bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing Challenges to Mobility Hub Implementation at Suburban Commuter Rail Parking Lots in Greater Toronto
Authors: Bowman Marcus 
Published: May 2021

<p>This paper examines the issue of parking demand and station area office development at station area mobility hubs. Metrolinx, the Provincial regional transit-planning agency in the Greater Toronto and Hamilton Area, has identified mobility hubs at locations with high transit connectivity and potential for mixed-use intensification. The Mobility Hub Guidelines provide a vision that emphasizes placemaking and station functionality. Attracting the desired form of development to mobility hubs will require a new approach to parking management and station access. This must address market realities and the double parking burden between the station and new developments. A variety of approaches are considered which could be implemented in various combinations at different mobility hub locations. These approaches include fine-tuning parking standards, reducing parking demand and facilitating a modal split shift in station access. The paper highlights that a number of innovative approaches are available, but will require proactive involvement from interested agencies. </p>
Gambaran Kemampuan Membayar Iuran BPJS Kesehatan pada Pedagang di Pasar Terong Kota Makassar
Authors: Syamsinar Suci , Batara Andi Surahman , A. Rizki Amelia  
Published: May 2021

Tercatat berdasarkan jumlah perserta yang menungak di Kelurahan Wajo Baru sebanyak 931 atau 11,40% peserta, dengan jumlah penunggakan keseluruhan di Kecamatan Bontoala sebanyak 8.164 peserta (BPJS 2020). Kemampuan membayar merupakan salah satu pertimbangan yang perlu diperhatikan dalam penetapan tarif iuran BPJS Kesehatan. Peran serta masyarakat dalam membayar iuran jaminan kesehatan sangat bergantung dengan Kemampuan Membayar (Ability to Pay) yang dimiliki oleh masyarakat. Tujuan penelitian ini untuk mengetahui gambaran besar kemanpuan (ATP) membayar iuran BPJS Kesehatan pada pedagang di Pasar Terong kelurahan Wajo Baru Kecamatan Bontoala Kota Makassar. Desain penelitian ini adalah penelitian kuantitatif dengan menggunakan studi deskriptif dengan menggunakan metode survey, merupakan penelitian deskriptif yang dilakukan terhadap sekumpulan objek. Populasi dalam penelitian ini adalah seluruh pedagang peserta BPJS mandiri. Sampel dalam penelitian ini sebanyak 92 responden. Hasil yang diperoleh dari penelitian yaitu jumlah anggota keluarga tertinggi adalah ≤ 4 jumlah anggota keluarga sebanyak 56 responden (60.9%) dan yang terendah adalah >4 sebanyak 36 responden (39.1%), mampu sebanyak 52 responden (56.5%) dan yang terendah adalah tidak mampu sebanyak 40 responden (43.5%), kelas III tertinggi sebanyak 59 responden (64.1%) dan yang terendah adalah kelas II sebanyak 33 responden (35.9%).
Relationship Between Different Risk Factor Patterns and Follow-Up Outcomes in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Chen Si , Che Qianzi , Zheng Qiwen , Zhang Yan , Jia Jia , Wu Yiqun , Huo Yong , Chen Dafang 
Published: May 2021

