bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary result of carbon-ion radiotherapy using the spot scanning method for prostate cancer
Authors: Takakusagi Yosuke , Katoh Hiroyuki , Kano Kio , Anno Wataru , Tsuchida Keisuke , Mizoguchi Nobutaka , Serizawa Itsuko , Yoshida Daisaku , Kamada Tadashi 
Published: May 2020

Abstract
Background
Carbon-ion radiotherapy (CIRT) for prostate cancer was initiated at Kanagawa Cancer Center in 2015. The present study analyzed the preliminary clinical outcomes of CIRT for prostate cancer.

Methods
The clinical outcomes of 253 patients with prostate cancer who were treated with CIRT delivered using the spot scanning method between December 2015 and December 2017 were retrospectively analyzed. The irradiation dose was set at 51.6 Gy (relative biological effectiveness) delivered in 12 fractions over 3 weeks. Biochemical relapse was defined using the Phoenix definition. Toxicities were assessed according to CTCAE version 4.0. Results: The median patient age was 70 (47–86) years. The median follow-up duration was 35.3 (4.1–52.9) months. According to the D’Amico classification system, 8, 88, and 157 patients were classified as having low, intermediate, and high risks, respectively. Androgen deprivation therapy was administered in 244 patients. The biochemical relapse-free rate in the low-, intermediate-, and high-risk groups at 3 years was 87.5, 88.0, and 97.5%, respectively (P = 0.036). Grade 2 acute urinary toxicity was observed in 12 (4.7%) patients. Grade 2 acute rectal toxicity was not observed. Grade 2 late urinary toxicity and grade 2 late rectal toxicity were observed in 17 (6.7%) and 3 patients (1.2%), respectively. Previous transurethral resection of the prostate was significantly associated with late grade 2 toxicity in univariate analysis. The predictive factor for late rectal toxicity was not detected.

Conclusion
The present study demonstrated that CIRT using the spot scanning method for prostate cancer produces favorable outcomes.
Durability of bioprosthetic aortic valves in patients under the age of 60 years – rationale and design of the international INDURE registry
Authors: Meuris Bart , Borger Michael A. , Bourguignon Thierry , Siepe Matthias , Grabenwöger Martin , Laufer Günther , Binder Konrad , Polvani Gianluca , Stefano Pierluigi , Coscioni Enrico , van Leeuwen Wouter , Demers Philippe , Dagenais Francois , Canovas Sergio , Theron Alexis , Langanay Thierry , Roussel Jean-Christian , Wendler Olaf , Mariscalco Giovanni , Pessotto Renzo , Botta Beate , Bramlage Peter , de Paulis Ruggero 
Published: May 2020

Abstract
Background
There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR.

Methods
The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20–22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery.
The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life.

Discussion
INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years.

Trial registration
ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018).
Diversity of hydrolase-producing halophilic bacteria and evaluation of their enzymatic activities in submerged cultures
Authors: Drissi Kaitouni Leila Batsoule , Anissi Jaouad , Sendide Khalid , El Hassouni Mohammed 
Published: May 2020

Abstract
Purpose
In this work, we assessed the diversity of culturable halophilic bacteria that produce hydrolytic enzymes from both natural and artificial hypersaline regions in the pre-Rif region of Morocco.

Methods
Bacteria were isolated from three hypersaline sites, in solid medium supplemented with various salt concentrations ranging from 0 to 330 g/L. Physical and chemical characteristics of samples from the isolation site were determined to suggest eventual correlations with the occurrence of the halophilic bacteria. Assays on enzymatic activities were performed in submerged cultures in the presence of various salt concentrations and appropriate substrates.

Results
Out of a collection of 227 halophilic bacteria, four halophilic groups were established as slightly halophilic, moderately halophilic, halotolerant, or extremely halophilic, with a predominance of halophilic bacteria in the natural hypersaline sites compared to the artificial one. Within this collection, 189 strains showed important hydrolytic activities in submerged cultures with enzymatic activities up to 76 U/mg. Strain characterization and identification was based on phenotypic and molecular traits and allowed the identification of at least 26 genera including Bacillus, Chthonibacter, Mariniabilia, Halobacillus, Salinococcus, Cerasicoccus, Ulvibacter, Halorubrum, Jeatgalicoccus, Brevibacterium, Sanguibacter, Shewanella, Exiguobacterium, Gemella, and Planomicrobium.

