bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing self-reported medication adherence measures with hair antiretroviral concentration among people living with HIV in Guangxi, China
Authors: Zhang Quan , Li Xiaoming , Qiao Shan , Shen Zhiyong , Zhou Yuejiao
Published: March 2020

Background

Antiretroviral adherence is essential to HIV treatment efficacy. Various self-reported measures are commonly used for assessing antiretroviral adherence. Limited data are available regarding the validity of those self-reported measures in comparison with long-term objective biomarkers of adherence measures such as hair measures.

Methods

Self-reported adherence (frequency, percentage, and visual analog scale [VAS]) and hair tenofovir concentration were evaluated at a single time point from 268 people living with HIV in China. The responses to each of three self-reported measures were converted into percentage and then dichotomized as “optimal” (100%) vs. “suboptimal” (less than 100%) adherence. Two composite adherence scores (CAS) were created from the three self-reported measures: (1) an overall adherence was the average percentage of the three self-reported measures; (2) responses were termed optimal adherence if participants reporting optimal adherence in all three self-reported measures, while were termed suboptimal adherence. Hair tenofovir concentration was also dichotomized as “optimal” (above the limit of quantitation, 36 pg/mg) vs. “suboptimal” adherence (blow 36 pg/mg). Spearman correlation, kappa statistics, and logistic regression analysis were used to calculate the correlations, agreements, and predictions of self-reported measures with hair measure, respectively.

Results

Overall adherence, but any of the three self-reported adherence, was correlated with hair tenofovir concentration (r = 0.13, p < 0.05). Self-reported optimal adherence in VAS and CAS measures were agreed with and predicted optimal adherence assessed by hair measure (Kappa = 0.107, adjusted OR = 1.88, 95% CI 1.03–3.45; Kappa = 0.109, adjusted OR = 1.80, 95% CI 1.02–3.18; all p < 0.05, respectively).

Conclusion

VAS may be a good individual self-reported measure for antiretroviral adherence, and CAS may be a good composite self-reported measure for antiretroviral adherence.
Optimal radiotherapy for patients with internal mammary lymph node metastasis from breast cancer
Authors: Yang Kyungmi , Kim Haeyoung , Choi Doo Ho , Park Won , Noh Jae Myoung , Cho Won Kyung
Published: March 2020

Background

This study aimed to determine the optimal radiotherapy (RT) regimen for patients with clinical metastasis to the internal mammary lymph node (cIMN+) from breast cancer.

Methods

We retrospectively reviewed the medical records of 84 patients with cIMN+ breast cancer treated with curative surgery, taxane-based chemotherapy, and postoperative RT between January 2009 and December 2014. Postoperative RT was administered to the whole breast or chest wall using 50 Gy in 2 Gy fractions. Boost RT to the internal mammary lymph node (IMN) was administered at the physician’s discretion. We categorized patients into two groups according to the IMN dose as follows: low-dose IMN RT (50.0–63.5 Gy) and high-dose IMN RT (63.6–70.4 Gy).

Results

After a median follow-up of 58 months (range, 12–111 months), IMN recurrence was observed in 2 patients (2.4%), and all IMN recurrences developed simultaneously with distant metastases. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 89.1, 72.0, and 81.2%, respectively. The triple-negative subtype, IMN size ≥1.0 cm, old age, and low-dose IMN were significantly associated with poor DFS. Among the patients with IMN size ≥1.0 cm, the 5-year DFS was significantly higher in those treated with high-dose IMN RT than in those treated with low-dose IMN RT (69.3% vs. 33.3%, p = 0.019).

Conclusions

IMN RT without IMN dissection resulted in favorable outcomes in cIMN+ breast cancer. For patients with a large IMN, a higher IMN radiation dose might be needed for disease control.
NanoVar: accurate characterization of patients’ genomic structural variants using low-depth nanopore sequencing
Authors: Tham Cheng Yong , Tirado-Magallanes Roberto , Goh Yufen , Fullwood Melissa J. , Koh Bryan T.H. , Wang Wilson , Ng Chin Hin , Chng Wee Joo , Thiery Alexandre , Tenen Daniel G. , Benoukraf Touati
Published: March 2020

The recent advent of third-generation sequencing technologies brings promise for better characterization of genomic structural variants by virtue of having longer reads. However, long-read applications are still constrained by their high sequencing error rates and low sequencing throughput. Here, we present NanoVar, an optimized structural variant caller utilizing low-depth (8X) whole-genome sequencing data generated by Oxford Nanopore Technologies. NanoVar exhibits higher structural variant calling accuracy when benchmarked against current tools using low-depth simulated datasets. In patient samples, we successfully validate structural variants characterized by NanoVar and uncover normal alternative sequences or alleles which are present in healthy individuals.
gscreend: modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection
Authors: Imkeller Katharina , Ambrosi Giulia , Boutros Michael , Huber Wolfgang
Published: March 2020

