bluuebunny/crossref_metadata_2025 huggingface dataset:
Bubble testing under polynomial trends
Authors: Wang Xiaohu , Yu Jun
Published: July 2022

This paper develops the asymptotic theory of the least squares estimator of the autoregressive (AR) coefficient in an AR(1) regression with intercept when data is generated from a polynomial trend model in different forms. It is shown that the commonly used right-tailed unit root tests tend to favour the explosive alternative. A new procedure, which implements the right-tailed unit root tests in an AR(2) regression, is proposed. It is shown that, when the data generating process has a polynomial trend, the test statistics based on the new procedure cannot find evidence of explosiveness. Whereas, when the data generating process is mildly explosive, the new procedure finds evidence of explosiveness. Hence, it enables robust bubble testing under polynomial trends. Empirical application of the proposed procedure using data from the US real estate market reveals some interesting findings. In particular, all the negative bubble episodes flagged by the traditional method are no longer regarded as bubbles by the new procedure.
Novel ACTN2 missense variant is associated with idiopathic ventricular fibrillation: a case report
Authors: Hou Cody R , Cortez Daniel
Published: July 2022

Background

Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion made in patients who experience VF without an attributable cause. Pathogenic variants of the ACTN2 gene encoding the sarcomeric protein alpha-actinin-2 are known to cause hypertrophic and dilated cardiomyopathy. We show that ACTN2 variants may also be associated with malignant arrhythmias in the absence of overt structural heart disease.

Case summary

A 48-year-old female presented with cardiac arrest due to VF without any history of cardiovascular disease or family history of sudden cardiac death. Troponin I was elevated at 0.698 ng/mL, but coronary angiography showed no significant coronary artery disease. Substance abuse testing showed elevated benzodiazepine and sertraline levels, which she was taking for anxiety. Electrocardiogram showed normal QRS complexes without prolonged PR or QTc intervals. She underwent therapeutic hypothermia. Cardiac magnetic resonance imaging at 2 weeks showed normal biventricular function without structural abnormalities, fibrosis, or evidence of myocardial infarction. A targeted gene panel revealed a heterozygous missense variant of unknown significance (VUS) in exon 18 of the ACTN2 gene (c.2162G > A/p.R721H).

Discussion

The identified VUS is located in a highly conserved residue of a spectrin-like repeat domain of alpha-actinin-2. Spectrin-like domains of alpha-actinin-2 bind and regulate the ion channels Nav1.5, Kv1.4, and Kv1.5, which contribute to the myocardial action potential. The VUS was predicted as pathogenic by MutationTaster, Polymorphism Phenotyping v2, and Sorting Intolerant From Tolerant in silico missense prediction tools. The c.2162G > A/p.R721H alpha-actinin-2 variant may result in dysregulation of cardiac ion channels, leading to arrhythmias.
The Rattlesnake W Chromosome: A GC-Rich Retroelement Refugium with Retained Gene Function Across Ancient Evolutionary Strata
Authors: Schield Drew R , Perry Blair W , Card Daren C , Pasquesi Giulia I M , Westfall Aundrea K , Mackessy Stephen P , Castoe Todd A
Published: July 2022

Sex chromosomes diverge after the establishment of recombination suppression, resulting in differential sex-linkage of genes involved in genetic sex determination and dimorphic traits. This process produces systems of male or female heterogamety wherein the Y and W chromosomes are only present in one sex and are often highly degenerated. Sex-limited Y and W chromosomes contain valuable information about the evolutionary transition from autosomes to sex chromosomes, yet detailed characterizations of the structure, composition, and gene content of sex-limited chromosomes are lacking for many species. In this study, we characterize the female-specific W chromosome of the prairie rattlesnake (Crotalus viridis) and evaluate how recombination suppression and other processes have shaped sex chromosome evolution in ZW snakes. Our analyses indicate that the rattlesnake W chromosome is over 80% repetitive and that an abundance of GC-rich mdg4 elements has driven an overall high degree of GC-richness despite a lack of recombination. The W chromosome is also highly enriched for repeat sequences derived from endogenous retroviruses and likely acts as a “refugium” for these and other retroelements. We annotated 219 putatively functional W-linked genes across at least two evolutionary strata identified based on estimates of sequence divergence between Z and W gametologs. The youngest of these strata is relatively gene-rich, however gene expression across strata suggests retained gene function amidst a greater degree of degeneration following ancient recombination suppression. Functional annotation of W-linked genes indicates a specialization of the W chromosome for reproductive and developmental function since recombination suppression from the Z chromosome.
Productivity within the epidemic-type seismicity model
Authors: Molchan G , Varini E , Peresan A
Published: July 2022

