bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and Ethnicity: Obstructive Sleep Apnea Risk Factors Poorly Represented in Sleep Apnea Screening Questionnaires
Authors: Chaudhry A , Nguyen L , Constantin E
Published: September 2022

BACKGROUND: The gold standard for the diagnosis of pediatric obstructive sleep apnea (OSA) is polysomnography, a resource-intensive tool that is not easily accessible. It has been shown thatquestionnaires cannot accurately diagnose OSA in children. However,questionnaires are often used as screening tools for OSA to help clinicians prioritize objective sleep testing in sleep laboratories. Although many tools exist to screen for OSA, there is significant variability in the elements they take into consideration.

OBJECTIVES: To identify all questionnaires that screen for OSA in children and to review and contrast items within these questionnaires.

DESIGN/METHODS: We conducted a review of the literature to identify all questionnaires for pediatric OSA. We searched PubMed (keywords: sleep disordered breathing, OSA, sleep apnea and risk factor) and the health and psychosocial instruments (HaPi) database. We also checked reference lists of all included articles. Questionnaires were included in the analysis if their primary goal was to identify or screen for pediatric OSA in children 0-18 years old. We described the questionnaires qualitatively by identifying all items within each questionnaire, including demographics, risk factors, signs, symptoms, and outcomes.

RESULTS: The search yielded 476 articles. After reviewing titles and abstracts, 130 articles were included of which 60 articles were deemed relevant for final analysis based on predetermined inclusion criteria. Forty-two questionnaires were identified. Thirty-two questionnaires containing 48 different items were included in the analysis. Items most commonly included in questionnaires were: snoring (78%), observed apnea (78%) and daytime sleepiness (75%). Other clinically relevant items, such as ethnicity (6%), and body mass index (31%), were not consistently included. Thirty-one questionnaires used quantitative scores to identify OSA. One questionnaire derived a formula to identify OSA, in which certain items (risk factors) were assigned relative weights. Moreover, most questionnaires sought to predict the diagnosis of OSA without emphasis on OSA severity.

CONCLUSION: There are currently several questionnaires that aim to screen children for OSA. However, these questionnaires rarely include known OSA risk factors such as ethnicityand obesityand are not able to screen for OSA severity.
Child and Adolescent Online Mental Health Information: Parent and Adolescent Perspectives to Inform Development of Canadian Mental Health E-Resources for Paediatrics
Authors: Jovanovic M , Monga S , Korczak D , Grewal S
Published: September 2022

BACKGROUND: Parents and adolescents are searching online for information about mental health. Google searches are frequently used, but do not always yield accurate and reliable information that is presented in a user-friendly manner. The first step toward the development of a useful online child mental health resource is to examine existing web content and understand parent and adolescent needs from online mental health material.

OBJECTIVES: The objectives of this study are two-fold (i) To conduct an environmental scan of existing online repositories of child and adolescent mental health information with respect to both parent and adolescent friendly content on three identified topic areas for the initial phase of the project (Anxiety, Eating Disorders, Suicide Prevention) (ii) To determine parent and adolescent needs from, and perspectives about, current web-based information with respect to site design, content and limitations to inform the creation of a pediatric hospital based web site with a broad range of information pertaining to child and adolescent mental health.

DESIGN/METHODS: An environmental scan was conducted to assess available online information about three identified topic areas as described above. As the project continues, the scan will be expanded to include other topic areas in child and adolescent mental health. Parallel parent needs assessment surveys were conducted. As our adolescent section was being developed, adolescents were surveyed for their feedback regarding illustrations and presentation of current content.

RESULTS: The environmental scan identified 17 hospital websites for in-depth review. Although some websites had information on diverse mental health topics, few contained comprehensive information on a broad range of topics. For example, only 9 had information about anxiety disorders. Additionally, an overall lack of adolescent specific content was noted. Parent surveys revealed significant interest in a strong stand-alone site where they could access mental health information. Parents also indicated that they would prefer separate parent and teen content areas.

CONCLUSION: Current websites providing information regarding child and adolescent mental health, while plentiful, lack sufficient scope, adolescent-friendly content, and interactivity that limit their utility for parents and families. Development of a high-quality and accessible child and adolescent mental health website requires an interdisciplinary collaboration of experts in mental health, website design, and knowledge dissemination. This study has informed the development of a new online resource, interactive elements of which will be shared as part of the oral presentation.
Validation of Hearts-Map, A Psychosocial Assessment Tool Applied to Children and Youth with Mental Health-Related Paediatric Emergency Visits
Authors: Lee A , Deevska M , Stillwell K , Black T , Meckler G , Eslami A , Park D , Doan Q
Published: September 2022

BACKGROUND: Mental health-related pediatric emergency department (PED) visits are increasing annually, and there is a need for a validated comprehensive standardized assessment tool to better manage these patients.

OBJECTIVES: The primary objective of this study was to evaluate HEARTSS-MAP, a psychosocial assessment tool, in terms of inter-rater agreement among clinicians as well as the tool’s performance in predicting needs for acute psychiatric consultation for hospitalization.

