bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel genes and pathways regulated by the orphan nuclear receptor COUP-TFII in mouse MA-10 Leydig cells
Authors: Mehanovic Samir , Mendoza-Villarroel Raifish E , de Mattos Karine , Talbot Philippe , Viger Robert S , Tremblay Jacques J
Published: July 2021

In males, Leydig cells are the main producers of testosterone and insulin-like 3 (INSL3), two hormones essential for sex differentiation and reproductive functions. Chicken ovalbumin upstream promoter-transcription factors I (COUP-TFI/NR2F1) and COUP-TFII (NR2F2) belong to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. In the testis, COUP-TFII is expressed and plays a role in the differentiation of cells committed to give rise to fully functional steroidogenic adult Leydig cells. Steroid production has also been shown to be diminished in COUP-TFII-depleted Leydig cells, indicating an important functional role in steroidogenesis. Until now, only a handful of target genes have been identified for COUP-TFII in Leydig cells. To provide new information into the mechanism of action of COUP-TFII in Leydig cells, we performed microarray analyses of COUP-TFII-depleted MA-10 Leydig cells. We identified 262 differentially expressed genes in COUP-TFII-depleted MA-10 cells. Many of the differentially expressed genes are known to be involved in lipid biosynthesis, lipid metabolism, male gonad development, and steroidogenesis. We validated the microarray data for a subset of the modulated genes by RT-qPCR. Downregulated genes included hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (Hsd3b1), cytochrome P450, family 11, subfamily a, polypeptide 1 (Cyp11a1), prolactin receptor (Prlr), nuclear receptor subfamily 0, group B, member 2 (Shp/Nr0b2), ferredoxin 1 (Fdx1), scavenger receptor class B, member 1 (Scarb1), inhibin alpha (Inha), and glutathione S-transferase, alpha 3 (Gsta3). Finally, analysis of the Gsta3 and Inha gene promoters showed that at least two of the downregulated genes are potentially new direct targets for COUP-TFII. These data provide new evidence that further strengthens the important nature of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation in mouse Leydig cells.
The National Academies Report on Sexually Transmitted Infections: Implications for Clinical Training, Licensing, and Practice Guidelines
Authors: Guilamo-Ramos Vincent , Thimm-Kaiser Marco , Benzekri Adam , Mead Aimee , Hook Edward W , Rietmeijer Cornelis A
Published: July 2021

Sexually transmitted infections (STIs) represent a sizable, longstanding, and growing challenge and a national public health priority. A recent National Academies report outlines new directions for STI prevention and control, including the adoption of a new sexual health paradigm and broader ownership and accountability for addressing sexual health and STIs among diverse clinical and nonclinical actors. These recommendations have important implications for infectious disease providers with STI and human immunodeficiency virus (HIV) expertise. As part of the envisioned shift toward greater prioritization of sexual health across systems for healthcare and health promotion, STI and HIV specialty providers will need to increasingly take on responsibilities as leaders in the provision of STI-related training; provision of technical assistance; and alignment of clinical training curricula, licensing criteria, and practice guidelines for healthcare generalists.
Autosomal dominant polycystic kidney disease: possibly the least silent cause of chronic kidney disease
Authors: Torra Roser , Pérez-Gómez Maria Vanessa , Furlano Mónica
Published: July 2021

Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but it remains infrequently and inconsistently measured across countries, studies and trials. The study by El-Damanawi et al. integrated a network of ADPKD expert clinicians, pain specialists, researchers and patient representatives from the national UK PKD charity, with the aim of addressing the lack of validated ADPKD-specific pain assessment tools (APATs). The APAT designed by the authors included several pain measurement tools and was tested in ADPKD patients, although further validation through assessment in larger cohorts is needed. Establishing a standardized instrument for pain measurement will ensure that pain is measured and reported in a consistent way to inform decision-making and identify effective interventions aimed at managing pain and minimizing the impact pain has on patients with ADPKD. In this context, the APAT established by the authors is to be warmly welcomed.
Role of agglutinin-like sequence protein 3 (Als3) in the structure and antifungal resistance of Candida albicans biofilms
Authors: Liu Chang , Xu Cheng , Du Yu , Liu Jia , Ning Yang
Published: July 2021

Agglutinin-like sequence protein 3 (Als3) is a cell surface glycoprotein of Candida albicans that plays essential roles in the processes of adherence and biofilm formation in vitro. In this study, we focused on the contribution of Als3 to the structure and drug susceptibility of biofilms. The C. albicans wild-type (WT) strain DAY185, the als3Δ/Δ null strain and the als3Δ/Δ + pALS3 complemented strain were used. Colony-forming unit enumeration, crystal violet and cell surface hydrophobicity assays, scanning electron microscopy and confocal laser scanning microscopy coupled with analyses using COMSTAT software were performed to evaluate the biomass and architecture of the biofilms. The detailed architectural analysis showed a significant variation in the biofilm parameters of the als3Δ/Δ biofilms compared with those of the WT biofilms. Fluconazole, miconazole and amphotericin B were selected as the antifungal agents for the antimycotic susceptibility test, and increased susceptibility was found with the ALS3 deletion biofilms. A quantitative real-time polymerase chain reaction analysis showed downregulation of biofilm formation-related genes (ALS1, EFG1, HWP1 and CSH1) and drug resistance-related genes (ERG11, CDR1, CDR2 and MDR1) in the als3Δ/Δ biofilms. We concluded that Als3 contributes to biofilm formation by changing the biofilm architecture and is involved in the antifungal resistance of C. albicans biofilms.
A method for the enrichment, isolation and validation of Mycobacterium smegmatis population surviving in the presence of bactericidal concentrations of rifampicin and moxifloxacin
Authors: Pradhan Atul , Swaminath Sharmada , Jakkala Kishor , Ajitkumar Parthasarathi
Published: July 2021