Pooled CRISPR screens are a powerful tool to probe genotype-phenotype relationships at genome-wide scale. However, criteria for optimal design are missing, and it remains unclear how experimental parameters affect results. Here, we report that random decreases in gRNA abundance are more likely than increases due to bottle-neck effects during the cell proliferation phase. Failure to consider this asymmetry leads to loss of detection power. We provide a new statistical test that addresses this problem and improves hit detection at reduced experiment size. The method is implemented in the R package gscreend, which is available at http://bioconductor.org/packages/gscreend.
Revised scored Sensory Perception Quotient reveals sensory hypersensitivity in women with autism
Authors: Taylor Emily , Holt Rosemary , Tavassoli Teresa , Ashwin Chris , Baron-Cohen Simon
Published: March 2020

Background

Previous research using the Sensory Perception Quotient (SPQ) has reported greater sensory hypersensitivity in people with autism spectrum condition (ASC) compared to controls, consistent with other research. However, current scoring of the SPQ does not differentiate between hyper and hyposensitivity, making it uncertain whether individuals with ASC might also show differences in hyposensitivity. Furthermore, no research to date has focused on sensory differences in females, and whether differences in sensory sensitivity extend to the broader autism phenotype (BAP). The present study aimed to fill these gaps.

Methods

The present study developed and validated a Revised Scoring of the Sensory Perception Quotient (SPQ-RS) in order to investigate self-reported hypersensitivity and hyposensitivity in three groups of adults: a female ASC group (n = 152), mothers of children with ASC (BAP mothers group; n = 103), and a control mothers group (n = 74). All participants completed the SPQ as a self-report measure of sensory processing and the Autism-Spectrum Quotient (AQ) as a measure of the degree of autism traits.

Results

The female ASC group reported significantly more hypersensitivity, but not more hyposensitivity, compared to the control female and BAP mothers groups. The BAP mothers group did not differ from the control mothers group in either reported hypersensitivity (p = .365) or hyposensitivity (p = .075), suggesting atypical sensory sensitivity is not a BAP trait within females. SPQ-RS hypersensitivity scores positively correlated with autistic traits in the female ASC (r = .266) and BAP mothers groups (r = .350).

Conclusions

The present findings revealed greater sensory hypersensitivity, but not hyposensitivity, in females with ASC compared to BAP and control female groups, and that a greater degree of autism traits relates to higher hypersensitivity in ASC females. The results offer support for the enhanced perceptual functioning model using large samples of females, who are an understudied population, and demonstrate the validity of the SPQ-RS as a valuable new research tool for exploring self-reported hypersensitivity and hyposensitivity.
Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis
Authors: Chen Jia-Jin , Lee Cheng-Chia , Kuo George , Fan Pei-Chun , Lin Chan-Yu , Chang Su-Wei , Tian Ya-Chung , Chen Yung-Chang , Chang Chih-Hsiang
Published: March 2020

Background

The optimal timing of renal replacement therapy (RRT) initiation is debatable. Many articles in this field enrolled trials not based on acute kidney injury. The safety of the watchful waiting strategy has not been fully discussed, and late RRT initiation criteria vary across studies. The effect of early RRT initiation in the AKI population with high plasma neutrophil gelatinase-associated lipocalin (NGAL) has not been examined yet.

Methods

In accordance with PRISMA guidelines, the PubMed, Embase, and Cochrane databases were systemically searched for randomized controlled trials (RCTs). Trials not conducted in the AKI population were excluded. Data of study characteristics, primary outcome (all-cause mortality), and related secondary outcomes [mechanical ventilation (MV) days, length of hospital stay, RRT days, and length of ICU stay] were extracted. The outcomes were compared between early and late RRT groups by estimating the pooled odds ratio (OR) for binary outcomes and the weighted mean difference for continuous outcomes. Prospective trials were also examined and analyzed using the same method.

Results

Nine RCTs with 1938 patients were included. Early RRT did not provide a survival benefit (pooled OR, 0.88; 95% confidence interval [CI] 0.62–1.27). However, the early RRT group had significantly fewer MV days (pooled mean difference, − 3.98 days; 95% CI − 7.81 to − 0.15 days). Subgroup analysis showed that RCTs enrolling the surgical population (P = .001) and the AKI population with high plasma NGAL (P = .031) had favorable outcomes regarding RRT days in the early initiation group. Moreover, 6 of 9 RCTs were selected for examining the safety of the watchful waiting strategy, and no significant differences were found in primary and secondary outcomes between the early and late RRT groups.