Objective: Few studies have been concerned with the combined influences of the presence of multiple risk factors on follow-up outcomes in AMI patients. Our study aimed to identify risk factor patterns that may be associated with 1-year survival in male patients with ST-segment elevation myocardial infarction (STEMI).Methods: Data were from the China STEMI Care Project Phase 2 (CSCAP-2) collected between 2015 and 2018. A total of 15,675 male STEMI patients were enrolled in this study. Risk factor patterns were characterized using latent class analysis (LCA) according to seven risk factors. Associations between risk factor patterns and follow-up outcomes, including the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death, were investigated by Cox proportional hazard regression analysis.Results: We obtained four risk factor patterns as “young and middle-aged with low levels of multimorbidity,” “middle-aged with overweight,” “middle-aged and elderly with normal weight,” and “elderly with high multimorbidity.” Four patterns had significant differences in event-free survival (P &lt; 0.001). As compared with the patients of “young and middle-aged with low levels of multimorbidity” pattern, the risk of incidence of MACCE and all-cause death were increased in patients of “middle-aged with overweight” pattern (All-cause death: HR = 1.70, 95% CI:1.29~2.23; MACCE: HR = 1.49, 95% CI:1.29~1.72), “middle-aged and elderly with normal weight” pattern (All-cause death: HR = 3.04, 95% CI: 2.33~3.98; MACCE: HR = 1.82, 95% CI: 1.56~2.12), and “elderly with high multimorbidity” pattern (All-cause death: HR = 5.78, 95% CI: 4.49~7.42; MACCE: HR = 2.67, 95% CI: 2.31~3.10).Conclusions: By adopting a Latent Class Analysis Approach, STEMI patients can be characterized into four risk factor patterns with significantly different prognosis. The data is useful for the improvement of community health management in each specific subgroup of patients, which indicates a particular risk factor pattern.
Reconstruction of Cultivated Land in the Northeast Margin of Qinghai–Tibetan Plateau and Anthropogenic Impacts on Palaeo-Environment During the Mid-Holocene
Authors: Wende Zhuoma , Hou Guangliang , Gao Jingyi , Chen Xiaoliang , Jin Sunmei , Lancuo Zhuoma 
Published: May 2021

The study of past global change is paramount to comprehending the present and future, as well as to better understand the mechanisms and influences of human–land interactions in a given region. The northeastern margin of the Qinghai–Tibetan Plateau has complex natural environments, sensitive to global change, and renowned for its long history of human occupancy. This makes it an ideal region for the study of anthropogenic impacts on the paleo-natural environment. This paper reconstructed the prehistoric temporal and spatial distribution of cultivated lands on the northeast margin of Qinghai–Tibetan Plateau, and analyzed the Dianziping pollen assemblage to disclose the anthropogenic impacts on the paleo-environment. The results demonstrated that around 4.3–4.0 cal ka BP, the rapid development of the Majiayao culture boosted the population to approximately 39,200 people, over 460 km2 of the land area was converted to cropland, concomitantly, evidence of tree pollen decreased significantly. This marked the earliest identification of anthropogenic impacts on vegetation through agricultural activity in this region. At 4.0–3.6 cal ka BP, the population appeared to have diminished in conjunction with the cultivated land area. Nevertheless, forested areas continued to decrease, primarily due to adverse climatic conditions, but, anthropogenic activities played an undeniable role. Dianziping profile demonstrated the existence of natural forest in the Hehuang Valley during Qijia cultural Period. There was also evidence for the occurrence of regional fire events, suggesting large-scale burning of land cover in the area. This further illustrates anthropogenic impacts. At 3.6–2.6 cal ka BP, populations reached approximately 61,300 people, coinciding with the peak of cropland expansion. Consequently, more of the natural vegetation were converted to crops, and the superimposed influences of farming and grazing aggravated the process of deforestation and vegetation succession. Likewise, deforestation during the historical period can be explained, mostly by human driven causes with limited influence from climatic factors. The extensive exploitation of forest and expansion of cropland consequently resulted in extensive land deterioration, leaving the region with forest islands scattered in less populated, mountainous regions.
PiggyBac-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report
Authors: Li Chenggong , Sun Yan , Wang Jing , Tang Lu , Jiang Huiwen , Guo Tao , Liu Lin , Wu Yaohui , Ai Lisha , Xia Linghui , Wu Jianjun , Lin Zhicai , Qian Qijun , Hu Yu , Mei Heng 
Published: May 2021

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. PiggyBac transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with piggyBac-generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of piggyBac-produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.
Colorectal Carcinoma Affected Patients Are Significantly Poor Responders Against the Oncogenic JC Polyomavirus
Authors: Torreggiani Elena , Bononi Ilaria , Pietrobon Silvia , Mazzoni Elisa , Guerra Giovanni , Feo Carlo , Martini Fernanda , Tognon Mauro 
Published: May 2021

