bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurons in the Dorso-Central Division of Zebrafish Pallium Respond to Change in Visual Numerosity
Authors: Messina Andrea , Potrich Davide , Schiona Ilaria , Sovrano Valeria Anna , Fraser Scott E , Brennan Caroline H , Vallortigara Giorgio
Published: June 2021

We found a region of the zebrafish pallium that shows selective activation upon change in the numerosity of visual stimuli. Zebrafish were habituated to sets of small dots that changed in individual size, position, and density, while maintaining their numerousness and overall surface. During dishabituation tests, zebrafish faced a change in number (with the same overall surface), in shape (with the same overall surface and number), or in size (with the same shape and number) of the dots, whereas, in a control group, zebrafish faced the same stimuli as during the habituation. Modulation of the expression of the immediate early genes c-fos and egr-1 and in situ hybridization revealed a selective activation of the caudal part of the dorso-central division of the zebrafish pallium upon change in numerosity. These findings support the existence of an evolutionarily conserved mechanism for approximate magnitude and provide an avenue for understanding its underlying molecular correlates.
Efficacy and limitations of senolysis in atherosclerosis
Authors: Garrido Abel Martin , Kaistha Anuradha , Uryga Anna K , Oc Sebnem , Foote Kirsty , Shah Aarti , Finigan Alison , Figg Nichola , Dobnikar Lina , Jørgensen Helle , Bennett Martin
Published: June 2021

Aims

Traditional markers of cell senescence including p16, Lamin B1, and senescence-associated beta galactosidase (SAβG) suggest very high frequencies of senescent cells in atherosclerosis, while their removal via ‘senolysis’ has been reported to reduce atherogenesis. However, selective killing of a variety of different cell types can exacerbate atherosclerosis. We therefore examined the specificity of senescence markers in vascular smooth muscle cells (VSMCs) and the effects of genetic or pharmacological senolysis in atherosclerosis.

Methods and results

We examined traditional senescence markers in human and mouse VSMCs in vitro, and in mouse atherosclerosis. p16 and SAβG increased and Lamin B1 decreased in replicative senescence and stress-induced premature senescence (SIPS) of cultured human VSMCs. In contrast, mouse VSMCs undergoing SIPS showed only modest p16 up-regulation, and proliferating mouse monocyte/macrophages also expressed p16 and SAβG. Single cell RNA-sequencing (scRNA-seq) of lineage-traced mice showed increased p16 expression in VSMC-derived cells in plaques vs. normal arteries, but p16 localized to Stem cell antigen-1 (Sca1)+ or macrophage-like populations. Activation of a p16-driven suicide gene to remove p16+ vessel wall- and/or bone marrow-derived cells increased apoptotic cells, but also induced inflammation and did not change plaque size or composition. In contrast, the senolytic ABT-263 selectively reduced senescent VSMCs in culture, and markedly reduced atherogenesis. However, ABT-263 did not reduce senescence markers in vivo, and significantly reduced monocyte and platelet counts and interleukin 6 as a marker of systemic inflammation.

Conclusions

We show that genetic and pharmacological senolysis have variable effects on atherosclerosis, and may promote inflammation and non-specific effects respectively. In addition, traditional markers of cell senescence such as p16 have significant limitations to identify and remove senescent cells in atherosclerosis, suggesting that senescence studies in atherosclerosis and new senolytic drugs require more specific and lineage-restricted markers before ascribing their effects entirely to senolysis.
Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review
Authors: van Kessel Sophie A M , Olde Hartman Tim C , Lucassen Peter L B J , van Jaarsveld Cornelia H M
Published: June 2021

Background

It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild (managed in the outpatient setting) COVID-19 infection. Currently, research on these persistent symptoms mainly focuses on patients with severe infections (managed in an inpatient setting) whereas patients with mild disease are rarely studied.

Objective

The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID-19 infection.

Methods

Systematic literature searches were performed in Pubmed, Embase and PsychINFO on 2 February 2021. Quantitative studies, qualitative studies, clinical lessons and case reports were considered eligible designs.

Results

In total, nine articles were included in this literature review. The frequency of persistent symptoms in patients after mild COVID-19 infection ranged between 10% and 35%. Symptoms persisting after a mild COVID-19 infection can be distinguished into physical, mental and social symptoms. Fatigue was the most frequently described persistent symptom. Other frequently occurring persistent symptoms were dyspnoea, cough, chest pain, headache, decreased mental and cognitive status and olfactory dysfunction. In addition, it was found that persisting symptoms after a mild COVID-19 infection can have major consequences for work and daily functioning.

