One Sentence Summary

We identified Novobiocin as a specific POLθ inhibitor that selectively kills naïve and PARPi resistance HR-deficient tumorsin vitroandin vivo.
A synoptic revision ofPohliella(Podostemaceae) with notes onAulea, CipoiaandSaxicolella
Authors: Cheek Martin
Published: May 2020

SaxicolellaEngl., an African genus of the waterfall specialist plant family Podostemaceae, was shown to be polyphyletic as currently delimited. One clade, sampled from species in Ghana, is sister to AmericanCeratolacis(Tul.)Wedd.,PodostemumMichx. and all Old World Podostemoideae (podostemoids). The second clade, sampled from Cameroonian material, was embedded within the major clade of African podostemoids. In this paper the generic nomenclature applied toSaxicolellasensu lato (Saxicolella, PohliellaEngl., AuleaLebrun & Stork nom. inval.), is reviewed and the morphological support for the two clades and their correct generic names is determined.Pohliellais shown to be the correct name for the first clade (based onPohliella laciniataEngl., Cameroon) and a synoptic treatment of its three published species is given, one of which is extinct, and two are threatened. However, a fourth, unpublished species exists. The new combinationsPohliella submersa(J.B.Hall) Cheek andPohliella amicorum(J.B. Hall) Cheek are made for the two published Ghanaian species. The recently described New World genusCipoiaC.T. Philbrick, Novelo & Irgang is revealed as being morphologically identical toPohliella, but in view of the geographical disjunction, confirmation from molecular evidence is awaited before its two species are also transferred toPohliella. The correct name for the second clade, embedded in African podostemoids, isSaxicolella(sensu stricto), now with two known species,Saxicolella nanaEngl. (type ofSaxicolella,Cameroon) andSaxicolella flabellata(G.Taylor) C. Cusset (Nigeria).
Jointly modeling prevalence, sensitivity and specificity for optimal sample allocation
Authors: Larremore Daniel B. , Fosdick Bailey K. , Zhang Sam , Grad Yonatan H.
Published: May 2020

The design and interpretation of prevalence studies rely on point estimates of the performance characteristics of the diagnostic test used. When the test characteristics are not well defined and a limited number of tests are available, such as during an outbreak of a novel pathogen, tests can be used either for the field study itself or for additional validation to reduce uncertainty in the test characteristics. Because field data and validation data are based on finite samples, inferences drawn from these data carry uncertainty. In the absence of a framework to balance those uncertainties during study design, it is unclear how best to distribute tests to improve study estimates. Here, we address this gap by introducing a joint Bayesian model to simultaneously analyze lab validation and field survey data. In many scenarios, prevalence estimates can be most improved by apportioning additional effort towards validation rather than to the field. We show that a joint model provides superior estimation of prevalence, as well as sensitivity and specificity, compared with typical analyses that model lab and field data separately.
Characterization and Functional Annotation of Uncharacterized ABC Transporter ATP-Binding Protein Rv0986 ofMycobacterium tuberculosis(Strain ATCC 25618 / H37Rv)
Authors: Mohammad Saikat Abu Saim
Published: May 2020

The most significant ancient infectious disease tuberculosis is causes by a human pathogen,Mycobacterium tuberculosis(MTB). Amazingly, tuberculosis (TB) has become one of the major causes of human death worldwide. The protein Rv0986 is associated with the ATP-binding cassette domain of the transporters involved in the export of lipoprotein and macrolide, and cell division protein, therefore, related to mycobacterial infection. But the protein Rv0986 is not yet explored. As a result, identification, characterization, and functional annotation of uncharacterized protein Rv0986 were predicted where the structure modeling was generated by using Modeller, Phyre2, and Swiss Model with the structural quality assessment by Ramachandran Plot (PROCHECK), Verify 3d, and Swiss-Model Interactive Workplace as well. Z-scores obtained from Prosa-web were also applied for overall 3D model quality. This in-silico method will uncover the significance of undiscovered uncharacterized protein Rv0986 present in MTB, and indeed it can accelerate the way to enrich our knowledge in the pathogenesis and drug-targeting opportunity against infection by MTB.
Canagliflozin Extends Lifespan in Genetically Heterogeneous Male But Not Female Mice
Authors: Miller Richard A. , Harrison David E. , Allison David B. , Bogue Molly , Diaz Vivian , Fernandez Elizabeth , Galecki Andrzej , Garvey W. Timothy , Kumar Navasuja , Javors Martin A. , Ladiges Warren C. , Macchiarini Francesca , Nelson James , Reifsnyder Peter , Rosenthal Nadia A. , Salmon Adam B. , Smith Daniel L. , Snyder Jessica M. , Lombard David B. , Strong Randy
Published: May 2020

