bluuebunny/crossref_metadata_2025_split huggingface dataset:
SEPATH: benchmarking the search for pathogens in human tissue whole genome sequence data leads to template pipelines
Authors: Gihawi Abraham , Rallapalli Ghanasyam , Hurst Rachel , Cooper Colin S. , Leggett Richard M. , Brewer Daniel S. 
Published: October 2019

Abstract

Background
Human tissue is increasingly being whole genome sequenced as we transition into an era of genomic medicine. With this arises the potential to detect sequences originating from microorganisms, including pathogens amid the plethora of human sequencing reads. In cancer research, the tumorigenic ability of pathogens is being recognized, for example, Helicobacter pylori and human papillomavirus in the cases of gastric non-cardia and cervical carcinomas, respectively. As of yet, no benchmark has been carried out on the performance of computational approaches for bacterial and viral detection within host-dominated sequence data.

Results
We present the results of benchmarking over 70 distinct combinations of tools and parameters on 100 simulated cancer datasets spiked with realistic proportions of bacteria. mOTUs2 and Kraken are the highest performing individual tools achieving median genus-level F1 scores of 0.90 and 0.91, respectively. mOTUs2 demonstrates a high performance in estimating bacterial proportions. Employing Kraken on unassembled sequencing reads produces a good but variable performance depending on post-classification filtering parameters. These approaches are investigated on a selection of cervical and gastric cancer whole genome sequences where Alphapapillomavirus and Helicobacter are detected in addition to a variety of other interesting genera.

Conclusions
We provide the top-performing pipelines from this benchmark in a unifying tool called SEPATH, which is amenable to high throughput sequencing studies across a range of high-performance computing clusters. SEPATH provides a benchmarked and convenient approach to detect pathogens in tissue sequence data helping to determine the relationship between metagenomics and disease.
Treatment of lumbar vertebra epithelioid hemangioma with radiation therapy: a case report
Authors: Siltumens Aldis P. , Smith Na L. , Sharain Rosalind F. , Haddock Michael G. , Hooten W. Michael 
Published: October 2019

Abstract

Background
Although epithelioid hemangiomas involving bone have been described in previous case reports and case series, the effects of radiation therapy on vertebral epithelioid hemangioma has not been fully reported. Here we provide a case report of tumor response to radiation therapy in a young adult with a large epithelioid hemangioma involving the fourth lumbar vertebrae.

Case presentation
A 27-year-old Latino man with a past medical history of type 1 diabetes and a 3-year history of low back pain presented to a hospital emergency department following acute worsening of back pain. On transfer to our tertiary medical center, he described the pain as “shock-like” which originated at the lateral aspect of his right hip and radiated down to his right knee. Paresthesia was also reported along the medial aspect of his lower right leg. Imaging included a computed tomography scan and magnetic resonance imaging which revealed fourth lumbar and right iliac lytic bone lesions. Image-guided biopsies of the lytic lesions were consistent with a diagnosis of epithelioid hemangioma and radiation therapy was recommended as the primary treatment. Our patient’s low back and leg pain were initially managed with acetaminophen, oxycodone, pregabalin, and lidocaine patch 5%. He noted improvement in pain after his third fraction of radiation. Pain intensity continued to decline and oxycodone was discontinued.

Conclusions
This case report demonstrates an unusual etiology of back and leg pain in a young man and elucidates the palliative effects of radiation therapy for epithelioid hemangioma involving the lumbar spine.
Recombinant expressing angiopep-2 fused anti-VEGF single chain Fab (scFab) could cross blood–brain barrier and target glioma
Authors: Ji Xuemei , Wang Hongyan , Chen Yue , Zhou Junfei , Liu Yu 
Published: October 2019

