bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of SARS‐CoV‐2 outbreak on heart and lung transplant: A patient‐perspective survey
Authors: Bennett David , De Vita Elda , Ventura Vittoria , Bernazzali Sonia , Fossi Antonella , Paladini Piero , Luzzi Luca , Maccherini Massimo , Valente Serafina , Bargagli Elena , Frediani Bruno , Sestini Piersante 
Published: August 2020

AbstractBackgroundThe risk of COVID‐19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID‐19 and the impact of the SARS‐CoV‐2 outbreak on the personal hygiene and expectations in heart and lung transplant recipients.MethodsA telephone survey of heart (n = 69) and lung (n = 41) transplant patients and a group of controls (n = 41) was conducted concerning personal hygiene before and after the outbreak; the impact on subjective expectations regarding graft outcome; symptoms possibly associated with SARS‐CoV‐2 infection; and diagnosis of COVID‐19.ResultsSeventy nine percent of the patients declared they increased the use of face masks and handwash. Behavior at home regarding self‐isolation did not change. About half the patients said they were afraid of the virus. A higher percentage of Lung transplant (LTX) were convinced that SARS‐CoV‐2 could have a negative impact on the outcome of their graft. 28% declared that they were afraid to come to the hospital for routine examinations and asked to postpone. Nine LTX and five Heart transplant (HTX) patients experienced symptoms that could have been associated with SARS‐CoV‐2 infection, but none of them underwent a nasopharyngeal swab. Only one LTX was diagnosed with the infection.ConclusionsIn our study, we observed a low incidence of COVID‐19 in heart and lung transplant patients (0.9%), similar to that of the general population of our Region. Isolation measures were already observed before the pandemic and were further strengthened in most cases. Particular attention should also be paid to new psychological and physical complications indirectly linked to the COVID‐19 pandemic.
Use of a rapid electronic survey methodology to estimate blood donors' potential exposure to emerging infectious diseases: Application of a statistically representative sampling methodology to assess risk in US blood centers
Authors: Whitaker Barbee I. , Walderhaug Mark , Hinkins Susan , Steele Whitney R. , Custer Brian , Kessler Debra , Leparc German , Gottschall Jerome L. , Bialkowski Walter , Stramer Susan L. , Dodd Roger Y. , Crowder Lauren , Vahidnia Farnaz , Shaz Beth H. , Kamel Hany , Rebosa Mark , Stern Michael , Anderson Steven A. 
Published: August 2020

BackgroundRisk assessments of transfusion‐transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donorsʼ demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk.Study Design and MethodsThis article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS‐CoV).ResultsA total of 7128 responses were received from 54 256 invitations. The age‐adjusted estimated total number of blood donors potentially exposed to MERS‐CoV was approximately 15 640 blood donors compared to a lower U.S. general population‐based estimate of 9610 blood donors.ConclusionThe structured donor demographic sample–based data provided an assessment of blood donorsʼ potential exposure to an emerging pathogen that was 63% larger than the U.S. population–based estimate. This illustrates the need for tailored blood donor–based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making.
Incidence and costs of cardiovascular events in Spanish patients with type 2 diabetes mellitus: a comparison with general population, 2015
Authors: Jodar Esteban , Artola Sara , Garcia-Moll Xavier , Uría Estefany , López-Martínez Noemí , Palomino Rosa , Martín Virginia 
Published: August 2020

