bluuebunny/crossref_metadata_2025 huggingface dataset:
Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi‐institutional retrospective cohort study
Authors: Rose Kyle M. , Narang Gopal , Rosen Geoffrey , Labatte Craig , Dumitrascu Catalina I. , Campagna Justin , Yu Alice , Manley Brandon J. , Spiess Phillippe E. , Li Roger , Adibi Mehrad , Murray Katie S. , Sexton Wade J. , Humphreys Mitchell R.
Published: October 2022

Objectives

To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy.

Patients and Methods

Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post‐therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy.

Results

Thirty‐two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow‐up and there were no treatment‐related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow‐up of 13.0 months post induction.

Conclusions

Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.
Bibliometric investigation of the integration of animal personality in conservation contexts
Authors: Collins Sydney M. , Hendrix Jack G. , Webber Quinn M. R. , Boyle Sean P. , Kingdon Katrien A. , Blackmore Robert J. , d'Entremont Kyle J. N. , Hogg Jennifer , Ibáñez Juan P. , Kennah Joanie L. , Lamarre Jessika , Mejías Miguel , Newediuk Levi , Richards Cerren , Schwedak Katrina , Wijekulathilake Chirathi , Turner Julie W.
Published: October 2022

Consistent individual differences in behavior, commonly termed animal personality, are a widespread phenomenon across taxa that have important consequences for fitness, natural selection, and trophic interactions. Animal personality research may prove useful in several conservation contexts, but which contexts remains to be determined. We conducted a structured literature review of 654 studies identified by combining search terms for animal personality and various conservation subfields. We scored the relevance of personality and conservation issues for each study to identify which studies meaningfully integrated the 2 fields as opposed to surface‐level connections or vague allusions. We found a taxonomic bias toward mammals (29% of all studies). Very few amphibian or reptile studies applied personality research to conservation issues (6% each). Climate change (21%), invasive species (15%), and captive breeding and reintroduction (13%) were the most abundant conservation subfields that occurred in our search, though a substantial proportion of these papers weakly integrated conservation and animal personality (climate change 54%, invasive species 51%, captive breeding and reintroduction 40%). Based on our results, we recommend that researchers strive for consistent and broadly applicable terminology when describing consistent behavioral differences to minimize confusion and improve the searchability of research. We identify several gaps in the literature that appear to be promising and fruitful avenues for future research, such as disease transmission as a function of sociability or exploration as a driver of space use in protected areas. Practitioners can begin informing future conservation efforts with knowledge gained from animal personality research.
Giant cell tumor of tendon sheath: A report of 216 cases
Authors: Huang Cong‐Gai , Li Meng‐Ze , Wang Shao‐Hua , Tang Xiao‐Qin , Zhang Hui‐Ling , Haybaeck Johannes , Yang Zhi‐Hui
Published: October 2022

Background

In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment.

Methods

The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature.

Results

Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male‐to‐female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial‐like monocytes, small monocytes, and osteoclast‐like giant cells.

Conclusion

Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long‐term follow‐up is the preferred management.
British exports and foreign tariffs: Insights from the Board of Trade's foreign tariff compilation for 1902
Authors: Varian Brian D.
Published: October 2022

This research note contributes to the debate over whether British exports were elastic to foreign tariffs before the First World War. In doing so, this study is the first to make econometric use of the commodity‐ and country‐disaggregated foreign tariff data that Britain's Board of Trade compiled for the year 1902. Contrary to previous literature, British exports were indeed elastic to foreign tariffs across a range of manufactured commodities, with a conservative estimate of the elasticity being 3.1, which is not low by modern standards. Counterfactually, if foreign countries had emulated Britain's policy of free trade in manufactures in 1902, a partial‐equilibrium estimate is that British exports would have been 57 per cent higher. If the trade‐liberalizing trend of the mid‐nineteenth century persisted into the late‐nineteenth century, then much of the late‐Victorian deceleration of British exports would have been avoided.
Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from theFREEDOMS IIstudy
Authors: Wang Liang , Tan Hongmei , Yu Jian , ZhangBao Jingzi , Huang Wenjuan , Chang Xuechun , Zhou Lei , Lu Chuanzhen , Xiao Yiqin , Lu Jiahong , Zhao Chongbo , Wang Min , Wu Xue , Wu Mengyun , Dong Qiang , Ngew Kok Yew , Quan Chao
Published: October 2022

Background and purpose

The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing–remitting multiple sclerosis (RRMS).

Methods

Analyses were conducted post hoc of this 24‐month, phase III, double‐blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.