Abstract
In 2009, the FDA approved bevacizumab for the treatment of adult patients diagnosed with recurrent glioblastoma. However, the poor permeability of the macromolecules across the blood–brain barrier, determined by multifactorial anatomical and physiological milieu, restricts the clinical therapeutic effect of bevacizumab. The low-density lipoprotein receptor related protein 1 (LRP1) is highly expressed in the endothelial cells of the brain capillary and the glioma cells. Angiopep-2 (ANG) is a 19-aa oligopeptide that can bind to LRP1 and penetrate the blood–brain barrier by receptor-mediated transport. Therefore, ANG can be used as a dual-targeting drug delivery carrier into the brain and the glioma sites. In this study, ANG gene was fused with the C-terminal domain of single-chain antigen binding fragment (scFab) of the anti-VEGF antibody and recombinant scFab-ANG protein was expressed and purified using Rosatte (DE3) strain. We confirmed that ANG could carry anti-VEGF-scFab, penetrate a three-dimensional model of the brain tumor, and cross the hCMEC/D3 monolayer in the in vitro blood–brain barrier model. The animal experiments demonstrated that 3 h after the tail intravenous protein injection, the fluorescent signals in the brains of the mice in the scFab-ANG group were stronger than that in the scFab group. Furthermore, the study of the in situ rat glioma model shows that scFab-ANG could target glioma while anti-VEGF-scFab could not. These findings indicate that scFab-ANG had stronger transepithelial permeability and glioma targeting capacity. Thus, it can be a potential candidate drug for glioblastoma therapy.
Dietary fibre enrichment of supplemental feed modulates the development of the intestinal tract in suckling piglets
Authors: Van Hees H. M. J. , Davids M. , Maes D. , Millet S. , Possemiers S. , den Hartog L. A. , van Kempen T. A. T. G. , Janssens G. P. J. 
Published: October 2019

Abstract

Background
Commercial pre-weaning diets are formulated to be highly digestible and nutrient-dense and contain low levels of dietary fibre. In contrast, pigs in a natural setting are manipulating fibre-rich plant material from a young age. Moreover, dietary fibre affects gastrointestinal tract (GIT) development and health in older pigs. We hypothesised that supplemental diets that contain vegetal fibres are accelerating GIT development in suckling piglets in terms of size and functionality. From d 2 of life, sow-suckled piglets had access to a low fibre diet (CON), a diet with a fermentable long-chain arabinoxylan (lc-AXOS), a diet with a largely non-fermentable purified cellulose (CELL), or a diet containing both fibres. During the initial 2 weeks, the control diet was a high-density milk replacer, followed by a dry and highly digestible creep meal. Upon weaning at 25 d, 15 piglets from each treatment group, identified as eaters and originating from six or seven litters, were sacrificed for post-mortem examination of GIT morphology, small intestinal permeability and metabolic profile of the digesta. The microbiota composition of the mid-colon was evaluated in a sub-set of ten piglets.

Results
No major statistical interactions between the fibre sources were observed. Piglets consumed the fibre-containing milk supplements and creep diets well. Stomach size and small intestinal permeability was not affected. Large intestinal fill was increased with lc-AXOS only, while relative large intestinal weight was increased with both fibre sources (P < 0.050). Also, CELL decreased ileal pH and tended to increase ileal DM content compared to CON (P < 0.050). Moreover, the concentration of volatile fatty acids was increased in the caecum (P < 0.100) and mid-colon (P < 0.050) by addition of CELL. lc-AXOS only stimulated caecal propionate (P < 0.050). The microbiota composition showed a high individual variation and limited dietary impact. Nonetheless, CELL induced minor shifts in specific genera, with notable reductions of Escherichia-Shigella.

Conclusions
Adding dietary fibres to the supplemental diet of suckling piglets altered large intestinal morphology but not small intestinal permeability. Moreover, dietary fibre showed effects on fermentation and modest changes of microbial populations in the hindgut, with more prominent effects from the low-fermentable cellulose.
Survival data following phase 1/2 studies using precision tumor-targeted gene delivery to advanced chemotherapy-resistant malignancies.
Authors: Gordon Erlinda Maria , Chawla Sant P. , Hall Frederick L 
Published: October 2019

