bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐cultural adaptation, translation, and validation of the Spanish Foot and Ankle Outcome Score questionnaire
Authors: Navarro‐Flores Emmanuel , Losa‐Iglesias Marta Elena , Becerro‐de‐Bengoa‐Vallejo Ricardo , Reina‐Bueno María , López‐López Daniel , Romero‐Morales Carlos , Palomo‐López Patricia , Calvo‐Lobo César
Published: May 2020

The Spanish Foot and Ankle Outcome Score questionnaire (FAOS‐S) may be considered a health evaluation tool with 42 questions for assessing foot health disorders. To date, FAOS has been validated in different languages, but a Spanish version was lacking. Consequently, the purpose of this study was to translate and validate the Spanish version of the FAOS (FAOS es). A suitable method was developed for the translation protocol and cross‐cultural validation from Swedish to Spanish. Regarding the total marks from each domain, agreement degrees and confidence were analysed using the Cronbach's α and intraclass correlation coefficient, respectively. In addition, the mean ± SD differences between pretest and posttests were calculated and completed using of the Bland and Altman distribution plots. Excellent agreement between the two versions based on Cronbach's α was demonstrated. Five domains consisting of pain, symptoms of foot disorders, activities of daily living, sports and recreation, and foot and ankle quality of life were added together to obtain the total score. Excellent retest reliability was shown for the total score. Test/retest reliability was excellent for the pain, stiffness, other foot disorder‐related symptoms, and quality of life domains. There were no significant differences among any domain (P > .05). There were no statistically significant differences (P = .000) for the mean ± SD differences between pretest and posttests (56.2524 ± 19.064 [51.98–60.52] and 57.45 ± 21.02 [52.74–62.16] points, respectively). Bland and Altman plots or clinically pertinent variations were not statistically significantly different. The FAOS is considered a strong and valid questionnaire with adequate repeatability in the Spanish community.
Improved thermal conductivity of β‐Si3N4 ceramics by lowering SiO2/Y2O3 ratio using YH2 as sintering additive
Authors: Wang Weide , Yao Dongxu , Liang Hanqin , Xia Yongfeng , Zuo Kaihui , Yin Jinwei , Zeng Yu‐Ping
Published: May 2020

A two‐step sintering process was conducted to produce β‐Si3N4 ceramics with high thermal conductivity. During the first step, native SiO2 was eliminated, and Y2O3 was in situ generated by a metal hydride reduction process, resulting in a high Y2O3/SiO2 ratio. The substitution YH2 for Y2O3 endow Si3N4 ceramics with an increase of 29% in thermal conductivity from 95.3 to 123 W m−1 K−1 after sintered at 1900°C for 12 hours despite an inferior sinterability. This was primarily attributed to the purified enlarged grains, devitrified grain boundary phase, and reduced lattice oxygen content in the YH2‐MgO‐doped material.
Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life
Authors: Nguyen T.V. , Damiani G. , Orenstein L.A.V. , Hamzavi I. , Jemec G.B.
Published: May 2020

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients' quality of life. It is characterized by recurrent painful nodules, abscesses and draining sinus tracts in primarily intertriginous areas. We aimed to review the most up‐to‐date information regarding the epidemiology, clinical presentation, diagnostic studies, pathogenesis, comorbidities and quality of life of patients with hidradenitis suppurativa. We performed a systematic search of Medline, Embase database (from inception to September 2019) and review of bibliographies without restrictions on year or language. HS has an estimated global prevalence of 0.00033–4.1% (but most likely 0.7–1.2% in the European‐US population). Patients still experience a significant diagnostic delay, up to several years. In the absence of pathognomonic tests, the diagnosis of HS is made from clinical observation and the disease narrative. Phenotypic variation renders diagnosis and severity assessment difficult. Ultrasound imaging is an emerging assessment tool for deep‐seated lesions. The Hurley Staging System is still widely used in severity rating. Follicular hyperkeratosis and dilatation, follicular rupture and chronic inflammation with architectural tissue changes have been implicated in the pathogenesis of HS. HS has been associated with metabolic syndrome and other risk factors for cardiovascular disease, diabetes mellitus type II, polycystic ovarian syndrome, depression, suicide and substance use disorders. It has been linked to other immune‐mediated diseases such as inflammatory bowel disease and spondyloarthropathy. Pain, pruritus, malodour, low self‐esteem, sleep and sexual dysfunctions, and poor mental health are chronic symptoms or consequences of uncontrolled disease. HS is an under‐diagnosed and under‐treated disease with a profound negative impact on patients' quality of life. In the light of its associated comorbidities, an interdisciplinary management approach may be needed to ensure the best outcomes.
The Convoy Model andLater‐LifeFamily Relationships
Authors: Fuller Heather R. , Ajrouch Kristine J. , Antonucci Toni C.
Published: May 2020