Conclusions

Overall, early RRT initiation did not provide a survival benefit, but a possible benefit of fewer MV days was detected. Early RRT might also provide the benefit of shorter MV or RRT support in the surgical population and in AKI patients with high plasma NGAL. Depending on the conventional indication for RRT initiation, the watchful waiting strategy is safe on the basis of all primary and secondary outcomes.
Detection of dynamic location primary user emulation on mobile cognitive radio networks using USRP
Authors: Cadena Muñoz Ernesto , Rodriguez-Colina Enrique , Pedraza Luis Fernando , Paez Ingrid Patricia
Published: March 2020

The study and the detection of possible network attacks are essential for wireless networks, in particular for mobile cognitive radio networks due to its characteristics such as the dynamic spectrum allocation and constant frequency hopping. The primary user emulation attack is one of the most significant attacks in cognitive radio, because it hazards the complete cognitive cycle. The techniques used for the detection of primary user emulation found in the literature are based on a fixed attacker location. However, in a mobile environment, the attacker usually has dynamic locations and this compromises the current applied security techniques and generates inefficient attack detection. Therefore, our work proposes a novel technique using cross-layer design for the detection of primary user emulation with mobility. This attack detection technique was tested with experiments using software-defined radio equipment and mobile phones at indoor scenarios with dynamic locations and with a mobile phone base station built up also with software-defined radio. The obtained results show that the combination of the three utilized techniques, energy detection, motion estimation, and application information analysis, are able to optimize the detection with around 100% of effectiveness for the primary user emulation attack with dynamic location. The proposed technique shows that the energy detection time is around 100 ms and for the processing time of the information analysis in the mobile phone is about 30 s. This result shows a practical and effective approach to detect primary emulation attacks. The proposed technique, to the best of the authors’ knowledge, has not been presented before in the literature with experiments neither with mobility conditions of the attacker as presented in our proposed work.
Pricing cloud IaaS computing services
Authors: Dimitri Nicola
Published: March 2020

The economics of cloud computing has recently attracted increasing attention. In particular, a topic which is still under debate is how prices charged to customers for cloud resources are formed, since alternative pricing rules could be considered. Based on three pricing schemes inspired by those used by Amazon EC2, the main global cloud service provider, in the paper we address two main issues. First we present a methodology for the relevant parameters of the pricing rules to be determined in an optimal way, that is to maximise the provider’s revenue. Moreover, we discuss reasons for co-existence of three pricing rules, rather than fewer, to access the cloud. Our findings suggest that this may be due to a larger coverage of the potential demand, since customers applying for cloud services vary in their willingness to pay for the job, the time length of the service, the computational power requested etc. Furthermore, the pricing rule in the so-called, spot market, can provide the platform with useful information on the customers willingness to pay for cloud services. This is because in the spot market users offer a price for service, but pay less than that if their request is satisfied.
A rare case of atropine-resistant bradycardia following sugammadex administration
Authors: Yoshida Takayuki , Sumi Chisato , Uba Takeo , Miyata Haruka , Umegaki Takeshi , Kamibayashi Takahiko
Published: March 2020

Background

Profound bradycardia caused by sugammadex has been reported, although its mechanism is unclear. Herein, we suggest a possible culprit for this phenomenon.

Case presentation

A 50-year-old woman without comorbidity except mild obesity underwent a transabdominal hysterectomy and right salpingo-oophorectomy. After surgery, sugammadex 200 mg was intravenously administered. Approximately 4 min later, her heart rate decreased to 36 bpm accompanied by hypotension (41/20 mmHg) and ST depression in limb lead electrocardiogram (ECG). Atropine 0.5 mg was injected intravenously without improving the hemodynamics. Intravenous adrenaline 0.5 mg was added despite the lack of signs suggesting allergic reactions. Her heart rate and blood pressure quickly recovered and remained stable thereafter, although 12-lead ECG taken 1 h later still showed ST depression.

Conclusions

In this case, the significant bradycardia appeared attributable to coronary vasospasm (Kounis syndrome) induced by sugammadex, considering the ECG findings and high incidence of anaphylaxis due to sugammadex.
First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model
Authors: Chen Xinguang , Yu Bin
Published: March 2020

Background

Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively.

Methods

In this study, we used a second derivative model to characterize the coronavirus epidemic in China with cumulatively diagnosed cases during the first 2 months. The analysis was further enhanced by an exponential model with a close-population assumption. This model was built with the data and used to assess the detection rate during the study period, considering the differences between the true infections, detectable and detected cases.

