bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED: Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study
Authors: Nicholson Brian D , Aveyard Paul , Price Sarah J , Hobbs FD Richard , Koshiaris Constantinos , Hamilton Willie 
Published: August 2020

Abstract

Objective
To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).

Design
Diagnostic accuracy study.

Setting
Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England.

Participants
63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012.

Main outcome measures
Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios.

Results
Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites.

Conclusion
The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.
Assessing the impact of a local community subsidised rideshare programme on road traffic injuries: an evaluation of the Evesham Saving Lives programme
Authors: Humphreys David K , Degli Esposti Michelle , Williams Frances M , Kondo Michelle C , Morrison Christopher 
Published: August 2020

BackgroundAlcohol-related vehicle crashes pose a significant challenge to public health in suburban communities. The Evesham Saving Lives programme operated between late 2015 and 2019 in two townships (Evesham and Voorhees) in New Jersey. The programme subsidised rideshare (eg, Uber) trips from bars and restaurants between the hours of 21:00 and 02:00 to prevent alcohol-related traffic injuries.MethodsThis study used data from the New Jersey Department of Transportation to examine changes to rates of injury crashes between 2010 and 2018. We used an ecological difference-in-difference design with Bayesian conditional autoregressive Poisson models to compare rates of injury crashes between participating municipalities (n=2) and non-participating municipalities (n=75). Sensitivity analyses included comparison with a weighted synthetic control series.ResultsThe Evesham Saving Lives programme was associated with 18% fewer injury crashes overall (IRR=0.82, 95% credible interval (CrI): 0.76, 0.88). Reductions in crashes were estimated to be greatest at night (IRR=0.62, 95% CrI: 0.48, 0.79), with moderate reductions in the afternoon (IRR=0.80, 95% CrI: 0.72, 0.88). We estimate that around three lives were saved (95% CrI: 2, 5) and around 371 injuries were prevented (95% CrI: 204, 625), potentially making considerable savings in terms of medical and economic expenses.ConclusionsThese findings support the claim that improving the convenience and reducing the costs of alternative night-time transportation can prevent road traffic injuries. Future studies should aim to replicate these analyses in programmes that have been implemented in other suburban communities across the US.
Nek9,a sensitive immunohistochemical marker for Schwannian, melanocytic and myogenic tumours
Authors: Shen Wenping , Han Qun , Sun Feifei , Li Zhishuang , Li Li 
Published: August 2020

AimsIn our previous study, striking Nek9 staining was observed in peripheral nerves for the first time. Therefore, in the current study, we aimed to detect Nek9 expression in peripheral nerve sheath tumours, melanocytic tumours and their mimics.MethodsThe expression of Nek9 was analysed in 234 mesenchymal tumours including schwannoma, neurofibroma, malignant peripheral nerve sheath tumour (MPNST), melanoma and their mimics adopting immunohistochemistry. In addition, S-100 and SOX10 were detected in all tumours.ResultsThe results revealed an intense and diffuse staining of Nek9 in all schwannomas (30/30) and melanomas (20/20). The neurofibromas (86%, 19/22) and MPNSTs (76%, 18/21) showed a high frequency of positive Nek9 staining. Nek9 showed a comparable sensitivity to S-100, and better sensitivity and less specificity than that of SOX10. Among the histological mimics, Nek9 was only strongly and diffusely expressed in rhabdomyosarcomas (RSs) (97%,37/38) while negatively stained in most of the other tumours. It was noted that Nek9 immunoresponse was more diffuse than that of MyoD1 and myogenin in RS.ConclusionsIn summary, Nek9 has a good sensitivity in the diagnosis of tumours with Schwannian, melanocytic and skeletal muscle differentiations. The immunohistochemical analysis of Nek9 expression may be helpful in the diagnosis and differential diagnosis of the aforementioned tumours.
Spinal cannabinoid receptor 2 activation reduces hypersensitivity associated with bone cancer pain and improves the integrity of the blood–spinal cord barrier
Authors: Wang Chenchen , Xu Ke , Wang Yu , Mao Yanting , Huang Yulin , Liang Ying , Liu Yue , Hao Jing , Gu Xiaoping , Ma Zhengliang , Sun Yu'e 
Published: August 2020

Background
Disruption of the blood–spinal cord barrier (BSCB) can facilitate inflammation that results in pain hypersensitivity. Proinflammatory cytokines produced by activated microglia and astrocytes damage the BSCB. This study aims to explore whether the BSCB is damaged in the bone cancer pain (BCP) model and to investigate a potential role and mechanism of JWH015 ((2-methyl-1-propyl-1H-indol-3-yl)−1-naphthalenylmethanone), a selective cannabinoid receptor 2 (CB2R) agonist, in preserving the BSCB integrity in the BCP model.