The convoy model of social relations was developed to provide a heuristic framework for conceptualizing and understanding social relationships. In this Original Voices article, we begin with an overview of the theoretical tenets of the convoy model, including its value in addressing situational and contextual influences, especially variability in family forms and cultural diversity across the life span, but particularly in older adulthood. We also consider the contributions of the convoy model to the field of family gerontology by illustrating concepts, methods, and measures used to test the model, as well as its usefulness and limitations in addressing contemporary issues facing older adults. Finally, we discuss opportunities for innovation and application of the convoy model to the study of later‐life family relationships. In summary, we emphasize the benefits and inclusiveness of the convoy model for guiding current and future research to address challenges facing family gerontology now and in the future.
Advancing Research and Theory on Aging Military Veterans in a Relational Context
Authors: Monk J. Kale , Proulx Christine , Marini Christina , Fiori Katherine
Published: May 2020

Relationships are important for successful aging, but older military veterans (aged 65 and older) experience distinct barriers and challenges to social connection. We argue that theories of social connectedness and health in older adults do not fully reflect the experiences of veterans despite providing fundamental insight into the social needs of individuals in later life. Thus, the purpose of this article is to (a) articulate the importance of social relationships for older adult veterans, (b) describe the theories commonly used to understand social connectedness and health in older adults, (c) delineate the limitations of applying these frameworks in military veteran populations in their current form, and (d) suggest potential ways to adapt these theories for older veterans. In line with this goal, we conclude by offering recommendations for understanding older adult veterans in a relational context in order to set a research and practice agenda for military family scholars and practitioners.
Maintenance of photosynthetic capacity in flooded tomato plants with reduced ethylene sensitivity
Authors: De Pedro Leandro Federico , Mignolli Francesco , Scartazza Andrea , Melana Colavita Juan Pablo , Bouzo Carlos Alberto , Vidoz María Laura
Published: May 2020

Ethylene is considered one of the most important plant hormones orchestrating plant responses to flooding stress. However, ethylene may induce deleterious effects on plants, especially when produced at high rates in response to stress. In this paper, we explored the effect of attenuated ethylene sensitivity in the Never ripe (Nr) mutant on leaf photosynthetic capacity of flooded tomato plants. We found out that reduced ethylene perception in Nr plants was associated with a more efficient photochemical and non‐photochemical radiative energy dissipation capability in response to flooding. The data correlated with the retention of chlorophyll and carotenoids content in flooded Nr leaves. Moreover, leaf area and specific leaf area were higher in Nr, indicating that ethylene would exert a negative role in leaf growth and expansion under flooded conditions. Although stomatal conductance was hampered in flooded Nr plants, carboxylation activity was not affected by flooding in the mutant, suggesting that ethylene is responsible for inducing non‐stomatal limitations to photosynthetic CO2 uptake. Upregulation of several cysteine protease genes and high protease activity led to Rubisco protein loss in response to ethylene under flooding. Reduction of Rubisco content would, at least in part, account for the reduction of its carboxylation efficiency in response to ethylene in flooded plants. Therefore, besides its role as a trigger of many adaptive responses, perception of ethylene entails limitations in light and dark photosynthetic reactions by speeding up the senescence process that leads to a progressive disassembly of the photosynthetic machinery in leaves of flooded tomato plants.
Profiling the pattern of human TRB/IGH‐CDR3 repertoire in liver transplantation patients via high‐throughput sequencing analysis
Authors: Han Fei‐fei , Fan Hua , Ren Lu‐lu , Wang Hua‐guang , Wang Chunlin , Ma Xu , Liu Li‐hong , He Qiang , Guo Chang‐long
Published: May 2020

Immune processes in liver transplantation remain poorly understood. Acute allograft rejection in liver transplantation is a kind of T cell–mediated inflammatory disease accompanied by inflammatory cell infiltration. However, the effect of acute allograft rejection on the immunological characteristics of TCRs in peripheral blood mononuclear cell is unknown. In this study, we characterized the pattern of the human T cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) complementarity‐determining region 3 (CDR3) repertoires via high‐throughput sequencing in 11 acute allograft rejection (AG) cases, 23 patients with stable allograft liver function (ST) who had liver transplantation performed and 20 healthy controls (HC). The diversity of TRB‐CDR3 was significantly reduced in the AG group compared with the ST group and healthy controls (HC). The CDR3 and N‐addition length distribution were not significantly different between the AG and ST groups. However, N‐addition length distribution was significantly changed compared to HC. It seemed that AG used more short N‐additions and healthy people used more long N‐additions in TRB‐CDR3 repertoire. Our findings suggested that the TRB‐CDR3 region of AG had distinctive V gene use compared with that of HC. The characteristics of ST seemed to be in between those of AG and HC although the difference is not significant. Cluster analysis showed that the TRB repertoire could not effectively distinguish AG from ST. This research might give to a better understanding of the immune process of liver transplantation.
Validation of flood risk maps using open source optical and radar satellite imagery
Authors: Quirós Elia , Gagnon Alexandre S.
Published: May 2020