Results

Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = −1.085,p = 0.018), lower brain volume (r = 0.025,p = 0.006) and deep gray matter volume (r = 0.731,p < 0.0001), worse visual acuity (r = −19.846,p < 0.0001) and longer duration since diagnosis (r = −0.258,p = 0.018). At month 12, low baseline RNFLT (<86 μm) versus high baseline RNFLT (≥99 μm) was associated with a greater brain volume loss (percentage change −0.605% vs. −0.315%,p = 0.035) in patients without optic neuritis history. At month 24, low baseline RNFLT versus high baseline RNFLT was associated with a higher number of new or newly enlarged T2 lesions (mean number 4.0 vs. 2.8,p = 0.014) and a higher risk of subsequent RNFL thinning (hazard ratio 2.55; 95% confidence interval 1.84–3.53;p < 0.001). The atrophy of the RNFL in the inferior quadrant was alleviated with fingolimod 0.5 mg versus placebo at month 24 (Δ(least squares mean) = 1.8,p = 0.047).

Conclusion

Retinal nerve fiber layer thickness could predict disease progression in RRMS.

Trial registration

Clinicaltrials.gov identifier: NCT00355134,https://clinicaltrials.gov/ct2/show/NCT00355134.
Dual‐phase 18F‐FP‐CIT positron emission tomography and cardiac 123I‐MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body‐first type?
Authors: Kim Min Seung , Park Don Gueu , An Young‐Sil , Yoon Jung Han
Published: October 2022

Background and purpose

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA‐PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta‐iodobenzylguanidine (MIBG) uptake of GBA‐PD in comparison to sPD.

Methods

Through next‐generation sequencing analysis targeting 41 genes, a total of 16 GBA‐PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual‐phase [18F]‐N‐(3‐fluoropropyl)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl) nortropane (18F‐FP‐CIT) positron emission tomography (PET) and cardiac 123I‐MIBG scintigraphy results were compared between the two groups.

Results

The GBA‐PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early‐phase 18F‐FP‐CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA‐PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate‐to‐putamen ratio were similar between the two groups. The GBA‐PD group had a lower heart‐to‐mediastinum uptake ratio in 123I‐MIBG scintigraphy than the sPD group.

Conclusions

The GBA‐PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non‐motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA‐PD than sPD. These findings suggest that GBA‐PD patients have more widespread peripheral (extranigral) α‐synuclein accumulation, representing a body‐first PD subtype.
SCN1A gain‐of‐function mutation causing an early onset epileptic encephalopathy
Authors: Clatot Jérôme , Parthasarathy Shridhar , Cohen Stacey , McKee Jillian L. , Massey Shavonne , Somarowthu Ala , Goldberg Ethan M. , Helbig Ingo
Published: October 2022

Objective

Loss‐of‐function variants in SCN1A cause Dravet syndrome, the most common genetic developmental and epileptic encephalopathy (DEE). However, emerging evidence suggests separate entities of SCN1A‐related disorders due to gain‐of‐function variants. Here, we aim to refine the clinical, genetic, and functional electrophysiological features of a recurrent p.R1636Q gain‐of‐function variant, identified in four individuals at a single center.

Methods

Individuals carrying the recurrent SCN1A p.R1636Q variant were identified through diagnostic testing. Whole cell voltage‐clamp electrophysiological recording in HEK‐293 T cells was performed to compare the properties of sodium channels containing wild‐type Nav1.1 or Nav1.1‐R1636Q along with both Navβ1 and Navβ2 subunits, including response to oxcarbazepine. To delineate differences from other SCN1A‐related epilepsies, we analyzed electronic medical records.

Results

All four individuals had an early onset DEE characterized by focal tonic seizures and additional seizure types starting in the first few weeks of life. Electrophysiological analysis showed a mixed gain‐of‐function effect with normal current density, a leftward (hyperpolarized) shift of steady‐state inactivation, and slower inactivation kinetics leading to a prominent late sodium current. The observed functional changes closely paralleled effects of pathogenic variants in SCN3A and SCN8A at corresponding positions. Both wild type and variant exhibited sensitivity to block by oxcarbazepine, partially correcting electrophysiological abnormalities of the SCN1A p.R1636Q variant. Clinically, a single individual responded to treatment with oxcarbazepine. Across 51 individuals with SCN1A‐related epilepsies, those with the recurrent p.R1636Q variants had the earliest ages at onset.

