bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic Placental Disease, Preterm Delivery, and Their Association With Opioid Use During Pregnancy
Authors: Esposito Daina B , Bateman Brian , Werler Martha , Straub Loreen , Mogun Helen , Hernandez-Diaz Sonia , Huybrechts Krista
Published: June 2021

Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited. Using a cohort of pregnant women in the US nationwide Medicaid Analytic eXtract (2000–2014), we compared women with ≥2 opioid dispensings in pregnancy with unexposed women. Given an uncertain etiologically relevant window, we assessed exposure occurring in early pregnancy, late and not early pregnancy, and both early and late pregnancy. For placental abruption, preterm delivery, small for gestational age (SGA), and preeclampsia, we estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) using Cox proportional hazard models adjusting for demographic factors, indications/comorbidities, and medications. Among 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled in 6.5%. We observed an early exposure aHR of 1.34 (95% CI: 1.26, 1.43) for placental abruption, 1.21 (95% CI: 1.18, 1.23) for preterm delivery, 1.13 (95% CI: 1.09, 1.17) for SGA, and 0.95 (0.91, 0.98) for preeclampsia. Estimates for late exposure were attenuated. Early and late exposure was associated with higher aHRs for placental abruption, 1.62 (95% CI: 1.47, 1.78); preterm delivery, 1.37 (95% CI: 1.33, 1.42); and SGA, 1.26 (95% CI: 1.19, 1.33); but not preeclampsia, 0.99 (95% CI: 0.93, 1.05). Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia.
A novel graph attention model for predicting frequencies of drug–side effects from multi-view data
Authors: Zhao Haochen , Zheng Kai , Li Yaohang , Wang Jianxin
Published: June 2021

Identifying the frequencies of the drug–side effects is a very important issue in pharmacological studies and drug risk–benefit. However, designing clinical trials to determine the frequencies is usually time consuming and expensive, and most existing methods can only predict the drug–side effect existence or associations, not their frequencies. Inspired by the recent progress of graph neural networks in the recommended system, we develop a novel prediction model for drug–side effect frequencies, using a graph attention network to integrate three different types of features, including the similarity information, known drug–side effect frequency information and word embeddings. In comparison, the few available studies focusing on frequency prediction use only the known drug–side effect frequency scores. One novel approach used in this work first decomposes the feature types in drug–side effect graph to extract different view representation vectors based on three different type features, and then recombines these latent view vectors automatically to obtain unified embeddings for prediction. The proposed method demonstrates high effectiveness in 10-fold cross-validation. The computational results show that the proposed method achieves the best performance in the benchmark dataset, outperforming the state-of-the-art matrix decomposition model. In addition, some ablation experiments and visual analyses are also supplied to illustrate the usefulness of our method for the prediction of the drug–side effect frequencies. The codes of MGPred are available at https://github.com/zhc940702/MGPred and https://zenodo.org/record/4449613.
Tracking the pipeline: immunoinformatics and the COVID-19 vaccine design
Authors: Rezaei Shokouh , Sefidbakht Yahya , Uskoković Vuk
Published: June 2021

With the onset of the COVID-19 pandemic, the amount of data on genomic and proteomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stored in various databases has exponentially grown. A large volume of these data has led to the production of equally immense sets of immunological data, which require rigorous computational approaches to sort through and make sense of. Immunoinformatics has emerged in the recent decades as a field capable of offering this approach by bridging experimental and theoretical immunology with state-of-the-art computational tools. Here, we discuss how immunoinformatics can assist in the development of high-performance vaccines and drug discovery needed to curb the spread of SARS-CoV-2. Immunoinformatics can provide a set of computational tools to extract meaningful connections from the large sets of COVID-19 patient data, which can be implemented in the design of effective vaccines. With this in mind, we represent a pipeline to identify the role of immunoinformatics in COVID-19 treatment and vaccine development. In this process, a number of free databases of protein sequences, structures and mutations are introduced, along with docking web servers for assessing the interaction between antibodies and the SARS-CoV-2 spike protein segments as most commonly considered antigens in vaccine design.
Iodoacetic acid affects estrous cyclicity, ovarian gene expression, and hormone levels in mice
Authors: Gonsioroski Andressa , Meling Daryl D , Gao Liying , Plewa Michael J , Flaws Jodi A
Published: June 2021