DESIGN/METHODS: The HEARTSS-MAP evaluation was done in two phases. We retrospectively reviewed 101 cases randomly sampled from a cohort of patients who sought care at the BC Children’s Hospital (BCCH) PED for mental health complaints. Narratives pertaining to each patient’s psychosocial assessment were recorded. Clinicians, including two emergency physicians, a bedside nurse, a nurse practitioner, and two psychiatrists, were blinded to the patients' outcomes, and individually applied the HEARTSS-MAP tool to the clinical narratives. The inter-rater agreement was calculated using Cohen’s kappa statistics. We then evaluated the tool’s sensitivity and specificity in predicting admission for the retrospective cohort, as well as a prospective cohort of 62 patients assessed and managed by a PED clinician using the HEARTSS-MAP.

RESULTS: There was substantial agreement between the two pediatric emergency reviewers (κ=0.7), and moderate agreement between the pedi-atric emergency physicians and the nurse practitioner (κ=0.6), and the bedside nurse (κ=0.5). Pediatric psychiatrists had fair agreement between themselves (κ=0.3), and between psychiatrists and emergency physicians (κ=0.4). Based on retrospective data, HEARTSS-MAP had a sensitivity of 91% (95%CI: 71 to 99%), and a specificity of 41% (95%CI: 30 to 53%). When applied to prospectively collected data, the sensitivity was 100% (95%CI: 75 to 100%), and specificity was 33% (95%CI: 20 to 48%).

CONCLUSION: HEARTSS-MAP, the first standardized psychosocial assessment tool to be implemented at BCCH PED, demonstrates strong inter-rater reliability between emergency clinicians, with a high sensitivity in identifying patients with mental health complaints requiring hospital admission.
Biochemical Derangements in Patients with Hypoxic Ischemic Encephalopathy Treated With Therapeutic Hypothermia
Authors: Hagel J , Tomlinson C
Published: September 2022

BACKGROUND: Therapeutic hypothermia is the standard of care for treating moderate or severe hypoxic ischemic encephalopathy (HIE) due to birth asphyxia. During the cooling period, altered intermediary metabolism coupled with multi-organ injury due to the underlying hypoxia may result in significant metabolic and biochemical derangements. Since the introduction of therapeutic hypothermia we have noticed an apparent increase in hyperglycemia and hyponatremia though such has not been formally documented.

OBJECTIVES: This study sought to determine if there is a difference in the incidence of biochemical derangements in patients undergoing therapeutic hypothermia for moderate to severe HIE compared to a historical control group receiving standard supportive care.

DESIGN/METHODS: A retrospective chart review was performed with a cluster sampling technique to select all patients ≥35 weeks PMA with a primary admission diagnosis of HIE in the years 2006, 2009, and 2012 at a single institution. This covered a time period before therapeutic hypothermia was established as standard of care, when it was in its implementation phase, and once fully established. Other than the hypothermia itself, there were no major changes in management of these patients, particularly, no change in fluid management regimens. Gestational age, birth weight, APGARs, severity of HIE, medications, blood glucose, electrolytes, liver and renal function were collected retrospectively at all time points during the 72 hour cooling window. Analysis was performed using unpaired students ttest using 0.05 as a definition of statistical significance.

RESULTS: 155 patients were identified, 20 were excluded due to gestational age or suspected/confirmed underlying genetic disorder leaving n=60 cooled neonates and n=75 uncooled. The average gestational age in the cooled group was 39 and 3/7 weeks and in the uncooled group it was 38 and 5/7 weeks. In both groups, there were slightly more males than females with 57% (n=34) in the cooled group and 59% (n=44) in the uncooled group. There is a statistically significant increase in plasma glucose in the cooled group on day one (7.37±1.73 vs. 5.49±1.89, P<0.01) and day two (6.26±1.61 vs 5.34±1.79, P <0.05). There was no difference on day three. Serum sodium was lower in the cooled group on all three days, though it was only statistically significant on day 1 (130.29±4.84 vs. 132.27±4.58, P<0.05). CONCLUSION: Our results suggest that without significant changes in fluid management, therapeutic hypothermia is associated with an increased incidence of hyperglycemia and hyponatremia. Further work is needed to determine if these derangements significantly affect short or long-term outcomes.
Prolonged Nasoenteral Tube Feeding in Children Contradicts Best Practice Guidelines
Authors: Turner J , Abobo M , Blatz D , Hartfield D , Mager D
Published: September 2022

BACKGROUND: Expert consensus guidelines from the Canadian Pediatric Society and the American Academy of Pediatrics state that naso-enteral tube feeding is not appropriate for long term home nutrition support. Therefore, gastrostomy tubes are recommended for nutrition support predicted to last 2-3 months or more. A 2010 survey of pediatric health care providers at our institution demonstrated that 73% were unaware of these guidelines and 47% would consider a G tube only after 3-6 months.

OBJECTIVES: The objective of this study is to determine whether the duration of nasoenteral tube feeding in children at our centre is consistent with expert consensus guidelines.

DESIGN/METHODS: Prospectivechart review of all patients younger than 17 years of age referred for home nutrition support from January 2014 - July 2015 was conducted, with data collection until the present.

RESULTS: 310 children were referred for nutrition support. Excluding patients out of province, lost to follow-up or deceased within a year from referral, 237 children were included. 88% were initially fed with a nasoen-teral tube; 76% of them were predicted to require tube feeding for months to years. 70% were fed with a nasoenteral tube for more than 3 months, with a mean duration of 4.8 months (range 0.07-20.3 months). 10% eventually underwent gastrostomy tube insertion, with a mean time to insertion of 9.7 months (0.07-20.3 months).

