bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103+conventional dendritic cells
Authors: Zhou Yifan , Slone Natalie , Chrisikos Taylor T , Kyrysyuk Oleksandr , Babcock Rachel L , Medik Yusra B , Li Haiyan S , Kleinerman Eugenie S , Watowich Stephanie S 
Published: April 2020

BackgroundType 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+cDC1s in mice, CD141+cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied.MethodsWe generated murine CD103+cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+cDC1s.ResultsIn vitro-generated CD103+cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, and demonstrated antigen cross-presentation activity on stimulation with the toll-like receptor 3 agonist polyinosinic:polycytidylic acid (poly I:C). In vitro-generated CD103+cDC1s also migrated to TdLNs following poly I:C treatment and intratumoral delivery. Vaccination with poly I:C-activated and tumor antigen-loaded CD103+cDC1s enhanced tumor infiltration of tumor antigen-specific and interferon-γ+CD8+T cells, and suppressed melanoma and osteosarcoma growth. CD103+cDC1s showed superior antitumor efficacy compared with MoDC vaccination, and led to complete regression of 100% of osteosarcoma tumors in combination with CTLA-4 antibody-mediated checkpoint blockade. In vitro-generated CD103+cDC1s effectively protected mice from pulmonary melanoma and osteosarcoma metastases.ConclusionsOur data indicate an in vitro-generated CD103+cDC1 vaccine elicits systemic and long-lasting tumor-specific T cell-mediated cytotoxicity, which restrains primary and metastatic tumor growth. The CD103+cDC1 vaccine was superior to MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade.
Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence
Authors: Du Wanliang , Zhao Xingquan , Wang Yilong , Pan Yuesong , Liu Gaifen , Wang Anxin , Ji Ruijun , Liu Liping , Gu Hongqiu , Dong Kehui , Wang Penglian , Wang Yongjun 
Published: April 2020

Objective
Gastrointestinal (GI) bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence. However, it is unknown whether GI bleeding increases risk for recurrence of stroke. In this study, we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke (AIS), using the China National Stroke Registry (CNSR).

Methods
This study included 22 216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008. We analysed baseline patient characteristics, GI bleeding and outcomes of patients who had an AIS, specifically stroke recurrence at 3, 6 and 12 months. We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.

Results
Of the 12 415 patients included in our study, 12.3%, 15.5% and 17.7% had a stroke recurrence at 3, 6 and 12 months, respectively. GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months (adjusted OR 1.481, 95% CI 1.118 to 1.962), 6 months (adjusted OR 1.448, 95% CI 1.106 to 1.896) and 12 months (adjusted OR 1.350; 95% CI 1.034 to 1.763).

Conclusion
GI bleeding was associated with the increased risk of stroke recurrence after an AIS.
Naming God: Exodus 3:14-15 in Augustine’s Enarrationes in Psalmos
Authors: Glowasky Michael 
Published: April 2020

Abstract
Augustine discusses Exodus 3:14-15 on 49 different occasions in his written corpus, 14 of which are found in his Enarrationes in Psalmos. Scholars have been quick to note the importance of God’s self-disclosure as I AM in verse 14 for Augustine’s conception of the divine as esse. However, far less attention has been paid to the place of verse 15 in Augustine’s thought, despite his claim that this verse reveals God’s “other name” (aliud nomen): the God of Abraham, Isaac and Jacob. In this article, I discuss four key passages from his Enarrationes in Psalmos – two from the redemptive-historical psalms and two from the psalms of ascent – where Augustine addresses the relationship between the two divine names God reveals to Moses in Exodus 3:14-15. In these four passages, I suggest, Augustine presents temporality and materiality as ongoing necessities for the knowledge of God, despite what he appears to suggest elsewhere.
Chimeric antigen receptor–T cells with cytokine neutralizing capacity
Authors: Tan Adrian H. J. , Vinanica Natasha , Campana Dario 
Published: April 2020