The bacterial populations surviving in the presence of antibiotics contain cells that have gained genetic resistance, phenotypic resistance and tolerance to antibiotics. Isolation of live bacterial population, surviving against antibiotics, from the milieu of high proportions of dead/damaged cells will facilitate the study of the cellular/molecular processes used by them for survival. Here we present a Percoll gradient centrifugation based method for the isolation of enriched population of Mycobacterium smegmatis surviving in the presence of bactericidal concentrations of rifampicin and moxifloxacin. From the time of harvest, throughout the enrichment and isolation processes, and up to the lysis of the cells for total RNA preparation, we maintained the cells in the presence of the antibiotic to avoid changes in their metabolic status. The total RNA extracted from the enriched population of live antibiotic-surviving population showed structural integrity and purity. We analysed the transcriptome profile of the antibiotic-surviving population and compared it with the orthologue genes of Mycobacterium tuberculosis that conferred antibiotic tolerance on tubercle bacilli isolated from the tuberculosis patients under treatment with four antitubercular antibiotics. Statistically significant comparability between the gene expression profiles of the antibiotic tolerance associated genes of M. smegmatis and M. tuberculosis validated the reliability/utility of the method.
Analysis of university student responses to the pandemic in a formal microbiology assessment
Authors: Çakar Zeynep Petek , Redfern James , Verran Joanna
Published: July 2021

During the coronavirus pandemic, second-year students on the B.Sc. molecular biology and genetics degree at Istanbul Technical University sat an open-ended online exam for a microbiology course in which one of the compulsory questions asked how the course had helped them during the first phase of the pandemic (April–July 2020). Fifty of 69 students gave consent for their (anonymous) responses to be analysed in order to discern any key ways in which their knowledge had been applied. The aim of the study was to investigate whether taking an advanced microbiology course increases understanding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic and has a positive impact on student behaviours with respect to public health practices. Findings were divided into four major themes: course content (information), application of course content to behavioural change (practice), professionalism and their ‘audience’ whilst at home in lockdown (family and friends). Social distancing, wearing face masks, and hand and surface hygiene were described as important behaviours, with this practice informed by their basic microbiology knowledge. This paper describes a scenario where rote assessment can be used to assess wider scientific literacy with respect to application in society, providing students with an opportunity to incorporate and apply their learning into real-life situations, whilst tutors can assess constructivist learning, conceptual understanding and impact on student behaviour.
Classification and genetic counselling for a novel splicing mutation of the MLH1 intron associated with Lynch syndrome in colorectal cancer
Authors: Wang Ling-Ling , Zou Shuang-Mei , Dong Lin , Yang Ming , Qi Dan , Lu Zhao , Chen Jia-Nan , Mei Shi-Wen , Zhao Zhi-Xun , Guan Xu , Jiang Zheng , Liu Qian , Liu Zheng , Wang Xi-Shan
Published: July 2021

Background

Lynch-syndrome-associated cancer is caused by germline pathogenic mutations in mismatch repair genes. The major challenge to Lynch-syndrome screening is the interpretation of variants found by diagnostic testing. This study aimed to classify the MLH1 c.1989 + 5G>A mutation, which was previously reported as a variant of uncertain significance, to describe its clinical phenotypes and characteristics, to enable detailed genetic counselling.

Methods

We reviewed the database of patients with Lynch-syndrome gene detection in our hospital. A novel variant of MLH1 c.1989 + 5G>A identified by next-generation sequencing was further investigated in this study. Immunohistochemical staining was carried out to assess the expression of MLH1 and PMS2 protein in tumour tissue. In silico analysis by Alamut software was used to predict the MLH1 c.1989 + 5G>A variant function. Reverse transcription-polymerase chain reaction and sequencing of RNA from whole blood were used to analyse the functional significance of this mutation.

Results

Among affected family members in the suspected Lynch-syndrome pedigree, the patient suffered from late-stage colorectal cancer but had a good prognosis. We found the MLH1 c.1989 + 5G>A variant, which led to aberrant splicing and loss of MLH1 and PMS2 protein in the nuclei of tumour cells. An aberrant transcript was detectable and skipping of MLH1 exon 17 in carriers of MLH1 c.1989 + 5G>A was confirmed.

Conclusions

MLH1 c.1989 + 5G>A was detected in a cancer family pedigree and identified as a pathological variant in patients with Lynch syndrome. The mutation spectrum of Lynch syndrome was enriched through enhanced genetic testing and close surveillance might help future patients who are suspected of having Lynch syndrome to obtain a definitive early diagnosis.
Causes of America’s Lagging Life Expectancy: An International Comparative Perspective
Authors: Ho Jessica Y
Published: July 2021

Objectives

This study assesses how American life expectancy compares to other high-income countries and identifies key age groups and causes of death responsible for the U.S. life expectancy shortfall.

