bluuebunny/crossref_metadata_2025_split huggingface dataset:
Readily accessible CT scoring method to quantify fibrosis in IPF
Authors: Fraser Emily , St Noble Victoria , Hoyles Rachel K , Benamore Rachel , Ho Ling-Pei 
Published: June 2020

IntroductionThere is currently no readily accessible measure to specifically quantify the amount of fibrosis in idiopathic pulmonary fibrosis (IPF). Such a measure could isolate contribution of fibrosis from other comorbidities to lung function abnormality and deterioration of disease, and potentially help determine if there has been response to antifibrotic treatment.MethodsIn a pilot study of 39 IPF patients, we used a CT-based visual scoring method to examine the correlation between the sum of all fibrotic features (all traction bronchiectasis, ground glass with traction bronchiectasis, honeycombing and reticulation; referred to as Total Fibrosis Score, TFS) or the individual fibrotic features, with lung function, Composite Physiologic Index (CPI) and time to death in the 5 years following CT measurement.ResultsTFS measurements were highly reproducible (r=0.982; p<0.001) and correlated significantly with TLCO, FVC and CPI. Traction bronchiectasis score was superior to others in its correlation to lung function and CPI, and as good as TFS. TFS and traction bronchiectasis score were also the best correlates (individually) to time to death (r=0.60 for both, and p=0.002 and p=0.004, respectively).ConclusionWe suggest that TFS and our 6-slices method of quantifying traction bronchiectasis on CT scans could be readily accessible and simple methods of quantifying lung fibrosis in IPF. These scores could assist in determining if clinical deterioration is due to worsening fibrosis, for correlation of research findings to amount of lung fibrosis, and to stratify patients for established drug treatment and clinical trials. Our findings also provide a basis for larger studies to validate these findings and determine if the scores could measure change in fibrosis.
Single inclusive jet photoproduction at very forward rapidities in pp and pPb collisions at the LHC
Authors: Gonçalves V. P. , Sampaio dos Santos G. , Sena C. R. 
Published: June 2020

AbstractThe particle production at very forward rapidities is expected to be sensitive to the non-linear effects in the QCD dynamics at high energies. In this paper we present, for the first time, the predictions of the Color Dipole formalism for the single inclusive jet photoproduction in pp and pPb collisions considering the very forward rapidities probed by the CMS-CASTOR calorimeter, which will be characterized by a jet in the rapidity range of $$5.2 \le Y \le 6.6$$5.2≤Y≤6.6, a rapidity gap in the rapidity range probed by the central CMS detector and one of the incident hadrons remaining intact in the final state. The transverse momentum distributions and energy spectra are estimated considering the more recent phenomenological models for the dipole-proton scattering amplitude, which are based on the Color Glass Condensate formalism and are able to describe the inclusive and exclusive ep HERA data. Our results indicate that a future experimental analysis of this process is, in principle, feasible and useful to constrain the description of the QCD dynamics at high energies.
The Influence of Immune Heterogeneity on the Effectiveness of Immune Checkpoint Inhibitors in Multifocal Hepatocellular Carcinomas
Authors: Huang Manling , He Minghui , Guo Yu , Li Heping , Shen Shunli , Xie Yubin , Li Xiaoxing , Xiao Han , Fang Lujing , Li Dongming , Peng Baogang , Liang Lijian , Yu Jun , Kuang Ming , Xu Lixia , Peng Sui 
Published: June 2020

Abstract

Purpose:
Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.

Experimental Design:
We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti–programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated.

Results:
The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti–PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti–PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma.