Conclusion

There is already some evidence that symptoms of mild COVID-19 persist after 3 weeks in a third of patients. However, there is a lack of data about symptoms persisting after 3 months (long-COVID). More research is needed to help GPs in managing long-COVID.
Does decentralization of health systems translate into decentralization of authority? A decision space analysis of Ugandan healthcare facilities
Authors: Chen John , Ssennyonjo Aloysius , Wabwire-Mangen Fred , Kim June-Ho , Bell Griffith , Hirschhorn Lisa
Published: June 2021

Since the 1990s, following similar reforms to its general politico-administrative systems, Uganda has decentralized its public healthcare system by shifting decision-making power away from its central Ministry of Health and towards more distal administrative levels. Previous research has used decision space—the decision-making autonomy demonstrated by entities in an administrative hierarchy—to measure overall health system decentralization. This study aimed to determine how the decision-making autonomy reported by managers of Ugandan healthcare facilities (de facto decision space) differs from that which they are allocated by official policies (de jure decision space). Additionally, it sought to determine associations between decision space and indicators of managerial performance. Using quantitative primary healthcare data from Ugandan healthcare facilities, our study determined the decision space expressed by facility managers and the performance of their facilities on measures of essential drug availability, quality improvement and performance management. We found managers reported greater facility-level autonomy than expected in disciplining staff compared with recruitment and promotion, suggesting that managerial functions that require less financial or logistical investment (i.e. discipline) may be more susceptible to differences in de jure and de facto decision space than those that necessitate greater investment (i.e. recruitment and promotion). Additionally, we found larger public health facilities expressed significantly greater facility-level autonomy in drug ordering compared with smaller facilities, which indicates ongoing changes in the Ugandan medical supply chain to a hybrid ‘push-pull’ system. Finally, we found increased decision space was significantly positively associated with some managerial performance indicators, such as essential drug availability, but not others, such as our performance management and quality improvement measures. We conclude that increasing managerial autonomy alone is not sufficient for improving overall health facility performance and that many factors, specific to individual managerial functions, mediate relationships between decision space and performance.
A Creative Model for an Interdisciplinary Approach to Service-Learning
Authors: Marx Meghan A , Glaser Rivka L , Moran Christine E , Tucker Kimberly Pause
Published: June 2021

Synopsis

The biological sciences are inherently interdisciplinary and important advances in biology cannot be made without collaboration. Despite the increasing emphasis on interdisciplinarity in higher education, science courses only rarely extend to content outside of the STEM discipline. Classes are typically taught by one faculty member in one discipline. To demonstrate relevance while addressing genuine community needs, faculty can use service-learning in their courses. Service-learning is an experiential learning strategy where students learn course content and additional relevant skills through completing service with a community partner. Community needs are frequently beyond the scope of a single course or discipline. In order to better meet community needs, an interdisciplinary collaboration provides a more comprehensive experience that highlights the application and interconnection of course content. This article presents a generalisable model for successful interdisciplinary collaborations. While the nature of course scheduling, academic department structure, and faculty workload can be barriers to collaboration between faculty, they are not insurmountable and accomplishable within this framework. The benefits to the students and the community far outweigh navigating these challenges. Using an interdisciplinary approach in teaching will not only enrich course content and expand student learning in multiple areas, but also increase collaboration within the academy while better meeting community needs.
Adjuvant chemotherapy improves survival outcomes after complete resection of thymic squamous cell carcinoma: a retrospective study of 116 patients
Authors: Gao Lanting , Wang Changlu , Liu Mina , Fang Wentao , Lv Changxing , Fu Xiaolong
Published: June 2021

OBJECTIVES

The aim of this study was to evaluate the efficacy of adjuvant chemotherapy (ACT) for thymic squamous cell carcinoma after completely resection.

METHODS

Patients with thymic squamous cell carcinoma treated with complete resection between January 2009 and December 2016 were retrospectively identified. Kaplan–Meier analysis was used to summarize the time-to-event variables. Univariable and multivariable Cox proportional hazards regression analyses were performed.

RESULTS

A total of 116 patients were analysed with 44 patients in the non-ACT group and 72 patients in the ACT group. No significant difference was found in the 5-year recurrence-free survival (RFS) rate (58.1% vs 51%, P = 0.33) or the 5-year overall survival (OS) rate (77.7% vs 67.1%, P = 0.26) between the ACT group and the non-ACT group. Masaoka stage was the only independent prognostic factor for both RFS and OS. Subgroup analysis showed significant improvement in 5-year RFS for Masaoka stage II patients (P = 0.035) and 5-year OS (P = 0.036) for Masaoka stage III patients when comparing ACT with non-ACT. No chemotherapy-related death occurred. The most frequent adverse effect higher than grade 3 was neutropenia.

CONCLUSIONS

For completely resected thymic squamous cell carcinoma, ACT significantly improved the 5-year RFS in Masaoka stage II patients and the 5-year OS in Masaoka stage III patients.
Management of bronchopleural fistula with endobronchial valve in hybrid operating room following transbronchial microwave ablation
Authors: Mak Ka Lun , Chan Joyce W Y , Lau Rainbow W H , Ng Calvin S H
Published: June 2021

Transbronchial microwave ablation for the treatment of lung nodules is gaining popularity. In the present case, transbronchial microwave ablation to a right middle lobe lesion was performed under electromagnetic navigation bronchoscopy guidance. It was complicated with pneumothorax and persistent air leak despite chest drainage and chemical pleurodesis. A diagnosis of bronchopleural fistula was reached and an endobronchial valve was implanted to the middle lobe segmental bronchus with almost immediate cessation of air leak. Our case demonstrated that endobronchial valve is safe and effective in managing bronchopleural fistula after transbronchial microwave ablation.
Ignoring the Messenger? Limits of Populist Rhetoric on Public Support for Foreign Development Aid
Authors: Bayram A Burcu , Thomson Catarina P
Published: June 2021