Flood risk maps delineate areas potentially at risk of flooding and are thus a crucial tool in flood risk management. In Spain, such maps are provided as open geospatial data. This article compares the flood‐prone areas according to those maps for floods of different return periods with the spatial extent of two floods that severely affected southwestern Spain using open source optical and radar satellite imagery. Results using the recall metric were found to be very good and are the most relevant to emergency preparedness services as this metric focuses on the correctly predicted flooded areas. It was also found that the 500‐year flood risk map was the one with the best precision and accuracy for both flood events. The results confirm the accuracy of the flood risk maps based on open source remote sensing imagery and hence demonstrate the potential of publicly available and freely distributed remote sensing data in their development.
Pragmatic nativisation of thanking in South Asian Englishes
Authors: Funke Nina
Published: May 2020

As South Asian Englishes have been studied regarding their structural levels but only few studies have focused on their pragmatics, this study investigates thanking strategies in the spoken parts of the British, Indian, and Sri Lankan components of the International Corpus of English. The paper answers the questions: Do variety, speaker age and gender, context formality, position within the speaker turn, and the presence of a benefactor, intensifier, and reason influence the choice between thank and thanks; and what implications do these findings have for the notion of pragmatic nativisation? In a multifactorial analysis, a conditional inference tree identifies age, benefactor, intensifier, and variety as significant predictors while a random forest highlights the importance of variable interactions with variety.
La minería de carbón en Colombia y la situación económica de las mujeres rurales: la comunidad El Hatillo (Cesar, Colombia)
Authors: Gerstenberg Feline , Villegas González Paula Andrea
Published: May 2020

El carbón es el segundo producto más importante para el mercado de exportación de Colombia. Desde el inicio del siglo XX, los gobiernos han creado condiciones cada vez más favorables para que empresas transnacionales establezcan o amplíen sus proyectos mineros en el país. Como consecuencia, el volumen de extracción ha aumentado desde entonces. Pero mientras que el Gobierno colombiano afirmó, en el año 2012, que la explotación minera es una de las “locomotoras para el desarrollo”, y datos a nivel macro evidencian lo mismo, es dudoso que solo parte de la población colombiana se beneficie de este modelo de desarrollo. Este artículo tiene como propósito responder a la siguiente pregunta: ¿hasta qué punto la minería de carbón a gran escala cambia la situación económica de las mujeres rurales del país? Con el fin de encontrar la respuesta el artículo hace énfasis en las experiencias de ellas y cuenta la realidad desde su perspectiva. Se analizaron estudios previos y fueron realizadas entrevistas cualitativas con mujeres de una comunidad que debe ser reasentada desde el año 2012: El Hatillo - Cesar, Colombia. Como resultado de la investigación, se formularon cuatro hipótesis relacionadas con los retos que la minería genera para las mujeres rurales confrontación con la destrucción de sus medios de subsistencia; alteración con su rol tradicional dentro de la comunidad y la familia; pocas posibilidades de acceder a trabajos en las minas y se presenta un alto nivel de desigualdad de género dentro del sector.
Development of two-color resonant ionization sputtered neutral mass spectrometry and microarea imaging for Sr
Authors: Zhao Yue , Yoshida Takeru , Ohmori Yuzuka , Miyashita Yuta , Morita Masato , Sakamoto Tetsuo , Kato Kotaro , Terabayashi Ryohei , Sonnenschein Volker , Tomita Hideki , Kawai Toshihide , Okumura Takeo , Satou Yukihiko , Miyabe Masabumi , Wakaida Ikuo
Published: May 2020

Two-color resonant laser ionization sputtered neutral mass spectrometry offers high elemental selectivity. In this study, two-color resonance ionization in sputtered neutral Sr was confirmed by combining a grating type Ti:sapphire laser system and a time-of-flight secondary ion mass spectrometry (TOF-SIMS) system. The authors compared the ionization efficiencies of Sr of the two-color three-photon ionization scheme 1 (first step: 460.862 nm; second step: 767.519 nm) and the two-color two-photon ionization scheme 2 (first step: 460.862 nm; second step: 405.200 nm). The resonant ionization efficiency of the latter was found to be 50 times larger than that of the former. Finally, the authors mapped the microarea distribution of Sr by two-color resonant ionization sputtered neutral mass spectrometry.
Analysis of useful ion yield for Si in GaN by secondary ion mass spectrometry
Authors: Senevirathna M. K. Indika , Vernon Mark , Cooke Graham A. , Cross Garnett B. , Kozhanov Alexander , Williams Michael D.
Published: May 2020

The optimum detection levels that can be achieved by a secondary ion mass spectrometer are dependent on how efficiently a particular species of interest can be ionized and detected. One can determine in advance whether the analysis of a particular ion in the sample is possible, if the useful ion yield is known. The useful ion yield depends on the element, instrument transmission, the analytical conditions, the sample matrix, etc. The value of the useful ion yield for a species can diverge from one instrument type to another due to its different transmission and ionization probabilities. However, the same tendencies in the results may be expected for all types of instruments. In this paper, the authors present a quantitative secondary ion mass spectrometry analysis of the useful ion yield for the silicon dopant species in a gallium nitride matrix grown by metal organic chemical vapor deposition. Positively ionized cesium was used as the primary ion beam, and its energy was varied in the range from 0.5 to 5 kV. A quadrupole mass analyzer was utilized to collect secondary ion species of interest. The analysis results can be used to determine the primary beam energies for optimal Si sensitivity.
Diagnosis and Treatment of Arterial Thoracic Outlet Syndrome in a Collegiate Volleyball Player: A Case Report
Authors: Craig Katherine , Jordan Shannon L. , Chilek Daniel R. , Boatwright Doug , Morales Julio
Published: May 2020

