bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes of metallic endobronchial stents in lung transplant recipients are not affected by bacterial colonization
Authors: Izhakian Shimon , Wasser Walter G , Vainshelboim Baruch , Pertzov Barak , Gorelik Oleg , Kramer Mordechai R
Published: September 2020

OBJECTIVES

We evaluated associations of endobronchial stenting with airway bacterial colonization, the antimicrobial resistance profile, hospitalizations for pneumonia and survival in lung transplant recipients.

METHODS

This is a retrospective single-centre study of 582 recipients of lung transplant during 2002–2018. We compared outcomes of 57 patients (9.7%) who received endobronchial stents (intervention group) to a control group of 57 patients without stents who were matched one to one for age, sex, year of transplantation, unilateral/bilateral transplantation and underlying disease.

RESULTS

For the intervention compared to the control group, airway colonization was more common for Pseudomonas (86% vs 35%, P < 0.001), Acinetobacter (21% vs 7%, P = 0.05), Klebsiella (21% vs 5%, P = 0.02) and Staphylococcus species (11% vs 0%, P = 0.02). The respective proportions of patients with positive bronchoalveolar lavage cultures on the third post-transplantation day, the day of stent insertion and 6-month post-stent insertion were 47.4%, 50.9% and 65.4% for Pseudomonas sp.; 15.8%, 12.3% and 3.8% for Klebsiella sp.; and 8.8%, 5.3% and 5.8% for Acinetobacter sp. The mean number of hospitalizations for pneumonia per patient was higher, without statistical significance, in the intervention than the control group (1.5 ± 1.7 vs 0.9 ± 1.5, P = 0.1). Kaplan–Meier survival curves did not show a statistically significant difference between the intervention group and the entire group without endobronchial stents (n = 525) (P = 0.4).

CONCLUSIONS

Lung transplant recipients with endobronchial stents were more likely to be colonized with pathologic bacteria and having pneumonia; however, stent placement was not associated with increased long-term mortality with appropriate stent maintenance.
Dietary taurine supplementation attenuates lipopolysaccharide-induced inflammatory responses and oxidative stress of broiler chickens at an early age
Authors: Han Hongli , Zhang Jingfei , Chen Yanan , Shen Mingming , Yan Enfa , Wei Chengheng , Yu Caiyun , Zhang Lili , Wang Tian
Published: September 2020

This study was conducted to investigate the effect of taurine as a prophylactic treatment on antioxidant function and inflammatory responses of broilers challenged with lipopolysaccharide (LPS). A total of 256 one-day-old male Arbor Acres broiler chicks were randomly assigned to four treatments with eight replicates of eight birds (eight birds per cage). Four treatment groups were designated as follows: 1) in the CON group, broilers fed a basal diet; 2) in the LPS group, LPS-challenged broilers fed a basal diet; 3) in the LPS + T1 group, LPS-challenged broilers fed a basal diet supplemented with 5.0 g/kg taurine; and 4) in the LPS + T2 group, LPS-challenged broilers fed a basal diet supplemented with 7.5 g/kg taurine. The LPS-challenged broilers were intraperitoneally injected with 1 mg/kg body weight (BW) of LPS at 16, 18, and 20 d of age, whereas the CON group received an injection of sterile saline. The results showed that broilers injected with LPS exhibited decreased (P < 0.05) the average daily gain (ADG) and the 21-d BW (P < 0.05), while taurine supplementation alleviated the negative effects of LPS. Additionally, the LPS-induced increases (P < 0.05) in serum alanine transaminase and aspartate transaminase activities were reversed by taurine supplementation. The taurines could alleviate the hepatic oxidative stress, with the presence of lower content of malondialdehyde (P < 0.05), higher content of glutathione (P < 0.05), and an increased glutathione peroxidase (GSH-Px) activity (P < 0.05). The concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the liver were measured by ELISA kits, and the result showed that dietary taurine supplementation prevented these cytokines increases in the liver of LPS-induced broilers. Taurine reduced the genes expression of IL-1β, TNF-α, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase, whereas it boosted the expression levels of antioxidant-related genes (nuclear factor erythroid 2-related factor 2, heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, and GSH-Px) in the liver of LPS-induced broilers. In conclusion, dietary taurine supplementation in broilers mitigated LPS-induced defects in ADG, oxidative stress, and inflammatory responses.
Bta-miR-34b inhibits proliferation and promotes apoptosis via the MEK/ERK pathway by targeting MAP2K1 in bovine primary Sertoli cells
Authors: Zhang Linlin , Ma Tiantian , Tao Qibing , Tan Wushuang , Chen Huatao , Liu Wei , Lin Pengfei , Zhou Dong , Wang Aihua , Jin Yaping , Tang Keqiong
Published: September 2020