The negative impact of populist anti-aid rhetoric on public opinion has been based on anecdotal reports to date. Here, we take a systematic and empirical look at this inquiry. We hypothesize that even though populist rhetoric decreases support for foreign development aid in donor publics, this effect is conditioned by individuals’ preexisting beliefs about populist leaders. Using data from original survey experiments conducted with representative samples of American and British adults, we find that exposure to different variants of populist frames decreases individuals’ willingness to support their government providing development aid through an international organization. However, this effect is moderated by whether people think populist leaders stand up for the little guy or scapegoat out-groups. Connecting foreign aid and populism literatures, our results suggest that the future of global development might not be as bleak as previously feared in the age of populism.
Temperature-Dependent Biological Control Effectiveness of Tamarixia radiata (Hymenoptera: Eulophidea) Under Laboratory Conditions
Authors: Ramos Aguila Luis Carlos , Atlihan Remzi , Ashraf Hafiza Javaria , Keppanan Ravindran , Lei Lijin , Bamisile Bamisope Steve , Cerda Hugo , Wang Liande
Published: June 2021

The parasitism rate and host-feeding rate of Tamarixia radiata (Hymenoptera: Eulophidae), an ectoparasitoid of Diaphorina citri (Hemiptera: Liviidae), were evaluated at 20, 27.5, 30, and 35°C, at 70 ± 5% RH, and 14 h of photoperiod. The biological control efficacy of T. radiata was evaluated by linking the age-stage predation rate with the two-sex life table. The net host-feeding rate (C0) by T. radiata was 32.05, 54.40, 17.25, and 1.92 nymphs per female parasitoid at 20, 27.5, 30, and 35°C, respectively. The total net nymphs killing rate (Z0) was 103.02, 223.82, 72.95, and 6.60 nymphs per female parasitoid at 20, 27.5, 30, and 35°C, respectively. Noneffective parasitism rate was observed at 35°C because of high mortality at this temperature. Our results indicated that temperature had meaningful effects on parasitism and host-feeding rate parameters in the laboratory, and may affect biological control efficiency of the parasitoid in the field. The highest host-feeding rate and total biological control efficiency of T. radiata were recorded at 27.5°C. Most importantly, we found that host-feeding activity of the parasitoid is temperature-dependent, and changed across temperature regimes: the host-feeding rate increased as the temperature increased up to 30°C, started to decrease after this temperature and declined to its minimum level at 35°C. This information is valuable for developing biological control and integrated pest management techniques for Asian citrus psyllid management.
IMRT improves local control in patients with nasopharyngeal carcinoma compared with conventional radiotherapy: propensity score-matched analysis
Authors: Ma Zichang , Umezawa Rei , Yamamoto Takaya , Ishikawa Yojiro , Takahashi Noriyoshi , Takeda Kazuya , Suzuki Yu , Tang Liuwei , Ito Kengo , Kadoya Noriyuki , Jingu Keiichi
Published: June 2021

Background

It is still controversial whether intensity-modulated radiotherapy has an obvious advantage over conventional radiotherapy. The purposes of this study were to evaluate prognostic factors in pre-treatment characteristics for nasopharyngeal carcinoma and to compare treatment outcomes in patients who received intensity-modulated radiotherapy and patients who received two-dimensional radiotherapy or three-dimensional radiotherapy.

Methods

We reviewed patients with nasopharyngeal carcinoma who received chemoradiotherapy in our hospital during the period from 2000 to 2017, and we excluded patients who had a history of surgery for nasopharyngeal carcinoma and those who had distant metastases before treatment. A total of 72 patients who were treated by radiotherapy with concurrent chemotherapy were enrolled. All of the patients were irradiated with a total dose of 58–70 Gy. Overall survival, locoregional control and progression-free survival rates were compared in the groups treated by intensity-modulated radiotherapy and two-dimensional/three-dimensional radiotherapy. Propensity score matching was performed to homogenize the two groups.

Results

The median follow-up period was 62.5 months. After propensity score matching, in patients treated with intensity-modulated radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 73.5, 95.2 and 72.7%, respectively. In patients treated with two-dimensional/three-dimensional radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 69.1, 67.7 and 51.8%, respectively. There was a significant difference between the groups only in locoregional control. Late toxicities of grade 2 or higher were occurred in 38.5 and 24.2% of the patients treated by two-dimensional/three-dimensional radiotherapy and intensity-modulated radiotherapy, respectively.