CONCLUSION: The duration of nasoenteral tube feeding in a significant proportion of children is longer than recommended by expert consensus guidelines. An important contributing factor is lack of knowledge amongst pediatric health care practitioners about existing best practice guidelines.
The First Step to Helping: Asking About Poverty
Authors: Teicher J , Qadri J Ysselstein , Bloch G , Ford-Jones L , Orkin J
Published: September 2022

BACKGROUND: Canadian children living in poverty are more likely to experience poor health outcomes. Physicians have a unique opportunity to screen for poverty and other social determinants of health (SDOH) in order to intervene early and change their patients' health trajectories. It is well known in the literature to date that addressing SDOH in clinical practice can improve health outcomes, however, significant barriers have been identified that limit a physician’s ability to address these issues. The Child Poverty Assessment Tool (CPAT) was developed by an inter-professional team of physicians, social workers and community child health agency partners to provide healthcare providers with screening questions for the SDOH and resources to address identified SDOH needs. The tool was created to support physicians with links to the community and simple screening approaches to common social issues.

OBJECTIVES: To develop an understanding of physicians' current SDOH screening practices and attitudes to screening for the SDOH in clinical practice; To explore the feasibility, accessibility, and relevance of the CPAT for paediatricians at an academic health science centre.

DESIGN/METHODS: Using a qualitative grounded theory approach, seven consultant academic paediatricians were individually interviewed. The interviews were conducted using a semi-structured interview guide, and were digitally recorded and transcribed verbatim. Two team members independently coded the transcripts for recurrent themes. This project was undertaken as a Quality Improvement project and was conducted with appropriate ethical approval.

RESULTS: Three major themes emerged regarding benefits of screening for SDOH: improved assessment of social issues, increased referrals to community supports and agencies, and appropriate modifications to treatment plans as informed by social issues. In addition to limiting billing models and time constraints, five major themes were identified as challenges to screening for SDOH: lack of knowledge of resources, upsetting family expectations, the physician’s own comfort in asking questions regarding the SDOH, the biomedical model of training, and physicians' understanding of their scope of practice. The CPAT was found to address some, but not all of these challenges.

CONCLUSION: The results from the project elucidated important factors that influence the SDOH screening practices of paediatricians. While a structured tool (i.e. the CPAT) may provide support to physicians conducting screening, systemic and medical cultural barriers exist. Further research is needed to examine the effectiveness of implementing screening tools in clinical practice, and to identify solutions for systemic barriers to screening for poverty in paediatric populations.
Generalized Health Impact of Social and Material Deprivation on Perinatal Outcomes In Nova Scotia, Canada
Authors: Orkin J , O'Campo P , Shankardass K , Dodds L , Joseph KS , Allen V
Published: September 2022

BACKGROUND: Poverty is associated with multiple adverse perinatal outcomes including low birth weight, small for gestational age, pregnancy induced hypertension, gestational diabetes as well as an increased risk for neonatal death. Recent research has attempted to align social theory (i.e., that adverse social exposures impact multiple outcomes) with new statistical modeling that reflects this theory. The Generalized Health Impact (GHI) model looks at the impact on a myriad of adverse outcomes of exposure to negative social risk factor such as low income or poverty. Growing research examines how multiple perinatal outcomes are influenced by social and material deprivation. In particular, having a lower social and economic position in society (socioeconomic position) or being raised in low-income setting has been independently linked to multiple negative health outcomes.

OBJECTIVES: To understand the generalized health impact (GHI) on perinatal health for mothers and their children that socioeconomic position (SEP) can have on health.

DESIGN/METHODS: Data from the Nova Scotia Atlee Perinatal Database was used. A partnership with Statistics Canada facilitated a confidential linkage with income tax information for the year in which delivery occurred. Multiple logistic regression models were used to examine the relationship between multiple indicators of family income and multiple adverse perinatal and maternal outcomes. In the second stage of analysis, multinomial logistic regression was used to examine effects on a tally of the number of adverse outcomes (0, 1, 2 or ≥3). The study was approved by the IWK Health Centre Research Ethics Board.

RESULTS: 117 734 individuals were included. Total family income was less than $23 587 in approximately 62% of families. Effect of low socioeco-nomic position on concomitant adverse perinatal health outcomes was seen with the risk of having 3 or more conditions was highest amongst single mothers (PR 3.1 CI: 2.92-3.27) and families reported as having an income below the low income cut off (PR 2.33 CI:2.16-2.51). Higher material deprivation in the neighbourhood of residence was associated with increased risk of multiple negative perinatal outcomes including pre-term birth and small for gestational age.

CONCLUSION: This study highlights the importance of understanding the cumulative effect of SEP on generalized health outcomes for negative perinatal health outcomes. This research should inform clinical practice to recognize that social determinants of health and negative health outcomes occur not in isolation but as a collective. Further research on adequate screening for poverty and clinical assessment of social determinants of health is required.
A Single Nutristep™ Question as a Food Insecurity Screening Tool
Authors: Borkhoff CM , Bayoumi I , Nurse KM , Chen Y , Maguire JL , Parkin PC , Birken C
Published: September 2022

BACKGROUND: Food insecurity could pose serious health risks, deficiencies, and be harmful to early children’s healthy growth and development. Many family health teams use the Nutrition Screening Tool for Every Preschooler (NutriSTEP™) as a tool to provide a fast, valid way to assess the eating habits of toddlers and preschoolers and identify individual kids at risk. Furthermore, the NutriSTEP™ questionnaire is being rolled out in Public Health Units in Ontario.