Iodoacetic acid (IAA) is a water disinfection byproduct that is an ovarian toxicant in vitro. However, information on the effects of IAA on ovarian function in vivo was limited. Thus, we determined whether IAA exposure affects estrous cyclicity, steroidogenesis, and ovarian gene expression in mice. Adult CD-1 mice were dosed with water or IAA (0.5–500 mg/L) in the drinking water for 35–40 days during which estrous cyclicity was monitored for 14 days. Ovaries were analyzed for expression of apoptotic factors, cell cycle regulators, steroidogenic factors, estrogen receptors, oxidative stress markers, and a proliferation marker. Sera were collected to measure pregnenolone, androstenedione, testosterone, estradiol, inhibin B, and follicle-stimulating hormone (FSH) levels. IAA exposure decreased the time that the mice spent in proestrus compared to control. IAA exposure decreased expression of the proapoptotic factor Bok and the cell cycle regulator Ccnd2 compared to control. IAA exposure increased expression of the proapoptotic factors Bax and Aimf1, the antiapoptotic factor Bcl2l10, the cell cycle regulators Ccna2, Ccnb1, Ccne1, and Cdk4, and estrogen receptor Esr1 compared to control. IAA exposure decreased expression of Sod1 and increased expression of Cat, Gpx and Nrf2. IAA exposure did not affect expression of Star, Cyp11a1, Cyp17a1, Hsd17b1, Hsd3b1, Esr2, or Ki67 compared to control. IAA exposure decreased estradiol levels, but did not alter other hormone levels compared to control. In conclusion, IAA exposure alters estrous cyclicity, ovarian gene expression, and estradiol levels in mice.
Non-coding RNAs in cardiac inflammation: key drivers in the pathophysiology of heart failure
Authors: Sansonetti Marida , De Windt Leon J
Published: June 2021

Heart failure is among the most progressive diseases and a leading cause of morbidity. Despite several advances in cardiovascular therapies, pharmacological treatments are limited to relieve symptoms without curing cardiac injury. Multiple observations point to the involvement of immune cells as key drivers in the pathophysiology of heart failure. In particular, there is a growing recognition that heart failure is related to a prolonged and insufficiently repressed inflammatory response leading to molecular, cellular, and functional cardiac alterations. Over the last decades, non-coding RNAs are recognized as prominent mediators of cardiac inflammation, affecting the function of several immune cells. In the current review, we explore the contribution of the diverse immune cells in the progression of heart failure, revealing mechanistic functions for non-coding RNAs in cardiac immune cells as a new and exciting field of investigation.
Effectiveness and Safety of Adalimumab Biosimilar SB5 in Inflammatory Bowel Disease: Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naïve SB5 Observational Cohorts
Authors: Derikx Lauranne A A P , Dolby Heather W , Plevris Nikolas , Lucaciu Laura , Rees Caitlin S , Lyons Mathew , Siakavellas Spyros I , Constantine-Cooke Nathan , Jenkinson Philip , Su Shanna , O’Hare Claire , Kirckpatrick Laura , Merchant Lynne M , Noble Colin , Arnott Ian D , Jones Gareth-Rhys , Lees Charlie W
Published: June 2021

Background and Aims

Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort].

Methods

We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected.

Results

In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event.

Conclusion

Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up.
Transcriptome-wide identification and characterization of microRNAs in diverse phases of wood formation in Populus trichocarpa
Authors: Wang Ruiqi , Reng Mengxuan , Tian Shuanghui , Liu Cong , Cheng He , Liu Yingying , Zhang Huaxin , Saqib Muhammad , Wei Hairong , Wei Zhigang
Published: June 2021

We applied miRNA expression profiling method to Populus trichocarpa stems of the three developmental stages, primary stem (PS), transitional stem (TS), and secondary stem (SS), to investigate miRNA species and their regulation on lignocellulosic synthesis and related processes. We obtained 892, 872, and 882 known miRNAs and 1727, 1723, and 1597 novel miRNAs, from PS, TS, and SS, respectively. Comparisons of these miRNA species among different developmental stages led to the identification of 114, 306, and 152 differentially expressed miRNAs (DE-miRNAs), which had 921, 2639, and 2042 candidate target genes (CTGs) in the three respective stages of the same order. Correlation analysis revealed 47, 439, and 71 DE-miRNA-CTG pairs of high negative correlation in PS, TS, and SS, respectively. Through biological process analysis, we finally identified 34, 6, and 76 miRNA-CTG pairs from PS, TS, and SS, respectively, and the miRNA target genes in these pairs regulate or participate lignocellulosic biosynthesis-related biological processes: cell division and differentiation, cell wall modification, secondary cell wall biosynthesis, lignification, and programmed cell death processes. This is the first report on an integrated analysis of genome-wide mRNA and miRNA profilings during multiple phases of poplar stem development. Our analysis results imply that individual miRNAs modulate secondary growth and lignocellulosic biosynthesis through regulating transcription factors and lignocellulosic biosynthetic pathway genes, resulting in more dynamic promotion, suppression, or regulatory circuits. This study advanced our understanding of many individual miRNAs and their essential, diversified roles in the dynamic regulation of secondary growth in woody tree species.
Gaps to Address in Ecological Studies of Temperament and Physiology
Authors: McMahon Elyse K , Cavigelli Sonia A
Published: June 2021