Conclusions

Our results suggested that intensity-modulated radiotherapy is more effective than two-dimensional/three-dimensional radiotherapy in patients with nasopharyngeal carcinoma, especially in locoregional control.
A new species of Molossus (Chiroptera: Molossidae) from Argentina
Authors: Montani M Eugenia , Tomasco Ivanna H , Barberis Ignacio M , Romano Marcelo C , Barquez Rubén M , Díaz M Mónica
Published: June 2021

Fourteen species of bats in the genus Molossus currently are recognized in the Neotropical region; only three are known from Argentina. Here, we describe a new species based on specimens collected in the province of Santa Fe, Argentina, in the Pampa ecoregion. The new species can be distinguished from its congeners by its general strong orange coloration, forearm length > 41 mm, dorsal hairs bicolor and long (~5 mm), infraorbital foramen laterally oriented, and long and forward-projected (pincer-like) upper incisors. The external and cranial morphology of the new species are described and comparisons made with other species of similar size and with those present in its distributional area. Wilcoxon tests and multivariate analyses (nonmetric multidimensional scaling ordination and PERMANOVA) were carried out to determine the morphometric differences between the new species and other seven species of Molossus. The species tree, estimated by *BEAST from the concatenation of mitochondrial and nuclear genes, suggests that Molossus sp. nov. is basal within the clade formed by {{M. aztecus, M. rufus}, {{M. currentium, M. pretiosus}, M. sinaloae}} with a posterior probability of 0.82.
Biotic and abiotic factors determine species diversity–productivity relationships in mountain meadows
Authors: Liu Jia-Jia , Xu Yong , Shan You-Xia , Burgess Kevin S , Ge Xue-Jun
Published: June 2021

Aims

Species diversity–productivity relationships in natural ecosystems have been well documented in the literature. However, biotic and abiotic factors that determine their relationships are still poorly understood, especially under future climate change scenarios.

Methods

Randomized block factorial experiments were performed in three meadows along an elevational gradient on Yulong Mountain, China, where open-top chambers and urea fertilizer manipulations were used to simulate warming and nitrogen addition, respectively. Besides species diversity, we measured functional diversity based on five traits: plant height, specific leaf area and leaf carbon, nitrogen and phosphorus contents. Several abiotic factors relating to climate (air temperature and precipitation) and soil chemistry (pH, organic carbon concentration, total nitrogen concentration and phosphorus concentration) were also measured. Generalized linear mixed-effect models were used to investigate the responses of species diversity and productivity to elevation, warming, nitrogen addition and their interactions. The effects of biotic and abiotic factors on the direction and magnitude of their relationship were also assessed.

Important Findings

Species diversity decreased with increasing elevation and declined under warming at mid-elevation, while productivity decreased with increasing elevation. Functional richness, maximum air temperature, soil pH and their interactions showed strong but negative influences on the species diversity–productivity relationship; the relationship shifted from positive to neutral and then to slightly negative as these sources of variation increased. Our study highlights the negative effects of short-term warming on species diversity and emphasizes the importance of both biotic and abiotic drivers of species diversity–productivity relationships in mountain meadow communities.
Diagnostic Value of Circular RNA hsa_circ_0002874 Expression in Peripheral Blood of Patients with Gastric Cancer
Authors: Sun Xiaoye , Kong Shang , Jiang Chen , Jing Rongrong , Ju Shaoqing , Cong Hui
Published: June 2021

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P < .001) and lymph node metastasis (U = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC.
Gradient measurement of synchrotron polarization diagnostic: Application to spatially separated emission and Faraday rotation regions
Authors: Wang Ru-Yue , Zhang Jian-Fu , Lazarian Alex , Xiao Hua-Ping , Xiang Fu-Yuan
Published: June 2021

Considering the spatially separated polarization radiation and Faraday rotation regions to simulate complex interstellar media, we study synchrotron polarization gradient techniques’ measurement capabilities. We explore how to trace the direction of projected magnetic field of emitting-source region at the multifrequency bands, using the gradient technique compared with the traditional polarization vector method. Furthermore, we study how Faraday rotation density in the foreground region, i.e. a product of electron number density and parallel component of magnetic fields along the line of sight, affects the measurement of projected magnetic field. Numerical results show that synchrotron polarization gradient technique could successfully trace projected magnetic field within emitting-source region independent of radio frequency. Accordingly, the gradient technique can measure the magnetic field properties for a complex astrophysical environment.
Dynamical confirmation of a stellar mass black hole in the transient X-ray dipping binary MAXI J1305-704
Authors: Mata Sánchez D , Rau A , Álvarez Hernández A , van Grunsven T F J , Torres M A P , Jonker P G
Published: June 2021

MAXI J1305-704 has been proposed as a high-inclination candidate black hole X-ray binary in view of its X-ray properties and dipping behaviour during outburst. We present photometric and spectroscopic observations of the source in quiescence that allow us to reveal the ellipsoidal modulation of the companion star and absorption features consistent with those of an early K-type star ($T_{\rm eff}=4610^{+130}_{-160}\, {\rm K}$). The central wavelengths of the absorption lines vary periodically at $P_{\rm orb}=0.394\pm 0.004\, {\rm d}$ with an amplitude of $K_2=554\pm 8\, {\rm km \, s^{-1}}$. They imply a mass function for the compact object of $f(M_1)=6.9\pm 0.3\, {\rm M}_\odot$, confirming its black hole nature. The simultaneous absence of X-ray eclipses and the presence of dips set a conservative range of allowed inclinations $60\, {\rm deg}\lt i\lt 82\, {\rm deg}$, while modelling of optical light curves further constrain it to $i=72^{+5}_{-8}\, {\rm deg}$. The above parameters together set a black hole mass of $M_1= 8.9_{-1.0}^{+1.6}\, {\rm M}_{\odot }$ and a companion mass of $M_2= 0.43\pm 0.16\, {\rm M}_{\odot }$, much lower than that of a dwarf star of the observed spectral type, implying it is evolved. Estimates of the distance to the system ($d=7.5^{+1.8}_{-1.4}\, {\rm kpc}$) and space velocity ($v_{\rm space}=270\pm 60 \, {\rm km\, s^{-1}}$) place it in the Galactic thick disc and favour a significant natal kick during the formation of the BH if the supernova occurred in the Galactic Plane.
Study of rotational splittings in δ Scuti stars using pattern finding techniques
Authors: Ramón-Ballesta A , García Hernández A , Suárez J C , Rodón J R , Pascual-Granado J , Garrido R
Published: June 2021

