bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR18: A novel immunomodulatory strategy of targeting glyco-immune checkpoints using EAGLE technology to treat cancer
Authors: Peng Li , Petrone Adam , Cao Lizhi , Broderick James 
Published: June 2021

Abstract
Cancer therapy has been revolutionized by inhibiting immune checkpoints to harness the power of the immune system in fighting cancer. However, the majority of patients are resistant to the current immuno-oncology drugs. There is a strong need to identify novel mechanisms of immune evasion in cancer and explore novel therapeutic modalities. Recently, glyco-immune checkpoints have been identified as an important modulator in cancer immune escape. Upon ligation of cancer-specific sialylated glycans, glyco-immune checkpoints suppress multiple facets of cancer immunity, including cancer antigen release, cancer antigen presentation, and priming and activation anticancer T-cell immunity. However, due to the complexity and heterogeneity of cancer sialylated glycans and the profound species differences of the glyco-immune checkpoints between human and mouse, this immunomodulatory pathway remains unexplored for therapeutic interventions. Here we described a novel multifunctional antibody-like therapeutic modality, named EAGLE (Enzyme-Antibody Glyco-Ligand Editing), to target this glyco-immune checkpoint axis. EAGLE overcomes the complexity of cancer glycans and specifically cleaves the immunosuppression-mediating key sugar moieties, the terminal sialic acids of various sialylated glycans on tumor cells. We hypothesized that EAGLE could block the immunosuppressive glyco-immune checkpoints in the tumor microenvironment and potentiate innate and adaptive immune responses to treat cancer. Indeed, systematic delivery of an EAGLE molecule decreased the levels of immunosuppressive sialic acids on tumor cells, and increased T-cell infiltration and activation in syngeneic tumor models. EAGLE treatment led to 50% complete regressions of established tumors as a monotherapy, and 100% cures in combination with anti-PD1 mAb. Furthermore, cured mice from EAGLE treatment completely rejected the rechallenge of tumor cells, suggesting that EAGLE induced antitumor immunologic memory. In summary, we demonstrated that this novel therapeutic modality, EAGLE, can release glyco-immune checkpoint-mediated immunosuppression in the tumor microenvironment and potentiate innate and adaptive antitumor immunity, which offers a novel and promising immunomodulatory strategy to treat cancer.
This abstract is also being presented as Poster A91.
Citation Format: Li Peng, Adam Petrone, Lizhi Cao, James Broderick. A novel immunomodulatory strategy of targeting glyco-immune checkpoints using EAGLE technology to treat cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr PR18.
Abstract PR21: IL-35+ B cells establish immunosuppressive network in pancreatic ductal adenocarcinoma
Authors: Mirlekar Bhalchandra , Pylayeva-Gupta Yuliya 
Published: June 2021

Abstract
Despite advances in our understanding of the mutational landscape in pancreatic ductal adenocarcinoma (PDAC), this devastating disease is now the third-leading cause of U.S. cancer-related deaths. While recent successes of cancer immunotherapy have generated considerable excitement, this form of treatment has been largely ineffective in patients with pancreatic cancer. A major barrier for immunotherapeutic approaches is marked immunosuppression within the PDAC milieu. We have previously identified a novel role for IL-35-producing B cells in the pathogenesis of pancreatic cancer. However, little is known about the mechanisms behind IL-35 activity in cancer. Here, we set out to elucidate molecular and cellular mechanisms by which IL-35 facilitates the emergence of pancreatic cancer. Our results demonstrate that IL-35, but not IL-10, potentiates PDAC growth. This correlates with induction of regulatory T cells and suppression of effector T-cell activity, suggesting that IL-35 controls endogenous antitumor immune responses in PDAC. Furthermore, while IL-35 is expressed by several immune cell types in PDAC, we show that its expression specifically in B cells is essential for suppression of antitumor T-cell responses. Importantly, while PDAC is typically resistant to anti-PD-1 immunotherapy, we demonstrate robust synergistic reduction in tumor growth when IL-35 deficiency is combined with anti-PD-1 treatment. Insights gleaned from these and further mechanistic studies of IL-35 in PDAC may be expeditiously translated into IL-35 targeted combination immunotherapy.
This abstract is also being presented as Poster A28.
Citation Format: Bhalchandra Mirlekar, Yuliya Pylayeva-Gupta. IL-35+ B cells establish immunosuppressive network in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr PR21.
New species of Asphondylia (Diptera, Cecidomyiidae, Asphondyliini) from Brazil
Authors: Maia Valéria Cid , Oliveira Lázaro Araújo 
Published: June 2021