Conclusions:
The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti–PD-1 therapy.
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?
Authors: Khasraw Mustafa , Reardon David A. , Weller Michael , Sampson John H. 
Published: June 2020

Abstract
Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint inhibitors and programmed cell death (PD)-1/PD-L1 inhibitors have transformed the landscape of cancer treatment and improved patient survival in a number of different cancer types. With the exception of few select cases (e.g., patients with Lynch syndrome) the neuro-oncology community is still awaiting evidence that PD-1 blockade can lead to meaningful clinical benefit in glioblastoma. This lack of progress in the field is likely to be due to multiple reasons, including inherent challenges in brain tumor drug development, the blood–brain barrier, the unique immune environment in the brain, the impact of corticosteroids, as well as inter- and intratumoral heterogeneity. Here we critically review the clinical literature, address the unique aspects of glioma immunobiology and potential immunobiological barriers to progress, and contextualize new approaches to increase the efficacy of PD-1/PD-L1 inhibitors in glioblastoma that may identify gaps and testable relevant hypotheses for future basic and clinical research and to provide a novel perspective to further stimulate preclinical and clinical research to ultimately help patients with glioma, including glioblastoma, which is arguably one of the greatest areas of unmet need in cancer. Moving forward, we need to build on our existing knowledge by conducting further fundamental glioma immunobiology research in parallel with innovative and methodologically sound clinical trials.
Tumor Endothelial Cell–Mediated Antigen-Specific T-cell Suppression via the PD-1/PD-L1 Pathway
Authors: Taguchi Kazuhiro , Onoe Takashi , Yoshida Tomoaki , Yamashita Yoshinori , Tanaka Yuka , Ohdan Hideki 
Published: June 2020

AbstractTumor endothelial cells (TEC) play multiple roles in the regional specialization of vascular structure and physiology. Because TECs in the tumor microenvironment come in contact with circulating immune cells, they might influence not only trafficking but also the antitumor cellular immune response. In a mouse tumor implantation model with B16 melanoma cells, TECs expressed MHC class II, costimulating molecules, and programmed death-ligand 1 (PD-L1), suggesting that they are antigen (Ag)-presenting cells with suppressive activity. Furthermore, TECs were able to take up and present tumor-derived ovalbumin (OVA) peptide on MHC class I molecules. In functional assays, B16-OVA tumor–derived TECs significantly suppressed the proliferation and Ag-specific cytotoxicity of OVA-specific CD8+ T cells relative to those of B16 tumor–derived TECs. This suppressive activity required cell–cell contact and was abrogated by PD-L1 blockade. TECs impaired proinflammatory cytokine production of CD8+ T cells, including IL2, TNFα, and IFNγ. B16-OVA tumor–derived TECs induced immunosuppressive CD4+ T cells that suppressed OVA-specific CD8+ T-cell proliferation via inhibitory cytokines, including IL10 and TGFβ. Deficiency of PD-L1 in TECs, but not in hematopoietic cells, impaired suppression and apoptosis of tumor-infiltrating CD8+ T cells, resulting in inhibition of tumor development in vivo model. These data suggest that TECs might regulate the immune response of tumor Ag–specific CD8+ T cells via the PD-1/PD-L1 pathway and induce immune suppressive CD4+ T cells in an Ag-specific manner, contributing to tumor immune evasion.Implications:The findings of this study might encourage the further development of novel anticancer therapies and strategies.
ADAM (a Disintegrin and Metalloproteinase) 15 Deficiency Exacerbates Ang II (Angiotensin II)–Induced Aortic Remodeling Leading to Abdominal Aortic Aneurysm
Authors: Jana Sayantan , Chute Michael , Hu Mei , Winkelaar Gerrit , Owen Caroline A. , Oudit Gavin Y. , Kassiri Zamaneh 
Published: June 2020

Objective:
ADAM (a disintegrin and metalloproteinase) 15—a membrane-bound metalloprotease from the ADAM (disintegrin and metalloproteinase) family—has been linked to endothelial permeability, inflammation, and metastasis. However, its function in aortic aneurysm has not been explored. We aimed to determine the function of ADAM15 in the pathogenesis of aortic remodeling and aneurysm formation.

