bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a Hematopoietic Cell Transplant-Composite Risk (HCT-CR) Model for Post-Transplant Survival Prediction in Patients with Hematologic Malignancies
Authors: Ciurea Stefan O. , Kongtim Piyanuch , Hasan Omar , Ramos Perez Jorge M. , Torres Janet , Rondon Gabriela , Champlin Richard E. 
Published: February 2020

Abstract

Purpose:
Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant–comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT.

Experimental Design:
Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested.

Results:
The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P &lt; 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P &lt; 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the “treat all” or “treat none” strategy and the use of the DRI-R and HCT-CI/Age model separately.

Conclusions:
The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.
27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6–JAK–STAT3 Signaling in Prostate Cancer Cells
Authors: Dambal Shweta , Alfaqih Mahmoud , Sanders Sergio , Maravilla Erick , Ramirez-Torres Adela , Galvan Gloria C. , Reis-Sobreiro Mariana , Rotinen Mirja , Driver Lucy M. , Behrove Matthew S. , Talisman Tijana Jovanovic , Yoon Junhee , You Sungyong , Turkson James , Chi Jen-Tsan , Freeman Michael R. , Macias Everardo , Freedland Stephen J. 
Published: February 2020

Abstract

We recently reported that restoring the CYP27A1–27hydroxycholesterol axis had antitumor properties. Thus, we sought to determine the mechanism by which 27HC exerts its anti–prostate cancer effects. As cholesterol is a major component of membrane microdomains known as lipid rafts, which localize receptors and facilitate cellular signaling, we hypothesized 27HC would impair lipid rafts, using the IL6–JAK–STAT3 axis as a model given its prominent role in prostate cancer. As revealed by single molecule imaging of DU145 prostate cancer cells, 27HC treatment significantly reduced detected cholesterol density on the plasma membranes. Further, 27HC treatment of constitutively active STAT3 DU145 prostate cancer cells reduced STAT3 activation and slowed tumor growth in vitro and in vivo. 27HC also blocked IL6-mediated STAT3 phosphorylation in nonconstitutively active STAT3 cells. Mechanistically, 27HC reduced STAT3 homodimerization, nuclear translocation, and decreased STAT3 DNA occupancy at target gene promoters. Combined treatment with 27HC and STAT3 targeting molecules had additive and synergistic effects on proliferation and migration, respectively. Hallmark IL6–JAK–STAT gene signatures positively correlated with CYP27A1 gene expression in a large set of human metastatic castrate-resistant prostate cancers and in an aggressive prostate cancer subtype. This suggests STAT3 activation may be a resistance mechanism for aggressive prostate cancers that retain CYP27A1 expression. In summary, our study establishes a key mechanism by which 27HC inhibits prostate cancer by disrupting lipid rafts and blocking STAT3 activation.

Implications:
Collectively, these data show that modulation of intracellular cholesterol by 27HC can inhibit IL6–JAK–STAT signaling and may synergize with STAT3-targeted compounds.
Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells
Authors: Cortese Nina , Capretti Giovanni , Barbagallo Marialuisa , Rigamonti Alessandra , Takis Panteleimon G. , Castino Giovanni F. , Vignali Debora , Maggi Giulia , Gavazzi Francesca , Ridolfi Cristina , Nappo Gennaro , Donisi Greta , Erreni Marco , Avigni Roberta , Rahal Daoud , Spaggiari Paola , Roncalli Massimo , Cappello Paola , Novelli Francesco , Monti Paolo , Zerbi Alessandro , Allavena Paola , Mantovani Alberto , Marchesi Federica 
Published: February 2020

Abstract

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor–infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.
Immunosuppressive Mediators Impair Proinflammatory Innate Lymphoid Cell Function in Human Malignant Melanoma
Authors: Ercolano Giuseppe , Garcia-Garijo Andrea , Salomé Bérengère , Gomez-Cadena Alejandra , Vanoni Giulia , Mastelic-Gavillet Beatris , Ianaro Angela , Speiser Daniel E. , Romero Pedro , Trabanelli Sara , Jandus Camilla 
Published: February 2020

