bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of chlorprothixene as a potential drug that induces apoptosis and autophagic cell death in acute myeloid leukemia cells
Authors: Du Yuxin , Li Kening , Wang Xiangeng , Kaushik Aman Chandra , Junaid Muhammad , Wei Dongqing
Published: October 2019

Although acute myeloid leukemia (AML) is a highly heterogeneous malignance, the common molecular mechanisms shared by different AML subtypes play critical roles in AML development. It is possible to identify new drugs that are effective for various AML subtypes based on the common molecular mechanisms. Therefore, we developed a hypothesis‐driven bioinformatic drug screening framework by integrating multiple omics data. In this study, we identified that chlorprothixene, a dopamine receptor antagonist, could effectively inhibit growth of AML cells from different subtypes. RNA‐seq analysis suggested that chlorprothixene perturbed a series of crucial biological processes such as cell cycle, apoptosis, and autophagy in AML cells. Further investigations indicated that chlorprothixene could induce both apoptosis and autophagy in AML cells, and apoptosis and autophagy could act as partners to induce cell death cooperatively. Remarkably, chlorprothixene was found to inhibit tumor growth and induce in situ leukemic cell apoptosis in the murine xenograft model. Furthermore, chlorprothixene treatment could reduce the level of oncofusion proteins PML‐RARα and AML1‐ETO, thus elevate the expression of apoptosis‐related genes, and lead to AML cell death. Our results provided new insights for drug repositioning of AML therapy and confirmed that chlorprothixene might be a potential candidate for treatment of different subtypes of AML by reducing expression of oncofusion proteins.

Database

RNA‐seq data are available in GEO database under the accession number GSE124316.
The growth of juvenile native mussels (Elliptio complanata) in lakes varies with sediment characteristics and site exposure
Authors: Cyr Hélène
Published: October 2019

Unionid mussels are among the largest and longest‐lived freshwater invertebrates and can play an important role in these ecosystems. They are also one of the most endangered groups of organisms. The juvenile stage is a particularly vulnerable part of mussel life history and is one of the most poorly known.

I compared the growth of young Elliptio complanata at 17 nearshore sites, in shallow (polymictic) and stratified lake basins, along gradients of sediment characteristics and site exposure (effective fetch). At each site, the growth of six to 14 small (20–68 mm) mussels collected on the sediment surface was measured, using internal growth lines. The growth of very young endobenthic mussels (22–40 mm) was also measured on four to six mussels at each of two sites.

Juveniles spend several years in the sediments, and I found that during this period growth is not constant but declines rapidly with age. Shifts in δ15N signatures suggest that juveniles change their habitat use towards a more planktonic baseline around the time of maturation, when they reach a length of 30–50 mm. Identical δ13C signatures in juveniles and adults suggest that both rely on food of planktonic origin, whether deposited or suspended.

The growth of juvenile mussels varies in a complex but predictable manner with sediment characteristics and wind‐driven physical forces. Growth was highest in fine sediments with low organic content, in highly organic but coarse sediments, and in protected nearshore areas with low effective fetch. Interestingly, I also found high growth rates at exposed nearshore areas with fine sediments, suggesting that areas where bottom topography creates a refuge from currents and waves may provide particularly good conditions for the early growth of juvenile mussels.

Some parts of the shoreline may be more important than others for native mussel populations, and if we can identify those, they may warrant additional protection.
Laying the groundwork: Building relationships for public and patient involvement in pre‐clinical paediatric research
Authors: Costello Wendy , Dorris Emma
Published: October 2019

Context

Public and patient involvement is increasingly becoming an expectation of research funders and policy makers. Not all areas of health research are public‐facing. Here, we outline an approach for building the skills and developing the relationships required for downstream public and patient involvement in pre‐clinical adolescent rheumatology research.

Objective

To design a methodology for improving researcher‐adolescent communications specifically aimed at mutual relationship building for PPI. Deliberate and effective preparation in advance of research involvement to improve the downstream success of that involvement.

Design

A research seminar and research skills workshop conducted entirely in ‘plain English’ for adolescents and their siblings aged 10‐20. Upskilling of pre‐clinical researchers for effective public involvement.

Setting and participants

Study co‐design between the voluntary charity Irish Children's Arthritis Network and the academic research centre UCD Centre for Arthritis Research. Fifteen adolescents aged 10‐20 years old living with arthritis, four pre‐clinical researchers and one qualitative researcher investigating adolescent or paediatric arthritis.

Main variables studied

Relationship building and communications for effective downstream public involvement in pre‐clinical and laboratory research.

Results

The methodology outlined here was received extremely positively. Both researchers and adolescents living with arthritis felt more comfortable communicating, more knowledgeable about juvenile arthritis and research, and more able to engage in co‐operative dialogue.

Discussion

Engaging early, considering the needs of the community and developing appropriate involvement methodology can enable involvement in pre‐clinical research.

Conclusions

Dedicating resources to building relationships and skills necessary for co‐operative research involvement can overcome some of the barriers to public involvement in pre‐clinical and laboratory‐based research.
The association between periodontal disease and root/coronal caries
Authors: AlQobaly Lina , Sabbah Wael
Published: October 2019

Objectives

To examine whether there is an association between periodontal disease and each of root caries and coronal caries among adults (aged 35 and over), using a nationally representative sample of adults in England, Northern Ireland and Wales.