OBJECTIVES: The objectives of this study were to assess the criterion and construct validity of the 1-item on the NutriSTEP™ questionnaire: “I have difficulty buying food I want to feed my child because food is expensive” for measuring food insecurity.

DESIGN/METHODS: A cross-sectional study of healthy children, aged 18 months to 5 years, seen for primary care between June 2008 and January 2015 was conducted through the TARGet Kids! practice-based research network. A parent of each participant completed the NutriSTEP™ questionnaire for toddlers aged 18–35 months or for children aged 3–5 years. Parents also responded to the 2-item Food Insecurity Screen (which comes from the 18-item Household Food Security Survey). Criterion validity was evaluated by comparing the responses of the 1-item NutriSTEP™ to the 2-item FI Screen as a gold standard and testing the sensitivity, specificity, and likelihood ratios for a positive and negative result. Convergent validity (the correspondence between the 1-item screen and theoretically related variables) was assessed with multivariable logistic regression.

RESULTS: 1174 children (mean age 37 months) were included: 53 (4.5%) children were categorized as food insecure. An affirmative response to the 1-item NutriSTEP™ had a sensitivity of 84.9% (95% CI: 72.4-93.3) and a specificity of 91.2 % (95% CI: 89.4- 92.8). A positive or food insecure NutriSTEP™ response is 9.6 times more likely to occur in a participant with a food insecure response than a food secure response to the FI Screen. A negative or food secure NutriSTEP™ response is 6 times less likely to occur in a participant with a food insecure response than a food secure response to the FI Screen. An affirmative response to the 1-item NutriSTEP™ was associated with increased odds of a low self-reported after-tax annual household income of $0 - $29,999 (adjusted odds ratio [aOR]: 7.6; (95% CI: 89.4- 92.8); P<0.001).

CONCLUSION: Children who were food insecure were identified with the 1-item NutriSTEP™, suggesting that this single question may be an effective screening tool for food insecurity.
Quick-Wee: A Novel Non-Invasive Urine Collection Method for Infants in the Emergency Department
Authors: Kaufman J , Tosif S , Fitzpatrick P , Donath S , Hopper S , Bryant P , Babl F
Published: September 2022

BACKGROUND: Urinary tract infection is one of the commonest paedi-atric infections, and important to diagnose or exclude in young children with fever. Limitations exist with all current urine collection methods, guidelines vary, and clinicians have different preferences. Clean catch urine (CCU) is a preferred non-invasive collection method and is convenient and painless compared to suprapubic aspirate and catheterisation. However, it can be unreliable and time-consuming, with high rates of sample contamination and collection failure. Only 12% void within 5 minutes based on recent data. An ideal method of urine collection would be fast, reliable and simple. Suprapubic stimulation may trigger involuntary parasympathetic detrusor contraction, inducing voiding via early childhood exteroceptive somato-bladder reflexes.

OBJECTIVES: We conducted a pilot study using a novel method (termed ‘Quick-Wee’) of gentle cutaneous suprapubic stimulation with saline-soaked gauze, to hasten voiding for non-invasive urine collection.

DESIGN/METHODS: Prospective pilot study of 40 pre-continent children age 1-24 months requiring CCU in a paediatric emergency department in Australia. Standard CCU was augmented by 5 minutes of suprapubic cutaneous stimulation (Quick-Wee method), with either cold (3 degrees Celsius) or room-temperature saline-soaked gauze. PRIMARY OUTCOME: Void <5 minutes. SECONDARY OUTCOMES: Successful catch of sample (if voids), contamination rate, parental/clinician satisfaction with technique.

RESULTS:

CONCLUSION: Gentle cutaneous suprapubic stimulation with saline-soaked gauze appears to be a promising technique with 30% voiding in <5 minutes, a rate higher than observed without such stimulation. A randomised controlled trial comparing Quick-Wee to standard CCU without suprapubic stimulation is now underway.
Evaluation of Delayed Puberty: What Diagnostic Tests Should be Done in the Seemingly Otherwise Well Adolescent?
Authors: Abitbol L , Zborovski S , Palmert M
Published: September 2022

BACKGROUND: Delayed puberty (DP) is defined as the lack of puberty by an age that is 2-2.5 standard deviations beyond the population mean. Although it generally represents a normal variant in pubertal timing, DP can be the initial presentation of a serious underlying disorder and can be a source of significant anxiety for patients and their parents. Despite its clinical importance, the initial diagnostic approach to this condition is variable and may include tests that are unnecessary and costly.

OBJECTIVES: To review the current recommendations regarding the initial evaluation of DP in the seemingly otherwise well adolescent and provide a rationale for revisiting these recommendations using data from our centre.

DESIGN/METHODS: We reviewed clinical and laboratory data of patients seen for DP in the Endocrinology Clinic at the Hospital for Sick Children through retrospective chart review of patients seen between 08/2012 and 12/2013 and prospective chart review of those seen between 01/2014 and 07/2014.