IntroductionCardiovascular (CV) disease affects a high percentage of patients with type 2 diabetes mellitus (T2DM), especially in the hospital setting, impacting on mortality, complications, quality of life and use of health resources. The aim of this study was to estimate the incidence, mean length of hospital stay (LOHS) and costs attributable to hospital admissions due to CV events in patients with T2DM versus patients without diabetes mellitus (non-DM) in Spain.Research design and methodsRetrospective observational study based on the Spanish National Hospital Discharge Database for 2015. Hospital admissions for patients aged ≥35 years with a diagnosis of CV death, non-fatal acute myocardial infarction (AMI), non-fatal stroke, unstable angina, heart failure and revascularization were evaluated. The International Classification of Diseases, Ninth Revision (250.x0 or 250.x2) coding was used to classify records of patients with T2DM. For each CV complication, the hospital discharges of the two groups, T2DM and non-DM, were precisely matched and the number of hospital discharges, patients, LOHS and mean cost were quantified. Additional analyses assessed the robustness of the results.ResultsOf the 276 925 hospital discharges analyzed, 34.71% corresponded to patients with T2DM. A higher incidence was observed in all the CV complications studied in the T2DM population, with a relative risk exceeding 2 in all cases. The mean LOHS (days) was longer in the T2DM versus the non-DM group for: non-fatal AMI (7.63 vs 7.02, p<0.001), unstable angina (5.11 vs 4.78, p=0.009) and revascularization (7.96 vs 7.57, p<0.001). The mean cost per hospital discharge was higher in the T2DM versus the non-DM group for non-fatal AMI (€6891 vs €6876, p=0.029) and unstable angina (€3386 vs €3304, p<0.001).ConclusionsPatients with T2DM had a higher incidence and number of hospital admissions per patient due to CV events versus the non-DM population. This generates a significant clinical and economic burden given the longer admission stay and higher costs associated with some of these complications.
Impact of body composition on outcomes from anti-PD1 +/− anti-CTLA-4 treatment in melanoma
Authors: Young Arissa C , Quach Henry T , Song Haocan , Davis Elizabeth J , Moslehi Javid J , Ye Fei , Williams Grant R , Johnson Douglas B 
Published: August 2020

BackgroundImmune checkpoint inhibitors (ICIs) have transformed treatment for melanoma, but identifying reliable biomarkers of response and effective modifiable lifestyle factors has been challenging. Obesity has been correlated with improved responses to ICI, although the association of body composition measures (muscle, fat, etc) with outcomes remains unknown.MethodsWe performed body composition analysis using Slice-o-matic software on pretreatment CT scans to quantify skeletal muscle index (SMI=skeletal muscle area/height2), skeletal muscle density (SMD), skeletal muscle gauge (SMG=SMI × SMD), and total adipose tissue index (TATI=subcutaneous adipose tissue area + visceral adipose tissue area/height2) of each patient at the third lumbar vertebrae. We then correlated these measures to response, progression-free survival (PFS), overall survival (OS), and toxicity.ResultsAmong 287 patients treated with ICI, body mass index was not associated with clinical benefit or toxicity. In univariable analyses, patients with sarcopenic obesity had inferior PFS (HR 1.4, p=0.04). On multivariable analyses, high TATI was associated with inferior PFS (HR 1.7, p=0.04), which was particularly strong in women (HR 2.1, p=0.03). Patients with intermediate TATI and high SMG had the best outcomes, whereas those with low SMG/high TATI had inferior PFS and OS (p=0.02 for both PFS and OS).ConclusionsBody composition analysis identified several features that correlated with improved clinical outcomes, although the associations were modest. As with other studies, we identified sex-specific associations that warrant further study.
Biallelic mutations in theTOGARAM1gene cause a novel primary ciliopathy
Authors: Morbidoni Valeria , Agolini Emanuele , Slep Kevin C , Pannone Luca , Zuccarello Daniela , Cassina Matteo , Grosso Enrico , Gai Giorgia , Salviati Leonardo , Dallapiccola Bruno , Novelli Antonio , Martinelli Simone , Trevisson Eva 
Published: August 2020