Material and Methods

In this cross‐sectional study, data from the Adult Dental Health Survey 2009 were used. Adults aged 35 years or older who had periodontal and caries assessment were included. Two sets of negative binomial regression were conducted for each of coronal caries and root caries adjusting for periodontal diseases, dental visits, country, sex, age, education, job classification, oral hygiene and smoking.

Results

Overall, 4738 were included in the analysis. Periodontal disease was significantly associated with each of coronal and root caries. In the fully adjusted model, those with PD/ LoA ≥ 4 mm had 1.03 rate ratio (RR) for coronal caries (95% CI: 1.01‐1.05). In the model pertaining to root caries, the RR for those with periodontitis was 1.23 (95% CI: 1.16‐1.30). Smoking, sex, age and oral hygiene were the variables that showed a consistent and significant association with coronal and root caries.

Conclusion

Individuals with periodontal diseases appeared to be at higher risk of coronal and root caries. While root exposure could be a plausible explanation for the relationship between periodontitis and root caries, the association with coronal caries could be attributed to the irritation of carious cavities, or common risk factors such as poor oral hygiene, or co‐occurrence of different health risk behaviours related to both caries and periodontitis and socioeconomic conditions.
Estimates for quality of life loss due to Respiratory Syncytial Virus
Authors: Hodgson David , Atkins Katherine E. , Baguelin Marc , Panovska‐Griffiths Jasmina , Thorrington Dominic , van Hoek Albert Jan , Zhao Hongxin , Fragaszy Ellen , Hayward Andrew C. , Pebody Richard
Published: October 2019

Background

In children aged <5 years in whom severe respiratory syncytial virus (RSV) episodes predominantly occur, there are currently no appropriate standardised instruments to estimate quality of life years (QALY) loss.

Objectives

We estimated the age‐specific QALY loss due to RSV by developing a regression model which predicts the QALY loss without the use of standardised instruments.

Methods

We conducted a surveillance study which targeted confirmed RSV episodes in children aged <5 years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases). All participants were asked to complete questions regarding their health during the infection, with the suspected cases additionally providing health‐related quality of life (HR‐QoL) loss estimates by completing EQ‐5D‐3L‐Y or EQ‐5D‐3L instruments. We used the responses from the suspected cases to calibrate a regression model which estimates the HR‐QoL and QALY loss due to infection.

Findings

For confirmed RSV cases in children under 5 years of age who sought health care, our model predicted a QALY loss per RSV episode of 3.823 × 10−3 (95% CI 0.492‐12.766 × 10−3), compared with 3.024 × 10−3 (95% CI 0.329‐10.098 × 10−3) for under fives who did not seek health care. Quality of life years loss per episode was less for older children and adults, estimated as 1.950 × 10−3 (0.185‐9.578 × 10−3) and 1.543 × 10−3 (0.136‐6.406 × 10−3) for those who seek or do not seek health care, respectively.

Conclusion

Evaluations of potential RSV vaccination programmes should consider their impact across the whole population, not just young child children.
Significance of inducibility of atrial fibrillation after pulmonary vein isolation in patients with healthy left atrium substrate
Authors: Kosiuk Jedrzej , Gründig Sebastian , Dinov Borislav , Müssigbrodt Andreas , Richter Sergio , Sommer Philipp , Hindricks Gerhard , Bollmann Andreas
Published: October 2019

Background

The significance of the inducibility of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF remains disputable and polarizing. Therefore, we investigated the prognostic value of the inducibility of AF on long‐term outcome after PVI in patients without low‐voltage left atrial (LA) substrate.

Methods

Two hundred forty‐five patients (mean age 59+/−9years, 72% male) without LA low‐voltage areas (defined as electrogram amplitudes <0.5 mV) undergoing first PVI procedure were included in the study. Following successful PVI, inducibility was assessed by burst pacing from coronary sinus with a cycle length (CL) of 300, 250, and 200 ms or the shortest CL resulting in 1:1 atrial capture. During the follow‐up period of up to 3 years, the rhythm outcome was monitored by serial 7‐days Holter electrocardiogram.

Results

AF was induced in 38 patients (16%). Atypical atrial flutter was observed in six patients (2%), while typical flutter in three cases (1%).

Within the first 3 months, early recurrence was diagnosed in 39 patients (16%), while late recurrence was detected in 58 patients (24%) after a mean AF free survival of 28 ± 1 months.

While there was no impact on early recurrence, AF inducibility affected long‐term recurrence (31 ± 1 vs 23 ± 3 months; P = .001). In multivariate analysis, AF inducibility (hazard ratio [HR] 2.14; 95% confidence interval [CI], 1.03‐4.45; P = .041) and persistent type of AF (HR 2.17; 95%CI, 1.06–4.47; P = .034) were associated with late AF recurrence.