Methods

Data from the Human Mortality Database, World Health Organization Mortality Database, and vital statistics agencies for 18 high-income countries are used to examine trends in U.S. life expectancy gaps and how American age-specific death rates compare to other countries. Decomposition is used to estimate the contribution of 19 age groups and 16 causes to the U.S. life expectancy shortfall.

Results

In 2018, life expectancy for American men and women was 5.18 and 5.82 years lower than the world leaders and 3.60 and 3.48 years lower than the average of the comparison countries. Americans aged 25–29 experience death rates nearly 3 times higher than their counterparts. Together, injuries (drug overdose, firearm-related deaths, motor vehicle accidents, homicide), circulatory diseases, and mental disorders/nervous system diseases (including Alzheimer’s disease) account for 86% and 67% of American men’s and women’s life expectancy shortfall, respectively.

Discussion

American life expectancy has fallen far behind its peer countries. The U.S.’s worsening mortality at the prime adult ages and eroding old-age mortality advantage drive its deteriorating performance in international comparisons.
Introduction: new trends in Gulf international relations and transnational politics
Authors: Soubrier Emma , Moritz Jessie , Freer Courtney
Published: July 2021

Arabian Peninsula politics are in a period of enormous transformation. In the context of a new generation of rulers seeking legitimacy through ambitious foreign policy regimes, shifting relations with Iran, the 2017–2021 Qatar crisis, and ongoing conflict in Yemen, this article introduces the July 2021 special section of International Affairs, which examines how the Arab states of the Gulf are adapting to these new realities. Questions addressed include: how have transnational identities been manipulated by states during regional disputes? How have oil and gas revenues been redirected to build up religious soft power and enhance state branding efforts? In an increasingly authoritarian world, how has transnational repression interacted with politicized diasporas to impact opposition mobilization? And, how do disputes over airspace help us understand the process of sovereignty-building in the modern Middle East? In pursuing these questions, the special section challenges the particularism still apparent in many analyses of the Gulf region, and seeks to bridge International Relations with fieldwork-based Gulf studies. The research presented in the section highlights new findings within contemporary research on the Gulf that will be of interest both to policy-makers and others seeking to understand the long-term sustainability and balance of power in this critical region.
Turkish foreign policy in a post-western order: strategic autonomy or new forms of dependence?
Authors: Kutlay Mustafa , Öniş Ziya
Published: July 2021

Turkish foreign policy has dramatically transformed over the last two decades. In the first decade of the Justice and Development Party's (AKP) rule, the ‘logic of interdependence’ constituted the driving motive of Turkish foreign policy. In the second decade, however, the ‘logic of interdependence’ and the soft power-driven ‘mediator–integrator’ role were gradually replaced with a quest for ‘strategic autonomy’, accompanied by interventionism, unilateralism and coercive diplomacy. This article explores the causes of this dramatic shift. We argue that ‘strategic autonomy’, which goes beyond a moderate level of status-seeking compatible with Turkey's material power credentials, has a double connotation in the Turkish context. First, it constitutes a framework for the Turkish ruling elite to align with the non-western great powers and balance the US-led hierarchical order. Second, and more importantly, it serves as a legitimating foreign policy discourse for the government to mobilize its electoral base at home, fragment opposition and accrue popular support. We conclude that the search for autonomy from its western allies and the move towards the Russia–China axis has led to Turkey's isolation and permitted the emergence of new forms of dependence.
The Diversity of Photosensitivity and its Implications for Light Pollution
Authors: Alaasam Valentina J , Kernbach Meredith E , Miller Colleen R , Ferguson Stephen M
Published: July 2021

Synopsis

Artificial light at night (ALAN) is a pervasive anthropogenic pollutant, emanating from urban and suburban developments and reaching nearly all ecosystems from dense forests to coastlines. One proposed strategy for attenuating the consequences of ALAN is to modify its spectral composition to forms that are less disruptive for photosensory systems. However, ALAN is a complicated pollutant to manage due to the extensive variation in photosensory mechanisms and the diverse ways these mechanisms manifest in biological and ecological contexts. Here, we highlight the diversity in photosensitivity across taxa and the implications of this diversity in predicting biological responses to different forms of night lighting. We curated this paper to be broadly accessible and inform current decisions about the spectrum of electric lights used outdoors. We advocate that efforts to mitigate light pollution should consider the unique ways species perceive ALAN, as well as how diverse responses to ALAN scale up to produce diverse ecological outcomes.
On the Finite Field Cone Restriction Conjecture in Four Dimensions and Applications in Incidence Geometry
Authors: Koh Doowon , Lee Sujin , Pham Thang
Published: July 2021

The first purpose of this paper is to solve completely the finite field cone restriction conjecture in four dimensions with $-1$ non-square. The second is to introduce a new approach to study incidence problems via restriction theory. More precisely, using the cone restriction estimates, we will prove sharp point-sphere incidence bounds associated with complex-valued functions for sphere sets of small size. Our incidence bounds with a specific function improve significantly, a result given by Cilleruelo, Iosevich, Lund, Roche-Newton, and Rudnev.
Circulating biomarkers associated with pelvic organ prolapse risk in late gestation sows
Authors: Kiefer Zoë E , Studer Jamie M , Chipman Amanda L , Adur Malavika K , Mainquist-Whigham Christine , Gabler Nicholas K , Keating Aileen F , Ross Jason W
Published: July 2021

