bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Tumor Cell Subtypes and T-cell Populations as Prognostic Biomarkers to Combination Immunotherapy in Patients with Metastatic Genitourinary Cancer
Authors: Chalfin Heather J. , Pramparo Tiziano , Mortazavi Amir , Niglio Scot A. , Schonhoft Joseph D. , Jendrisak Adam , Chu Yen-Lin , Richardson Robin , Krupa Rachel , Anderson Amanda K.L. , Wang Yipeng , Dittamore Ryan , Pal Sumanta K. , Lara Primo N. , Stein Mark N. , Quinn David I. , Steinberg Seth M. , Cordes Lisa M. , Ley Lisa , Mallek Marissa , Sierra Ortiz Olena , Costello Rene , Cadena Jacqueline , Diaz Carlos , Gulley James L. , Dahut William L. , Streicher Howard , Wright John J. , Trepel Jane B. , Bottaro Donald P. , Apolo Andrea B. 
Published: December 2020

Abstract

Purpose:
Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy.

Experimental Design:
Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test.

Results:
From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline (P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9–2.3 vs. 28.2 months; P &lt; 0.0001–0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS (P = 0.045). PD-L1+ CTCs on-therapy were associated with worse OS (P &lt; 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category.

Conclusions:
Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1+ CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies.
Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity
Authors: Kim Sang-In , Park Anthony K. , Chaurasiya Shyambabu , Kang Seonah , Lu Jianming , Yang Annie , Sivanandam Venkatesh , Zhang Zhifang , Woo Yanghee , Priceman Saul J. , Fong Yuman , Warner Susanne G. 
Published: December 2020

AbstractAlthough it is known that oncolytic viruses can inflame and recruit immune cells to otherwise immunosuppressed tumor microenvironments, the influence of the antiviral immune response on antitumor immunity is less clear across viral platforms and tumor types. CF33 is a recombinant orthopoxvirus backbone effective against colon cancer. We tested derivatives of CF33 with and without immune-checkpoint inhibition (anti–PD-L1) in mouse models of colon cancer. Results showed that the efficacy of CF33 backbone with J2R deletion (single-deleted) against colon cancer is not altered by additional deletion of F14.5L in vitro or in vivo. CF33 infection upregulated PD-L1 expression on tumor cells and led to an increased influx of lymphocytes and macrophages in tumors. Also, the levels of active CD8+ (IFNγ+) T cells in the virus-treated tumors were higher than those in control-treated tumors. Furthermore, a combination of CF33 derivatives with anti–PD-L1 resulted in durable tumor regression and long-term survival, resistant to tumor rechallenge. Analysis of immune cells from the treated mice showed that tumor-specific T cell activation occurred more robustly in tumors treated with the virus and that T cells were more strongly activated against the virus than against tumor, in an MHC-I–dependent manner. Our findings warrant further studies on the role of cross-priming of T cells against viral and tumor antigens, in the overall success of viroimmunotherapy.
Personal Neoantigen Cancer Vaccines: A Road Not Fully Paved
Authors: Fritsch Edward F. , Burkhardt Ute E. , Hacohen Nir , Wu Catherine J. 
Published: December 2020