The productivity of a magnitude m event can be characterized in term of triggered events of magnitude above m − Δ: it is the number of direct ‘descendants’ $\nu _\Delta$ and the number of all ‘descendants’ $V_\Delta$. There is evidence in favour of the discrete exponential distribution for both $\nu _\Delta$ and $V_\Delta$ with a dominant initial magnitude m (the case of aftershock cluster). We consider the general Epidemic Type Aftershock Sequence model adapted to any distribution of $\nu _\Delta$. Our first result shows that models with branching aftershock structure do not allow for the coincidence of distribution types of $\nu _\Delta$ and $V_\Delta$ (say, the discrete exponential, as in the scientific literature). The second problem is related to the tail behaviour of the $V_\Delta$ distribution. We show the fundamental difference in tail behaviour of the $V_\Delta$-distributions for general-type clusters and clusters with a dominant initial magnitude: the tail is heavy in the former case and light in the latter. The real data demonstrate the possibilities of this kind. This result provides theoretical and practical constraints for distributional analysis of $V_\Delta$.
Functional analysis of GCNT3 for cell migration and EMT of castration-resistant prostate cancer cells
Authors: Yamamoto Daiki , Sasaki Katsumasa , Kosaka Takeo , Oya Mototsugu , Sato Toshinori
Published: July 2022

Castration-resistant prostate cancer (CRPC) is a malignant tumor that is resistant to androgen deprivation therapy. Treatments for CRPC are limited, and no diagnostic markers are currently available. O-glycans are known to play an important role in cell proliferation, migration, invasion, and metastasis of cancer cells. However, the differences in the O-glycan expression profiles for normal prostate cancer (PCa) cells compared with CRPC cells have not yet been investigated. In this study, the saccharide primer method was employed to analyze the O-glycans expressed in CRPC cells. Expression levels of core 4-type O-glycans were significantly increased in CRPC cells. Furthermore, the expression level of N-Acetylglucosaminyltransferase 3 (GCNT3), a core 4-type O-glycan synthase gene, was increased in CRPC cells. The expression of core 4-type O-glycans and GCNT3 was presumed to be regulated by androgen deprivation. GCNT3 knockdown induced cell migration and epithelial-mesenchymal transition. These observations elucidate the mechanism of acquisition of castration resistance in PCa and offer new possibilities for the development of diagnostic markers and therapeutic targets in the treatment of PCa.
The Value of a Dedicated IBD Flare Clinic to Effectively Manage Exacerbations of Inflammatory Bowel Disease: The Edinburgh IBD Unit
Authors: Grant Rebecca K , Brindle William M , Arnott Ian D R
Published: July 2022

Lay Summary

We assessed the impact of a dedicated inflammatory bowel disease flare clinic. Attenders had more changes to maintenance medications made and less steroid use than inflammatory bowel disease patients reviewed at the Acute Receiving Unit. This model of care may potentially reduce hospital admissions.
Femoral de-rotation osteotomy versus hip arthroscopy for management of femoroacetabular impingement in adult patients with decreased femoral anteversion: a matched retrospective cohort study
Authors: Mastel Matthew S , Federico Alyssa , Desy Nicholas M , Johnston Kelly D
Published: July 2022

Femoral de-rotation osteotomy (FDO) and hip arthroscopy are both recognized surgical options for the management of femoroacetabular impingement (FAI) in the setting of decreased femoral anteversion (<5°). Minimal comparative data exist regarding the difference in outcomes between these two techniques, and we believe this is the first study to provide that comparison. This retrospective cohort study included a total of 20 patients with such pathology, matched for age, gender and body mass index. A total of 10 patients were included in the FDO group [median anteversion −0.5° (true retroversion); average follow-up 17.9 months]. In total, 10 patients were included in the hip arthroscopy group [median anteversion −0.5° (true retroversion); average follow-up 28.5 months]. Both groups demonstrated statistically and clinically significant improvement in the post-operative International Hip Outcome Tool (iHOT-33) scores [median improvement: FDO group, 37.7 points (r 14–58.8; P < 0.041); hip arthroscopy group, 35.9 points (r 11.1–81; P < 0.05)], noting that the minimal clinically important difference for the iHOT-33 is 6.1 points. However, the study was not adequately powered to delineate a difference in improvement between the two groups. The findings suggest significant improvement in patient-reported outcomes, and clinical findings can be achieved with either FDO or hip arthroscopy for FAI in the setting of decreased femoral anteversion. However, selection of the most suitable surgical procedure using a patient-specific approach may optimize outcomes in this challenging population.
Minimally invasive treatment of an amebic empyema secondary to the transdiaphragmatic rupture of a liver abscess: a case report
Authors: Abello Vaamonde Jorge A , White Elizabeth Gil , López Alfredo Muñoz , Lorenzo Silva José M
Published: July 2022