Detecting and understanding rotation in stellar interiors is nowadays one of the unsolved problems in stellar physics. Asteroseismology has been able to provide insights on rotation for the Sun, solar-like stars, and compact objects like white dwarfs. However, this is still very difficult for intermediate-mass stars. These stars are moderate-to-rapid rotators. Rotation splits and shifts the oscillation modes, which makes the oscillation spectrum more complex and harder to interpret. Here we study the oscillation patterns of a sample of benchmark δ Sct stars belonging to eclipsing binary systems with the objective of finding the frequency spacing related to the rotational splitting (δr). For this task, we combine three techniques: the Fourier transform, the autocorrelation function, and the histogram of frequency differences. The last two showed a similar behaviour. For most of the stars, it was necessary to determine the large separation (Δν) prior to spot δr. This is the first time we may clearly state that one of the periodicities present in the p modes oscillation spectra of δ Sct stars corresponds to the rotational splitting. This is true independent of the stellar rotation rate. These promising results pave the way to finding a robust methodology to determine rotational splittings from the oscillation spectra of δ Sct stars and, thus, understanding the rotational profile of intermediate-mass pulsating stars.
Association of T2285C polymorphism in PARP1 gene coding region with its expression, activity and NSCLC risk along with prognosis
Authors: Wang Yan , Xia Xiao Bing , Tang Hui Zhuo , Cai Jing Ran , Shi Xiang Kui , Ji Huai Xue , Yan Xiao Nan , Xu Tie
Published: June 2021

Poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair gene, is the crucial player in the maintenance of genome integrity. T2285C polymorphism in coding region of PARP1 has been reported to be associated with susceptibility to tumours. We explored the relationship and mechanism of T2285C polymorphism of PARP1 to its expression and activity along with risk and prognosis in non-small cell lung cancer (NSCLC). mRNA expression was measured using quantitative RT–PCR assay or collected from TCGA dataset. Protein expression was examined with immunoblotting assay. Genotypes were determined by PCR-RFLP and sequencing approaches. PARP1 activity was determined with enzyme activity assay. Regulation of SIRT7 to PARP1 was determined by overexpression and small interference experiment. Association of PARP1 T2285C polymorphism with NSCLC risk was evaluated via multiple logistic regression analysis. Comparison of treatment response and progression-free survival (PFS) of NSCLC patients among different genotypes or regimens was made by chi-square test. Results indicated that mRNA and protein expression of PARP1 dramatically increased in NSCLC tissues in comparison with paired para-carcinoma tissues (P < 0.05). TC/CC mutant genotypes were associated with markedly enhanced PARP1 mRNA level compared with TT genotype (P = 0.011). No significant difference was discovered in PARP1 protein expression among TT, TC or CC genotypes (P > 0.05). Subjects with variant allele C had higher risk of NSCLC in comparison with allele T carriers [odds ratio = 1.560; P = 0.000]. NSCLC patients carrying mutational TC or CC genotypes were correlated with unfavourable response to platinum-based chemotherapy (TT vs. TC vs. CC, P = 0.010), and shorter PFS compared with TT genotype (TT vs. TC vs. CC, P = 0.009). T2285C mutation of PARP1 resulted in the enhancement of its mRNA, but the decrease of enzyme activity in tumour cell. Overexpression of SIRT7 attenuated PARP1 expression and activity. These findings suggest the variant allele C of T2285C polymorphism of PARP1 linked to an increase of NSCLC risk, and unfavourable efficacy and prognosis of NSCLC patients with platinum-based chemotherapy, which might be associated with enhancement of its mRNA expression and the diminishment of activity. Identification of PARP1 T2285C polymorphism and mRNA expression may be the promising way for the individualised treatment of NSCLC.
Osteobiologics
Authors: Golubovsky Joshua L , Ejikeme Tiffany , Winkelman Robert , Steinmetz Michael P
Published: June 2021

BACKGROUND

Osteobiologics are engineered materials that facilitate bone healing and have been increasingly used in spine surgery. Autologous iliac crest bone grafts have been used historically, but morbidity associated with graft harvesting has led surgeons to seek alternative solutions. Allograft bone, biomaterial scaffolds, growth factors, and stem cells have been explored as bone graft substitutes and supplements.