Abstract
Personal neoantigen–based cancer vaccines are designed to target antigens arising from tumor-specific mutations within individual cancers and present a tremendous opportunity to capitalize on their favorable and intrinsic properties of escape from central tolerance and exquisite tumor specificity. With the endpoint of creating an optimal T-cell army to attack a tumor, neoantigen-based vaccines have demonstrated the ability to coax naïve T-cell recruits against epitopes that do not induce spontaneous immunity to raise long-lasting T-cell responses against multiple tumor-specific epitopes and subsequently to extend the breadth of responses, as immunity begets immunity via epitope spreading. Importantly, on both preclinical and clinical fronts, the association of T-cell responses to neoantigens and favorable outcomes has been demonstrated time and time again. We recognize, however, that the path forward remains long and winding and requires the field to address several key challenges, particularly overcoming evolved tumor escape mechanisms and optimizing vaccine-induced immunity. Some challenges stem from gaps in science that enable in silico prediction of antigen presentation and recognition by T-cell receptors, whereas others stem from the logistical obstacles and cost of personalization. Nevertheless, with perseverance and innovative solutions, we have little doubt that the ability of neoantigen vaccination to induce potent cancer-specific T cells will fundamentally succeed in enabling greater effectiveness of a broad array of immunotherapies. We provide our perspective on the progress and the remaining challenges to realizing the opportunity of personal neoantigen cancer vaccines.
Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation
Authors: Xie Stephanie Z. , Kaufmann Kerstin B. , Wang Weijia , Chan-Seng-Yue Michelle , Gan Olga I. , Laurenti Elisa , Garcia-Prat Laura , Takayanagi Shin-ichiro , Ng Stanley W.K. , Xu ChangJiang , Zeng Andy G.X. , Jin Liqing , McLeod Jessica , Wagenblast Elvin , Mitchell Amanda , Kennedy James A. , Liu Qiang , Boutzen Héléna , Kleinau Melissa , Jargstorf Joseph , Holmes Gareth , Zhang Yang , Voisin Veronique , Bader Gary D. , Wang Jean C.Y. , Hannun Yusuf A. , Luberto Chiara , Schroeder Timm , Minden Mark D. , Dick John E. 
Published: December 2020

Abstract

Acute myeloid leukemia (AML) is a caricature of normal hematopoiesis driven from leukemia stem cells (LSC) that share some hematopoietic stem cell (HSC) programs including responsiveness to inflammatory signaling. Although inflammation dysregulates mature myeloid cells and influences stemness programs and lineage determination in HSCs by activating stress myelopoiesis, such roles in LSCs are poorly understood. Here, we show that S1PR3, a receptor for the bioactive lipid sphingosine-1-phosphate, is a central regulator that drives myeloid differentiation and activates inflammatory programs in both HSCs and LSCs. S1PR3-mediated inflammatory signatures varied in a continuum from primitive to mature myeloid states across cohorts of patients with AML, each with distinct phenotypic and clinical properties. S1PR3 was high in LSCs and blasts of mature myeloid samples with linkages to chemosensitivity, whereas S1PR3 activation in primitive samples promoted LSC differentiation leading to eradication. Our studies open new avenues for therapeutic target identification specific for each AML subset.

Significance:
S1PR3 is a novel regulator of myeloid fate in normal hematopoiesis that is heterogeneously expressed in AML. S1PR3 marks a subset of less primitive AML cases with a distinct inflammatory signature and therefore has clinical implications as both a therapeutic target and a biomarker to distinguish primitive from mature AML.
See related commentary by Yang et al., p. 3.
This article is highlighted in the In This Issue feature, p. 1
The Phenomenon of Dynasties of Jewish Doctors in the Mamluk Period (1250–1517)
Authors: Mazor Amir , Lev Efraim 
Published: December 2020

Abstract
This article discusses the phenomenon of dynasties of Jewish physicians in the Late Middle Ages in Egypt and Syria. Based on Muslim Arabic historiographical literature on the one hand, and Jewish sources such as Genizah documents on the other, this paper reconstructs fourteen dynasties of Jewish physicians that were active in the Mamluk Sultanate (1250–1517). Examination of the families reveals that the most distinguished dynasties of court physicians were of Jewish origin, and had to convert to Islam during the Mamluk period. Moreover, the office of the “Head of the Physicians” was occupied mainly by members of these convert Jewish dynasties. This situation stands in stark contrast to the pre-Mamluk period, in which dynasties of unconverted Jewish court physicians flourished. However, Jewish sources reveal that dynasties of doctors who were also communal leaders continued to be active also during the Mamluk period.
ONSTAGE, the Online Data System of Theatre in Amsterdam from the Golden Age to Today
Authors: Blom Frans R. E. , Nijboer Harm , van der Zalm Rob 
Published: December 2020