Sow mortality, as the result of pelvic organ prolapse (POP), has been increasing in the last decade in the U.S. swine industry. The objective of this study was to identify potential biological markers associated with risk of POP in sows. We hypothesized that sows differing in perineal score (PS) from PS1–PS3 (PS1—a presumed low POP risk; PS2—a presumed moderate POP risk; and PS3—a presumed high POP risk) would differ in circulatory biomarkers of inflammation and hormonal profiles. On gestation week 15, 2,864 individual sows were assigned a PS, and subsequently, 1.0%, 2.7%, and 23.4% of PS1, PS2, or PS3 sows, respectively, experienced POP. During PS assignment at days 107–116 of gestation, blood samples were collected from sows on two farms of similar genetics, feed sources, and health status. Whole blood was subjected to complete blood count (CBC) analysis (n = 212) and steroid hormones were measured in serum from a subset (n = 110) of animals assigned PS3 parity matched to PS1. Lipopolysaccharide-binding protein (LBP), tumor necrosis factor-alpha (TNF-α), haptoglobin, C-reactive protein (CRP), and creatine kinase (CK) levels were also evaluated. Complete blood count analysis revealed decreased (P ≤ 0.05) mean platelet volume (3.9%), lymphocytes (6.5%), and monocytes (7.5%) in PS3 compared to PS1 sows. Increased (P ≤ 0.02) abundance of androstenedione (13.4%), androsterone (18.2%), estrone (24.8%), and 17β-estradiol (26.2%) was observed in PS3 compared to PS1 sows. Additionally, a 25.8% increase (P = 0.04) in LBP in PS3 compared to PS1 sows was observed. Many dynamic physiological changes occur in sows during late gestation as they approach farrowing. The data presented herein demonstrate that distinct differences in concentrations of circulating biomarkers exist between late gestation sows at high or low risk for POP and may serve as a useful tool for understanding the etiology of POP and evaluation of mitigation strategies.
Unusual aggregation property of recombinantly expressed cancer-testis antigens in mammalian cells
Authors: Ahmadi Hannaneh , Shogen Kohei , Fujita Kana , Honjo Tomoko , Kakimi Kazuhiro , Futami Junichiro
Published: July 2021

Transient expression of human intracellular proteins in human embryonic kidney (HEK) 293 cells is a reliable system for obtaining soluble proteins with biologically active conformations. Contrary to conventional concepts, we found that recombinantly expressed intracellular cancer-testis antigens (CTAs) showed frequent aggregation in HEK293 cells. Although experimental subcellular localization of recombinant CTAs displayed proper cytosolic or nuclear localization, some proteins showed aggregated particles in the cell. This aggregative property was not observed in recombinant housekeeping proteins. No significant correlation was found between the aggregative and biophysical properties, such as hydrophobicity, contents of intrinsically disordered regions and expression levels, of CTAs. These results can be explained in terms of structural instability of CTAs, which are specifically expressed in the testis and aberrantly expressed in cancer cells and function as a hub in the protein–protein network using intrinsically disordered regions. Hence, we speculate that recombinantly expressed CTAs failed to form this protein complex. Thus, unfolded CTAs formed aggregated particles in the cell.
AMF colonization and community of a temperate invader and co-occurring natives grown under different CO2 concentrations for 3 years
Authors: Lu Xiu-Rong , Feng Wei-Wei , Wang Wen-Jun , Chen Ji-Xin , Sun Jian-Kun , Qu Bo , Liu Ming-Chao , Feng Yu-Long
Published: July 2021

Global changes such as atmospheric CO2 enrichment often facilitate exotic plant invasions and alter soil arbuscular mycorrhizal fungi (AMF) community. However, it is still unclear whether the effects of CO2 enrichment on exotic plant invasions are associated with its effects on root-AMF symbiosis of invasive and native plants. To address this issue, the annual invasive plant Xanthium strumarium and two phylogenetically related annual natives were compared under ambient and elevated CO2 concentrations for three consecutive years. Atmospheric CO2 enrichment increased AMF colonization rates for the species only in few cases, and the invader did not benefit more from CO2 enrichment in terms of AMF colonization. Under ambient CO2 concentration, however, the invader had a higher AMF colonization rate than the natives in the first year of the study, which disappeared in the second and third year of the study due to the increase of AMF colonization rates in the natives but not in the invader. The influences of species, CO2 concentrations and planting year on AMF colonization were associated with their effects on both soil nutrient and AMF community, and the former may be more important as it also influenced the latter. Our results indicate that the invader could more quickly form symbiosis with soil AMF, contributing to adaptation and occupation of new habitats, and that it is necessary to consider the roles of AMF and the effects of time when determining the effects of global changes such as atmospheric CO2 enrichment on exotic plant invasions.
Increased risk of severe malaria in travellers during the COVID-19 pandemic
Authors: de Laval Franck , Maugey Nancy , Bonet d’Oléon Albane , Pommier de Santi Vincent , Ficko Cécile
Published: July 2021