101 Background: Targeted gene delivery in vivo has long been considered the “Holy Grail” of gene therapy. Methods: We reviewed long-term data of patients with advanced chemotherapy-resistant malignancies, previously-treated patients with two tumor-targeted retrovectors: (1) encoding cytotoxic dominant negative cyclin G1, DeltaRex-G (formerly Rexin-G), and (2) encoding cytokine GMCSF plus suicide gene HStk, DeltaVax (formerly Reximmune-C). Results: Ninety-nine patients received > 5,000 intravenous infusions of DeltaRex-G; another 16 patients received 288 intravenous infusions of DeltaRex-G + 96 infusions of DeltaVax followed by valacyclovir p.o. No therapy-related bone marrow suppression, organ dysfunction or delayed treatment related adverse events were observed. Survival analysis showed 5.0% 10-year overall survival rate for patients who received DeltaRex-G alone, and 18.8% for DeltaRex-G + DeltaVax. Conclusions: Data analysis indicates that tumor-targeted gene delivery in vivo, represented by cytocidal DeltaRex-G, with or without immuno-stimulatory DeltaVax, has induced prolonged ( > 10 years) sustained remissions in cancer patients presenting with advanced chemotherapy-resistant solid and hematologic malignancies—plausibly due to safety, selectivity, and immune modulation. While the curative potential of precision targeted genetic medicine necessarily remains an academic question; it is clear that these initial long-term, cancer-free ( > 10 year) survivors represent a major milestone in both cancer therapy and immunotherapy. Phase 2-3 clinical trials are planned for these hard-to treat malignancies.
Geriatric head and neck squamous carcinomas treated with modulated radiotherapy: Learning curve.
Authors: Basu Trinanjan , Karpe Ashay , Kendre Pradip , Nayek Deepika , Rao Satish , Ambulkar Indu B 
Published: October 2019

107 Background: Geriatric head and neck squamous carcinomas (GHNC) treatment remains challenging due to multiple patient and treatment related factors. We analysed preliminary data for seventy HNC patients beyond 70 years of age treated by modulated radiotherapy (MRT). The objective was to realise the learning curve ahead. Methods: There were 70 patients (M:56,F:14) with median age of 78 years (70-96) treated by MRT at our centre. They were analysed for efficacy and acute side effects. Besides demographic and disease related parameters compliance to treatment, rate of hospitalisation, dependency of WHO ladder 3 analgesia and early clinico-radiological outcomes were analysed. Results: The median follow up was 12 months. 65% patients were locally advanced stage and 65% received radical MRT. For radical MRT the dose ranged between 66-70 Gy in 30-33 fractions and 5 patients received palliative MRT. 83% completed intended treatment with 30% had MRT interruptions. 48% patients required hospitalisation. 60% had comorbidities with 35% two or more types. 13 patients had concurrent chemotherapy and 48% had hospitalisation and 60% had feeding tubes.65% and 30% had post MRT endoscopic evaluation and imaging respectively. Among them 80% are loco-regionally controlled. 30% patients are long term (more than 3 months) tube dependent and morphine dependent. There were 5 deaths while on MRT both due to associated cardiac and pulmonary comorbidities. 40% and 65% of palliative and radical MRT patients respectively had complete response post MRT. All patients underwent psychological counselling and dietician evaluation. The median G8 screening score was 15. Conclusions: GHNC are a unique group with its own challenge. The learning curve was need of specialised setting and modern MRT for effective outcome. Non disease related concerns like alteration in daily quality of life, social engagement related issues, dementia and end of life care emerged as prominent issues beyond disease control.
Development of expert system that improve the decision-making process with an emphasis on health-related quality of life in elderly patients with a colon cancer.
Authors: Shilo Polina , Kanina Aleksandra 
Published: October 2019