Significance

The recurrent SCN1A p.R1636Q variant causes a clinical entity with a wider clinical spectrum than previously reported, characterized by neonatal onset epilepsy and absence of prominent movement disorder. Functional consequences of this variant lead to mixed loss and gain of function that is partially corrected by oxcarbazepine. The recurrent p.R1636Q variant represents one of the most common causes of early onset SCN1A‐related epilepsies with separate treatment and prognosis implications.
Delaying quantitative resistance to pesticides and antibiotics
Authors: Hardy Nate B.
Published: October 2022

How can we best vary the application of pesticides and antibiotics to delay resistance evolution? Previous theoretical comparisons of deployment strategies have focused on qualitative resistance traits and have mostly assumed that resistance alleles are already present in a population. But many real resistance traits are quantitative, and the evolution of resistant genotypes in the field may depend on de novo mutation and recombination. Here, I use an individual‐based, forward‐time, quantitative‐genetic simulation model to investigate the evolution of quantitative resistance. I evaluate the performance of four application strategies for delaying resistance evolution, to wit, the (1) sequential, (2) mosaic, (3) periodic, and (4) combined strategies. I find that which strategy is best depends on initial efficacy. When at the onset, xenobiotics completely prevent reproduction in treated demes, a combined strategy is best. On the other hand, when populations are partially resistant, the combined strategy is inferior to mosaic and periodic strategies, especially when resistance alleles are antagonistically pleiotropic. Thus, the optimal application strategy for managing against the rise of quantitative resistance depends on pleiotropy and whether or not partial resistance is already present in a population. This result appears robust to variation in pest reproductive mode and migration rate, direct fitness costs for resistant phenotypes, and the extent of refugial habitats.
Evidence of hard‐selective sweeps suggests independent adaptation to insecticides in Colorado potato beetle (Coleoptera: Chrysomelidae) populations
Authors: Cohen Zachary P. , Chen Yolanda H. , Groves Russell , Schoville Sean D.
Published: October 2022

Pesticide resistance provides one of the best examples of rapid evolution to environmental change. The Colorado potato beetle (CPB) has a long and noteworthy history as a super‐pest due to its ability to repeatedly develop resistance to novel insecticides and rapidly expand its geographic and host plant range. Here, we investigate regional differences in demography, recombination, and selection using whole‐genome resequencing data from two highly resistant CPB populations in the United States (Hancock, Wisconsin and Long Island, New York). Demographic reconstruction corroborates historical records for a single pest origin during the colonization of the Midwestern and Eastern United States in the mid‐ to late‐19th century and suggests that the effective population size might be higher in Long Island, NY than Hancock, WI despite contemporary potato acreage of Wisconsin being far greater. Population‐based recombination maps show similar background recombination rates between these populations, as well as overlapping regions of low recombination that intersect with important metabolic detoxification genes. In both populations, we find compelling evidence for hard selective sweeps linked to insecticide resistance with multiple sweeps involving genes associated with xenobiotic metabolism, stress response, and defensive chemistry. Notably, only two candidate insecticide resistance genes are shared among both populations, but both appear to be independent hard selective sweep events. This suggests that repeated, rapid, and independent evolution of genes may underlie CPB's pest status among geographically distinct populations.
Plant disease detection using machine learning approaches
Authors: Ahmed Imtiaz , Yadav Pramod Kumar
Published: October 2022

Plant health care is the science of anticipating and diagnosing the advent of life‐threatening diseases in plants. The fatality rate of plants can be reduced by diagnosing them for any signs early on. The early detection of such diseases is one possibility for lowering plant mortality rates. Machine learning (ML), a type of artificial intelligence technology that allows researchers to enhance and develop without being explicitly programmed, is used in this study to build early prediction models for plant disease diagnosis. Due to the similarities of crops throughout the early phonological phases, crop classification has proved problematic. ML can be applied to a variety of tasks recognize different types of crops at low altitude platforms with the help of drones that provide high‐resolution optical imagery. The drones are employed to photograph phonological stages, and these greyscale photographs are then utilized to develop grey level co‐occurrence matrices‐based characteristics. In this article, the proposed plant disease detection models are developed using ML approaches such as random forest‐nearest neighbours, linear regression, Naive Bayes, neural networks, and support vector machine. The performance of the generated plants disease risk evaluation model is calculated using unbiased metrics such as true positive rate, true negative rate, precision, recall, and F1‐score method are all factors to consider. The results revealed that the ensemble plants disease model outperforms the other proposed and developed plant disease detection models. The proposed and developed plant disease prediction models aimed to predict disease detection in the early stages, allowing for early preventive actions and predictive maintenance.
Influence of novel shrinkage‐reducing polycarboxylate superplasticizer on the nature of calcium–silicate–hydrates
Authors: Zhang Jian , Ma Yuefeng , Huang Jiale , Zeng Haoyu , Liu Zihao , Hua Tengfei , Liu Jiaping , Hu Zhangli
Published: October 2022

