bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma
Authors: Tran Linda , Allen Clint T. , Xiao Roy , Moore Ellen , Davis Ruth , Park So-Jin , Spielbauer Katie , Van Waes Carter , Schmitt Nicole C. 
Published: November 2017

AbstractHead and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti–PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing in vitro, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti–PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti–PD-L1/PD-1 therapy. Cancer Immunol Res; 5(12); 1141–51. ©2017 AACR.
Intratumoral CD8+ T-cell Apoptosis Is a Major Component of T-cell Dysfunction and Impedes Antitumor Immunity
Authors: Horton Brendan L. , Williams Jason B. , Cabanov Alexandra , Spranger Stefani , Gajewski Thomas F. 
Published: November 2017

AbstractSubsets of human tumors are infiltrated with tumor antigen–specific CD8+ T cells [tumor-infiltrating lymphocytes (TILs)] despite tumor progression. These TILs are thought to be inactivated by the immunosuppressive tumor microenvironment, through the engagement of inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific CD8+ TILs are not functionally inert but are undergoing activation in situ. Here, we show that antigen-specific CD8+ TILs are actively proliferating, yet also undergo high rates of apoptosis, leading to a vicious cycle of activation and death that limits immune efficacy. Preventing CD8+ TIL apoptosis by Bcl-xL overexpression enabled accumulation and improved tumor control. Effective combination immunotherapy with an agonist 4-1BB mAb plus either CTLA-4 or PD-L1 neutralization led to a marked accumulation of specific CD8+ TILs through decreased apoptosis rather than increased T-cell entry or proliferation. Our data suggest that antigen-driven apoptosis of CD8+ TILs is a barrier to effective spontaneous antitumor immunity and should be considered as a critical factor in the development of cancer immunotherapies. Cancer Immunol Res; 6(1); 14–24. ©2017 AACR.
Combination of CD40 Agonism and CSF-1R Blockade Reconditions Tumor-Associated Macrophages and Drives Potent Antitumor Immunity
Authors: Wiehagen Karla R. , Girgis Natasha M. , Yamada Douglas H. , Smith Andressa A. , Chan Szeman Ruby , Grewal Iqbal S. , Quigley Michael , Verona Raluca I. 
Published: November 2017

AbstractEfficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared with monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu. Anti-CD40/anti–CSF-1R–treated tumors contain decreased tumor-associated macrophages and Foxp3+ regulatory T cells. This combination approach increases maturation and differentiation of proinflammatory macrophages and dendritic cells and also drives potent priming of effector T cells in draining lymph nodes. As a result, tumor-infiltrating effector T cells exhibit improved responses to tumor antigen rechallenge. These studies show that combining therapeutic approaches may simultaneously remove inhibitory immune populations and sustain endogenous antitumor immune responses to successfully impair cancer progression. Cancer Immunol Res; 5(12); 1109–21. ©2017 AACR.
Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease
Authors: Walker Keenan A. , Power Melinda C. , Hoogeveen Ron C. , Folsom Aaron R. , Ballantyne Christie M. , Knopman David S. , Windham B. Gwen , Selvin Elizabeth , Jack Clifford R. , Gottesman Rebecca F. 
Published: November 2017

Background and Purpose—
It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.

Methods—
Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)—a nonspecific marker of inflammation—and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.

Results—

We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (−0.09 SD; 95% confidence interval, −0.15 to −0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03–0.15) in deep WM and lower fractional anisotropy (−0.07 SD; 95% confidence interval, −0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (
P
interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among
APOE
ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01–0.26;
P
interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.

Conclusions—
Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.
Hêlēl ben-Šaḥar and the Chthonic Sun: A New Suggestion for the Mythological Background of Isa 14:12-15
Authors: Quick Laura 
Published: November 2017

Abstract
This paper will explore the oft investigated problem of the mythological referents which inform Isa 14:12-15. Crucial to this will be a reinterpretation of the mysterious hêlēl ben-šaḥar of v. 12, almost universally understood by commentators and translators alike to refer to the ‘Day Star, son of the Dawn’, and thus taken to refer to the ‘morning star’, the planet Venus. Much of the scholarship has approached the ancient Near Eastern material with this meaning in mind, yet no myth hitherto proposed has provided a complete analogy to Isa 14:12-15. Thus I will begin by exploring the problems with these previous analogies, before reconsidering the meaning of hêlēl ben-šaḥar. Understanding the phrase to metonymically remind of the sun itself, the Ugaritic conception of the chthonic sun will be proposed to provide a much more satisfying parallel with our Isaiah passage.
The Negation of Abnegation
Authors: Landa Ishay 
Published: November 2017

