bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic, microbial and environmental standardization in animal experimentation limiting immunological discovery
Authors: Enriquez Josue , Mims Brianyell Mc Daniel , Trasti Scott , Furr Kathryn L. , Grisham Matthew B.
Published: September 2020

Background

The use of inbred mice housed under standardized environmental conditions has been critical in identifying immuno-pathological mechanisms in different infectious and inflammatory diseases as well as revealing new therapeutic targets for clinical trials. Unfortunately, only a small percentage of preclinical intervention studies using well-defined mouse models of disease have progressed to clinically-effective treatments in patients. The reasons for this lack of bench-to-bedside transition are not completely understood; however, emerging data suggest that genetic diversity and housing environment may greatly influence muring immunity and inflammation.

Results

Accumulating evidence suggests that certain immune responses and/or disease phenotypes observed in inbred mice may be quite different than those observed in their outbred counterparts. These differences have been thought to contribute to differing immune responses to foreign and/or auto-antigens in mice vs. humans. There is also a growing literature demonstrating that mice housed under specific pathogen free conditions possess an immature immune system that remarkably affects their ability to respond to pathogens and/or inflammation when compared with mice exposed to a more diverse spectrum of microorganisms. Furthermore, recent studies demonstrate that mice develop chronic cold stress when housed at standard animal care facility temperatures (i.e. 22–24 °C). These temperatures have been shown alter immune responses to foreign and auto-antigens when compared with mice housed at their thermo-neutral body temperature of 30–32 °C.

Conclusions

Exposure of genetically diverse mice to a spectrum of environmentally-relevant microorganisms at housing temperatures that approximate their thermo-neutral zone may improve the chances of identifying new and more potent therapeutics to treat infectious and inflammatory diseases.
The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway
Authors: Liang Jinhua , Ning Yongzhong , Dong Li , Ma Xiufeng , Li Shu , Yang Heran , Li Qi , Chen Ling , Gao Lingjuan , Xu Yanmin
Published: September 2020

Background

Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP.

Results

Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction.

Conclusion

These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner.
Comparative chloroplast genome analyses of Avena: insights into evolutionary dynamics and phylogeny
Authors: Liu Qing , Li Xiaoyu , Li Mingzhi , Xu Wenkui , Schwarzacher Trude , Heslop-Harrison John Seymour
Published: September 2020

Background

Oat (Avena sativa L.) is a recognized health-food, and the contributions of its different candidate A-genome progenitor species remain inconclusive. Here, we report chloroplast genome sequences of eleven Avena species, to examine the plastome evolutionary dynamics and analyze phylogenetic relationships between oat and its congeneric wild related species.

Results

The chloroplast genomes of eleven Avena species (size range of 135,889–135,998 bp) share quadripartite structure, comprising of a large single copy (LSC; 80,014–80,132 bp), a small single copy (SSC; 12,575–12,679 bp) and a pair of inverted repeats (IRs; 21,603–21,614 bp). The plastomes contain 131 genes including 84 protein-coding genes, eight ribosomal RNAs and 39 transfer RNAs. The nucleotide sequence diversities (Pi values) range from 0.0036 (rps19) to 0.0093 (rpl32) for ten most polymorphic genes and from 0.0084 (psbH-petB) to 0.0240 (petG-trnW-CCA) for ten most polymorphic intergenic regions. Gene selective pressure analysis shows that all protein-coding genes have been under purifying selection. The adjacent position relationships between tandem repeats, insertions/deletions and single nucleotide polymorphisms support the evolutionary importance of tandem repeats in causing plastome mutations in Avena. Phylogenomic analyses, based on the complete plastome sequences and the LSC intermolecular recombination sequences, support the monophyly of Avena with two clades in the genus.

Conclusions

Diversification of Avena plastomes is explained by the presence of highly diverse genes and intergenic regions, LSC intermolecular recombination, and the co-occurrence of tandem repeat and indels or single nucleotide polymorphisms. The study demonstrates that the A-genome diploid-polyploid lineage maintains two subclades derived from different maternal ancestors, with A. longiglumis as the first diverging species in clade I. These genome resources will be helpful in elucidating the chloroplast genome structure, understanding the evolutionary dynamics at genus Avena and family Poaceae levels, and are potentially useful to exploit plastome variation in making hybrids for plant breeding.
Asymmetrical cortical vein sign predicts early neurological deterioration in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion
Authors: Li Wei , Xiao Wei-Min , Luo Gen-Pei , Liu Yong-Lin , Qu Jian-Feng , Fang Xue-Wen , Wang Fang , Chen Yang-Kun
Published: September 2020

Background

Susceptibility weighted imaging (SWI) provides an approximate assessment of tissue perfusion and shows prominent hypointense cortical veins in the ischemic territory because of the increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO).