113 Background: Health-Related Quality of Life (HRQoL) is an important issue for elderly patients with colon cancer. We created the expert system which allows to predict low level of HRQoL and accessed it’s quality by using several simulation studies. Methods: We performed a systematic review to figure out the known factors associated with low level of HRQoL in elderly colon cancer patients. The searches were performed in PubMed. We accessed the possible impact of several factors affecting HRQoL, including symptoms, comorbidities and treatment toxicity. All relevant factors were included in prediction model. We assigned the different weights to different factors based on evaluation of clinical studies to develop the logistic regression and Markov stochastic model later. As we needed a binary dependent variable we performed the ROC analysis to figure out an optimal cutoff of HRQoL. Then we simulated a partly virtual dataset based on elderly colon cancer patients diagnosed in Davidovskiy Hospital to evaluate the prediction model quality. All statistical calculations were performed in RStudio. The simulation part was performed using simFrame R package. Results: Twenty two studies with a total number of 2516 patients were included in our systematic review. The 39 factors with different weights were included prediction model with different weights assigned. The weights range varied from 1 to 18.6. The adjusted proportion of summary score's variance (R2 ) varied from 0.09 to 0.47 in univariate analysis. The final logistic regression model quality was moderate: the Nagelkerke R-square coefficient was 57.9. However, the developed model showed a 76% sensitivity and 61% specificity in predicting of lower HRQoL level. Conclusions: Our prediction model allows to prospectively manage of elderly colon cancer patients, making the emphasis on HRQoL. However, the present study has some restrictions: simulation nature of internal validation, possible underestimating of the rare events impact. The long-term comprehensive approach with external validation using large real data analysis is needed to evaluate our prediction model.
Irreversible electroporation followed by chemotherapy vs. chemotherapy alone for locally advanced pancreatic cancer: A large cohort propensity score analysis.
Authors: He Chaobin , Li Shengping 
Published: October 2019

117 Background: Locally advanced pancreatic cancer (LAPC) has a dismal prognosis with the standard chemotherapy and the local progression contributed to nearly one-third of deaths of these patients. Irreversible electroporation (IRE) is a local destructive method which is feasible for the treatment of LAPC. The aim of this study was to evaluate IRE combined with chemotherapy as a new treatment and compared its efficacy with that of chemotherapy alone for LAPC patients. Methods: Data of LAPC patients who received chemotherapy combined IRE or not were extracted from database of the Surveillance, Epidemiology, and End Results (SEER) and Sun Yat-sen University Cancer Center (SYSUCC). The efficacy of these two treatments was compared based on data analyzed with propensity score matching (PSM) analysis. Results: In all, 3515 LAPC patients from SEER database were included, including 3348 patients received chemotherapy and 167 patients received combination therapy of IRE and chemotherapy. Additionally, 36 patients who received IRE plus chemotherapy and another 96 patients who received chemotherapy from the SYSUCC were included. After PSM, survival rates were compared between two groups. Patients in combination group achieved better survival than those in chemotherapy group [SEER: overall survival (OS), 16.0 months (95% CI, 12.0-21.0) vs 9.0 months (95% CI, 7.2-11.6), P < 0.001; SYSUCC: OS, 21.6 months (95% CI, 17.8-25.3) vs 7.1 months (95% CI, 5.4-9.5), P = 0.006]. Moreover, similar better results in terms of cancer-specific survival (CSS) and progression-free survival (PFS) were observed in patients who received combination therapy compared with chemotherapy alone. IRE combined with chemotherapy was shown as a favorable factor for OS, CSS and PFS in LAPC patients. Conclusions: Patients with LAPC who received IRE combined with chemotherapy had better survival compared with those after chemotherapy treatment alone. This combination method may be a more suitable way of treatment for patients with LAPC.
Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.
Authors: Jung Seung Pil , Bae Soo Youn , Lee Jeong Hyeon , Bae Joung Won 
Published: October 2019

119 Background: Triple negative breast cancer (TNBC) exhibits a higher rate of early recurrence and more aggressive behavior. Despite unfavorable prognoses, TNBCs are known to be highly reactive to chemotherapy and show higher pathologic complete response rates after neoadjuvant chemotherapy. However, TNBC patients with residual cancer have significantly worse prognoses than patients with non-TNBC associated residual cancer. TP53 mutations are the most common genetic alterations in breast cancer and are highly linked to basal subtype carcinomas. Past studies have investigated if TP53 mutation can predict the response of cancer to chemotherapy or affect a difference in prognosis; however, the lack of consistent results has hampered clinical applications. Because immunostaining studies can be easily performed, those results may be more useful until Next generation sequencing results are clinically applicable. The aim of this study was to determine whether p53 expression in TNBC could predict the response to neoadjuvant chemotherapy and the resulting prognosis. Methods: From 2009 to 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. Results: Two patients (22.2%, 2/9) achieved pCR in p53(+) TNBC and four patients (50%, 5/10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression ( P= 0.350). Based on pre-chemotherapy p53 expression, there was no significant difference in DFS between p53(+) TNBC and p53(-) TNBC ( P= 0.335) . However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC ( P= 0.099). Based on pre-chemotherapy p53 expression, p53(+) TNBC had better OS than p53(-) TNBC, but the difference was not statistically significant ( P= 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC ( P = 0.018). Conclusions: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53 (+) TNBC had a better OS than p53 (-) TNBC in patients who underwent neoadjuvant chemotherapy.
A SEER population analysis of stage IB resected gastric cancer: Who can benefit from adjuvant therapy?
Authors: Wang Yue 
Published: October 2019