Conclusion

In patients without low‐voltage substrate undergoing PVI, AF inducibility is a significant predictor of long‐term outcome. The pathomechanisms of this phenomenon must be further studied to be addressed by additional treatment.
Effects of focal impulse and rotor modulation‐guided ablation on atrial arrhythmia termination and inducibility: Impact on outcomes after treatment of persistent atrial fibrillation
Authors: Kirzner Jared M. , Raelson Colin A. , Liu Christopher F. , Thomas George , Ip James E. , Lerman Bruce B. , Markowitz Steven M. , Cheung Jim W.
Published: October 2019

Introduction

The role of focal impulse and rotor modulation (FIRM)‐guided ablation for the treatment of atrial fibrillation (AF) remains unclear. Previous studies on the FIRM‐guided ablation outcomes have been limited by a focus on AF termination as an endpoint and by patient population heterogeneity. We sought to determine differences in rates of AF termination, inducibility, and recurrence in patients with persistent AF undergoing first‐time ablation with a FIRM‐guided approach compared with patients undergoing conventional ablation.

Methods and Results

Eight‐five consecutive patients (38 FIRM, 47 conventional) with persistent AF undergoing first‐time ablation were retrospectively analyzed. There were no significant differences in the rates of AF termination in the FIRM group compared to the conventional group (26% vs 15%; P = .15). Rates of inducible AF after ablation were 37% in the FIRM group and 30% in the conventional group (P = .32). Over a median follow‐up of 2.4 years, the rates of freedom from AF were similar between the FIRM and conventional groups (1‐year freedom from AF 65% vs 50%, respectively; P = .18). Procedural termination of AF with either FIRM ablation or conventional ablation was not associated with any significant reduction in AF recurrence.

Conclusion

A FIRM‐guided approach was not associated with a significant difference in freedom from AF when compared to conventional ablation. Termination of AF with ablation was not associated with increased freedom from AF. While AF termination using substrate‐based ablation may have mechanistic implications for understanding AF rotor physiology, its impact on clinical outcomes remains unclear.
Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling
Authors: Zhao Lina , Zhai Meili , Yang Xu , Guo Hongjie , Cao Ying , Wang Donghui , Li Ping , Liu Chong
Published: October 2019

Dexmedetomidine (Dex) has been proven to exert protective effects on multiple organs in response to ischaemia‐reperfusion injury, but the specific mechanism by which this occurs has not been fully elucidated. The purpose of this study was to investigate whether Dex attenuates spinal cord ischaemia‐reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS). Our team established a model of SCIRI and utilized the endoplasmic reticulum agonist thapsigargin. Dex (25 g/kg) was intraperitoneally injected 30 minutes before spinal cord ischaemia. After 45 minutes of ischaemia, the spinal cord was reperfused for 24 hours. To evaluate the neuroprotective effect of Dex on SCIRI, neurological function scores were assessed in rats and apoptosis of spinal cord cells was determined by TUNEL staining. To determine whether the endoplasmic reticulum apoptosis pathway CNPY2‐PERK was involved in the neuroprotective mechanism of Dex, the expression levels of related proteins (CNPY2, GRP78, PERK, CHOP, caspase‐12, caspase‐9 and caspase‐3) were detected by western blot analysis and RT‐PCR. We observed that Dex significantly increased the neurological function scores after SCIRI and decreased apoptosis of spinal cord cells. The expression of ERS‐related apoptosis proteins was significantly increased by SCIRI but was significantly decreased in response to Dex administration. Taken together, the results of this study indicate that Dex may attenuate SCIRI by inhibiting the CNPY2‐ERS apoptotic pathway.
Behind the EU's Energy and Climate Policy Conundrum: Erroneous Power Toolbox, Deadlocks and the Way Forward
Authors: Proedrou Filippos
Published: October 2019

This article discusses EU energy and climate policy through the prism of multidimensional power. In so doing, it explores the forms of power EU policy draws from and employs. The article argues that through its gas first policy the EU misused its productive power and failed to shift structural power dynamics, while overplaying its institutional and compulsory power to fulfil its energy/climate goals despite the EU's obvious limitations in the former and impotence in the latter. This mismatch between means and goals points to the need for an alternative power toolbox. This consists in the exercise of productive power to signify clean energy as the new normal; the use of coercive structural and market power to shape and regulate clean energy markets and the increased use of institutional power deriving from a comprehensive energy transition. This power toolbox relaxes the shortcomings of the EU's gas first policy, cements EU energy security and supports the global uptake of transitions to renewable energy.
Use of medication for attention‐deficit/hyperactivity disorder and risk of unintentional injuries in children and adolescents with co‐occurring neurodevelopmental disorders
Authors: Ghirardi Laura , Chen Qi , Chang Zheng , Kuja‐Halkola Ralf , Skoglund Charlotte , Quinn Patrick D. , D'Onofrio Brian M. , Larsson Henrik
Published: October 2019

Background

Attention‐deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co‐occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co‐occurring NDs.

Methods

Using a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on‐treatment with the rate of injuries during periods off‐treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs).

Results

For children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78–0.92) and TBIs (HR = 0.27; 95% CIs = 0.20–0.38) during medicated periods was lower than during non‐medicated periods. Similar results were found among individuals with co‐occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77–1.01) and for TBIs (HR = 0.27; 95% CI = 0.16–0.44).