Approach and Results:

Male
Adam15
-deficient and WT (wild type) mice (10 weeks old), on standard laboratory diet, received Ang II (angiotensin II; 1.5 mg/kg per day) or saline (Alzet pump) for 2 or 4 weeks. Ang II increased ADAM15 in WT aorta, while
Adam15
-deficiency resulted in abdominal aortic aneurysm characterized by loss of medial smooth muscle cells (SMCs), elastin fragmentation, inflammation, but unaltered Ang II–mediated hypertension. In the abdominal aortic tissue and primary aortic SMCs culture,
Adam15
deficiency decreased SMC proliferation, increased apoptosis, and reduced contractile properties along with F-actin depolymerization to G-actin. Ang II triggered a markedly greater increase in THBS (thrombospondin) 1 in
Adam15
-deficient aorta, primarily the medial layer in vivo, and in aortic SMC in vitro; increased SSH1 (slingshot homolog 1) phosphatase activity and cofilin dephosphorylation that promoted F-actin depolymerization and G-actin accumulation. rhTHBS1 (recombinant THBS1) alone was sufficient to activate the cofilin pathway, increase G-actin, and induce apoptosis of aortic SMCs, confirming the key role of THBS1 in this process. Further, in human abdominal aortic aneurysm specimens, decreased ADAM15 was associated with increased THBS1 levels and loss of medial SMCs.

Conclusions:
This study is the first to demonstrate a key role for ADAM15 in abdominal aortic aneurysm through regulating the SMC function, thereby placing ADAM15 in a critical position as a potential therapeutic target for abdominal aortic aneurysm.
The Emaciated Soul: Four Women’s Self-Inscriptions on Their Portraits in Late Imperial China
Authors: Wang Yuanfei 
Published: June 2020

Abstract
This article examines the emaciated self-images of four women’s self-inscription poems on their own portraits. They are Huang Hong (early seventeenth century), Xi Peilan (1760­­­–after 1829), Tan Yinmei (fl. mid-eighteenth to early nineteenth century) and Zheng Lansun (1819-61). These women similarly describe their self-images as qiaocui (emaciated), alluding to the legendary girl poet Feng Xiaoqing. Inherently ambivalent, qiaocui could imply sexual and erotic appeal, the virtuous mind of a recluse, sickness, ordinariness, melancholy, as well as aging and death. The article argues for the importance of the rhetoric of qiaocui and the topoi of Feng Xiaoqing in the self-inscriptions by women in Hangzhou and the broader Jiangnan region as a medium to construct their female subjectivity. This article suggests that, initially a persona publicly circulated in the late Ming, the topoi of Feng Xiaoqing came to define the women’s personhood in private spaces in late eighteenth and early nineteenth centuries.
Masculinity, Femininity, Sacrifice, and Celebrity during China’s War of Resistance: Telling the Lives of the Aviators Yan Haiwen (1916-37) and Lee Ya-Ching (1912-98)
Authors: Baumler Alan 
Published: June 2020

Abstract
During the War of Resistance against Japan (1937-1945) the Chinese government publicized heroic pilots to win domestic and international support for the war effort and to raise money. These pilots also helped create a gendered image of China that was used by both state and non-state actors. The male pilot and martyr Yan Haiwen (1916-37) was part of a masculine discourse of sacrifice aimed at domestic audiences. The female pilot Lee Ya-Ching (1912-98) presented a modern, technologized Chinese femininity which assisted in the Chinese war effort by appealing to white audiences, but was also used by Overseas Chinese communities for their own purposes.
Knowledge without “Experience”
Authors: Williams Michael 
Published: June 2020

Abstract
Genia Schönbaumsfeld argues that Cartesian skepticism is an illusion induced by the “Cartesian Picture” of perceptual knowledge, in which knowledge of the “external world” depends on an inference from how things subjectively seem to one to how they actually are. To show its incoherence, she draws on the work of John McDowell, which she sees as elaborating a central theme from Wittgenstein’s On Certainty. I argue that Cartesian skepticism is not an illusion, as Schönbaumsfeld understands ‘illusion’, and that McDowell’s account of perceptual knowledge is both untenable and incompatible with Wittgenstein’s ideas about knowledge. Schönbaumsfeld thinks that, to understand how perception can engender knowledge of the world, we need a non-Cartesian account of perceptual reasons. Wittgenstein offers a much more radical break with the Cartesian Picture: an account of knowledge without ‘experience’.
Efficacy of Velopharyngeal Surgery for Positional Obstructive Sleep Apnea Hypopnea Syndrome
Authors: Sun Nian , Ye Jingying , Zhang Junbo , Kang Dan , Tai Jun , Wang Shengcai , Zhang Jie , Ni Xin 
Published: June 2020

