bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of Wheat Bran Acid Hydrolysate by Rhodotorula mucilaginosa Y-MG1 for Microbial Lipid Production as Feedstock for Biodiesel Synthesis
Authors: Ayadi Ines , Belghith Hafedh , Gargouri Ali , Guerfali Mohamed
Published: December 2019

The lignocellulosic hydrolysate was used as the fermentation feedstock of Rhodotorula mucilaginosa Y-MG1 for the production of microbial lipids as the potential raw material for biodiesel synthesis. On synthetic media and under nitrogen-limiting condition, the Y-MG1 strain produces 2.13 g/L of lipids corresponding to 32.7% of lipid content. This strain was able to assimilate a wide range of substrates, especially C5 and C6 sugars as well as glycerol and sucrose. Fatty acid composition shows a divergence depending on the nature of used carbon source with a predominance of oleic acid or linoleic acid. An effective hydrolysis process, based on diluted acid treatment, was established for providing the maximum of fermentable sugars from different characterized lignocellulosic wastes. The highest yield of reducing sugars (56.6 g/L) could be achieved when wheat bran was used as the raw material. Hydrolysate detoxification step was not required in this study since the Y-MG1 strain was shown to grow and produce lipids in the presence of inhibitors and without the addition of external elements. Operating by controlled fed-batch fermentation yielded a dry biomass and oil yield of up to 11 g/L and 38.7% (w/w), respectively. The relative fatty acid composition showed the presence of increased levels of monounsaturated (66.8%) and saturated (23.4%) fatty acids in lipids of Y-MG1 grown on wheat bran. The predictive determination of biodiesel properties suggests that this oil may effectively be used for biodiesel production.
SprI/SprR Quorum Sensing System ofSerratia proteamaculans94
Authors: Zaitseva Yulia V. , Koksharova Olga A. , Lipasova Valentina A. , Plyuta Vladimir A. , Demidyuk Ilya V. , Chernin Leonid S. , Khmel Inessa A.
Published: December 2019

In this study, we investigated the quorum sensing (QS) regulatory system of the psychrotrophic strainSerratia proteamaculans94 isolated from spoiled refrigerated meat. The strain produced severalN-acyl-L-homoserine-lactone (AHL) QS signal molecules, withN-(3-oxo-hexanoyl)-L-homoserine lactone andN-(3-hydroxy-hexanoyl)-L-homoserine lactone as two main types. ThesprIandsprRgenes encoding an AHL synthase and a receptor regulatory protein, respectively, were cloned and sequenced. Analysis of their nucleotide sequence showed that these genes were transcribed convergently and that their reading frames partly overlapped by 23 bp in the terminal regions. The genes were highly similar to theluxI/luxR-type QS genes of other Gram-negative bacteria. Anspr-box (analog of thelux-box) was identified upstream of thesprRgene and found to be overlapped with the sequence of −10 sequence site in the promoter region of this gene. Inactivation of thesprIgene led to the absence of AHL synthesis, chitinolytic activity, and swimming motility; decrease of extracellular proteolytic activity; affected the cellular fatty acid composition; and reduced suppression of the fungal plant pathogen mycelium growth by volatile compounds emitted by strainS. proteamaculans94. The data obtained demonstrated the important role of the QS system in the regulation of cellular processes inS. proteamaculans94.
Optimal High-Speed Railway Timetable by Stop Schedule Adjustment for Energy-Saving
Authors: Chen Dingjun , Li Sihan , Li Junjie , Ni Shaoquan , Liu Xiaolong
Published: December 2019

Timetable optimization techniques offer opportunity for saving energy and hence reducing operational costs for high-speed rail services. The existing energy-saving timetable optimization is mainly concentrated on the train running state adjustment and the running time redistribution between two stations. Not only the adjustment space of timetables is limited, but also it is hard for the train to reach the optimized running state in reality, and it is difficult to get feasible timetable with running time redistribution between two stations for energy-saving. This paper presents a high-speed railway energy-saving timetable based on stop schedule optimization. Under the constraints of safety interval and stop rate, with the objective of minimizing the increasing energy consumption of train stops and the shortest travel time of trains, the high-speed railway energy-saving timetable optimization model is established. The fuzzy mathematics programming method is used to design an efficient algorithm. The proposed model and algorithm are demonstrated in the actual operation data of Beijing-Shanghai high-speed railway. The results show that the total operating energy consumption of the train is reduced by 3.7%, and the total travel time of the train is reduced by 11 minutes.
Predictive Factors of Concerns about Falling in People with Parkinson’s Disease: A 3-Year Longitudinal Study
Authors: Lindh-Rengifo Magnus , Jonasson Stina B. , Mattsson Niklas , Ullén Susann , Nilsson Maria H.
Published: December 2019