AbstractThis essay revisits Karl Marx’s understanding of consumption, in an effort to rescue it from the overshadowing legacy of critical theory which has construed Marx as inveighing against false needs. It is argued that Marx regarded the expansion of needs entailed by capitalism in a generally favourable way, but saw capitalism as a system yoking use-value to the imperatives of profit accumulation, hence limiting and subjugating the consumption of the masses. While Marx’s position was radically different from conventional anti-consumerism it is equally incompatible with complacent affirmations of ‘the consumer society’ in that Marx at all times aimed at a revolutionary change which will transform consumption both quantitatively and qualitatively. Marx’s views are first discussed as expressed in the perennially-cited text, the 1844Economic and Philosophical Manuscripts. The second part moves on to examine the further evolution of Marx’s ideas as found in later texts, particularly theGrundrisse.
Alexander Tall Tower! A Study of the Boundary Layer on the Ross Ice Shelf, Antarctica
Authors: Mateling Marian E. , Lazzara Matthew A. , Keller Linda M. , Weidner George A. , Cassano John J. 
Published: November 2017

AbstractBecause of the harsh weather conditions on the Antarctic continent, year-round observations of the low-level boundary layer must be obtained via automated data acquisition systems. Alexander Tall Tower! is an automatic weather station on the Ross Ice Shelf in Antarctica and has been operational since February 2011. At 30 m tall, this station has six levels of instruments to collect environmental data, including temperature, wind speed and direction, relative humidity, and pressure. Data are collected at 30-, 15-, 7.5-, 4-, 2-, and 1-m levels above the snow surface. This study identifies short-term trends and provides an improved description of the lowest portion of the boundary layer over this portion of the Ross Ice Shelf for the February 2011–January 2014 period. Observations indicate two separate initiations of the winter season occur annually, caused by synoptic-scale anomalies. Sensible and latent heat flux estimates are computed using Monin–Obukhov similarity theory and vertical profiles of potential air temperature and wind speed. Over the three years, the monthly mean sensible heat flux ranges between 1 and 39 W m−2 (toward the surface) and the monthly mean latent heat flux ranges between −8 and 0 W m−2. Net heat fluxes directed toward the surface occur most of the year, indicating an atmospheric sink of energy.
Phenotypic and treatment outcome data on SUNCT and SUNA, including a randomised placebo-controlled trial
Authors: Weng Hsing-Yu , Cohen Anna S , Schankin Christoph , Goadsby Peter J 
Published: November 2017

Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are two rare headache syndromes classified broadly as Trigeminal Autonomic Cephalalgias (TACs). Methods Here, 65 SUNCT (37 males) and 37 SUNA (18 males) patients were studied to describe their clinical manifestations and responses to treatment. Results Pain was almost always unilateral and side-locked. There were three types of attack: Single stabs, stab groups, and a saw-tooth pattern, with some patients experiencing a mixture of two types. As to cranial autonomic symptoms, SUNA patients mainly had lacrimation (41%) and ptosis (40%). Most cases of the two syndromes had attack triggers, and the most common triggers were touching, chewing, or eating for SUNCT, and chewing/eating and touching for SUNA. More than half of each group had a personal or family history of migraine that resulted in more likely photophobia, phonophobia and persistent pain between attacks. For short-term prevention, both syndromes were highly responsive to intravenous lidocaine by infusion; for long-term prevention, lamotrigine and topiramate were effective for SUNCT, and lamotrigine and gabapentin were efficacious in preventing SUNA attacks. A randomized placebo-controlled cross-over trial of topiramate in SUNCT using an N-of-1 design demonstrated it to be an effective treatment in line with clinical experience. Conclusions SUNCT and SUNA are rare primary headache disorders that are distinct and very often tractable to medical therapy.
Efficacy of a Prevention Program for Medial Elbow Injuries in Youth Baseball Players
Authors: Sakata Jun , Nakamura Emi , Suzuki Tatsuhiro , Suzukawa Makoto , Akaike Atsushi , Shimizu Kuniaki , Hirose Norikazu 
Published: November 2017

