bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Regulation of a Single Adaptively EvolvingTrans-Regulatory Element Contributes to Spermatogenetic Expression Divergence inDrosophila
Authors: Huang Yumei , Shang Rui , Lu Guang-An , Zeng Weishun , Huang Chenglong , Zou Chuangchao , Tang Tian 
Published: June 2022

AbstractDue to extensive pleiotropy, trans-acting elements are often thought to be evolutionarily constrained. While the impact of trans-acting elements on gene expression evolution has been extensively studied, relatively little is understood about the contribution of a single trans regulator to interspecific expression and phenotypic divergence. Here, we disentangle the effects of genomic context and miR-983, an adaptively evolving young microRNA, on expression divergence between Drosophila melanogaster and D. simulans. We show miR-983 effects promote interspecific expression divergence in testis despite its antagonism with the often-predominant context effects. Single-cyst RNA-seq reveals that distinct sets of genes gain and lose miR-983 influence under disruptive or diversifying selection at different stages of spermatogenesis, potentially helping minimize antagonistic pleiotropy. At the round spermatid stage, the effects of miR-983 are weak and distributed, coincident with the transcriptome undergoing drastic expression changes. Knocking out miR-983 causes reduced sperm length with increased within-individual variation in D. melanogaster but not in D. simulans, and the D. melanogaster knockout also exhibits compromised sperm defense ability. Our results provide empirical evidence for the resolution of antagonistic pleiotropy and also have broad implications for the function and evolution of new trans regulators.
Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation
Authors: Keller Josephine Geertsen , Hymøller Kirstine Mejlstrup , Thorsager Maria Eriksen , Hansen Noriko Y , Erlandsen Jens Uldum , Tesauro Cinzia , Simonsen Anne Katrine W , Andersen Anne Bech , Vandsø Petersen Kamilla , Holm Lise Lolle , Stougaard Magnus , Andresen Brage Storstein , Kristensen Peter , Frøhlich Rikke , Knudsen Birgitta R 
Published: June 2022

Abstract
We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.
Work environment and labour market participation in early adulthood
Authors: Sandholm K , Winding T Nøhr 
Published: June 2022

Abstract

Background
Investigating whether a poor physical or psychosocial work environment is associated with low labour market participation in early adulthood is important to avoid negative health-related consequences and to improve job prospects.

Aims
To investigate associations between the physical or psychosocial work environment and labour market participation in early adulthood.

Methods
The study was based on data from the West Jutland Cohort, an ongoing study of individuals born in 1989 who lived in the western part of Jutland, Denmark, in 2004. Participants were employed individuals who had questionnaire data on their work environment at age 28 and register information on labour market participation at ages 28–29 (n = 1312). The outcome was categorized into low (&gt;4 weeks) versus high (≤4 weeks) labour market participation based on the total number of weeks receiving any unemployment or health-related benefits during a 52-week period. Logistic regression analyses were performed to examine associations between work environment factors and labour market participation, taking confounders into account.

Results
Low influence, low quality of leadership, high job insecurity and temporary employment were associated with low labour market participation. High job insecurity (OR: 2.2; 95% CI 1.5–3.1) and temporary employment (OR: 3.1; 95% CI 2.1–4.5) were strongly associated with low labour market participation. An association was seen between hard physical work and low labour market participation.

Conclusions
Several physical and psychosocial work environment factors, especially high job insecurity and temporary employment, have a negative impact on labour market participation in early adulthood.
Antibodies to Human Herpesviruses and Rate of Incident Cardiovascular Events and All-Cause Mortality in the UK Biobank Infectious Disease Pilot Study
Authors: Chu Petrina , Cadogan Sharon Louise , Warren-Gash Charlotte 
Published: June 2022

Abstract

Background
Associations between human herpesviruses (HHVs) and cardiovascular disease/mortality have been reported, but evidence is inconsistent. We investigated associations between 3 common herpesviruses and (1) incident stroke or myocardial infarction (MI) and (2) all-cause mortality.