Introduction. Fear of falling (FOF) is more common in people with Parkinson’s disease (PD) than in healthy controls. It can lead to several negative consequences such as restrictions in everyday life. Moreover, FOF is a risk factor for future falls. Aim. This study aimed to identify predictive factors of FOF (conceptualized as concerns about falling) after three years, with and without adjusting for concerns about falling at baseline, in people with PD. Methods. This study included 151 participants (35% women) with PD. At baseline, their mean (SD) age and PD duration were 68 (±9.0) and 9 (±6.1) years, respectively. The Falls Efficacy Scale-International (FES-I) was used as the dependent variable in multivariable linear regression analyses. Results. The mean (SD) FES-I score increased from 28.1 (11.9) to 33.1 (14.0) three years later (p<0.001). The strongest (according to the standardized regression coefficient, β) predictor of concerns about falling was walking difficulties (β = 0.378), followed by age (0.227), problems maintaining balance while dual tasking (0.172), and needing help in daily activities (0.171). When adjusting for baseline FES-I scores, the strongest predictive factor was problems maintaining balance while dual tasking (β = 0.161), which was followed by age (0.131) and female sex (0.105). Conclusions. This study pinpoints several predictive factors of concerns about falling that are modifiable and which could be addressed in rehabilitation: perceived walking difficulties, having problems maintaining balance while dual tasking, and dependence on others in daily activities. The importance of dual tasking is a novel finding, which future studies need to confirm or refute. One should be aware of the fact that an increased age predicts concerns about falling with and without adjusting for baseline FES-I scores, whereas female sex predicts concerns about falling only when adjusting for baseline FES-I scores.
The Utility of Rapid On-Site Evaluation during Bronchoscopic Biopsy: A 2-Year Respiratory Endoscopy Central Experience
Authors: Wang Hansheng , Wei Na , Tang Yijun , Wang Yunyun , Luo Guoshi , Ren Tao , Xiong Chang , Li Hongbo , Wang Meifang , Qian Xin
Published: December 2019

Background. Rapid on-site evaluation (ROSE) is commonly used to evaluate the adequacy of biopsy materials in fine-needle aspiration; however, the diagnostic performance of ROSE during fiber optic bronchoscopy (FOB) biopsy under direct vision is rarely reported. Here, we evaluated the role of ROSE during FOB biopsy of visible lesion in trachea or bronchi. Methods. The role of ROSE was prospectively evaluated in consecutive bronchoscopy specimens obtained between January 2016 and January 2018. The agreement and accuracy between ROSE and final histopathological interpretation were assessed. The frequency and possible reasons for discrepancy between ROSE and definitive histopathology results were identified. Histological and cytological classification was performed according to the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) criteria of lung ADCs classification. Results. The study enrolled 651 patients, of which 33 were excluded because of insufficient cells. Final diagnosis of malignancy was achieved in 462 cases (74.8%), whereas 156 cases (25.2%) were nonmalignant. ROSE and pathology were well correlated for the diagnosis of squamous cell carcinoma (SCC) (Kappa = 0.718, p<0.05), adenocarcinoma (AdC) (Kappa = 0.662; p<0.05) and small cell lung cancer (SCLC) (Kappa = 0.955; p<0.05). In 24 cases diagnosed as malignant by ROSE and nonmalignant by pathology, the lesion tissues were surgically excised and re-analyzed, and the 24 cases were finally confirmed as malignant by pathology. Conclusions. ROSE technique allows bronchoscopists to obtain viable and adequate material for the diagnosis of histopathology, and provides them with an onsite preliminary diagnosis especially in cases with inconclusive macroscopic appearance. ROSE and pathology should be used in combination to increase the accuracy of diagnosis.
Optimal Control Strategy for a Discrete Time to the Dynamics of a Population of Diabetics with Highlighting the Impact of Living Environment
Authors: Kouidere Abdelfatah , Balatif Omar , Ferjouchia Hanane , Boutayeb Abdesslam , Rachik Mostafa
Published: December 2019

Nowadays, Diabetes is one of the most common diseases, which has a huge and growing socio-economic burden affecting individuals, families, and the whole society. In this paper, we propose an optimal control approach modeling the evolution from pre-diabetes to diabetes with and without complications and the effect of living environment. We show the existence of an optimal control and then use a numerical implicit finite-difference method to monitor the size of population in each compartment.
Fractional Hardy–Sobolev Inequalities with Magnetic Fields
Authors: Liu Min , Jiang Fengli , Guo Zhenyu
Published: December 2019

A fractional Hardy–Sobolev inequality with a magnetic field is studied in the present paper. Under appropriate conditions, the achievement of the best constant of the fractional magnetic Hardy–Sobolev inequality is established.
Decision Tree Analysis: A Retrospective Analysis of Postoperative Recurrence of Adhesions in Patients with Moderate-to-Severe Intrauterine
Authors: Zhu Ru , Duan Hua , Wang Sha , Gan Lu , Xu Qian , Li Jinjiao
Published: December 2019