Background: Positional obstructive sleep apnea hypopnea syndrome (P-OSAHS) is a distinct OSAHS type. Whether velopharyngeal surgery is efficacious for patients with P-OSAHS remains unclear. Aim/Objective: To investigate the efficacy and factors influencing velopharyngeal surgery for treatment of patients with P-OSAHS, defined as the apnea hypopnea index (AHI) in different body postures (supine AHI ≥2*nonsupine AHI). Materials and Methods: A total of 44 patients with P-OSAHS who underwent velopharyngeal surgery were retrospectively studied. The clinical data of these patients, including polysomnography (PSG), physical examination, and surgical information, were collected for analysis. All patients underwent a PSG about 6 months after surgery to determine the treatment outcomes. Results: The overall AHI of the 44 patients decreased from 40.2 ± 18.7 events/h to 18.5 ± 17.5 events/h after surgery ( P < .001). There were 29 responders (65.9%) according to the classical definition of surgical success. The percentage of sleep time with oxygen saturation below 90% (CT90) was the only predictive parameter for surgical success ( P = .014, odds ratio value = 0.894). There was no significant difference between the change in supine AHI (−55.9 ± 35.2%) and the change in nonsupine AHI (−43.4 ± 74.1%; P = .167), and these 2 parameters were significantly correlated ( r = 0.616, P < .001). Among the 38 patients with residual OSAHS (residual AHI ≥5), 28 had persistent P-OSAHS, and the percentage was as high as 82.4%. Conclusions and Significance: Patients with P-OSAHS with a lower CT90 value are more likely to benefit from velopharyngeal surgery. Positional therapy could be indicated for most of the patients who are not cured by such surgery.
Medical cannabis in the UK: From principle to practice
Authors: Schlag Anne Katrin , Baldwin David S , Barnes Michael , Bazire Steve , Coathup Rachel , Curran H Valerie , McShane Rupert , Phillips Lawrence D , Singh Ilina , Nutt David J 
Published: June 2020

Background: In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet, to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast, a recent patient survey by the Centre for Medical Cannabis (Couch, 2020) found 1.4 m people are using illicit cannabis for medical problems. Aims: Such a mismatch between demand and supply is rare in medicine. This article outlines some of the current controversies about medical cannabis that underpin this disparity, beginning by contrasting current medical evidence from research studies with patient-reported outcomes. Outcomes: Although definite scientific evidence is scarce for most conditions, there is significant patient demand for access to medical cannabis. This disparity poses a challenge for prescribers, and there are many concerns of physicians when deciding if, and how, to prescribe medical cannabis which still need to be addressed. Potential solutions are outlined as to how the medical profession and regulators could respond to the strong demand from patients and families for access to medical cannabis to treat chronic illnesses when there is often a limited scientific evidence base on whether and how to use it in many of these conditions. Conclusions: There is a need to maximise both clinical research and patient benefit, in a safe, cautious and ethical manner, so that those patients for whom cannabis is shown to be effective can access it. We hope our discussion and outlines for future progress offer a contribution to this process.
Evaluation of emergency medical services staff knowledge in breaking bad news to patients
Authors: Rasmus Paweł , Kozłowska Elżbieta , Robaczyńska Katarzyna , Pękala Krzysztof , Timler Dariusz , Lipert Anna 
Published: June 2020

Objective The aim of the study was to investigate knowledge of breaking bad news (BBN) among medical personnel in the emergency medical services (EMS). Methods A cross-sectional survey was conducted of 148 individuals employed in EMS. An interview was conducted using a structured questionnaire. Results Of study participants, 89.2% were not aware of any formal BBN procedure and 58.1% had not participated in any form of training. Compared with males, females were more likely to report that dealing with the emotional state of the family or the patient was the most difficult aspect of BBN. Only a few participants were aware of the SPIKES protocol for BBN, and none knew what the acronym meant. Sex, educational level, occupation, work experience and workplace were not associated with knowledge of BBN procedures. Conclusions Knowledge of BBN in both male and female EMS staff was insufficient. EMS personnel held different opinions about the method of BBN. Even staff who have participated in specific BBN training or have extensive professional experience were pessimistic about BBN skills in self-assessments.
Cefiderocol: A Siderophore Cephalosporin
Authors: El-Lababidi Rania M. , Rizk John George 
Published: June 2020