We observed an increase in severe cases of falciparum malaria among French service members (who were travellers in endemic areas) in 2020, which was associated with an increase in the time between onset of symptoms and diagnosis/treatment. The COVID-19 epidemic may have lengthened the malaria diagnosis process, mainly due to clinical similarities.
The formation of binary star clusters in the Milky Way and Large Magellanic Cloud
Authors: Darma R , Arifyanto M I , Kouwenhoven M B N
Published: July 2021

Recent observations of young embedded clumpy clusters and statistical identifications of binary star clusters have provided new insights into the formation process and subsequent dynamical evolution of star clusters. The early dynamical evolution of clumpy stellar structures provides the conditions for the origin of binary star clusters. Here, we carry out N-body simulations in order to investigate the formation of binary star clusters in the Milky Way and in the Large Magellanic Cloud (LMC). We find that binary star clusters can form from stellar aggregates with a variety of initial conditions. For a given initial virial ratio, a higher degree of initial substructure results in a higher fraction of binary star clusters. The number of binary star clusters decreases over time due to merging or dissolution of the binary system. Typically, $\sim 45{{\ \rm per\ cent}}$ of the aggregates evolve into binary/multiple clusters within t = 20 Myr in the Milky Way environment, while merely $\sim 30{{\ \rm per\ cent}}$ survives beyond t = 50 Myr, with separations ≲ 50 pc. On the other hand, in the LMC, $\sim 90{{\ \rm per\ cent}}$ of the binary/multiple clusters survive beyond t = 20 Myr and the fraction decreases to $\sim 80{{\ \rm per\ cent}}$ at t = 50 Myr, with separations ≲ 35 pc. Multiple clusters are also rapidly formed for highly substructured and expanding clusters. The additional components tend to detach and the remaining binary star cluster merges. The merging process can produce fast rotating star clusters with mostly flat rotation curves that speed up in the outskirts.
The divergence-free condition in axisymmetric magnetohydrodynamic models
Authors: Taroyan Y , Hovhannisyan G , Sumner C
Published: July 2021

Axisymmetric magnetohydrodynamic (MHD) models are useful in studies of magnetized winds and non-linear Alfvén waves in solar and stellar atmospheres. We demonstrate that a condition often used in these models for the determination of a nearly vertical magnetic field is applicable to a radial field instead. A general divergence-free condition in curvilinear coordinates is self-consistently derived and used to obtain the correct condition for the variation of a nearly vertical magnetic field. The obtained general divergence-free condition along with the transfield equation completes the set of MHD equations in curvilinear coordinates for axisymmetric motions and could be useful in studies of magnetized stellar winds and non-linear Alfvén waves.
MOMC-4. Proteogenomic and metabolomic characterization of glioblastoma
Authors: Wang Liang-Bo , Karpova Alla , Gritsenko Marina , Kyle Jennifer , Cao Song , Li Yize , Rodland Karin , Liu Tao , Ding Li
Published: July 2021

Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs. We identified key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation as well as potential targets for EGFR-, TP53- and RB1-altered tumors. We detected immune subtypes, driven by the presence of distinct immune cell populations using bulk omics, validated by single nulcei RNA sequencing (snRNA-seq), and they were correlated with specific expression and histone acetylation patterns. Acetylation of histone H2B in classical-like and immune-low GBM was driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identified specific lipid distributions across subtypes and distinct global metabolic changes in IDH mutated tumors. This work highlights biological relationships which could potentially aid GBM patient stratifications for more effective treatments.
OPTC-4. Bioinformatic analysis of COLXIα1 gene expression and its alternative splicing regulation in Paediatric Diffuse Intrinsic Pontine Gliomas (DIPGs)
Authors: Jedrysik Malwina , Loveson Katie L , Kozusko Nikita , Singh Poonam , Allison Kieren , Fillmore Helen L
Published: July 2021

Paediatric Diffuse Intrinsic Pontine Glioma (DIPGs), is a rare aggressive childhood malignancy that arise in a region and age specific manner, with no cure and children seldom survive 2 years after diagnosis. There has been significant advances in genomic and molecular identification of driver genes as well as signature mutations that help with diagnosis. A multi-methodological approach to begin to profile the DIPG/host landscape in the context of developing brainstem was conducted. Bioinformatic analyses of a DIPG dataset and normal developing brain dataset to help separate expression associated with development from tumour was conducted. In parallel; fixed-formalin paraffin embedded DIPG tissue was obtained from post-mortem brain for focused RNA arrays and RNAseq. Two of several overlapping genes that were overexpressed in DIPG was tenascin C and the collagen XI (α1) gene (COL11A1). A common feature of these genes is that they are alternatively spliced. Therefore, the aim of this study was to focus on COL11A1, further explore its expression in diffuse midline gliomas (DMGs), to determine association with H3K27M alterations and to explore the use of bioinformatic programmes that could potentially predict the specific Col11α1 isoform expression in DIPG. The following programs were used to determine if a bioinformation approach could aid in our understanding of alternative splicing in development and DIPG: R2: Genomics Analysis and Visualization Platform, SnapGene program, Basic Local Alignment Search Tools (BLAST), RNA Interactome Database (RNAInter). In silico analysis highlited an RNA-binding protein eIF4A3 as a candidate of alternative splicing regulator of COL11A1 gene. EIF4A3 gene was shown to be upreguated in DIPG using publicly available datasets. Results shows that isoform A is the most likely isoform present in DIPG. The data obtained will help inform future in vitro and in vivo investigations into the potential role of COL11A1 and its isoforms in DIPG.
Coronavirus Disease 2019 in a Patient With a Systemic Autoinflammatory Syndrome due to an NLRC4 Inflammasomopathy
Authors: Duncan-Lowey Jeffrey K , Chowdhary Vaidehi , Dunne Dana W
Published: July 2021