Liver abscesses are a common complication in patients with amebiasis. Rarely, these will rupture across the diaphragm causing life-threatening empyemas. Evidence justifies performing surgical debridement or decortication for their treatment, given the better overall performance in comparison to open surgeries. However, no current guideline specifies which is the best approach. This report presents the case of a 39-year-old male with clinical, radiographical and microbiological evidence of an amebic empyema secondary to an amebic liver abscess, who received treatment by video-assisted thoracoscopy. The case description highlights the surgical technique, findings and operative outcomes that could be taken into consideration by other physicians to timely manage similar cases. The latter is especially relevant in underdeveloped and developing countries, where the burden of amebiasis appears to be greater. To the best of the authors’ knowledge, this is the first description of a transdiaphragmatic amebic infection treated in a minimally invasive fashion.
Laparoscopic Roux-en-Y gastric bypass in a patient with situs inversus totalis: case report
Authors: Zorrilla-Blanco Pablo Gerardo , Muñoz-Maldonado Gerardo , Zorrilla-Nuñez Luis Fernando , Núñez-Jasso Noé , González-Zorrilla Fernando , Mata-De Anda Lilia Andrea , de la O-Escamilla Manuel
Published: July 2022

The purpose of this report is to present the case of a patient with situs inversus totalis (SIT) who underwent laparoscopic gastric bypass and review of the literature. Situs inversus is a rare congenital abnormality that occurs in ~0.01% of the population and is characterized by transposition of the abdominal viscera1. When associated with dextrocardia, it is known as SIT. Electrocardiography reveals a reversal of the electrical waves of the heart and is the diagnostic measure of choice. Roux-en-Y laparoscopic gastric bypass for morbid obesity is one of the most effective bariatric procedures currently considered as the gold standard in bariatric surgery. We present the case of a 19-year-old male with morbid obesity and diagnosis of SIT, who underwent a laparoscopic gastric bypass adjusting the technique to the anatomical changes typical of this variant. It can be concluded, based on the previously compared cases and what was reported in ours, that in patients who have an indication to perform bariatric surgery and present SIT, surgery is not contraindicated, obtaining favorable results.
The authorship of George a Greene, the Pinner of Wakefield
Authors: Ilsemann Hartmut
Published: July 2022

Establishing the authorship of George a Greene, the Pinner of Wakefield can be seen within the wider context of detecting a collaborative or single-authored canon of early Shakespeare plays which, perhaps, he did not want to see as part of his dramatic work if we are to trust Heminges’ and Condell’s references to ‘surrepetitious copies, maimed, and deformed by the frauds and stealthes of injurious imposters, that expos’d them’ (First Folio preface). The fact that the remaining plays of the First Folio [are] ‘absolute in their numbers as he [Shakespeare] conceived them,’ has in some way a ring of self-amputation. The conclusion of the present study, based on the acknowledged methodological advances in non-traditional stylometric tools, contained in the R Stylo suite, is that George a Greene, the Pinner of Wakefield was originally written by William Shakespeare, even though the play may have been shortened for performances outside London with a reduced company of players during the plague years of 1592 and 1593.
Transcriptional profiles of genes related to mitochondrial aging in placental pathologies
Authors: Bartho Lucy A , McKeating Daniel R , Hannan Natalie J , Kaitu’u-Lino Tu’uhevaha J , Perkins Anthony V
Published: July 2022

As the placenta develops across gestation, the mitochondria and other organelles like the endoplasmic reticulum (ER) must continue to adapt to stressors such as oxidative stress. As pregnancy approaches term, these stressors may contribute to placental aging, including mitochondrial changes leading to cellular senescence. When these processes are exacerbated, pregnancy pathologies arise. This study aimed to identify correlations between genes related to mitochondria, ER and cellular senescence in placentae complicated by pregnancy complications. Placental samples from pregnancies classified as preterm, term, post-term, preterm with foetal growth restriction (FGR), preterm with preeclampsia (PE) and preterm with PE and FGR were used to measure gene expression of TOMM20, MFN1, TFAM, MFN2, PARK2, PINK1, EIF2AK3, TP53 and ERN1. MetaboAnalyst 5.0 was used to generate heatmaps, principal component analysis plots, correlation graphs and receiver operating characteristic analysis. This study found that genes-related mitochondrial dynamics and aging undergo changes in placentae affected by pregnancy pathologies. The TOMM20/PARK2 ratio may be a promising marker to discriminate between healthy and unhealthy placental tissue. Future studies should explore circulating biomarkers of mitochondrial aging and dysfunction as indicators of placental health.
Quantitative multiplexed analysis of MMP-11 and CD45 in metastatic breast cancer tissues by immunohistochemistry-assisted LA–ICP–MS
Authors: Johnson Dylan , Clases David , Fernández-Sánchez Maria Luisa , Eiro Noemi , González Luis O , Vizoso Francisco J , Doble Philip A , Gonzalez de Vega Raquel
Published: July 2022