Objective. To establish and validate a decision tree model to predict the recurrence of intrauterine adhesions (IUAs) in patients after separation of moderate-to-severe IUAs. Design. A retrospective study. Setting. A tertiary hysteroscopic center at a teaching hospital. Population. Patients were retrospectively selected who had undergone hysteroscopic adhesion separation surgery for treatment of moderate-to-severe IUAs. Interventions. Hysteroscopic adhesion separation surgery and second-look hysteroscopy 3 months later. Measurements and Main Results. Patients’ demographics, clinical indicators, and hysteroscopy data were collected from the electronic database of the hospital. The patients were randomly apportioned to either a training or testing set (332 and 142 patients, respectively). A decision tree model of adhesion recurrence was established with a classification and regression tree algorithm and validated with reference to a multivariate logistic regression model. The decision tree model was constructed based on the training set. The classification node variables were the risk factors for recurrence of IUAs: American Fertility Society score (root node variable), isolation barrier, endometrial thickness, tubal opening, uterine volume, and menstrual volume. The accuracies of the decision tree model and multivariate logistic regression analysis model were 75.35% and 76.06%, respectively, and areas under the receiver operating characteristic curve were 0.763 (95% CI 0.681–0.846) and 0.785 (95% CI 0.702–0.868). Conclusions. The decision tree model can readily predict the recurrence of IUAs and provides a new theoretical basis upon which clinicians can make appropriate clinical decisions.
Incidence and Survival Changes in Patients with Esophageal Adenocarcinoma during 1984–2013
Authors: Haiyu Zhang , Xiaofeng Pei , Xiangqiong Mo , Junlan Qiu , Xiaobin Zheng , Shuncong Wang , Huanhuan Sun , Haiqing Ma
Published: December 2019

Purpose. The morbidity of esophageal adenocarcinoma (EAC) has significantly increased in Western countries. We aimed to identify trends in incidence and survival in patients with EAC in the recent 30 years and then analyzed potential risk factors, including race, sex, age, and socioeconomic status (SES). Methods. All data were collected from the Surveillance, Epidemiology, and End Results or SEER database. Kaplan–Meier analysis and the Cox proportional hazards model were conducted to compare the differences in survival between variables, including sex, race, age, and SES, as well as to evaluate the association of these factors with prognosis. Results. A total of 16,474 patients with EAC were identified from 1984 to 2013 in the United States. Overall incidence increased every 10 years from 1.8 to 3.1 to 3.9 per 100. Overall survival gradually improved (p<0.0001), which was evident in male patients ((hazard ratio (HR) = 1.111; 95% confidence interval (CI) (1.07, 1.15)); however, the 5-year survival rate remained low (20.1%). The Cox proportional hazards model identified old age, black ethnicity, and medium/high poverty as risk factors for EAC (HR = 1.018; 95% CI (1.017, 1.019; HR = 1.240, 95% CI (1.151,1.336), HR = 1.000, 95% CI (1.000, 1.000); respectively). Conclusions. The incidence of EAC in the United States increased over time. Survival advantage was observed in white patients and patients in the low-poverty group. Sex was an independent prognostic factor for EAC, but this finding has to be confirmed by further research.
An Improved Discrete Artificial Bee Colony Algorithm for Flexible Flowshop Scheduling with Step Deteriorating Jobs and Sequence‐Dependent Setup Times
Authors: Xuan Hua , Zhang Huixian , Li Bing
Published: December 2019

This paper studies a flexible flowshop scheduling problem with step‐deteriorating jobs and sequence‐dependent setup times (FFSP‐SDJ&SDST) where there are multiple unrelated parallel machines at each stage. The actual processing time of each job is modeled as a step function of its starting time. An integer programming model is first formulated with the objective of minimizing the total weighted completion time. Since this problem is NP‐complete, it becomes an interesting and challenging topic to develop effective approximation algorithms for solving it. The artificial bee colony (ABC) algorithm has been successfully applied to solve both continuous and combinatorial optimization problems with the advantages of fewer control parameters and ease of implementation. So, an improved discrete artificial bee colony algorithm is proposed. In this algorithm, a dynamic generation mechanism of initial solutions is designed based on job permutation encoding. A genetic algorithm and a modified variable neighborhood search are introduced, respectively, to obtain new solutions for the employed and onlooker bees. A greedy heuristic is proposed to generate the solutions of the scout bees. Finally, to verify the performance of the proposed algorithm, an orthogonal test is performed to optimize the parameter settings. Simulation results on different scale problems demonstrate that the proposed algorithm is more effective compared against several presented algorithms from the existing literatures.
Jerky Movement with Ceftazidime: A Case of Ceftazidime-Induced Neurotoxicity with a Review of the Literature
Authors: Al-Sadawi Mohammed , Rodriguez Ortega Romy , Sun Natalie , Abdurahimova Madina , McFarlane Samy I.
Published: December 2019