Methods

One hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as an increase in the National Institutes of Health Stroke Scale score ≧2 points despite standard treatment in the first 72 h after admission. The APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI.

Results

Thirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P = 0.001). Patients with APCVS were more likely to have END (40.0%, vs. 12.2%, P = 0.001) than those without END. Multivariate logistic regression indicated that APCVS (OR = 4.349, 95% C.I. = 1.580–11.970, P = 0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume.

Conclusions

In acute ischemic stroke patients with SIASO, the APCVS might be a useful neuroimaging marker for predicting END, which suggests the importance of evaluation of perfusion status.
Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach
Authors: Zhang Yaowen , Wang Jianpo , Dai Ningtao , Han Peng , Li Jian , Zhao Jiangman , Yuan Weilan , Zhou Jiahuan , Zhou Fuyou
Published: September 2020

Background

To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC).

Methods

A total of 46 ESCC patients were included in this study. Gas chromatography time-of- flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis.

Results

Five differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid (p = 0.0129), linoleic acid (p = 0.0137), citric acid (p = 0.0473) were upregulated, while L-histidine (p = 0.0155), 3′4 dihydroxyhydrocinnamic acid (p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity.

Conclusion

The present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy.
Changes in ocular biometric measurements after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment repair
Authors: Liu Rui , Li Qingchen
Published: September 2020

Background

To observe the changes in ocular biometric measurements after vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment (RRD) repair.

Methods

Sixty-three phakic, macula-off RRD eyes underwent vitrectomy with silicone oil tamponade but not lens extraction were included in this retrospective study. Measurements of axial length (AL), anterior chamber depth (ACD), lens thickness (LT) using the new Zeiss IOLMaster 700 and derivative lens position (LP), relative lens position (RLP) and lens-retina distance (LRD) were compared and analyzed between preoperative and postoperative in phakic, macula-off eyes with RRD.

Results

Preoperative AL, ACD, LT, LP, RLP and LRD were 24.94 ± 1.82 mm, 3.45 ± 0.42 mm, 4.34 ± 0.16 mm, 5.55 ± 0.41 mm, 0.22 ± 0.01 and 19.52 ± 1.82 mm. After a mean 4.85-month duration of silicone oil tamponade, postoperative AL, ACD, LT, LP, RLP and LRD were 25.42 ± 2.20 mm, 3.30 ± 0.41 mm, 4.43 ± 0.21 mm, 5.46 ± 0.40 mm, 0.22 ± 0.02 and 20.17 ± 2.36 mm, respectively. The differences in all measurements are significant (all P < 0.05). Preoperative AL and LRD are positively while RLP is negatively correlated with change in LRD. Change in AL but not in LT or LP is correlated with change in LRD. Biometric measurements except LT between preoperative and postoperative were in close agreement.

Conclusion

The underestimation of AL and anterior shifting of lens in phakic, macula-off eyes with RRD after vitrectomy with silicone oil tamponade.
Epidemiology, prenatal diagnosis, and neonatal outcomes of congenital heart defects in eastern China: a hospital-based multicenter study
Authors: Zhang Xiaohui , Sun Yu , Zhu Jiajun , Zhu Yuning , Qiu Liqian
Published: September 2020

Background

Congenital heart defect is the leading malformation in China. There may have been changes in congenital heart defect incidence because of birth policy shift in China over past years. This study aimed to investigate the epidemiology, prenatal diagnosis, and outcomes of congenital heart disease to improve medical and policy decisions.

Methods

Data on cases of congenital heart disease identified during 2014–2018 were taken from the Zhejiang provincial birth defects surveillance system. Chi-square test, odds ratio (OR) and 95% confidence interval (CI) were used to explore epidemiology, prenatal diagnosis, and birth outcomes of congenital heart disease.