RESULTS: 519 charts were reviewed retrospectively and 58 met inclusion criteria; 6 additional patients were identified prospectively (n=64; 40 male, 24 female). Among the patients who were previously healthy, 70% had constitutional delay of growth and puberty, 18% had functional hypogo-nadotropic hypogonadism (FHH), 7% had permanent hypogonadotropic hypogonadism and 4% had hypergonadropic hypogonadism. Wide inter-practitioner variability in the number of diagnostic tests ordered, ranging from 3 to 27, was observed. The mean number of diagnostic tests ordered at the patient’s initial visit was 16 with a median of 17. Diagnostic tests ordered to identify FHH in the absence of signs or symptoms of an underlying disorder, including thyroid function testing, celiac antibodies and general screens for systemic illness were not helpful.

CONCLUSION: We found wide variability in the number of diagnostic tests ordered during the initial work-up of DP. Furthermore, the majority of tests ordered had a low diagnostic yield in patients with low pre-test probability. We propose that initial diagnostic testing in an otherwise healthy adolescent with DP should only consist of gonadotropins and close clinical monitoring. A bone age, while non-diagnostic, is useful for height prediction.
A Comparison of Prenatal Exposures in Children with and Without A Diagnosis of Autism Spectrum Disorder in an Atlantic Canadian City
Authors: Saunders A
Published: September 2022

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial disorder characterized by varying deficits in social interactions, disordered communication and repetitive behaviour patterns. Signs that a child has autism are present in the early developmental stages and the symptoms cause significant impairment in many areas of functioning, including social, educational/occupational, and performance of everyday activities. There have been established genetic correlates and noticeable heredity with ASD diagnoses, but so far chromosomal genetic changes have only been found in approximately 25% of children with autism who were studied and there was no single variance that predominated. This signifies that there may be other external factors at play for autism to develop from preexisting genetic risk. Current studies suggest that prenatal exposures are more important to future autism diagnoses than those that happen after birth; there appears to be disruption of neuron gene networks in the cell cycle, protein folding, DNA damage repair and cell apoptosis. Potential prenatal triggers are the focus of this study, with interest to one geographical area in Atlantic Canada.

OBJECTIVES: The study focused on the presence of environmental exposures during pregnancy in children who developed autism spectrum disorder and those who did not, with a specific focus on a specific Atlantic Canadian city. Exposures inquired about included: acetaminophen/ paracetamol use, air pollution, fever, parental age, maternal diabetes, prenatal vitamin use, workplace exposures, recreational drug use, seafood consumption, obesity, and maternal thyroid issues.

DESIGN/METHODS: Mothers of children aged 0-10 years were asked to participate in a telephone interview regarding environmental exposures during their pregnancy. This was followed up by a prenatal chart review. There were two groups of participants: 107 from the autism group and 108 from the non-autism group. The data was analyzed with univariate tests and a logistic regression.

RESULTS: Univariate analysis revealed significant differences between groups for presence of siblings with ASD, presence of family members with ASD, presence of fever, use of medications, use of cigarettes, and gesta-tional age at the start of prenatal vitamins. Logistic regression analysis found significance with use of medications, use of cigarettes, and gesta-tional age at the start of prenatal vitamins.

CONCLUSION: The use of medications and cigarettes during pregnancy are associated with an increased rate of autism diagnosis. As well, a later starting date for use of prenatal vitamins was associated wth autism. Working towards an understanding of factors that come together to create a diagnosis of autism will be helpful for families, physicians, and allocating government resources.
Lily HD-Zip I Transcription Factor LlHB16 Promotes Thermotolerance by Activating LlHSFA2 and LlMBF1c
Authors: Wu Ze , Li Ting , Zhang Dehua , Teng Nianjun
Published: September 2022

HD-Zip I transcription factors play important roles in plant development and response to abiotic stresses; however, their roles in thermotolerance are largely unknown. Through transcriptome analysis in lily (Lilium longiflorum), we isolated and identified a HD-Zip I gene differentially expressed at high temperatures, LlHB16, which belongs to the β2 subgroup and positively regulates thermotolerance. The expression of LlHB16 was rapidly and continuously activated by heat stress. LlHB16 protein localized to the nucleus and exhibited transactivation activity in both plant and yeast cells, and its C-terminus contributed to its transcriptional activity. Overexpressing LlHB16 in Arabidopsis and lily improved thermotolerance and activated the expression of heat-related genes in both plants, especially that of HSFA2 and MBF1c. In addition, LlHB16 overexpression in Arabidopsis also caused growth defects, delayed flowering and abscisic acid (ABA) insensitivity. Further analysis revealed that LlHB16 directly binds to the promoters of LlHSFA2 and LlMBF1c and activates their expressions. Similarly, the expression of AtHSFA2 and AtMBF1c was also elevated in LlHB16 transgenic Arabidopsis lines. Together, our findings demonstrate that LlHB16 participates in the establishment of thermotolerance involved in activating LlHSFA2 and LlMBF1c, and LlHB16 overexpression resulted in ABA insensitivity in transgenic plants, suggesting that LlHB16 links the basal heat-responsive pathway and ABA signal to collaboratively regulate thermotolerance.
An ankylosing spondylitis risk variant alters osteoclast differentiation
Authors: Wu Fangyi , Han Xuling , Liu Jing , Zhang Zhenghua , Yan Kexiang , Wang Beilan , Yang Lin , Zou Hejian , Yang Chengde , Huang Wei , Jin Li , Wang Jiucun , Qian Feng , Niu Zhenmin
Published: September 2022

Objective

To explore whether the variants in non MHC proteasome gene are associated with AS and explain the role of the variant in the disease.