Conclusion
Data from this study give insights about the origin and the occurrence of halophilic bacteria in natural hypersaline environments compared to artificial hypersaline sites. The occurrence of halophilic hydrolase enzymes from halophilic bacteria gives insights to different applications in biotechnology, thanks to their ability to produce adaptive enzymes and survival strategies to overcome harsh conditions.
A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome
Authors: Shoma Suresh K. , Bhat Samatha , Guru Bharath Raja , Muttigi Manjunatha S. , Seetharam Raviraja N. 
Published: May 2020

Abstract
Background
Mesenchymal stromal cell conditioned medium (MSC-CM) contains a cocktail of bioactive factors that act synergistically to induce therapeutic effects. This has been clearly demonstrated by in vivo applications of MSC-CM, but the establishment of controlled delivery systems is an unmet requirement for clinical translation.

Methods
We developed a nanocomposite-hydrogel (NP-H) comprised of poly-L-lactide nanoparticles (NPs) embedded in gelatin/hyaluronic acid (Gel/HA) hydrogel as a delivery vehicle for MSC-CM. First, we optimized the culture conditions for bone marrow-derived MSCs using serum-containing medium (SCM) and serum-free medium (SFM) and characterized the corresponding CM (serum-containing conditioned medium (ScCM) and serum-free conditioned medium (SfCM), respectively) for its potency and xeno markers. Then we prepared a composite matrix followed by physiochemical characterization and functional assays were performed.

Results
Nanocomposite hydrogel displayed an even distribution of NPs along with high porosity (> 60%) and swelling ratios > 1500%, while its protein release pattern corresponded to a mix of degradation and diffusion kinetics. Functional evaluation of the composites was determined using MSCs and human fibroblasts (HFFs). The cells seeded directly onto the composites displayed increasing metabolic activities over time, with ScCM-NP-H groups having maximum activity. The cells treated in vitro with 5% and 10% extracts of ScCM-NP-H and SfCM-NP-H exhibited a dose- and duration-dependent response. Cell activities reduced considerably for all groups, except 10% ScCM-NP-H, which displayed a significant increase over time.

Conclusion
We observed that sustained release of MSC-CM is required to prevent dose-dependent cytotoxicity. The proposed nanocomposite hydrogel for MSC-CM delivery can open up a new array for its clinical application.
Evaluation of oxidant/antioxidant status, metabolic profile and milk production in cows with metritis
Authors: Mikulková Karolína , Kadek Romana , Filípek Jaroslav , Illek Josef 
Published: May 2020

Abstract
Background
The aim of the study was to evaluate oxidant/antioxidant status in 21 Holstein dairy cows with metritis compared to 8 healthy controls. Blood samples were taken during the first 21 days postpartum. Malondialdehyde (MDA), a marker of oxidative stress, total antioxidant status (TAS) and antioxidant parameters such as glutathione peroxidase (GPx), selenium (Se), vitamins A and E and beta-carotene were determined from all cows. The differences in beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), calcium, bilirubin concentrations and aspartate aminotransferase (AST) activity were also monitored, as were milk production and milk composition. Metritis was defined by an unpleasant discharge of varying color (milky-grey/brown/sanguineous) and consistency (muco-purulent/purulent/watery) and by the presence of increased temperature (> 38.5 °C) in cows within 21 days postpartum. Rectal examination revealed increased uterine size, thickened uterine wall and increased uterine tone. The affected cows had significantly reduced daily milk production. Additionally, hematological parameters and haptoglobin concentration were also measured in metritic cows.

Results
Higher MDA concentration (P <  0.001) was recorded in cows with metritis, while vitamin A and vitamin E concentrations were lower (P <  0.01) compared to healthy cows. Higher BHB (P <  0.05), NEFA (P <  0.05), AST (P <  0.05) and bilirubin (P <  0.001) concentrations was recorded in cows with metritis as compared to the control group. Significant differences in beta-carotene concentration, GPx activity, and Se, TAS and Ca concentrations in cows with metritis compared to control group were not observed in the present study (P >  0.05). Milk production was decreased in the cows with metritis (P <  0.001) and alterations in milk composition were also observed in metritic cows as compared to healthy cows.

Conclusions
The results of the study showed that cows with metritis in early postpartum are exposed to a higher degree of oxidative stress and that the incidence of metritis can negatively affect milk production in dairy cows.
The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Chen Haifeng , Sheng Xiaoning , Luo Caimei , Qin Ruomeng , Ye Qing , Zhao Hui , Xu Yun , Bai Feng 
Published: May 2020

Abstract
Background
Subjective cognitive decline (SCD) is a preclinical stage along the Alzheimer’s disease (AD) continuum. However, little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in SCD.