Breast cancer is the leading cause of cancer death in woman and tremendous efforts are undertaken to limit its dissemination and to provide effective treatment. Various histopathological parameters are routinely assessed in breast cancer biopsies to provide valuable diagnostic and prognostic information. MMP-11 and CD45 are tumor-associated antigens and potentially valuable biomarkers for grading aggressiveness and metastatic probability. This paper presents methods for quantitative and multiplexed imaging of MMP-11 and CD45 in breast cancer tissues and investigates their potential for improved cancer characterization and patient stratification. An immunohistochemistry-assisted laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) method was successfully developed and optimized using lanthanide-tagged monoclonal antibodies as proxies to determine spatial distributions and concentrations of the two breast cancer biomarkers. The labeling degree of antibodies was determined via size exclusion–ICP–tandem mass spectrometry (SEC–ICP–MS/MS) employing online calibration via post-column isotope dilution analysis (IDA). The calibration of spatial distributions of labeled lanthanides in tissues was performed by ablating mold-prepared gelatin standards spiked with element standards. Knowledge of labeling degrees enabled the translation of lanthanide concentrations into biomarkers concentrations. The k-means clustering was used to select tissue areas for statistical analysis and mean concentrations were compared for sets of metastatic, non-metastatic and healthy samples. MMP-11 was expressed in stroma surrounding tumor areas, while CD45 was predominantly found inside tumor areas with high cell density. There was no significant correlation between CD45 and metastasis (P = 0.70); however, MMP-11 was significantly up-regulated (202%) in metastatic samples compared to non-metastatic (P = 0.0077) and healthy tissues (P = 0.0087).
DNA barcoded competitive clone-initiating cell analysis reveals novel features of metastatic growth in a cancer xenograft model
Authors: Aalam Syed Mohammed Musheer , Tang Xiaojia , Song Jianning , Ray Upasana , Russell Stephen J , Weroha S John , Bakkum-Gamez Jamie , Shridhar Viji , Sherman Mark E , Eaves Connie J , Knapp David J H F , Kalari Krishna R , Kannan Nagarajan
Published: July 2022

A problematic feature of many human cancers is a lack of understanding of mechanisms controlling organ-specific patterns of metastasis, despite recent progress in identifying many mutations and transcriptional programs shown to confer this potential. To address this gap, we developed a methodology that enables different aspects of the metastatic process to be comprehensively characterized at a clonal resolution. Our approach exploits the application of a computational pipeline to analyze and visualize clonal data obtained from transplant experiments in which a cellular DNA barcoding strategy is used to distinguish the separate clonal contributions of two or more competing cell populations. To illustrate the power of this methodology, we demonstrate its ability to discriminate the metastatic behavior in immunodeficient mice of a well-established human metastatic cancer cell line and its co-transplanted LRRC15 knockdown derivative. We also show how the use of machine learning to quantify clone-initiating cell (CIC) numbers and their subsequent metastatic progeny generated in different sites can reveal previously unknown relationships between different cellular genotypes and their initial sites of implantation with their subsequent respective dissemination patterns. These findings underscore the potential of such combined genomic and computational methodologies to identify new clonally-relevant drivers of site-specific patterns of metastasis.
Renal sarcoidosis
Authors: Mehta Swati , Lightle Andrea , Judson Marc A
Published: July 2022

Renal sarcoidosis (RS) is a rare form of sarcoidosis that results in granulomatous inflammation of renal parenchyma. We describe the epidemiology, pathogenesis, clinical features, diagnostic approach, treatment strategies and outcomes of this condition. RS occurs most commonly at the time of initial presentation of sarcoidosis but can at any time along the course of the disease. The most common presenting clinical manifestations of RS are renal insufficiency or signs of general systemic inflammation. End-stage renal disease (ESRD) requiring dialysis is a rare initial presentation of RS. The diagnosis of RS should be considered in patients who present with renal failure and have either a known diagnosis of sarcoidosis or have extra-renal features consistent with sarcoidosis. A renal biopsy helps to establish the diagnosis of RS, with interstitial non-caseating granulomas confined primarily to the renal cortex being the hallmark pathological finding. However, these histologic findings are not specific for sarcoidosis, and alternative causes for granulomatous inflammation of the renal parenchyma should be excluded. Corticosteroids are the drug of choice for RS. Although RS usually responds well to corticosteroids, the disease may have a chronic course and require long-term immunosuppressive therapy. The risk of progression to ESRD is rare.
Influence of county-level geographic/ancestral origin on glioma incidence and outcomes in US Hispanics
Authors: Walsh Kyle M , Neff Corey , Bondy Melissa L , Kruchko Carol , Huse Jason T , Amos Christopher I , Barnholtz-Sloan Jill S , Ostrom Quinn T
Published: July 2022

Background

Glioma incidence is 25% lower in Hispanics than White non-Hispanics. The US Hispanic population is diverse, and registry-based analyses may mask incidence differences associated with geographic/ancestral origins.

Methods

County-level glioma incidence data in Hispanics were retrieved from the Central Brain Tumor Registry of the United States. American Community Survey data were used to determine the county-level proportion of the Hispanic population of Mexican/Central American and Caribbean origins. Age-adjusted incidence rate ratios and incidence rate ratios (IRRs) quantified the glioma incidence differences across groups. State-level estimates of admixture in Hispanics were obtained from published 23andMe data.