BackgroundDysfunction in non-motile cilia is associated with a broad spectrum of developmental disorders characterised by clinical heterogeneity. While over 100 genes have been associated with primary ciliopathies, with wide phenotypic overlap, some patients still lack a molecular diagnosis.ObjectiveTo investigate and functionally characterise the molecular cause of a malformation disorder observed in two sibling fetuses characterised by microphthalmia, cleft lip and palate, and brain anomalies.MethodsA trio-based whole exome sequencing (WES) strategy was used to identify candidate variants in theTOGARAM1gene. In silico, in vitro and in vivo (Caenorhabditis elegans) studies were carried out to explore the impact of mutations on protein structure and function, and relevant biological processes.ResultsTOGARAM1encodes a member of the Crescerin1 family of proteins regulating microtubule dynamics. Its orthologue inC. elegans,che-12, is expressed in a subset of sensory neurons and localises in the dendritic cilium where it is required for chemosensation. Nematode lines harbouring the corresponding missense variant inTOGARAM1were generated by CRISPR/Cas9 technology. Although chemotaxis ability on a NaCl gradient was not affected,che-12point mutants displayed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. Finally, in vitro analysis of microtubule polymerisation in the presence of wild-type or mutant TOG2 domain revealed a faster polymerisation associated with the mutant protein, suggesting aberrant tubulin binding.ConclusionsOur data are in favour of a causative role ofTOGARAM1variants in the pathogenesis of this novel disorder, connecting this gene with primary ciliopathy.
Assessment of patient decision-making capacity in the context of voluntary euthanasia for psychic suffering caused by psychiatric disorders: a qualitative study of approaches among Belgian physicians
Authors: Schweitser Frank , Stuy Johan , Distelmans Wim , Rigo Adelheid 
Published: August 2020

ObjectiveIn Belgium, people with an incurable psychiatric disorder can file a request for euthanasia claiming unbearable psychic suffering. For the request to be accepted, it has to meet stringent legal criteria. One of the requirements is that the patient possesses decision-making capacity. The patient’s decision-making capacity is assessed by physicians.The objective of our study is to provide insight in the assessment of decision-making capacity in the context of euthanasia for patients with psychic suffering caused by a psychiatric disorder.MethodTwenty-two semistructured interviews with psychiatrists and neurologists were analysed with NVivo, a qualitative analysis software to code and organise transcribed data.ResultsDifferent views and approaches regarding decision-making capacity in the context of euthanasia emerged from the data.Most of the physicians have some knowledge of the cognitive ability approach on decision-making capacity. According to this approach, four abilities constitute decision-making capacity: communication, understanding, appreciation and reasoning. We observed differences in the way these abilities are valued in relation to competence. Some physicians take additional elements into consideration when assessing decision-making capacity.Physicians acquired their knowledge on the subject in many different ways. Most of the physicians reported that decision-making capacity was not part of their training.ConclusionWe conclude that physicians assess decision-making capacity in different ways and that personal values and beliefs influence their approach. As such, a common approach in assessing the decision-making capacity of a patient among the interviewed physicians is lacking. Less arbitrariness could be obtained by consistently implementing the cognitive ability approach.
Decrease in cross-border tobacco purchases despite intensification of antitobacco policies in France
Authors: Gomajee Ramchandar , Torregrossa Hugo , Bolze Camille , Melchior Maria , El-Khoury Lesueur Fabienne 
Published: August 2020

BackgroundRecently, France has intensified tobacco control policies which included gradual increase in tobacco product price and the introduction of plain packaging. However, there has been suggestion that cross-border tobacco purchases from neighbouring countries, with lower tobacco prices, will increase. We examine trends in cross-border tobacco purchases among smokers concurrent with the implementation of tobacco control measures between 2016 and 2017.MethodsDescription des Perceptions, Images, et Comportements liés au Tabagisme is a two-wave cross-sectional national telephone survey of French adults aged 18–64 years, which recruited a total of 2167 smokers (2016: n=1238; 2017: n=929). Data were weighted to be representative of the French adult population. The association between study wave and cross-country tobacco purchases was examined across study waves using a multivariable logistic regression model (adjusted ORs: ORa(95% CI)).ResultsLess than half (38.5%) of smokers declared cross-border tobacco purchases in the last year, which were mostly done on occasional basis: 22.6% purchased tobacco cross-border once or twice yearly. In 2017, as compared with 2016, cross-border tobacco purchases by French smokers decreased (ORa=0.81, 95% CI 0.68 to 0.98). Other factors associated with cross-border tobacco purchases included sex, and driving distance to a border.ConclusionIn France, the increase in tobacco product price and the introduction of plain packaging did not contribute to increasing rates of out-of-country purchases of tobacco products, probably due to the overall decrease in smoking levels. However, a harmonisation of tobacco product prices and plain packaging policies across Europe might further improve tobacco control throughout the continent.
Highly reliable electromagnetic MOEMS scanning grating mirror based on folded torsion beam with fillet corners
Authors: Chen Liang , Gu Wenwen , Wen Quan , Li Dongling , Lei Hongjie , Huang Jie 
Published: August 2020