OBJECTIVE

To review current and emerging osteobiologic technologies.

METHODS

A literature review of English-language studies was performed in PubMed. Search terms included combinations of “spine,” “fusion,” “osteobiologics,” “autologous,” “allogen(e)ic,” “graft,” “scaffold,” “bone morphogenic protein,” and “stem cells.”

RESULTS

Evidence supports allograft bone as an autologous bone supplement or replacement in scenarios where minimal autologous bone is available. There are promising data on ceramics and P-15; however, comparative human trials remain scarce. Growth factors, including recombinant human bone morphogenic proteins (rhBMPs) 2 and 7, have been explored in humans after successful animal trials. Evidence continues to support the use of rhBMP-2 in lumbar fusion in patient populations with poor bone quality or revision surgery, while there is limited evidence for rhBMP-7. Stem cells have been incredibly promising in promoting fusion in animal models, but human trials to this point have only involved products with questionable stem cell content, thereby limiting possible conclusions.

CONCLUSION

Engineered stem cells that overexpress osteoinductive factors are likely the future of spine fusion, but issues with applying viral vector-transduced stem cells in humans have limited progress.
Genomic Basis of Transcriptome Dynamics in Rice under Field Conditions
Authors: Kashima Makoto , Sakamoto Ryota L , Saito Hiroki , Ohkubo Satoshi , Tezuka Ayumi , Deguchi Ayumi , Hashida Yoichi , Kurita Yuko , Iwayama Koji , Adachi Shunsuke , Nagano Atsushi J
Published: June 2021

How genetic variations affect gene expression dynamics of field-grown plants remains unclear. Expression quantitative trait loci (eQTL) analysis is frequently used to find genomic regions underlying gene expression polymorphisms. This approach requires transcriptome data for the complete set of the QTL mapping population under the given conditions. Therefore, only a limited range of environmental conditions is covered by a conventional eQTL analysis. We sampled sparse time series of field-grown rice from chromosome segment substitution lines (CSSLs) and conducted RNA sequencing (RNA-Seq). Then, by using statistical analysis integrating meteorological data and the RNA-Seq data, we identified 1,675 eQTLs leading to polymorphisms in expression dynamics under field conditions. A genomic region on chromosome 11 influences the expression of several defense-related genes in a time-of-day- and scaled-age-dependent manner. This includes the eQTLs that possibly influence the time-of-day- and scaled-age-dependent differences in the innate immunity between Koshihikari and Takanari. Based on the eQTL and meteorological data, we successfully predicted gene expression under environments different from training environments and in rice cultivars with more complex genotypes than the CSSLs. Our novel approach of eQTL identification facilitated the understanding of the genetic architecture of expression dynamics under field conditions, which is difficult to assess by conventional eQTL studies. The prediction of expression based on eQTLs and environmental information could contribute to the understanding of plant traits under diverse field conditions.
Life history, diversity, and distribution in parasitic flowering plants
Authors: Teixeira-Costa Luiza , Davis Charles C.
Published: June 2021

A review of parasitic plant diversity and outstanding disjunct distributions according to an updated functional classification based on these plants’ life cycles.
Skewed Allegiances: Recalibrating Humanitarian Accountability towards Gender
Authors: Lokot Michelle
Published: June 2021

Humanitarian actors often face competing accountabilities that may skew “upwards” in favour of donors. With increasing requirements on humanitarian actors to demonstrate efficiency and impact, accountability has often become depoliticised, reduced to technical frameworks and bureaucratic processes. Within humanitarian work focused on promoting gender equality, the problems in how accountability is framed have particular ramifications, affecting how gender issues are positioned, how gender-related data are presented and the assumptions underlying interventions that seek to address gender inequality. This article is based on ethnographic research in Jordan, specifically interviews with humanitarian practitioners and Syrian refugees. It explores how accountability for gender issues is positioned within the humanitarian sector. The article challenges the fixation on collecting quantitative data on gender-based violence and suggests that humanitarian assumptions about refugee populations may lead to stereotypical and homogenous representations about refugees that fail to recognise complexity. It provides examples of gaps in humanitarian assistance experienced by Syrian refugees in Jordan. The article also suggests that accountability for social transformation and change may be shifting from humanitarian actors towards refugees themselves. The article recommends that approaches to humanitarian accountability should prioritise listening, and being honest about failures and gaps in knowledge.
Basic mechanisms underlying persistent pain after nerve injury
Authors: Basbaum Allan Irwin
Published: June 2021

Animal models of nerve injury‐induced neuropathic pain have identified peripheral and CNS factors that initiate and maintain the condition. Among the major peripheral contributors are ectopic firing of injured afferents and abnormal interplay of sympathetic efferents and primary afferent nociceptors (‘pain fibers’). Peripheral nerve injury also triggers changes at the level of the dorsal horn, including loss of large fiber inhibition, loss of GABAergic interneurons, induction of microglia that are the source of pronociceptive molecules, as well as the loss of descending brainstem inhibitory controls and the release of descending facilitatory mechanisms. These changes sensitize spinal cord and brain pain transmission circuits, such that there is ongoing spontaneous activity as well as activation of pain transmission circuits by normally innocuous stimuli, leading to the condition of allodynia, in which pain is produced by non‐painful stimuli. The general consensus is that neuropathic pain responds rarely to non‐steroidal anti‐inflammatory drugs and is poorly managed by opiates. Alternative treatment approaches, including local anesthetics, anticonvulsants and anti‐depressants will be discussed.
Current Treatment of Chronic Pain
Authors: Pham Quynh Giao
Published: June 2021