AbstractInfusion of T lymphocytes expressing chimeric antigen receptors (CARs) can produce extraordinary antitumor activity in patients with leukemia, lymphoma, and myeloma. The signaling mechanisms activating T cells and provoking tumor cell killing also trigger cytokine secretion and macrophage activation, leading to cytokine release syndrome (CRS). CRS is a serious side effect of CAR–T cells, and proinflammatory interleukin-6 (IL-6) is central to its pathogenesis. To endow T cells with anti-CRS activity, we designed a nonsignaling membrane-bound IL-6 receptor (mbaIL6) constituted by a single chain variable fragment derived from an anti–IL-6 antibody linked to a transmembrane anchoring peptide. We found that mbaIL6 expressed on the surface of T cells could rapidly remove IL-6 from the culture supernatant. IL-6 removal was proportional to the number of mbaIL6+ cells, increased with T-cell proliferation, and neutralized IL-6 signaling and function. A construct encoding for mbaIL6 and an anti–CD19-41BB-CD3ζ CAR allowed simultaneous expression of both receptors. T cells with mbaIL6 and CAR neutralized macrophage-derived IL-6 while exerting powerful antitumor activity. Cytotoxicity and proliferation were identical to those of cells expressing CAR alone in vitro, and CAR–T cells were effective in xenograft models regardless of mbaIL6 expression. Levels of human IL-6 in mice, however, were greatly reduced if T cells expressed both receptors instead of CAR alone. Thus, CAR–T cells with on-board capacity to extinguish IL-6 represent a new approach to prevent CRS and suppress its severity without affecting the antitumor potential of CAR–T cells.
Efficacy of ruxolitinib in subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis
Authors: Lévy Romain , Fusaro Mathieu , Guerin Frédéric , Chetouani Ahmed , Moshous Despina , Fischer Alain , de Saint Basile Geneviève , Sepulveda Fernando E. , Neven Bénédicte 
Published: April 2020

Key Points
First evidence of ruxolitinib efficacy for subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic lymphohistiocytosis. Supporting rationale for ruxolitinib use, not more aggressive treatment, in this context, questioning this condition’s neoplastic nature.
Application of the Chinese version of the addiction profile index (API) in drug users: an analysis of validity and measurement invariance across genders
Authors: Gao Huiyuan , Liu Meizhu , Luo Xu , Zhang Jun , Cai Taisheng 
Published: April 2020

Abstract
Background
In China, substance use disorders represent a significant burden on public health and the economy. However, while the range of drugs and drug markets expands and diversifies, the instruments available to evaluate users’ dependence statuses from multiple dimensions have become insufficient. Accordingly, the present study presents the Chinese version of the Addiction Profile Index (API), explores its reliability and validity, and investigates the measurement invariance between males and females with substance use disorders.

Methods
The API, a self-report questionnaire, was administered to 2252 people with substance use disorders who were undergoing treatment in compulsory detoxification institutions located in five provinces in China (943 females; mean age = 33.5 years old, SD = 8.6). Additionally, to ensure the authenticity of the collected data, the study’s volunteers completed the Drug Use Disorders Identification Test (DUDIT), DUDIT-Extended (DUDIT-E), and the Health Scale for Drug Abusers (HSDA).

Results
The revised API, with its updated substance list, featured 34 items. The new four-factor model, incorporating behavioral symptoms of dependence, impact on social life, cravings, and motivations for detoxification, explained 55.30% of the total variance, indicating a good fit. Moreover, Cronbach’s α and mean item coefficient values showed good internal consistency reliability. Regarding criterion validity, the revised factors were moderately to highly correlated with their corresponding subscales in the DUDIT, DUDIT-E, and HSDA. In addition, the multigroup confirmatory factor analysis demonstrated that a measurement invariance of the revised four-factor model across genders was supported, fully assuming different degrees of invariance. The three factors of symptoms, social life, and motivation exhibited significant differences between male and female participants in the t test results (p < 0.01).

Conclusions
The Chinese version of the API shows good psychometric properties in terms of reliability and validity, and exhibits measurement equivalence across the genders. Therefore, it could be used to comprehensively assess the severity of drug dependence in people with substance use disorders.
The use of digitally collected patient-reported outcome measures for newly operated patients with total knee and hip replacements to improve post-treatment recovery: study protocol for a randomized controlled trial
Authors: Kuklinski David , Oschmann Laura , Pross Christoph , Busse Reinhard , Geissler Alexander 
Published: April 2020

Abstract
Background
The number of total knee replacements (TKRs) and total hip replacements (THRs) has been increasing noticeably in high-income countries, such as Germany. In particular, the number of revisions is expected to rise because of higher life expectancy and procedures performed on younger patients, impacting the budgets of health-care systems. Quality transparency is the basis of holistic patient pathway optimization. Nevertheless, a nation-wide cross-sectoral assessment of quality from a patient perspective does not yet exist. Several studies have shown that the use of patient-reported outcome measures (PROMs) is effective for measuring quality and monitoring post-treatment recovery. For the first time in Germany, we test whether early detection of critical recovery paths using PROMs after TKR/THR improves the quality of care in a cost-effective way and can be recommended for implementation into standard care.

Methods/design
The study is a two-arm multi-center patient-level randomized controlled trial. Patients from nine hospitals are included in the study. Patient-centered questionnaires are employed to regularly measure digitized PROMs of TKR/THR patients from the time of hospital admission until 12 months post-discharge. An expert consortium has defined PROM alert thresholds at 1, 3, and 6 months to signal critical recovery paths after TKR/THR. An algorithm alerts study assistants if patients are not recovering in line with expected recovery paths. The study assistants contact patients and their physicians to investigate and, if needed, adjust the post-treatment protocol. When sickness funds’ claims data are added, the cost-effectiveness of the intervention can be analyzed.