Ecology is a diverse field with many researchers interested in drivers and consequences of variability within populations. Two aspects of variability that have been addressed are behavioral and physiological. While these have been shown to separately influence ecological outcomes such as survival, reproductive success, and fitness, combined they could better predict within-population variability in survival and fitness. Recently there has been a focus on potential fitness outcomes of consistent behavioral traits that are referred to as personality or temperament (e.g., boldness, sociability, and exploration). Given this recent focus, it is an optimal time to identify areas to supplement in this field, particularly in determining the relationship between temperament and physiological traits. To maximize progress, in this perspective paper, we propose that the following two areas be addressed: (1) increased diversity of species and (2) increased number of physiological processes studied, with an eye toward using more representative and relatively consistent measures across studies. We first highlight information that has been gleaned from species that are frequently studied to determine how animal personality relates to physiology and/or survival/fitness. We then shine a spotlight on important taxa that have been understudied and that can contribute meaningful, complementary information to this area of research. And last, we propose a brief array of physiological processes to relate to temperament, and that can significantly impact fitness, and that may be accessible in field studies.
Colonial Lives of the Carceral Archipelago: Rethinking the Neoliberal Security State
Authors: Axster Sabrina , Danewid Ida , Goldstein Asher , Mahmoudi Matt , Tansel Cemal Burak , Wilcox Lauren
Published: June 2021

Mass incarceration, police brutality, and border controls are part and parcel of the everyday experiences of marginalized and racialized communities across the world. Recent scholarship in international relations, sociology, and geography has examined the prevalence of these coercive practices through the prism of “disciplinary,” “penal,” or “authoritarian” neoliberalism. In this collective discussion, we argue that although this literature has brought to the fore neoliberalism's reliance on state violence, it has yet to interrogate how these carceral measures are linked to previous forms of global racial ordering. To rectify this moment of “colonial unknowing,” the collective discussion draws on decolonial approaches, Indigenous studies, and theories of racial capitalism. It demonstrates that “new” and “neoliberal” forms of domestic control must be situated within the global longue durée of racialized and colonial accumulation by dispossession. By mapping contemporary modes of policing, incarceration, migration control, and surveillance onto earlier forms of racial–colonial subjugation, we argue that countering the violence of neoliberalism requires more than nostalgic appeals for a return to Keynesianism. What is needed is abolition—not just of the carceral archipelago, but of the very system of racial capitalism that produces and depends on these global vectors of organized violence and abandonment.
Democracy and the Transnational Dimensions of Low-Level Conflict and State Repression
Authors: Roessler Martin , Zwerschke Patrick , Old Jonathan
Published: June 2021

This paper examines the transnational dimensions of low-level conflict and state repression. In this regard, special emphasis is placed on the role of political regimes. Drawing on a simple model, we argue that democracy has opposing effects on conflict intensity. On one hand, democracy satisfies demand for political participation and thus reduces conflict potential, while, on the other hand, we highlight that domestic democracy may spur dissatisfaction and conflict abroad, which, in turn, may induce conflict spillovers. As a result, the net effect of democracy on low-level conflict and state repression is ambiguous and depends on the level of democracy in the neighborhood: We predict that democracy is more pacifying in democratic environments and may spur conflict in autocratic environments. By the symmetry of the model, we also predict that democratic environments are more pacifying for democratic countries and may spur conflict in autocracies. Empirical evidence using panel data on different types of low-level conflict and state repression for 160 countries in the period from 1950 to 2011 supports these hypotheses. Additionally, two case studies illustrate the mechanisms of our model.
Thermoregulatory and physiological responses of nonpregnant, mid-gestation, and late-gestation sows exposed to incrementally increasing dry bulb temperature
Authors: McConn Betty R , Gaskill Brianna N , Schinckel Allan P , Green-Miller Angela R , Lay Donald C , Johnson Jay S
Published: June 2021