122 Background: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT. Methods: We retrospectively included 1935 stage IB GC patients who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). Risk factors associated with AT were examined using univariate/multivariate analyses. A nomogram to project overall survival (OS) of AT was established and internally validated. Results: Five variables, which were significantly related with OS of AT, were incorporated in the nomogram. These variables were sex, age, examined lymph nodes, tumor site, and family income. The C-index of the model was 0.636 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0-47%. Then the entire cohort was separated into low-risk (≤107 points) as well as high-risk ( > 107 points) groups based on the projected 5-year OS. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (P < 0.001); on the other hand, there was a comparable OS for low-risk patients (P = 0.067). Conclusions: We have developed an effective, intuitional and applied prognostic tool based on nomogram to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.
Sensitization of immunotherapeutic efficiency in HCC by polyinosinic-polycytidylic acid-triggered CXCL10 secretion in liver sinusoidal endothelial cells.
Authors: Wen Liang , Liang Tingbo , Bai Xueli , Zhao Jianhui 
Published: October 2019

126 Background: Nowadays, the efficiency of immune checkpoint blockades (ICBs) in the treatment of advanced hepatocellular carcinoma (HCC) was low. The previous study we published in Hepatology demonstrated that polyinosinic-polycytidylic acid (PolyIC), a TLR3 agonist, could trigger the accumulation, proliferation and activation of CTLs, which contributes to the enhanced anti-tumor efficiency of PD-L1 Ab in HCC. However, the mechanism remains unclear. Methods: The mouse HCC model was established by hydrodynamic transfection of combinational c-Myc/N-Ras oncogenes. PolyIC, CTLA-4 Ab, PD-L1 Ab, CD8 Ab and CXCR3 Ab were all intraperitoneal injected. Mice liver non-parenchymal cells (NPCs) were isolated after liver perfusion and multistep centrifugation. The proliferation, activation and cytotoxic function of CTLs were assessed by flow cytometry. Liver sinusoidal endothelial cells (LSECs) were isolated by magnetic cell sorting. Expressions of TLR3 and CXCL10 were quantitatively analyzed by qRT-PCR and ELISA. LSECs were cultured in vitro by using DMEM medium. Results: Combination of polyIC and PD-L1 Ab (or CTLA-4 Ab) had a synergistic anti-tumor effect on the treatment of mouse HCC. PolyIC induced the accumulation, proliferation, activation and cytotoxic function of CTLs in liver, which were further enhanced when combined ICBs. And CTLs depletion by CD8 Ab attenuated the synergistic anti-tumor effect of polyIC when combined with ICBs. TLR3 expression was much higher in NPCs than other cells in liver, especially in LSECs. Also, polyIC dramatically induced the expressions of CXCL10 in LSECs both in vivo and in vitro. And in vitro, after treated by polyIC, the CXCL10 expression in the medium and cells were all elevated. What’s more, CXCL10/CXCR3 signaling blockade by CXCR3 Ab attenuated the combinational effects of polyIC and ICBs. Meanwhile, after CXCL10/CXCR3 signaling blockade, the accumulation, proliferation and activation of CTLs were all inhibited. Conclusions: PolyIC specifically targets LSECs to induce CXCL10 expression and secretion, which contributes to the CTLs transformation and enhanced efficiency of ICBs in the treatment of HCC.