bluuebunny/crossref_metadata_2025_split huggingface dataset:
A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors—A single‐centre, prospective, explorative study
Authors: Choi Yunsuk , Choi Eun‐Ji , Park Han‐Seung , Lee Jung‐Hee , Lee Je‐Hwan , Lee Young‐Shin , Kang Young‐A , Jeon Mijin , Woo Ji Min , Kang Hyeran , Baek Seunghyun , Kim Su Mi , Bong Chae‐Eun , Lee Kyoo‐Hyung 
Published: November 2022

SummaryIn a prospective, explorative study, the donor‐source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft‐versus‐host disease (GVHD) in HF‐HCT patients (49%, 7%, and 16% for HF‐, MS‐ and UD‐HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF‐HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri‐engraftment acute GVHD was not observed in MS‐HCT or UD‐HCT patients. Additionally, a significantly higher proportion of HF‐HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF‐, MS‐ and UD‐HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non‐relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG‐containing conditioning, stronger donor–patient alloreactivity was observed in HF‐HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.
Early and extensive alterations of glial connexins, distal oligodendrogliopathy type demyelination, and nodal/paranodal pathology are characteristic of multiple system atrophy
Authors: Nishimura Yuji , Masaki Katsuhisa , Matsuse Dai , Yamaguchi Hiroo , Tanaka Tatsunori , Matsuo Eriko , Hayashida Shotaro , Watanabe Mitsuru , Matsushita Takuya , Sadashima Shoko , Sasagasako Naokazu , Yamasaki Ryo , Isobe Noriko , Iwaki Toru , Kira Jun‐ichi 
Published: November 2022

AbstractThe pathological hallmark of multiple system atrophy (MSA) is aberrant accumulation of phosphorylated α‐synuclein in oligodendrocytes, forming glial cytoplasmic inclusions (GCIs). Extensive demyelination occurs particularly in the olivopontocerebellar and striatonigral pathways, but its precise mechanism remains elusive. Glial connexins (Cxs), which form gap junction channels between astrocytes and oligodendrocytes, play critical roles in myelin maintenance, and have not been studied in MSA. Therefore, we immunohistochemically investigated glial Cx changes in the cerebellar afferent fibers in 15 autopsied patients with MSA. We classified demyelinating lesions into three stages based on Klüver–Barrera staining: early (Stage I), intermediate (Stage II), and late (Stage III) stages showing subtle, moderate, and severe myelin reduction, respectively. Myelin‐associated glycoprotein, but not myelin oligodendrocyte glycoprotein, was preferentially decreased in Stage I, suggesting distal oligodendrogliopathy type demyelination. Accumulation of phosphorylated α‐synuclein in oligodendrocytes was frequently seen in Stage I but less frequently observed in Stages II and III. Tubulin polymerization‐promoting protein (TPPP/p25α)‐positive oligodendrocytes were preserved in Stage I but successively decreased in Stages II and III. Even at Stage I, Cx32 was nearly absent from myelin, despite the relative preservation of other nodal proteins, such as neurofascin, claudin‐11/oligodendrocyte‐specific protein, and contactin‐associated protein 1, which successively decreased in the later stages. Cx32 was re‐distributed in the oligodendrocyte cytoplasm and co‐localized with GCIs. Cx47 gradually decreased at the oligodendrocyte surface in a stage‐dependent manner but was not co‐localized with GCIs. Astrocytic Cx43 was down‐regulated in Stage I but up‐regulated in Stages II and III, reflecting astrogliosis. Cx43/Cx47 gap junctions significantly decreased from Stage I to III. Activated microglia/macrophages and T cells infiltrated in Stage I rather than Stages II and III. Therefore, early and extensive alterations of glial Cxs, particularly Cx32 loss, occur in MSA and may accelerate distal oligodendrogliopathy type demyelination and nodal/paranodal dysfunction through disruption of inter‐glial communication.
Determinants of resource use in lizard assemblages from the semiarid Caatinga, Brazil
Authors: Gonçalves‐Sousa José Guilherme , Cavalcante Leonides Azevedo , Mesquita Daniel Oliveira , Ávila Robson Waldemar 
Published: November 2022