Results

The average incidence of congenital heart disease was 16.0 per 1000 births, which increased by 62.2% during 2014–2018(χ2trend = 181.41, P < 0.001). However, the average critical congenital heart incidence was 1.6 per 1000 births, which remained stable over time. Women aged ≤20 years (OR2.1, 95% CI 1.9–2.3) or ≥ 35 years (OR 1.2, 95% CI 1.2–1.3) were at higher risk of having babies with congenital heart disease than women aged 21–34 years. Women who gave birth in urban areas (OR 1.2, 95% CI 1.2–1.3), had a son (OR 1.3, 95% CI 1.3–1.4), or had multiple births (OR 4.0, 95% CI 3.7–4.4) were also at higher risk than those giving birth in rural areas, to girls, or single births, respectively. The three major subtypes of congenital heart disease were atrial septal defect (67.9%), patent ductus arteriosus (34.7%), and ventricular septal defect (6.4%). The prenatal detection rate of critical congenital heart disease was 90.0%, which was far higher than total congenital heart disease, at 22.2% (χ2 = 1687.67, P < 0.001). There were 1457 (17.1%) stillbirths, 106 (1.2%) early neonatal deaths, and 6983 (81.7%) live births associated with congenital heart disease.

Conclusions

The high incidence of congenital heart disease in Zhejiang might be attributable to the large proportion of mild congenital heart disease. The incidence of critical congenital heart disease, the prenatal detection rate, and perinatal deaths from congenital heart disease are comparable to those in other studies.
Towards more efficient use of intravenous lumens in multi-infusion settings: development and evaluation of a multiplex infusion scheduling algorithm
Authors: Doesburg Frank , Oelen Roy , Renes Maurits H. , Bult Wouter , Touw Daan J. , Nijsten Maarten W.
Published: September 2020

Background

Multi-drug intravenous (IV) therapy is one of the most common medical procedures used in intensive care units (ICUs), operating rooms, oncology wards and many other hospital departments worldwide. As drugs or their solvents are frequently chemically incompatible, many solutions must be administered through separate lumens. When the number of available lumens is too low to facilitate the safe administration of these solutions, additional (peripheral) IV catheters are often required, causing physical discomfort and increasing the risk for catheter related complications. Our objective was to develop and evaluate an algorithm designed to reduce the number of intravenous lumens required in multi-infusion settings by multiplexing the administration of various parenteral drugs and solutions.

Methods

A multiplex algorithm was developed that schedules the alternating IV administration of multiple incompatible IV solutions through a single lumen, taking compatibility-related, pharmacokinetic and pharmacodynamic constraints of the relevant drugs into account. The conventional scheduling procedure executed by ICU nurses was used for comparison. The number of lumens required by the conventional procedure (LCONV) and multiplex algorithm (LMX) were compared.

Results

We used data from 175,993 ICU drug combinations, with 2251 unique combinations received by 2715 consecutive ICU patients. The mean ± SD number of simultaneous IV solutions was 2.8 ± 1.6. In 27% of all drug combinations, and 61% of the unique combinations the multiplex algorithm required fewer lumens (p < 0.001). With increasing LCONV, the reduction in number of lumens by the multiplex algorithm further increased (p < 0.001). In only 1% of cases multiplexing required > 3 lm, versus 12% using the conventional procedure.

Conclusion

The multiplex algorithm addresses a major issue that occurs in ICUs, operating rooms, oncology wards, and many other hospital departments where several incompatible drugs are infused through a restricted number of lumens. The multiplex algorithm allows for more efficient use of IV lumens compared to the conventional multi-infusion strategy.
Children as sentinels of tuberculosis transmission: disease mapping of programmatic data
Authors: Gunasekera Kenneth S. , Zelner Jon , Becerra Mercedes C. , Contreras Carmen , Franke Molly F. , Lecca Leonid , Murray Megan B. , Warren Joshua L. , Cohen Ted
Published: September 2020

Background

Identifying hotspots of tuberculosis transmission can inform spatially targeted active case-finding interventions. While national tuberculosis programs maintain notification registers which represent a potential source of data to investigate transmission patterns, high local tuberculosis incidence may not provide a reliable signal for transmission because the population distribution of covariates affecting susceptibility and disease progression may confound the relationship between tuberculosis incidence and transmission. Child cases of tuberculosis and other endemic infectious disease have been observed to provide a signal of their transmission intensity. We assessed whether local overrepresentation of child cases in tuberculosis notification data corresponds to areas where recent transmission events are concentrated.