Immature Sertoli cell (SC) proliferation determines the final number of mature SCs and further regulates spermatogenesis. Accumulating evidence demonstrated that microRNAs (miRNAs) play an important role in SC proliferation, differentiation, and apoptosis. However, the effect and molecular mechanism of miRNA on bovine immature SC remain to be poorly understood. In this study, miRNA sequencing of testes collected in mature (24-mo old) and immature (neonatal) bulls was conducted to determine the miRNA expression profiles. MicroRNA-34b was one of the differentially expressed miRNAs and was selected for in-depth functional studies pertaining to SC growth. The results showed that miR-34b mimic transfection in primary Sertoli cells (PSC) inhibited cell proliferation and induced cell cycle arrested at G2 phase and decreased the expression of cell cycle-related genes such as CCNB1, CDK1, CDC25C, and C-MYC. MicroRNA-34b overexpression also leads to increased cell apoptosis, with proapoptotic genes P53 and BAX upregulated, while antiapoptotic gene BCL2 decreased. However, miR-34b knockdown had the opposite effects. Through a combination of transcriptome sequencing, bioinformatics analysis, dual-luciferase reporter assay, and Western blotting, mitogen-activated protein kinase kinase1 (MAP2K1), also known as MEK1, was identified as a target of miR-34b. In addition, PSC proliferation inhibition was mediated by cell cycle arrest and apoptosis with MAP2K1 interference. Overexpression of MAP2K1 effectively reversed the miR-34b-repressed PSC cell growth. Moreover, both miR-34b overexpression and MAP2K1 knockdown decreased the protein levels of P-ERK1/2, while MAP2K1 overexpression showed opposite effects. In summary, data suggest that miR-34b regulates PSC proliferation and apoptosis through the MEK/ERK signaling pathway. These data provide a theoretical and experimental framework for further clarifying the regulation of cell growth in PSC of bovine.
What Do They Know and What Do They DO? A National Evaluation of Landscape Integrated Pest Management Knowledge and Use in the United States
Authors: Diaz John M , Warner Laura A , Oi Faith , Gusto Cody
Published: September 2020

Individual residents in the United States increasingly practice do-it-yourself pest management in their lawns and gardens. This self-managed pest control is frequently characterized by unnecessary and sometimes indiscriminate applications of pesticide that are often ineffective and environmentally damaging. Given residential consumers account for most of the world’s pesticide expenditures, the need to increase adoption of IPM best practices is critical. Through its education and technical training programming, we argue that Cooperative Extension is uniquely positioned to nudge residential DIY pest management away from an exclusive reliance on pesticide application and towards IPM best practices. To assess how best to encourage an increase in IPM adoption, we examined the relationship between an individual user’s knowledge of IPM practices and adoption of IPM behavior. Survey results from individual residents responsible for their lawn and garden management indicate that where there is high knowledge of IPM best practices, there appears to be a strong likelihood of behavior adoption. Results also show, however, that a significant number of respondents have little to no knowledge of IPM. To address this gap, we argue for the need to increase IPM-related education and provide recommendations for future research.
Von Economo Neuron Pathology in Familial Dysautonomia: Quantitative Assessment and Possible Implications
Authors: Jacot-Descombes Sarah , Keshav Neha , Brosch Carla Micaela Santos , Wicinski Bridget , Warda Tahia , Norcliffe-Kaufmann Lucy , Kaufmann Horacio , Varghese Merina , Hof Patrick R
Published: September 2020

Von Economo neurons (VENs) and fork cells are principally located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI). Both of these regions integrate inputs from the autonomic nervous system (ANS) and are involved in decision-making and perception of the emotional states of self and others. Familial dysautonomia (FD) is an orphan disorder characterized by autonomic dysfunction and behavioral abnormalities including repetitive behavior and emotional rigidity, which are also seen in autism spectrum disorder. To understand a possible link between the ANS and the cortical regions implicated in emotion regulation we studied VENs and fork cells in an autonomic disorder. We determined the densities of VENs, fork cells, and pyramidal neurons and the ratio of VENs and fork cells to pyramidal neurons in ACC and FI in 4 FD patient and 6 matched control brains using a stereologic approach. We identified alterations in densities of VENs and pyramidal neurons and their distributions in the ACC and FI in FD brains. These data suggest that alterations in migration and numbers of VENs may be involved in FD pathophysiology thereby supporting the notion of a functional link between VENs, the ANS and the peripheral nervous system in general.
A Practical Approach to Differentiate the Frontotemporal Tauopathy Subtypes
Authors: Forrest Shelley L , Halliday Glenda M , Sizemova Anastasia , van Roijen Marloes , McGinley Ciara V , Bright Fiona , Kapur Milan , McGeachie Andrew B , McCann Heather , Shepherd Claire E , Tan Rachel H , Affleck Andrew J , Huang Yue , Kril Jillian J
Published: September 2020