Material and methods

Case-control analysis to identify AS predisposition genes; dual-luciferase reporter assay, immunoblot analysis and osteoclastogenesis assays to detect the function of the positive variant. Affected individuals were diagnosed according to the modified New York Criteria by at least two experienced rheumatologists, and rechecked by another rheumatologist.

Results

The study included 1037 AS patients and 1014 no rheumatic and arthritis disease controls. The main age of AS onset is between 16 and 35 years old. HLA-B27-positive subjects comprised 90.0% of patients. A nonsynonymous SNP rs12717 in proteasome gene PSMB1 significantly associated with AS. Individuals with CC genotype had a higher onset risk compared with those with GG/GC genotypes (OR = 1.89, P = 0.0047). We also discovered that PSMB1 regulates the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) signalling pathway and the disease-associated variant PSMB1-Pro11 significantly inhibits RANKL-induced NF-κB pathway in osteoclast differentiation via the degradation of IKK-β compared with PSMB1-Ala11. RANKL induced osteoclast differentiation was significantly lower in primary monocyte osteoclast precursor from individuals with genotype PSMB131C/31C compared with individuals with genotype PSMB131G/31G.

Conclusions

These results reveal a novel understanding of the bone formation and reabsorbing imbalance in AS. The new bone formation phenotype can be attributed to the inhibition of osteoclast differentiation by a more functional PSMB1 gene.
The Lasting Labor-Market Effects of Cash Transfers: Evidence from South Africa’s Child Support Grant
Authors: Tondini Alessandro
Published: September 2022

Can unconditional cash transfers have long-term benefits for women’s employment in developing countries? This study exploits discontinuous exposure to the South African Child Support Grant for mothers whose children were born one year apart to identify the short- and long-term effects of a positive income shock of roughly $400 ($650 PPP in 2010). In the short term, there is a considerable increase in the probability of being active and looking for a job. Five years after receiving the transfer, mothers who benefited for one year are as likely to be employed as those who never received it; the type of occupation is also similar, other than a small decrease in work in the agricultural sector. Overall, the grant appears to facilitate job search for single mothers in the presence of high search costs, but does not significantly change job prospects.
A specialized channel for encoding auditory transients in the magnocellular division of the human medial geniculate nucleus
Authors: Meng Qianli , Schneider Keith A.
Published: September 2022

We test the hypothesis that there exists a generalized magnocellular system in the brain optimized for temporal processing. In the visual system, it is well known that the magnocellular layers in the lateral geniculate nucleus (LGN) are strongly activated by transients and quickly habituate. However, little is known about the perhaps analogous magnocellular division of the medial geniculate nucleus (MGN), the auditory relay in the thalamus. We measured the functional responses of the MGN in 11 subjects who passively listened to sustained and transient nonlinguistic sounds, using functional MRI. We observed that voxels in the ventromedial portion of the MGN, corresponding to the magnocellular division, exhibited a robust preference to transient sounds, consistently across subjects, whereas the remainder of the MGN did not discriminate between sustained and transient sounds. We conclude that the magnocellular neurons in the MGN parallel the magnocellular neurons in its visual counterpart, LGN, and constitute an information stream specialized for encoding auditory dynamics.
Generating polyketide diversity in
Dictyostelium
: a Steely hybrid polyketide synthase produces alternate products at different developmental stages
Authors: Saito Tamao , Iijima Tomoyuki , Koyama Kohei , Shinagawa Tomonori , Yamanaka Ayaka , Araki Tsuyoshi , Suzuki Noriyuki , Usuki Toyonobu , Kay Robert R.
Published: September 2022

The soil is a rich ecosystem where many ecological interactions are mediated by small molecules, and in which amoebae are low-level predators and also prey. The social amoeba
Dictyostelium discoideum
has a high genomic potential for producing polyketides to mediate its ecological interactions, including the unique ‘Steely’ enzymes, consisting of a fusion between a fatty acid synthase and a chalcone synthase. We report here that
D. discoideum
further increases its polyketide potential by using the StlB Steely enzyme, and a downstream chlorinating enzyme, to make both a chlorinated signal molecule, DIF-1, during its multi-cellular development, and a set of abundant polyketides in terminally differentiated stalk cells. We identify one of these as a chlorinated dibenzofuran with potent anti-bacterial activity. To do this, StlB switches expression from prespore to stalk cells in late development and is cleaved to release the chalcone synthase domain. Expression of this domain alone in StlB null cells allows synthesis of the stalk-associated, chlorinated polyketides. Thus, by altered expression and processing of StlB, cells make first a signal molecule, and then abundant secondary metabolites, which we speculate help to protect the mature spores from bacterial infection.
Conscious awareness is necessary to assess trust and mimic facial expressions, while pupils impact trust unconsciously
Authors: Prochazkova E. , Venneker D. , de Zwart R. , Tamietto M. , Kret M. E.
Published: September 2022

People make rapid inferences about others' thoughts and intentions. For example, they observe facial movements and pupil size of others and unwittingly make use of this information when deciding whether to trust someone or not. However, whether spontaneous mimicry depends on visual awareness of the stimulus and whether these processes underlie trust decisions is still unknown. To investigate whether visual awareness modulates the relationship between emotional expressions, mimicry and trust, participants played a series of trust games and saw either their partners’ faces with a neutral, happy or fearful expression, or their partners' eyes in which the pupil size was large, medium or small. Subjects' trust investments, facial movements and pupil responses were measured. In half of the trials, the stimuli were rendered invisible by continuous flash suppression. Results showed that facial expressions were mimicked and influenced trust decisions during the conscious condition, but not during the unconscious (suppressed) condition. The opposite was found for pupil size, which influenced trust decisions during states of unawareness. These results suggest that the neurobiological pathway linking the observation of facial expressions to mimicry and trust is predominantly conscious, whereas partner pupil size influences trust primarily when presented unconsciously.