Neurotoxicity manifested as confusion and seizures has been recognized as a side effect of multiple cephalosporins including ceftazidime. Renal impairment and inappropriate dosing are the most common contributors to the development of neurological abnormalities in patients receiving these antibiotics. The presence of baseline neurological abnormalities likely contributes to the frequency of these adverse events. Here, we present a case of a 78-year-old man that developed altered mental status and myoclonic movement after initiation of ceftazidime in the setting of mild renal dysfunction. Resolution of clinical picture was evident after 48 hours of discontinuation of the antibiotic without additional interventions.
Static Wind Load Evaluation under Steady‐State Wind Flow for 2‐Edge Sloped Box Girder by Using Wind Tunnel Test
Authors: Lee Hoyeop , Moon Jiho
Published: December 2019

The two‐edge box girder has been widely used as a stiffened girder in cable‐stayed bridges. However, such girders have weakness in aerodynamic stability. To improve its aerodynamic stability, some previous researchers have given slope to the edge box instead of installing additional attachments to aerodynamically stabilize the bridge. For wind load design, an angle of attack (AOA) has to be considered. However, the effect of AOA has not been studied for sloped box girder yet. In the present study, the effect of AOA on the static wind load coefficient was investigated for 2‐edge sloped box girder. A series of wind tunnel tests was performed by varying the box slope angle from 0° to 17° where AOA was set from −10° to 10°. Results showed that the lateral wind force is considerably reduced with the increase of the box slope angle except the case with the physical angle of 8°–11°. For practical AOA range, the box slope should be larger than 15° to minimize the aerodynamic static lateral force on the girder.
Adnexal Torsion in Pediatric Age: Does Bolli’s Score Work? Report of Two Cases
Authors: Giambanco L. , Iannone V. , Borriello M. , Scibilia G. , Sozzi G. , Chiantera V. , Scollo P.
Published: December 2019

Adnexal torsion is a surgical emergency requiring early diagnosis in order to avoid demolitive surgery. Adnexal torsion’s diagnosis could be very difficult in pediatric patients because children cannot explain symptoms accurately. Furthermore reproductive organs lie high in abdomen, causing unclear examinations findings. For reducing diagnostic mistakes or delay clinical and hematological criteria could be useful. No radiological criteria (CT or MRI) should be taken in count because of the costs and the required time. By combining clinical presentation in patients with OT three useful diagnostic variables have been identified: age, duration of pain, vomiting. Presence of vomiting, short duration of abdominal pain and high CRP levels have great predictive value for the diagnosis of adnexal torsion. In those patients an exploratory laparoscopy should be performed without any doubt and/or delay. These data may aid physicians in the evaluation of abdominal pain in premenarchal girls.
Beyond Angiogenesis: Exploiting Angiocrine Factors to Restrict Tumor Progression and Metastasis
Authors: Singhal Mahak , Augustin Hellmut G.
Published: December 2019

Looking beyond tumor angiogenesis, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines, but exerts active “angiocrine” gatekeeper roles, controlling their microenvironment in an instructive manner. While vascular niches host disseminated cancer cells and promote their stemness, endothelial cell–derived angiocrine signals orchestrate a favorable immune milieu to facilitate metastatic growth. Here, we discuss recent advances in the field of tumor microenvironment research and propose angiocrine signals as promising targets of future mechanism-driven antimetastatic therapies, which may prove useful to synergistically combine with chemotherapy and immunotherapy.
lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP
Authors: Li Nan , Yang Guohua , Luo Liyun , Ling Li , Wang Xiaorong , Shi Lejuan , Lan Junsong , Jia Xiaoting , Zhang Qiong , Long Ze , Liu Jinbao , Hu Weimin , He Zhimin , Liu Haiying , Liu Wanqing , Zheng Guopei
Published: December 2019

Purpose:

Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC.

Experimental Design:

The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1 was verified. Various in vitro and in vivo experiments were performed to investigate the interaction between THAP9-AS1 and YAP signaling.

Results:

We demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. THAP9-AS1 promotes PDAC cells growth both in vitro and in vivo. THAP9-AS1 exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of THAP9-AS1 knockdown. Inversely, YAP knockdown diminished the effects of THAP9-AS1 overexpression. THAP9-AS1 acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, THAP9-AS1 binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes THAP9-AS1 transcription to form a feed-forward circuit. Importantly, THAP9-AS1 level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC.

Conclusions:

Our findings indicate that THAP9-AS1 plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates THAP9-AS1 transcription. THAP9-AS1/YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment.
A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
Authors: Oza Amit M. , Matulonis Ursula A. , Alvarez Secord Angeles , Nemunaitis John , Roman Lynda D. , Blagden Sarah P. , Banerjee Susana , McGuire William P. , Ghamande Sharad , Birrer Michael J. , Fleming Gini F. , Markham Merry Jennifer , Hirte Hal W. , Provencher Diane M. , Basu Bristi , Kristeleit Rebecca , Armstrong Deborah K. , Schwartz Benjamin , Braly Patricia , Hall Geoff D. , Nephew Kenneth P. , Jueliger Simone , Oganesian Aram , Naim Sue , Hao Yong , Keer Harold , Azab Mohammad , Matei Daniela
Published: December 2019

Purpose:

Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

Patients and Methods:

Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS).