Methods
We used a male mouse model of BCP. Pain hypersensitivity was measured over time. Evans blue dye extravasation, transmission electron microscopy and Western blotting were performed to investigate the permeability and structural integrity of the BSCB. Immunofluorescence staining and western blotting were used to investigate the effect of JWH015 on the activation of glial cells and the levels of proinflammatory cytokines.

Results
A single intrathecal injection of JWH015 ameliorated pain hypersensitivity, the BSCB disruption and microglia and astrocyte activation. Decreases in the expression of ZO-1 and claudin-5 were partially restored by JWH015. The levels of the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α and the enzyme MMP9 were reduced by JWH015. However, all effects were prevented by pretreatment with a CB2R-selective antagonist, AM630 ((6-iodo-2-methyl-1-(2-morpholinoethyl)−1H-indol-3-yl)(4-methoxyphenyl)methanone).

Conclusions
JWH015 alleviates neuroinflammation and maintains the BSCB integrity and permeability in a mouse model of BCP, which is probably mediated by inhibiting glial cells activation. This study reveals the new analgesic mechanism of JWH015 on BCP and provides a perspective to explore novel drugs that target the BSCB to control BCP.
Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey
Authors: Flower Barnaby , Brown Jonathan C , Simmons Bryony , Moshe Maya , Frise Rebecca , Penn Rebecca , Kugathasan Ruthiran , Petersen Claire , Daunt Anna , Ashby Deborah , Riley Steven , Atchison Christina Joanne , Taylor Graham P , Satkunarajah Sutha , Naar Lenny , Klaber Robert , Badhan Anjna , Rosadas Carolina , Khan Maryam , Fernandez Natalia , Sureda-Vives Macià , Cheeseman Hannah M , O'Hara Jessica , Fontana Gianluca , Pallett Scott J C , Rayment Michael , Jones Rachael , Moore Luke S P , McClure Myra O , Cherepanov Peter , Tedder Richard , Ashrafian Hutan , Shattock Robin , Ward Helen , Darzi Ara , Elliot Paul , Barclay Wendy S , Cooke Graham S 
Published: August 2020

BackgroundAccurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.MethodsSensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two ‘in-house’ ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum.Findings95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%–99.8%).InterpretationLFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.
Influence of anisotropy, tilt and pairing of Weyl nodes: the Weyl semimetals TaAs, TaP, NbAs and NbP
Authors: Grassano Davide , Pulci Olivia , Cannuccia Elena , Bechstedt Friedhelm 
Published: August 2020

Abstract

By means of ab initio band structure methods and model Hamiltonians we investigate the electronic, spin and topological properties of four monopnictides crystallizing in bct structure. We show that the Weyl bands around a WP W1 or W2 possess a strong anisotropy and tilt of the accompanying Dirac cones. These effects are larger for W2 nodes than for W1 ones. The node tilts and positions in energy space significantly influence the DOS of single-particle Weyl excitations. The node anisotropies destroy the conventional picture of (anti)parallel spin and wave vector of a Weyl fermion. This also holds for the Berry curvature around a node, while the monopole charges are independent as integrated quantities. The pairing of the nodes strongly modifies the spin texture and the Berry curvature for wave vectors in between the two nodes. Spin components may change their orientation. Integrals over planes perpendicular to the connection line yield finite Zak phases and winding numbers for planes between the two nodes, thereby indicating the topological character.

Graphical abstract
Abstract A02: Photodynamic therapy in combination with immunotherapy enhances the long-term cure of bladder cancer in tumored mice
Authors: Durrani Farukh , Aly Ahmed , Guru Khurshid , Pandey Ravindra 
Published: August 2020

