bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

ABSTRACTRenal 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

Abstract

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 &lt; 0.0001), glioblastoma (IRR = 0.86; P &lt; 0.0001), diffuse/anaplastic astrocytoma (IRR = 0.78; P &lt; 0.0001), oligodendroglioma (IRR = 0.82; P &lt; 0.0001), ependymoma (IRR = 0.88; P = 0.012), and pilocytic astrocytoma (IRR = 0.76; P &lt; 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

Abstract

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 &lt; 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80–9.26]; p &lt; 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 &lt; 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 &lt; 0.01), which was evident in RTK I (p = 0.03) and RTK II (p &lt; 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

AbstractSkin 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractFebuxostat 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.