Abstract

ONSTAGE is the data repository for Amsterdam’s first and most prominent public theatre venue: the Schouwburg. In theatre history, the Amsterdam Schouwburg has a fairly unique place due to its rich body of extant account books, programs and administrative records of annual play lists, and registers of expenses and revenues. These sources, as a most sensitive finger on the theatre’s pulse, can be used as analytical tools that provide access to the theatre’s artistic business, from its foundation in 1638 until today. This data paper is an assessment of the new ONSTAGE data system, in terms of its structure, the nature of the data and enrichment, and the research potential. The paper also explores future growth in linked data systems.
Investigating Open-access Booking in New Brunswick Occupational Therapy
Authors: Speed David , Fyffe Shelley 
Published: December 2020

Background. Open-access booking (OAB) describes administrative changes to improve system efficiency. However, OAB studies have focused on GP practices and have not applied OAB to other health care services. Purpose. The purpose of the study was to investigate the associations between OAB and administrative outcomes in the Saint John region. Method. Evaluators compared three years of pre-OAB data against two years of post-OAB data using an interrupted-time series design (February 2014–January 2019). Findings. OAB was associated with a 12% jump in the likelihood of being discharged within three months even though clients received an equivalent level of service. OAB was not associated with more missed appointments (∼8% vs. ∼7%). While OAB was not associated with reduced wait times, the post-OAB period handled a larger number of client referrals, which may explain the null finding. Implications. OAB shows potential for improving administrative outcomes, but further research is needed.
Bilateral Eagle Syndrome
Authors: Dabrowski Dominik S. , Ghali Ghali E. , Cotelingam James D. 
Published: December 2020

Significance Statement Unilateral Eagle Syndrome is relatively rare and highlights important concepts in anatomy and pathophysiology. Bilateral Eagle Syndrome is exponentially more rare and has only been mentioned several times in the literature. Understanding the impact this can have on the human body and the severity of symptoms and sequelae is valuable for several types of specialists that treat this disorder.
Comparative effects on pain arising from injury to the knee meniscus in adults: A systematic review and network meta-analysis
Authors: Zhang Yongni , Cao Wuting , Cao Qin , Zhu Yi 
Published: December 2020

Objective: To identify the most effective pain management method for meniscus injuries by comparing pain relief observed with several common interventions including combined different combinations of surgery and exercise, surgery alone, supervised exercise alone and home exercise alone. Methods: PubMed, Embase, CINAHL, Cochrane Library, Web of Science, SportDiscus, and PEDro were searched from database inception through October 15, 2020. Randomized controlled trials investigating the effect of surgery and exercise for meniscus injuries by using the visual analogue scale (VAS) assessment were eligible for inclusion. Primary outcome was mean change in VAS score from baseline. Comparisons between interventions were made through use of random-effects network meta-analysis over the short-term (three months) and mid-term (12 months). Relative ranking of therapies was assessed by the surface-under-the-cumulative ranking possibilities. All reference lists of included studies were hand-searched. Results: We investigated six RCTs (total n = 796 patients). No significant difference was found between different treatments of pain control in three months and 12 months. The surface under the cumulative ranking curves suggested that supervised exercise combined with surgery was considered most likely to overshadow other treatments in reducing short-term pain (surface under cumulative ranking curve (SUCRA) values: 98.1; mean ranks: 1.1) and mid-term pain (SUCRA values: 97.2; mean rank: 1.1). Conclusion: There is not sufficient evidence to identify any preferred or more effective surgical and/or exercise-based treatment program.
Impact of neurotrophic factors combination therapy on retinitis pigmentosa
Authors: Yin Xiaobei , He Ting , Chen Rui , Cui Hui , Li Genlin 
Published: December 2020