Methods

We visualized spatial clustering of children < 5 years old notified to Peru’s National Tuberculosis Program from two districts of Lima, Peru, from 2005 to 2007 using a log-Gaussian Cox process to model the intensity of the point-referenced child cases. To identify where clustering of child cases was more extreme than expected by chance alone, we mapped all cases from the notification data onto a grid and used a hierarchical Bayesian spatial model to identify grid cells where the proportion of cases among children < 5 years old is greater than expected. Modeling the proportion of child cases allowed us to use the spatial distribution of adult cases to control for unobserved factors that may explain the spatial variability in the distribution of child cases. We compare where young children are overrepresented in case notification data to areas identified as transmission hotspots using molecular epidemiological methods during a prospective study of tuberculosis transmission conducted from 2009 to 2012 in the same setting.

Results

Areas in which childhood tuberculosis cases are overrepresented align with areas of spatial concentration of transmission revealed by molecular epidemiologic methods.

Conclusions

Age-disaggregated notification data can be used to identify hotspots of tuberculosis transmission and suggest local force of infection, providing an easily accessible source of data to target active case-finding intervention.
Intraosseous epidermoid cysts of adjacent digits in a dog
Authors: Vagias Michail , Cassidy Joseph P. , Skelly Cliona , Mullins Ronan A.
Published: September 2020

Background

Intraosseous epidermoid cyst (IEC) is a rare, non-neoplastic, pathology in animals and humans that most commonly affects the distal phalanx. In dogs, it is important to differentiate this lesion from malignant digital tumours causing bone lysis. In previous reports, IEC has been described to affect only a single digit at the time of diagnosis which is usually based on histopathology. This is the first case report to describe immunohistochemically confirmed IECs affecting simultaneously multiple digits.

Case presentation

A 4-and-a-half-year-old female spayed Great Dane was presented with a 2-month history of progressive swelling of the distal phalanx (PIII) of digits IV and V of the right pelvic limb. Eleven weeks prior to presentation, the dog had a low-grade cutaneous mast cell tumour completely excised from the craniolateral base of its left pinna. A history of trauma to 1 of the nails of the same pes 4 years prior to referral was also reported. Examination of the right pelvic limb identified firm non-painful swelling of PIII of digits IV and V, with concurrent deformation of the nails. Radiographs of the right pes obtained by the primary veterinarian identified an expansile lesion of PIII of digits IV and V. Computed tomography identified large expansile lesions of PIII of digits IV and V, with associated cortical thinning and soft tissue swelling. Neoplasia was considered the most likely radiographic diagnosis. Histopathology of Jamshidi bone biopsies was consistent with intraosseous epidermoid cyst, which was confirmed with immunohistochemistry. Amputation of PIII of digits IV and V at the level of mid-PII was performed as definitive treatment. No recurrence of the lesion occurred during the 10-month follow-up period.

Conclusions

Intraosseous epidermoid cysts should be included in the differential diagnosis for expansile lesions affecting the canine digit. It is important to differentiate them from other digital lesions, with bone involvement, such as malignant digital tumours, which often require more extensive surgery for definitive treatment. The case herein highlights that this lesion can affect simultaneously multiple digits. Definitive diagnosis can be achieved by identification of keratin-producing epithelial cells on histopathology and confirmed by pancytokeratin labelling.
Value of metalloproteinases in predicting COPD in heavy urban smokers
Authors: Tsay Jun-Chieh J. , Hu Yingjie , Goldberg Judith D. , Wang Bin , Vijayalekshmy Soumya , Yie Ting-An , Bantis Katrina , Sterman Daniel H. , Rom William N.
Published: September 2020

Background

Emphysema in asymptomatic heavy smokers can be detected during CT-scan screening for lung cancer. Metalloproteinases (MMPs) have been found to play a role in the pathogenesis of chronic obstructive pulmonary disease and to possibly serve as biomarkers for emphysema.

Methods

The NYU Lung Cancer Biomarker Center enrolled study subjects over 50 years of age with lung cancer risk factors from January 1, 2010, to December 31, 2015. These subjects received chest multi-detector computed tomography, spirometry, and provided serum for immunoassays for metalloproteinases (MMP) -1, -2, -7, -9, -10 and tissue inhibitor of metalloproteinases (TIMP) -1 and -2.

Results

Three hundred sixteen study subjects were enrolled. Of the 222 patients who met the inclusion criteria, 46% had emphysema. Smokers with emphysema had increased pack-years of smoking compared to smokers without emphysema (51 ± 24 pack-years (mean ± sd) versus 37 ± 20; p < 0.0001). Smokers with emphysema also had lower FEV1/FVC percent compared to smokers without emphysema (68 ± 11 (mean ± sd) versus 75 ± 8; p < 0.0001). Increased age and pack-years of smoking were associated with increased odds of emphysema. None of the metalloproteinases or tissue inhibitors of metalloproteinases were useful to predict the presence of emphysema in smokers.