This article is part of the theme issue ‘Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience’.
PERSPECTIVES FOR POPULATION MANAGEMENT OF FELIDS IN INDIAN ZOOS
Authors: R Lakshminarasimha , Mallapur Gowri , Ghosh Sonali , Yadav Satya Prakash
Published: September 2022

The family: Felidae (hereafter referred to as felids) is among the commonly represented species in animal collections in Indian zoos. Of the globally recognised 45 species, 15 species (>30%) are housed in Indian zoos. Since 2007, the Central Zoo Authority has laid emphasis on ex situ conservation for seven threatened species by initiating planned breeding programmes.

We investigated the demographics of felids housed in Indian zoos using data from CZA annual inventory records. Between 1995-96 and 2019-20, the population of large felids have remained stable with a mean growth rate (λ) of 1.01; whereas the population of small felids have a marginally higher mean growth rate (λ) of 1.03. We further use Sustainability-index analysis to investigate whether the observed growth patterns arise from intrinsic (i.e. births/deaths) or extrinsic (acquisition/disposal) factors.

The management of felids in Indian zoos requires careful consideration of many factors including space, hybridisation, lack of pedigree knowledge, addition of wild-rescued specimens and colormorphs. We provide the first insights on how felids populations have fared at the family-level and species-level based on analysis of longitudinal data. The said analysis intends to inform plans to manage felid collections in Indian zoos. It should further present an outlook and also guide ongoing planned breeding programs of felids. Given the relatively large collection size and the corresponding conservation attention accorded to felids, our analysis will aid in setting priorities for collection planning, conservation education messaging, integration of in situ and ex situ efforts in the context of IUCN One Plan Approach.
Molecular and morphological analyses of the genus Episoriculus with the description of a new subgenus
Authors: Liu Yingxun , Wang Xuming , He Kai , Wan Tao , Liao Rui , Shunde Chen , Liu Shaoying , Yue Bisong
Published: September 2022

Shrews in the genus Episoriculus are among the least known mammals in China. It occurs mainly in the Himalayas and the Hengduan Mountains. We report the sequencing and analyses of one mitochondrial gene (Cyt b) and three nuclear genes (Apob, Brca1, and Rag2) for 77 specimens, and analyses of morphological measurements for 56 specimens. Phylogenetic and morphological studies answer three longstanding questions. First, Episoriculus sacratus and E. umbrinus are valid species, and not subspecies of E. caudatus. Second, Pseudosoriculus fumidus is a valid taxon that does not belong to the genus Episoriculus. Third, the genus Episoriculus has eight valid species: E. baileyi, E. caudatus, E. leucops, E. macrurus, E. sacratus, E. soluensis, Episoriculus sp., and E. umbrinus. Ultimately, we erected subgenus Longacauda subgen. nov. for morphologically distinct E. macrurus, which leaves the nominate subgenus Episoriculus with the remaining seven congeners.
Transnational Solidarities and Competing Visions of Europe: Vienna's Vote on the Russo‐Japanese War
Authors: BRANDENBURG ULRICH
Published: September 2022

The 1904–05 Russo‐Japanese War is commonly described as a clash between a European power (Russia) and an Asian one (Japan). This binary framing is problematic, however, as ideas of Europeanness and Asianness were hotly contested during the war. Both Russia and Japan laid claim to being more European than the other, based on competing notions of racial and ideological kinship. The Russo‐Japanese War instantaneously became a first‐rate media event that galvanised audiences worldwide, prompting them to take sides with one or the other of the belligerents. This article examines reactions to the war in the public sphere of Vienna in neutral Austria‐Hungary. It focusses especially on an opinion survey launched by the popular newspaper Illustrirtes Wiener Extrablatt in late February 1904, which attracted more than 12,000 responses and resulted in a narrow victory for Japan. The survey provides us with a valuable sample of ordinary people's voices on the war and reveals that Viennese society was deeply split between solidarity with Russia and with Japan, reflecting the contested socio‐political situation in the city and in the Austro‐Hungarian Empire as a whole. While supporters of Russia excluded Japan from a racially, religiously and geographically defined vision of Europe, supporters of Japan often envisioned a community of civilisation, freedom and justice, which excluded Russia and included Japan. Additionally, competing racisms against ‘yellow’ Japan and Slav Russia reveal substantial disagreement about whether Japan or Russia should be regarded as Europe's Other.
Combined effect of beet powder and lentil flour as a partial nitrite substitute on physicochemical, texture and sensory characteristics, color, and oxidative stability of pork bologna
Authors: Kim Jihan , Shand Phyllis J.
Published: September 2022