Results:

Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group.

Conclusions:

Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.
Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer
Authors: Hammer Stefanie , Hagemann Urs B. , Zitzmann-Kolbe Sabine , Larsen Aasmund , Ellingsen Christine , Geraudie Solene , Grant Derek , Indrevoll Baard , Smeets Roger , von Ahsen Oliver , Kristian Alexander , Lejeune Pascale , Hennekes Hartwig , Karlsson Jenny , Bjerke Roger M. , Ryan Olav B. , Cuthbertson Alan S. , Mumberg Dominik
Published: December 2019

Purpose:

Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha therapy (TAT) has shown early signs of activity in patients with prostate cancer refractory to beta radiation. We describe a novel, antibody-based TAT, the PSMA-targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting of the alpha-particle emitter thorium-227 complexed by a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody.

Experimental Design:

PSMA-TTC was characterized for affinity, mode of action, and cytotoxic activity in vitro. Biodistribution, pharmacokinetics, and antitumor efficacy were investigated in vivo using cell line and patient-derived xenograft (PDX) models of prostate cancer.

Results:

PSMA-TTC was selectively internalized into PSMA-positive cells and potently induced DNA damage, cell-cycle arrest, and apoptosis in vitro. Decrease in cell viability was observed dependent on the cellular PSMA expression levels. In vivo, PSMA-TTC showed strong antitumor efficacy with T/C values of 0.01 to 0.31 after a single injection at 300 to 500 kBq/kg in subcutaneous cell line and PDX models, including models resistant to standard-of-care drugs such as enzalutamide. Furthermore, inhibition of both cancer and cancer-induced abnormal bone growth was observed in a model mimicking prostate cancer metastasized to bone. Specific tumor uptake and efficacy were demonstrated using various PSMA-TTC doses and dosing schedules. Induction of DNA double-strand breaks was identified as a key mode of action for PSMA-TTC both in vitro and in vivo.

Conclusions:

The strong preclinical antitumor activity of PSMA-TTC supports its clinical evaluation, and a phase I trial is ongoing in mCRPC patients (NCT03724747).
Investigation of Antigen-Specific T-Cell Receptor Clusters in Human Cancers
Authors: Zhang Hongyi , Liu Longchao , Zhang Jian , Chen Jiahui , Ye Jianfeng , Shukla Sachet , Qiao Jian , Zhan Xiaowei , Chen Hao , Wu Catherine J. , Fu Yang-Xin , Li Bo
Published: December 2019

Purpose:

Cancer antigen–specific T cells are key components in antitumor immune response, yet their identification in the tumor microenvironment remains challenging, as most cancer antigens are unknown. Recent advance in immunology suggests that similar T-cell receptor (TCR) sequences can be clustered to infer shared antigen specificity. This study aims to identify antigen-specific TCRs from the tumor genomics sequencing data.

Experimental Design:

We used the TRUST (Tcr Repertoire Utilities for Solid Tissue) algorithm to assemble the TCR hypervariable CDR3 regions from 9,700 bulk tumor RNA-sequencing (RNA-seq) samples, and developed a computational method, iSMART, to group similar TCRs into antigen-specific clusters. Integrative analysis on the TCR clusters with multi-omics datasets was performed to profile cancer-associated T cells and to uncover novel cancer antigens.

Results:

Clustered TCRs are associated with signatures of T-cell activation after antigen encounter. We further elucidated the phenotypes of clustered T cells using single-cell RNA-seq data, which revealed a novel subset of tissue-resident memory T-cell population with elevated metabolic status. An exciting application of the TCR clusters is to identify novel cancer antigens, exemplified by our identification of a candidate cancer/testis gene, HSFX1, through integrated analysis of HLA alleles and genomics data. The target was further validated using vaccination of humanized HLA-A*02:01 mice and ELISpot assay. Finally, we showed that clustered tumor-infiltrating TCRs can differentiate patients with early-stage cancer from healthy donors, using blood TCR repertoire sequencing data, suggesting potential applications in noninvasive cancer detection.