To overcome the problems of poor structural reliability, high driving voltage and small scanning angle, a novel electromagnetic MOEMS scanning grating mirror (SGM) with folded torsion beam is reported in this work. Compared with the conventional straight torsion beam, the folded torsion beam has better elastic torsion property and can effectively improve the structural reliability of the MOEMS SGM. Furthermore, the fillet structure is added to the folded torsion beam to prevent stress concentration. The stress analysis and impact resistance of the proposed MOEMS SGM are simulated by FEM (ANSYS 18.2), and the simulation results are compared with that of the MOEMS SGM without fillet structure. The stress simulation is carried out under different fillet radius of 40–70 [Formula: see text]m, the maximum stress can be reduced to 85[Formula: see text] and the stress is redistributed uniformly. Meanwhile, in the impact resistance simulation, the impact displacement can be reduced by 10.1[Formula: see text]. A prototype is fabricated and tested, it has a large mirror area of 6 mm ×7 mm. The MOEMS SGM can reach the maximum scanning half angle of [Formula: see text] at 7.63 V under resonance (@602.1 Hz), which means that the full mechanical scanning angle of the MOEMS SGM can reach [Formula: see text].
The simple essence of algebraic subtyping: principal type inference with subtyping made easy (functional pearl)
Authors: Parreaux Lionel 
Published: August 2020

MLsub extends traditional Hindley-Milner type inference with subtyping while preserving compact principal types, an exciting new development. However, its specification in terms of biunification is difficult to understand, relying on the new concepts of bisubstitution and polar types, and making use of advanced notions from abstract algebra. In this paper, we show that these are in fact not essential to understanding the mechanisms at play in MLsub. We propose an alternative algorithm called Simple-sub, which can be implemented efficiently in under 500 lines of code (including parsing, simplification, and pretty-printing), looks more familiar, and is easier to understand.
We present an experimental evaluation of Simple-sub against MLsub on a million randomly-generated well-scoped expressions, showing that the two systems agree. The mutable automaton-based implementation of MLsub is quite far from its algebraic specification, leaving a lot of space for errors; in fact, our evaluation uncovered several bugs in it. We sketch more straightforward soundness and completeness arguments for Simple-sub, based on a syntactic specification of the type system.
This paper is meant to be light in formalism, rich in insights, and easy to consume for prospective designers of new type systems and programming languages. In particular, no abstract algebra is inflicted on readers.
A Proof of Concept for Biomarker-Guided Targeted Therapy against Ovarian Cancer Based on Patient-Derived Tumor Xenografts
Authors: Palmer Adam C. , Plana Deborah , Gao Hui , Korn Joshua M. , Yang Guizhi , Green John , Zhang Xiamei , Velazquez Roberto , McLaughlin Margaret E. , Ruddy David A. , Kowal Colleen , Muszynski Julie , Bullock Caroline , Rivera Stacy , Rakiec Daniel P. , Elliott GiNell , Fordjour Paul , Meyer Ronald , Loo Alice , Kurth Esther , Engelman Jeffrey A. , Bitter Hans , Sellers William R. , Williams Juliet A. , Sorger Peter K. 
Published: August 2020

Abstract

Advanced ovarian cancers are a leading cause of cancer-related death in women and are currently treated with surgery and chemotherapy. This standard of care is often temporarily successful but exhibits a high rate of relapse, after which, treatment options are few. Here we investigate whether biomarker-guided use of multiple targeted therapies, including small molecules and antibody–drug conjugates, is a viable alternative. A panel of patient-derived ovarian cancer xenografts (PDX), similar in genetics and chemotherapy responsiveness to human tumors, was exposed to 21 monotherapies and combination therapies. Three monotherapies and one combination were found to be active in different subsets of PDX. Analysis of gene expression data identified biomarkers associated with responsiveness to each of the three targeted therapies, none of which directly inhibits an oncogenic driver. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. The distribution of biomarker positivity in The Cancer Genome Atlas data suggests the potential for a similar precision approach in human patients.