The combined effect of beet powder (BP; 0.1%, 0.3%, and 0.5%) and 6% lentil flour (LF) as a partial nitrite substitute on quality attributes of pork bologna incorporated with 7.5% mechanically separated pork during 12 weeks of cold storage was evaluated. A randomized block experimental design with nine treatments and five storage times (0, 3, 6, 9, and 12 weeks) was used for pH, thiobarbituric acid reactive substance, protein oxidation (carbonyl and sulfhydryl), and color parameters. Bologna preparation at a pilot plant scale was replicated three times. LF addition resulted (p < 0.05) in higher viscosity, emulsion stability, and lower expressible drip. Together BP and LF decreased protein oxidation during storage but were not as effective as nitrite with respect to lipid oxidation. Bologna with BP addition showed lower lightness and higher redness, whereas LF increased lightness and decreased redness. A consumer panel rated color acceptability of bologna lower with LF addition, whereas BP raised color acceptability. However, addition of the highest BP level alone to the bologna was negatively perceived as a result of the low acceptability of purge color of the vacuum‐packaged bologna slices. Consequently, the combination of BP and LF could be used to improve eating quality and stability attributes when used as a potential nitrite substitute.
Determination of a clinically effective evobrutinib dose: Exposure–response analyses of a phaseIIrelapsing multiple sclerosis study
Authors: Papasouliotis Orestis , Mitchell David , Girard Pascal , Dangond Fernando , Dyroff Martin
Published: September 2022

The pharmacometric analysis of the double‐blind, randomized, phase II study (NCT02975349) investigating the safety and efficacy of evobrutinib, explored exposure–response relationships and suitable dosing regimens of evobrutinib for relapsing multiple sclerosis. Population pharmacokinetic (PK)/pharmacodynamic modeling was applied to data collected in fasted patients treated with placebo or evobrutinib (25 mg once‐daily [q.d.], 75 mg q.d., or 75 mg twice‐daily [b.i.d.]) for 24 weeks, followed by a 24‐week blinded extension (placebo patients switched to 25 mg q.d.). Model‐based exposures for PK and Bruton's tyrosine kinase occupancy (BTKO) were used for exposure–response analyses (maximum 207 patients). PK, BTKO profiles, and annualized relapse rate (ARR) after 48 weeks of treatment under alternative dosing regimens were simulated. Exposure–response modeling identified a relationship between evobrutinib exposure and clinical response for total number of T1 Gd+ and new/enlarging T2 lesions at weeks 12–24, and ARR at week 48. Area under the concentration–time curve over 24 h at steady‐state (AUC0–24,SS) of 468 and ≥400 ng/ml h was associated with T1 Gd+/T2 lesion reduction and ARR improvement, respectively. These exposures were associated with steady‐state (SS) predose BTKO ≥95%. Based on PK and BTKO profile simulations, evobrutinib 75 mg b.i.d. while fasted is predicted to maintain SS predose BTKO >95% in 92% of patients. Evobrutinib 45 mg b.i.d. with food is predicted to achieve similar exposure as 75 mg b.i.d. while fasted (predose BTKO >95% in 93% of patients). Evobrutinib 45 mg b.i.d. with food is predicted to have comparable exposure and BTKO to 75 mg b.i.d. without food (phase II) and will be pharmacologically effective and appropriate for clinical use in phase III multiple sclerosis studies.
Leading women in respiratory medicine and research: Opportunities for international societies to support women with examples from the American Thoracic Society
Authors: Rebuli Meghan E. , Jaspers Ilona
Published: September 2022

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Crise Sanitária e Estado de Exceção
Authors: Leite Sampaio José Adércio , De Moura Guerra Almeida Larissa , Mathias Souto Luana
Published: September 2022

O presente artigo tem por objetivo oferecer reflexões sobre as implicações que o uso do sistema constitucional de crises provoca na fruição de direitos fundamentais. Diante do contexto da pandemia de COVID-19, buscar-se-á demonstrar como a teoria de estado de exceção desenvolvida por Giorgio Agamben é factual, quando ao provocar a indiscernibilidade entre nomos e anomia, a decisão soberana sobre a exceção permite que esta se torne a regra. Metodologicamente, utilizar-se-á de revisão bibliográfica, análise de dados empíricos relativos ao tema e uso de exemplos históricos que visam corroborar a conclusão sobre a criação de subprodutos em face da declaração constitucional de medidas de exceção.
A Pandemia frente a Constituição Fragilizada: impactos da Emenda 95
Authors: Costa Junior Ernane Salles da
Published: September 2022

O problema que orienta essa investigação pode ser formulado da seguinte maneira: quais as implicações da Emenda 95, que instituiu o teto de gastos públicos para as despesas primárias por 20 anos no Brasil, para o enfrentamento efetivo dos efeitos da pandemia da COVID-19? A partir de uma pesquisa qualitativa embasada em estudo bibliográfico e análise documental, a hipótese defendida aqui é a de que tal Emenda desestruturou as políticas sociais necessárias para uma resposta consistente e imediata do Estado a uma crise econômica e sanitária desse calibre. Desse modo, conclui-se que a pandemia expõe a lógica perversa de aceleração econômica e crescimento escalar contida no teto de gastos, o que revela a fragilidade, desde então, da Constituição e do Estado para enfrentar os desafios agora colocados.