Objective: This article reviews the available data on the chemistry, spectrum of activity, pharmacokinetic and pharmacodynamic properties, clinical efficacy, and potential place in therapy of cefiderocol. Data Sources: A literature search through PubMed, Google Scholar, and ClinicalTrials.gov was conducted (2009 to March 2020) using the search terms cefiderocol and S-649266. Abstracts presented at recent conferences, prescribing information, and information from the US Food and Drug Administration (FDA) and the manufacturer’s website were reviewed. Study Selection and Data Extraction: All relevant published articles, package inserts, and unpublished meeting abstracts on cefiderocol were reviewed. Data Synthesis: Cefiderocol is the first siderophore antibiotic to be approved by the FDA. It was shown to be active against a wide range of resistant Gram-negative pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae, and Stenotrophomonas maltophilia. Cefiderocol was studied in the treatment of adult patients with complicated urinary tract infections (cUTIs) and nosocomial pneumonia and was well tolerated. In a recently completed prospective study, higher mortality was observed with cefiderocol in the treatment of serious infections caused by carbapenem-resistant (CR) Gram-negative pathogens. Relevance to Patient Care and Clinical Practice: The approval of cefiderocol provides a new option in the treatment of cUTIs and potentially treatment of nosocomial pneumonia caused by resistant Gram-negative pathogens. Given the higher mortality observed with cefiderocol, its use in the treatment of CR Gram-negative infections should be carefully considered. Conclusion: Cefiderocol shows promising activity against MDR Gram-negative pathogens. Its use in the treatment of serious infections caused by CR Gram-negative bacteria needs further evaluation in phase III clinical studies.
Sense of coherence in adults with congenital heart disease in 15 countries: Patient characteristics, cultural dimensions and quality of life
Authors: Moons Philip , Apers Silke , Kovacs Adrienne H , Thomet Corina , Budts Werner , Enomoto Junko , Sluman Maayke A , Wang Jou-Kou , Jackson Jamie L , Khairy Paul , Cook Stephen C , Chidambarathanu Shanthi , Alday Luis , Oechslin Erwin , Eriksen Katrine , Dellborg Mikael , Berghammer Malin , Johansson Bengt , Mackie Andrew S , Menahem Samuel , Caruana Maryanne , Veldtman Gruschen , Soufi Alexandra , Fernandes Susan M , White Kamila , Callus Edward , Kutty Shelby , Luyckx Koen ,   the APPROACH-IS consortium and the International Society for Adult Congenital Heart Disease (ISACHD)
Published: June 2020

Abstract

Background
Previous studies have found that sense of coherence (SOC) is positively related to quality of life (QoL) in persons with chronic conditions. In congenital heart disease (CHD), the evidence is scant.

Aims
We investigated (i) intercountry variation in SOC in a large international sample of adults with CHD; (ii) the relationship between demographic and clinical characteristics and SOC; (iii) the relationship between cultural dimensions of countries and SOC; and (iv) variation in relative importance of SOC in explaining QoL across the countries.

Methods
APPROACH-IS was a cross-sectional, observational study, with 4028 patients from 15 countries enrolled. SOC was measured using the 13-item SOC scale (range 13–91) and QoL was assessed by a linear analog scale (range 0–100).

Results
The mean SOC score was 65.5±13.2. Large intercountry variation was observed with the strongest SOC in Switzerland (68.8±11.1) and the lowest SOC in Japan (59.9±14.5). A lower SOC was associated with a younger age; lower educational level; with job seeking, being unemployed or disabled; unmarried, divorced or widowed; from a worse functional class; and simple CHD. Power distance index and individualism vs collectivism were cultural dimensions significantly related to SOC. SOC was positively associated with QoL in all participating countries and in the total sample, with an explained variance ranging from 5.8% in Argentina to 30.4% in Japan.

Conclusion
In adults with CHD, SOC is positively associated with QoL. The implementation of SOC-enhancing interventions might improve QoL, but strategies would likely differ across countries given the substantial variation in explained variance.