Results

Compared to predominantly Caribbean-origin counties, predominantly Mexican/Central American-origin counties had lower age-adjusted risks of glioma (IRR = 0.83; P < 0.0001), glioblastoma (IRR = 0.86; P < 0.0001), diffuse/anaplastic astrocytoma (IRR = 0.78; P < 0.0001), oligodendroglioma (IRR = 0.82; P < 0.0001), ependymoma (IRR = 0.88; P = 0.012), and pilocytic astrocytoma (IRR = 0.76; P < 0.0001). Associations were consistent in children and adults and using more granular geographic regions. Despite having lower glioma incidence, Hispanic glioblastoma patients from predominantly Mexican/Central American-origin counties had poorer survival than Hispanics living in predominantly Caribbean-origin counties. Incidence and survival differences could be partially explained by state-level estimates of European admixture in Hispanics with European admixture associated with higher incidence and improved survival.

Conclusions

Glioma incidence and outcomes differ in association with the geographic origins of Hispanic communities, with counties of predominantly Mexican/Central American origin at significantly reduced risk and those of Caribbean origin at comparatively greater risk. Although typically classified as a single ethnic group, appreciating the cultural, socioeconomic, and genetic diversity of Hispanics can advance cancer disparities research.
DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients
Authors: Drexler Richard , Schüller Ulrich , Eckhardt Alicia , Filipski Katharina , Hartung Tabea I , Harter Patrick N , Divé Iris , Forster Marie-Therese , Czabanka Marcus , Jelgersma Claudius , Onken Julia , Vajkoczy Peter , Capper David , Siewert Christin , Sauvigny Thomas , Lamszus Katrin , Westphal Manfred , Dührsen Lasse , Ricklefs Franz L
Published: July 2022

Background

DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive.

Methods

Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma.

Results

345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64–1.28]; p = 0.56; MES: 0.69 [0.47–1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36–6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80–9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68–3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19–0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34–0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27–1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33).

Conclusion

We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.
Lethal Dermal Sarcoma in Immunosuppressed Patients
Authors: Azin Marjan , Ameri Amir H , Foreman Ruth K , Neel Victor A , Lorenzo Mayra E , Demehri Shadmehr
Published: July 2022

Skin cancer is the leading malignancy in immunosuppressed patients, including organ transplant recipients (OTRs), which is increasing in incidence as OTRs live longer. We performed a single-center case series of 4 patients with scalp pleomorphic dermal sarcoma and a history of multiple keratinocyte carcinomas. Outcomes included incidence of dermal sarcoma, dermal sarcoma-related mortality, and histopathologic findings. Out of more than 200 patients followed over a 3-year period in Massachusetts General Hospital High Risk Skin Cancer Clinics, all skin cancer-related deaths (2/2) were due to metastatic dermal sarcoma. Three of 4 patients diagnosed with scalp dermal sarcoma were OTRs and had been on at least one immunosuppressive medication for a median of 9 years. For patients who died from dermal sarcoma, the median time between diagnosis and death was 6 months. Our findings suggest pleomorphic dermal sarcoma contributes to skin cancer-related morbidity and mortality in OTRs.
Maize Shrek1 encodes a WD40 protein that regulates pre-rRNA processing in ribosome biogenesis
Authors: Liu Hui , Xiu Zhihui , Yang Huanhuan , Ma Zhaoxing , Yang Dalin , Wang Hongqiu , Tan Bao-Cai
Published: July 2022

Ribosome biogenesis is a fundamental and highly orchestrated process that involves hundreds of ribosome biogenesis factors. Despite advances that have been made in yeast, the molecular mechanism of ribosome biogenesis remains largely unknown in plants. We uncovered a WD40 protein, Shrunken and Embryo Defective Kernel 1 (SHREK1), and showed that it plays a crucial role in ribosome biogenesis and kernel development in maize (Zea mays). The shrek1 mutant shows an aborted embryo and underdeveloped endosperm and embryo-lethal in maize. SHREK1 localizes mainly to the nucleolus and accumulates to high levels in the seed. Depleting SHREK1 perturbs pre-rRNA processing and causes imbalanced profiles of mature rRNA and ribosome. The expression pattern of ribosomal-related genes is significantly altered in shrek1. Like its yeast (Saccharomyces cerevisiae) ortholog Periodic tryptophan protein 1 (PWP1), SHREK1 physically interacts with ribosomal protein ZmRPL7a, a transient component of the PWP1-subcomplex involved in pre-rRNA processing in yeast. Additionally, SHREK1 may assist in the A3 cleavage of the pre-rRNA in maize by interacting with the nucleolar protein ZmPOP4, a maize homolog of the yeast RNase mitochondrial RNA-processing complex subunit. Overall, our work demonstrates a vital role of SHREK1 in pre-60S ribosome maturation, and reveals that impaired ribosome function accounts for the embryo lethality in shrek1.
Research and clinical translation of trilayer stent-graft of expanded polytetrafluoroethylene for interventional treatment of aortic dissection
Authors: Wang Gang , Gao Caiyun , Xiao Benhao , Zhang Jie , Jiang Xunyuan , Wang Qunsong , Guo Jingzhen , Zhang Deyuan , Liu Jianxiong , Xie Yuehui , Shu Chang , Ding Jiandong
Published: July 2022