Methods
We included participants from the UK Biobank Infectious Disease pilot study with valid serum antibody (IgG) measurements taken at cohort entry (2006–2010) for herpes simplex virus type 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV). Linked hospital and mortality records up to December 30 2019 provided information on rates of (1) incident first stroke or MI and (2) all-cause mortality. Hazard ratios (HRs) from Cox proportional hazards regression models were used to assess relationships between (1) HHV seropositivity, (2) HHV titer and incident stroke/MI, and death outcomes. Fully adjusted models accounted for sociodemographic information (age, sex, ethnicity, education, deprivation quintile, birthplace, population density), baseline comorbidities (including diabetes and hypertension), smoking status, body mass index, and serum cholesterol.

Results
Of 9429 study participants (56% female, 95% White, median age 58 years), 41% were seropositive for all 3 HHVs. Human herpesvirus seropositivity was not associated with stroke/MI (fully adjusted HRs and 95% confidence intervals [CIs]: HSV1 = 0.93 [CI, 0.72–1.22], VZV = 0.78 [CI, 0.51–1.20], CMV = 0.91 [CI, 0.71–1.16]) or all-cause mortality (HSV1 = 1.21 [CI, 1.00–1.47], VZV = 0.79 [CI, 0.58–1.07], CMV = 0.90 [CI, 0.76–1.06]). Human herpesvirus titers were not associated with outcomes.

Conclusions
In this mostly White UK Biobank subset, neither HHV seropositivity nor titers were associated with stroke/MI or all-cause mortality.
SUPPRESSOR of MAX2 1 (SMAX1) and SMAX1-LIKE2 (SMXL2) Negatively Regulate Drought Resistance in Arabidopsis thaliana
Authors: Feng Zhonghui , Liang Xiaohan , Tian Hongtao , Watanabe Yasuko , Nguyen Kien Huu , Tran Cuong Duy , Abdelrahman Mostafa , Xu Kun , Mostofa Mohammad Golam , Ha Chien Van , Mochida Keiichi , Tian Chunjie , Tanaka Maho , Seki Motoaki , Liang Zhengwei , Miao Yuchen , Tran Lam-Son Phan , Li Weiqiang 
Published: June 2022

Abstract
Recent investigations in Arabidopsis thaliana suggest that SUPPRESSOR of MORE AXILLARY GROWTH 2 1 (SMAX1) and SMAX1-LIKE2 (SMXL2) are negative regulators of karrikin (KAR) and strigolactone (SL) signaling during plant growth and development, but their functions in drought resistance and related mechanisms of action remain unclear. To understand the roles and mechanisms of SMAX1 and SMXL2 in drought resistance, we investigated the drought-resistance phenotypes and transcriptome profiles of smax1 smxl2 (s1,2) double-mutant plants in response to drought stress. The s1,2 mutant plants showed enhanced drought-resistance and lower leaf water loss when compared with wild-type (WT) plants. Transcriptome comparison of rosette leaves from the s1,2 mutant and the WT under normal and dehydration conditions suggested that the mechanism related to cuticle formation was involved in drought resistance. This possibility was supported by enhanced cuticle formation in the rosette leaves of the s1,2 mutant. We also found that the s1,2 mutant plants were more sensitive to abscisic acid in assays of stomatal closure, cotyledon opening, chlorophyll degradation and growth inhibition, and they showed a higher reactive oxygen species detoxification capacity than WT plants. In addition, the s1,2 mutant plants had longer root hairs and a higher root-to-shoot ratio than the WT plants, suggesting that the mutant had a greater capacity for water absorption than the WT. Taken together, our results indicate that SMAX1 and SMXL2 negatively regulate drought resistance, and disruption of these KAR- and SL-signaling-related genes may therefore provide a novel means for improving crop drought resistance.
Resistance to Extinction of Evaluative Fear Conditioning in Delusion Proneness
Authors: Louzolo Anaïs , Lebedev Alexander V , Björnsdotter Malin , Acar Kasim , Ahrends Christine , Kringelbach Morten L , Ingvar Martin , Olsson Andreas , Petrovic Predrag 
Published: June 2022