A 19-year-old female volleyball player reported shoulder pain, numbness, tingling, and difficulty gripping in her left arm. Provocation tests were positive for thoracic outlet syndrome (TOS). Duplex ultrasonography revealed occlusion of the subclavian artery. The athlete underwent a first rib resection and scalenectomy. A cervical rib and 75% of the first rib were excised. Rehabilitation consisted of regaining range of motion and strength. Return to play occurred after 14 weeks of rehabilitation. Thoracic outlet syndrome is rare and often misdiagnosed. All sports medicine professionals should have an understanding of TOS symptoms and path to diagnosis.
Is There an Association Between Self-Reported Physical Activity and Self-Rated Vision Over Time? Results From the Irish Longitudinal Study of Ageing
Authors: McMullan Ilona I. , Bunting Brendan P. , Smith Lee , Koyanagi Ai , Tully Mark A.
Published: May 2020

Research suggests that physical activity (PA) has many health benefits for an aging population. Evidence exploring the association between PA and vision is limited. This study includes the measures of self-reported PA (International Physical Activity Questionnaire) and self-rated vision at three points in time over a 6-year period used in the Irish Longitudinal study of Ageing, a cohort of community-dwelling older adults (50 years or older). A path analysis found that PA was indirectly associated with vision over 6 years controlling for age, sex, marital status, employment, education, depression (Centre for Epidemiologic Studies Depression Scale), self-reported general health, cardiovascular disease (e.g., heart attack), high blood pressure, diabetes, eye disease (e.g., glaucoma, diabetic eye disease, macular degeneration, cataract), and disabilities associated with activities of daily living. Further research is needed to fully understand the relationship over time and generalize the findings.
LGBT Diversity and Inclusion, Community Characteristics, and Success
Authors: Cunningham George B. , Nite Calvin
Published: May 2020

Drawing from concepts in institutional theory, the purpose of this study was to examine how community measures intersect with lesbian, gay, bisexual, and transgender inclusiveness to predict organizational success. The authors collected publicly available data about National Collegiate Athletic Association departments (N = 65) and their communities. Moderated regression analyses demonstrated significant interactive effects, such that performance was highest when the department followed an inclusive strategy and (a) the lesbian, gay, and bisexual population density was high and (b) the state-level implicit bias toward sexual minorities was low. Importantly, there were no negative effects in following an inclusive strategy, even when institutional logics did not prescribe such an approach. The models explained 60–62% of the variance in performance. The authors discuss theoretical and practical implications.
Structural basis of broad HIV neutralization by a vaccine-induced cow antibody
Authors: Stanfield Robyn L. , Berndsen Zachary T. , Huang Ruiqi , Sok Devin , Warner Gabrielle , Torres Jonathan L. , Burton Dennis R. , Ward Andrew B. , Wilson Ian A. , Smider Vaughn V.
Published: May 2020

Structure and mutagenesis studies show that a potent vaccine-elicited cow bnAb binds with a compact footprint to HIV gp120 CD4bs.
Efficient communication over complex dynamical networks: The role of matrix non-normality
Authors: Baggio Giacomo , Rutten Virginia , Hennequin Guillaume , Zampieri Sandro
Published: May 2020

Non-normal networks efficiently spread information in the face of interference between successive transmissions and readout noise.
Feature-rich covalent stains for super-resolution and cleared tissue fluorescence microscopy
Authors: Mao Chenyi , Lee Min Yen , Jhan Jing-Ru , Halpern Aaron R. , Woodworth Marcus A. , Glaser Adam K. , Chozinski Tyler J. , Shin Leonard , Pippin Jeffrey W. , Shankland Stuart J. , Liu Jonathan T.C. , Vaughan Joshua C.
Published: May 2020

FLARE enables rapid, feature-rich stains of chemical groups in biological samples for super-resolution and cleared tissue imaging.
High mantle seismic P-wave speeds as a signature for gravitational spreading of superplumes
Authors: Stern Tim , Lamb Simon , Moore James D. P. , Okaya David , Hochmuth Katharina
Published: May 2020

High mantle P-wave speeds beneath oceanic plateaus define a new strain fabric indicative of flow in the head of a superplume.
Quantitative Proteome Profiling Reveals Cellobiose-Dependent Protein Processing and Export Pathways for the Lignocellulolytic Response in Neurospora crassa
Authors: Liu Dan , Liu Yisong , Zhang Duoduo , Chen Xiaoting , Liu Qian , Xiong Bentao , Zhang Lihui , Wei Linfang , Wang Yifan , Fang Hao , Liesche Johannes , Wei Yahong , Glass N. Louise , Hao Zhiqi , Chen Shaolin
Published: May 2020

Lignocellulases are important industrial enzymes for sustainable production of biofuels and bio-products. Insoluble cellulose has been commonly used to induce the production of lignocellulases in filamentous fungi, which causes a difficult fermentation operation and enzyme loss due to adsorption to cellulose. The disadvantages can be overcome by using soluble inducers, such as the disaccharide cellobiose. Quantitative proteome profiling of the model filamentous fungus
Neurospora crassa
revealed cellobiose-dependent pathways for cellulase production, including protein processing and export. A protein (CWH43) potentially involved in protein processing was found to be a positive regulator of lignocellulase production. The cellobiose-dependent mechanisms provide new opportunities to improve the production of lignocellulases in filamentous fungi.
Degradation of MicroRNA miR-466d-3p by Japanese Encephalitis Virus NS3 Facilitates Viral Replication and Interleukin-1β Expression
Authors: Jiang Hui , Bai Lige , Ji Lina , Bai Zhuofang , Su Jianwei , Qin Tian , Wang Guojun , Balasubramaniam Vinod , Wang Xiao , Cui Min , Ye Jing , Cao Shengbo , Li Guangpeng , Yang Yang
Published: May 2020

Host miRNAs have been reported to regulate JEV-induced inflammation in the CNS. We found that JEV infection could reduce expression of host miRNA. The helicase region of the NS3 protein bound specifically to miRNA precursors and could lead to incorrect unwinding of miRNA precursors, thereby reducing the expression of mature miRNAs. This observation led to two major findings. First, our results suggested that JEV NS3 protein induced miR-466d-3p degradation, which promoted IL-1β expression and JEV replication. Second, arginine molecules on NS3 were the main miRNA-binding sites, because we demonstrated that miRNA degradation was abolished if arginines at R226 and R202 were mutated. Our study provides new insights into the molecular mechanism of JEV and reveals several amino acid sites that could be mutated for a JEV vaccine.
Draft Genome Sequence of an Unusually Multidrug-Resistant Strain of Achromobacter xylosoxidans from a Blood Isolate
Authors: Choi Hosoon , Jinadatha Chetan , Chatterjee Piyali , Allton Yonhui , Navarathna Dhammika H.
Published: May 2020

Achromobacter xylosoxidans
strain DN2019 was isolated from blood of a septicemia patient. We describe the draft genome and antibiotic susceptibility of this strain.
Microbial Diversity of the Hell Creek Watershed at the Tri-Faith Community in Nebraska, Based on 16S rRNA Gene Amplicon Sequencing
Authors: Kyndt John A.
Published: May 2020

Hell Creek’s watershed is a historically important native land area located in Omaha, Nebraska, that includes Hell Creek and an adjacent flood plain. This initial microbial analysis showed that even though samples were isolated from the same watershed area, there were significant differences between the creek itself and the nearby pond.
Cost-effectiveness of different strategies for screening and treatment ofStrongyloides stercoralisin migrants from endemic countries to the European Union
Authors: Wikman-Jorgensen Philip Erick , Llenas-Garcia Jara , Shedrawy Jad , Gascon Joaquim , Muñoz Jose , Bisoffi Zeno , Requena-Mendez Ana
Published: May 2020

Background

The best strategy for controlling morbidity due to imported strongyloidiasis in migrants is unclear. We evaluate the cost-effectiveness of six possible interventions.

Methods

We developed a stochastic Markov chain model. The target population was adult migrants from endemic countries to the European Union; the time horizon, a lifetime and the perspective, that of the health system. Average and incremental cost-effectiveness ratios (ACER and ICER) were calculated as 2016 EUR/life-year gained (LYG). Health interventions compared were: base case (no programme), primary care-based presumptive treatment (PCPresTr), primary care-based serological screening and treatment (PCSerTr), hospital-based presumptive treatment (HospPresTr), hospital-based serological screening and treatment (HospSerTr), hospital-based presumptive treatment of immunosuppressed (HospPresTrim) and hospital-based serological screening and treatment of the immunosuppressed (HospSerTrim). The willingness to pay threshold (WTP) was €32 126.95/LYG.

Results

The base case model yielded a loss of 2 486 708.24 life-years and cost EUR 3 238 393. Other interventions showed the following: PCPresTr: 2 488 095.47 life-years (Δ1 387.23LYG), cost: EUR 8 194 563; ACER: EUR 3573/LYG; PCSerTr: 2 488 085.8 life-years (Δ1377.57LYG), cost: EUR 207 679 077, ACER: EUR 148 407/LYG; HospPresTr: 2 488 046.17 life-years (Δ1337.92LYG), cost: EUR 14 559 575; ACER: EUR 8462/LYG; HospSerTr: 2 488 024.33 life-years (Δ1316.08LYG); cost: EUR 207 734 073; ACER: EUR 155 382/LYG; HospPresTrim: 2 488 093.93 life-years, cost: EUR 1 105 483; ACER: EUR −1539/LYG (cost savings); HospSerTrim: 2 488 073.8 life-years (Δ1365.55LYG), cost: EUR 4 274 239; ACER: EUR 759/LYG. One-way and probabilistic sensitivity analyses were undertaken; HospPresTrim remained below WTP for all parameters’ ranges and iterations.

Conclusion

Presumptively treating all immunosuppressed migrants from areas with endemicStrongyloideswould generate cost savings to the health system.
Cohort profile: the Australian genetics of depression study
Authors: Byrne Enda M , Kirk Katherine M , Medland Sarah E , McGrath John J , Colodro-Conde Lucia , Parker Richard , Cross Simone , Sullivan Lenore , Statham Dixie J , Levinson Douglas F , Licinio Julio , Wray Naomi R , Hickie Ian B , Martin Nicholas G
Published: May 2020

Purpose

Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants.

Participants

A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail.

Findings to date

95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed.

Future plans

A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.
Mental health among Ebola survivors in Liberia, Sierra Leone and Guinea: results from a cross-sectional study
Authors: Secor Andrew , Macauley Rose , Stan Laurentiu , Kagone Meba , Sidikiba Sidibe , Sow Sadou , Aronovich Dana , Litvin Kate , Davis Nikki , Alva Soumya , Sanderson Jeff
Published: May 2020

Objectives

To describe the prevalence and correlates of depression and anxiety among adult Ebola virus disease (EVD) survivors in Liberia, Sierra Leone and Guinea.

Design

Cross-sectional.

Setting

One-on-one surveys were conducted in EVD-affected communities in Liberia, Sierra Leone and Guinea in early 2018.

Participants

1495 adult EVD survivors (726 male, 769 female).

Primary and secondary outcome measures

Patient Health Questionnaire-9 (PHQ-9) depression scores and Generalised Anxiety Disorder-7 (GAD-7) scores.

Results

Prevalence and severity of depression and anxiety varied across the three countries. Sierra Leone had the highest prevalence of depression, with 22.0% of participants meeting the criteria for a tentative diagnosis of depression, compared with 20.2% in Liberia and 13.0% in Guinea. Sierra Leone also showed the highest prevalence of anxiety, with 10.7% of participants meeting criteria for generalized anxiety disorder (GAD-7 score ≥10), compared with 9.9% in Liberia and 4.2% in Guinea. Between one-third and one-half of respondents reported little interest or pleasure in doing things in the previous 2 weeks (range: 47.0% in Liberia to 37.6% in Sierra Leone), and more than 1 in 10 respondents reported ideation of self-harm or suicide (range: 19.4% in Sierra Leone to 10.4% in Guinea). Higher depression and anxiety scores were statistically significantly associated with each other and with experiences of health facility-based stigma in all three countries. Other associations between mental health scores and respondent characteristics varied across countries.

Conclusions

Our results indicate that both depression and anxiety are common among EVD survivors in Liberia, Sierra Leone and Guinea, but that there is country-level heterogeneity in prevalence, severity and correlates of these conditions. All three countries should work to make mental health services available for survivors, and governments and organisations should consider the intersection between EVD-related stigma and mental health when designing programmes and training healthcare providers.
Nomogram for contrast-induced acute kidney injury in patients with chronic kidney disease undergoing coronary angiography in China: a cohort study
Authors: Lei Li , Xue Yan , Guo Zhaodong , Liu Bowen , He Yibo , Liu Jin , Nie Zhiqiang , Chen Liling , Chen Kaihong , Huang Zhidong , Liang Min , Chen Shiqun , Liu Yong , Chen Jiyan
Published: May 2020

Objectives

To establish a nomogram for contrast-induced acute kidney injury (CI-AKI) risk assessment among patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).

Design

Prospective observational cohort study.

Setting

Southern China.

Interventions

None.

Participants

643 consecutive patients with CKD (defined as estimated glomerular filtration rate calculated by Modification of Diet in Renal Disease formula <60 mL/min/1.73 mm2) were enrolled.

Outcome measures

The end point was CI-AKI defined as serum creatinine elevation ≥0.5 mg/dL or 25% from baseline within the first 48–72 hours following contrast exposure.Predictors of CI-AKI were selected by multivariable logistic regression and stepwise approach. A nomogram based on these predictors was constructed and compared with the classic Mehran Score. For validation, a bootstrap method (1000 times) was performed.

Results

The nomogram including age, weight, heart rate, hypotension, PCI and β-blocker demonstrated a better predictive value than the classic Mehran Score (area under the curve: 0.78 vs 0.71, p=0.024), as well as a well-fitted calibration curve (χ2=12.146, p=0.145). Validation through the bootstrap method (1000 times) also indicated a good discriminative power (adjusted C-statistic: 0.76).

Conclusions

With fewer predictors and higher discriminative power, the present nomogram may be a simple and reliable tool to identify patients with CKD at risk of CI-AKI, whereas further external validations are needed.
Association of artificial turf and concussion in competitive contact sports: a systematic review and meta-analysis
Authors: O' Leary Frank , Acampora Nic , Hand Fiona , O' Donovan James
Published: May 2020

Objective

To determine the incidence of head injuries and concussion in contact sports, comparing natural grass with artificial turf surfaces.

Design

Systematic review and meta-analysis via the RevMan V.5.3 software.

Eligibility criteria for selecting studies

All studies describing competitive contact sports played on both natural grass and artificial turf. The primary outcome measured was occurrence of head injury and concussion.