The treatment of chronic pain requires a multidisciplinary approach. In addition to the primary ailment, patients with chronic pain often suffer from depression as well as physical deconditioning. The management of these patients involves multiple treatment approaches, which may include patient and family education, medication management, physical and/or occupational therapy, behavioral therapy, and interventional procedures such as nerve blocks and joint/soft tissue injections. This talk will focus on the various classes of medications used in the treatment of chronic pain, physical and occupational treatment approaches, psychological treatment approaches, and various interventional procedures.
Biophysical assessment of AQP9 as real membrane pathway in hepatocyte glycerol uptake
Authors: Calamita Giuseppe , Fanelli Elena , Svelto Maria , Gena Patrizia
Published: June 2021

Glycerol, released from adipocytes, flows through bloodstream to liver where it is taken up to supply gluconeogenesis. Although glycerol is central to metabolic homeostasis, the molecular mechanism underlying the glycerol uptake across the hepatocyte basolateral plasma membrane (BLPM) is mostly elusive. Here, we evaluate biophysically whether AQP9, an aquaglyceroporin channel, is entry route in liver glycerol uptake. Facilitated diffusion of glycerol across the hepatocyte BLPM was proved by the low Ea (3.5 kcal/mol) and strong phloretin and HgCl2 inhibitions characterizing the transport of glycerol. Fasting (vs feeding) markedly increased liver AQP9 expression in a time‐dependent manner. The highest levels of AQP9 transcript and protein were seen after 18 h of fasting. AQP9 returned to basal levels after 72 h refeeding. Of note, both the BLPM glycerol permeability and AQP9 protein extents changed accordingly to the variations in plasma glycerol levels. The expression of AQP8, the other hepatocyte aquaporin, was unchanged. Overall, these results prove real functional relevance for AQP9 in liver glycerol uptake and suggest a new important player underlying metabolic and energy (dys)balance.
N‐acetylcysteine attenuates ventilator‐induced diaphragm dysfunction in rats
Authors: Agten Anouk , Maes Karen , Smuder Ashley , Powers Scott K , Decramer Marc , Gayan‐Ramirez Ghislaine
Published: June 2021

Controlled mechanical ventilation (CMV) results in diaphragmatic dysfunction and oxidative stress. We examined whether an anti‐oxidant, N‐acetylcysteine (NAC), would restore the redox‐balance in the diaphragm and prevent the deleterious effects of CMV.

Anesthetized rats were submitted for 24h to either spontaneous breathing while receiving 150mg/kg NAC (SBNAC) or saline (SBSAL) or to CMV while receiving 150mg/kg NAC (MVNAC) or saline (MVSAL).

After 24 hours, diaphragm forces were significantly lower in MVSAL compared to all groups (−21%, p<0.01). Administration of NAC completely abolished this decrease. Protein oxidation was significantly increased in MVSAL (+43%, p<0.0001) and was restored in MVNAC. Diaphragm caspase‐3 and calpain activity were significantly increased in MVSAL compared to all groups (p<0.0001). These data show that the administration of NAC was able to preserve the diaphragm from the deleterious effects of CMV.

Supported by AstraZeneca Farmaceuticals and FWO Vlaanderen
Fenofibrate reduces mitochondrial oxidative stress and alters membrane composition in the hypertrophied rat heart
Authors: Le Catherine H , Mulligan Christopher M , Routh Melissa A , Sterrenberg Timothy R , Bouma Gerrit J , Chicco Adam J
Published: June 2021

Peroxisome proliferator activated receptor‐alpha (PPARa) is a lipogenic transcription factor known to exert pleiotropic effects in the cardiovascular system by mechanisms that are incompletely understood. We examined the effect of the PPARα agonist fenofibrate (FENO; 150 mg/kg/d for 4 weeks) on mitochondrial production of reactive oxygen species (ROS), lipoxidative stress, and the fatty acid composition of myocardial phospholipids in 14 month old male SHHF rats with severe hypertension and left ventricular (LV) hypertrophy. FENO had no significant effect on LV function or morphology, but significantly reduced mitochondrial ROS production and mitochondrial content of 4‐hydroxynonenal (HNE)‐protein adducts compared to untreated animals. Interestingly, FENO also induced a 50% decrease in relative proportion of arachidonic acid (20:4n6) and a 60% increase in DHA (22:6n3) in myocardial phospholipids, indicating potent alterations in the metabolism of polyunsaturated fatty acids favoring synthesis of anti‐ vs. pro‐inflammatory eicosanoids. The precise mechanisms and long‐term consequences of these novel phenomena are currently being examined in our laboratories. These studies suggest that FENO may elicit cardioprotective effects in the hypertrophied heart by reducing generation of ROS and altering polyunsaturated fatty acid metabolism. Supported by a grant from the American Heart Association.
Regulation of NADPH Oxidase Mediated Oxidative Stress in Macrophages
Authors: Sarna Lindsei Kathryn , Wu Nan , Siow Yaw L. , Pierce Grant , Karmin O
Published: June 2021