Canagliflozin (Cana) is an inhibitor of the sodium glucose transporter 2 (SGLT2), and is thought to act by blocking renal reuptake and intestinal absorption of glucose. Cana is FDA-approved for treatment of diabetes, and affords protection from cardiovascular and kidney diseases. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing 180 ppm Cana at 7 months of age until their death. Cana extended median survival of male mice by 14%, with p < 0.001 by log-rank test. Cana also increased by 9% the age for 90th percentile survival (p < 0.001 by Wang/Allison test), with parallel effects seen at each of three test sites. Cana did not alter the distribution of inferred cause of death, nor of incidental pathology findings at end-of-life necropsies. No benefits were seen in female mice. The lifespan benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e. slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.
Experimental evidence of memory-based foraging decisions in a large wild mammal
Authors: Ranc Nathan , Moorcroft Paul R. , Ossi Federico , Cagnacci Francesca
Published: May 2020

Many animals restrict their movements to a characteristic home range. This pattern of constrained space-use is thought to result from the foraging benefits of memorizing the locations and quality of heterogeneously distributed resources. However, due to the confounding effects of sensory perception, the role of memory in home range movement behavior lacks unequivocal evidence in the wild. Here, we analyze the foraging decisions of a large mammal during a field resource manipulation experiment designed to disentangle the effects of memory and perception. Using a cognitive movement model, we demonstrate that roe deer (Capreolus capreolus) rely on memory, not perception, to track the spatio-temporal dynamics of resources within their home range. Our findings show a memory-based spatial transition model parametrized with experimental data can successfully be used to quantify cognitive processes and to predict how animals respond to resource heterogeneity in space and time.
Direct digital sensing of protein biomarkers in solution
Authors: Krainer Georg , Saar Kadi L. , Arter William E. , Welsh Timothy J. , Czekalska Magdalena A. , Jacquat Raphaël P.B. , Peter Quentin , Traberg Walther C. , Pujari Arvind , Jayaram Akhila K. , Challa Pavankumar , Taylor Christopher G. , van der Linden Lize-Mari , Franzmann Titus , Owens Roisin M. , Alberti Simon , Klenerman David , Knowles Tuomas P.J.
Published: May 2020

The detection of proteins is of central importance to biomolecular analysis and diagnostics, yet fundamental limitations due to the surface-based nature of most sensing approaches persist, and limited improvements have been designed to integrate multimodal information beyond concentration measurements. Here we present a single-molecule microfluidic sensing platform for digital protein biomarker detection in solution, termed digital immunosensor assay (DigitISA). DigitISA is based on microchip electrophoretic separation combined with single-molecule detection and enables absolute number–concentrations quantification of proteins in a single, solution-phase step. Applying DigitISA to a range of targets including amyloid aggregates, exosomes, and biomolecular condensates, we demonstrate that the assay provides information beyond stoichiometric interactions, and enables characterization of immunochemistry, binding affinity, and protein biomarker abundance. Together, DigitISA constitutes a new experimental paradigm for the digital sensing of protein biomarkers, and enables analyses of targets that would otherwise be hard or impossible to address by conventional immuno-sensing techniques.
Endothelial CXCL12 regulates neovascularization during tissue repair and tumor progression
Authors: Maan Zeshaan N. , Hu Michael S. , Rennert Robert , Barrera Janos A. , Duscher Dominik , Januszyk Michael , Whittam Alexander , Padmanabhan Jagannath , Vial Nicholas , Ho Natalie , Fischer Lauren H. , Riegler Johannes , Wu Joseph C. , Longaker Michael T. , Gurtner Geoffrey C.
Published: May 2020

CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1 [SDF-1]), primarily known for its role in embryogenesis and hematopoiesis, has also been implicated in tumor biology and neovascularization. However, its specific role and mechanism of action remain poorly understood. We previously demonstrated that CXCL12 expression is Hypoxia-Inducible Factor (HIF)-1 responsive. Here we use a conditional CXCL12 knockout mouse to show that endothelial-specific deletion of CXCL12 (eKO) does not affect embryogenesis, but reduces the survival of ischemic tissue, altering tissue repair and tumor progression. Loss of vascular endothelial CXCL12 disrupts endothelial – fibroblast crosstalk necessary for stromal growth and vascularization. Single-cell gene expression analysis in combination with a parabiosis model reveals a specific population of non-inflammatory circulating cells, defined by genes regulating neovascularization, which is recruited by endothelial CXCL12. These findings indicate an essential role for endothelial CXCL12 expression during the adult neovascular response in tissue injury and tumor progression.