AbstractNonsessile animals could partition the use of resources in different axes, reducing the effects of competition and allowing coexistence. Here, we investigated the spatial and trophic niche dimensions in four lizard assemblages in the Neotropical semiarid Caatinga to investigate the determinants of resource use and the extent to which lizards partition their niches. We sampled each lizard assemblage once, for 10 days, in the dry season of 2017 and 2018. In two lizard assemblages, we detected nonrandom niche overlap patterns that were higher or lower than expected by chance. The high niche overlap patterns suggest that either there is intense current competition for available microhabitats or an abundance of microhabitats. The lower niche overlap may be influenced by the presence of species adapted to sandy habitats (psammophilous), suggesting that spatial partitioning detected has historical basis, which is supported by the pPCA results and by the lack of patterns in the realized niche distribution of species across niche space. We detected trophic niche partitioning in three lizard assemblages. In one assemblage, we discovered random spatial and trophic niche overlap patterns, revealing that competition is not a determining factor in the structure of that assemblage. In fact, phylogenetic effects were predominantly the main determinants of resource use in the four studied lizard assemblages. Arid and semiarid habitats cover about one third of land surface of the world. Comparisons between our findings and those from other regions of the world may aid identify general trends in the lizard ecology of dry environments.
Advisory machinery for large‐scale crises and a risky future
Authors: Mitchell James R. 
Published: November 2022

AbstractThis short article provides a practitioner's perspective in response to Iacobucci and Trebilcock's (2022) article “Existential threats: Climate change, pandemics and institutions.” It offers some thoughts on: the many kinds of advisory bodies on whose advice governments can draw; the options for and constraints on institutional change; and what the federal and provincial governments could do to better equip themselves for dealing with the next “existential crisis.” The goal is to point to the full range of sources of scientific and policy advice for governments, to encourage better appreciation of when different sources of advice might be best served by different institutional underpinnings, and to emphasize the important role of the public service and “soft” machinery in fielding advice from diverse sources in an increasingly risky future.
Existential threats: Climate change, pandemics and institutions
Authors: Iacobucci Edward , Trebilcock Michael 
Published: November 2022

AbstractThis article considers the optimal structure of institutions that respond to existential threats such as climate change and pandemics. While science must play a central role in guiding policy responses, there are many values at stake that ought to be reflected in institutional design. There is a distinction between risk assessment, a science‐driven analysis in these contexts, and risk management, in which trade‐offs are considered in responding to the threats. Moreover, the nature of these threats depends on complex, uncertain and fluid scientific knowledge that requires institutions to be sensitive to communication challenges. Finally, institutions should consider collective action problems and defer or delegate to jurisdictions and institutions whose scope of mandate is appropriate. We assess the Canadian response to the COVID‐19 pandemic from an institutional perspective and conclude that, amongst other things, it was insufficiently multidisciplinary, which risked marginalizing the non‐public health costs of policy responses to the pandemic.
Cancer‐associated fibroblasts promote tumor cell growth via miR‐493‐5p in intrahepatic cholangiocarcinoma
Authors: Toshida Katsuya , Itoh Shinji , Harada Noboru , Morinaga Akinari , Yugawa Kyohei , Tomiyama Takahiro , Kosai‐Fujimoto Yukiko , Tomino Takahiro , Kurihara Takeshi , Nagao Yoshihiro , Morita Kazutoyo , Oda Yoshinao , Yoshizumi Tomoharu 
Published: November 2022

AbstractThe association between tumor microenvironment (TME) and cancer‐associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR‐493‐5p on tumor cell lines were examined. Additionally, databases were used to identify miR‐493‐5p targets, and the relationship between prognosis of ICC patients and cocaine‐ and amphetamine‐regulated transcript propeptide (CARTPT), one of the targets of miR‐493‐5p, expression in ICC tissues was retrospectively analyzed. Compared with NF‐derived CM and EVs, CAF‐derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR‐493‐5p was significantly increased in CAF‐derived EVs compared to NF‐derived EVs. Tumor cell lines transfected with miR‐493‐5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence‐free survival rates were significantly worse in the CARTPT‐negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence‐free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR‐493‐5p in EVs.
Immunostimulatory oncolytic activity of coxsackievirus A11 in human malignant pleural mesothelioma
Authors: Okamura Koji , Inoue Hiroyuki , Tanaka Kentaro , Ikematsu Yuki , Furukawa Rie , Ota Keiichi , Yoneshima Yasuto , Iwama Eiji , Okamoto Isamu 
Published: November 2022