This study proposes a practical approach, using the minimum number of brain regions and stains, to consolidate previously published neuropathological criteria into one operationalized schema to differentiate subtypes of frontotemporal lobar degeneration with tau-immunopositive inclusions (FTLD-tau). This approach uses the superior frontal and precentral cortices and hippocampus stained for phosphorylated-tau, p62 and modified Bielschowsky silver, and the midbrain stained only for modified Bielschowsky silver. Accuracy of interrater reliability was determined by 10 raters in 24 FTLD-tau cases (Pick disease = 4, corticobasal degeneration = 9, progressive supranuclear palsy = 5, globular glial tauopathy = 6) including 4 with a mutation in MAPT collected with consent by Sydney Brain Bank. All brain regions and stains assessed proved informative for accurate pathological subtyping, and many neuropathological features were identified as common across the FTLD-tau subtypes. By identifying subtype-specific neuropathological features in the sections selected, 10 independent observers assigned the cases to a FTLD-tau subtype with almost perfect agreement between raters, emphasizing the requirement for the assessment of subtype-specific features for the accurate subtyping of FTLD-tau. This study consolidates current consensus diagnostic criteria for classifying FTLD-tau subtypes with an efficient, simple and accurate approach that can be implemented in future clinicopathological studies.
Low-Grade Gemistocytic Morphology in H3 G34R-Mutant Gliomas and Concurrent K27M Mutation: Clinicopathologic Findings
Authors: Morris Meaghan , Driscoll Meghan , Henson John W , Cobbs Charles , Jiang LiQun , Gocke Christopher D , Chen Liam , Rodriguez Fausto J
Published: September 2020

Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.
Overcoming the Odds: Toward a Molecular Profile of Long-Term Survival in Glioblastoma
Authors: Richardson Timothy E , Kumar Ashwani , Xing Chao , Hatanpaa Kimmo J , Walker Jamie M
Published: September 2020

For over a century, gliomas were characterized solely by histologic features. With the publication of the WHO Classification of Tumours of the Central Nervous System, Revised 4th Edition in 2016, integrated histologic and molecular diagnosis became the norm, providing improved tumor grading and prognosis with IDH1/2 (isocitrate dehydrogenase 1 and 2) mutation being the most significant prognostic feature in all grades of adult diffuse glioma. Since then, much work has been done to identify additional molecular prognostic features, but the bulk of the progress has been made in defining aggressive features in lower grade astrocytoma. Although there have been several large case series of glioblastomas with long-term survival (LTS; overall survival ≥36 months), less is known about the clinical and molecular features of these cases. Herein, we review 19 studies examining LTS glioblastoma patients from 2009 to 2020 that include variable molecular analysis, including 465 cases with survival of 36 months or more (total n = 2328). These studies suggest that while there is no definitive molecular signature of long survival, younger age, IDH mutation, and MGMT (methyl guanine methyl transferase) promoter hypermethylation are associated with longer overall survival, and in IDH-wildtype tumors, chromosome 19/20 co-gain and lack of EGFR amplification, chromosome 7 gain/10 loss, and TERT promoter mutation are associated with LTS.
Minimally invasive left atrial appendage (LAA) clip insertion after challenging LAA occluder implantation to minimize the risk of stroke
Authors: Cetinkaya Ayse , Zeriouh Mohamed , Liakopoulos Oliver-Joannis , Hein Stefan , Siemons Tamo , Bramlage Peter , Schönburg Markus , Choi Yeong-Hoon , Richter Manfred
Published: September 2020

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, requiring lifelong anticoagulation or interventional, transseptal left atrial appendage (LAA) occluder implantation to minimize stroke risk. Incomplete LAA closure post implantation is a frequent observation. Incomplete LAA occlusion after transseptal occluder implantation necessitates anticoagulation in cases of persistent AF to minimze risk of embolism and/or apoplexy. Patients with contraindications to lifelong anticoagulation therapy are challenging to treat and alternative options are needed. We present a case of a patient with persistent AF who underwent frustraneous LAA occluder implantation. The patient’s anatomy necessitated surgical closure of the LAA, which was accomplished with an LAA clip 4 weeks after implantation. The patient was discharged in excellent clinical status 5 days after the surgery. No further complications were observed within the following year.
Ambiguity and long-run cooperation in strategic games
Authors: Rojas Marco , Vergara Damián
Published: September 2020