Conclusion

Emphysema was detected by CT in almost half of heavy urban smokers. Serum MMP levels provided minimal additional information to improve the detection of mild emphysema among smokers given their clinical characteristics (age, pack-years, and FEV1/FVC ratio).
Role of inflammasomes in multiple sclerosis and their potential as therapeutic targets
Authors: Govindarajan Vaidya , de Rivero Vaccari Juan Pablo , Keane Robert W.
Published: September 2020

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), and it remains the most common immune-mediated disorder affecting the CNS. While the cause of MS is unclear, the underlying pathomechanisms are thought to be either destruction by autoimmune T cells or dysfunction of myelin-producing cells. Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. Here we review the literature to date on the role of different inflammasome signaling pathways in the pathogenesis of MS and how these pathways may be targeted to reduce deleterious inflammatory processes and improve outcomes in this patient population.
An in-vitro evaluation of the flow haemodynamic performance of Gore-Tex extracardiac conduits for univentricular circulation
Authors: McHugo Shane , Nolke Lars , Delassus Patrick , MacCarthy Eugene , Morris Liam , McMahon Colin Joseph
Published: September 2020

Objective(s)

The Fontan procedure is a common palliative intervention for sufferers of single ventricle congenital heart defects that results in an anastomosis of the venous return to the pulmonary arteries called the total cavopulmonary connection (TCPC). In patients with palliated single ventricular heart defects, the Fontan circulation passively directs systemic venous return to the pulmonary circulation in the absence of a functional sub-pulmonary ventricle. Therefore, the Fontan circulation is highly dependent on favourable flow and energetics, and minimal energy loss is of great importance. The majority of in vitro studies, to date, employ a rigid TCPC model. Recently, few studies have incorporated flexible TCPC models, without the inclusion of commercially available conduits used in these surgical scenarios.

Method

The methodology set out in this study successfully utilizes patient-specific phantoms along with the corresponding flowrate waveforms to characterise the flow haemodynamic performance of extracardiac Gore-Tex conduits. This was achieved by comparing a rigid and flexible TCPC models against a flexible model with an integrated Gore-Tex conduit.

Results

The flexible model with the integrated Gore-Tex graft exhibited greater levels of energy losses when compared to the rigid walled model. With this, the flow fields showed greater levels of turbulence in the complaint and Gore-Tex models compared to the rigid model under ultrasound analysis.

Conclusion

This study shows that vessel compliance along with the incorporation of Gore-Tex extracardiac conduits have significant impact on the flow haemodynamics in a patient-specific surgical scenario.
Modelling email traffic workloads with RNN and LSTM models
Authors: Om Khandu , Boukoros Spyros , Nugaliyadde Anupiya , McGill Tanya , Dixon Michael , Koutsakis Polychronis , Wong Kok Wai
Published: September 2020

Analysis of time series data has been a challenging research subject for decades. Email traffic has recently been modelled as a time series function using a Recurrent Neural Network (RNN) and RNNs were shown to provide higher prediction accuracy than previous probabilistic models from the literature. Given the exponential rise of email workloads which need to be handled by email servers, in this paper we first present and discuss the literature on modelling email traffic. We then explain the advantages and limitations of different approaches as well as their points of agreement and disagreement. Finally, we present a comprehensive comparison between the performance of RNN and Long Short Term Memory (LSTM) models. Our experimental results demonstrate that both approaches can achieve high accuracy over four large datasets acquired from different universities’ servers, outperforming existing work, and show that the use of LSTM and RNN is very promising for modelling email traffic.
Non-destructive collection survey of the historical Classense Library. Part II: Conservation scenarios
Authors: Coppola Floriana , Brown Natalie , Amicucci Floriana , Strlič Matija , Modelli Alberto
Published: September 2020