Currently, a novel shrinkage‐reducing polycarboxylate superplasticizer (SR‐PCA) is used to control cementitious shrinkage. To clarify its mechanism when applied in cementitious materials, the influence of SR‐PCA on the composition, morphology, and structure of synthetic calcium–silicate–hydrate (C–S–H), together with the interaction between SR‐PCA and C–S–H at the atomic level, is investigated. For comparison, a commercial polycarboxylate superplasticizer (PCA) is also employed. The results show PCA and SR‐PCA can adsorb on the C–S–H surface rather than intercalate into the layers. Compared with PCA, SR‐PCA has a milder impact on C–S–H crystallinity. SR‐PCA refines the pore structure of C–S–H drastically, whereas PCA loosens the structure by increasing the mesopore volume. In addition, the adsorption effect of SR‐PCA on the C–S–H surface is less significant than that of PCA. At the atomic level, this less adsorption of SR‐PCA is attributed to the lower adhesion energy of the C–S–H/SR‐PCA interface due to the weaker Ca–O bond strength.
Fostering science interests through head‐mounted displays
Authors: Andersen Martin Stolpe , Klingenberg Sara , Petersen Gustav Bøg , Creed Peter A. , Makransky Guido
Published: October 2022

Background

Research suggests that head‐mounted displays (HMD) can spark situational interest when they are used to provide science learning experiences that are not possible in traditional classroom settings. However, few studies have investigated the lasting effects of using HMDs in an authentic instructional intervention.

Objectives

We investigated the effects of a one‐time experience of a virtual field trip to Greenland in a sample of 105 middle school students.

Methods

Students used either a standard 2D video (video condition; N = 50) or an HMD (HMD condition; N = 55) as part of a six‐lesson educational activity on the topic of climate change. Informed by social cognitive career theory (SCCT), we investigated the effects of the different conditions (video vs. HMD) on the outcomes of self‐efficacy, outcome expectations, interest, and science intentions across three time points.

Results and Conclusions

The results showed that using the HMD‐based virtual field trip, compared to the video, had a positive immediate effect on self‐efficacy and interest, and total later effects on self‐efficacy, outcome expectations, and interest an average of two and a half weeks after the virtual field trip. The results suggest that HMD‐based virtual field trips can influence self‐efficacy, outcome expectations, and interest more than a video‐based virtual field trip when measured approximately two and a half weeks after the intervention.
GIGANTEA orthologs, E2 members, redundantly determine photoperiodic flowering and yield in soybean
Authors: Wang Lingshuang , Li Haiyang , He Milan , Dong Lidong , Huang Zerong , Chen Liyu , Nan Haiyang , Kong Fanjiang , Liu Baohui , Zhao Xiaohui
Published: October 2022

Soybean (Glycine max L.) is a typical photoperiod‐sensitive crop, such that photoperiod determines its flowering time, maturity, grain yield, and phenological adaptability. During evolution, the soybean genome has undergone two duplication events, resulting in about 75% of all genes being represented by multiple copies, which is associated with rampant gene redundancy. Among duplicated genes, the important soybean maturity gene E2 has two homologs, E2‐Like a (E2La) and E2‐Like b (E2Lb), which encode orthologs of Arabidopsis GIGANTEA (GI). Although E2 was cloned a decade ago, we still know very little about its contribution to flowering time and even less about the function of its homologs. Here, we generated single and double mutants in E2, E2La, and E2Lb by genome editing and determined that E2 plays major roles in the regulation of flowering time and yield, with the two E2 homologs depending on E2 function. At high latitude regions, e2 single mutants showed earlier flowering and high grain yield. Remarkably, in terms of genetic relationship, genes from the legume‐specific transcription factor family E1 were epistatic to E2. We established that E2 and E2‐like proteins form homodimers or heterodimers to regulate the transcription of E1 family genes, with the homodimer exerting a greater function than the heterodimers. In addition, we established that the H3 haplotype of E2 is the ancestral allele and is mainly restricted to low latitude regions, from which the loss‐of‐function alleles of the H1 and H2 haplotypes were derived. Furthermore, we demonstrated that the function of the H3 allele is stronger than that of the H1 haplotype in the regulation of flowering time, which has not been shown before. Our findings provide excellent allelic combinations for classical breeding and targeted gene disruption or editing.
Real‐time, closed‐loop, or open‐loop stimulation? Navigating a terminological jungle
Authors: Antony James W. , Ngo Hong‐Viet V. , Bergmann Til Ole , Rasch Björn
Published: October 2022

Recent advancements in real‐time brain stimulation in the sleep field have led to many exciting findings. However, they have also opened up terminological ambiguities about what constitutes “open‐loop”, “closed‐loop”, and “real‐time” designs. Here, we address core theoretical aspects of these terms in the hopes of strengthening future research on this topic.
Enterococcus duransinfection and diarrhea in Thoroughbred foals
Authors: Williams Natasha J. , Slovis Nathan M. , Browne Nimet S. , Troedsson Mats H. T. , Giguėre Steeve , Hernandez Jorge A.
Published: October 2022

Background

Diarrhea remains an important cause of morbidity and mortality in neonatal foals, and correct identification of etiologic agents is essential for effective disease management.

Objective

To examine the association between diarrhea and detection ofEnterococcus duransor other enteropathogens in neonatal foals on 1 breeding farm in Kentucky, USA.

Animals

Fifty‐nine Thoroughbred foals and their broodmares.

Methods

Prospective observational study. Study foals and broodmares were sampled and tested forE. duransand other enteropathogens during the first 10 days after foaling. The frequency of foals in whichE. duransor other enteropathogens was compared between foals with or without diarrhea.

Results

Seven of 59 foals developed diarrhea. The frequency of foals withE. duransinfection was higher in foals with diarrhea 5/7 (71%), compared to foals without diarrhea 0/51 (0%;P < .01). Detection ofE. duransin foals was associated with detection ofE. duransin broodmares; in 2/7 (29%) foals with diarrhea, the 2 broodmares tested positive forE. durans, and, in 51/51 (100%) foals without diarrhea, all broodmares tested negative toE. durans(P = .01). Based on the spatial and temporal distribution of foals with diarrhea, 5 of 6 additional cases of diarrhea were attributed to lateral transmission ofE. duransinfection.

Conclusions and Clinical Importance

Detection ofE. duranswas associated with diarrhea in foals. Implementation of enhanced biosecurity measures might mitigate disease transmission associated withE. duransinfection in foals.
Relational linguistic continuity
Authors: Song Seunghyun
Published: October 2022

This paper develops a concept of relational linguistic continuity as a new basis to defend the right to linguistic survival. Relational linguistic continuity refers to a condition whereby individuals may continuously form human relations and have social interactions with others with whom they share the language of origin or of socialisation. The paper proceeds as follows. Section 2 critically engages with two distinct arguments that tackle the issue of linguistic survival: one based on equality of autonomy and another based on equality of dignity. Then, I point out that both arguments are insufficient for a full‐fledged defence of linguistic survival. Section 3 develops a concept of relational linguistic continuity. I first introduce the seminal idea of linguistic security proposed by Leslie Green and Denise Réaume, which will be critically revised in order to develop my concept of relational linguistic continuity. I conclude with Section 4 by defending the right to linguistic survival and addressing potential criticisms. I argue that my concept of relational linguistic continuity successfully provides a basis to defend the right to linguistic survival.
Evolution of neuroglia
Authors: Verkhratsky Alexei , Arranz Amaia M. , Ciuba Katarzyna , Pękowska Aleksandra
Published: October 2022

The evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed of electrically excitable neuronal networks connected by chemical synapses and nonexcitable glial cells that provide for homeostasis and defense. The evolution of neuroglia began with the emergence of the centralized nervous system and proceeded through a continuous increase in their complexity. In the primate brain, especially in the brain of humans, the astrocyte lineage is exceedingly complex, with the emergence of new types of astroglial cells possibly involved in interlayer communication and integration.
Functional magnetic resonance imaging activation for different vergence eye movement subtypes
Authors: Fogt Nick , Toole Andrew J. , Li Xiangrui , Owusu Emmanuel , Manning Steven T. , Kulp Marjean T.
Published: October 2022

Introduction

Maddox suggested that there were four convergence subtypes, each driven by a different stimulus. The purpose of this study was to assess the neural correlates for accommodative convergence, proximal convergence (convergence stimulus provided), disparity convergence and voluntary convergence (no specific convergence stimulus provided) using functional magnetic resonance imaging (fMRI).

Methods

Ten subjects (mean age = 24.4 years) with normal binocular vision participated. The blood oxygenation level‐dependent (BOLD) signals of the brain from fMRI scans were measured when subjects made vergence eye movements while: (1) alternately viewing letters monocularly where one eye viewed through a −2.00 D lens, (2) alternately viewing Difference of Gaussian targets monocularly at distance and near, (3) viewing random dot stereograms with increasing disparity and (4) voluntarily converging the eyes with binocular viewing.

Results

The accommodative convergence paradigm resulted in activation on the right side in the right fusiform cortex and the right middle occipital cortex. The proximal convergence stimulus mainly activated areas in the right occipital lobe. The disparity stimulus activated areas in the left occipital cortex and the left frontal cortex. Finally, the voluntary convergence paradigm resulted in activation primarily in the occipital lobe and mostly bilaterally.

Conclusion

The accommodative, proximal, disparity and voluntary convergence paradigms resulted in activation in unique areas in the brain with functional MRI. Activation was found in more areas in the proximal and voluntary conditions compared with the accommodative and disparity conditions.
Deep Disagreement (Part 1): Theories of Deep Disagreement
Authors: Ranalli Chris , Lagewaard Thirza
Published: October 2022

Some disagreements concern our most fundamental beliefs, principles, values, or worldviews, such as those about the existence of God, society and politics, or the trustworthiness of science. These are ‘deep disagreements’. But what exactly are deep disagreements? This paper critically overviews theories of deep disagreement. It does three things. First, it explains the differences between deep and other kinds of disagreement, including peer, persistent, and widespread disagreement. Second, it critically overviews two mainstream theories of deep disagreement, the Wittgensteinian account and the Fundamental Epistemic Principle account, before introducing a Hybrid account. Finally, it explores the notion that deep disagreements can be deeper than others.
Salt‐like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin‐specific protease 21 to stabilize Yin Yang 1
Authors: Wang Qing‐Dong , Liu Li‐Li , Li Di , Gao Li , Zhang Mei‐Jia
Published: October 2022

Laryngeal cancer (LC) is a rare and challenging clinical problem. Our aim was to investigate the mechanism of salt‐like transcription factor 4 (SALL4) in LC. LC tissue and paracancerous tissue were collected. Relative mRNA or protein levels were measured by quantitative real‐time polymerase chain reaction or Western blot. MTT, wound healing, and transwell assay were performed to evaluate cell proliferation, migration and invasion. The binding relationship between SALL4 and USP21 promoter was verified by dual‐luciferase assay and ChIP. Co‐IP and glutathione‐S‐transferase (GST)‐pull down were performed to measure the protein interaction between USP21 and YY1. Additionally, YY1 ubiquitination level was analyzed. It was found that SALL4 mRNA and SALL4 protein levels were elevated in LC clinical tissues and various LC cells. Knockdown of SALL4 inhibited epithelial–mesenchymal transition (EMT) of LC cells. USP21 was transcriptionally activated by SALL4. Co‐IP and GST‐pull down confirmed USP21 interacted with YY1. USP21 protected YY1 from degradation through deubiquitination. Furthermore, overexpression of USP21 reversed the effect of knockdown of SALL4 on YY1 and EMT in LC cells. In general, SALL4 facilitated EMT of LC cells through modulating USP21/YY1 axis.
Sooner or later? A study of report timing
Authors: Menon Rahul , Nan Lin
Published: October 2022

This study examines the optimal reporting time a regulator should choose for firms to report their information when the firms' effort choices influence the outcome of projects. Our analysis shows that, the regulator's optimal choice of reporting time to maximize overall efficiency is contingent on a trade‐off between motivating a firm's effort to improve the outcome and saving the liquidation value for the creditor to reduce the firm's financing cost. We also find that to induce the firm's effort, the reporting time should be either early enough or late enough—depending on the effectiveness of the effort to turn bad projects into successes. Furthermore, we examine the regulator's optimal choice of reporting time for an economy with heterogenous firms/industries, and we show that the optimal reporting time changes nonmonotonically in the probability of good projects in the economy.
Combining Cytotoxic Agents with Continuous Dose Levels in Seamless Phase I-II Clinical Trials
Authors: Jiménez José L. , Tighiouart Mourad
Published: October 2022

Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: (i) a first stage in which dose is escalated based only on toxicity data and we look for the maximum tolerated dose (MTD) set and (ii) a second stage in which we search for the most efficacious dose within the MTD set. Current available approaches in the area of continuous dose levels involve fixing the MTD after stage I and discarding all collected stage I efficacy data. However, this methodology is clearly inefficient when there is a unique patient population present across stages. In this article, we propose a two-stage design for the combination of two cytotoxic agents assuming a single patient population across the entire study. In stage I, conditional escalation with overdose control is used to allocate successive cohorts of patients. In stage II, we employ an adaptive randomisation approach to allocate patients to drug combinations along the estimated MTD curve, which is constantly updated. The proposed methodology is assessed with extensive simulations in the context of a real case study.
Heterogeneous ribonucleoprotein D selectively regulates the expression of genes in the immune system
Authors: Chen Xiaoqi , Zheng Feng , Ke Jianjuan , Zhang Qianhui , Chen Min
Published: October 2022

The immune response is critical for the elimination of pathogens. However, uncontrolled immune responses can lead to tissue damage and inflammatory diseases. The generation of an immune response requires the activation, differentiation and proliferation of various immune cells and the production of cytokines that are regulated directly or indirectly by multiple pathways, including posttranscriptional regulation by RNA‐binding proteins (RBPs). Heterogeneous ribonucleoprotein D (hnRNPD), an RBP that is also known as AU‐rich elements/poly(U)‐binding/degradation factor 1 (AUF1), can regulate the expression of various target RNAs, including mRNAs, miRNAs, lncRNAs, by binding to their Au‐rich elements (AREs) or U‐/GU‐rich sequences. The target RNAs of hnRNPD range from cytokines, inflammatory receptors and growth factors to G protein‐coupled receptors; thus, hnRNPD influences various physiological processes, including the immune response. In addition, hnRNPD is strongly expressed in multiple lymphocytic tissues, suggesting that it may play an important role in the immune system. In this review, we discuss the roles of hnRNPD in the immune system and autoimmune diseases.
Immigrant status and neighborhood context on perceptions of police procedural justice
Authors: Yuan Yue , Wu Yuning , Vera Sanchez Claudio
Published: October 2022