Objective We aimed to determine the location of neurotrophic receptors tropomyosin receptor kinase (Trk)B, TrkC, and ciliary neurotrophic factor receptor (CNTFR)α in the retina of retinal degeneration ( rd) mice and to explore the dynamic changes of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X-protein (Bax), and microtubule-associated protein light chain 3 (LC3) expression and ultrastructure in the retina of rd mice intravitreally injected with neurotrophic factors. Methods Rd mice aged 2 and 3 weeks post-natally (PN) received intravitreal injections of neurotrophic factors. Two weeks later, their retinas were harvested for the detection of Bax, Bcl-2, and LC3 mRNA and protein expression. Results TrkB and TrkC expression levels were lower at 3 weeks PN compared with 0, 1, and 2 weeks PN, but CNTFRα expression was still detected in certain layers. The three receptors were expressed in different retinal layers at the same timepoint. Bax expression was downregulated in, rhBDNF + rhCNTF, rhBDNF + rhNT-3, groups 2 weeks after intravitreal injection; Bcl-2 expression was upregulated in the rhBDNF + rhCNTF + rhNT-3 group at PN-4w; and LC3 expression was upregulated in rhBDNF + rhCNTF + rhNT-3 groups. Conclusions The combined use of neurotrophic factors had a more significant effect on Bax, Bcl-2, and LC3 expression than the same factors used alone.
Can Patient-Reported Outcomes Predict the Need for Secondary Surgeries After Hip Arthroscopy?
Authors: Shapira Jacob , Bheem Rishika , Kyin Cynthia , Rosinsky Philip J. , Meghpara Mitchell B. , Maldonado David R. , Lall Ajay C. , Domb Benjamin G. 
Published: December 2020

Background: Patient-reported outcomes (PROs) capture the postoperative period and reflect the patient’s perspective of one’s own recovery. However, it is unknown if PROs can reflect and predict the need for secondary surgeries after a primary hip arthroscopy. Purpose: To examine if PROs at 3 months and 1 year after primary hip arthroscopy were correlated with future reoperations and determine the critical thresholds for significant PROs utilizing a multivariate logistic regression analysis and receiver operator characteristic (ROC) analysis. Study Design: Case-control study; Level of evidence, 3. Methods: Data on consecutive patients who underwent primary hip arthroscopy between February 2008 and August 2018 was retrospectively reviewed. Patients were included for analysis if they had the following PROs preoperatively and at 3 months and 1 year postoperatively: modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and visual analog scale (VAS) for pain. Patients were split into 2 groups: those who underwent secondary surgery and those who did not. Patient variables, intraoperative labral treatment, preoperative PROs, and postoperative PROs were compared between the 2 groups. A multivariate logistic regression analysis and ROC analysis were deployed to evaluate the correlation between PROs and the need for future surgery. Results: A total of 911 primary arthroscopy cases were included in this study. While age, body mass index, labral treatment, and 3-month and 1-year follow-up mHHS, NAHS, and VAS were significant in the bivariate analysis, the multivariate logistic regression analysis only found 1-year mHHS to be significant in the final model ( P < .05). The ROC curve for 1-year mHHS demonstrated acceptable discrimination between patients requiring secondary surgery and patients not requiring secondary surgery with an area under the curve of 0.73. Using the Youden index, a threshold of 80.5 was determined for the 1-year mHHS. Conclusion: The risk for secondary procedures may be evaluated with mHHS at 1 year after primary hip arthroscopy. Surpassing a score of 80.5 may be associated with a 74.4% reduction in risk for either a revision hip arthroscopy or a conversion to hip replacement.
A systematic approach towards implementing value-based health care in heart failure: Understandings from retrospective analysis methods in South London
Authors: Burnhope Emma , Waring Michael , Guilder Andrew , Malhotra Bharti , Cardoso Jorge M , Razavi Reza , Carr-White Gerald 
Published: December 2020