The effects of environmental and conservation management scenarios on the permanence of the historical book collections housed at the Classense Library (Ravenna, Italy) were investigated. Non-destructive material surveys delivered paper pH and degree of polymerisation data that, in conjunction with the Collections Demography dose–response function, provide heritage managers with estimations of the predicted collection lifetimes in diverse environmental management scenarios. For the first time, quantitative measurements of paper properties obtained in a historical library collection were used to elaborate isochrone and demographic plots, evaluated against the long-term planning horizon of 500 years. The scenarios include preventive and interventive actions aiming to preserve the fitness-for-use of collection items in terms of their ability to withstand manual handling, and consider cooling, dehumidification and deacidification, as well as combinations thereof. The results inform the conservation decision-makers about the preservation outcomes of environmental management options, to be considered for further action, once environmental, economic and social sustainability of such scenarios is considered.
Vaginal cuff dehiscence following transvaginal oocyte retrieval: a case report
Authors: O’Connor Sarah K. , Ryley David A. , Obasiolu Charles W. , Esselen Katharine M. , Skiadas Christine C. , Kuohung Wendy
Published: September 2020

Background

Vaginal cuff dehiscence (VCD) is a rare but potentially serious complication following hysterectomy with an estimated incidence of 0.14–1.4%. There is a wide range of risk factors thought to contribute to VCD, but due to its rare occurrence, much still remains to be learned about the true impact of risk factors leading to dehiscence. We present here the second known report of VCD to occur in a patient undergoing transvaginal oocyte retrieval during her fertility treatment. This case highlights what may become a more common clinical scenario as more premenopausal women are diagnosed with reproductive tract cancers and access assisted reproductive therapies to preserve fertility.

Case presentation

Our patient is a 35-year-old G1 P0 A1 who had undergone ovary-sparing total laparoscopic hysterectomy (TLH) following diagnosis of endometrial adenocarcinoma. She underwent two in-vitro fertilization (IVF) cycles after TLH to bank frozen blastocysts, the first vaginal oocyte retrieval (VOR) taking place 12 weeks following hysterectomy. She experienced VCD during her second VOR that occurred 17 weeks after TLH, the second case of VCD to be reported in the literature during fertility preservation treatment following hysterectomy. The patient underwent an emergent and uncomplicated repair of the defect vaginally the same day.

Conclusions

Currently there are no guidelines in place for women who have undergone hysterectomy with regard to when they can begin fertility treatment in the post-operative period. Based on now two case reports, it is worth considering extension of the typical 6-week timeline of avoidance of vaginal procedures to allow for full cuff healing. Infertility providers should also be mindful of limiting transvaginal ultrasounds where possible to reduce force along the cuff.
Development and application of perfect SSR markers in cotton
Authors: WU Yuzhen , HUANG Longyu , ZHOU Dayun , FU Xiaoqiong , LI Chao , WEI Shoujun , PENG Jun , KUANG Meng
Published: September 2020

Background

This study aimed to develop a set of perfect simple sequence repeat (SSR) markers with a single copy in the cotton genome, to construct a DNA fingerprint database suitable for authentication of cotton cultivars. We optimized the polymerase chain reaction (PCR) system for multi-platform compatibility and improving detection efficiency. Based on the reference genome of upland cotton and 10× resequencing data of 48 basic cotton germplasm lines, single-copy polymorphic SSR sites were identified and developed as diploidization SSR markers. The SSR markers were detected by denaturing polyacrylamide gel electrophoresis (PAGE) for initial screening, then fluorescence capillary electrophoresis for secondary screening. The final perfect SSR markers were evaluated and verified using 210 lines from different sources among Chinese cotton regional trials.

Results

Using bioinformatics techniques, 1 246 SSR markers were designed from 26 626 single-copy SSR loci. Adopting a stepwise (primary and secondary) screening strategy, a set of 60 perfect SSR markers was selected with high amplification efficiency and stability, easy interpretation of peak type, multiple allelic variations, high polymorphism information content (PIC) value, uniform chromosome distribution, and single-copy characteristics. A multiplex PCR system was established with ten SSR markers using capillary electrophoresis detection.

Conclusions

A set of perfect SSR markers of cotton was developed and a high-throughput SSR marker detection system was established. This study lays a foundation for large-scale and standardized construction of a cotton DNA fingerprint database for authentication of cotton varieties.
Integrating art and science to communicate the social and ecological complexities of wildfire and climate change in Arizona, USA
Authors: Colavito Melanie , Satink Wolfson Barbara , Thode Andrea E. , Haffey Collin , Kimball Carolyn
Published: September 2020

Background

This paper describesFires of Change, a collaborative art exhibit designed to communicate about the shifting fire regimes of the United States Southwest through the lens of multimedia art. The Southwest Fire Science Consortium and Landscape Conservation Initiative, both of which are boundary organizations that facilitate collaboration among managers and scientists to develop and apply actionable science, organizedFires of Changeby convening scientists, managers, and artists in the co-production of science-based artwork. Surveys were conducted withFires of Changeexhibit visitors to assess the impacts of viewing the exhibit, as well as with exhibit creators to assess the effects of participating in the project.