AbstractMalignant pleural mesothelioma (MPM) is an aggressive solid cancer with a poor prognosis, whereas coxsackievirus A11 (CVA11) is a potential oncolytic virus for cancer treatment. We here investigated the oncolytic activity of CVA11 with human MPM cell lines. CVA11 infection was cytotoxic in all six MPM cell lines examined and showed no or minimal cytotoxicity toward normal human normal cell lines. MPM cells with a higher surface level of intercellular adhesion molecule‐1 (ICAM‐1) expression tended to be more susceptible to CVA11‐induced cytotoxicity, and a neutralizing antibody to ICAM‐1 attenuated such cytotoxicity. CVA11 infection activated signaling by Akt and extracellular signal‐regulated kinase (ERK) pathways, and inhibitors of such signaling also abrogated CVA11‐mediated cytotoxicity. Furthermore, CVA11 infection‐triggered multiple modes of tumor cell death including apoptosis, pyroptosis, and necroptosis, and such death was accompanied by the release or exposure of the proinflammatory cytokine interleukin‐1β and damage‐associated molecular patterns such as calreticulin, high‐mobility group box‐1, annexin A1, and heat shock protein 70, which are hallmarks of immunogenic cell death. Notably, in vivo treatment of human MPM xenografts with intratumoral CVA11 injection resulted in significant suppression of tumor growth in SCID mice, and all mice infected with CVA11 showed no significant change in body weight. Our findings collectively suggest that the oncolytic activity of CVA11 for MPM is dependent on ICAM‐1 as a virus receptor, as well as on Akt and ERK signaling, and that oncolytic virotherapy with CVA11 is a promising treatment modality with immunostimulatory activity for human MPM.
Changes in survival of patients with non–small cell lung cancer in Japan: An interrupted time series study
Authors: Taniyama Yukari , Oze Isao , Koyanagi Yuriko N. , Kawakatsu Yukino , Ito Yuri , Matsuda Tomohiro , Matsuo Keitaro , Mitsudomi Tetsuya , Ito Hidemi 
Published: November 2022

AbstractThe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) gefitinib and erlotinib were approved for metastatic or relapsed non–small cell lung cancer (NSCLC) in Japan in 2002 and 2007, respectively. EGFR mutation testing was also approved in 2007. Although clinical trials showed efficacy in NSCLC patients harboring activating EGFR mutations, these effects have rarely been reported in real‐world practice. We evaluated changes in survival in NSCLC patients following introduction of these agents and EGFR mutation testing by extracting patients diagnosed with NSCLC from 1993 through 2011 from six prefectural population‐based cancer registries in Japan. Relative survival (RS) was calculated by sex, histological subtype, and cancer stage. We conducted interrupted time series analysis to assess survival changes following introduction of EGFR‐TKIs and EGFR mutation testing. 120,068 patients with NSCLC were analyzed. One‐ and three‐year RS gradually increased in overall NSCLC for men and women. For adenocarcinoma, among men, slopes of 1‐ and 3‐year RS increased steeply in patients diagnosed from 2007 through 2011; among women, significant level increases were seen in 1‐year RS in patients diagnosed in 2002 (4.55% [95% confidence interval: 1.76‐7.33]) and 2007 (3.40% [1.27‐5.52]). These significant level increases were particularly obvious in women with adenocarcinoma at an advanced stage. Our results suggest that recent improvements in survival in men and women with adenocarcinoma are due at least partly to introduction of EGFR‐TKIs into real‐world practice, and to prescription based on appropriate patient selection following introduction of EGFR mutation testing into real‐world practice in Japan.
Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9
Authors: Liang Jiaxin , Liu Qiang , Xia Longzheng , Lin Jinguan , Oyang Linda , Tan Shiming , Peng Qiu , Jiang Xianjie , Xu Xuemeng , Wu Nayiyuan , Tang Yanyan , Su Min , Luo Xia , Yang Yiqing , Liao Qianjin , Zhou Yujuan 
Published: November 2022

AbstractMetabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras‐related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.
The authoritarian trade‐off: A synthetic control analysis of development and social coercion in the Xinjiang Uyghur Autonomous Region
Authors: Peng Linan , Callais Justin T. 
Published: November 2022