Background: Youth baseball players are at high risk for elbow injuries, which can lead to future functional disability. Purpose: To evaluate the effectiveness of a prevention program to lower the risk of medial elbow injury in these athletes. Study Design: Cohort study; Level of evidence, 2. Methods: Youth baseball players, 8 to 11 years old, without a history of elbow and shoulder pain, were allocated to either the intervention (n = 136) or control (n = 169) group. The intervention consisted of 9 strengthening and 9 stretching exercises, performed during warm-up or at home, with high compliance defined as completion of the program 1 or more times per week. The following outcome variables were measured: clinical assessment of the elbow and shoulder joint, ultrasonography assessment of the elbow, and assessment of physical function (passive range of motion of the elbow, shoulder, and hip; strength of the shoulder and scapular muscles; and measurement of the thoracic kyphosis angle). The clinical and ultrasonography assessments were measured at baseline and at 3-month intervals over the 1-year follow-up. Physical function outcomes were measured at baseline and at the endpoint of the follow-up. The primary endpoint of effectiveness was the incidence of medial elbow injury. Secondary endpoints were absolute measures of physical function and change in these measures over the 1-year follow-up. Results: The incidence rate of medial elbow injury was significantly lower in the intervention group (0.8/1000 athlete-exposures) than the control group (1.7/1000 athlete-exposures) (hazard ratio, 50.8%; 95% CI, 0.292-0.882; P = .016). The program improved total range of shoulder rotation (dominant side), hip internal rotation (nondominant side), shoulder internal rotation deficit (bilaterally), lower trapezius muscle strength (dominant side), and the thoracic kyphosis angle. Improvements in the following variables of physical function were predictive of a lower rate of medial elbow injury: increased total shoulder total rotation (odds ratio [OR], 0.973; 95% CI, 0.950-0.997), increased hip internal rotation of the nondominant side (OR, 0.962; 95% CI, 0.936-0.989), and decreased thoracic kyphosis angle (OR, 1.058; 95% CI, 1.015-1.103). Conclusion: A prevention program aiming to improve physical function can prevent medial elbow injury in youth baseball players.
A Qualitative Analysis of Information Sharing in Hospice Interdisciplinary Group Meetings
Authors: Washington Karla T. , Demiris George , Parker Oliver Debra , Swarz Jeffrey A. , Lewis Alexandria M. , Backonja Uba 
Published: November 2017

Background: In the United States, hospice agencies are required to convene interdisciplinary group (IDG) meetings no less frequently than every 15 days to review patients’ care plans. Challenges associated with information sharing during these meetings can impede efficiency and frustrate attendees. Objectives: We sought to examine information sharing in the context of hospice IDG meetings as a first step toward developing an informatics tool to support interdisciplinary collaboration in this setting. Specifically, we wanted to better understand the purpose of information sharing in IDG meetings and determine the type(s) of information required to fulfill that purpose. Methods, Setting, and Participants: In this qualitative descriptive study, we analyzed video recordings of care plan discussions (n = 57) in hospice IDG meetings and individual interviews of hospice providers (n = 24). Results: Data indicated that sharing physical, psychosocial, and spiritual information is intended to optimize hospice teams’ ability to deliver whole-person care that is aligned with patient and family goals and that satisfies regulatory requirements. Conclusion: Information sharing is a key function of hospice teams in IDG meetings. Informatics tools may optimize IDG meeting efficiency by succinctly presenting well-organized and required information that is relevant to all team members. Such tools should highlight patient and family goals and ensure that teams are able to satisfy regulatory requirements.
Endovascular Treatment of Aortic Arch Lesions Using Scalloped Endografts
Authors: Fernández-Alonso Leopoldo , Fernández Alonso Sebastián , Martínez Aguilar Esther , Santamarta Fariña Estéfana , Alegret Solé Jordi , López San Martín Marina , Atienza Pascual Margarita , Fernández-Domper Leopoldo , Centeno Vallepuga Roberto 
Published: November 2017