Results

The visitor survey results demonstrate thatFires of Changeexhibits increased visitors’ understanding of the effect of climate change on fire regimes and increased visitors’ support for management actions to address the effects of climate change on fire behavior. The exhibit creator survey results demonstrate that the development ofFires of Changecreated new relationships and networks among the participants and increased appreciation for collaborations among scientists, managers, and artists. Specifically, science-management relationships, networks, and boundary organizations may have facilitated the project.

Conclusions

Fires of Changedemonstrates that art can be an effective mechanism for communicating about complex ecological issues and that, by collaborating in the development of artwork, scientists and managers can create new partnerships.
Bilateral cochlear implantation: simultaneous versus sequential
Authors: Elrashidy Reham , Khater Ahmed Mohamed , Shabana Mohmad , Khashaba Ahmed , Tharwat Adel
Published: September 2020

Background

Bilateral cochlear implantation (BiCI) has been provided with an intent to promote binaural hearing and improve quality of life (QoL). Binaural hearing maximum benefit could be optimized with BiCI, when indicated in the early stages of life through preserving the cortical hearing development. Actually, BiCI benefits wide variables among patients, and in this work, we aimed to analyze the benefit of bilateral cochlear implantation over unilateral and the simultaneous over sequential implantation in peri- and post-lingual patients. The analysis based on common clinically used audiological tests such as aided hearing threshold and speech perception measures.

Results

The results of the aided threshold and speech perception measures in all patients revealed a significantly better response in the bilateral implantations than in unilateral each implant separately. Overall, the best response was seen in the simultaneous bilateral group followed by sequential bilateral groups. In post-lingual patients, a better response was observed in sequential and similar bilateral than in sequential and different device groups with significant differences.

Change of performance across time revealed aided threshold improvement of the from 3 to 6 months. In speech perception measures, the post-lingual group revealed significant improvement of high-context sentence test (HCST) scores from 3 to 6 months and 12 months. In the peri-lingual group, Early Speech Perception test (ESPT) revealed a change in performance with time at 3, 6, and 12 months. In addition, the simultaneous patient’s scores were significantly better than sequential similar patient’s scores.

Conclusion

The main finding of our study was that bilateral cochlear implants (BiCI) are better than unilateral cochlear implant, and simultaneous BiCI is preferred than the sequential cochlear implant even after escaping the early stage of language development.
Effect of Teriparatide on Bone Remodeling and Density in Premenopausal Idiopathic Osteoporosis: A Phase II Trial
Authors: Cohen Adi , Shiau Stephanie , Nair Nandini , Recker Robert R , Lappe Joan M , Dempster David W , Nickolas Thomas L , Zhou Hua , Agarwal Sanchita , Kamanda-Kosseh Mafo , Bucovsky Mariana , Williams John M , McMahon Donald J , Stubby Julie , Shane Elizabeth
Published: September 2020

Context

Premenopausal women with idiopathic osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR).

Objectives

Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response.

Design

6M phase 2 randomized controlled trial (RCT) followed by open extension.

Setting

Tertiary referral centers.

Patients

Premenopausal women with IOP.

Interventions

A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M.

Main Outcome Measures

6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD.

Findings

Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: −0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated.

Conclusions

Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.
Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems
Authors: Wachtel Heather , Hutchens Troy , Baraban Ezra , Schwartz Lauren E , Montone Kathleen , Baloch Zubair , LiVolsi Virginia , Krumeich Lauren , Fraker Douglas L , Nathanson Katherine L , Cohen Debbie L , Fishbein Lauren
Published: September 2020

Purpose

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.

Methods

The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan–Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).

Results

From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low–moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score.

Conclusion

Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.
Visual signal evolution along complementary color axes in four bird lineages
Authors: Krishnan Anand , Singh Avehi , Tamma Krishnapriya
Published: September 2020