AbstractThe Xinjiang Uyghur Autonomous Region (XUAR) has recently experienced a series of policies seeking economic development and intensive methods of social coercion. A unique leader, Chen Quanguo, brought these changes to the XUAR in 2016. This paper seeks to examine the effects of Chen's regime. We specifically examine three outcomes: GDP per capita, arrest rates, and spending on public security. Using the synthetic control method, we find that Chen's regime had no significant effect on the development. However, his policies led to much higher rates of arrest and larger spending on public security.
Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?
Authors: Coupier Antoine , Gallien Yves , Boillot Olivier , Walter Thomas , Guillaud Olivier , Vallin Mélanie , Thimonier Elsa , Erard Domitille , Dumortier Jérôme 
Published: November 2022

AbstractBackgroundMalignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy.MethodsAll LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included.ResultsThe study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1–68) and was 63.0 (18–79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)‐based to an everolimus‐based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5‐year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non‐PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non‐PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy.ConclusionsThe present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.
Risk of cognitive impairment in men with advanced prostate cancer treated with NHAs: A systematic review and network meta‐analysis
Authors: Huang Shi‐Wei , Chen Li‐Chin , Tseng Chi‐Shin , Chen Chung‐Hsin , Yuan Lun‐Hsiang , Shau Wen‐Yi , Pu Yeong‐Shiau 
Published: November 2022

AbstractNovel hormonal agents (NHAs) have significantly improved outcomes in men with advanced prostate cancer. However, it remains unclear whether NHAs are associated with subsequent cognitive impairment. Thus, we sought to perform a network meta‐analysis to compare the risk of cognitive impairment across NHA types. Databases (PubMed, Embase, Scopus, and Web of Science), trial registries (Clinicaltrial.gov), the European Medicines Agency, and the US Food and Drug Administration drug safety reports were searched from inception through July 30, 2021. Eligible studies were clinical trials evaluating the risk of cognitive impairment between NHAs and placebo/standard care. Two independent investigators extracted the data and performed quality assessments using the Cochrane Risk of Bias Tool and ROBINS‐I. We estimated the risk ratios by the frequentist approach and calculated the ranking probabilities of all treatments with the surface under the cumulative ranking probabilities. The primary outcome and secondary outcome were odds ratio (OR) and incidence rate ratio of cognitive impairment, respectively. We identified 15 trials with 14,723 participants comparing HNAs with placebo/standard care. Treatments associated with cognitive impairment, from the most to the least, were enzalutamide (OR, 3.66; 95% confidence interval [CI], 2.84–4.73), apalutamide (OR, 1.76; 95% CI, 1.08–2.87), abiraterone acetate (OR, 1.64; 95% CI, 1.01–2.45), and darolutamide (OR, 1.11 95% CI, 0.51–2.39). After adjustment of treatment time duration, enzalutamide still had the highest risk of cognitive impairment with an incidence rate ratio of 2.17 (95% CI, 1.65–2.78). These findings suggest that NHAs, especially enzalutamide, may increase the risk of cognitive impairment compared with placebo/standard care.
Systematic review with meta‐analysis: Branched‐chain amino acid supplementation in liver disease
Authors: van Dijk Anne M. , Bruins Slot Alexandra S. , Portincasa Piero , Siegerink Sebastiaan N. , Chargi Najiba , Verstraete Carina J. R. , de Bruijne Joep , Vleggaar Frank P. , van Erpecum Karel J. 
Published: November 2022

AbstractBackgroundDietary supplementation with branched‐chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease.MethodsWe searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease‐control group (placebo or no intervention) using search terms ‘liver cirrhosis’, ‘hepatocellular carcinoma’, ‘branched chain amino acids’ and relevant synonyms. Risk of bias was assessed using ROBINS‐I and RoB 2.0 tools. Meta‐analyses were performed with a random‐effects model. Results were reported following EQUATOR guidelines.ResultsOf 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case–control studies, 13 retrospective case–control studies: in total 2308 patients BCAA supplementation, 2876 disease‐controls). Risk of bias was high/serious for almost all studies. According to meta‐analyses, long‐term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event‐free survival (p = .008; RR .61 95% CI .42–.88) and tended to improve overall survival (p = .05; RR .58 95% CI .34–1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA.ConclusionsProphylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients.