bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous emphysematous splenitis: Radiographic and ultrasonographic findings in three Golden Retriever dogs
Authors: Battiato Pierantonio , Fernandez Yordan , Salgüero Raquel , Novellas Rosa , Espada Yvonne , Biller David , Anselmi Carlo 
Published: December 2020

AbstractSpontaneous emphysematous splenitis is a life‐threatening condition reported rarely in humans; however, published reports in dogs are currently lacking. The aim of this multicentric, retrospective, case series design study was to describe radiographic and ultrasonographic imaging findings in Golden Retriever dogs diagnosed with spontaneous emphysematous splenitis. A total of three dogs were sampled. All dogs had a history of lethargy, diarrhea, and weight loss. Radiographic findings in all dogs included a mass effect with focal or multifocal coalescing “vesicular‐like” gas pattern in the splenic region and focal loss of serosal detail. Ultrasonographic findings in all dogs included focal or multifocal irregularly shaped, hypoechoic areas containing a mixture of hyperechoic fluid and gas within the splenic parenchyma, hyperechoic abdominal free fluid, and generalized hyperechoic mesenteric fat without evidence of splenic torsion. Pneumoperitoneum was detected ultrasonographically and radiographically in two dogs. All three dogs underwent splenectomy and splenic torsion was definitively ruled out at surgery. One dog died three days after surgery, whereas the other two dogs recovered uneventfully. Culture of the splenic tissue and free abdominal fluid was positive for Clostridium spp. in all three cases. Findings supported inclusion of spontaneous emphysematous splenitis and septic peritonitis as differential diagnoses for dogs with this combination of clinical and imaging characteristics.
A VIROCENTRIC PERSPECTIVE ON EVIL
Authors: Schilling Mirjam 
Published: December 2020

AbstractAbstract. The coronavirus pandemic has stirred interest in viruses. This has been accompanied by a proliferation of popular works trying to explain how viruses fit into the Christian worldview. In an anthropocentric perspective, viruses are easily regarded as malicious entities. This article, however, shows that a proper understanding of the biology of viruses actually adds another level of complexity to our perception of good and evil. Interestingly, this additional layer of complexity might help us solve some of the most urgent difficulties in the discussion about good and evil, if we recognize the subjective nature of what we call natural evil. We need to be more nuanced not merely in our theological discussion about good and evil, but also in the way we talk about viruses.
Assessment of patient burden from dry eye disease using a combination of five visual analogue scales and a radar graph: a pilot study of the PENTASCORE
Authors: Labetoulle Marc , Benichou Jérémie , M’nafek Nabila , Garnier Flavie , Rabut Ghislaine , Ben Hadj Salah Wassim , Labbé Antoine , Rousseau Antoine , Baudouin Christophe 
Published: December 2020

Background/aimsDry eye disease (DED) questionnaires would ideally be easy and fast to answer and explore the main aspects of disease burden and satisfaction (efficacy and tolerability) with treatment. This pilot study evaluates the Pentascore questionnaire for routinely assessing DED.MethodsThe Pentascore combines five visual analogue scales (VAS) to assess the intensity and frequency of ocular pain/discomfort, the impact of DED on daily activities and visual tasks and the efficacy and tolerability of ongoing DED treatment(s). This retrospective study compared Pentascore to the Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear break-up-time, corneal staining and Schirmer I test.ResultsFor 161 DED patients, the algebraic mean (±SE) for the Pentascore was 52.6±1.8, the mean standardised area of the radar graph was 32.1±1.7 (out of 100) and the mean score for the OSDI was 52.6±1.8. Both questionnaires were highly statistically correlated (R=0.74 for both algebraic score and radar area, p<0.001), and each of five Pentascore VAS was significantly correlated with the OSDI (p<0.05). Corneal staining score (CSS) was correlated with two Pentascore VAS (impact of DED on daily activities and visual tasks), and there was a trend towards a correlation between CSS and the area of the radar graph (p=0.09).ConclusionsThis pilot study indicates that the Pentascore can rapidly and effectively assess the burden of DED and satisfaction with treatments. Compared with the algebraic mean, the estimation of the area of the radar graph likely improves the sensitivity for detecting differences/changes in symptoms and treatment follow-up.
Knowledge and understanding of cardiovascular disease risk factors in Sierra Leone: a qualitative study of patients’ and community leaders’ perceptions
Authors: Ignatowicz Agnieszka , Odland Maria Lisa , Bockarie Tahir , Wurie Haja , Ansumana Rashid , Kelly Ann H , Willott Chris , Witham Miles , Davies Justine 
Published: December 2020

ObjectivesPrevalence of cardiovascular disease risk factors (CVDRF) is increasing, especially in low-income countries. In Sierra Leone, there are no previous studies on the knowledge and the awareness of these conditions in the community. This study aimed to explore the knowledge and understanding of CVDRF, as well as the perceptions of the barriers and facilitators to accessing care for these conditions, among patients and community leaders in Sierra Leone.DesignQualitative study employing semistructured interviews and focus group discussions.SettingUrban and rural Bo District, Sierra Leone.ParticipantsInterviews with a purposive sample of 37 patients and two focus groups with six to nine community leaders.ResultsWhile participants possessed general knowledge of their conditions, the level and complexity of this knowledge varied widely. There were clear gaps in knowledge regarding the coexistence of CVDRF and their consequences, as well as the link between behavioural factors and CVDRF. An overarching theme from the data was the need to create an understanding and awareness of CVDRF in the community in order to prevent and improve management of these conditions. Cost was also seen as a major barrier to accessing care for CVDRFs.ConclusionsThe knowledge gaps identified in this study highlight the need to design strategies and interventions that improve knowledge and recognition of CVDRF in the community. Interventions should specifically consider how to develop and enhance awareness about CVDRF and their consequences. They should also consider how patients seek help and where they access it.
Attitudes of pharmacy students towards patient safety: a cross-sectional study from six developing countries
Authors: Naser Abdallah Y , Alsairafi Zahra Khalil , Awaisu Ahmed , Alwafi Hassan , Awwad Oriana , Dahmash Eman Zmaily , Hussain Salman , Alyami Hamad S , Alsharif Alaa , Singh Avinash Kumar , Jeragh-Alhaddad Fatima B , Kautsar Angga Prawira , AbuAlhommos Amal Khaleel 
Published: December 2020

ObjectiveTo evaluate the attitudes of undergraduate pharmacy students towards patient safety in six developing countries.DesignA cross-sectional study.SettingParticipants were enrolled from the participating universities in six countries.ParticipantsUndergraduate pharmacy students from the participating universities in six developing countries (Jordan, Saudi Arabia, Kuwait, Qatar, India and Indonesia) were invited to participate in the study between October 2018 and September 2019.Primary outcomeAttitudes towards patient safety was measured using 14-item questionnaire that contained five subscales: being quality-improvement focused, internalising errors regardless of harm, value of contextual learning, acceptability of questioning more senior healthcare professionals’ behaviour and attitude towards open disclosure. Multiple-linear regression analysis was used to identify predictors of positive attitudes towards patient safety.ResultsA total of 2595 students participated in this study (1044 from Jordan, 514 from Saudi Arabia, 134 from Kuwait, 61 from Qatar, 416 from India and 429 from Indonesia). Overall, the pharmacy students reported a positive attitude towards patient safety with a mean score of 37.4 (SD=7.0) out of 56 (66.8%). The ‘being quality-improvement focused’ subscale had the highest score, 75.6%. The subscale with the lowest score was ‘internalising errors regardless of harm’, 49.2%. Female students had significantly better attitudes towards patient safety scores compared with male students (p=0.001). Being at a higher level of study and involvement in or witnessing harm to patients while practising were important predictors of negative attitudes towards patient safety (p<0.001).ConclusionPatient safety content should be covered comprehensively in pharmacy curricula and reinforced in each year of study. This should be more focused on students in their final year of study and who have started their training. This will ensure that the next generation of pharmacists are equipped with the requisite knowledge, core competencies and attitudes to ensure optimal patient safety when they practice.
Does tension applied in kinesio taping affect pain or function in older women with knee osteoarthritis? A randomised controlled trial
Authors: Pinheiro Yago Tavares , Barbosa Germanna Medeiros , Fialho Hilmaynne Renaly Fonseca , Silva César Augusto Medeiros , Anunciação Jaciara de Oliveira , Silva Hugo Jário de Almeida , Souza Marcelo Cardoso de , Lins Caio Alano de Almeida 
Published: December 2020

ObjectiveTo analyse the short-term effects of kinesio taping (KT) with tension (KTT) or without tension (KTNT) in older women with knee osteoarthritis (KOA), and compare them to controls who did not receive KT.DesignRandomised controlled trial.SettingUniversity physiotherapy school clinic.ParticipantsForty-five older women (fifteen participants per group) with 66.8 (±5.6) years and clinical diagnosis of KOA were assessed pre, post and 3 days after intervention.InterventionsParticipants were randomly allocated to KTT, who received two simultaneous applications of KT with tension on the knee and rectus femoris; KTNT, who received the same application as the KTT group, but without tension and a control group that attended a class on KOA.Primary and secondary outcome measuresPrimary outcome was pain intensity and secondary outcomes were knee-related health status, functional capacity, muscle strength and global rating of change.ResultsNo between-group differences were observed in pain after the first intervention (KTT vs KTNT: mean difference (MD), −1.8 points; 95% CI −4.2 to 0.5; KTT vs control: MD, −1.2 points; 95% CI −3.6 to 1.2; KTNT vs control: MD, 0.66 points; 95% CI −1.7 to 3.0) or 3 days later (KTT vs KTNT: MD, −1.3 points; 95% CI −3.7 to 1.0; KTT vs control: MD, 0.13 points; 95% CI −2.2 to 2.5; KTNT vs control: MD, 1.4 points; 95% CI −0.9 to 3.8). The lack of between-group differences was also found for secondary outcomes.ConclusionThe short-term use of KT with or without tension in older woman with KOA had no beneficial effects on pain and function. These findings call into question the clinical use of KT as a non-pharmacological therapy for this population.Trial registration numberNCT03624075.
Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19
Authors: van Zelst Cathelijne M , Janssen Matthijs L , Pouw Nadine , Birnie Erwin , Castro Cabezas Manuel , Braunstahl Gert-Jan 
Published: December 2020

BackgroundSeveral characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19.MethodsA prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity—assessed by an increased waist–hip ratio—and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses.ResultsIn total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014).ConclusionThis study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference.Trial registration numberNL8580.
A Very Long-Acting PARP Inhibitor Suppresses Cancer Cell Growth in DNA Repair-Deficient Tumor Models
Authors: Fontaine Shaun D. , Ashley Gary W. , Houghton Peter J. , Kurmasheva Raushan T. , Diolaiti Morgan , Ashworth Alan , Peer Cody J. , Nguyen Ryan , Figg William D. , Beckford-Vera Denis R. , Santi Daniel V. 
Published: December 2020

Abstract

PARP inhibitors are approved for treatment of cancers with BRCA1 or BRCA2 defects. In this study, we prepared and characterized a very long-acting PARP inhibitor. Synthesis of a macromolecular prodrug of talazoparib (TLZ) was achieved by covalent conjugation to a PEG40kDa carrier via a β-eliminative releasable linker. A single injection of the PEG∼TLZ conjugate was as effective as ∼30 daily oral doses of TLZ in growth suppression of homologous recombination-defective tumors in mouse xenografts. These included the KT-10 Wilms' tumor with a PALB2 mutation, the BRCA1-deficient MX-1 triple-negative breast cancer, and the BRCA2-deficient DLD-1 colon cancer; the prodrug did not inhibit an isogenic DLD-1 tumor with wild-type BRCA2. Although the half-life of PEG∼TLZ and released TLZ in the mouse was only ∼1 day, the exposure of released TLZ from a single safe, effective dose of the prodrug exceeded that of oral TLZ given daily over one month. μPET/CT imaging showed high uptake and prolonged retention of an 89Zr-labeled surrogate of PEG∼TLZ in the MX-1 BRCA1-deficient tumor. These data suggest that the long-lasting antitumor effect of the prodrug is due to a combination of its long t1/2, the high exposure of TLZ released from the prodrug, increased tumor sensitivity upon continued exposure, and tumor accumulation. Using pharmacokinetic parameters of TLZ in humans, we designed a long-acting PEG∼TLZ for humans that may be superior in efficacy to daily oral TLZ and would be useful for treatment of PARP inhibitor-sensitive cancers in which oral medications are not tolerated.

Significance:
These findings demonstrate that a single injection of a long-acting prodrug of the PARP inhibitor talazoparib in murine xenografts provides tumor suppression equivalent to a month of daily dosing of talazoparib.
Robust p53 Stabilization Is Dispensable for Its Activation and Tumor Suppressor Function
Authors: Kon Ning , Churchill Michael , Li Huan , Mukherjee Siddhartha , Manfredi James J. , Gu Wei 
Published: December 2020

Abstract

p53 is a short-lived protein with low basal levels under normal homeostasis conditions. However, upon DNA damage, levels of p53 dramatically increase for its activation. Although robust stabilization of p53 serves as a “trademark” for DNA damage responses, the requirement for such dramatic protein stabilization in tumor suppression has not been well addressed. Here we generated a mutant p53KQ mouse where all the C-terminal domain lysine residues were mutated to glutamines (K to Q mutations at K367, K369, K370, K378, K379, K383, and K384) to mimic constitutive acetylation of the p53 C-terminus. Because of p53 activation, p53KQ/KQ mice were perinatal lethal, yet this lethality was averted in p53KQ/− mice, which displayed normal postnatal development. Nevertheless, p53KQ/− mice died prematurely due to anemia and hematopoiesis failure. Further analyses indicated that expression of the acetylation-mimicking p53 mutant in vivo induces activation of p53 targets in various tissues without obviously increasing p53 levels. In the well-established pancreatic ductal adenocarcinoma (PDAC) mouse model, expression of the acetylation-mimicking p53-mutant protein effectively suppressed K-Ras–induced PDAC development in the absence of robust p53 stabilization. Together, our results provide proof-of-principle evidence that p53-mediated transcriptional function and tumor suppression can be achieved independently of its robust stabilization and reveal an alternative approach to activate p53 function for therapeutic purposes.

Significance:
Although robust p53 stabilization is critical for acute p53 responses such as DNA damage, this study underscores the important role of low basal p53 protein levels in p53 activation and tumor suppression.
Glia-Selective Deletion of Complement C1q Prevents Radiation-Induced Cognitive Deficits and Neuroinflammation
Authors: Markarian Mineh , Krattli Robert P. , Baddour Jabra D. , Alikhani Leila , Giedzinski Erich , Usmani Manal T. , Agrawal Anshu , Baulch Janet E. , Tenner Andrea J. , Acharya Munjal M. 
Published: December 2020

Abstract

The adverse neurocognitive sequelae following clinical radiotherapy (RT) for central nervous system (CNS) malignancies are often long-lasting without any clinical recourse. Despite recent progress, the cellular mechanisms mediating RT-induced cognitive deficits (RICD) are poorly understood. The complement system is an immediate sensor of a disturbed inflammatory environment and a potent mediator of gliosis with a range of nonimmune functions in the CNS, including synaptic pruning, which is detrimental if dysregulated. We hypothesize that complement-mediated changes in glial cell function significantly contribute to RICD. The underlying alterations in CNS complement cascade proteins (C1q, C3), TLR4, and colabeling with glia (IBA1, GFAP) were examined using gene expression, immunofluorescence, and in silico modeling approaches in the adult mouse brain following 9 Gy cranial RT. Three-dimensional volumetric quantification showed elevated molecular signatures of gliosis at short- and long-term post-RT times. We found significant elevations in complement C1q, C3, and TLR4 post-RT accompanied by increased colabeling of astrocytes and microglia. To address the mechanism of RT-induced complement cascade activation, neuroinflammation, and cognitive dysfunction, we used a genetic approach—conditional, microglia-selective C1q (Flox) knockdown mice—to determine whether a glia-specific, upstream complement cascade contributes to RICD. C1q-Flox mice exposed to cranial RT showed no cognitive deficits compared with irradiated WT mice. Further, irradiated C1q-Flox mice were protected from RT-induced microglial activation and synaptic loss, elevation of anaphylatoxin C5a receptor, astrocytic-C3, and microglial-TLR4 expression in the brain. Our findings demonstrate for the first time a microglia-specific mechanism of RICD involving an upstream complement cascade component, C1q.

Significance:
Clinically-relevant radiotherapy induces aberrant complement activation, leading to brain injury. Microglia-selective genetic deletion of CNS complement C1q ameliorates radiation-induced cognitive impairments, synaptic loss, and neuroinflammation, highlighting the potential for C1q as a novel therapeutic target.
See related commentary by Korimerla and Wahl, p. 1635
Dissecting the Functional Significance of DNA Polymerase Mutations in Cancer
Authors: Wisdom Amy J. , Kirsch David G. 
Published: December 2020

Abstract
DNA polymerase mutations can cause hypermutant cancers, but the mechanisms of tumorigenesis and the impact of various DNA polymerase mutations on treatment response is poorly understood. In this issue of Cancer Research, Galati and colleagues investigate the effects of cancer-associated DNA polymerase ε (Pole) mutations on tumorigenesis and response to immune checkpoint blockade. They describe novel genetically engineered mouse models harboring cancer-associated Pole mutations and examine the effects of these mutations on tumorigenesis, the tumor mutational landscape, and the tumor immune microenvironment. Integrating this information with an emerging understanding of how different tumor mutations influence the response to immunotherapy may aid in prediction, diagnosis, and treatment of Pole-mutant tumors.
See related article by Galati et al., p. 5606
Macrophages Come To The Rescue
Authors: Coppes Robert P. 
Published: December 2020

Abstract
The study by Zhao and colleagues, in this issue of Cancer Research, builds on previous work where they showed that transient activation of Hedgehog signaling within the murine submandibular gland rescued radiation-induced salivary gland dysfunction. The current study provides mechanistic insight into this phenomenon by showing that restoration of radiation-depleted resident macrophages through prorepair paracrine interactions with endothelial cells and epithelial progenitors rescued salivary function.
See related article by Zhao et al., p. 5531
Opportunities for Gene and Environment Research in Cancer: An Updated Review of NCI's Extramural Grant Portfolio
Authors: Ghazarian Armen A. , Simonds Naoko Ishibe , Lai Gabriel Y. , Mechanic Leah E. 
Published: December 2020

Abstract

Background:
The study of gene–environment (GxE) interactions is a research priority for the NCI. Previously, our group analyzed NCI's extramural grant portfolio from fiscal years (FY) 2007 to 2009 to determine the state of the science in GxE research. This study builds upon our previous effort and examines changes in the landscape of GxE cancer research funded by NCI.

Methods:
The NCI grant portfolio was examined from FY 2010 to 2018 using the iSearch application. A time–trend analysis was conducted to explore changes over the study interval.

Results:
A total of 107 grants met the search criteria and were abstracted. The most common cancer types studied were breast (19.6%) and colorectal (18.7%). Most grants focused on GxE using specific candidate genes (69.2%) compared with agnostic approaches using genome-wide (26.2%) or whole-exome/whole-genome next-generation sequencing (NGS) approaches (19.6%); some grants used more than one approach to assess genetic variation. More funded grants incorporated NGS technologies in FY 2016–2018 compared with prior FYs. Environmental exposures most commonly examined were energy balance (46.7%) and drugs/treatment (40.2%). Over the time interval, we observed a decrease in energy balance applications with a concurrent increase in drug/treatment applications.

Conclusions:
Research in GxE interactions has continued to concentrate on common cancers, while there have been some shifts in focus of genetic and environmental exposures. Opportunities exist to study less common cancers, apply new technologies, and increase racial/ethnic diversity.

Impact:
This analysis of NCI's extramural grant portfolio updates previous efforts and provides a review of NCI grant support for GxE research.