We study the effects of ambiguity on long-run cooperation in infinitely repeated strategic games. Using a simple parametric model of ambiguity, we study conditions for sustaining cooperative equilibria in the long-run. We apply our framework to the prisoner’s dilemma and duopoly models. We find that (i) ambiguity may affect the game’s structure eventually making the noncooperative equilibrium ex ante preferred; (ii) higher levels of ambiguity make long-run cooperation less likely since it makes punishment schemes less effective; and (iii) large levels of ambiguity may preclude the possibility of mutually beneficial long-run agreements, even when cooperation is beneficial from an ex ante perspective.
RADON CONCENTRATION IN SOIL AND GROUNDWATER OF WEST COASTAL AREA, BANGLADESH
Authors: Deeba Farah , Rahman Syed Hafizur , Kabir Mohammad Zafrul
Published: September 2020

On-site radon concentration has been measured in soil gas and ground water using AlphaGUARD PQ2000 PRO (Saphymo, Germany) radon monitor at the west coastal area of Bangladesh. The measured radon concentration in ground water samples is in the range of 1.41 ± 0.29 to 3.2 ± 0.59 Bq/l with the mean value of 2.33 ± 0.50 Bq/l, which lies within the safe limit recommended by UNSCEAR (2008). The total annual effective dose estimated due to radon concentration in ground water ranges from 3.85 to 8.74 μSv/y with the mean value of 6.37 μSv/y, which is lower than the safe limit set by WHO (2004) and EU (1998). In soil samples, radon concentration has been measured at three different depths (0, 20 and 40 cm) in each location. The highest and the lowest concentrations are 4790 ± 51 and 10 ± 04 Bq/m3 at 40 and 0 cm (surface) depth, respectively, which lie within the natural background levels.
The Protection and Assistance of Internally Displaced Persons under the Kampala Convention: An Institutional Approach
Authors: Adeola Romola
Published: September 2020

The Kampala Convention has emerged as a significant regional framework for the protection and assistance of internally displaced persons (IDPs) in Africa. Over the last decade, the importance of this framework has been reflected at various levels of governance. However, one gap in the literature relates to the institutional arrangements surrounding the Kampala Convention, even as it moves beyond the first decade and has been ratified by nearly two-thirds of the current Member States of the African Union. This issue is the thrust of this article. In particular, it examines how the institutions of the wider African Union system can shape the implementation of the Kampala Convention and better ensure protection and assistance for IDPs in this region.
Is the alignment between public research organisations' R&D competence and policies really critical for technology transfer?
Authors: Son Hosung , Chung Yanghon , Yoon Sangpil
Published: September 2020

This study examines the effects of commercially-oriented research and development (R&D) competence and technology commercialisation (TC) policies in public research organisations (PROs) on R&D efficiency of companies when they receive technology transfer from PROs. This study especially uses three-stage data envelopment analysis in order to control the companies’ absorptive capacity and innovation hurdles that affect the efficiency. The results show that companies that receive technology transfer from PROs that have good alignment between commercially-oriented R&D competence and TC policies have higher R&D efficiency than companies that do not. On the other hand, the misalignment between PROs’ commercially-oriented R&D competence and TC policies can have negative effects on R&D efficiency of companies that receive technology transfer. Consequently, this study discloses that the alignment between technology transferor's commercially-oriented R&D competence and TC policies is critical for improving the R&D efficiency of companies when the companies acquire technologies from external organisations.
Influence of mandibular advancement on tongue dilatory movement during wakefulness and how this is related to oral appliance therapy outcome for obstructive sleep apnea
Authors: Jugé Lauriane , Yeung Jade , Knapman Fiona L , Burke Peter G R , Lowth Aimee B , Gan Ken Z C , Brown Elizabeth C , Butler Jane E , Eckert Danny J , Ngiam Joachim , Sutherland Kate , Cistulli Peter A , Bilston Lynne E
Published: September 2020

Study Objectives

To characterize how mandibular advancement splint (MAS) alters inspiratory tongue movement in people with obstructive sleep apnea (OSA) during wakefulness and whether this is associated with MAS treatment outcome.

Methods

A total of 87 untreated OSA participants (20 women, apnea–hypopnea index (AHI) 7–102 events/h, aged 19–76 years) underwent a 3T MRI with a MAS in situ. Mid-sagittal tagged images quantified inspiratory tongue movement with the mandible in a neutral position and advanced to 70% of the maximum. Movement was quantified with harmonic phase methods. Treatment outcome was determined after at least 9 weeks of therapy.

Results

A total of 72 participants completed the study: 34 were responders (AHI < 5 or AHI ≤ 10events/h with >50% reduction in AHI), 9 were partial responders (>50% reduction in AHI but AHI > 10 events/h), and 29 nonresponders (change in AHI <50% and AHI ≥ 10 events/h). About 62% (45/72) of participants had minimal inspiratory tongue movement (<1 mm) in the neutral position, and this increased to 72% (52/72) after advancing the mandible. Mandibular advancement altered inspiratory tongue movement pattern for 40% (29/72) of participants. When tongue dilatory patterns altered with advancement, 80% (4/5) of those who changed to a counterproductive movement pattern (posterior movement >1 mm) were nonresponders and 71% (5/7) of those who changed to beneficial (anterior movement >1 mm) were partial or complete responders.