Abstract
Delusional beliefs consist of strong priors characterized by resistance to change even when evidence supporting another view is overwhelming. Such bias against disconfirmatory evidence (BADE) has been experimentally demonstrated in patients with psychosis as well as in delusion proneness. In this fMRI-study, we tested for similar resistance to change and associated brain processes in extinction of fear learning, involving a well-described mechanism dependent of evidence updating. A social fear conditioning paradigm was used in which four faces had either been coupled to an unconditioned aversive stimulus (CS+) or not (CS−). For two of the faces, instructions had been given about the fear contingencies (iCS+/iCS−) while for two other faces no such instructions had been given (niCS+/niCS−). Interaction analysis suggested that individuals who score high on delusion-proneness (hDP; n = 20) displayed less extinction of evaluative fear compared to those with low delusion proneness (lDP; n = 23; n = 19 in fMRI-analysis) for non-instructed faces (F = 5.469, P = .024). The resistance to extinction was supported by a difference in extinction related activity between the two groups in medial prefrontal cortex and its connectivity with amygdala, as well as in a cortical network supporting fear processing. For instructed faces no extinction was noted, but there was a larger evaluative fear (F = 5.048, P = 0.03) and an increased functional connectivity between lateral orbitofrontal cortex and fear processing regions for hDP than lDP. Our study links previous explored BADE-effects in delusion associated phenotypes to fear extinction, and suggest that effects of instructions on evaluative fear learning are more pronounced in delusion prone subjects.
My Wellness Coach: evaluation of a mobile app designed to promote integrative health among underserved populations
Authors: Yuan Nicole P , Brooks Audrey J , Burke Molly K , Crocker Robert , Stoner Gates Matthew , Cook Paula , Chen Mei-Kuang , Bautista Juan , Petralba Patricia , Whitewater Shannon , Maizes Victoria 
Published: June 2022

Abstract
Underserved populations, including those from racial and ethnic groups and with low socioeconomic status, often lack access to mobile apps aimed at reducing health risk factors. This study evaluated the feasibility, acceptability, and preliminary effectiveness of the mobile app, My Wellness Coach (MWC), designed to promote behavior change in seven core areas of integrative health among underserved populations. Patients and staff were recruited from clinic and other settings. Some participants used MWC in a weekly group setting (n = 5); others on their own with support from a coordinator (n = 36). Health outcomes were assessed at baseline and 3 months. Mobile app ratings were collected at 5 weeks and 3 months. Goal setting data were analyzed at 3 months. Most participants (76%) set at least one goal, 71% created action steps for goals, and 29% completed a goal. Patients in the group setting had the highest rate of goal completion (60%) compared to patients (20%) and staff (27%) using the app on their own. Significant (p &lt; .05) changes in pre- and post-test scores were documented for overall wellbeing, global physical health, BMI, vigorous physical activity, and eHealth literacy. Most participants (75%–91%) gave MWC high ratings for impact on behavior change, help seeking, intent to change, attitudes, knowledge, and awareness. This study documented preliminary evidence of the potential benefits of MWC among underserved communities. Future evaluations of Spanish and Android versions and comparisons between group and individual administration will inform implementation strategies for scaling MWC-based interventions to reach underserved communities nationally.
Improving active travel to school and its surveillance: an overlooked opportunity in health promotion and chronic disease prevention
Authors: George Stephanie M , Sliwa Sarah A , Cornett Kelly A , Do Van , Bremer Andrew A , Berrigan David 
Published: June 2022

AbstractIncreasing active travel to school (ATS) could reduce the deficit in youth physical activity participation; however, surveillance of ATS is limited. Given that ATS contributes to our understanding of children’s physical activity patterns nationwide, is influenced by local contexts and state laws, and occurs within communities, surveillance could be informative at the national, state, and local levels. Following a National Collaborative on Childhood Obesity Research workshop, this commentary offers insights into strengthening surveillance and data collection of ATS behavior as well as ATS environmental, policy, and program supports.
Assessment of genotoxic potential of the treated hospital wastewater using cytogenetic assays
Authors: Mathur Priyanka , Rani Kusum , Bhatnagar Pradeep 
Published: June 2022