Objective: To present our early and midterm results using thoracic endovascular aortic repair (TEVAR) with a custom-made proximal scalloped stent graft to accommodate left common carotid artery (LCCA) and innominate artery (IA) in treating aortic lesions involving the arch. Materials and Methods: Between February 2014 and April 2017, select patients presenting with aortic arch lesions and short proximal landing zone were treated by proximal scalloped Relay Plus stent grafts. Patient demographics, operative details, clinical outcomes, and complications were analyzed. Results: Six patients (50% male) with a median age of 71 years (range, 60-82) underwent scalloped TEVAR using thoracic custom-made Relay Plus stent graft to preserve flow in the proximal supra-aortic trunks. Target vessels for the scallop were LCCA in 5 cases and IA in 1 case. The technical success rate was 100%, and proximal seal was achieved in all cases with no type I endoleaks on completion angiography. The median follow-up period was 20 (7-32) months. No conversion to open surgical repair and no aortic rupture occurred. One patient had a distal type I endoleak on the 6-month computed tomography (CT) scan, and 1 patient had a proximal type I endoleak on the 12-month CT scan. There was no stroke, paraplegia, retrograde type A dissection, or other aortic-related complication. We routinely used temporary rapid right ventricular pacing to obtain a near-zero blood pressure level during the graft deployment. No complications were observed related to the use of rapid pacing. Conclusion: When anatomy allows, proximal scalloped stent graft to accommodate LCCA and IA is a viable therapeutic option in treating aortic lesions involving the arch with short proximal landing zones. In addition, these findings represent a strong argument for the use of temporary rapid pacing during graft deployment.
The doctor–patient relationship and patient resilience in chronic pain: A qualitative approach to patients’ perspectives
Authors: Náfrádi Lilla , Kostova Zlatina , Nakamoto Kent , Schulz Peter J 
Published: November 2017

Objectives To study patients’ perspectives about the role of the doctor–patient relationship in promoting the resilience process. Methods We conducted in-depth interviews with 20 chronic pain patients. Using open-ended questions, the interviews explored aspects of the doctor–patient relationship that impacted the patients’ perceptions of their resilience. Thematic analysis built on an inductive, adaptive approach to data coding was employed to organize a representation of key factors affecting resilience. Results The themes emerging from the interviews inform us about how the different aspects of the doctor–patient relationship can promote patient resilience in chronic pain. Three main themes emerged: the doctor providing psychological support, promoting patients’ health literacy related to chronic pain and its treatment, and empowering the patients to cooperate in finding the right treatment. This fosters patients’ direct outcomes (feeling validated, health literate, and empowered), which, in turn, lead to adaptive coping responses and day-to-day disease management. These direct outcomes are crucial for patients to maintain socially and personally meaningful activities and their functional (physical) capacity. Discussion A doctor–patient relationship following the precepts of the patient-centered care is a significant resource that can lead to increased patient resilience. Thus, future interventions promoting patient resilience might consider addressing the doctor–patient relationship.
Imaging of Folate Receptor Expressing Macrophages in the Rat Groove Model of Osteoarthritis: Using a New DOTA-Folate Conjugate
Authors: de Visser Huub M. , Korthagen Nicoline M. , Müller Cristina , Ramakers Ruud M. , Krijger Gerard C. , Lafeber Floris P. J. G. , Beekman Freek J. , Mastbergen Simon C. , Weinans Harrie 
Published: November 2017

Objective To evaluate the presence and localization of folate receptor expressing macrophages in the rat groove model of osteoarthritis and determine the suitability of a new folate conjugate with albumin-binding entity (cm09) for in vivo SPECT (single-photon emission computed tomography) analysis. Design In male Wistar rats, local cartilage damage was induced in addition to a standard ( n = 10) or high-fat diet ( n = 6). After 12 weeks, 111In labeled folate conjugates were administered, and SPECT/CT (computed tomography) imaging was performed after 24 hours. Subsequently, osteoarthritis severity and folate receptor expression were assessed using (immuno)-histological sections. Results In vivo SPECT/CT imaging of the new folate conjugate (cm09) was as useful as a folate conjugate without albumin-binding entity in the groove model of osteoarthritis with less renal accumulation. Induction of cartilage damage on a standard diet resulted in no effect on the amount of folate receptor expressing macrophages compared with the contralateral sham operated joints. In contrast, inducing cartilage damage in the high-fat diet group resulted in 28.4% increase of folate receptor expression as compared with the nondamaged control joints. Folate receptor expressing cells were predominantly present in the synovial lining and in subchondral bone as confirmed by immunohistochemistry. Conclusions Folate receptor expression, and thus macrophage activation, can clearly be demonstrated in vivo, in small animal models of osteoarthritis using the new 111In-folate conjugate with specific binding to the folate receptor. Increased macrophage activity only plays a role in the groove model of osteoarthritis when applied in a high-fat diet induced dysmetabolic condition, which is in line with the higher inflammatory state of that specific model.