Conclusions

The mandibular advancement action on upper airway dilator muscles differs between individuals. When mandibular advancement alters inspiratory tongue movement, therapeutic response to MAS therapy was more common among those who convert to a beneficial movement pattern.
A conserved role for sleep in supporting Spatial Learning inDrosophila
Authors: Melnattur Krishna , Kirszenblat Leonie , Morgan Ellen , Militchin Valentin , Sakran Blake , English Denis , Patel Rushi , Chan Dorothy , van Swinderen Bruno , Shaw Paul J
Published: September 2020

Sleep loss and aging impair hippocampus-dependent Spatial Learning in mammalian systems. Here we use the fly Drosophila melanogaster to investigate the relationship between sleep and Spatial Learning in healthy and impaired flies. The Spatial Learning assay is modeled after the Morris Water Maze. The assay uses a “thermal maze” consisting of a 5 × 5 grid of Peltier plates maintained at 36–37°C and a visual panorama. The first trial begins when a single tile that is associated with a specific visual cue is cooled to 25°C. For subsequent trials, the cold tile is heated, the visual panorama is rotated and the flies must find the new cold tile by remembering its association with the visual cue. Significant learning was observed with two different wild-type strains—Cs and 2U, validating our design. Sleep deprivation prior to training impaired Spatial Learning. Learning was also impaired in the classic learning mutant rutabaga (rut); enhancing sleep restored learning to rut mutants. Further, we found that flies exhibited a dramatic age-dependent cognitive decline in Spatial Learning starting at 20–24 days of age. These impairments could be reversed by enhancing sleep. Finally, we find that Spatial Learning requires dopaminergic signaling and that enhancing dopaminergic signaling in aged flies restored learning. Our results are consistent with the impairments seen in rodents and humans. These results thus demonstrate a critical conserved role for sleep in supporting Spatial Learning, and suggest potential avenues for therapeutic intervention during aging.
Eco-Epidemiological Uncertainties of Emerging Plant Diseases: The Challenge of Predicting Xylella fastidiosa Dynamics in Novel Environments
Authors: Occhibove Flavia , Chapman Daniel S. , Mastin Alexander J. , Parnell Stephen S. R. , Agstner Barbara , Mato-Amboage Rosa , Jones Glyn , Dunn Michael , Pollard Chris R. J. , Robinson James S. , Marzano Mariella , Davies Althea L. , White Rehema M. , Fearne Andrew , White Steven M.
Published: September 2020

In order to prevent and control the emergence of biosecurity threats such as vector-borne diseases of plants, it is vital to understand drivers of entry, establishment, and spatiotemporal spread, as well as the form, timing, and effectiveness of disease management strategies. An inherent challenge for policy in combatting emerging disease is the uncertainty associated with intervention planning in areas not yet affected, based on models and data from current outbreaks. Following the recent high-profile emergence of the bacterium Xylella fastidiosa in a number of European countries, we review the most pertinent epidemiological uncertainties concerning the dynamics of this bacterium in novel environments. To reduce the considerable ecological and socio-economic impacts of these outbreaks, eco-epidemiological research in a broader range of environmental conditions needs to be conducted and used to inform policy to enhance disease risk assessment, and support successful policy-making decisions. By characterizing infection pathways, we can highlight the uncertainties that surround our knowledge of this disease, drawing attention to how these are amplified when trying to predict and manage outbreaks in currently unaffected locations. To help guide future research and decision-making processes, we invited experts in different fields of plant pathology to identify data to prioritize when developing pest risk assessments. Our analysis revealed that epidemiological uncertainty is mainly driven by the large variety of hosts, vectors, and bacterial strains, leading to a range of different epidemiological characteristics further magnified by novel environmental conditions. These results offer new insights on how eco-epidemiological analyses can enhance understanding of plant disease spread and support management recommendations.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Early adolescent subchronic low-dose nicotine exposure increases subsequent cocaine and fentanyl self-administration in Sprague–Dawley rats
Authors: Cardenas Anjelica , Martinez Maricela , Saenz Mejia Alejandra , Lotfipour Shahrdad
Published: September 2020