BackgroundMany investigations reported the association between human tumors and JCPyV, a polyomavirus with oncogenic potential. The association has been supported by studies that found JCPyV footprints in CRC and gliomas of different types. Indeed, JCPyV footprints including its nucleic acids and Tag oncoprotein have been revealed in CRC tissues.MethodsHerein, sera from colorectal carcinoma (CRC) affected patients and healthy individuals (HS), employed as control, were analysed for immunoglobulin G (IgG) antibodies against specific JCPyV viral capsid protein 1 (VP1) antigens. The investigation was carried out employing an innovative immunological assay. Indeed, an indirect enzyme-linked immunosorbent assay (ELISA) with JCPyV VP1 mimotopes was used. JCPyV VP1 mimotopes consisted of synthetic peptides mimicking VP1 epitopes.ResultsSera from CRC affected patients, evaluated using indirect ELISAs with synthetic mimotopes, showed a significant lower prevalence of IgG antibodies against JCPyV VP1 mimotopes (26%) compared to HS (51%), p&lt;0.005. These data were confirmed by another method, the hemagglutination inhibition (HAI) assay. Altogether these results, i.e. the prevalence of serum IgG antibodies against JCPyV VP1 mimotopes from patients with CRC is approximately 50% lower than in HS, are of interest.DiscussionOur data suggest that patients with CRC are significantly poor responders against JCPyV VP1 antigens. It is possible that CRC patients are affected by a specific immunological deregulation. This immunological dysfunction, revelled in CRC patients, may account for their predisposition to the colorectal carcinoma onset.
Enhancement of the Tolerogenic Phenotype in the Liver by ImmTOR Nanoparticles
Authors: Ilyinskii Petr O. , Roy Christopher J. , LePrevost Julie , Rizzo Gina L. , Kishimoto Takashi Kei 
Published: May 2021

ImmTOR biodegradable nanoparticles encapsulating rapamycin have been shown to induce a durable tolerogenic immune response to co-administered biologics and gene therapy vectors. Prior mechanism of action studies have demonstrated selective biodistribution of ImmTOR to the spleen and liver following intravenous (IV) administration. In the spleen, ImmTOR has been shown to induce tolerogenic dendritic cells and antigen-specific regulatory T cells and inhibit antigen-specific B cell activation. Splenectomy of mice resulted in partial but incomplete abrogation of the tolerogenic immune response induced by ImmTOR. Here we investigated the ability of ImmTOR to enhance the tolerogenic environment in the liver. All the major resident populations of liver cells, including liver sinusoidal endothelial cells (LSECs), Kupffer cells (KC), stellate cells (SC), and hepatocytes, actively took up fluorescent-labeled ImmTOR particles, which resulted in downregulation of MHC class II and co-stimulatory molecules and upregulation of the PD-L1 checkpoint molecule. The LSEC, known to play an important role in hepatic tolerance induction, emerged as a key target cell for ImmTOR. LSEC isolated from ImmTOR treated mice inhibited antigen-specific activation of ovalbumin-specific OT-II T cells. The tolerogenic environment led to a multi-pronged modulation of hepatic T cell populations, resulting in an increase in T cells with a regulatory phenotype, upregulation of PD-1 on CD4+and CD8+T cells, and the emergence of a large population of CD4–CD8–(double negative) T cells. ImmTOR treatment protected mice in a concanavalin A-induced model of acute hepatitis, as evidenced by reduced production of inflammatory cytokines, infiltrate of activated leukocytes, and tissue necrosis. Modulation of T cell phenotype was seen to a lesser extent after administration by empty nanoparticles, but not free rapamycin. The upregulation of PD-1, but not the appearance of double negative T cells, was inhibited by antibodies against PD-L1 or CTLA-4. These results suggest that the liver may contribute to the tolerogenic properties of ImmTOR treatment.
Identification of an Autoantibody Against ErbB-3-Binding Protein-1 in the Sera of Patients With Chronic Hepatitis B Virus Infection
Authors: Jiang Li , Niu Wei , Zheng Qian , Meng Gang , Chen Xiaoling , Zhang Mengjun , Deng Guohong , Mao Qing , Wang Li 
Published: May 2021