Objective

This study examines the relationship between immigration generational status and people's perception of police procedural justice, net of individual‐level and neighborhood‐level control variables. It also explores the importance of contextual variables, particularly neighborhood foreign‐born concentration and collective efficacy, on residents’ perceptions of police procedural justice.

Methods

With a multi‐stage, clustered sample approach, we randomly selected census tracts in San José, California, and then households inside each tract were chosen to participate in a survey. We used multi‐level modeling to explore factors that were associated with procedural justice.

Results

Results show first‐generation immigrants, compared to second or third‐and‐plus‐generation immigrants, are more positive in their evaluations of police procedural justice. Results also show that neighborhood collective efficacy can significantly affect people's perceptions of procedural justice, even after controlling for individual‐level predictors and neighborhood characteristics.

Conclusion

Both individual‐level immigration measures and neighborhood factors should be included in future research.
Education and polypharmacy: A national study of racial and ethnic variations
Authors: Hill Terrence D. , Ford Jason A. , Nicholson Harvey L.
Published: October 2022

Objective

We examine the association between college education and the number of medications used/misused in the past year. We also consider the possibility of differential socioeconomic returns to health for racial/ethnic minorities.

Methods

The data come from the 2015–2019 National Survey on Drug Use and Health (n = 144,589).

Results

In accordance with human capital theory, we found that, in the full sample and white subsample, college education was associated with lower levels of polypharmacy, even with adjustments for financial insecurity, health, and lifestyle. Consistent with the diminished return theory, we observed that college education was mostly unrelated to polypharmacy among black and Hispanic individuals. While health commodity theory was supported among Asians, health disparity theory was confirmed among individuals of other races and ethnicities.

Conclusion

The most important implication of our study is that polypharmacy can be simultaneously structured by durable systems of social stratification, including education, race, and ethnicity.
Multifunctional chemical inhibitors of the florigen activation complex discovered by structure‐based high‐throughput screening
Authors: Taoka Ken‐ichiro , Kawahara Ikumi , Shinya Shoko , Harada Ken‐ichi , Yamashita Eiki , Shimatani Zenpei , Furuita Kyoko , Muranaka Tomoaki , Oyama Tokitaka , Terada Rie , Nakagawa Atsushi , Fujiwara Toshimichi , Tsuji Hiroyuki , Kojima Chojiro
Published: October 2022

Structure‐based high‐throughput screening of chemical compounds that target protein–protein interactions (PPIs) is a promising technology for gaining insight into how plant development is regulated, leading to many potential agricultural applications. At present, there are no examples of using high‐throughput screening to identify chemicals that target plant transcriptional complexes, some of which are responsible for regulating multiple physiological functions. Florigen, a protein encoded by FLOWERING LOCUS T (FT), was initially identified as a molecule that promotes flowering and has since been shown to regulate flowering and other developmental phenomena such as tuber formation in potato (Solanum tuberosum). FT functions as a component of the florigen activation complex (FAC) with a 14‐3‐3 scaffold protein and FD, a bZIP transcription factor that activates downstream gene expression. Although 14‐3‐3 is an important component of FAC, little is known about the function of the 14‐3‐3 protein itself. Here, we report the results of a high‐throughput in vitro fluorescence resonance energy transfer (FRET) screening of chemical libraries that enabled us to identify small molecules capable of inhibiting FAC formation. These molecules abrogate the in vitro interaction between the 14‐3‐3 protein and the OsFD1 peptide, a rice (Oryza sativa) FD, by directly binding to the 14‐3‐3 protein. Treatment with S4, a specific hit molecule, strongly inhibited FAC activity and flowering in duckweed, tuber formation in potato, and branching in rice in a dose‐dependent manner. Our results demonstrate that the high‐throughput screening approach based on the three‐dimensional structure of PPIs is suitable in plants. In this study, we have proposed good candidate compounds for future modification to obtain inhibitors of florigen‐dependent processes through inhibition of FAC formation.
Frequency and characterization of RHD and RHCE variants in the Noir Marron population from French Guiana
Authors: Laget Laurine , Izard Caroline , Durieux‐Roussel Elisabeth , Filosa Lugdivine , Bailly Pascal , Mazières Stéphane , Chiaroni Jacques
Published: October 2022

Background

The RH system is one of the most polymorphic blood group systems due to the proximity and opposite orientation of RHD and RHCE genes. Numerous alleles are described and can affect Rh protein expression. This complexity is especially evident in populations of African origin. We performed RHD and RHCE genotyping of the Noir Marron population in French Guiana. This population belongs to the Maroon community who are direct descendants of African slaves, who escaped from Dutch plantations, in the current day Suriname, during the 17th century. They represent an original ethnic group with highly blended culture.