Significance:
This study exploits a panel of patient-derived xenografts to demonstrate that most ovarian tumors can be matched to effective biomarker-guided treatments.
Polyamine Blocking Therapy Decreases Survival of Tumor-Infiltrating Immunosuppressive Myeloid Cells and Enhances the Antitumor Efficacy of PD-1 Blockade
Authors: Alexander Eric T. , Mariner Kelsey , Donnelly Julia , Phanstiel Otto , Gilmour Susan K. 
Published: August 2020

Abstract
Despite unprecedented advances in the treatment of cancer through the use of immune checkpoint blockade (ICB), responses are not universal and alternative strategies are needed to enhance responses to ICB. We have shown previously that a novel polyamine blocking therapy (PBT), consisting of cotreatment with α-difluoromethylornithine (DFMO) to block polyamine biosynthesis and a Trimer polyamine transport inhibitor, decreases myeloid-derived suppressor cells (MDSC) and M2-like tumor-associated macrophages (TAM). Both MDSCs and TAMs promote tumor progression, inhibit antitumor immunity, and limit the efficacy of ICB. In this study, we investigated the use of PBT to heighten therapeutic responses to PD-1 blockade in mice bearing 4T1 mammary carcinoma and B16F10 melanoma tumors. Whereas PBT inhibited primary tumor growth in both tumor models, 4T1 lung metastases were also dramatically decreased in mice treated with PBT. Reductions in MDSC and TAM subpopulations in 4T1 tumors from PBT-treated mice were accompanied by reduced cytoprotective autophagy only in tumor-infiltrating MDSC and macrophage subpopulations but not in the lung or spleen. PBT treatment blunted M2-like alternative activation of bone marrow–derived macrophages and reduced STAT3 activation in MDSC cultures while increasing the differentiation of CD80+, CD11c+ macrophages. PBT significantly enhanced the antitumor efficacy of PD-1 blockade in both 4T1 and B16F10 tumors resistant to anti–PD-1 monotherapy, increasing tumor-specific cytotoxic T cells and survival of tumor-bearing animals beyond that with PBT or PD-1 blockade alone. Our results suggest that cotreatment with DFMO and the Trimer polyamine transport inhibitor may improve the therapeutic efficacy of immunotherapies in patients with cancer with resistant tumors.
Prognostic and Predictive Biomarkers in Patients with Metastatic Colorectal Cancer Receiving Regorafenib
Authors: Liu Yingmiao , Lyu Jing , Bell Burdett Kirsten , Sibley Alexander B. , Hatch Ace J. , Starr Mark D. , Brady John C. , Hammond Kelli , Marmorino Federica , Rossini Daniele , Goldberg Richard M. , Falcone Alfredo , Cremolini Chiara , Owzar Kouros , Ivanova Anastasia , Moore Dominic T. , Lee Michael S. , Sanoff Hanna K. , Innocenti Federico , Nixon Andrew B. 
Published: August 2020

Abstract
Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here, we report biomarker results from LCCC1029, a randomized, placebo-controlled, phase II trial of chemotherapy ± regorafenib in patients with second-line mCRC. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL6, PlGF, VEGF-R1, OPN, and IL6R) were found to be prognostic for PFS. Nine markers (IL6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx = 0.0167), VCAM-1 (Pintx = 0.0216), and PDGF-AA (Pintx = 0.0435) appeared to predict for PFS benefit from regorafenib compared with placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared with placebo (Pintx = 0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 patients with late-stage mCRC received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit, while multiple protein markers may be prognostic of outcome in patients with mCRC.