BackgroundStudies have shown that autoimmune response contributes to chronic hepatitis B (CHB) development.AimThis study aimed to identify autoantibodies in the sera of patients with CHB and to investigate the association of autoimmune response with disease severity in CHB.MethodsProteins from human liver carcinoma cell line HepG2 were separated by two-dimensional electrophoresis. The candidate autoantigens were recognized by serum autoantibodies from Chinese CHB patients. Immunohistochemical staining was performed to determine the hepatic expression of the autoantigen in CHB patients with different inflammatory grades. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the prevalence and the levels of serum autoantibody in CHB patients with different disease severity. Flow cytometry analysis was carried out to assess the autoreactive T cell response in the peripheral circulation of CHB patients.ResultsErbB-3-binding protein-1 (EBP-1) was identified as an autoantigen of serum autoantibodies in CBP patients. EBP-1 protein expression was upregulated in the liver of CHB patients with high-grade hepatic inflammation. The prevalence and levels of serum anti-EBP1 IgG were significantly increased in CHB patients with severe diseases compared with those with mild or moderate diseases, but none was detectable in the healthy controls. EBP-1 peptides induced proinflammatory cytokine expression in CD4+ T cells from CHB patients.ConclusionOur results demonstrate the presence of an autoantibody against EBP-1 in the sera as well as EBP-1-reactive T cells in the peripheral blood of CHB patient. EBP-1-induced autoimmune response is positively associated with the disease severity, suggesting that EBP-1-induced autoimmune response possibly contributes to progressive liver failure.
Connective Tissue Growth Factor Is Overexpressed in Explant Lung Tissue and Broncho-Alveolar Lavage in Transplant-Related Pulmonary Fibrosis
Authors: Vanstapel Arno , Goldschmeding Roel , Broekhuizen Roel , Nguyen Tri , Sacreas Annelore , Kaes Janne , Heigl Tobias , Verleden Stijn E. , De Zutter Alexandra , Verleden Geert , Weynand Birgit , Verbeken Erik , Ceulemans Laurens J. , Van Raemdonck Dirk E. , Neyrinck Arne P. , Schoemans Helene M. , Vanaudenaerde Bart M. , Vos Robin 
Published: May 2021

BackgroundConnective tissue growth factor (CTGF) is an important mediator in several fibrotic diseases, including lung fibrosis. We investigated CTGF-expression in chronic lung allograft dysfunction (CLAD) and pulmonary graft-versus-host disease (GVHD).Materials and MethodsCTGF expression was assessed by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry in end-stage CLAD explant lung tissue (bronchiolitis obliterans syndrome (BOS), n=20; restrictive allograft syndrome (RAS), n=20), pulmonary GHVD (n=9). Unused donor lungs served as control group (n=20). Next, 60 matched lung transplant recipients (BOS, n=20; RAS, n=20; stable lung transplant recipients, n=20) were included for analysis of CTGF protein levels in plasma and broncho-alveolar lavage (BAL) fluid at 3 months post-transplant, 1 year post-transplant, at CLAD diagnosis or 2 years post-transplant in stable patients.ResultsqPCR revealed an overall significant difference in the relative content of CTGF mRNA in BOS, RAS and pulmonary GVHD vs. controls (p=0.014). Immunohistochemistry showed a significant higher percentage and intensity of CTGF-positive respiratory epithelial cells in BOS, RAS and pulmonary GVHD patients vs. controls (p&lt;0.0001). BAL CTGF protein levels were significantly higher at 3 months post-transplant in future RAS vs. stable or BOS (p=0.028). At CLAD diagnosis, BAL protein content was significantly increased in RAS patients vs. stable (p=0.0007) and BOS patients (p=0.042). CTGF plasma values were similar in BOS, RAS, and stable patients (p=0.74).ConclusionsLung CTGF-expression is increased in end-stage CLAD and pulmonary GVHD; and higher CTGF-levels are present in BAL of RAS patients at CLAD diagnosis. Our results suggest a potential role for CTGF in CLAD, especially RAS, and pulmonary GVHD.
When the Good Syndrome Goes Bad: A Systematic Literature Review
Authors: Shi Yiyun , Wang Chen 
Published: May 2021