The aortic dissection (AD) is a life-threatening disease. The transcatheter endovascular aortic repair (EVAR) affords a minimally invasive technique to save the lives of these critical patients, and an appropriate stent-graft gets to be the key medical device during an EVAR procedure. Herein, we report a trilayer stent-graft and corresponding delivery system used for the treatment of the AD disease. The stent-graft is made of nitinol stents with an asymmetric Z-wave design and two expanded polytetrafluoroethylene (ePTFE) membranes. Each of the inner and outer surfaces of the stent-graft was covered by an ePTFE membrane, and the two membranes were then sintered together. The biological studies of the sintered ePTFE membranes indicated that the stent-graft had excellent cytocompatibility and hemocompatibility in vitro. Both the stent-graft and the delivery system exhibited satisfactory mechanical properties and operability. The safety and efficacy of this stent-graft and the corresponding delivery system were demonstrated in vivo. In nine canine experiments, the blood vessels of the animals implanted with the stent-grafts were of good patency, and there were no thrombus and obvious stenosis by angiography after implantation for 6 months. Furthermore, all of the nine clinical cases experienced successful implantation using the stent-graft and its postrelease delivery system, and the 1-year follow-ups indicated the preliminary safety and efficacy of the trilayer stent-graft with an asymmetric Z-wave design for interventional treatment.
Reading the Tied Letters of Cotton Nero A.x.
Authors: Dwyer Seamus
Published: July 2022

This article examines the relationship between the script and the literary language of British Library, MS Cotton Nero A.x., particularly Pearl, Cleanness, and Sir Gawain and the Green Knight, arguing that the manuscript’s penmanship, little studied, offers an interpretation of its poems. It begins with an extended analysis of and reflection on the script itself, identified as a form of textualis. The script is then connected to the aesthetic ideals of the texts through the language of Cleanness, in a scene adapted from the Book of Daniel that describes God’s ‘writing on the wall’ as ‘tied letters’. This representation of an inscriptional process internal to the poem reflects on the visual effect of the manuscript’s own textualis. By tracking other instances where ‘tied’ and its synonyms are used to describe embellishment in Pearl and Gawain as well as Cleanness, the article opens up a broader analysis of the poetic themes in Cotton Nero, bringing an ideal of calligraphic inscription into a constellation of rich material metaphors for divine transcendence. By connecting Cotton Nero’s script to the ideals of its poetry, this article ultimately argues that the script is fully unified with the poetry in a common aesthetics that sees material writing as a ready vehicle for immaterial elevation.
Melatonin-Primed MSCs Alleviate Intrauterine Adhesions by Affecting MSC-Expressed Galectin-3 on Macrophage Polarization
Authors: Jiang Qi , Li Jingman , Pan Yuchen , Wang Jiali , Yang Jingjing , Shen Sunan , Hou Yayi
Published: July 2022

Intrauterine adhesion (IUA) is characterized by the presence of fibrosis in the uterine cavity. It is mainly caused by infection or trauma to the endometrium, and it imposes a great challenge to female reproductive health. Mesenchymal stem cells (MSCs) have been used to regenerate the human endometrium in patients with IUA, but stem cell therapy is not curative in some patients. Melatonin (MT) was reported as a potential modulator of MSCs. However, it remains unclear whether MSCs pretreated with MT exert an improved therapeutic effect on IUA. In this study, an IUA model was established using our invented electric scratching tool. Our results illustrated that MT-pretreated MSCs significantly attenuated the development of IUA. Moreover, MT-pretreated MSCs highly expressed galectin-3 (Gal-3), which enhanced MSC proliferation and migration and influenced macrophage polarization. Of note, IUA mice exhibited colonic injury, and MT-pretreated MSCs alleviated this injury by normalizing colonic microbial communities and recruiting macrophages. Furthermore, inhibition of sympathetic nerves had no effect on IUA progression but delayed colonic injury, and Gal-3 combined with norepinephrine better promoted M2-like macrophage polarization and inhibited M1-like macrophage polarization. Together, these data indicated that MT-primed MSCs can ameliorate injury of both the uterus and colon in an IUA model through high Gal-3 expression to influence sympathetic nerves and in turn affect the polarization and recruitment of macrophages.
Social Work Licensure Portability: A Necessity in a Post-COVID-19 World
Authors: Apgar Dawn
Published: July 2022