Background Value-Based Health Care (VBHC) is an evolving model of healthcare delivery aimed at achieving better patient outcomes at lower costs to the healthcare provider. The practise of VBHC requires efficient information systems with good reporting capability and subsequent outcome measuring. Information systems within the National Health Service (NHS) are often multiple and not necessarily integrated to one another. We therefore developed a systematic approach to collecting, validating and analysing data from multiple sources and information systems, with the aim of designing and endorsing an automatic system to capture health outcomes data in heart failure to support future VBHC models. Methods A retrospective cohort of heart failure patients with reduced ejection fraction undergoing Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) procedures within a limited geographical area in South London were evaluated. A purpose built database was created to integrate, transform and validate health care data from multiple information systems. Results Validation analysis shows that our implemented methodology has produced a robust dataset. Our limited cohort of 134 patients does not allow for any complex statistical analysis however has identified some important themes related to outcomes and costs. Conclusion We have created a validated database specific to our Trust that can be upscaled locally with ease and transferred to other health diseases. Due to variations in local procedure from one Trust to another, this methodology now requires implementation across multiple sites to understand differences in transformation of data and outcome measuring.
Effects of transcutaneous electrical acupuncture point stimulation on peripheral capillary oxygen saturation in elderly patients undergoing colonoscopy with sedation: a prospective randomized controlled trial
Authors: Chen Yongming , Gong Yin , Huai Xiaorong , Gu Xiyao , Su Diansan , Yu Weifeng , Xie Hong 
Published: December 2020

Introduction: This study investigated whether transcutaneous electrical acupuncture point stimulation (TEAS) at PC6 can reduce the proportion of elderly patients experiencing a drop of ⩾4% in peripheral capillary oxygen saturation (SpO2) while undergoing colonoscopy under sedation. Methods: A total of 32 elderly patients (aged ⩾ 65 years) scheduled for colonoscopy were randomly assigned in a 1:1 ratio to receive either real or sham TEAS (treatment or control groups, respectively). Each patient received oxygen (2 L/min) delivered routinely via nasal cannula. The treatment group was given TEAS at PC6 for 20 min at 2 Hz frequency and 6 mA intensity; the control group underwent the same procedures but with zero frequency/intensity. SpO2 and other physiological parameters were measured prior to sedation and colonoscopy (baseline) and at seven other timepoints through departure from recovery. Depth of anesthesia was measured using a Narcotrend monitor. Results: Significantly fewer patients in the treatment group experienced a ⩾4% decrease from baseline SpO2 (2/16) than patients in the control group (10/16; p = 0.004). The two groups were comparable with regard to respiratory rate, systolic and diastolic blood pressures, mean arterial pressure, and heart rate. Conclusion: TEAS applied at PC6 with 2 Hz frequency was feasible and may be helpful in reducing the rate of hypoxia in elderly patients during colonoscopy. Trial registration number: NCT03775122 (ClinicalTrials.gov).
Quantifying cognition and fatigue to enhance the sensitivity of the EDSS during relapses
Authors: Morrow Sarah A , Conway Devon , Fuchs Tom , Wojcik Curtis , Unverdi Mahmut , Yasin Faizan , Pol Jeta , Eckert Sveltlana , Hojnacki David H , Dwyer Michael , Zivadinov Robert , Weinstock-Guttman Bianca , Benedict Ralph HB 
Published: December 2020

Background: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. Objective: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS. Methods: This prospective study recruited PwMS from three dedicated MS centers. All subjects had EDSS, SDMT, and Fatigue Severity Scale (FSS) administered. Subjects experiencing a relapse were assigned to the relapse group (RG). Matched controls from the larger cohort were assigned to the stable group (SG). RG and SG subjects underwent the same evaluation at relapse and 3 months later. Our main outcomes were a modified CFSS (m-CFSS) and modified EDSS (m-EDSS), incorporating SDMT and FSS, accounting for cognitive performance and fatigue rating, during relapse. Results: The full cohort included 592 subjects; 80 qualified for RG and 72 were matched to the SG. The m-CFSS was significantly higher than CFSS at baseline (median = 2 vs. median = 0, p < 0.001) and relapse (median = 2 vs. median = 1, p < 0.001). The m-EDSS was higher than EDSS (median 3.0 vs. 2.5, p = 0.02) at relapse, where 35 RG subjects (43.8%) had higher m-EDSS than EDSS at relapse. Conclusion: This study demonstrates that incorporating the SDMT and FSS improves the accuracy of the EDSS, by accounting for cognitive changes, during relapse activity.