Conclusions:

Our analysis on the antigen-specific TCR clusters provides a unique resource for alternative antigen discovery and biomarker identification for cancer immunotherapies.
Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention
Authors: Omene Coral , Ma Lin , Moore Jade , Ouyang Haoxu , Illa-Bochaca Irineu , Chou William , Patel Manan S. , Sebastiano Christopher , Demaria Sandra , Mao Jian-Hua , Karagoz Kubra , Gatza Michael L. , Barcellos-Hoff Mary Helen
Published: December 2019

Because the incidence of breast cancer increases decades after ionizing radiation exposure, aging has been implicated in the evolution of the tumor microenvironment and tumor progression. Here, we investigated radiation-induced carcinogenesis using a model in which the mammary glands of 10-month-old BALB/c mice were transplanted with Trp53-null mammary tissue 3 days after exposure to low doses of sparsely ionizing γ-radiation or densely ionizing particle radiation. Mammary transplants in aged, irradiated hosts gave rise to significantly more tumors that grew more rapidly than those in sham-irradiated mice, with the most pronounced effects seen in mice irradiated with densely ionizing particle radiation. Tumor transcriptomes identified a characteristic immune signature of these aggressive cancers. Consistent with this, fast-growing tumors exhibited an immunosuppressive tumor microenvironment with few infiltrating lymphocytes, abundant immunosuppressive myeloid cells, and high COX-2 and TGFβ. Only irradiated hosts gave rise to tumors lacking cytotoxic CD8+ lymphocytes (defined here as immune desert), which also occurred in younger irradiated hosts. These data suggest that host irradiation may promote immunosuppression. To test this, young chimera mice were fed chow containing a honeybee-derived compound with anti-inflammatory and immunomodulatory properties, caffeic acid phenethyl ester (CAPE). CAPE prevented the detrimental effects of host irradiation on tumor growth rate, immune signature, and immunosuppression. These data indicated that low-dose radiation, particularly densely ionizing exposure of aged mice, promoted more aggressive cancers by suppressing antitumor immunity. Dietary intervention with a nontoxic immunomodulatory agent could prevent systemic effects of radiation that fuel carcinogenesis, supporting the potential of this strategy for cancer prevention.
A New Case with Corpus Callosum Abnormalities, Microcephaly and Seizures Associated with a 2.3-Mb 1q43-q44 Deletion
Authors: Lloveras Elisabet , Canellas Anna , Barranco Laura , Alves Claudia , Vila-Real Marta , Ventura Vania , Fernández Daniel , Mendez Begona , Piqué Meritxell , Reis-Lima Margarida , de la Iglesia Cristina , Palau Nuria , Costa Marta , Yeste Diana , Auge Marc , Perez Cristina
Published: December 2019

1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain not entirely clear. We present a patient with a 2.3-Mb 1q44 deletion, including AKT3, ZBTB18, and HNRNPU, who shows microcephaly, developmental delay, abnormal corpus callosum, and seizures. The genetic findings in this case and a review of the literature spotlight a region between 243 Mb and 245 Mb on chromosome 1q related to the genesis of the typical symptoms of 1q44 deletion.
Linked Color Imaging Highlights Flat Early Gastric Cancer
Authors: Kubo Kimitoshi , Kimura Noriko , Matsuda Soichiro , Tsuda Momoko , Kato Mototsugu
Published: December 2019

While linked color imaging (LCI) may allow flat early gastric cancer to be detected early, the endoscopic and pathological features of lesions detected by LCI remain poorly described. Screening esophagogastroduodenoscopy performed on a 68-year-old woman revealed a yellowish, flat lesion shown to be reddish in its central area, located in the anterior wall of the gastric lower body on white light imaging (WLI). On LCI, the lesion was highlighted as an orangish, flat lesion shown to be purple-colored in its central area, surrounded by lavender-colored tissue. Endoscopic submucosal dissection performed led to the patient being diagnosed with tubular adenocarcinoma, well-differentiated type (tub1), pT1a (M). This case suggests that LCI may prove more useful than WLI for the detection of flat early gastric cancer lesions.
Subjetivación de la blanquitud por jóvenes universitarios: un estudio comparativo.
Authors: Ortiz-Piedrahíta Vanessa
Published: December 2019

Este trabajo se inscribe en los estudios interdisciplinarios y decoloniales sobre la blanquitud. Describe la construcción subjetiva de la identidad blanca por jóvenes universitarios de Brasilia y Medellín, ello a partir de categorías que se interrelacionan, como la clase social, la etnicidad y la raza. Por medio de un abordaje metodológico
cualitativo y comparativo se logró captar el universo significativo de los participantes. Finalmente, se presentan algunas reflexiones sobre el proceso performativo, y a veces contradictorio, que implica el reconocerse a través de los valores y privilegios que otorga la blanquitud en espacios tanto académicos como extracurriculares.
Extracorporeal Membrane Oxygenation Use in Acute Myocardial Infarction in the United States, 2000 to 2014
Authors: Vallabhajosyula Saraschandra , Prasad Abhiram , Bell Malcolm R. , Sandhu Gurpreet S. , Eleid Mackram F. , Dunlay Shannon M. , Schears Gregory J. , Stulak John M. , Singh Mandeep , Gersh Bernard J. , Jaffe Allan S. , Holmes David R. , Rihal Charanjit S. , Barsness Gregory W.
Published: December 2019

Background:

Extracorporeal membrane oxygenation (ECMO) is increasingly used in acute myocardial infarction (AMI); however, there are limited large-scale national data.