Data sources

The databases include PubMed, Embase, Cochrane, Medline and Sport Discus. The last search took place on 23 May 2019. The Newcastle-Ottawa Quality Assessment Scale evaluated the methodological quality of the selected studies with a funnel plot designed to determine publication bias. Study screening and data extraction were performed by two independent reviewers.

Results

Initial screening generated 42 publications, with 12 meeting criteria for inclusion. Eight studies described concussion only. The rate ratio (RR) of head injury and concussion was less on artificial turf compared with natural grass (RR=0.89, 95% CI 0.77 to 1.04) as was the rate ratio of concussion only (RR=0.72, 95% CI 0.58 to 0.89).

Conclusion

Analysis of published data demonstrates a decreased incidence of head injury and concussion when contact sports are played on artificial turf. This difference was most marked for sports such as rugby and American football. However, artificial turf has no association with the incidence of head injury or concussion while playing soccer.
Granzyme B PET imaging of immune-mediated tumor killing as a tool for understanding immunotherapy response
Authors: LaSalle Thomas , Austin Emily E , Rigney Grant , Wehrenberg-Klee Eric , Nesti Sarah , Larimer Benjamin , Mahmood Umar
Published: May 2020

Background

Cancer immunotherapy research is expanding to include a more robust understanding of the mechanisms of treatment response and resistance. Identification of drivers of pro-tumor and anti-tumor immunity during treatment offers new strategies for effective alternative or combination immunotherapies. Currently, tissue or blood samples are collected and analyzed, then dichotomized based on clinical end points that may occur months or years after tissue is collected. While overall survival is ultimately the desired clinical outcome, this dichotomization fails to incorporate the nuances that may occur during an anti-tumor response. By failing to directly measure immune activation at the time of sampling, tumors may be misclassified and potentially obscure important biological information. Non-invasive techniques, such as positron emission tomography (PET), allow for global and quantitative measurements of cancer specific processes and are widely used clinically to help manage disease.

Methods

We have previously developed a novel PET agent that can non-invasively quantify granzyme B release in tumors and have demonstrated its ability to predict response to checkpoint inhibitor therapy in multiple murine models of cancer. Here, we used the quantitative measurement of granzyme B release as a direct and time-matched marker of immune cell activation in order to determine immune cell types and cytokines that correlate with effective checkpoint inhibitor therapy in both tumors and tumor-draining lymph nodes.

Results

Through PET imaging, we were able to successfully distinguish distinct microenvironments, based on tumor type, which influenced immune cell subpopulations and cytokine release. Although each tumor was marked by functionally distinct pathways of immune cell activation and inflammation, they also shared commonalities that ultimately resulted in granzyme B release and tumor killing.

Conclusions

These results suggest that discrete tumor immune microenvironments can be identified in both responsive and non-responsive tumors and offers strategic targets for intervention to overcome checkpoint inhibitor resistance.
ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma
Authors: Sheng Hailong , Huang Yan , Xiao Yazhi , Zhu Zhenru , Shen Mengying , Zhou Peitao , Guo Zeqin , Wang Jian , Wang Hui , Dai Wencong , Zhang Wanjun , Sun Jingyuan , Cao Chuanhui
Published: May 2020

Background

Radioimmunotherapy has a promising antitumor effect in hepatocellular carcinoma (HCC), depending on the regulatory effect of radiotherapy on tumor immune microenvironment. Ionizing radiation (IR)-induced DNA damage repair (DDR) pathway activation leads to the inhibition of immune microenvironment, thus impairing the antitumor effect of radioimmunotherapy. However, it is unclear whether inhibition of the DDR pathway can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of DDR inhibitor AZD6738 on the combination of radiotherapy and immune checkpoint inhibitors (ICIs) in HCC.

Methods

C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control and tumor recurrence inhibition. Effects of each treatment regimen on the alterations of immunophenotypes including the quantification, activation, proliferating ability, exhaustion marker expression, and memory status were assessed by flow cytometry.

Results

AZD6738 further increased radiotherapy-stimulated CD8+T cell infiltration and activation and reverted the immunosuppressive effect of radiation on the number of Tregs in mice xenografts. Moreover, compared with radioimmunotherapy (radiotherapy plus anti-PD-L1 (Programmed death ligand 1)), the addition of AZD6738 boosted the infiltration, increased cell proliferation, enhanced interferon (IFN)-γ production ability of TIL (tumor-infiltrating lymphocyte) CD8+T cells, and caused a decreasing trend in the number of TIL Tregs and exhausted T cells in mice xenografts. Thus, the tumor immune microenvironment was significantly improved. Meanwhile, triple therapy (AZD6738 plus radiotherapy plus anti-PD-L1) also induced a better immunophenotype than radioimmunotherapy in mice spleens. As a consequence, triple therapy displayed greater benefit in antitumor efficacy and mice survival than radioimmunotherapy. Mechanism study revealed that the synergistic antitumor effect of AZD6738 with radioimmunotherapy relied on the activation of cyclic GMP–AMP synthase /stimulator of interferon genes (cGAS/STING) signaling pathway. Furthermore, triple therapy led to stronger immunologic memory and lasting antitumor immunity than radioimmunotherapy, thus preventing tumor recurrence in mouse models.