The effect of autoinflammatory diseases on severe acute respiratory syndrome coronavirus 2 infection remains unknown. We report a case of coronavirus disease 2019 (COVID-19) in a patient with autoinflammation with infantile enterocolitis with inflammatory flares due to a mutation in the inflammasome component NLRC4. This case highlights the role of immunosuppression in patients with autoinflammation with COVID-19.
Spectrum composition of galactic center X-ray emission with point and diffuse X-ray sources
Authors: Nobukawa Masayoshi , Koyama Katsuji
Published: July 2021

This paper reports that the X-ray spectrum from the Galactic Center X-ray Emission (GCXE) is expressed by an assembly of active binaries, non-magnetic cataclysmic variables, magnetic cataclysmic variables (X-ray active stars: XASs), cold matter, and diffuse sources. In the fitting of the limited components of the XASs, the GCXE spectrum exhibits significant excesses with χ2/d.o.f. = 5.67. The excesses are found at the energies of Kα, Heα, Lyα, and the radiative recombination continuum of S, Fe, and Ni. By adding components of the cold matter and the diffuse sources, the GCXE spectrum is nicely reproduced with χ2/d.o.f. = 1.53, which is the first quantitative model for the origin of the GCXE spectrum. The drastic improvement is mainly due to the recombining plasmas in the diffuse sources, which indicate the presence of high-energy activity of Sgr A* in the past of >1000 yr.
Breastfeeding, Personal Responsibility and Financial Incentives
Authors: Hoskins Katelin , Schmidt Harald
Published: July 2021

Should financial incentives be offered to mothers for breastfeeding? Given the significant socioeconomic and sociodemographic differences in breastfeeding in the USA, researchers and policymakers are exploring the role of financial incentives for breastfeeding promotion with the objective of increasing uptake and reducing disparities. Despite positive outcomes in other health domains, the acceptability of financial incentives is mixed. Financial incentives in the context of infant feeding are particularly controversial given the complex obligations that characterize decisions to breastfeed. After situating the specific ethical tensions related to personal responsibility, fairness, and intrusiveness, we argue that exploring carefully designed financial incentives can be ethically justified to support breastfeeding uptake particularly given (i) established medical guidelines that support breastfeeding benefits, (ii) wide socioeconomic and racial/ethnic disparities and (iii) notable influences in the broader choice architecture of infant feeding in the USA. Additional empirical research is warranted to better understand effectiveness, cost and specific ethical concerns related to free and informed choice.
Suicidal ideation in the perinatal period: findings from the Thailand–Myanmar border
Authors: Fellmeth G , Nosten S , Khirikoekkong N , Oo M M , Gilder M E , Plugge E , Fazel M , Fitzpatrick R , McGready R
Published: July 2021

Background

Suicide is a leading cause of maternal death globally. Migrant and refugee populations may experience higher risk of suicide. We report data on suicidal ideation from migrant and refugee women living on the Thailand–Myanmar border.

Methods

Women were recruited in their first trimester of pregnancy. Depression status was assessed by diagnostic interview in the first, second and third trimesters and at 1 month post-partum. We calculated prevalence of suicidal ideation and used logistic regression to identify associated socio-demographic factors.

Results

During the perinatal period, 5.3% (30/568) women experienced suicidal ideation. Refugee women were more likely to experience suicidal ideation than migrant women (8.0 versus 3.1%; P = 0.01). Most women with suicidal ideation did not have severe depression. Previous trauma (OR 2.32; 95% CI: 1.70–3.15) and unplanned pregnancy (OR 2.74; 95% CI: 1.10–6.86) were significantly associated with suicidal ideation after controlling for all other variables.

Conclusions

Suicidal ideation represents an important symptom among migrant and refugee women on the Thailand–Myanmar border. Screening only those with severe depression may be insufficient to identify women at risk of suicide. Community-level interventions addressing social and gender inequalities and prioritization of family planning programmes are needed alongside targeted suicide prevention initiatives to help lower the rates of people dying by suicide.
Cross-sectional associations between domain-specific sitting time and other lifestyle health behaviours: the Stormont study
Authors: Kettle Victoria E , Hamer Mark , Munir Fehmidah , Houdmont Jonathan , Wilson Kelly , Kerr Robert , Addley Ken , Sherar Lauren B , Clemes Stacy A
Published: July 2021

Background

There is a dearth of literature on how different domains of sitting time relate to other health behaviours. Therefore, this study aimed to explore these associations in a sample of office workers.

Methods

7170 Northern Irish Civil Servants completed an online survey which included information on workday and non-workday sitting time in five domains (travel, work, TV, computer-use, leisure-time), physical activity, fruit and vegetable intake, alcohol consumption and cigarette smoking. An unhealthy behaviour score was calculated by summing the number of health behaviours which did not meet the current guidelines. Multinomial regressions examined associations between unhealthy behaviour score and each domain of sitting time.