Gestating sows may be more susceptible to increasing dry bulb temperatures (TDB) due to greater metabolic heat production and increased body mass, especially as gestation advances. However, there are few studies on the thermoregulatory and physiological responses of sows at differing gestation stages exposed to gradually increasing temperatures. The study objective was to determine the thermoregulatory and physiological responses of nonpregnant (n = 12; parity 3.27 ± 0.86), mid-gestation (59.7 ± 9.6 d pregnant, n = 12; parity 3.25 ± 0.83), and late-gestation (99.0 ± 4.8 d pregnant, n = 12; parity 3.33 ± 0.75) sows exposed to increasing TDB. Prior to the experiment (5.0 ± 0.7 d), jugular catheters were placed in all sows. During the experiment, the TDB was increased incrementally by 2.45 ± 0.43 °C every 60 min from 19.84 ± 2.15 to 35.54 ± 0.43 °C over 400 min, and relative humidity was recorded at 40.49 ± 18.57%. Respiration rate (RR), heart rate (HR), skin temperature, and vaginal temperature were measured, and blood samples were obtained via the jugular catheter every 20 min. Data were analyzed using PROC MIXED in SAS 9.4. RR increased at a lower TDB (P < 0.01) in late-gestation sows compared with mid-gestation and nonpregnant sows, but no differences were detected between mid-gestation and nonpregnant sows. Overall, late-gestation sows had greater RR (P < 0.01; 23 ± 2 breaths per min [brpm]) compared with mid-gestation (16 ± 2 brpm) and nonpregnant (15 ± 2 brpm) sows. Late-gestation sows had an overall greater HR (P < 0.01; 84 ± 5 beats per min [bpm]) than mid-gestation (76 ± 5 bpm) and nonpregnant (69 ± 5 bpm) sows. Late-gestation sows had overall reduced bicarbonate and total carbon dioxide levels (P = 0.02; 23.89 ± 1.97 and 25.41 ± 2.07 mmol/L, respectively) compared with mid-gestation (27.03 ± 1.97 and 28.58 ± 2.07 mmol/L, respectively) and nonpregnant (26.08 ± 1.97 and 27.58 ± 2.07 mmol/L, respectively) sows. Moreover, late-gestation sows had overall greater nitric oxide levels (P < 0.01; 248.82 ± 34.54 µM) compared with mid-gestation (110.47 ± 34.54 µM) and nonpregnant (41.55 ± 34.54 µM) sows. In summary, late-gestation sows appear to be more sensitive to increasing TDB as indicated by thermoregulatory and physiological responses when compared with mid-gestation or nonpregnant sows. The results from this study provide valuable information regarding thermoregulatory thresholds of sows at differing gestation stages.
High Dose Ascorbic Acid During Acute Resuscitation in Critically Burn Patients
Authors: Flores Eva , Sánchez-Sánchez Manuel , Gutierrez Claudio , Estébanez Belen , Millán Pablo , Gutierrez Carola , Gonzalez Alvaro , Garcia de Lorenzo Abelardo
Published: June 2021

Ascorbic acid (AA) is a potent oxygen–free radical scavenger. We hypothesized that treating severe burn patients with high doses of AA (HDAA) can reduce fluid resuscitation requirements and prevent organ dysfunction. We performed a unicentric, retrospective case-control study of 75 burn patients: 25 patients admitted from 2018 to 2019 with more than 30% Total Surface Body Surface Area (TSBA) burned who received HDAA (66 mg/kg/h as soon as possible after admission until 36 h after injury), and 50 patients admitted from 2014 to 2017 with similar Abbreviated Burn Severity Index (ABSI)/Baux scores who were treated with the same protocol but did not receive HDAA. During the first 24 hours of burn resuscitation the HDAA group required less fluids than the control group (3.06 ± 0.87 ml/kg/%TBSA vs 4.32 ± 1.51 P < .05), but the overall reduction of fluid requirements during the first 72 hours was not significant. There were no significant differences in Sequential Organ Failure Assessment (SOFA), other hemodynamic parameters, complications, or mortality. We also did not find an increase acute kidney injury in patients who received HDAA even though the mean urine oxalate/creatinine ratio was 0.61 (0.02–0.96). We conclude that in severe burn patients treated with a restrictive fluid therapy protocol, administration of HDAA can decrease only the initial fluid requirements but not total fluid intakes. We did not find differences in severity score after resuscitation or in mortality. Nor did we find an increase in renal failure in patients administered with HDAA.
The Effectiveness of Laser Therapy for Hypertrophic Burn Scars in Pediatric Patients: A Prospective Investigation
Authors: Zuccaro Jennifer , Kelly Charis , Perez Manuela , Doria Andrea , Fish Joel S
Published: June 2021

Laser therapy has become a valuable treatment option for hypertrophic burn scars. Improvements in scar symptoms have been achieved using the ablative fractional carbon dioxide laser as well as the pulsed dye laser. However, research regarding the use of laser therapy among pediatric patients remains limited. Thus, the aim of this study was to investigate the effectiveness of using laser therapy to improve hypertrophic burn scars in a pediatric population using a comprehensive scar assessment protocol. A pragmatic, single-center, prospective observational study was conducted at a tertiary pediatric hospital. Twenty participants with hypertrophic burn scars were included. Laser procedures were administered at approximately two month intervals and scars were evaluated at five time points over one year using the Vancouver Scar Scale, the Patient and Observer Scar Assessment Scale, conventional ultrasound, ultrasound elastography, and a multi-probe skin analysis device. Seventy-one laser procedures were performed with most participants receiving treatment with both the ablative fractional carbon dioxide laser and the pulsed dye laser at the same session (83%). From baseline to study completion, significant improvements in all scar measures were observed (p < .05). In particular, improvements in overall scarring and in specific scar properties including thickness, stiffness, and color were found (p < .05). To the best our knowledge, this is the most comprehensive study to date to evaluate the effect of laser treatment on hypertrophic burn scars in a pediatric population. Our findings suggest that laser therapy is a beneficial treatment for burn-injured children as evidenced by the improvements in subjective and objective scar assessment measures.
High Prevalence of Borrelia mayonii (Spirochaetales: Spirochaetaceae) in Field-Caught Tamias striatus (Rodentia: Sciuridae) From Northern Wisconsin
Authors: Siy Patricia N , Larson Ryan T , Zembsch Tela E , Lee Xia , Paskewitz Susan M
Published: June 2021