Conclusions

Our findings indicate that AZD6738 might be a potential synergistic treatment for radioimmunotherapy to control the proliferation of HCC cells, prolong survival, and prevent tumor recurrence in patients with HCC by improving the immune microenvironment.
Neoantigen load and HLA-class I expression identify a subgroup of tumors with a T-cell-inflamed phenotype and favorable prognosis in homologous recombination-proficient high-grade serous ovarian carcinoma
Authors: Matsushita Hirokazu , Hasegawa Kosei , Oda Katsutoshi , Yamamoto Shogo , Asada Kayo , Karasaki Takahiro , Yabuno Akira , Nishijima Akira , Nejo Takahide , Kobayashi Yukari , Sato Sho , Ikeda Yuji , Miyai Manami , Takahashi Yusuke , Yamaguchi Rui , Fujiwara Keiichi , Aburatani Hiroyuki , Kakimi Kazuhiro
Published: May 2020

Background

There is increasing evidence for the benefit of poly ADP ribose polymerase (PARP) inhibitors in a subset of high-grade serous ovarian carcinoma (HGSC) patients, especially those with homologous recombination (HR)-deficient tumors. However, new treatment strategies, such as immune checkpoint inhibition, are required for patients with HR-proficient tumors.

Methods

A total of 80 cases of HGSC were analyzed in this study. Whole exome and RNA sequencing was performed for these tumors. Methylation arrays were also carried out to examineBRCA1andRAD51Cpromoter methylation status. Mutations, neoantigen load, antigen presentation machinery, and local immune profile were investigated, and the relationships of these factors with clinical outcome were also analyzed.

Results

As expected, the numbers of predicted neoAgs were lower in HR-proficient (n=46) than HR-deficient tumors (n=34). However, 40% of the patients with HR-proficient tumors still had higher than median numbers of neoAgs and better survival than patients with lower numbers of neoAgs. Incorporation of human leukocyte antigen (HLA)-class I expression status into the survival analysis revealed that patients with both high neoAg numbers and high HLA-class I expression (neoAghiHLAhi) had the best progression-free survival (PFS) in HR-proficient HGSC (p=0.0087). Gene set enrichment analysis demonstrated that the genes for effector memory CD8 T cells, TH1 T cells, the interferon-γ response, and other immune-related genes, were enriched in these patients. Interestingly, this subset of patients also had better PFS (p=0.0015) and a more T-cell-inflamed tumor phenotype than patients with the same phenotype (neoAghiHLAhi) in HR-deficient HGSC.

Conclusions

Our results suggest that immune checkpoint inhibitors might be an alternative to explore in HR-proficient cases which currently do not benefit from PARP inhibition.
Granzyme B is correlated with clinical outcome after PD-1 blockade in patients with stage IV non-small-cell lung cancer
Authors: Hurkmans Daan P. , Basak Edwin A. , Schepers Nina , Oomen-De Hoop Esther , Van der Leest Cor H. , El Bouazzaoui Samira , Bins Sander , Koolen Stijn L. W. , Sleijfer Stefan , Van der Veldt Astrid A. M. , Debets Reno , Van Schaik Ron H. N. , Aerts Joachim G. J. V. , Mathijssen Ron H. J.
Published: May 2020

Background

A minority of patients with advanced non-small-cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Ineffective effector function of activated T and NK cells may lead to reduced tumor cell death, even when these activated effector cells are released from their immune checkpoint brake. Hence, in this study we aimed to assess the association of baseline serum granzyme B, as well as germline variation of theGZMBgene, with clinical outcome to programmed cell death protein 1 (PD-1) blockade.

Methods

A total of 347 patients with stage IV NSCLC who started nivolumab treatment between June 2013 and June 2017 were prospectively included. Baseline serum and whole blood was available, allowing for protein quantification and targeted DNA sequencing. Clinical outcome was based on best overall response (BOR) according to Response Evaluation Criteria in Solid Tumors, V.1.1, progression-free survival (PFS), and overall survival (OS).

Results

Patients with low serum levels of granzyme B had worse PFS (HR: 1.96; 95% CI: 1.12 to 3.43; p=0.018) and worse OS (HR: 2.08; 95% CI: 1.12 to 3.87; p=0.021) than patients with high baseline serum levels. To validate the findings, germline variation ofGZMBrs8192917 was assessed. Patients with homozygous and heterozygous variants ofGZMBrs8192917 had worse BOR (OR: 1.60; 95% CI: 1.01 to 2.52; p=0.044) and worse PFS (HR: 1.38; 95% CI:1.02 to 1.87; p=0.036) than wild types.

Conclusions

A low baseline serum level of granzyme B and germline variation ofGZMBwas associated with worse clinical outcome in NSCLC, emphasizing the relevance and additional value of monitoring germline genetic variations which mirror cytotoxic functions of T cells in ICI therapy.

Trail registration number

Dutch Trial Registry (NL6828).