Oxidative stress contributes to the pathogenesis of human diseases including atherosclerosis. The NADPH oxidase is a key source of oxidative stress in atherogenesis. Our objectives were to determine the effect of berberine, herbal medicinal compound, on NADPH oxidase‐mediated production in monocyte‐derived macrophage (THP‐1). Cells were pretreated with berberine (10–50umol/L) followed by the addition of lipopolysaccharide (LPS) (10ug/L) to induce activation of NADPH oxidase. Treatment with LPS significantly increased intracellular O2− over a 24 h period. Pre‐incubation with berberine resulted in a concentration‐dependent inhibition of O2− generation in these cells. Real‐time PCR analysis revealed an increased expression of all NADPH oxidase subunits in LPS‐treated cells. However, pretreatment with berberine (25umol/L) display a significant reduction in gp91phoxmRNA expression. Transfection with gp91phox siRNA abolished LPS‐induced O2− generation in macrophages, confirming the essentiality of this subunit to oxidase activation. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase‐mediated O2− generation in macrophages, did not affect cell viability. In conclusion, berberine can effectively regulate NADPH oxidase activity in stimulated macrophages by selectively inhibiting the expression of the catalytic subunit gp91phox.
Selectivity of PKC isoforms in the regulation of Na+‐K+‐2Cl− cotransporter (NKCC1) in secretory epithelia
Authors: TANG JUN , Bouyer Patrice , Mykoniatis Andreas , Buschmann Mary , Matlin Karl S. , Matthews Jeffrey B.
Published: June 2021

NKCC1 drives basolateral Cl− entry in secretory epithelia. Activation of PKC by phorbol 12‐myristate 13‐acetate (PMA) reduces colonic epithelial Cl− secretory response to cAMP and surface NKCC1. The study was to define selectivity of PKCs in regulating epithelial NKCC1.

T84 monolayers uninfected or infected with adenoviruses expressing human PKC (α, δ, ε)‐specific shRNAs or non‐target LacZ‐shRNA were treated with PMA or vehicle, followed by measurement of Cl− secretion (short‐circuit current, Isc). NKCC1 signal in the cells was assessed by immunofluorescence. NKCC1 surface expression was examined by basolateral surface biotinylation assay.

We found proteins of PKC (α, δ, ε) in shPKCs cells were decreased by ~85% after 72h infection. PMA reduced forskolin (FSK)‐stimulated Cl− secretion much less in shPKCδ or shPKCε cells than shLacZ or uninfected cells. There was no significant difference in PMA‐reduced Cl− secretion between shPKCα and shLacZ. In shLacZ and shPKCα cells, PMA induced a redistribution of NKCC1 signal to intracellular vesicles; the effect was not observed in shPKCδ or shPKCε cells. PMA caused a dramatic decrease in basolateral biotinylated NKCC1 in shLacZ or shPKCα, but not in shPKCδ or shPKCε cells.

In conclusion, depletion of PKC δ or ε, but not PKCα, prevents PMA inhibition of T84 Cl− secretion via a mechanism involving stabilization of the basolateral membrane NKCC1.

Received NIH grant DK48010.
Reconstitution of nanosized HDL for targeted delivery of bioflavonoids
Authors: Khumsupan Panupon , Manansala Chris , Narayanaswami Vasanthy
Published: June 2021

High‐density lipoproteins (HDL) are lipid‐protein particles that are involved in transport of plasma cholesterol from peripheral tissues to the liver in a process called reverse cholesterol transport. In humans a subclass of HDL contains apolipoprotein E (apoE), an anti‐atherogenic protein. ApoE serves as a ligand for the low‐density lipoprotein receptor family of proteins that serve to internalize lipoprotein particles. Our objective is to prepare reconstituted HDL containing recombinant human apoE3 as a vehicle to transport and target curcumin, an anti‐amyloid and anti‐inflammatory flavonoid, to the cells comprising the blood brain barrier. Unfortunately, dietary curcumin is converted to less potent metabolites by the liver; therefore it is important to deliver active curcumin at inflammatory or amyloid aggregation sites. We prepared discoidal HDL containing phospholipid, cholesterol and human apoE3. The particles recapitulate the geometry, mass and particle composition of naturally occurring pre‐beta HDL. Curcumin was incorporated by direct addition into reconstituted HDL. A dramatic shift in the wavelength of maximal fluorescence emission of curcumin was noted from ~550 nm in dimethylsulfoxide or aqueous buffer or Triton X‐100 micelles to ~490 nm in HDL. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin‐containing HDL. Its presence in the context of a lipoprotein complex bearing apoE offers the potential for its delivery across the blood brain barrier in an active form for treatment of Alzheimer's disease. Source of research support: Tobacco Related Disease Research Program, American Heart Association, Women & Philanthropy and SCAC award.