AbstractInnate lymphoid cells (ILC) are a family of immune cells that are emerging as potent orchestrators of immune responses. In cancer, ILCs display both pro- and antitumorigenic functions depending on the nature of the tumor and the involved ILC subset. Little is known about the ILC–tumor cross-talk in human melanoma. Here, we showed that ILC1s were enriched but functionally impaired in cytokine secretion in both peripheral blood mononuclear cells and tumor-infiltrated lymph nodes of melanoma patients. These findings were confirmed in vivo in murine cutaneous melanoma. Multiple immunosuppressive mechanisms are described in the melanoma microenvironment. Among others, adenosine and kynurenines were shown to suppress antitumor immune responses. By exposing ILCs to adenosine and kynurenines, we observed a similar shift toward the ILC1 subset distribution and impairment in proinflammatory cytokine production to that of patient samples studied ex vivo. Thus, we hypothesized that the immunosuppressive microenvironment of malignant melanoma might shape ILC subpopulations. Hence, we provide a rationale for the use of drugs targeting adenosine and kynurenine pathways in melanoma patients.
γδ T-cell Receptors Derived from Breast Cancer–Infiltrating T Lymphocytes Mediate Antitumor Reactivity
Authors: Janssen Anke , Villacorta Hidalgo Jose , Beringer Dennis X. , van Dooremalen Sanne , Fernando Febilla , van Diest Eline , Terrizi Antonela R. , Bronsert Peter , Kock Sylvia , Schmitt-Gräff Annette , Werner Martin , Heise Kerstin , Follo Marie , Straetemans Trudy , Sebestyen Zsolt , Chudakov Dmitry M. , Kasatskaya Sofya A. , Frenkel Felix E. , Ravens Sarina , Spierings Eric , Prinz Immo , Küppers Ralf , Malkovsky Miroslav , Fisch Paul , Kuball Jürgen 
Published: February 2020

Abstract

γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCR) from tumor-infiltrating γδ T lymphocytes (γδ TIL) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCRγ or TCRδ chains of γδ TILs and observed a higher proportion of Vδ2+ T cells compared with other tumor types. By reconstructing matched Vδ2– TCRγ and TCRδ pairs derived from single-cell sequencing, our data suggest that γδ TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCRγ and TCRδ chains and was independent of additional costimulation through other innate immune receptors. We conclude that γδ TILs can mediate tumor reactivity through their individual γδ TCR pairs and that engineered T cells expressing TCRγ and δ chains derived from γδ TILs display potent antitumor reactivity against different cancer cell types and, thus, may be a valuable tool for engineering immune cells for adoptive cell therapies.
Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments
Authors: Xie Yushu Joy , Dougan Michael , Ingram Jessica R. , Pishesha Novalia , Fang Tao , Momin Noor , Ploegh Hidde L. 
Published: February 2020

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of cancers of hematopoietic origin. In the immunosuppressive solid tumor environment, CAR T cells encounter obstacles that compromise their efficacy. We developed a strategy to address these barriers by having CAR T cells secrete single-domain antibody fragments [variable heavy domain of heavy chain antibodies (VHH) or nanobodies] that can modify the intratumoral immune landscape and thus support CAR T-cell function in immunocompetent animals. VHHs are small in size and able to avoid domain swapping when multiple nanobodies are expressed simultaneously—features that can endow CAR T cells with desirable properties. The secretion of an anti-CD47 VHH by CAR T cells improves engagement of the innate immune system, enables epitope spreading, and can enhance the antitumor response. CAR T cells that secrete anti–PD-L1 or anti–CTLA-4 nanobodies show improved persistence and demonstrate the versatility of this approach. Furthermore, local delivery of secreted anti-CD47 VHH-Fc fusions by CAR T cells at the tumor site limits their systemic toxicity. CAR T cells can be further engineered to simultaneously secrete multiple modalities, allowing for even greater tailoring of the antitumor immune response.
Jung, Neumann and Gebser
Authors: Mitchell Robert L. 
Published: February 2020