Conclusions

Beneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co‐occurring NDs.
Flat‐Detector CT to Quantify Response to Intra‐Arterial Spasmolytic Therapy for Cerebral Vasospasm
Authors: O'Connor Kyle P. , Milton Camille K. , Strickland Allison , Apple Blair , Bohnstedt Bradley N.
Published: October 2019

BACKGROUND AND PURPOSE

Cerebral vasospasm in the setting of subarachnoid hemorrhage causes morbidity and mortality due to delayed cerebral ischemia and permanent neurological deficits. Vasospasm treatment includes intra‐arterial injection of a spasmolytic during cerebral angiography. To evaluate effectiveness, neurointerventionalists subjectively examine a posttreatment cerebral angiogram to determine change in vessel diameter or increase in microvascular perfusion. Flat‐detector computed tomography (FDCT) scanner has the ability to quantitatively measure cerebral blood volume (CBV) within the parenchyma and detect a quantitative change following treatment.

METHODS

This is a prospective study at a single institution between October 5, 2017 and June 3, 2019 that examines CBV studies from the Artis Q biplane (Siemens). Regions of interest were made in various territories to measure the CBV within the parenchyma before and after treatment with the spasmolytic verapamil. All instances of vasospasm involved vasculature within the left middle cerebral artery or internal carotid artery. The Wilcoxon signed‐rank test was used to determine significance before and after treatment.

RESULTS

Our cohort consists of 6 patients who underwent Digital Subtraction Angiography (DSA) and FDCT scans for cerebral vasospasm within the left hemisphere. After intra‐arterial injection of 20 mg of verapamil, average increases in blood volume were 59%, 22%, and 24% for the temporal, frontal, and parietal lobes, respectively. P‐values associated were .03. We also observed decrease in the mean arterial blood pressure and transcranial Doppler values after treatment.

CONCLUSION

In conclusion, FDCT could measure the effectiveness of a change in CBV from infusion of verapamil in the setting of cerebral vasospasm. The authors believe quantifying the change allows for reassurance of improvement of cerebral vasospasm.
Adaptation and validation of the health belief model scale for colorectal cancer screening
Authors: Lee Shin‐Young , Lee Eunice E. , Rhee Young Sun , Yang Eun Young , Shin Jeong Ha , Lee Seonah
Published: October 2019

Korea has the second highest incidence of colorectal cancer in the world. Instruments that are culturally and contextually sensitive, as well as valid and reliable, for determining health beliefs regarding colorectal cancer screening are essential for obtaining accurate information. The purpose of this study was to adapt and validate the health belief model scale for Koreans regarding colorectal cancer and fecal occult blood test utilization. Individual and cognitive interviews (also known as cognitive debriefing) with 33 Koreans, expert reviews with seven nursing practitioners and professors, and a pilot test with 18 Koreans were conducted to make the existing health belief model scale culturally and contextually sensitive. Subsequently, a cross‐sectional survey with 728 Koreans aged >50 years was conducted. Exploratory and confirmatory factor analyses of the construct validity and internal consistency reliability supported the adapted health belief model scale. The adapted and validated health belief model scale in this study could contribute to the assessment of health beliefs regarding the fecal occult blood test among Koreans with a greater degree of accuracy with respect to Korean culture and context.
PIRIN2 suppresses S‐type lignin accumulation in a noncell‐autonomous manner in Arabidopsis xylem elements
Authors: Zhang Bo , Sztojka Bernadette , Escamez Sacha , Vanholme Ruben , Hedenström Mattias , Wang Yin , Turumtay Halbay , Gorzsás András , Boerjan Wout , Tuominen Hannele
Published: October 2019

PIRIN (PRN) genes encode cupin domain‐containing proteins that function as transcriptional co‐regulators in humans but that are poorly described in plants. A previous study in xylogenic cell cultures of Zinnia elegans suggested a role for a PRN protein in lignification. This study aimed to identify the function of Arabidopsis (Arabidopsis thaliana) PRN proteins in lignification of xylem tissues.

Chemical composition of the secondary cell walls was analysed in Arabidopsis stems and/or hypocotyls by pyrolysis–gas chromatography/mass spectrometry, 2D‐nuclear magnetic resonance and phenolic profiling. Secondary cell walls of individual xylem elements were chemotyped by Fourier transform infrared and Raman microspectroscopy.

Arabidopsis PRN2 suppressed accumulation of S‐type lignin in Arabidopsis stems and hypocotyls. PRN2 promoter activity and PRN2:GFP fusion protein were localised specifically in cells next to the vessel elements, suggesting a role for PRN2 in noncell‐autonomous lignification of xylem vessels. Accordingly, PRN2 modulated lignin chemistry in the secondary cell walls of the neighbouring vessel elements.

These results indicate that PRN2 suppresses S‐type lignin accumulation in the neighbourhood of xylem vessels to bestow G‐type enriched lignin composition on the secondary cell walls of the vessel elements. Gene expression analyses suggested that PRN2 function is mediated by regulation of the expression of the lignin‐biosynthetic genes.
Stress‐adaptive gene discovery by exploiting collective decision‐making of decentralized plant response systems
Authors: Chivasa Stephen , Goodman Heather Louise
Published: October 2019

Despite having a network of cytoplasmic interconnections (plasmodesmata) facilitating rapid exchange of metabolites and signal molecules, plant cells use the extracellular matrix as an alternative route for cell–cell communication. The need for extracellular signalling in plasmodesmata‐networked tissues is baffling. A hypothesis is proposed that this phenomenon defines the plant extracellular matrix as a ‘democratic space’ for collective decision‐making in a decentralized system, similar to quorum‐sensing in bacteria. Extracellular communication enables signal integration and coordination across several cell layers through ligand‐activated plasma membrane receptors. Recent results from drought stress‐adaptive responses and light‐mediated signalling in cell death activation show operational utility of this decision‐making process. Opportunities are discussed for new innovations in drought gene discovery using platforms targeting the extracellular matrix.
Toward a Theory of Fiscal Slack
Authors: Gorina Evgenia , Maher Craig , Park Sungho
Published: October 2019

Though the fiscal slack literature has advanced over the past decade, more research is needed for a systematic understanding of the determinants and uses of fiscal reserves at the local level. This paper reviews theory and empirical evidence on the determinants of municipal fiscal reserves offers a conceptual framework for analyzing fiscal reserves accumulation and tests a series of hypotheses using a panel of 2007–2012 financial data for 145 U.S. cities from 21 states. Generalized least squares models show that unassigned general fund balances and unrestricted net assets are positively associated with general fund surpluses in the previous year and with local household incomes, while not being related to measures of fiscal risk, revenue effort, and voter characteristics. Overall, the findings suggest a relatively stronger influence of the capacity to save than the need to save on local fiscal reserves.
Frequent appearance of club cell (Clara cell)‐like cells as a histological marker for ALK‐positive lung adenocarcinoma
Authors: Miyata‐Morita Kana , Morita Shigeki , Matsutani Noriyuki , Kondo Fukuo , Soejima Yurie , Sawabe Motoji
Published: October 2019

Anaplastic lymphoma kinase‐rearranged (ALK+) lung cancers show characteristic histological features, such as solid signet ring cell patterns and mucinous cribriform patterns; however, these features are not always observed in ALK+ lung cancers. We noticed that club cell (Clara cell)‐like cells (CLCs) were frequently present in the papillary portion of ALK+ lung adenocarcinomas. In this study, we investigated the importance of CLCs in papillary patterns of ALK+ lung cancers. We compared the histological features of 18 ALK+ cases with 62 control cases (22 epidermal growth factor receptor‐positive (EGFR+) and 40 ALK‐ and EGFR‐negative (ALK−/EGFR−) cases). The present study analyzed presence of papillary pattern, proportion of papillary pattern area, presence of micropapillary pattern, frequency of CLCs and lengths of snout. The frequency of CLCs in ALK+ cases was significantly higher than that in EGFR+ cases and ALK−/EGFR− cases. Micropapillary pattern was more frequently observed in ALK+ cases than that in ALK−/EGFR− cases (P < 0.001). The present study indicated that the high frequency of CLCs in papillary patterns was significantly associated with ALK+ cases. When solid signet ring cell patterns and mucinous cribriform patterns are absent, the high frequency of CLCs in papillary adenocarcinoma could be a useful histological marker for ALK+ lung cancers.
Achievements and future perspectives of embryo transfer technology in pigs
Authors: Martinez Emilio A. , Martinez Cristina A. , Cambra Josep M. , Maside Carolina , Lucas Xiomara , Vazquez Jose L. , Vazquez Juan Maria , Roca Jordi , Rodriguez‐Martinez Heriberto , Gil Maria Antonia , Parrilla Inmaculada , Cuello Cristina
Published: October 2019

Commercial embryo transfer (ET) has unprecedented productive and economic implications for the pig sector. However, pig ET has been considered utopian for decades mainly because of the requirements of surgical techniques for embryo collection and embryo deposition into recipients, alongside challenges to preserve embryos. This situation has drastically changed in the last decade since the current technology allows non‐surgical ET and short‐ and long‐term embryo preservation. Here, we provide a brief review of the improvements in porcine ET achieved by our laboratory in the past 20 years. This review includes several aspects of non‐surgical ET technology and different issues affecting ET programmes and embryo preservation systems. The future perspectives of ET technology are also considered. We will refer only to embryos produced in vivo since they are the only type of embryos with possible short‐term use in pig production.
Alternatives in Donkey semen cryopreservation: Mare vs. Jenny Colostrum
Authors: Álvarez Cristina , González Noelia , Luño Victoria , Martínez Felisa , Gil Lydia
Published: October 2019

The aim of this study was to test and compare two new components in extenders for freezing donkey semen: mare colostrum and jenny colostrum. Colostrum was obtained from four mares and four jennies right after the foal's birth. Ejaculates were collected from five fertile donkeys. Sperm samples were pooled, diluted and cryopreserved in three different experimental extender groups: lactose supplemented with egg yolk extender (20%) as the control group, lactose supplemented with jenny colostrum extender (20%), and lactose supplemented with mare colostrum extender (20%). After thawing, we evaluated the sperm motility by means of computer‐assisted analysis, viability by SYBR‐14 and propidium iodide (PI), membrane functional by HOS test and acrosome integrity by isothiocyanate conjugated with peanut agglutinin (FITC‐PNA) and PI. The results demonstrated that lactose–jenny colostrum extender displayed significantly higher values (p < .05) in nearly all parameters evaluated – Total Motility, Viability, HOS test, VCL, VSL, VAP, LIN, STR and WOB –, compared with mare colostrum and egg yolk extenders after thawing. In conclusion, the extender containing jenny colostrum used for donkey semen cryopreservation improved the donkey sperm quality after the freezing–thawing process.
Is sperm cryopreservation in absence of permeable cryoprotectants suitable for subfertile donkeys?
Authors: Diaz‐Jimenez Maria , Dorado Jesús , Pereira Blasa , Consuegra Cesar , Ortiz Isabel , Hidalgo Manuel
Published: October 2019

Contents

Sperm from fertile donkeys have been successfully frozen in absence of permeable cryoprotectants. The aim of this study was to determine whether this cryopreservation method is suitable for subfertile donkeys in comparison to conventional sperm freezing with glycerol. Ejaculates were collected from four Andalusian Donkeys: three fertile and one subfertile. Semen was frozen with an extender containing glycerol (GLY), or adding instead sucrose 0.25 molar and 1% bovine serum albumin (SUC) as non‐permeable cryoprotectants. After thawing, samples were assessed for total (TM, %) and progressive (PM, %) sperm motility by CASA, plasma membrane integrity (PMI, %) by epifluorescence microscopy and DNA integrity (DFI, %) by SCSA. Results (mean ± SD) were compared between extenders in fertile and subfertile donkeys using the Student's t test. No differences between GLY and SUC treatments were found in the fertile group for the sperm parameters assessed. In subfertile donkey ejaculates, GLY resulted in significantly higher values than SUC for TM (25.5 ± 3.1 vs. 19.6 ± 1.9) and PM (13.3 ± 5.1 vs. 4.0 ± 1.2), respectively. In conclusion, considering all the sperm parameters assessed, sperm freezing in absence of permeable cryoprotectants may not be still an option for cryopreservation of subfertile donkey sperm.
Pregnancy‐induced changes in the transcript levels of prolactin receptor and its suppressor in the ovine hypothalamus and adenohypophysis
Authors: Szczesna Malgorzata , Kirsz Katarzyna , Misztal Tomasz , Zieba Dorota A.
Published: October 2019

The aim of this study was to analyse changes in the abundance of prolactin (PRL) receptor (PRLR) and suppressor of cytokine signalling‐3 (SOCS‐3) mRNA in the ventro‐/dorsomedial nucleus (VMH/DMH) and arcuate nucleus (ARC) of the hypothalamus as well as in the median eminence (ME) and adenohypophysis (AP) in sheep at 30, 60, 90 and 120 d of pregnancy compared to non‐pregnant animals. In the VMH/DMH, PRLR transcripts were detected only in non‐pregnant ewes. In the ARC, the abundances of PRLR mRNA were higher in pregnant sheep on days 30 (p < .01), 90 (p < .01) and 120 (p < .05) than in non‐pregnant sheep. In contrast, the expression of PRLR mRNA in the ME was lower (p < .01) in pregnant ewes at days 30 and 60 than in non‐pregnant ewes and was undetectable at later stages of gestation. In all studied stages of pregnancy except day 60, the abundance of PRLR mRNA was higher (p < .01) in the ARC than in the AP, while in non‐pregnant sheep, there were no differences (p ≥ .05) in the transcript levels between these two tissues. In non‐pregnant ewes, the abundance of SOCS‐3 mRNA in the AP was lower than that in any other studied tissue (p < .05‐p < .01). In conclusion, the observed changes in PRLR and SOCS‐3 mRNA abundance in the hypothalamus and AP during pregnancy may be important components of the mechanisms regulating the action of PRL in energy homeostasis and neuroendocrine interactions within the hypothalamic–pituitary axis.
“Welcome! Oh, wait…” Transgender Military Service in a Time of Uncertainty
Authors: Embser‐Herbert Máel
Published: October 2019

In 2014, the Department of Defense began a broad review of transgender military service. Following this review, in 2016, the Obama Administration announced a policy of transgender inclusion in the military. However, in 2017, before enactment of that policy, President Trump announced the reinstatement of a ban on transgender military service. Although, in the last five years, these events have garnered much media attention, sociologists have generally left them unexplored. In this article, I begin the process of incorporating transgender military experience into sociological discussions by examining how transgender service members navigate their uncertain status vis‐à‐vis military service. In so doing, I explore how transgender personnel might be “doing transgender” (Connell, Gender & Society24(1):31) in the context of shifting norms about who can and cannot officially exist within the ranks of the military as well as possibilities for future research examining transgender military experience more broadly.
Race and Politics: Predicting Support for 2016 Presidential Primary Candidates among White Americans
Authors: Levchak Philip J. , Levchak Charisse C.
Published: October 2019

Using a sample of up to 859 white Americans in the United States, we examine how racial resentment, perceptions of discrimination toward majority and minority populations, white identity salience, and American identity salience influence support for five candidates running for President in 2016. Using data from the American National Election Studies 2016 Pilot Study, we find that racial resentment influences support for both Republican and Democratic presidential candidates, and white identity salience increases support for Trump and Clinton. Although policy issues, including the economy, health care, immigration, and terrorism, also shape attitudes toward political candidates, the effects of racial resentment and white identity salience persist. We conclude by arguing that America continues to be shaped by a white racial frame which views minorities as inferior and that this view is perpetuated through support for candidates who support white supremacy.
Effectiveness of tigecycline in the treatment of infections caused by carbapenem‐resistant gram‐negative bacteria in pediatric liver transplant recipients: A retrospective study
Authors: Chen Fang , Shen Chuan , Pang Xiaoyun , Zhang Zaili , Deng Yuxiao , Han Longzhi , Chen Xiaosong , Zhang Jianjun , Xia Qiang , Qian Yongbing
Published: October 2019

Introduction

Tigecycline (TGC) is effective for the infections caused by carbapenem‐resistant gram‐negative bacteria (CRGNB) in adults, but it is not investigated systematically in children because of concern about adverse effects. This study aimed to analyze the effectiveness of TGC in treating CRGNB infections in children after receiving liver transplant.

Methods

The subjects in this retrospective study were pediatric liver transplant recipients treated with TGC for at least 3 days to fight microbiologically verified CRGNB infection after initial antibiotic failure during the period from January 2014 to May 2018. Clinical and microbiological outcomes were reviewed to evaluate the efficacy and safety of TGC.

Results

Of the 1177 pediatric liver transplant recipients, 13 patients were eligible for inclusion in this analysis. All the patients received TGC at dose of 2 mg/kg every 12 hours for a duration of 10.1 ± 5.1 days on average to treat CRGNB infections, including complicated intra‐abdominal infection, ventilator‐associated pneumonia, and bloodstream infection. The isolates included Klebsiella pneumoniae (69.2%, 9/13) and Acinetobacter baumannii (30.8%, 4/13). Clinical efficacy was achieved in 84.6% (11/13) and pathogen eradicated in 69.2% (9/13) of the patients. The overall mortality rate was 15.4% (2/13). No TGC‐related serious adverse event was reported.

Conclusion

Tigecycline can be considered in combination antimicrobial regimen for treating CRGNB‐related infections in pediatric liver transplant recipients.
Natural genetic variation in photosynthesis: an untapped resource to increase crop yield potential?
Authors: Faralli Michele , Lawson Tracy
Published: October 2019

Raising crop yield potential is a major goal to ensure food security for the growing global population. Photosynthesis is the primary determinant of crop productivity and any gain in photosynthetic CO2 assimilation per unit of leaf area (A) has the potential to increase yield. Significant intraspecific variation in A is known to exist in various autotrophic organs that represent an unexploited target for crop improvement. However, the large number of factors that influence photosynthetic rates often makes it difficult to measure or estimate A under dynamic field conditions (i.e. fluctuating light intensities or temperatures). This complexity often results in photosynthetic capacity, rather than realized photosynthetic rates being used to assess natural variation in photosynthesis. Here we review the work on natural variation in A, the different factors determining A and their interaction in yield formation. A series of drawbacks and perspectives are presented for the most common analyses generally used to estimate A. The different yield components and their determination based on different photosynthetic organs are discussed with a major focus on potential exploitation of various traits for crop improvement. To conclude, an example of different possibilities to increase yield in wheat through enhancing A is illustrated.
Tissue‐specific inactivation by cytosine deaminase/uracil phosphoribosyl transferase as a tool to study plant biology
Authors: Leonhardt Nathalie , Divol Fanchon , Chiarenza Serge , Deschamps Sabrina , Renaud Jeanne , Giacalone Cécile , Nussaume Laurent , Berthomé Richard , Péret Benjamin
Published: October 2019

Recent advances in the study of plant developmental and physiological responses have benefited from tissue‐specific approaches, revealing the role of some cell types in these processes. Such approaches have relied on the inactivation of target cells using either toxic compounds or deleterious genes; however, both tissue‐specific and truly inducible tools are lacking in order to precisely target a developmental window or specific growth response. We engineered the yeast fluorocytosine deaminase (FCY1) gene by creating a fusion with the bacterial uracil phosphoribosyl transferase (UPP) gene. The recombinant protein converts the precursor 5‐fluorocytosine (5‐FC) into 5‐fluorouracyl, a drug used in the treatment of a range of cancers, which triggers DNA and RNA damage. We expressed the FCY‐UPP gene construct in specific cell types using enhancer trap lines and promoters, demonstrating that this marker acts in a cell‐autonomous manner. We also showed that it can inactivate slow developmental processes like lateral root formation by targeting pericycle cells. It also revealed a role for the lateral root cap and the epidermis in controlling root growth, a faster response. The 5‐FC precursor acts systemically, as demonstrated by its ability to inhibit stomatal movements when supplied to the roots in combination with a guard cell‐specific promoter. Finally, we demonstrate that the tissular inactivation is reversible, and can therefore be used to synchronize plant responses or to determine cell type‐specific functions during different developmental stages. This tool will greatly enhance our capacity to understand the respective role of each cell type in plant physiology and development.
Loss of function of Arabidopsis NADP‐malic enzyme 1 results in enhanced tolerance to aluminum stress
Authors: Badia Mariana Beatriz , Maurino Verónica Graciela , Pavlovic Tatiana , Arias Cintia Lucía , Pagani María Ayelén , Andreo Carlos Santiago , Saigo Mariana , Drincovich María Fabiana , Gerrard Wheeler Mariel Claudia
Published: October 2019

In acidic soils, aluminum (Al) toxicity is a significant limitation to crop production worldwide. Given its Al‐binding capacity, malate allows internal as well as external detoxification strategies to cope with Al stress, but little is known about the metabolic processes involved in this response. Here, we analyzed the relevance of NADP‐dependent malic enzyme (NADP‐ME), which catalyzes the oxidative decarboxylation of malate, in Al tolerance. Plants lacking NADP‐ME1 (nadp‐me1) display reduced inhibition of root elongation along Al treatment compared with the wild type (wt). Moreover, wt roots exposed to Al show a drastic decrease in NADP‐ME1 transcript levels. Although malate levels in seedlings and root exudates are similar in nadp‐me1 and wt, a significant increase in intracellular malate is observed in roots of nadp‐me1 after long exposure to Al. The nadp‐me1 plants also show a lower H2O2 content in root apices treated with Al and no inhibition of root elongation when exposed to glutamate, an amino acid implicated in Al signaling. Proteomic studies showed several differentially expressed proteins involved in signal transduction, primary metabolism and protection against biotic and other abiotic stimuli and redox processes in nadp‐me1, which may participate directly or indirectly in Al tolerance. The results indicate that NADP‐ME1 is involved in adjusting the malate levels in the root apex, and its loss results in an increased content of this organic acid. Furthermore, the results suggest that NADP‐ME1 affects signaling processes, such as the generation of reactive oxygen species and those that involve glutamate, which could lead to inhibition of root growth.
The impact of patient blood management on blood utilization and clinical outcomes in complex spine surgery
Authors: Visagie Mereze , Qin Caroline X. , Cho Brian C. , Merkel Kevin R. , Kajstura Tymoteusz J. , Amin Raj M. , Purvis Taylor E. , Kebaish Khaled M. , Frank Steven M.
Published: October 2019

BACKGROUND

Patient blood management (PBM) is especially applicable in major spine surgery, during which bleeding and transfusion are common. What remains unclear in this setting is the overall impact of bundled PBM measures on transfusion requirements and clinical outcomes. We compared these outcomes before and after implementing a PBM program.

STUDY DESIGN AND METHODS

We conducted a retrospective review of 928 adult complex spine surgery patients performed by a single surgeon between January 2009 and June 2016. Although PBM measures were phased in over time, tranexamic acid (TXA) administration became standard protocol in July 2013, which defined our pre‐ and post‐PBM periods. Transfusion rates for all blood components before and after PBM implementation were compared, as were morbid event rates and mortality.

RESULTS

Baseline characteristics were similar before and after PBM. Before PBM, the mean number of units/patient decreased for red blood cells (RBCs; by 19.5%; p = 0.0057) and plasma (by 33%; p = 0.0008), but not for platelets (p = 0.15). After risk adjustment by multivariable analyses, the composite outcome of morbidity or mortality showed a nonsignificant trend toward improvement after PBM (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.39‐1.01; p = 0.055), and the risk of thrombotic events was unchanged (OR, 1.12; 95% CI, 0.42‐2.58; p = 0.80).

CONCLUSION

In complex spine surgery, a multifaceted PBM program that includes TXA can be advantageous by reducing transfusion requirements without changing clinical outcomes.
Acute mesenteric ischemia–like syndrome associated with suspected Spirocerca lupi aberrant migration in dogs
Authors: Lerman Omer , Israeli Inbar , Weingram Tomer , Benzioni‐Bar Hadas , Milgram Josh , Shipov Anna
Published: October 2019

Objective

To describe acute mesenteric infarction due to suspected Spirocerca lupi aberrant migration in 5 dogs.

Case Series Summary

All dogs were large breed, none of which exhibited typical clinical signs associated with spirocercosis. All dogs were eventually diagnosed with septic peritonitis. On exploratory laparotomy, thickening of the jejunal arteries, surrounding mesojejunum, and segmental necrosis were identified. Similar thickening and hematoma formation were found in other regions of the mesentery. In 4 of the cases, the necrotic segment was located in the distal jejunum. Histology revealed thrombotic mesenteric vessels with intralesional S. lupi nematode larvae. Resection and anastomosis of the necrosed section was performed and all but 1 dog survived and were discharged within 1–6 days.

New or Unique Information Provided

Spirocerca lupi is a potential cause of mesenteric infarction in endemic areas when no other obvious etiology is identified.