Abstract
The cytogenetic study using hospital effluent was carried out engaging three cytogenetic end points—chromosomal aberration (CA) assay, mitotic indices (MIs), and micronucleus (MN) Analysis. These bioassays were performed in hematopoietic bone marrow cells of Mus musculus. The experiment commenced with the collection of hospital effluent from the final outlet when wastewater gets collected after undergoing treatment by a multistep process. The pure treated sample water was collected at different times between March 2019 to January 2020 and was given ad libitum to mice at its low (90% dilution) and high (pure form), i.e. 100% concentration for 3 different durations i.e. 7, 15, and 30 days, respectively. The results indicated a significant (P &lt; 0.01) decrease in the MI in all the groups but was more pronounced in the group which was given 100% concentrated sample water collected in the month of March 2019. Besides this, the major finding was presence of CAs like breaks, fragments, rings, and pulverization in bone marrow cells in different groups; however, the frequency of these aberrations varied from group to group. A significant (P &lt; 0.01) increase in MN Induction and decreased ratio (P &lt; 0.01) of polychromatic to normonochromatic erythrocytes were observed in samples collected in month of March both at 10% and 100% concentrations. However, decrease in the ratio was observed in the samples of September and January at low-concentration sample water. The results thus indicated that there was some lacuna in the treatment process earlier in the month of March, which was rectified to some extent in the subsequent months. Hence, the treated wastewater collected in the month of January next year was more suitable for its use than other samples. Summary: These findings thus draw attention toward ensuring efficiency of the treatment plant and quality of water by the hospital management before it being disposed off into the municipal supply; a step that can help society to live a healthy life. With these findings, it is conveyed that all the hospitals, diagnostic labs, and other health care establishments must pay utmost attention at liquid waste disposal mechanism to make environment pollution-free.
Phthalate Exposures and Placental Health in Animal Models and Humans: A Systematic Review
Authors: Seymore Talia N , Rivera-Núñez Zorimar , Stapleton Phoebe A , Adibi Jennifer J , Barrett Emily S 
Published: June 2022

Abstract
Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children’s health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.
Trajectories of Pain Severity and Interference Among Adolescent and Young Adults With Cancer
Authors: Darabos Katie , Li Yimei , O’Hagan Bridget , Palermo Toyna , King-Dowling Sara , Jubelirer Tracey , Huang Jing , Barakat Lamia P. , Schwartz Lisa A. 
Published: June 2022

Objective:
Cancer-related pain is a pervasive concern among adolescent and young adults (AYA) with cancer and is an emerging long-term health concern. Few studies have examined the complex contributions to pain among AYA. We aimed to fill a gap by (1) identifying subgroups of AYA with distinct patterns of pain severity and interference over time and (2) explore possible predictors of these patterns.

Methods:
Daily text messages over a 9-week period were used to model group-based trajectory analyses of pain severity and interference by identifying subgroups of AYA who experience common patterns of changes in pain. Demographic, medical, physical symptom burden, and psychological distress were examined as possible predictors of these patterns.

Results:
AYA were on average 16.93 years old and 2.5 years since diagnosis. Subgroups of AYA were identified for pain severity and interference over time: high variability (37.7%; 37.7%, respectively), consistent high pain (35.8%; 18.9%, respectively), and consistent low pain (26.4%; 43.4%, respectively). AYA with greater psychological distress were more likely to belong to the high consistent pain severity and interference groups. AYA with greater physical symptoms were more likely to belong to the high consistent pain interference group. No significant associations between demographic/medical characteristics and trajectory subgroups were found.

Conclusions:
AYA with elevated physical and psychological symptoms were more likely to experience high consistent pain severity and pain interreference over time. Interventions aimed at reducing pain through focusing on teaching AYA how to alleviate physical symptoms and teaching coping skills to manage psychological distress may be beneficial.
Reexamining the Role of Postoperative ICU Admission for Patients Undergoing Elective Craniotomy: A Systematic Review*
Authors: Azad Tej D. , Shah Pavan P. , Kannapadi Nivedha V. , Rincon-Torroella Jordina , Xia Yuanxuan , Bernhardt Lydia J. , Hansen Landon J. , Materi Joshua , Raj Divyaansh , Jackson Christopher M. , Mukherjee Debraj , Gallia Gary L. , Weingart Jon , Suarez Jose I. , Brem Henry , Bettegowda Chetan 
Published: June 2022

OBJECTIVES:
The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy.

DATA SOURCES:
A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021.

STUDY SELECTION:
Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care.

DATA EXTRACTION:
Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies—of Interventions tool, respectively.

DATA SYNTHESIS:
In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation.

CONCLUSIONS:
Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.