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关键词： Prognostic factors   Rituximab   CHOP   Large B-cell lymphoma   Primary mediastinal  

摘要： Background R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. Materials and Methods We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients <= 65 years treated with R-CHOP +/- radiotherapy in a multicenter setting in Greece and Cyprus. Results With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) >= 2 times upper limit of normal (model A) were significantly associated with FFP;E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%-27% of patients [pts]) with approximately 19%-23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. Conclusion The combination of E/IV with either bulky disease or LDH >= 2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. Implications for Practice By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radioth

关键词： Squamous cell carcinoma   Secondary primary carcinoma   Pectoralis major myocutaneous flap   Oral cavity   Metaplastic transformation  

摘要： A 54-year-old man presented with a second primary tongue squamous cell carcinoma, which developed in the pectoralis major myocutaneous flap used for the reconstruction of the right side of the tongue 20 years previously. The patient had originally undergone concurrent chemoradiotherapy and subtotal glossectomy. We believe that the carcinoma was likely caused by metaplastic transformation of the flap skin due to its chronic exposure to stimuli not normally experienced by the skin. The findings in this case suggest that patient education and long-term follow-up are required following flap reconstruction in cases of advanced oral cancer. (C) 2021 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.

关键词： carcinoma of unknown primary   cervical intraepithelial neoplasia   human papillomavirus   squamous cell carcinoma   synchronous cancer   TP53  

摘要： We report a case of synchronous high-grade cervical intraepithelial neoplasia (CIN) and metastatic squamous cell carcinomas (SCCs) of unknown primary in the rectum. A 74-year-old woman was diagnosed with CIN3 by biopsy of the uterine cervix. Magnetic resonance imaging showed two masses in the outer rectal wall. They were diagnosed as SCCs by transrectal biopsy from one mass. On surgical treatment, CIN3 and SCCs in the rectum were identified, respectively. Pathological analysis revealed that SCCs were observed in serosa of the rectum, not mucosa, indicating that these tumors were metastatic SCCs. Gene analysis showed HPV31-positive and TP53 mutation in CIN3, and HPV16-positive in rectal SCCs. Pretreatment examination did not detect the primary site of metastatic SCCs in the rectum. We diagnosed the patient with synchronous CIN3 and metastatic SCCs of unknown primary in the rectum. In this case, gene analysis was useful to clarify the relationship between CIN3 and SCCs.

关键词： Epstein-Barr virus   BRLF1   Primary infection   Transcriptome   Pre-mRNA splicing  

摘要： The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

关键词： peptidesparasitedisulfidepeptide chemical synthesisautoimmune diseasecolitisprotein structure  

摘要： The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% of the world's population. Current treatments available for autoimmune diseases are inadequate, expensive, and tend to focus on symptommanagement rather than cure. Clinical trials have shown that live helminthic therapy can decrease chronic inflammation associated with inflammatory bowel disease and other gastrointestinal autoimmune inflammatory conditions. As an alternative and better controlled approach to live infection, we have identified and characterized two peptides, Acan1 and Nak1, from the excretory/secretory component of parasitic hookworms for their therapeutic activity on experimental colitis. WesynthesizedAcan1 andNak1 peptides fromthe Ancylostoma caninum and Necator americanus hookworms and assessed their structures and protective properties in human cell-based assays and in a mouse model of acute colitis. Acan1 and Nak1 displayed anticolitic properties via significantly reducing weight loss and colon atrophy, edema, ulceration, and necrosis in 2,4,6-trinitrobenzene sulfonic acid-exposed mice. These hookworm peptides prevented mucosal loss of goblet cells and preserved intestinal architecture. Acan1 upregulated genes responsible for the repair and restitution of ulcerated epithelium, whereas Nak1 downregulated genes responsible for epithelial cell migration and apoptotic cell signaling within the colon. These peptides were nontoxic and displayed key immunomodulatory functions in human peripheral blood mononuclear cells by suppressing CD4(+) T cell proliferation and inhibiting IL-2 and TNF production. We conclude that Acan1 and Nak1 warrant further development as therapeutics for the treatment of autoimmunity, particularly gastrointestinal inflammatory conditions.

关键词： Bovine   Primary cells   Respiratory epithelial cells   Influenza D virus   Nasal turbinate   Soft palate   Trachea  

摘要： Influenza D virus (IDV) is a novel type of influenza virus that infects and causes respiratory illness in bovines. Lack of host-specific in vitro model that can recapitulate morphology and physiology of in vivo airway epithelial cells has impeded the study of IDV infection. Here, we established and characterized bovine primary respiratory epithelial cells from nasal turbinate, soft palate, and trachea of the same calf. All three cell types showed characteristics peculiar of epithelial cells, polarized into apical-basolateral membrane, and formed tight junctions. Furthermore, these cells expressed both alpha-2,3- and alpha-2,6-linked sialic acids with alpha-2,3 linkage being more abundant. IDV strains replicated to high titers in these cells, while influenza A and B viruses exhibited moderate to low titers, with influenza C virus replication not detected. These findings suggest that bovine primary airway epithelial cells can be utilized to model infection biology and pathophysiology of IDV and other respiratory pathogens.