Methods:

Using the National Inpatient Sample database from 2000 to 2014, a retrospective cohort of AMI utilizing ECMO was identified. Use of percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous left ventricular assist device (LVAD) was also identified in this population. Outcomes of interest included temporal trends in utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD), in-hospital mortality, and resource utilization.

Results:

In ≈9 million AMI admissions, ECMO was used in 2962 (<0.01%) and implanted a median of 1 day after admission. ECMO was used in 0.5% and 0.3% AMI admissions complicated by cardiogenic shock and cardiac arrest, respectively. ECMO was used more commonly in admissions that were younger, nonwhite, and with less comorbidity. ECMO use was 11× higher in 2014 as compared with 2000 (odds ratio, 11.37 [95% CI, 7.20–17.97]). Same-day percutaneous coronary intervention was performed in 23.1%; intra-aortic balloon pump/percutaneous LVAD was used in 57.9%, of which 30.3% were placed concomitantly. In-hospital mortality with ECMO was 59.2% overall but decreased from 100% (2000) to 45.1% (2014). Durable LVAD and cardiac transplantation were performed in 11.7% as an exit strategy. Of the hospital survivors, 40.8% were discharged to skilled nursing facilities. Older age, male sex, nonwhite race, and lower socioeconomic status were independently associated with higher in-hospital mortality with ECMO use.

Conclusions:

In AMI admissions, a steady increase was noted in the utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD). In-hospital mortality remained high in AMI admissions treated with ECMO.
Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort
Authors: Dula Adrienne N. , Mlynash Michael , Zuck Nathan D. , Albers Gregory W. , Warach Steven J. ,   for the DEFUSE 3 Investigators
Published: December 2019

Background and Purpose—

Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke).

Methods—

DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans.

Results—

All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9–18.4) in women versus 12.6 mL (2.7–29.6) in men, for T
max
>6 seconds 89.0 mL (63.8–131.7) versus 133.9 mL (87.0–175.4), and for mismatch 82.1mL (53.8–112.8) versus 108.2 (64.1–149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15–0.46) versus 0.39 (0.26–0.57),
P
=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (
P
=0.003).

Conclusions—

In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions.

Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02586415.
Mantik, Rhetorik und Poetologie
Authors: Kuhn-Treichel Thomas
Published: December 2019

Lucian’s dialogue with Hesiod appears to be a straightforward dispute on a defined topic in which the poet rather awkwardly defends himself against a most legitimate charge and ends up being justly convicted by Lycinus. Upon closer investigation, however, one can detect several remarkable subtexts that make the dialogue a sophisticated pleasure for learned readers. This paper discusses three possible subtexts: mantic, rhetoric, and poetology. Seen against this backdrop, Lucian’s Hesiod emerges as a pretentious mantis, rhetor and (maybe) poetologist, who, in a certain sense, can be compared to the pretentious πεπαιδευµένοι attacked in so many of Lucian’s works.
Marx’s Economic Manuscript of 1867–68 (Excerpt)
Authors: Marx Karl
Published: December 2019

This archive manuscript is an English translation of a 25-page excerpt from Marx’s Manuscript of 1867–68, which was published for the first time in German in 2012 in the MEGA, Volume II/4.3. This excerpt is Marx’s first and only attempt to incorporate unequal turnover times across industries into his theory of the equalisation of the profit rate and prices of production. The excerpt considers three cases: unequal turnover times across industries, unequal compositions of capital across industries, and both of these inequalities together. It also emphasises two concepts of the rate of profit: rate of profit on capital advanced and rate of profit on the cost price (capital consumed).
The Scythian Kingdom in the Crimea in the 2nd Century BC and Its Relations with the Greek States in the North Pontic Region
Authors: Ivantchik Askold I.
Published: December 2019