Results

≥7 hours sitting at work and ≥2 hours TV viewing on a workday both more than doubled the odds of partaking in ≥3 unhealthy behaviours [Odds ratio, OR = 2.03, 95% CI, (1.59–2.61); OR = 2.19 (1.71–2.80)] and ≥3 hours of TV viewing on a non-workday nearly tripled the odds [OR = 2.96 (2.32–3.77)].

Conclusions

High sitting time at work and TV viewing on a workday and non-workday are associated with increased odds of partaking in multiple unhealthy behaviours. Interventions need to focus on these domains and public health policy should consider sitting time as an important health behaviour.
COMPARISON OF PHOTON-COUNTING AND FLAT-PANEL DIGITAL MAMMMOGRAPHY FOR THE PURPOSE OF 3D IMAGING USING A NOVEL IMAGE PROCESSING METHOD
Authors: Svahn T M , Gordon R , Ast J C , Riffel J , Hartbauer M
Published: July 2021

The purpose of the present work was to compare the quality of low-dose projections from a photon-counting with a flat-panel system, and to evaluate a novel image processing method. Images were acquired of phantoms in both systems at average glandular doses ranging from ~ 0.15 to 1.4 mGy. Automated detection of low-contrast features and modulation transfer functions were evaluated in phantom images. The novel image processing method was compared with standard processing in a series of clinical cases. At low-doses (~0.15) the photon-counting system out-performed the flat-panel system with a much higher detectability of low-contrast features. The novel algorithm was superior to both manufacturers’ processing in terms of conspicuity of soft-tissue lesions (p > 0.05), whereas it was not significantly different in calcification conspicuity. Photon-counting should allow more low-dose projections to be acquired at the same total dose. The novel image enhancer can help to further increase the image quality.
The publicness of publicly funded research
Authors: Link Albert N , Wagner Caroline S
Published: July 2021

In this paper, we chronicle key US legislative initiatives during the post–World War II history of public policy related to the ownership of publicly funded research-based knowledge. Our motivation for recording this history is the observation that many scholars, who are appropriately concerned about taxpayer rights, have argued for the need for public policy to clarify ownership of the publicness or openness of publicly funded research results when in fact such public policies have long been in place. We conclude this historical trace with the proposition that if the past is prologue to the future, one might expect future administrations to continue to acknowledge the importance of public access to findings from publicly funded research, be that research having occurred in federal laboratories, universities, or private-sector organizations.
Efficacy of a stepped care approach to deliver cognitive-behavioral therapy for insomnia in cancer patients: a noninferiority randomized controlled trial
Authors: Savard Josée , Ivers Hans , Savard Marie-Hélène , Morin Charles M , Caplette-Gingras Aude , Bouchard Stéphane , Lacroix Guy
Published: July 2021

Study Objectives

Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended first-line treatment for cancer-related insomnia, but its accessibility is very limited in routine care. A stepped care approach has been recommended as a cost-effective way to make CBT-I more widely accessible. However, no controlled study has yet been published about the efficacy of this approach. The goal of this noninferiority randomized controlled trial (RCT) was to compare the short and long-term efficacy of a stepped care CBT-I (StepCBT-I) to a standard face-to-face CBT-I (StanCBT-I).

Methods

A total of 177 cancer patients were randomized to: (1) StanCBT-I (6 face-to-face CBT-I sessions; n = 59) or (2) StepCBT-I (n = 118). In the StepCBT-I group, patients with less severe insomnia first received a web-based CBT-I (n = 65), while those with more severe insomnia received 6 face-to-face CBT-I sessions (n = 53). In both cases, patients could receive up to three booster sessions of CBT-I if they still had insomnia symptoms following this first step.

Results

Results indicated that the Step-CBT-I group showed an Insomnia Severity Index score reduction and a sleep efficiency (on a sleep diary) increase that was not significantly inferior to that of StanCBT-I at all post-treatment time points. Analyses of secondary outcomes indicated significant time effects (ps < .001) and no significant group-by-time interactions (ps from .07 to .91) on other sleep diary parameters, sleep medication use, depression, anxiety, fatigue, and quality of life scores.

Conclusion(s)

The efficacy of stepped care CBT-I is not inferior to that of a standard face-to-face intervention and is a valuable approach to making this treatment more widely accessible to cancer patients.

Trial registration

ClinicalTrials.gov Identifier: NCT01864720 (https://clinicaltrials.gov/ct2/show/NCT01864720?term=Savard&draw=2&rank=6; Stepped Care Model for the Wider Dissemination of Cognitive-Behavioural Therapy for Insomnia Among Cancer Patients).
Phylogenomic Species Delimitation Dramatically Reduces Species Diversity in an Antarctic Adaptive Radiation
Authors: Parker Elyse , Dornburg Alex , Struthers Carl D , Jones Christopher D , Near Thomas J
Published: July 2021