关键词： evolution of co‐   operation   natural selection   simulation   theory  

摘要： A fundamental task of evolutionary biology is to explain the pervasive impression of organismal design in nature, including traits benefiting kin. Inclusive fitness is considered by many to be a crucial piece in this puzzle, despite ongoing discussion about its scope and limitations. Here, we use individual-based simulations to study what quantity (if any) individual organisms become adapted to maximize when genetic architectures are more or less suitable for the presumed main driver of biological adaptation, namely cumulative multi-locus evolution. As an expository device, we focus on a hypothetical situation called Charlesworth's paradox, in which altruism is seemingly predicted to evolve, yet altruists immediately perish along with their altruistic genes. Our results support a recently proposed re-definition of inclusive fitness, which is concerned with the adaptive design of whole organisms as shaped by multi-locus evolution, rather than with selection for any focal gene. They also illustrate how our conceptual understanding of adaptation at the phenotypic level should inform our choice of genetic assumptions in abstract simplified models.

关键词： NSCLC   relapse   recurrence   survival   utilization  

摘要： Aims Adjuvant chemotherapy has been shown to improve survival in patients with completely resected early-stage non-small cell lung cancer (NSCLC). This study evaluated real-world relapse rates and healthcare resource utilization in patients with stage II-IIIB NSCLC receiving adjuvant therapy in a community oncology setting after complete resection. Patients and Methods The study included patients with stage II-IIIB NSCLC and complete resection receiving any adjuvant therapy during 06/2008-04/2017 at US Oncology Network clinics, with follow-up through 04/2019. Primary endpoints were rate of relapse, time to relapse (TTR), disease-free survival (DFS), overall survival (OS), and monthly emergency department (ED) visits and hospitalizations before and after relapse. Results The study identified 456 patients;median age was 66 years, 50% were male. In patients with relapse (45.2%), median follow-up was 31.7 months and median TTR was 13.7 months. Median DFS in the overall population was 42.9 months. Median OS was 82.4 months in the overall population and shorter in patients with relapse than without relapse (41.6 months vs. not reached, p < 0.0001). Patients with relapse had significantly more monthly ED visits (mean [SD] 0.10 [0.24] vs. 0.03 [0.08], p < 0.0001) and hospitalizations (mean [SD] 0.20 [0.43] vs. 0.05 [0.10], p < 0.0001) following relapse than before relapse. Conclusions Patients with stage II-IIIB NSCLC treated with adjuvant therapy after complete resection had high relapse rates, reduced survival, and significantly increased healthcare resource use when relapse occurred. New therapeutic options to reduce relapse rates in patients with early-stage NSCLC could reduce healthcare utilization and costs.

关键词： Wearable healthcare   convolution neural network (CNN)   ECG classification   resource efficiency   global average pooling  

摘要： Nowadays, with the increasing shortage of traditional medical resources, the existing portable monitoring healthcare device is no longer satisfactory. Thus, wearable healthcare device with diagnostic capability is becoming much more desirable. However, the design of wearable healthcare device faces the challenge of limited hardware resource and high diagnostic accuracy. In this paper, an efficient hardware architecture is proposed to implement a 1-D CNN with global average pooling (GAP) specially for embedded electrocardiogram (ECG) classification. The GAP is implemented by substituting division into shifting operation without extra computing resource consumption and it can largely reduce the parameters of the network. The fully pipelined processing unit (PU) array is designed to increase computing efficiency. A sign bit based dynamic activation strategy is developed for removing redundant multiplications and resource consumption of ReLU. The proposed efficient hardware architecture is implemented on Xilinx Zyny ZC706 hoard and achieves an average performance of 25.7 GOP/s under 200-MHz with resource consumption of 1538 LUT, which makes resource efficiency improved by more than 3x compared with non-optimized case. The averaged classification accuracy of five ECG beats classes is 99.10%. In brief, the proposed efficient hardware design is prospective for wearable healthcare device especially in ECG classification area.

关键词： Anterior chamber   PACD   Low-add-power IOL   Cataract surgery   Hydrophilic  

摘要： Purpose To evaluate the temporary changes in visual outcomes and anterior segment parameters after cataract surgery plus low-add bifocal intraocular lens (IOL) implantation for primary angle closure disease (PACD). Methods This retrospective comparative case-control study included two groups: low-add-power segmented IOL and monofocal IOL. Postoperative examination involved evaluation of uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), uncorrected intermediate visual acuity (UIVA), and spherical equivalent (SE). Anterior segment examination was performed using anterior segment optical coherence tomography. Results This study included 19 eyes of 11 consecutive patients who underwent cataract surgery. The low-add group had better UDVA than the monofocal group at 3 months postoperatively, better UIVA at 1 month postoperatively, better UNVA at 1 week postoperatively. In the low-add group, SE increased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the monofocal group, objective SE decreased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the low-add group, the anterior chamber depth (ACD) became significantly deep gradually at 1 and 3 months compared with at 1 week postoperatively. In the monofocal group, the ACD became significantly shallow gradually at 1 and 3 months than at 1 week postoperatively. Conclusion The low-add-power segmented IOL achieved better far and intermediate distance visual acuity after cataract surgery in PACD patients than did the monofocal IOL. The ACD became deeper and SE showed a hyperopic shift with the low-add-power segmented IOL at 1 and 3 months after cataract surgery compared with at 1 week after cataract surgery.