Discussion
The study is expected to deliver an important contribution to test PROMs as an intervention tool and examine the determinants of high-quality endoprosthetic care. Depending on a positive and cost-effective impact, the goal is to transfer the study design into standard care. During the trial design phase, several insights have been discovered, and there were opportunities for efficient digital monitoring limited by existing legacy care models. Digitalization in hospital processes and the implementation of digital tools still represent challenges for hospital personnel and patients. Furthermore, data privacy regulations and the separation between the in- and outpatient sector are roadblocks to effectively monitor and assess quality along the full patient pathway.

Trial registration
German Clinical Trials Register: DRKS00019916. Registered November 26, 2019 – retrospectively registered.
Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series
Authors: Agrawal Gaurav , Clancy Annabel , Huynh Roy , Borody Thomas 
Published: April 2020

Abstract
Background
Crohn’s disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology—Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.

Results
Ten patients were identified to have achieved prolonged remission for 3–23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection.

Conclusions
Prolonged remission has been achieved for 3–23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.
Distribution of genes related to Type 6 secretion system and lipooligosaccharide that induced ganglioside mimicry among Campylobacter jejuni isolated from human diarrhea in Thailand
Authors: Serichantalergs Oralak , Wassanarungroj Patcharawalai , Khemnu Nuanpan , Poly Frédéric , Guerry Patricia , Bodhidatta Ladaporn , Crawford John , Swierczewski Brett 
Published: April 2020

AbstractBackgroundCampylobacter jejuni(C. jejuni) is one of the most common bacteria responsible for human gastroenteritis worldwide. The mode of human transmission is foodborne infections due to consumption of contaminated food, especially poultry. Type 6 secretion systems (T6SS) were described recently asCampylobactervirulence mechanisms. Furthermore, infection sequelae associated with neurological disorders like Guillain–Barré (GBS) and Miller Fisher (MF) syndromes can become serious health problems in some patients afterCampylobactergastroenteritis. Our objective was to determine the distribution of these virulence genes amongC. jejuniisolated from stool of human diarrhea.MethodsA total of 524C. jejunistrains from travelers and pediatric cases of acute diarrhea in Thailand were selected for this study. All isolates belonged to one of 20 known capsule types and all were assayed by PCR for T6SS, a hemolysin co-regulated protein (hcp) gene, and GBS-associated genes (cgtA,cgtB,cstIIHS19andcstIIHS2) which are involved in sialic acid production in the lipooligosaccharide (LOS) cores ofC. jejuni. The distribution of these genes are summarized and discussed.ResultsOf all isolates with these 20 capsule types identified, 328 (62.6%) were positive forhcp, ranging from 29.2 to 100% among 10 capsule types. The GBS-associated LOS genes were detected among 14 capsule type isolates with 24.4% and 23.3% ofC. jejuniisolates possessed eithercstIIHS19or all three genes (cgtA,cgtBandcstIIHS19), which were classified as LOS classes A and B whereas 9.2% ofC. jejuniisolates possessingcstIIHS2were classified as LOS class C. TheC. jejuniisolates of LOS A, B, and C together accounted for 56.9% of the isolates among 14 different capsule types while 31.1% of allC. jejuniisolates did not possess any GBS-associated genes. No significant difference was detected fromC. jejuniisolates possessing GBS-associated LOS genes among travelers and children, but changes between those withhcpwere significant (p < 0.05).ConclusionsOur results suggested a high diversity ofhcpand GBS-associated LOS genes among capsule types ofC. jejuniisolated from Thailand.
The predictive value of tumor mutation burden for immune checkpoint inhibitors therapy in non-small cell lung cancer is affected by patients’ age
Authors: Wu Yongfeng , Xu Jinming , Xu Jiawei , Wang Yiqing , Wang Luming , Lv Wang , Hu Jian 
Published: April 2020

AbstractHigh tumor mutation burden (TMB), which is associated with increased tumor immunogenicity, has been identified to predict improved response to immune checkpoint inhibitors (ICIs) therapy in non-small cell lung cancer (NSCLC). As host immunity is also significant to eliminate cancer cells, however, its clinical impact on cancer immunotherapy is still largely unknown. Here we explored the influence of age, which is an important characteristic to evaluate immune response of patients, on TMB-based predictive system for ICIs therapy in NSCLC. Our results showed that high TMB was capable of predicting better durable clinical benefit (DCB) in agelow group, while it was insignificant in agehigh group. Besides, the predictive power of TMB for progression-free survival (PFS) and overall survival (OS) was better in agelow group than in agehigh group. Our study illustrated that the predictive value of TMB for ICIs therapy was better in young patients than in elderly patients in NSCLC.
Improvements of poly(3-hydroxybutyrate) production in an air-lift reactor using simple production media
Authors: Ortiz-Veizán Nancy , Daga-Quisbert Jeanett , Perez-Zabaleta Mariel , Guevara-Martínez Mónica , Larsson Gen , Quillaguamán Jorge 
Published: April 2020