Borrelia mayonii is a recently discovered bacterial spirochete that causes Lyme disease and is transmitted by the blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae). To date, B. mayonii has been isolated from two vertebrate host species in Minnesota: field-caught white-footed mice (Peromyscus leucopus Rafinesque; Rodentia: Cricetidae) and American red squirrel (Tamiasciurus hudsonicus Erxleben). Here, we describe the first detection of B. mayonii in field-caught eastern chipmunks (Tamias striatus L. (Rodentia: Cricetidae)) from northern Wisconsin. During our study, we captured 530 unique small mammals and found an infection prevalence of 23.50% in field-caught eastern chipmunks (4/17) and 1.19% in Peromyscus spp. (5/420). Mean larval and nymphal burdens were determined for captured Blarina brevicauda (0, 0), Glaucomys volans (0.29, 0.14), Myodes gapperi (0.27, 0), Napaeozapus insignis (0, 0.25), Peromyscus spp. (1.88, 0.11), T. striatus (1.06, 0.65), and Sorex cinereus (0.09, 0). The high B. mayonii infection prevalence in eastern chipmunks suggests that the species may be an important reservoir for B. mayonii in the Upper Midwest.
Complications 18 years after polyacrylamide hydrogel augmentation mammoplasty: a case report and histopathological analysis
Authors: DeLuca Matthew , Shapiro Alexandra , Banayan Elliot , Zielinski Gregory , Karanetz Irena , Asarian Armand , Xiao Philip
Published: June 2021

Polyacrylamide hydrogel (PAAG) is a synthetic substance previously used as an injectable material for augmentation mammoplasty. Current literature has demonstrated that the average time from PAAG injection to the onset of complication ranges from 6 to 39 months. We present a unique case report describing the onset of complications 18 years after PAAG augmentation mammoplasty. To the best of our knowledge, the presentation of a healthy female who experienced unprovoked expansion of breast tissue >15 years after polyacrylamide injection has not been previously reported in surgical literature. This suggests that serious complications of PAAG injection may occur later than the literature has previously described. Importantly, this case is the first demonstration of the successful surgical removal of polyacrylamide 18 years after injection. Additionally, this case also provides a histopathological analysis of breast capsules which showed evidence of an extensive chronic inflammatory reaction to polyacrylamide, consistent with previous reports.
SiCEP3, a C-terminally encoded peptide from Setaria italica, promotes ABA import and signaling
Authors: Zhang Lei , Ren Yue , Xu Qian , Wan Yiman , Zhang Shizhong , Yang Guodong , Huang Jinguang , Yan Kang , Zheng Chengchao , Wu Changai
Published: June 2021

C-terminally encoded peptides (CEPs) are small peptides, typically post-translationally modified, and highly conserved in many species. CEPs are known to inhibit plant growth and development, but the mechanisms are not well understood. In this study, 14 CEPs were identified in Setaria italica and divided into two groups. The transcripts of most SiCEPs were more abundant in roots than in other detected tissues. SiCEP3, SiCEP4, and SiCEP5 were also highly expressed in panicles. Moreover, expression of all SiCEPs was induced by abiotic stresses and phytohormones. SiCEP3 overexpression and application of synthetic SiCEP3 both inhibited seedling growth. In the presence of abscisic acid (ABA), growth inhibition and ABA content in seedlings increased with the concentration of SiCEP3. Transcripts encoding eight ABA transporters and six ABA receptors were induced or repressed by synthetic SiCEP3, ABA, and their combination. Further analysis using loss-of-function mutants of Arabidopsis genes functioning as ABA transporters, receptors, and in the biosynthesis and degradation of ABA revealed that SiCEP3 promoted ABA import at least via NRT1.2 (NITRATE TRANSPORTER 1.2) and ABCG40 (ATP-BINDING CASSETTE G40). In addition, SiCEP3, ABA, or their combination inhibited the kinase activities of CEP receptors AtCEPR1/2. Taken together, our results indicated that the CEP-CEPR module mediates ABA signaling by regulating ABA transporters and ABA receptors in planta.
A Novel Mutation of the Membrane Metallo-Endopeptidase Gene Related to Late-Onset Hereditary Polyneuropathy: Case Report and Review of the Literature
Authors: Tsamis Konstantinos I , Xiromerisiou Georgia , Nikas Ilias P , Giannakis Alexandros , Konitsiotis Spiridon , Sarmas Ioannis
Published: June 2021