Results

Results from the second derivative modeling suggest the coronavirus epidemic as nonlinear and chaotic in nature. Although it emerged gradually, the epidemic was highly responsive to massive interventions initiated on January 21, 2020, as indicated by results from both second derivative and exponential modeling analyses. The epidemic started to decelerate immediately after the massive actions. The results derived from our analysis signaled the decline of the epidemic 14 days before it eventually occurred on February 4, 2020. Study findings further signaled an accelerated decline in the epidemic starting in 14 days on February 18, 2020.

Conclusions

The coronavirus epidemic appeared to be nonlinear and chaotic, and was responsive to effective interventions. The methods used in this study can be applied in surveillance to inform and encourage the general public, public health professionals, clinicians and decision-makers to take coordinative and collaborative efforts to control the epidemic.
Preliminary validation of the insomnia severity index in Danish outpatients with a medical condition
Authors: Dieperink Karin Brochstedt , Elnegaard Caroline Matilde , Winther Bodil , Lohman Anna , Zerlang Ida , Möller Sören , Zangger Graziella
Published: March 2020

Purpose

Insomnia is a frequent sleeping disorder in the general and clinical population. With an increasing proportion of health care services being provided as outpatient care, a short, valid and reliable tool is needed to identify insomnia in medical patients under outpatient care in Denmark. The Insomnia Severity Index (ISI) could be the needed tool if found valid and reliable. Hence, the aim of this study is to evaluate elements of the psychometric properties of the Danish version of ISI (ISI-DK).

Methods

Outpatients from three hospital wards and one rehabilitation center were asked to complete the ISI-DK twice, 2 weeks apart. Internal consistency, discriminative validity, test-retest reliability, and measurement error was assessed.

Results

The ISI-DK was completed by 249 (79.0%) participants the first time, and 163 (65.5%) the second time. Respondents had a mean age of 58.2 years (SD 13.5) and 63.5% were women. All but one of the discriminative hypotheses was accepted. Internal consistency was high in the global scale at 0.90 and good with Cronbach’s alpha at 0.75–0.88 in the proposed subscales. The test-retest reliability was good, as the intraclass correlation was 0.90 (95% CI: 0.87; 0.93). Ceiling and floor effects were low < 4.4%. Standard error of measurement was 2.52 and smallest detectable change 6.99.

Conclusion

This preliminary assessment showed encouraging results supporting the ISI-DK as a valid and reliable tool for screening insomnia severity in Danish outpatients with a medical condition, but further assessments are needed.
The relationship of cannabis decriminalization in Colorado and cannabis use in individuals with alcohol use disorders
Authors: Hua Jeremy T. , Afshar Majid , Clark Brendan J. , Kovacs Elizabeth J. , Burnham Ellen L.
Published: March 2020

Objective

Over the past decade, cannabis use has become increasingly popular in states that include Colorado. During this time, alcohol use disorders (AUDs) and alcohol-related medical conditions have also been consistently recognized as public health problems with increasing prevalence in the state. Despite the widespread use of cannabis in Colorado, the epidemiology of cannabis use among those with AUDs has been poorly described. Therefore, we sought to examine cannabis use among individuals with likely AUDs and individuals with low-risk alcohol use during a time of major Colorado legislative changes before and after legalization of recreational cannabis in 2012.

Methods

This study was a secondary data analysis conducted with information from 303 participants (80% male) in the Denver, CO metropolitan enrolled between August 2007 and April 2016 for studies related to alcohol and lung health. Of these participants, 188 (62%) were completing inpatient alcohol detoxification with likely AUDs. All participants completed the Alcohol Use Disorder Identification Test (AUDIT) to establish their likelihood of an AUD, and all had information on current cannabis use assessed by questionnaire and urine toxicology testing.

Results

Individuals with likely AUDs more commonly used cannabis compared to control participants (42% vs 27%, p = 0.007). In multiple logistic regression analyses, participant type (likely AUD versus control), tobacco smoking, and age were significantly associated with cannabis smoking; however, the year of participant enrollment was not. Adjusted odds for cannabis use among participants with likely AUDs were 2.97 (1.51–5.82), p = 0.002, while odds for cannabis use among tobacco smokers were 3.67 (1.94–6.93), p < 0.0001. Among control participants, tobacco smoking increased odds of cannabis use seven-fold.