Application of genetic data to species delimitation often builds confidence in delimitations previously hypothesized using morphological, ecological, and geographic data and frequently yields recognition of previously undescribed cryptic diversity. However, a recent critique of genomic data-based species delimitation approaches is that they have the potential to conflate population structure with species diversity, resulting in taxonomic oversplitting. The need for an integrative approach to species delimitation, in which molecular, morphological, ecological, and geographic lines of evidence are evaluated together, is becoming increasingly apparent. Here, we integrate phylogenetic, population genetic, and coalescent analyses of genome-wide sequence data with investigation of variation in multiple morphological traits to delimit species within the Antarctic barbeled plunderfishes (Artedidraconidae: Pogonophryne). Pogonophryne currently comprises 29 valid species, most of which are distinguished solely by variation in the ornamentation of the mental barbel that projects from the lower jaw, a structure previously shown to vary widely within a single species. However, our genomic and phenotypic analyses result in a dramatic reduction in the number of distinct species recognized within the clade, providing evidence to support the recognition of no more than six species. We propose to synonymize 24 of the currently recognized species with five species of Pogonophryne. We find genomic and phenotypic evidence for a new species of Pogonophryne from specimens collected in the Ross Sea. Our findings represent a rare example in which the application of molecular data provides evidence of taxonomic oversplitting on the basis of morphology, clearly demonstrating the utility of an integrative species delimitation framework.[ddRADseq; multispecies coalescent; Notothenioidei; SNPs; Southern Ocean.]
Lactate and blood ammonia on admission as biomarkers to predict the prognosis of patients with acute mushroom poisoning and liver failure: a retrospective study
Authors: Gao Yanguo , Zhang Hongqiao , Zhong Hua , Yang Suosuo , Wang Qiuyan
Published: July 2021

The diagnosis of liver damage induced by mushroom poisoning is still challenging. This study aims to screen the early biological indexes that could predict acute mushroom poisoning with liver damage. The patients with acute mushroom poisoning and liver damage admitted to The First Affiliated Hospital of Dalian Medical University，China from July 2007 to August 2017 were analyzed retrospectively. A total of 66 patients were enrolled in this study, with 44 and 22 patients in the liver injury group and liver failure group, respectively. Ten patients in the liver failure group died, with a mortality of 45.5% in this group. Multivariable Cox regression showed that the blood ammonia (NH3) and lactic acid (Lac) at the time of admission were independently associated with the in-hospital time to death for patients with liver failure induced by mushroom poisoning. Lactate and blood ammonia at the time of admission could be used to predict the prognosis of patients with acute mushroom poisoning and liver failure.
Thymic lymphomas in a 6-Month rasH2-Tg mouse carcinogenicity study with the RORγt Inverse Agonist, BMS-986251
Authors: Haggerty Helen G , Sathish Jean G , Gleason Carol R , Al-Haddawi Muthafar , Brodie Thomas A , Bonnette Kimberly L , Lewis Bridget S , Graziano Michael J
Published: July 2021

BMS-986251 is a RORγt inverse agonist that was in development for the treatment of autoimmune diseases. RORγt is a nuclear hormone receptor and transcription factor that is involved in the differentiation and function of TH17 cells. RORγt-deficient (constitutive or conditional) mice develop thymic lymphomas with >50% mortality at 4 months, while heterozygous mice are normal. A six-month study was conducted in rasH2-Tg hemizygous mice to assess the potential carcinogenicity of BMS-986251. BMS-986251 was administered once daily by oral gavage to groups of 27 mice/sex at doses of 0 (water control), 0 (vehicle control), 5, 25, or 75 mg/kg. The positive control, N-methyl-N-nitrosourea, was administered by a single intraperitoneal injection to 15 mice/sex at a dose of 75 mg/kg. There were no tumors attributed to BMS-986251 except for thymic lymphomas. Thymic lymphoma was observed in 1 male (3.7%) and 3 females (11.1%) at the mid dose, and 6 females (22.2%) at the high dose. No lymphomas were observed in the negative control groups whereas the incidence of lymphomas in the positive control group was 47-60%. The incidence of thymic lymphomas in the BMS-986251-treated groups was higher than published literature and test facility historical control data. Furthermore, increased thymic lymphoid cellularity (lymphoid hyperplasia) was observed at the mid dose in males and at all doses in females. Since lymphoid hyperplasia may represent a pre-neoplastic change, a no-effect dose for potential tumor induction was not identified in this study. These results led to the discontinuation of BMS-986251 and underscores the challenges in targeting RORγt for drug development.
An Analysis and Evaluation of the Theory of Planned Behavior Using Fawcett and DeSanto-Madeya's Framework
Authors: Park Sungwon , Shin Hyewon
Published: July 2021

The theory of planned behavior has been prominently applied in nursing, but no known critique of the theory has been published. Using Fawcett and Desanto-Madeya's framework, we scrutinized and assessed the theory to determine its appropriateness for nursing investigations of behavior. The theory makes explicit assertions regarding human social behavior, incorporating some nursing metaparadigm concepts. Although not derived from the discipline, the theory's scope, content, and context are relevant to nursing, and its significance to nursing research and practice is clear. Studies incorporating all the theory's concepts and relationships are needed to confirm its testability and empirical and pragmatic adequacy.
Vascularized Pedicled Fibula for Pediatric Tibia Reconstruction
Authors: Medda Suman , King Matthew A. , Runyan Christopher M. , Frino John
Published: July 2021

This video reviews the technique of a vascularized fibula flap for pediatric tibia reconstruction. A 4-year-old boy with a history of a left tibial infected nonunion status after multiple debridements presented with segmental bone loss and difficulty with ambulation. An ipsilateral vascularized fibula flap was used for reconstruction. The patient proceeded to union and was independently ambulatory with bracing.