Abstract
In recent decades, indeterminate states of cultural identity in both individuals and nations have resulted from cross-cultural migrations and the resistance of host nations to critically re-evaluate traditional cultural complexes and welcome new influences. Jung’s theory of individuation, Neumann’s centroversion and Gebser’s integrality provide a new foundation in consciousness for re-evaluating both individual and national cultural identities. In terms of the development and education of children, the two common threads in these three theories are individuation and recapitulation theory. Individuation, re-imagined by Neumann as centroversion, parallels Gebser’s concept of integrality and provides a mediating foundation for comparing individuation and integrality. Both concepts are compared in terms of the first phase of the individuation process, characterized by the development and education of the child. The objective is to achieve an individuated-integral, spiritualized personality in the first half of life so that the spiritually mature adult can contribute to an evolved human consciousness and global cultural identity in the second half of life.
Enlarging the Severe Hail Database in Finland by Using a Radar-Based Hail Detection Algorithm and Email Surveys to Limit Underreporting and Population Biases
Authors: Tuovinen Jari-Petteri , Hohti Harri , Schultz David M. 
Published: February 2020

Abstract
Collecting hail reports to build a climatology is challenging in a sparsely populated country such as Finland. To expand an existing database, a new approach involving daily verification of a radar- and numerical weather prediction–based hail detection algorithm was trialed during late May–August for the 10-yr period, 2008–17. If the algorithm suggested a high likelihood of hail from each identified convective cell in specified locations, then an email survey was sent to people and businesses in these locations. Telephone calls were also used occasionally. Starting from 2010, the experiment was expanded to include trained storm spotters performing the surveys (project called TATSI). All the received hail reports were documented (severe or ≥2 cm, and nonsevere, excluding graupel), giving a more complete depiction of hail occurrence in Finland. In combination with reports from the general public, news, and social media, our hail survey resulted in a 292% increase in recorded severe hail days and a 414% increase in observed severe hail cases compared to a climatological study (1930–2006). More than 2200 email surveys were sent, and responses to these surveys accounted for 53% of Finland’s severe hail cases during 2008–17. Most of the 2200 emails were sent into rural locations with low population density. These additional hail reports allowed problems with the initial radar-based hail detection algorithm to be identified, leading to the introduction of a new hail index in 2009 with improved detection and nowcasting of severe hail. This study shows a way to collect hail reports in a sparsely populated country to mitigate underreporting and population biases.
Team Combat Identification: Effects of Gender, Spatial Visualization, and Disagreement
Authors: Baker Anthony L. , Keebler Joseph R. , Anania Emily C. , Schuster David , Plummer John P. 
Published: February 2020

Objective The combat identification (CID) abilities of same-gender and mixed-gender dyads were experimentally assessed, along with measures of spatial skills and team communication. Background CID is a high-stakes decision-making task involving discrimination between friendly and enemy forces. Literature on CID is primarily focused on the individual, but the extensive use of teams in the military means that more team-based research is needed in this area. Method After a set of training sessions, 39 dyads were tasked with identifying 10 armored vehicles in a series of pictures and videos. Team communication was recorded, transcribed, and coded for instances of disagreements. Results Analyses indicated that males scored higher on a spatial visualization measure than did females. M-M teams performed significantly better than M-F teams on the CID task, but when spatial ability and team disagreements were added as predictors, the effect of team gender composition became nonsignificant. Spatial ability and team disagreement were significant predictors of team CID performance. Conclusion Results suggest that spatial skills and team disagreement behaviors are more important for team CID performance than a team’s gender composition. To our knowledge, this is the first lab study of team CID. Application This research highlights the importance of understanding both individual differences (e.g., spatial skills) and team processes (e.g., communication) within CID training environments in the military context.
Cardiovascular Risk Factors and Benign Paroxysmal Positional Vertigo in Community Otolaryngology–Head and Neck Surgery
Authors: Singh Jeffrey M. , Corser William D. , Monsell Edwin M. 
Published: February 2020

ObjectiveCardiovascular risk factors have been associated with benign paroxysmal positional vertigo (BPPV), possibly causing degeneration of the utricular epithelium and subepithelium, but supportive evidence is mixed. This is the first study to examine the association between cardiovascular risk factors and BPPV as they present in the community practice of comprehensive otolaryngology–head and neck surgery.Study DesignCross‐sectional case‐matched case‐control series.SettingA community practice of otolaryngology–head and neck surgery with 3 clinical offices and a socioeconomically diverse patient population.Subjects and MethodsClinical data were collected retrospectively from the electronic health records of a continuous 4‐year series of 628 patients with BPPV and age‐ and sex‐matched controls.ResultsThere were no statistically significant associations found between BPPV and diabetes, hypertension, dyslipidemia, or body mass index in the study population in pairwise comparisons or multivariable modeling.ConclusionThis study suggests that BPPV as encountered in a community ear, nose, and throat practice is not generally associated with cardiovascular risk factors. The possibility that these or other cardiovascular risk factors may be causative in some cases cannot be excluded, though most cases of BPPV appear to be caused primarily by shedding of otoconia from the utricle that is idiopathic or at least in part by unconfirmed noncardiovascular factors.
Components of palliative care interventions addressing the needs of people with dementia living in long-term care: A systematic review
Authors: Kochovska Slavica , Garcia Maja V , Bunn Frances , Goodman Claire , Luckett Tim , Parker Deborah , Phillips Jane L , Sampson Elizabeth L , van der Steen Jenny T , Agar Meera R 
Published: February 2020