Methods
Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls (HC). Pearson correlation analysis was computed to assess the relationships among network metrics, neuropsychological performance and pathological biomarkers. Finally, we used the multiple kernel learning-support vector machine (MKL-SVM) to differentiate the SCD and HC individuals.

Results
SCD individuals showed higher nodal topological properties (including nodal strength, nodal global efficiency and nodal local efficiency) associated with amyloid-β levels and memory function than the HC, and these regions were mainly located in the default mode network (DMN). Moreover, increased local and medium-range connectivity mainly between the bilateral parahippocampal gyrus (PHG) and other DMN-related regions was found in SCD individuals compared with HC individuals. These aberrant functional network measures exhibited good classification performance in the differentiation of SCD individuals from HC individuals at an accuracy up to 79.23%.

Conclusion
The findings of this study provide insight into the compensatory mechanism of the functional connectome underlying SCD. The proposed classification method highlights the potential of connectome-based metrics for the identification of the preclinical stage of AD.
A systematic review on spatial crime forecasting
Authors: Kounadi Ourania , Ristea Alina , Araujo Adelson , Leitner Michael 
Published: May 2020

Abstract
Background
Predictive policing and crime analytics with a spatiotemporal focus get increasing attention among a variety of scientific communities and are already being implemented as effective policing tools. The goal of this paper is to provide an overview and evaluation of the state of the art in spatial crime forecasting focusing on study design and technical aspects.

Methods
We follow the PRISMA guidelines for reporting this systematic literature review and we analyse 32 papers from 2000 to 2018 that were selected from 786 papers that entered the screening phase and a total of 193 papers that went through the eligibility phase. The eligibility phase included several criteria that were grouped into: (a) the publication type, (b) relevance to research scope, and (c) study characteristics.

Results
The most predominant type of forecasting inference is the hotspots (i.e. binary classification) method. Traditional machine learning methods were mostly used, but also kernel density estimation based approaches, and less frequently point process and deep learning approaches. The top measures of evaluation performance are the Prediction Accuracy, followed by the Prediction Accuracy Index, and the F1-Score. Finally, the most common validation approach was the train-test split while other approaches include the cross-validation, the leave one out, and the rolling horizon.

Limitations
Current studies often lack a clear reporting of study experiments, feature engineering procedures, and are using inconsistent terminology to address similar problems.

Conclusions
There is a remarkable growth in spatial crime forecasting studies as a result of interdisciplinary technical work done by scholars of various backgrounds. These studies address the societal need to understand and combat crime as well as the law enforcement interest in almost real-time prediction.

Implications
Although we identified several opportunities and strengths there are also some weaknesses and threats for which we provide suggestions. Future studies should not neglect the juxtaposition of (existing) algorithms, of which the number is constantly increasing (we enlisted 66). To allow comparison and reproducibility of studies we outline the need for a protocol or standardization of spatial forecasting approaches and suggest the reporting of a study’s key data items.
Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non–Small-Cell Lung Cancer
Authors: Reck Martin , Wehler Thomas , Orlandi Francisco , Nogami Naoyuki , Barone Carlo , Moro-Sibilot Denis , Shtivelband Mikhail , González Larriba Jose Luis , Rothenstein Jeffrey , Früh Martin , Yu Wei , Deng Yu , Coleman Shelley , Shankar Geetha , Patel Hina , Kelsch Claudia , Lee Anthony , Piault Elisabeth , Socinski Mark A. 
Published: May 2020

PURPOSE Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. RESULTS Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly. CONCLUSION ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.
Multiple Myeloma Cost of Care Under the Oncology Care Model: The Influence of High-Cost Therapies
Authors: Theroux Haley , Williams Alaysia , Liu Mark , Dahl Alyssa , Dreyer Theresa , Horvath Keith , Isola Luis 
Published: May 2020