Abstract
Background
Halomonas boliviensis is a halophilic microorganism that accumulates poly(3-hydroxybutyrate) (PHB) using different carbons sources when nitrogen is depleted from the culture medium. This work presents an improved production of PHB using an air-lift reactor (ALR) that was fed with a concentrated solution of a carbon source, and was supplemented with an adequate airflow rate.

Results
Simple production media were used to study PHB production by H. boliviensis in an ALR. Glucose was first used as the main carbon source and was fed during the exponential phase of cell growth. The maximum CDW and PHB content were 31.7 g/L and 51 wt%, respectively, when the airflow rate entering the reactor varied between 0.5 and 1.2 L/min. Changing the air inflow to 0.5–0.9 L/min resulted in an improvement in PHB accumulation (62 wt%). A cultivation was performed by using the latter range of airflow rate and feeding glucose only when nitrogen was depleted from the medium; a considerable enhancement in PHB content (72 wt%) and CDW (27 g/L) was achieved under these conditions. Moreover, PHB was also produced using molasses as the main carbon source. Residual cell mass was about the same to that achieved with glucose, however the PHB content (52 wt%) was lower.

Conclusions
PHB production by H. boliviensis in an ALR using a simple medium is possible. CDW and PHB content in H. boliviensis can be improved with respect to batch cultivations previously reported when a carbon source is fed to the reactor. The best strategy for the production of PHB consisted of starting the cultivation in a batch mode while glutamate was present in the medium; glucose should be fed when glutamate is depleted from the medium to keep an excess of the carbon source during the synthesis of PHB.
Fenomenologia de Eros e de Afrodite em Safo
Authors: Araújo Fabíola Menezes 
Published: April 2020

Safo tece palavras que nascem como sinais enviados pelos deuses: é por permitir a tecitura de Afrodite (Ἀφροδίτα), tecelã de ardis (δολόπλοκε), que o Deus Eros é desejado e invocado constantemente em suas canções. Evocando-os a poeta vai contra o senso-comum grego, para quem estes deuses poderiam trazer apenas destruição, e nos permite pensar a superação da metafísica por um retorno à Grécia diferente do levado a cabo até hoje pela retórica de pensadores brancos. Aqui terá palavra uma mulher possivelmente negra. Não se furtará a extraordinária poeta a falar da morte (tanatos) que surge em meio à totalidade (panta), como advindas de um Deus, o amor, como quem, ao se realizar, realiza também a forma (eidos) e a justiça (dike) divinas. Palavras-chave: Afrodite; Eros, Safo, morte, totalidade.
High-speed and robust infrared-guiding multiuser eye localization
system for autostereoscopic display
Authors: Li Xicai , Wu Qinqin , Xiao Bangpeng , Liu Xuanyi , Xu Chen , Li Xueling , Xu Bin , Wang Yuanqing 
Published: April 2020

In order to localize the viewers’ eyes, a high-speed and robust
infrared-guiding multiuser eye localization system was fabricated in
this paper for a binocular autostereoscopic display, which can project
a pair of parallax images to corresponding eyes. The system is
composed of a low-resolution thermal infrared camera, a pair of
high-resolution left and right visible spectral cameras, and an
industrial computer. The infrared camera and the left visible spectral
camera, and the left and right visible spectral camera, can both form
the binocular vision system. The thermal infrared camera
can capture the thermography images. The left and right visible
spectral cameras can capture the left and right visible spectral
images, respectively. Owing to the temperature difference between the
face and background, the features of the face in thermography images
are prominent. We use the YOLO-V3 neural network to detect the
viewers’ faces in thermography images. Owing to the different features
of the pseudo and real faces in the infrared spectral, in the
thermography images, the pseudo-faces can be easily eliminated.
According to the positions and sizes of potential bounding boxes of
the detected faces in the thermography images, the industrial computer
can be guided to determine the left candidate regions in the left
visible spectral image. Then, the industrial computer can determine
the right candidate regions in the right visible spectral image. In
the left candidate regions, the industrial computer detects the faces
and localize the eyes by using the SeetaFace algorithm. The template
matching is performed between the left and right candidate regions to
calculate the accurate distance between the viewer and the system. The
average detection time of the proposed method is about 3–8 ms.
Compared with traditional methods, the localization time is improved
by 86.7%–90.1%. Further, the proposed method is hardly influenced by
the pseudo-faces and the strong ambient light.