An exponential rise in nicotine-containing electronic-cigarette use has been observed during the period of adolescence. Preclinical studies have shown that nicotine exposure during early adolescence, but not adulthood, increases subsequent drug intake and reward. Although growing clinical trends highlight that stimulant use disorders are associated with the opioid epidemic, very few studies have assessed the effects of adolescent nicotine exposure on opioid intake. The objective of our current study is to develop a new animal model to assess the causal relationship of adolescent nicotine exposure on subsequent opioid intake. In this effort, we first replicate previous studies using a well-established 4-day nicotine paradigm. Rats are pretreated with a low dose of nicotine (2 × , 30 μg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days 28–31) or adulthood (postnatal days 86–89). Following nicotine pretreatment on postnatal day 32 or postnatal day 90, animals underwent operant intravenous self-administration for the psychostimulant, cocaine [500 μg/kg/infusion (inf)] or the opioid, fentanyl (2.5 μg/kg/inf). We successfully show that adolescent but not adult, nicotine exposure enhances cocaine self-administration in male rats. Furthermore, we illustrate early adolescent but not adult nicotine exposure enhances fentanyl self-administration, independent of sex. Overall, our findings highlight that adolescence is a unique period of development that is vulnerable to nicotine-induced enhancement for cocaine and fentanyl self-administration in rats.
Diagnosis and Management of Intraamniotic Infection
Authors: Fan Shang-Rong , Liu Ping , Yan Shao-Mei , Peng Ji-Ying , Liu Xiao-Ping
Published: September 2020

Intraamniotic infection (IAI) or chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neonatal pneumonia, respiratory distress, meningitis, sepsis, and death. Maternal morbidities from intraamniotic infection include dysfunctional labor requiring increased intervention, cesarean birth, postpartum uterine atony with hemorrhage, endometritis, peritonitis, sepsis, adult respiratory distress syndrome and, rarely, death. Chorioamnionitis can result from an ascending infection, iatrogenic causes or transplacental passage from maternal blood-borne infections. The clinical findings of chorioamnionitis include maternal fever (≥38 °C), maternal (>100 beats per minute) and/or fetal tachycardia (>160 beats per minute), maternal leukocytosis on complete blood count (>15 000 cells/mm3), and uterine tenderness and/or purulent and/or foul-smelling amniotic fluid. The management of chorioamnionitis mainly includes antibiotic therapy and delivery. Women with previable preterm premature rupture of membranes should be offered realistic counseling from a multidisciplinary approach. The separation of the mother and the fetus to preserve the life of the mother should prioritize delivery methods that result in a living fetus if possible, with appropriate neonatal resuscitation available.
Noninvasive Prenatal Testing for Fetal XXY Aneuploidies Among Pregnancies in Beijing of China
Authors: Chang Jia-Zhen , Qi Qing-Wei , Zhou Xi-Ya , Jiang Yu-Lin , Hao Na , Liu Jun-Tao
Published: September 2020

Objective:

To evaluate the screening performance of noninvasive prenatal testing (NIPT) based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China.

Methods:

The study enrolled 26 913 consecutive pregnancies, 20–50 years old, who attended the Peking Union Medical College Hospital, Beijing, China, for prenatal screening from January 1, 2016 to December 31, 2019. Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure. Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis (IPD) for confirmation. Maternal DNA sequencing was performed, if necessary, to find other potential factors that may lead to high-risk results of XXY by NIPT.

Results:

Among a cohort of 26 913 pregnant women, 34 were high-risk for fetal XXY, among which 30 accepted IPD while 4 declined. In those who accepted IPD, 19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive. Among the 19 confirmed fetal XXY cases, 14 elected pregnancy termination. For all the 34 high-risk cases, two were verified maternal sex chromosome aneuploidy. The calculated detection rate, positive predictive value, and false-positive rate of NIPT for fetal XXY in this cohort was 100.00% (19/19), 63.33% (19/30), and 0.04% (11/26 890), respectively. And the percentage of pregnancy termination was 73.68% (14/19).

Conclusion:

NIPT could be used as a potential method for fetal XXY screening, although the accuracy needs to be improved. As NIPT is not diagnostic, IPD is strongly recommended for those with high-risk results. For cases with discordance between NIPT and fetal karyotyping, maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.
Prenatal Testing or Screening?
Authors: Evans Mark I. , Evans Shara M.
Published: September 2020

Over the past 50 years, the scope and extent of prenatal diagnosis and screening for genetic disorders have improved geometrically. There has been a pendulum like swing from testing to screening back and forth as new technologies emerge. The concurrent developments of cell free fetal DNA analysis of maternal blood has dramatically changed patient's choices towards screening. However, with the use of array comparative genomic hybridization of fetal DNA that requires diagnostic procedures (Chorionic villus sampling and amniocentesis), much more extensive diagnosis can be obtained. Until noninvasive methods can replicate what can be done with diagnostic procedures there still will be a “price to be paid” for opting for the non-invasive methods.
Association of an Increased Risk of Pre-eclampsia and Fetal Growth Restriction in Singleton and Twin Pregnancies with Female Fetuses
Authors: Bi Shilei , Zhang Lizi , Wang Zhijian , Tang Jingman , Xie Sushan , Gong Jingjin , Lin Lin , Ren Luwen , Huang Lijun , Zeng Shanshan , Chen Jingsi , Du Lili , Chen Dunjin
Published: September 2020

Objective:

To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.