The advent of next generation sequencing has revolutionized diagnostic approaches to hereditary polyneuropathies. Recently, mutations on the membrane metallo-endopeptidase (MME) gene, encoding neprilysin, have been related to the development of late-onset Charcot-Marie-Tooth disease type 2 (CMT2). Here, we report the first Greek patient presenting with a slowly progressive late-onset axonal polyneuropathy and a novel, likely pathogenic, heterozygous variant in the MME gene. In addition, we have performed a systematic review of all published case reports of patients with MME mutations. The results of the studies show that MME variants can be inherited as both fully penetrant autosomal-recessive and incompletely penetrant autosomal-dominant traits. A number of heterozygous variants characterized as incompletely penetrant impose an increased risk of developing a CMT2-like phenotype late in life, identical to the case study described here. Greater mutation numbers in different populations and mutation-specific functional studies will be essential to identify the pathogenicity and inheritance of more MME variants.
Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA
Authors: Garcia-Rodriguez Gabriela , Charlier Daniel , Wilmaerts Dorien , Michiels Jan , Loris Remy
Published: June 2021

The rnlAB toxin-antitoxin operon from Escherichia coli functions as an anti-phage defense system. RnlA was identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an inactive resting state and an active canonical HEPN dimer. Mutants interfering with the transition between states show that canonical HEPN dimerization via the highly conserved RX4-6H motif is required for activity. The antitoxin RnlB binds the canonical HEPN dimer conformation, inhibiting RnlA by blocking access to its active site. Single-alanine substitutions mutants of the highly conserved R255, E258, R318 and H323 show that these residues are involved in catalysis and substrate binding and locate the catalytic site near the dimer interface of the canonical HEPN dimer rather than in a groove located between the HEPN domain and the preceding TBP-like domain. Overall, these findings elucidate the structural basis of the activity and inhibition of RnlA and highlight the crucial role of conformational heterogeneity in protein function.
High-affinity five/six-letter DNA aptamers with superior specificity enabling the detection of dengue NS1 protein variants beyond the serotype identification
Authors: Matsunaga Ken-ichiro , Kimoto Michiko , Lim Vanessa Weixun , Tan Hui Pen , Wong Yu Qian , Sun William , Vasoo Shawn , Leo Yee Sin , Hirao Ichiro
Published: June 2021

Genetic alphabet expansion of DNA by introducing unnatural bases (UBs), as a fifth letter, dramatically augments the affinities of DNA aptamers that bind to target proteins. To determine whether UB-containing DNA (UB-DNA) aptamers obtained by affinity selection could spontaneously achieve high specificity, we have generated a series of UB-DNA aptamers (KD: 27−182 pM) targeting each of four dengue non-structural protein 1 (DEN-NS1) serotypes. The specificity of each aptamer is remarkably high, and the aptamers can recognize the subtle variants of DEN-NS1 with at least 96.9% amino acid sequence identity, beyond the capability of serotype identification (69−80% sequence identities). Our UB-DNA aptamers specifically identified two major variants of dengue serotype 1 with 10-amino acid differences in the DEN-NS1 protein (352 aa) in Singaporeans’ clinical samples. These results suggest that the high-affinity UB-DNA aptamers generated by affinity selection also acquire high target specificity. Intriguingly, one of the aptamers contained two different UBs as fifth and sixth letters, which are essential for the tight binding to the target. These two types of unnatural bases with distinct physicochemical properties profoundly expand the potential of DNA aptamers. Detection methods incorporating the UB-DNA aptamers will facilitate precise diagnoses of viral infections and other diseases.
How Affective Polarization Undermines Support for Democratic Norms
Authors: Kingzette Jon , Druckman James N , Klar Samara , Krupnikov Yanna , Levendusky Matthew , Ryan John Barry
Published: June 2021

Does affective polarization—the tendency to view opposing partisans negatively and co-partisans positively—undermine support for democratic norms? We argue that it does, through two mechanisms. First, in an age of elite polarization, norms have been politicized. This leads affectively polarized partisans to oppose particular constitutional protections when their party is in power but support them when their party is out of power, via a cue-taking mechanism. Second, affective polarization may generate biases that motivate voters to restrict the other party’s rights. Using nationally representative surveys, we find strong support for the cue-taking argument. In 2019, with a Republican administration in power, affectively polarized Republicans opposed constitutional protections while affectively polarized Democrats supported them. The reverse was true in 2012 during a Democratic administration. The findings have important, albeit troubling, implications for American democracy, as affective polarization undermines support for basic democratic principles.
Activity Levels in Survivors of the ICU
Authors: Gandotra Sheetal , Files D Clark , Shields Katherine L , Berry Michael , Bakhru Rita N
Published: June 2021

Objective

Limited data exists on the quantification of activity levels and functional status in critically ill patients as they transition from the intensive care unit (ICU) to the wards and subsequently, back into the community. We characterize the physical activity of critically ill patients from their ICU stay until seven days after hospital discharge, as well as correlate physical activity levels with an objective measure of physical function.

Methods

This prospective observational study of previously independent adults age 55 or older, undergoing mechanical ventilation for up to 7 days, recruited participants at the time of spontaneous breathing trials or < 24 hours after extubation. Participants received an accelerometer at enrollment to wear until one week after discharge.

Results

Twenty-two participants received accelerometers; 15 were suitable for analysis. Participants were 68 ± 9.6 years old; 47% female. Step counts (mean and 95% CI) were 95 [15–173] in the 3 days before ICU discharge, 257 [114–400] before hospital discharge, 1223 [376–2070] in the first 3 days at home and 1278 [349–2207] between day 4 and 6 post-hospital discharge. Physical activity was significantly higher post- compared to pre-hospital discharge. Short Physical Performance Battery scores (SPPB) were poor at ICU and hospital discharge; however, correlated moderately with physical activity levels immediately upon return home.

Conclusions

Physical activity remained low as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. Despite poor SPPB scores at both ICU and hospital discharge, participants were significantly more active immediately after discharge than in their last 3 days of hospitalization. This may represent rapid functional improvement or conversely, constrained physical activity in hospital.

Impact

This study highlights the need for further evaluation of physical activity constraints in hospital and ways to augment physical activity and function upon discharge.

Lay summary

Physical activity (step counts) increased modestly as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. This study highlights the need for further evaluation of physical activity constraints in the hospital setting and ways to augment physical activity and function post-discharge.
Novel Tests of the Key Innovation Hypothesis: Adhesive Toepads in Arboreal Lizards
Authors: Miller Aryeh H , Stroud James T
Published: June 2021

The evolution of key innovations—unique features that enable a lineage to interact with the environment in a novel way—may drive broad patterns of adaptive diversity. However, traditional tests of the key innovation hypothesis, those which attempt to identify the evolutionary effect of a purported key innovation by comparing patterns of diversity between lineages with and without the key trait, have been challenged on both conceptual and statistical grounds. Here, we explore alternative, untested hypotheses of the key innovation framework. In lizards, adhesive toepad structures increase grip strength on vertical and smooth surfaces such as tree trunks and leaves and have independently evolved multiple times. As such, toepads have been posited as a key innovation for the evolution of arboreality. Leveraging a habitat use data set applied to a global phylogeny of 2692 lizard species, we estimated multiple origins of toepads in three major clades and more than 100 origins of arboreality widely across the phylogeny. Our results suggest that toepads arise adaptively in arboreal lineages and are subsequently rarely lost while maintaining arboreal ecologies. Padless lineages transition away from arboreality at a higher rate than those with toepads, and high rates of invasion of arboreal niches by nonarboreal padbearing lineages provide further evidence that toepads may be a key to unlocking evolutionary access to the arboreal zone. Our results and analytical framework provide novel insights to understand and evaluate the ecological and evolutionary consequences of key innovations.[Arboreality; ecological transition; key innovation; macroevolution; phylogenetic comparative methods.]
Modifying influence of polyphenols on hematotoxicity, cardiotoxicity, and hepatotoxicity induced by liquefied petroleum gas in rats
Authors: Akinmoladun Afolabi Clement , Aladesanmi Olayinka Oluwaseun , Ojo Femi Emmanuel , Bello Morenikejimi , Taiwo Bobola Jeremiah , Akindahunsi Afolabi Akintunde
Published: June 2021

Objective

This study was designed to investigate the effects of liquefied petroleum gas (LPG) on hematotoxic, cardiotoxic, and hepatotoxic indices and the modifying influence of selected polyphenols.

Methods

Adult male Wistar rats were exposed to1000 ppm LPG for 10 min at 12-h interval for 30 days with or without cotreatment with 50 mg/kg rutin, quercetin, tannic acid, or gallic acid followed by hematological, biochemical, and histopathological evaluations in animal tissues.

Results

Exposure to LPG induced hematotoxicity, cardiotoxicity, and hepatotoxicity. This is reflected in alterations to levels or activities of blood parameters (hemoglobin, packed cell volume, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, and platelets), enzymatic and nonenzymatic oxidative stress markers, nitrite, lactate dehydrogenase, creatine kinase-MB, transaminases, γ-glutamyl transpeptidase, bilirubin, and plasma albumin. LPG exposure also caused dyslipidemia and histoarchitectural changes. Treatment with the selected polyphenols effectively attenuated LPG-induced toxicity in rat tissues.

Conclusion

The results indicate that continuous exposure to LPG could lead to blood-, heart-, and liver-related diseases and dietary polyphenols could provide benefits in diseases associated with LPG inhalation toxicity.
Hypertension across the lifespan
Authors: Hilliard Tara C. , Bruce Kellie , Esquibel Karen A. , Mello Inola , Moore Amy
Published: June 2021

Effective diagnosis and management in the older adult population can increase functional capacity and decrease morbidity and mortality.
An overview of abortion in the United States
Authors: Perkins Amanda
Published: June 2021

By furthering our knowledge and understanding, nurses can improve the care received by patients seeking and receiving this procedure.
Faith-Based Pregnancy Center Education Bridges the Maternal Health Gap
Authors: Walters Colleen P. , Vernon Marlo M.
Published: June 2021

Routine prenatal care in the United States has not been effective in reducing maternal mortality and preterm birth rates, nor addressing disparities among non-Hispanic Black women. Pregnant women from minority groups are more likely to be of low socioeconomic status and uninsured, and lacking resources to obtain preconception and early prenatal care to manage medical conditions. Faith-based pregnancy resource centers can help to fill the gap in maternal health among vulnerable populations. This article presents the development of an evidence-based prenatal education and social support program developed for those working in pregnancy resource centers to address disparities and improve outcomes in maternal mortality and preterm birth.
Spiritual Health First Aid for Self-Care
Authors: Green Cheryl
Published: June 2021

Nurses who provided care to patients with coronavirus (COVID-19) and supported patients in their transition from life to death in the absence of patients' families have been especially needful of spiritual self-care. A spiritual first aid kit can help nurses cope with these difficult times. Spiritual self-care is vital for all nurses to renew and preserve the psychological, spiritual, and physical self.
Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics
Authors: Quattrochi Brian , Russell-Goldman Eleanor
Published: June 2021

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade adnexal malignancy with a predilection for the eyelids of elderly White women, which is associated with invasive mucinous carcinoma with endocrine features in one-third of cases. EMPSGC is characterized by the presence of neuroendocrine differentiation and mucin production. However, EMPSGC displays a variety of architectural patterns including solid, cribriform, papillary, and cystic growth. In addition, EMPSGC may also display nonendocrine cytologic features, such as apocrine change. Because of their variable appearance, EMPSGC can show significant morphologic overlap with certain histologic mimics, namely basal cell carcinoma, hidrocystoma, apocrine hidradenoma, and tubular adenoma. In addition, the often limited sampling of this anatomically delicate area can make the diagnosis of EMPSGC challenging. EMPSGC expresses neuroendocrine markers, including synaptophysin and chromogranin, often in a focal distribution. However, insulinoma-associated protein 1 (INSM1) has been found to be a more sensitive marker for EMPSGC. Recent studies have also demonstrated the expression of the gel-forming mucin 2 (MUC2) in EMPSGC, possibly signifying a lacrimal or conjunctival origin of these neoplasms. In this article, we discuss EMPSGC in the context of its histologic mimics (BCC, hidrocystoma, apocrine hidradenoma, and tubular adenoma) and we investigate the utility of the immunohistochemical expression of INSM1 and MUC2 in the distinction of EMPSGC from them. We demonstrate that INSM1 and MUC2 can reliably distinguish EMPSGC from these histologic mimics.
Fetal Growth Trajectories Among Small for Gestational Age Babies and Child Neurodevelopment
Authors: Ferguson Kelly K. , Sammallahti Sara , Rosen Emma , van den Dries Michiel , Pronk Anjoeka , Spaan Suzanne , Guxens Mònica , Tiemeier Henning , Gaillard Romy , Jaddoe Vincent W.V.
Published: June 2021

Background:

Being born small for gestational age (SGA, <10th percentile) is a risk factor for worse neurodevelopmental outcomes. However, this group is a heterogeneous mix of healthy and growth-restricted babies, and not all will experience poor outcomes. We sought to determine whether fetal growth trajectories can distinguish who will have the worst neurodevelopmental outcomes in childhood among babies born SGA.

Methods:

The present analysis was conducted in Generation R, a population-based cohort in Rotterdam, the Netherlands (N = 5,487). Using group-based trajectory modeling, we identified fetal growth trajectories for weight among babies born SGA. These were based on standard deviation scores of ultrasound measures from mid-pregnancy and late pregnancy in combination with birth weight. We compared child nonverbal intelligence quotient (IQ) and attention deficit hyperactivity disorder (ADHD) symptoms at age 6 between SGA babies within each growth trajectory to babies born non-SGA.

Results:

Among SGA individuals (n = 656), we identified three distinct fetal growth trajectories for weight. Children who were consistently small from mid-pregnancy (n = 64) had the lowest IQ (7 points lower compared to non-SGA babies, 95% confidence interval [CI] = −11.0, −3.5) and slightly more ADHD symptoms. Children from the trajectory that started larger but were smaller at birth showed no differences in outcomes compared to children born non-SGA.

Conclusions:

Among SGA children, those who were smaller beginning in mid-pregnancy exhibited the worst neurodevelopmental outcomes at age 6. Fetal growth trajectories may help identify SGA babies who go on to have poor neurodevelopmental outcomes.
The Fibrinolytic System: Mysteries and Opportunities
Authors: Medcalf Robert L. , Keragala Charithani B.
Published: June 2021

The deposition and removal of fibrin has been the primary role of coagulation and fibrinolysis, respectively. There is also little doubt that these 2 enzyme cascades influence each other given they share the same serine protease family ancestry and changes to 1 arm of the hemostatic pathway would influence the other. The fibrinolytic system in particular has also been known for its capacity to clear various non-fibrin proteins and to activate other enzyme systems, including complement and the contact pathway. Furthermore, it can also convert a number of growth factors into their mature, active forms. More recent findings have extended the reach of this system even further. Here we will review some of these developments and also provide an account of the influence of individual players of the fibrinolytic (plasminogen activating) pathway in relation to physiological and pathophysiological events, including aging and metabolism.