BackgroundGood syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging from various infections to autoimmunity.ObjectiveThis study was to summarize patient characteristics, identify prognostic factors and define clinical subgroups of Good syndrome.MethodsA systematic literature review was conducted to include patients with Good syndrome identified in PubMed, Embase and Cochrane databases between January 2010 and November 2020. Logistic and Cox regressions were used to identify prognostic factors impacting outcomes. Clinical subgroups were defined by multiple correspondence analysis and unsupervised hierarchical clustering. A decision tree was constructed to characterize the subgroup placement of cases.ResultsOf 162 patients included in the current study, the median age at diagnosis was 58 years and 51% were male. Type AB was the most common histological subtype of thymoma, and infections as well as concurrent autoimmune disorders were identified in 92.6% and 51.2% patients, respectively. Laboratory workup showed typical findings of combined immunodeficiency. Thymoma status (odds ratio [OR] 4.157, confidence interval [CI] 1.219-14.177, p = 0.023), infections related to cellular immunity defects (OR 3.324, 95% CI 1.100-10.046, p = 0.033), infections of sinopulmonary tract (OR 14.351, 95% CI 2.525-81.576, p = 0.003), central nerve system (OR 6.403, 95% CI 1.205-34.027, p = 0.029) as well as bloodstream (OR 6.917, 95% CI 1.519-31.505, p = 0.012) were independent prognostic factors. The 10-year overall survival was 53.7%. Cluster analysis revealed three clinical subgroups with distinct characteristics and prognosis (cluster 1, infections related to cellular immunity defects; cluster 2, infections related to other immunity defects; cluster 3, infections related to humoral and phagocytic immunity defects). A decision tree using infection types (related to humoral and cellular immunity defects) could place patients into corresponding clusters with an overall correct prediction of 72.2%.ConclusionsInfection type and site were the main prognostic factors impacting survival of patients with Good syndrome. We identified three subgroups within Good syndrome associated with distinct clinical features, which may facilitate the study of underlying pathogenesis as well as development of targeted therapy.
Multi-Atlas MRI-Based Striatum Segmentation for 123I-FP-CIT SPECT (DAT-SPECT) Compared With the Bolt Method and SPECT-Atlas-Based Segmentation Method Toward the Accurate Diagnosis of Parkinson's Disease/Syndrome
Authors: Sohara Koji , Sekine Tetsuro , Tateno Amane , Mizumura Sunao , Suda Masaya , Sakayori Takeshi , Okubo Yoshiro , Kumita Shin-ichiro 
Published: May 2021

Aims: This study aimed to analyze the performance of multi-atlas MRI-based parcellation for 123I-FP-CIT SPECT (DAT-SPECT) in healthy volunteers. The proposed method was compared with the SPECT-atlas-based and Bolt methods. 18F-FE-PE2I-PET (DAT-PET) was used as a reference.Methods: Thirty healthy subjects underwent DAT-SPECT, DAT-PET, and 3D-T1WI-MRI. We calculated the striatum uptake ratio (SUR/SBR), caudate uptake ratio (CUR), and putamen uptake ratio (PUR) for DAT-SPECT using the multi-atlas MRI-based method, SPECT-atlas-based method, and Bolt method. In the multi-atlas MRI-based method, the cerebellum, occipital cortex, and whole-brain were used as reference regions. The correlation of age with DAT-SPECT activity and the correlations of SUR/SBR, CUR, and PUR between DAT-SPECT and DAT-PET were calculated by each of the three methods.Results: The correlation between age and SUR/SBR for DAT-SPECT based on the multi-atlas MRI-based method was comparable to that based on the SPECT-atlas-based method (r = −0.441 to −0.496 vs. −0.488). The highest correlation between DAT-SPECT and DAT-PET was observed using the multi-atlas MRI-based method with the occipital lobe defined as the reference region compared with the SPECT-atlas-based and Bolt methods (SUR, CUR, and PUR: 0.687, 0.723, and 0.676 vs. 0.698, 0.660, and 0.616 vs. 0.655).Conclusion: Multi-atlas MRI-based parcellation with the occipital lobe defined as the reference region was at least comparable to the clinical methods.