Methods:

This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18–55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR.

Results:

In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793) vs. 5.9% (1803/30,336), P < 0.05 and 3.5% (932/26,793) vs. 2.4% (745/30,336), P < 0.05, respectively). A female fetus was an independent risk factor for either PE or FGR (adjusted odds ratio: 1.169 or 1.563; 95% confidence interval: 1.036–1.319 or 1.349–1.810, respectively). In twin pregnancies, the incidence of early-onset PE was greater in pregnancies with two females compared with two males or one male plus one female (4.6% (46/1003) vs. 4.1% (54/1305) vs. 2.4% (33/1391), P < 0.05). Female-female twins was an independent risk factor for PE (adjusted odds ratio: 1.367, 95% confidence interval: 1.011–1.849), especially early-onset PE.

Conclusion:

The female fetus was associated with PE in both singleton and twin pregnancies and was also a risk factor of FGR in singleton pregnancies.
Conceptualizations of Mental Disorder at a US Academic Medical Center
Authors: Aftab Awais , Joshi Yash , Sewell Daniel
Published: September 2020

How health care professionals conceptualize mental illness has received relatively little attention in existing literature. This survey explored how health care professionals, academic faculty, and trainees at a US academic medical center (departments of psychiatry, neurology, family medicine, and geriatric medicine, as well as medical students, nurses, and social workers) conceptualize the notion of mental disorder. Respondents (N = 209) were asked to rate their agreement or disagreement with a variety of conceptual statements. Overall, distress and impairment were seen as essential features of mental disorder, and the presence of a biological abnormality was not considered necessary. There was significant correlation between disease status and biological etiology attribution for all conditions except homosexuality. Psychology trainees and psychologists were significantly less likely to call a condition a disease compared with other groups. There was a general lack of consensus regarding conceptual issues fundamental to psychiatry. Conceptualizations of mental disorder held by respondents were complex and did not fit easily within the “biological psychiatry” paradigm.
Adjuvant Guided Exercise Therapy Versus Self-Organized Activity in Patients With Major Depression
Authors: Haussleiter Ida S. , Bolsinger Brigitta , Assion Hans-Jörg , Juckel Georg
Published: September 2020

Exercise seems to be effective in reducing depression itself, as well as the risk of relapse. This study evaluated whether standardized guided exercise therapy (GET) in comparison with self-organized activity (SOA) is an effective augmentation therapy in depressive adults. A total of 111 inpatients (66.7% women; mean age, 45.05 ± 12.19 years) with major depression were randomly assigned to either GET or SOA. Interventions were performed three times a week, with each session lasting 50 minutes. Both GET and SOA exerted effects even after a short-term application of 6 weeks. GET was superior to SOA in reducing depression symptom severity, as measured by the Hamilton Depression Scale (p = 0.017), specifically improving suicidality (p = 0.028) as well as time (p = 0.003) and severity of diurnal variation (p = 0.027). The findings support the beneficial role of adjuvant GET in patients with major depression as a feasible treatment in a psychiatric short-term inpatient setting.
Screening strategies for the detection of anal high-grade squamous intraepithelial lesions in women living with HIV
Authors: Chiao Elizabeth Y. , Lensing Shelly Y. , Wiley Dorothy J. , Deshmukh Ashish A. , Lee Jeannette , Darragh Teresa M. , Einstein Mark H. , Jay Naomi , Berry-Lawhorn John Michael , Palefsky Joel M. , Wilkin Timothy , Barroso Luis F. , Cranston Ross D. , Levine Rebecca , Guiot Humberto M. , French Audrey L. , Citron Deborah , Rezaei Masoumeh Katayoon , Goldstone Stephen E. , Stier Elizabeth A.
Published: September 2020

Objective:

HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV.

Design:

Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies.

Methods:

Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone.

Results:

83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively.

Conclusion:

Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.
Microbe Profile: Cryptococcus neoformans species complex
Authors: Bahn Yong-Sun , Sun Sheng , Heitman Joseph , Lin Xiaorong
Published: September 2020

Cryptococcus neoformans is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans and other mammals. Cryptococcus deploys a multitude of traits to adapt to and survive within the host, including immunosuppression, an ability to replicate intra- and extra-cellularly in phagocytes, changes in morphology and ploidy, a predilection to infect the CNS, and the capacity to utilize neurotransmitters and unique carbon sources available in the brain. These pathogenic strategies displayed by this fungus might have evolved through its interactions with microbial predators in the environment.
Computational design of two new soluble epoxide hydrolase (sEH) inhibitors
Authors: Liem Jennifer , Adhikari Sambid , Huang Peishan , Siegel Justin B.
Published: September 2020