Conclusions

Our findings highlight the exceptionally high odds of cannabis use among individuals with likely AUDs undergoing alcohol detoxification at a Colorado treatment facility before and after legalization of recreational cannabis. Targeted investigations into the medical and psychiatric consequences of combined alcohol and cannabis use are urgently needed to define its health impact in these vulnerable individuals.
Orbit determination and time synchronization for BDS-3 satellites with raw inter-satellite link ranging observations
Authors: Ruan Rengui , Jia Xiaolin , Feng Laiping , Zhu Jun , Huyan Zongbo , Li Jie , Wei Ziqing
Published: March 2020

To provide competitive global positioning and timing services under the condition that monitoring stations are confined to Chinese territory, inter-satellite link (ISL) technology is used by the third-generation BeiDou Navigation Satellite System (BDS-3). The ISL, together with the dual one-way links between satellites and anchor stations, may enable autonomous navigation for BDS-3. In this paper, we propose a general observation model for orbit determination (OD) and time synchronization (TS) directly using non-simultaneous observations, such as raw ISL pseudoranges. With the proposed model, satellite orbits, clocks, and hardware delay biases of ISL equipment can be determined simultaneously by jointly processing inter-satellite one-way pseudorange data and observation data from ground monitoring stations. Moreover, autonomous OD and TS are also achievable with one-way pseudorange data from anchor stations and satellites. Data from eight BDS-3 satellites, two anchor stations, and seven monitoring stations located in China were collected to validate the proposed method. It is shown that by jointly processing data from the ISL and seven monitoring stations, the RMS of overlap orbit differences in radial direction is 0.019 m, the overlap clock difference (95%) is 0.185 ns, and the stability of the estimated hardware delay biases for each satellite is greater than 0.5 ns. Compared with the results obtained with the seven stations, the improvements of orbits in radial direction and clocks are 95.7% and 90.5%, respectively. When the hardware delay biases are fixed to predetermined values, the accuracies of orbits and clocks are further improved. By jointly processing pseudoranges from the satellites and the two anchor stations, the RMS of overlap orbit differences is 0.017 m in the radial direction, and the overlap clock difference (95%) is 0.037 ns. It has also been demonstrated that under the condition of one-way ranging links, the accuracies of orbits and clocks obtained by the above two modes are still significantly better than those obtained by using the data from the monitoring stations alone.
Androgens During Infancy, Childhood, and Adolescence: Physiology and Use in Clinical Practice
Authors: Mason Kelly A , Schoelwer Melissa J , Rogol Alan D
Published: March 2020

We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty.

Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement.

Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.
Planarian cell number depends on blitzschnell, a novel gene family that balances cell proliferation and cell death
Authors: Pascual-Carreras Eudald , Marin-Barba Marta , Herrera-Úbeda Carlos , Font-Martín Daniel , Eckelt Kay , de Sousa Nidia , García-Fernández Jordi , Saló Emili , Adell Teresa
Published: March 2020

Control of cell number is crucial to define body size during animal development and to restrict tumoral transformation. The cell number is determined by the balance between cell proliferation and cell death. Although many genes are known to regulate those processes, the molecular mechanisms underlying the relationship between cell number and body size remain poorly understood. This relationship can be better understood by studying planarians, flatworms that continuously change their body size according to nutrient availability. We identified a novel gene family, blitzschnell (bls), that consists of de novo and taxonomically restricted genes that control cell proliferation:cell death ratio. Their silencing promotes faster regeneration and increases cell number during homeostasis. Importantly, this increase in cell number leads to an increase in body size only in a nutrient-rich environment; in starved planarians, silencing results in a decrease in cell size and cell accumulation that ultimately produces overgrowths. bls expression is downregulated after feeding and is related to activity of the insulin/Akt/mTOR network, suggesting that the bls family evolved in planarians as an additional mechanism for restricting cell number in nutrient-fluctuating environments.
Control of tissue morphogenesis by the HOX gene Ultrabithorax
Authors: Diaz-de-la-Loza Maria-del-Carmen , Loker Ryan , Mann Richard S. , Thompson Barry J.
Published: March 2020

Mutations in the Ultrabithorax (Ubx) gene cause homeotic transformation of the normally two-winged Drosophila into a four-winged mutant fly. Ubx encodes a HOX family transcription factor that specifies segment identity, including transformation of the second set of wings into rudimentary halteres. Ubx is known to control the expression of many genes that regulate tissue growth and patterning, but how it regulates tissue morphogenesis to reshape the wing into a haltere is still unclear. Here, we show that Ubx acts by repressing the expression of two genes in the haltere, Stubble and Notopleural, both of which encode transmembrane proteases that remodel the apical extracellular matrix to promote wing morphogenesis. In addition, Ubx induces expression of the Tissue inhibitor of metalloproteases in the haltere, which prevents the basal extracellular matrix remodelling necessary for wing morphogenesis. Our results provide a long-awaited explanation for how Ubx controls morphogenetic transformation.
Leptin and fractalkine: Novel subcutaneous cytokines in burn injury
Authors: Friston Dominic , Junttila Sini , Lemes Julia Borges Paes , Laycock Helen , Torres-Perez Jose Vicente , Want Elizabeth , Gyenesei Attila , Nagy Istvan
Published: March 2020

Burn injury is a pathology underpinned by progressive and aberrant inflammation. It is a major clinical challenge to survival and quality of life. While burn injury's complex local and disseminating pathological processes ultimately stem from local tissue damage, to date relatively few studies have attempted to characterise the local inflammatory mediator profile. Here, cytokine content and associated transcriptional changes were measured in rat skin for three hours immediately following induction of a scald-type (60°C, 2 minutes) burn injury model. Leptin (p=0.0002) and fractalkine (p=0.0478) concentrations were significantly elevated post-burn above pre-burn and control site values, coinciding with the development of burn site oedema and differential expression of leptin mRNA (p=0.0004). Further, gene sequencing enrichment analysis indicated cytokine-cytokine receptor interaction (p=1.45x10−6). Subsequent behavioural studies demonstrated that, following subcutaneous injection into the dorsum of the paw, both leptin and fractalkine induced mechanical allodynia, heat hyperalgesia and the recruitment of macrophages. This is the first report of leptin's elevation specifically at the burn site and the first report of fractalkine's elevation in any tissue post-burn which, together with the functional findings, calls for exploration of the influence of these cytokines on pain, inflammation and burn wound progression. Additionally targeting these signalling molecules represents a therapeutic potential as early formative mediators of these pathological processes.
“If you please… draw me a cell”. Insights from immune cells
Authors: Moreau Hélène D. , Lennon-Duménil Ana-Maria , Pierobon Paolo
Published: March 2020

Studies in recent years have shed light on the particular features of cytoskeleton dynamics in immune cells, challenging the classical picture drawn from typical adherent cell lines. New mechanisms linking the dynamics of the membrane–cytoskeleton interface to the mechanical properties of immune cells have been uncovered and shown to be essential for immune surveillance functions. In this Essay, we discuss these features, and propose immune cells as a new playground for cell biologists who try to understand how cells adapt to different microenvironments to fulfil their functions efficiently.
Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2
Authors: Shartau R. B. , Baker D. W. , Harter T. S. , Aboagye D. L. , Allen P. J. , Val A. L. , Crossley D. A. , Kohl Z. F. , Hedrick M. S. , Damsgaard C. , Brauner C. J.
Published: March 2020

Acute (< 96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intra- and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at PCO2 tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver, and white muscle pHi during acute exposure to>4 kPa PCO2 (preferential pHi regulation) before pHe compensation was observed. Here we test the hypothesis that preferential pHi regulation is a wide spread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning 6 orders, 8 families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.
The ghost of temperature past: interactive effects of previous and current thermal conditions on gene expression in Manduca sexta
Authors: Alston Meggan A. , Lee Jeeyun , Moore M. Elizabeth , Kingsolver Joel G. , Willett Christopher S.
Published: March 2020

High temperatures can negatively impact performance and survival of organisms, particularly ectotherms. While an organism's response to high temperature stress clearly depends on current thermal conditions, its response may also be affected by the temporal pattern and duration of past temperature exposures. We used RNA sequencing of Manduca sexta larvae fat body tissue to evaluate how diurnal temperature fluctuations during development affected gene expression both independently and in conjunction with subsequent heat stress. Additionally, we compared gene expression between two M. sexta populations, a lab colony and a genetically related field population that have been separated for>300 generations and differ in their thermal sensitivities. Lab-adapted larvae were predicted to show increased expression responses to both single and repeated thermal stress, whereas recurrent exposure could decrease later stress responses for field individuals. We found large differences in overall gene expression patterns between the two populations across all treatments, as well as population-specific transcriptomic responses to temperature; most differentially expressed genes were upregulated in the field compared with lab larvae. Developmental temperature fluctuations alone had minimal effects on long-term gene expression patterns, with the exception of a somewhat elevated stress response in the lab population. Fluctuating rearing conditions did alter gene expression during exposure to later heat stress, but this effect depended on both the population and the particular temperature conditions. This study contributes to increased knowledge of molecular mechanisms underlying physiological responses of organisms to temperature fluctuations, which is needed for the development of more accurate thermal performance models.
Transitions between the steps of forward and reverse splicing of group IIC introns
Authors: Smathers Claire M. , Robart Aaron R.
Published: March 2020

Group II introns are mobile genetic elements that perform both self-splicing and intron mobility reactions. These ribozymes are comprised of a catalytic RNA core that binds to an intron-encoded protein (IEP) to form a ribonucleoprotein (RNP) complex. Splicing proceeds through two competing reactions: hydrolysis or branching. Group IIC intron ribozymes have a minimal RNA architecture, and splice almost exclusively through hydrolysis in ribozyme reactions. Addition of the IEP allows the splicing reaction to form branched lariat RNPs capable of intron mobility. Here we examine ribozyme splicing, IEP-dependent splicing, and mobility reactions of a group IIC intron from the thermophilic bacterium Thermoanerobacter italicus (Ta.it.I1). We show that Ta.it.I1 is highly active for ribozyme activity, forming linear hydrolytic intron products. Addition of purified IEP switches activity to the canonical lariat forming splicing reaction. We demonstrate that the Ta.it.I1 group IIC intron coordinates the progression of the forward splicing reaction through a π–π′ interaction between intron domains II and VI. We further show that branched splicing is supported in the absence of the IEP when the π–π′ interaction is mutated. We also investigated the regulation of the two steps of reverse splicing during intron mobility into DNA substrates. Using a fluorescent mobility assay that simultaneously visualizes all steps of intron integration into DNA, we show that completion of reverse splicing is tightly coupled to cDNA synthesis regardless of mutation of the π–π′ interaction.
Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
Authors: Abuga Kelvin M. , Rockett Kirk A. , Muriuki John Muthii , Koch Oliver , Nairz Manfred , Sirugo Giorgio , Bejon Philip , Kwiatkowski Dominic P. , Prentice Andrew M. , Atkinson Sarah H.
Published: March 2020

Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season.

Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season.

Results: We identified five IFNG haplotype-tagging SNPs (IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia.

Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.
Two-Sided Price Discrimination by Media Platforms
Authors: Lin Song
Published: March 2020

A theory of two-sided markets where media platforms can price discriminate among both advertisers and consumers.
The Implementation of Visual, Auditory, Kinesthetic (VAK) Learning Model in Improving Students’ Achievement in Writing Descriptive Texts
Authors: Ramadian Oki Dwi , Cahyono Bambang Yudi , Suryati Nunung
Published: March 2020

The English teaching in a public vocational school of Akomodasi Perhotelan (SMK AP) so far has shown unsatisfactory result. Based on the preliminary study it was found that the writing skill of the tent graders of SMK AP 3 was low. This classroom action research was aimed at improving the students’ writing skill of descriptive text by implementing VAK learning model. In this study 26 students were selected as subjects. This study was completed through one cycle using VAK learning model. The findings revealed that students’ writing scores increased after the researcher implemented the VAK learning model. The average score of the students improved 38.18 points into 81.49 compared to their scores in the preliminary study which was 43.31. Out of 26 students, there were only 7 (26.92%) who failed to achieve the minimum mastery criteria (KKM). It can be inferred from the findings that the VAK learning model succeeded in helping the students to improve their writing’ achievement. The result of this study implies that VAK learning model can be an alternative to improve the students’ writing skill.
The importance of a patient examination policy
Authors: Atkins Ben
Published: March 2020

Dentist Ben Atkins considers how a well-mapped patient journey – from meet and greet to follow-up appointment – can benefit everyone, including the dental nurse
We need a connection
Authors: Allingham Sue
Published: March 2020

The Government's inability to match policies with early years practice is potentially damaging to children's outcomes. Its inconsistent approach is also bad for the workforce which needs to be invested in and taken more seriously.
Up for discussion
Authors: Martland Rebecca
Published: March 2020

Under the new Ofsted inspection framework practitioners are expected to talk meaningfully about how their curriculum has achieved impact for children. But where is the best place to start?
Big school, big step
Authors: Rawstrone Annette
Published: March 2020

It is never too early to start planning for your child's move to school. In the first of a new series, Annette Rawstrone outlines how to get a feel for what your local primaries offer and which ones would be a good fit for your child.
Walking capacity in boys with Down's syndrome in Saudi Arabia
Authors: Allam Hatem H , Al-Walah Mosfer A , Elsayyad Lamiaa K
Published: March 2020

Background/Aims

Children with Down's syndrome are often considered to be sedentary and less likely to engage in the recommended levels of physical activity. The aim of this study was to compare the walking capacity of male children with Down's syndrome with a group of typically healthy age-matched children in Saudi Arabia.

Methods

A total of 78 male children aged from 8 to 12 years participated in the study. They were divided into two groups. The first group comprised 37 male children with Down's syndrome, recruited from the Down's Syndrome Charitable Association and Al-Nahda Schools. The second group comprised 41 male children with typical development, who were recruited from regular schools in the same region. Walking capacity was measured with the 6-Minute Walk Test.