Abstract
Introduction and Objectives: To investigate the utility of combination approach for treating bladder cancer, mice bearing UMUC3 (human transitional cell carcinoma) and T24 (human urinary bladder) tumors were treated with HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a)-PDT alone and in combination with BCG. The HPPH, a multifunctional agent, was selected as a photosensitizer because of its higher tumor avidity, improved fluorescence imaging ability, and limited skin phototoxicity than Photofrin, a current clinical standard.
Methods: Imaging: IVIS/Spectrum: A noninvasive in vivo, continuous wave fluorescence imaging apparatus used to assess the localization and distribution of the PS at variable time points. In vivo efficacy studies using UMUC3 and T24 tumors in SCID mice with PS HPPH in combination with BCG.
Results: Imaging: Tumor uptake in UMUC3 and T24 tumors using IVIS Imaging. PS HPPH showed high tumor uptake and significant difference in their pharmacokinetic profiles in UMUC3 and T24 tumors implanted in SCID mice: The SCID mice bearing either UMUC3 or T24 tumors (4-5 mm size) were injected with the PS HPPH. The tumored mice (3 mice/group) at a dose of 0.47 u-mol/kg) and imaged at variable time points. The uptake of tumor, liver, and skin was measured by IVIS system and interesting pharmacokinetic profiles of the PS were observed. The optimal tumors uptake in UMUC3 and T24 were at 24 hours and 8-12 hours, respectively. In vivo efficacy studies: PS (HPPH) in combination with BCG shows enhanced PDT efficacy CR (Cures) Day 30 = 14/22 = 63.6% and RG (Re-Growth) 6/22 = 36.4% in bladder tumors (UMUC3). To investigate the utility of combination treatment approach for treating bladder cancer, mice bearing UMUC3 tumors were injected intravenously with HPPH (0.47 u-mol/kg) and the tumors were exposed to laser light (135 J/cm2, 75 mW/cm2) at 24 h post-injection. One hour after the PDT treatment, BCG was injected (1-1.5 × 106 CFU), SQ weekly x 3 doses, and at day 30 the results are very encouraging.
Conclusions: The HPPH showed higher in vivo uptake (determined by fluorescence) in UMUC3 and T24 bladder cancer tumors with significant differences in the two tumor types. The treatment of HPPH-PDT in combination with BCG using SCID mice bearing UMUC3 tumors showed enhanced long-term tumor cure. Before initiating this approach to human phase I clinical trial, further studies are under way. Source of funding: Roswell Park Alliance Foundation.
Citation Format: Farukh Durrani, Ahmed Aly, Khurshid Guru, Ravindra Pandey. Photodynamic therapy in combination with immunotherapy enhances the long-term cure of bladder cancer in tumored mice [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A02.
Abstract A04: DNA damage repair gene mutations and associated tumor immune landscape as biomarkers of response to immunotherapy in muscle-invasive urothelial cancer
Authors: Vidotto Thiago , Nersesian Sarah , Graham Charles , Siemens David Robert , Koti Madhuri 
Published: August 2020

Abstract
Molecular subtyping of urothelial cancer (UC) has significantly advanced the understanding of bladder tumor heterogeneity and development of prognostic and predictive biomarkers. Evolving evidence across cancers strongly suggests that tumor immunoediting has a profound impact on the behavior of cancer cells and their adaptation to the coevolving microenvironment and response to treatment. In alignment with this concept, recent immune checkpoint blockade (ICB) therapies in UC have demonstrated the predictive potential of mutations in the DNA damage repair (DDR). A comprehensive understanding of DDR mutation-associated expression of immune regulatory genes could thus aid in expansion of current immunotherapies and predictive biomarkers for the design of patient-tailored combination treatments. We thus investigated the pretreatment tumor transcriptomic profiles of the five recently described molecular subtypes of muscle-invasive urothelial cancer (MIUC; n=408) from the Genomic Data Commons, to determine subtype-specific immune cell abundance, expression of 67 immune regulatory genes, and association with DDR gene mutation profiles. Analysis using CIBERSORT immune cell abundance determination tool showed significant differences in immune cell profiles and abundance between MIUC subtypes. Expression patterns of a selected panel of 67 genes including both immune-stimulatory and -inhibitory genes showed significant associations with subtypes and DDR mutation status. Findings from our study provide compelling evidence for coexpression of multiple immune checkpoint genes including PD-1, PD-L1, IDO1, TIGIT, TIM-3, TGFB1, LAG3, and others, that potentially contribute to compensatory immune evasion in bladder tumors. Our findings also emphasize the urgent need for biomarker discovery approaches that combine molecular subtype, DDR gene mutation status, tumor immune landscape classification, and immune checkpoint gene expression to increase the number of patients responding to immunotherapies.
Citation Format: Thiago Vidotto, Sarah Nersesian, Charles Graham, David Robert Siemens, Madhuri Koti. DNA damage repair gene mutations and associated tumor immune landscape as biomarkers of response to immunotherapy in muscle-invasive urothelial cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A04.
Abstract A11: Generation and characterization of immune-competent syngeneic model of muscle-invasive bladder cancer (MIBC)
Authors: Shah Shruti D. , Gillard Bryan , Karasik Ellen , Wrobel Michelle , Moser Michael T. , Foster Barbara A. 
Published: August 2020