PURPOSE: As expenditures for cancer care continue to grow substantially, value-based payment models are being tested to control costs. The Oncology Care Model (OCM) is the largest value-based payment program in oncology. The primary objective of this analysis was to determine the impact of high-cost novel agents on total cost of care for multiple myeloma (MM) episodes of care in the OCM. METHODS: This was a retrospective analysis using Medicare claims data for 258 MM OCM episodes initiated between July 1, 2016, and July 1, 2017. Patients were organized into 3 cohorts: those who received pomalidomide (cohort A), those who received lenalidomide (cohort B), and those who did not receive either drug but had received another chemotherapy agent (cohort C). We compared the actual episode expenditures and the Centers for Medicare and Medicaid target price to create an observed versus expected (O/E) ratio. RESULTS: The average O/E for cohort A (n = 73) was 1.73, compared with 1.31 for cohort B (n = 84) and 1.01 for cohort C (n = 101). The difference the in O/E ratio among the groups was statistically significant ( P < .001). The average episode target price for cohorts A, B, and C was $66,149, $63,483, and $63,937, respectively. Despite the high cost of pomalidomide and lenalidomide, there was no significant difference in the average episode target prices of the cohorts. CONCLUSION: The O/E ratio and target prices of the cohorts demonstrate a lack of adequate adjustment to the OCM target price for episodes in which pomalidomide and lenalidomide were used to treat patients with MM.
Corticosterone, Adrenal, and the Pituitary-Gonadal Axis in Neonatal Rats: Effect of Maternal Separation and Hypoxia
Authors: Gehrand Ashley L , Phillips Jonathan , Malott Kevin , Raff Hershel 
Published: May 2020

Abstract
Hypoxia, a common stressor in prematurity, leads to sexually dimorphic, short- and long-term effects on the adult hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We hypothesized that these effects are due to stress-induced increases in testosterone during early postnatal life. We evaluated this phenomenon by systematically assessing the short-term effects of normoxic or hypoxic separation on male and female pups at birth, postnatal hours (H) 2, 4, and 8, and postnatal days (PD) 2 to 7. Our findings were (a) hypoxic separation led to a large increase in plasma corticosterone from 4H-PD4, (b) neither normoxic nor hypoxic separation affected critical adrenal steroidogenic pathway genes; however, a significant decrease in baseline Cyp11a1, Mc2r, Mrap, and Star adrenal expression during the first week of neonatal life confirmed the start of the adrenal stress hyporesponsive period, (c) a luteinizing hormone/follicle-stimulating hormone–independent increase in plasma testosterone occurred in normoxic and hypoxic separated male pups at birth, (d) testicular Cyp11a1, Lhcgr, and Star expression was high at birth and decreased thereafter suggesting a hyporesponsive period in the testes, and (e) elevated estrogen in the early neonatal period occurred independently of gonadotropin stimulation. We conclude that a large corticosterone response to hypoxia during the first 5 days of life occurs as an adaptation to neonatal stress, that the testosterone surge during the first hours after birth occurs independently of gonadotropins but is associated with upregulation of the steroidogenic pathway genes in the testes, and that high postnatal estrogen production also occurs independently of gonadotropins.
Postcritical Howells: American Realism and Liberal Guilt
Authors: Wonham Henry B. 
Published: May 2020

Abstract
This essay explores the concept of liberal guilt in William Dean Howells’s fiction, focusing especially on his 1888 novel Annie Kilburn. Genealogies of liberal guilt rarely mention Howells, and yet no American writer has more painstakingly elaborated the embarrassing predicament of middle-class complicity in social arrangements that entail the widespread suffering of others. I provide a summary of theoretical positions on liberal guilt as a structure of feeling that entails what Richard Rorty calls “doubt about [one’s] own sensitivity to the pain and humiliation of others, doubt that present institutional arrangements are adequate to deal with this pain and humiliation.” Howells felt these doubts profoundly, and yet he understood liberal guilt as a productive emotional and intellectual predicament. Put simply, Howells viewed liberal guilt, like realism itself, as an attitude of resigned acceptance of persistent social injustices but an attitude capable of animating, rather than dissipating, liberal commitments and public agendas.
Readerly Revisions: Letters to the Editor in the Crisis
Authors: Quinn William Reed 
Published: May 2020

Abstract
This essay examines how the editorial staff of the Crisis positioned readers as collaborators and literary activists. Looking at letters to the editor, I argue that readers helped reevaluate representations of blackness in American literary taste. These letters bridge past, present, and future issues of the magazine and, therefore, evoke a temporality that exceeds the critical capacities of close reading. To address how editors, readers, and authors responded to each other over time, I combine close reading with topic modeling, a method of computational text analysis. This mixed methodology shows how readers participated in the magazine’s cultural campaign against racism by calling for socially progressive depictions of blackness.