Avian color patterns function in varied behavioral contexts, most being produced by only a handful of mechanisms including feather nanostructures and pigments. Within a clade, colors may not occupy the entire available space, and incorporating complementary colors may increase the contrast and efficacy of visual signals. Here, we describe plumage patterns in four ecologically and phylogenetically diverse bird families to test whether they possess complementary colors. We present evidence that plumage colors in each clade cluster along a line in tetrachromatic color space. Additionally, we present evidence that in three of these clades, this line contains colors on opposite sides of a line passing through the achromatic point (putatively complementary colors, presenting higher chromatic contrast). Finally, interspecific color variation over at least some regions of the body is not constrained by phylogenetic relatedness. By describing plumage patterns in four diverse lineages, we add to the growing body of literature suggesting that the diversity of bird visual signals is constrained. Further, we tentatively hypothesize that in at least some clades possessing bright colors, species-specific plumage patterns may evolve by swapping the distributions of a complementary color pair. Further research on other bird clades may help confirm whether these patterns are general across bird families.
Adenosine triphosphate Binding Cassette subfamily C member 1 (ABCC1) overexpression reduces APP processing and increases alpha- versus beta-secretase activity, in vitro
Authors: Jepsen Wayne M. , De Both Matthew , Siniard Ashley L. , Ramsey Keri , Piras Ignazio S. , Naymik Marcus , Henderson Adrienne , Huentelman Matthew J.
Published: September 2020

The organic anion transporter Adenosine triphosphate Binding Cassette subfamily C member 1 (ABCC1), also known as MRP1, has been demonstrated in murine models of Alzheimer's disease (AD) to export amyloid beta (Abeta) from the endothelial cells of the blood-brain barrier to the periphery, and that pharmaceutical activation of ABCC1 can reduce amyloid plaque deposition in the brain. Here, we show that ABCC1 is not only capable of exporting Abeta from the cytoplasm of human cells, but also that it's overexpression significantly reduces Abeta production and increases the ratio of alpha- versus beta-secretase mediated cleavage of the Amyloid Precursor Protein (APP), likely via indirect modulation of alpha-, beta-, and gamma-secretase activity.
Signalling codes for the maintenance and lineage commitment of embryonic gastric epithelial progenitors
Authors: Sayols Sergi , Klassek Jakub , Werner Clara , Möckel Stefanie , Ritz Sandra , Mendez-Lago Maria , Soshnikova Natalia
Published: September 2020

The identity of embryonic gastric epithelial progenitors is unknown. We used single-cell RNA sequencing, genetic lineage tracing and organoid assays to assess whether Axin2 and Lgr5 expressing cells are gastric progenitors in the developing mouse stomach. We show that Axin2+ cells represent a transient population of embryonic epithelial cells in the forestomach. Lgr5+ cells generate both glandular corpus and squamous forestomach organoids ex vivo. Only Lgr5+ progenitors give rise to zymogenic cells in culture. Modulating the activity of the WNT, BMP and Notch pathways in vivo and ex vivo, we found that WNTs are essential for the maintenance of Lgr5+ epithelial cells. Notch prevents differentiation of the embryonic epithelial cells along all secretory lineages and hence ensures their maintenance. While WNTs promote differentiation of the embryonic progenitors along zymogenic cell lineage, BMPs enhance their differentiation along the parietal lineage. In contrast, WNTs and BMPs are required to suppress differentiation of embryonic gastric epithelium along pit cell lineage. Thus, coordinated action of the WNT, BMP and Notch pathways controls cell fate determination in the embryonic gastric epithelium.
Phosphoregulation of the cytokinetic protein Fic1 contributes to fission yeast growth polarity establishment
Authors: Bohnert K. Adam , Rossi Anthony M. , Jin Quan-Wen , Chen Jun-Song , Gould Kathleen L.
Published: September 2020

Cellular polarization underlies many facets of cell behavior, including cell growth. The rod-shaped fission yeast Schizosaccharomyces pombe is a well-established, genetically tractable system for studying growth polarity regulation. S. pombe cells elongate at their two cell tips in a cell cycle-controlled manner, transitioning from monopolar to bipolar growth in interphase when new ends established by the most recent cell division begin to extend. We previously identified cytokinesis as a critical regulator of new end growth and demonstrated that Fic1, a cytokinetic factor, is required for normal polarized growth at new ends. Here, we report that Fic1 is phosphorylated on two C-terminal residues, which are each targeted by multiple protein kinases. Endogenously expressed Fic1 phosphomutants cannot support proper bipolar growth, and the resultant defects facilitate the switch into an invasive pseudohyphal state. Thus, phosphoregulation of Fic1 links the completion of cytokinesis to the re-establishment of polarized growth in the next cell cycle. These findings broaden the scope of signaling events that contribute to regulating S. pombe growth polarity, underscoring that cytokinetic factors constitute relevant targets of kinases affecting new end growth.

This article has an associated First Person interview with Anthony M. Rossi, joint first author of the paper.