COVID-19 highlights the need for portability of social work licensure to be a priority. The Association of Social Work Boards (ASWB) spearheaded some initiatives, such as the creation and promotion of the Social Work Registry and Model Social Work Practice Act, with the hope that these efforts would enhance the ability of social workers to be licensed in multiple states. Neither has solved the portability problem. Licensure endorsement, an approach historically supported by ASWB, does not have the advantages of mutual recognition that is being supported by other professions to facilitate interstate practice. This article, the first written on licensure portability in the social work scholarly literature, examines existing licensure portability models and supports the establishment of a social work interstate compact to overcome barriers to social work mobility and access to client care.
Training the next generation of behavioral medicine scientists to accelerate digital health
Authors: Castro Sweet Cynthia , Kaye Leanne , Alabduljabbar Manal , Myers Valerie
Published: July 2022

We trace the evolution of digital health industry careers for behavioral medicine specialists. We discuss the current misalignment of career opportunities in the private sector with the predominant graduate education training model that emphasizes the pursuit of academic positions. We describe the potential risks to the profession and public health if the field does not adapt professional training models to be inclusive of private sector industry roles. Finally, we offer a series of recommendations aimed at trainees, faculty advisors, and training programs to better prepare trainees for meaningful careers in industry.
Armoured Cars and Archbishops: Human Rights, Religious Pressure Groups, and Arms for El Salvador, 1977–8
Authors: Grealy David
Published: July 2022

David Owen, who was appointed as Foreign and Commonwealth Secretary following the death of Anthony Crosland in February 1977, committed the Labour government of Jim Callaghan to a human rights-based foreign policy, stating in his first major speech that Britain would take a ‘stand’ on human rights violations in every corner of the globe. This ambitious agenda faced a major challenge when, in October 1977, Owen was alerted to the imminent shipment of British Ferret and Saladin armoured vehicles to the repressive Salvadoran regime of Carlos Humberto Romero. By uncovering the machinations that led to the eventual cancellation of the armoured vehicles contract in January 1978, this article explores how the Catholic Institute for International Relations (CIIR) spearheaded a powerful lobbying campaign, bringing the combined pressure of sympathetic journalists, parliamentarians, civil servants, and representatives of the Catholic Church within Britain to bear on the foreign policy establishment. This article therefore contributes towards a greater understanding of Britain’s burgeoning human rights network, the connections it cultivated within Whitehall, and the processes through which it was able to effectively subvert traditional modes of foreign policymaking during a ‘breakthrough’ moment in human rights history.
Febuxostat Increases Ventricular Arrhythmogenesis Through Calcium Handling Dysregulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Zhu Yue , Zheng Bingyu , Cai Cheng , Lin Zhiqiao , Qin Huiyuan , Liu Hailei , Cui Chang , Chen Minglong
Published: July 2022

Febuxostat is a xanthine oxidase inhibitor used to reduce the formation of uric acid and prevent gout attacks. Previous studies have suggested that febuxostat was associated with a higher risk of cardiovascular events, including atrial fibrillation, compared with allopurinol, another anti-hyperuricemia drug. Whereas in our clinical practice, we identified 2 cases of febuxostat-associated ventricular tachycardia (VT) events. The proarrhythmogenic effects of febuxostat on human cardiomyocytes and underlined mechanisms remain poorly understood. In this study, we employed real-time cell analysis and calcium transient to investigate the effects of febuxostat on the cytotoxicity and electrophysiology properties of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Up to 10 μM febuxostat treatment did not show toxicity to cell viability. However, 48-h febuxostat exposure generated dose-dependent increased irregular calcium transients and decreased calcium transient amplitude. Furthermore, RNA-seq analysis indicated that the MAPK signaling pathway was enriched in the febuxostat-treated group, especially the protein kinases c-Jun N-terminal kinase (JNK). Western blotting of 3 main protein kinases demonstrated that JNK activation is related to febuxostat-induced arrhythmia rather than extracellular signal regulated kinases (ERK) or p38. The dysfunctional calcium dynamics of febuxostat-treated hiPSC-CMs could be ameliorated by SP600125, the inhibitor of JNK. In conclusion, our study demonstrated that febuxostat increases the predisposition to ventricular arrhythmia by dysregulating calcium dynamics.
The Postnatal Resolution of Developmental Toxicity Induced by Pharmacological Diacylglycerol Acyltransferase 2 (DGAT2) Inhibition During Gestation in Rats
Authors: Catlin Natasha R , Bowman Christopher J , Campion Sarah N , Lewis Elise M , Nowland William S , Stethem Christine , Cappon Gregg D
Published: July 2022

Ervogastat (PF-06865571) is a small molecule diacylglycerol acyltransferase 2 (DGAT2) inhibitor being developed for the oral treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. DGAT2 is a key enzyme in triglyceride synthesis in tissues and in regulating energy metabolism. Fertility and developmental toxicity studies with ervogastat were conducted in female rats and rabbits. There were no effects on female rat fertility or rabbit embryo-fetal development. Administration of ervogastat to pregnant rats during organogenesis reduced fetal weight and caused higher incidences of bent bones in fetuses that were shown to resolve by postnatal day 28 and were therefore considered to be transient variations secondary to developmental delay. Extended dosing in rats through the end of gestation and lactation (pre- and post-natal development study) caused impaired skin development, reduced offspring viability, and growth retardation. The spectrum of developmental effects in rats is consistent with the intended pharmacology (altered triglyceride metabolism) and the transient nature of the skeletal findings, along with the late gestational window of sensitivity for the effects on skin barrier development, reduce the concern for potential adverse developmental effects following unintended early gestational exposure to ervogastat in humans where treatment can be discontinued once pregnancy is determined.
17Theory on Theory
Authors: Carr Nicholas
Published: July 2022