Results

The children with Down's syndrome had significantly reduced 6-Minute Walk Distance scores than children with typical development.

Conclusions

There is a need to establish good strategies, programmes and early interventions designed to promote physical activity levels and improve the quality of life for people with Down's syndrome.
The Role of Pedagogical Practices in Novice Teachers' Work
Authors: Sasson Irit , Kalir David , Malkinson Noam
Published: March 2020

Achieving educational goals is based on the skills and competence of teachers; therefore, professional development of teachers is important to policy and decision-makers. Worldwide, the percentage of teachers who leave the profession within their first years of teaching is high therefore, professional support is essential to ease on their integration. Previous research indicates a positive and significant correlation between teachers' self-efficacy and their attitudes toward the teaching profession. Our study included three hypotheses: 1) teachers' pedagogical applications serve as mediators for the relationship between teachers' self-efficacy and their attitudes toward the profession; 2) participating in a professional development school (PDS) training program interacts with teachers' self-efficacy in predicting their attitudes toward the profession; and, 3) participation in a PDS training program will positively affect the two variables. A close and open-ended questionnaire was replied by 300 novice teachers, some of whom participated in the PDS program and others who did not. Findings indicate that the relationship between teachers' sense of self-efficacy and their attitudes towards the teaching profession was partially mediated by: applying constructivist pedagogical practices; matching to differences between learners; collaboration between fellow teachers; accountability; planning and teaching management; and academy-community relationships. Participation in a PDS program was not found as a moderator variable for this relationship, but novice teachers who participated in this program had a significant higher sense of self-efficacy and more positive attitudes towards the teaching profession. Findings are important for designing novice teacher training programs with an emphasis on the implementation of specific pedagogical practices.
Development and Performance Evaluation of a Pneumatic Solid Set Canopy Delivery System for High-Density Apple Orchards
Authors: Sinha Rajeev , Ranjan Rakesh , Bahlol Haitham Y. , Khot Lav R. , Hoheisel Gwen-Alyn , Grieshop Matthew J.
Published: March 2020

Abstract. Solid set canopy delivery systems (SSCDS) are fixed spray systems that consist of a network of permanently plumbed emitters in high-density tree-fruit orchard canopies. Most of the previously configured SSCDS worked on the principle of hydraulic spray delivery (HSD), which may not be suitable for large-scale installation due to the drop in operating pressure caused by frictional losses in the spray lines. Therefore, a pneumatic spray delivery (PSD) based SSCDS was developed in this study for potentially achieving uniform spray application at all locations along the spray lines. A reservoir subsystem was developed to contain a precisely metered amount of spray liquid. Once filled, compressed air pushed through the spray lines can pressurize the reservoir to help deliver uniform spray into the canopy through emitters. In this study, HSD and PSD systems of 91 m set length were installed in a high-density apple orchard. Both systems were evaluated for variations in operating pressure, spray output, and spray performance. Spray performance was quantified during the middle (BBCH 75) and late (BBCH 85) apple (cv. WA-38 on tall spindle architecture) crop growth stages. Deposition and coverage in three canopy zones and on both sides of leaves were evaluated using Mylar cards and water-sensitive papers (WSP) as samplers, respectively. The Mylar cards and WSP were respectively analyzed using fluorometry and image processing. Statistically similar operating pressure (p > 0.05) was observed for the HSD and PSD systems at 3 m (286.1 and 284.1 kPa, respectively), 33 m (268.4 and 270.5 kPa), 60 m (260.6 and 268.9 kPa), and 87 m (255.3 and 257.9 kPa) from the row inlet. Despite the operating pressure drop, the PSD system had uniform spray output along the 91 m spray line. Compared to the HSD system, about 4%, 3%, 5%, and 20% higher spray output was delivered with the PSD system at 3, 33, 60, and 87 m, respectively, along the spray line. Overall, the PSD system had significantly higher mean spray deposition (p < 0.01) compared to the HSD system during the middle (521 and 382 ng cm-2, respectively) and late (631 and 409 ng cm-2, respectively) growth stages. The PSD system also had numerically higher spray deposition compared to the HSD system for all the canopy zones and on either side of leaf surfaces. Spray coverage trends were similar to deposition; however, the differences were not significant. Overall, the PSD-based SSCDS shows potential for large-scale installation, with additional refinements, for uniform spray applications in high-density apple orchards. Keywords: Hydraulic spray delivery, Pneumatic spray delivery, Solid set canopy delivery system, Spray coverage, Spray deposition.