Abstract
Immunologically, MIBC tumors can be divided into inflamed and noninflamed phenotype. Inflamed tumors show high immune cell infiltration. In contrast, noninflamed tumors have little to no immune infiltration. Clinical evidence shows that response to therapy, particularly immune therapy, is associated with the immune phenotype of the tumor. In our preliminary analysis of the TCGA tumor expression data, we observed that patients with high CD8 T-cell infiltration expression signature show an improved overall survival irrespective of treatment. To study the molecular and immunologic drivers of CD8+ T-cell tumor infiltration in MIBC, we have generated immune-competent syngeneic models of bladder cancer. The mouse models were generated by inducing invasive disease by treating C57BL/6 mice with carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). The induced tumors were grafted into sex-matched immune-competent syngeneic hosts establishing allograft tumor lines. The models represent different clinical subtypes both molecularly and histologically. Currently we have 8 different models with squamous, sarcamatoid, or a more differentiated phenotype. RNA-seq analysis of the tumor lines was used to classify the models into basal-like and luminal-like tumors using the TCGA classifier system. Using the RNA-seq data, we applied a deconvolution algorithm to identify models that had inflamed or noninflamed immune phenotype. Flow cytometry data indicate that the inflamed tumors have a higher infiltration of the myeloid population. We treated 4/8 models with cisplatin, the current standard of care. The models show variable response to cisplatin, indicating the variability between the different models. In conclusion, we have successfully developed immune-competent syngeneic mouse models of MIBC that can be used to study the molecular and immune-driven processes of the disease.
Citation Format: Shruti D. Shah, Bryan Gillard, Ellen Karasik, Michelle Wrobel, Michael T. Moser, Barbara A. Foster. Generation and characterization of immune-competent syngeneic model of muscle-invasive bladder cancer (MIBC) [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A11.
Abstract A15: Uninflamed immunologic microenvironment of muscle-invasive bladder cancer associates with activating FGFR3 gene alterations
Authors: Weyerer Veronika , Stoehr Robert , Strissel Pamela , Strick Reiner , Bolenz Christian , Hartmann Arndt , Erben Philipp , Eckstein Markus 
Published: August 2020

Abstract
Background and Objective: Muscle-invasive bladder cancer (MIBC) is a complex disease for which perioperative chemotherapy followed by radical cystectomy is a standard treatment. In recent years new therapy options for advanced urothelial tumors have emerged, representing a personalized medicine approach for patients. For example, targeting fibroblast growth factor receptors (FGFR) as well as restoring antitumor activity using PD-1/PD-L1 inhibitors are currently being evaluated in clinical trials and show promising results. Our present goal in this study was to assess the relationship of FGFR3-gene alterations, immune cell types, gene expression of checkpoint inhibitors like PD-L1/PD-1, and immune-related genes in MIBC to gain insight into significant differential expression.
Materials and Methods: We analyzed the TCGA cohort (n=407). Tumors were identified with activating FGFR3-gene alterations (FGFR3-altered: mutation, amplification, fusion, gain). A comparison was performed between tumors with FGFR3-altered or wild-type tumors and tumor mutational burden (TMB), neoantigen load, immune checkpoint, and immune-related gene expression as well as specific immune cell populations using the CIBERSORT-algorithm.
Results: Activating FGFR3-altered tumors showed significantly less TMB and neoantigen load compared to wild-type cases (p=0.037 and p=0.04). Tumors with high expression of PD-1, PD-L1, CTLA4, and IDO1 were predominately not FGFR3-altered (p&lt;0.0001). Additionally, expression of immune-related genes like CD3Z, CD8A, FOXP3 and amounts of specific immune cell populations were significantly inversely associated with an FGFR3-altered status.
Conclusion: Strikingly, our analysis demonstrates that activating FGFR3 gene alterations in MIBC show low immune checkpoint and immune-related gene expression as well as low amounts of immune cells, demonstrating association with an uninflamed tumor microenvironment. Therefore, combination therapies targeting FGFR3 and, e.g., PD-1/PD-L1 might not be effective. It will be essential to validate these results in another MIBC cohort as well as unravel the role of aberrant signaling of FGFR3.
Citation Format: Veronika Weyerer, Robert Stoehr, Pamela Strissel, Reiner Strick, Christian Bolenz, Arndt Hartmann, Philipp Erben, Markus Eckstein. Uninflamed immunologic microenvironment of muscle-invasive bladder cancer associates with activating FGFR3 gene alterations [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A15.