Methods and materials

A total of 89 DNA samples were collected from four different ethnic groups of the Noir Marron population of French Guiana. RHD and RHCE genotyping was performed using DNA microarray and/or sequencing.

Results and discussion

Significant allelic diversity was shown, with 45% of individuals presenting an RHD gene variant (most common: RHD*DAU, RHD*DIVa, and RHD*DIIIa allele) and 9.4% with a partial D phenotype. Likewise, 85% presenting an RHCE gene variant and 9% a partial RH2 antigen. One original allele was identified in two D+ Noir Marron individuals: a hybrid RHD*DIIIa‐CE(9)‐D allele, encoding probably a partial D antigen and associated with an RHCE*ce(48C,733G,1006T) allele.

The African diversity of RHD and RHCE genes is found in this population with preserved genetic but mixed cultural backgrounds. These data allow us to describe the characteristics of the RH system antigen and highlights a significant number of partial antigens with a risk of alloimmunization.
Markers of tissue perfusion and their relation to mortality in dogs with blunt trauma
Authors: Poirier Maude , Stillion Jenefer R. , Boysen Søren R.
Published: October 2022

Objective

To evaluate admission Animal Trauma Triage (ATT) score, shock index (SI), and markers of perfusion, including base excess (BE), plasma lactate, and lactate clearance in dogs with blunt trauma.

Design

Prospective observational clinical study from 2013 to 2015.

Setting

Private veterinary referral and emergency center.

Animals

Forty‐four client‐owned dogs hospitalized following blunt trauma.

Intervention

Within 1 hour of presentation and prior to fluid administration an initial hematocrit, total plasma protein, blood glucose, plasma lactate, blood gas, and electrolytes were obtained for analysis. Plasma lactate concentrations were also measured 4 and 8 hours following initial measurement, and a 4‐hour lactate clearance was calculated if patients had an increased admission plasma lactate. ATT score and SI were calculated for each patient based on admission data. Outcome was defined as survival to hospital discharge.

Measurements and Main Results

Twenty‐nine dogs survived, 14 were euthanized, and 1 died. Nonsurviving dogs had a lower mean pH (7.28 ± 0.03 vs 7.36 ± 0.01,P = 0.006), lower median HCO3(15.7 vs 18.8 mmol/L,P = 0.004), lower median admission BE (–11.0 vs –7.0 mmol/L,P = 0.004), and higher median admission lactate (3.1 vs 2.4 mmol/L,P = 0.036) than those who survived. Median ATT was significantly higher in nonsurvivors (5 vsF 2,P < 0.001). The SI was not significantly different between survivors and nonsurvivors (P = 0.41). There was no difference in median 4‐hour lactate (P = 0.34), median 8‐hour lactate (P = 0.19), or 4‐hour lactate clearance (P = 0.83) in survivors compared to nonsurvivors. No other statistically significant differences were noted between groups.

Conclusion

Dogs hospitalized following blunt trauma with a lower admission pH, HCO3, and BE and a higher admission plasma lactate were less likely to survive to hospital discharge. Median ATT score was also significantly higher in nonsurvivors. Although lactate clearance was not predictive of survival, the sample size was small, and additional studies with a larger study population are warranted.
Presumed erlotinib‐induced bilateral corneal ulcers in a dog with lung tumor
Authors: Jung Sunjun
Published: October 2022

Objective

To report the corneal toxicity of erlotinib in dogs.

Animal studied

A 13‐year‐old castrated male Maltese dog.

Results

A dog with lung cancer presented with a month‐long history of mucoid discharge and blepharospasm in both eyes. Corneal ulcerations with stromal thinning were diagnosed in both eyes, which were refractory after 2 weeks of treatment with topical antibiotics and artificial tears. The dog was orally administered erlotinib (Tarceva®) by his owner for 2 months to treat his lung cancer. Urgent withholding of erlotinib was recommended, and after 2 weeks of discontinuation, the corneal defects resolved; however, corneal thinning remained until the six‐month follow‐up.

Conclusions

To the best of author's knowledge, this is the first report in the veterinary literature that describes bilateral corneal ulcers associated with erlotinib administration in a dog.