This chapter reviews recent contributions to the meta-discourses of theory and criticism. Theory on theory is bound always to be a protean and polymorphous category, and the discussion here is structured by a division into five themes, even though the works reviewed frequently range across more than one of them. Section 1 notes the emergence of a distinctive move to reinsert teaching into discussions of literary studies. Section 2 surveys a range of publications that continue the long work of historicizing theory, particularly in the French vein that is almost synonymous with understandings of (high) theory as a period. Building on that glance backward, Section 3 considers a number of works that propose new approaches or methods for our field. These proposals, at least in part, emerge from a virtually universal sense of crisis in the humanities, which is examined in Section 4. Finally, Section 5 considers the positing of a transdisciplinary world turn that is said to go well beyond the humanities. In this year’s melange of continuing practices, revivals, and innovations, theory on theory is revealed to be a lively and stimulating voice in the cultural conversations of the past year.
Clinical Indicators of Surgical Outcomes After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study
Authors: Nagoshi Narihito , Yoshii Toshitaka , Egawa Satoru , Sakai Kenichiro , Kusano Kazuo , Tsutsui Shunji , Hirai Takashi , Matsukura Yu , Wada Kanichiro , Katsumi Keiichi , Koda Masao , Kimura Atsushi , Furuya Takeo , Maki Satoshi , Nishida Norihiro , Nagamoto Yukitaka , Oshima Yasushi , Ando Kei , Nakashima Hiroaki , Takahata Masahiko , Mori Kanji , Nakajima Hideaki , Murata Kazuma , Miyagi Masayuki , Kaito Takashi , Yamada Kei , Banno Tomohiro , Kato Satoshi , Ohba Tetsuro , Inami Satoshi , Fujibayashi Shunsuke , Katoh Hiroyuki , Kanno Haruo , Watanabe Kota , Taneichi Hiroshi , Imagama Shiro , Kawaguchi Yoshiharu , Takeshita Katsushi , Nakamura Masaya , Matsumoto Morio , Yamazaki Masashi , Okawa Atsushi
Published: July 2022

Study Design.

A prospective multicenter study.

Objective.

This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL).

Summary of Background Data.

Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes.

Materials and Methods.

This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses.

Results.

Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% (P<0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery.

Conclusions.

Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL.
Recovery Kinetics after Commonly Performed Minimally Invasive Spine Surgery Procedures
Authors: Shinn Daniel , Mok Jung Kee , Vaishnav Avani S. , Louie Philip K. , Sivaganesan Ahilan , Shahi Pratyush , Dalal Sidhant , Song Junho , Araghi Kasra , Melissaridou Dimitra , Sheha Evan D. , Sandhu Harvinder , Dowdell James , Iyer Sravisht , Qureshi Sheeraz A.
Published: July 2022

Study Design.

Single-center, multi-surgeon, retrospective review.

Objective.

Evaluate the timing of return to commonly performed activities following minimally invasive spine surgery. Identify preoperative factors associated with these outcomes.

Summary of Background Data.

Studies have reported return to activities with open techniques, but the precise timing of when patients return to these activities after minimally invasive surgery remains uncertain.

Methods.

Patients who underwent either minimally invasive lumbar laminectomy (MI-L) or minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) were included. Patient reported outcome measures, return to drive, return to work and discontinuation of opioids data were reviewed. Regression was conducted to identify factors associated with return to driving by 15 days, return to work by 30 days, and for discontinuing opioids by 15 days. A composite group analysis was also performed for patients who returned to all three activities by 30 days.

Results.

In total, 123 MI-L patients and 107 MI-TLIF patients were included. 88.8% of MI-L patients and 96.4% of MI-TLIF patients returned to driving in 11 and 18.5 days, respectively. 91.9% of MI-L patients and 85.7% of MI-TLIF patients returned to work in 14 and 25 days. 88.7% of MI-L patients and 92.6% of MI-TLIF patients discontinued opioids in a median of 7 and 11 days. 96.2% of MI-L patients and 100% of MI-TLIF patients returned to all three activities, with a median of 27 and 31 days, respectively. Male gender (OR 3.57) and preoperative SF-12 PCS (OR 1.08) are associated with return to driving by 15 days. Male gender (OR 3.23) and preoperative SF-12 PCS (OR 1.07) are associated with return to work by 30 days. Preoperative VAS back was associated with decreased odds of discontinuing opioids by 15 days (OR 0.84).

Conclusion.

Most patients return to activity following MI-L and MI-TLIF. These findings serve as an important compass for preoperative counseling.