Background: People with dementia requiring palliative care have multiple needs, which are amplified in long-term care settings. The European Association for Palliative Care White Paper offers recommendations for optimal palliative care in dementia integral for this population, providing useful guidance to inform interventions addressing their specific needs. Aim: The aim of this study is to describe the components of palliative care interventions for people with dementia in long-term care focusing on shared decision-making and examine their alignment to the European Association for Palliative Care domains of care. Design: Systematic review with narrative synthesis (PROSPERO ID: CRD42018095649). Data sources: Four databases (MEDLINE, CINAHL, PsycINFO and CENTRAL) were searched (earliest records – July 2019) for peer-reviewed articles and protocols in English, reporting on palliative care interventions for people with dementia in long-term care, addressing European Association for Palliative Care Domains 2 (person-centred) or 3 (setting care goals) and ⩾1 other domain. Results: Fifty-one papers were included, reporting on 32 studies. For each domain (1–10), there were interventions found aiming to address its goal, although no single intervention addressed all domains. Domain 7 (symptom management; n = 19), 6 (avoiding overly aggressive treatment; n = 18) and 10 (education; n = 17) were the most commonly addressed; Domain 5 (prognostication; n = 7) and 4 (continuity of care; n = 2) were the least addressed. Conclusion: Almost all domains were addressed across all interventions currently offered for this population to various degrees, but not within a singular intervention. Future research optimally needs to be theory driven when developing dementia-specific interventions at the end of life, with the European Association for Palliative Care domains serving as a foundation to inform the best care for this population.
Impact of volume calculation formulae on volume estimation accuracy of different shaped objects: an in vitro ultrasound and CT study
Authors: Kodikara Iroshani , Gamage Dhanusha , Abeysekara Iroshini , Ilayperuma Isurani 
Published: February 2020

Background In image-assisted volume estimation, the volume of the object is calculated with a formula, using linear measurements of the objects. Since the volume estimation accuracy is thought to be influenced by the shape of the object, the volume estimation error would be related to the calculation formula used. Purpose To evaluate the volume estimation accuracy of selected volume calculation formulae, for different shaped objects. Material and Methods Globular (n = 5), elongated (n = 5), and near-spherical shaped plastic objects (n = 5), filled with water were subjected to ultrasound (US) and computed tomography (CT) in February 2018, to obtain the length, width, depth, and estimated volumes (EV). The volume was calculated manually using prolate, ellipsoid, and Lambert formulae. The actual volume (AV), EV, and calculated volumes were compared. Results The AV was in the range of 10–445 mL. The reliability of measurements was high as assessed by the intra-class variability (Cronbach’s alpha = 0.992). The EV has shown a high correlation to AV (US: ρ = 0.914, P < 0.001; CT: ρ = 0.943, P < 0.001; ellipsoid: ρ = 0.876, P < 0.001; prolate: ρ = 0.891, P < 0.001; Lambert: ρ = 0.876, P < 0.001). Regardless of the shape, the highest and lowest estimation accuracies were reported for prolate (bias = −0.7) and Lambert formulae (bias = +23.3), respectively. By any method, the globular objects were estimated with the highest accuracy: (US [bias = −0.31]; CT [bias = −0.14]; ellipsoid [bias = −1.5]; prolate [bias = −0.7]; Lambert [bias = 32.9]); and elongated objects were estimated with the lowest accuracy: (US [bias = −17.5]; CT [bias = −32.6]; ellipsoid [bias = −18.4]; prolate [bias = −0.3]; Lambert [bias = 11.4]). Conclusion The shape of the object and the calculation formula used has an impact on the volume estimation accuracy.