The new data that have become available in the last two decades show that the Scythian Kingdom with its capital in Neapolis Scythica, which existed in the Crimea in the 2nd century BC, was much closer to Hellenistic states ruled by barbarian dynasties than to nomadic kingdom of the Scythians of the 4th century BC. At the same time, these data allow us to return in part to the old view formulated by Rostovtzeff about continuity between the Scythia of the 4th century BC and the Late Scythian Kingdom, which most researchers have rejected during the last thirty years. It turned out that this continuity existed at least at the ideological level, and the excavations at Ak-Kaya (Vishennoe) filled the chronological gap between the Scythian Kingdoms of the 4th and 2nd century BC. Apparently, Ak-Kaya became one of the political centres of the Scythians as early as the late 4th century BC, before the fall of “Great Scythia”, and the capital of the Crimean Scythians was located there before it was moved to Neapolis Scythica. In the formation of Late Scythian culture and the Late Scythian Kingdom with its capital first in Ak-Kaya and then in Neapolis Scythica, apart from the Scythian elements, sedentary Tauri took part, as well as probably the Greeks and the Hellenized population of the chorai of the Greek cities in north-western Crimea. A key role in changing the character of Scythian culture was apparently played by a change in its economic-cultural type and the transition from nomadic pastoralism to settled agriculture. This article proposes a new interpretation of the inscription on the mausoleum of Argotas, discovered in Neapolis Scythica in 1999. Argotas was probably not a Scythian, but a Greek, despite his Scythian name. This Bosporan aristocrat with Scythian family ties married the widowed Bosporan queen Kamasarya in the second quarter of the 2nd century BC and is mentioned as her husband in the inscription CIRB 75. He played an important role in governing the Bosporan Kingdom and in protecting it against attacks from the East. Then, most likely after the death of Kamasarya, he moved to the neighbouring kingdom of the Scythians, where he became one of the leading generals, the right-hand man of the king and the tutor to his children. After his death in ca. 130-125 BC, he received from King Skiluros unprecedented honours – a heroon in front of the facade of the royal palace was erected for him and, moreover, this was the only truly Greek building in Neapolis Scythica: it was built in accordance with the rules of the architectural order and decorated with Greek statues and reliefs, as well as a metric epitaph with numerous Homeric forms and expressions.
Aesthetics of Muslim-ness: Art and the Formation of Muslim Identity Politics
Authors: Alhourani Ala Rabiha
Published: December 2019

The paper explores two opposing yet simultaneous forces of aesthetics as transformative and constitutive force of Muslim identity politics, religiosity and cultural style in Cape Town The ethnography focuses on Muslim artists in Cape Town, namely Thania Petersen and twin brothers Hasan and Husain Essop, whose artworks embody a ‘social drama’ of a lived experience of Muslims’ ongoing individual and collective active engagement with and appropriation of the plurality of competing discourses that are religious and secular, local and global. The discussion unpacks the ways in which the artworks of Petersen and the Essop brothers serve as a transformative force and as a politic of authenticity to Muslim identity, religiosity, and cultural style. The paper offers an appreciative but critical reading of Talal Asad’s idea of an anthropology of Islam. Taking into consideration the incommensurable diversity and internal contradiction that could be conceived as Islamic discursive traditions, this paper argues that the aesthetics of Muslimness is what inspires coherence within and across diverse, contradictory Islamic traditions.
The Right to Confidential Communication with Defence Counsel in JapanRecent Legal Disputes Over Mail Censorship and Photography in Visiting Rooms
Authors: Ono Teppei
Published: December 2019

In spite of the common global position of protecting the right to confidential communication, the Japanese prison authorities create barriers to communication between pre-trial inmates and defence counsel. Any correspondence, including correspondence between pre-trial inmates and defence counsel, may be opened and read by prison staff. In addition, prison authorities have established regulations to prohibit any visitors from bringing in cameras or mobile phones. They do not allow counsel to take photos in visiting rooms, claiming that these regulations are equally applicable to lawyers. This article examines the legality of the current practice regarding mail censorship and the prohibition of photography in visiting rooms, taking into consideration international human rights standards. It concludes that the current practice diverges from the international human rights standards including the Nelson Mandela Rules, which protects the full confidentiality of communication between inmates and lawyers, and access to effective legal aid. Since the arrest of Nissan’s former chairman Carlos Ghosn in November 2018, Japan’s ‘hostage justice’ system – in which suspects are held for a long period in harsh conditions to coerce a confession – has encountered a barrage of criticism. It should be noted, however, that interruption of inmates-defence counsel communication constitutes another dark side of Japanese criminal justice. This article will shed light on the everyday issues which Japanese defence counsel face in actual criminal cases.
The Case for Transformative Reparations for Conflict-Related Sexual Violence in Rakhine State at the asean Intergovernmental Commission on Human Rights
Authors: Bradley Samantha
Published: December 2019

This article addresses the question of whether Rohingya victims of conflict-related sexual violence (crsv) in Rakhine State in 2017 have recourse to transformative reparations at the Association of Southeast Asian Nations (asean) Inter-Governmental Commission on Human Rights (aichr). crsv was widespread during the August 2017 non-international armed conflict in Rakhine State. crsv also occurred in the context of longstanding subjugation of the Rohingya minority by the Government of Myanmar and Myanmar’s security forces perpetrating sexual violence against the Rohingya and other ethnic minorities. Transformative reparations for crsv are reparations intended to engender structural changes to improve victims’ circumstances and guarantee non-recurrence. An evaluation of asean’s human rights frameworks and the mandate, purposes and principles underpinning the aichr, reveals unexplored potential for transformative reparations for crsv at the aichr for Rohingya victims of crsv in Rakhine State in 2017. The asean Coordinating Centre for Humanitarian Assistance is well placed to coordinate the delivery of transformative reparations in Myanmar.