Inhibitors of soluble epoxide hydrolase (sEH) enzymes have shown great potential for the treatment of neuropathic pain. However, current sEH inhibitors have poor physicochemical properties and has not been proven to be safe for human treatments yet. New inhibitor designs could have the potential to improve current drugs’ efficacy, and so in this work, chemical intuition and bioisosteric replacement were used to computationally design two novel sEH inhibitors. These new candidates showed good pharmacokinetic properties and presented better docking scores compared to a known sEH inhibitor, t-TUCB, used in the treatment of pain in horses. Homology analysis revealed thatMus musculusmay not be suitable organism for preclinical trials studies of these novel inhibitors.
Restricted constrictors: Space use and habitat selection of native Burmese pythons in Northeast Thailand
Authors: Smith Samantha Nicole , Jones Max Dolton , Marshall Benjamin Michael , Waengsothorn Surachit , Gale George A. , Strine Colin Thomas
Published: September 2020

Animal movement and resource use are tightly linked. Investigating these links to understand how animals utilize space and select habitats is especially relevant in areas that have been affected by habitat fragmentation and agricultural conversion. We set out to explore the space use and habitat selection of Burmese pythons (Python bivittatus) in a patchy land use matrix dominated by agricultural crops and human settlements. We used radio telemetry to record daily locations of seven Burmese pythons over the course of our study period of approximately 22 months. We created dynamic Brownian Bridge Movement Models (dBBMMs) for all individuals, using occurrence distributions to estimate extent of movements and motion variance to reveal temporal patterns. Then we used integrated step selection functions to determine whether individual movements were associated with particular landscape features (aquatic agriculture, forest, roads, settlements, terrestrial agriculture, water), and whether there were consistent associations at the population level. Our dBBMM estimates suggested that Burmese pythons made use of small areas (98.97 ± 35.42 ha), with low mean individual motion variance characterized by infrequent moves and long periods at a single location. At both the individual and population level, Burmese pythons in the agricultural matrix were associated with aquatic environments. Only one individual showed a strong avoidance for human settlements which is troublesome from a human-wildlife conflict angle, especially as Burmese pythons have been observed entering human settlements and consuming livestock in our study site. Our study is one of the first to contribute to the knowledge of Burmese python ecology in their native range as the majority of studies have focused on invasive populations.
STAMPede: A Precision Oncology Catalogue of Solid Tumors
Authors: Chen Jessica W. , Kalantarian Haik , Kunder Christian A. , Zehnder James L. , Stehr Henning , Costa Helio A.
Published: September 2020

Molecular profiling of tumor specimens is a key contributor in the application of precision medicine toward patient care in oncology. The presence of genetic mutational data may provide insight into the etiology of the cancer and inform about the available therapeutic options for patients diagnosed with various cancer types. However, the ability to centrally organize, structure, and visualize this genetic data can be hindered by the lack of necessary computational infrastructure. Here we present a somatic tumor data visualization portal titled STAMPede that utilizes tumor sequencing data from an in-house solid tumor oncology sequencing panel at Stanford Health Care. STAMPede is intended to provide Stanford healthcare providers and clinical researchers an easy to navigate web-based portal to query and display gene-, variant-, and cancer-level summary statistics.
Cryo-EM of a viral RNA and RNA-protein complex reveals how structural dynamics and novel tRNA mimicry combine to hijack host machinery
Authors: Bonilla Steve L. , Sherlock Madeline E. , MacFadden Andrea , Kieft Jeffrey S.
Published: September 2020

Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo-EM, we visualized the structure of the mysterious viral tRNA-like structure (TLS) from brome mosaic virus (BMV), which affects replication, translation, and genome encapsidation. Structures in isolation and bound to tyrosyl-tRNA synthetase (TyrRS) show that this ∼55 kDa purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs dramatically from tRNA. Our studies reveal how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions and highlights the utility of cryo-EM for visualizing small conformationally dynamic structured RNAs.
Pain-related opioidergic and dopaminergic neurotransmission: Dual Meta-Analyses of PET Radioligand Studies
Authors: Garcia Sergio Guerra , Spadoni Andrea , Mitchell Jennifer , Strigo Irina A.
Published: September 2020

Abstract

Molecular mechanisms of the interaction between pain and reward associated with pain relief processes in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. For pain and reward studies, the most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis looks at 15 pain-related studies using opioid radioligands and 8 studies using dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences. SDM analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related processing, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation include the midbrain, inferior frontal gyrus, and left superior temporal gyrus. By investigating the regions of dopaminergic and opioidergic activation, we can potentially provide more targeted treatment to these sets of receptors in patients with pain conditions. These findings could eventually assist in the development of more targeted medication in order to help treat pain conditions and simultaneously prevent physical dependency.