Three new species of Asphondylia are described from Minas Gerais (Brazil): Asphondylia ingaiensis, A. rufae and A. zeyheriae. They induce galls on Moquiniastrum barrosoae (Asteraceae), Bauhinia rufa (Fabaceae), and Zeyheria montana (Bignoniaceae), respectively, all native to Brazil, being the last endemic. Illustrations of relevant morphological characters are provided. The new species are compared with congeneric Neotropical species. Types are deposited in the Museu Nacional, Entomological Collection.
Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial
Authors: Orlandi Marco , Masi Stefano , Bhowruth Devina , Leira Yago , Georgiopoulos Georgios , Yellon Derek , Hingorani Aroon , Chiesa Scott T. , Hausenloy Derek J. , Deanfield John , D’Aiuto Francesco 
Published: June 2021

Objective:
Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress.

Approach and Results:

Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group (
P
<0.05). RIPC attenuated the IPT-induced increase in IL-1β (interleukin-1β), E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and sTM (soluble thrombomodulin) levels between the baseline and day 1 (
P
for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group (
P
for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428–3.07],
P
=0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups.

Conclusions:
RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus.

Registration:

URL:
https://clinicaltrials.gov/ct2/show/NCT03072342
; Unique identifier: NCT03072342.
Obesity Prevalence and Risks Among Chinese Adults: Findings From the China PEACE Million Persons Project, 2014–2018
Authors: Mu Lin , Liu Jiamin , Zhou Guohai , Wu Chaoqun , Chen Bowang , Lu Yuan , Lu Jiapeng , Yan Xiaofang , Zhu Zhihong , Nasir Khurram , Spatz Erica S. , Krumholz Harlan M. , Zheng Xin 
Published: June 2021

Background:
China has seen a burgeoning epidemic of obesity in recent decades, but few studies reported nationally on obesity across socio-demographic subgroups. We sought to assess the prevalence and socio-demographic associations of obesity nationwide.

Methods:

We assessed the prevalence of overall obesity (body mass index ≥28 kg/m
2
) and abdominal obesity (waist circumference ≥85/90 cm for women/men) among 2.7 million community-dwelling adults aged 35 to 75 years in the China PEACE Million Persons Project from 2014 to 2018 and quantified the socio-demographic associations of obesity using multivariable mixed models.

Results:
Age-standardized rates of overall and abdominal obesity were 14.4% (95% CI, 14.3%–14.4%) and 32.7% (32.6%–32.8%) in women and 16.0% (15.9%–16.1%) and 36.6% (36.5%–36.8%) in men. Obesity varied considerably across socio-demographic subgroups. Older women were at higher risk for obesity (eg, adjusted relative risk [95% CI] of women aged 65–75 versus 35–44 years: 1.29 [1.27–1.31] for overall obesity, 1.76 [1.74–1.77] for abdominal obesity) while older men were not. Higher education was associated with lower risk in women (eg, adjusted relative risk [95% CI] of those with college or university education versus below primary school: 0.47 [0.46–0.48] for overall obesity, 0.61 [0.60–0.62] for abdominal obesity) but higher risk in men (1.07 [1.05–1.10], 1.17 [1.16–1.19]).

Conclusions:
In China, over 1 in 7 individuals meet criteria for overall obesity, and 1 in 3 for abdominal obesity. Wide variation exists across socio-demographic subgroups. The associations of age and education with obesity are significant and differ by sex. Understanding obesity in contemporary China has broad domestic policy implications and provides a valuable international reference.
Personalized, Electronic Health Record–Integrated Decision Aid for Stroke Prevention in Atrial Fibrillation: A Small Cluster Randomized Trial and Qualitative Analysis of Efficacy and Acceptability
Authors: Schott Stacey L. , Berkowitz Julia , Dodge Shayne E. , Petersen Curtis L. , Saunders Catherine H. , Sobti Navjot Kaur , Xu Keren , Coylewright Megan 
Published: June 2021

Background:
Shared decision-making in cardiology is increasingly recommended to improve patient-centeredness of care. Decision aids can improve patient knowledge and decisional quality but are infrequently used in real-world practice. This mixed-methods study tests the efficacy and acceptability of a decision aid integrated into the electronic health record (Integrated Decision Aid [IDeA]) and delivered by clinicians for patients with atrial fibrillation considering options to reduce stroke risk. We aimed to determine whether the IDeA improves patient knowledge, reduces decisional conflict, and is seen as acceptable by clinicians and patients.

Methods:
A small cluster randomized trial included 6 cardiovascular clinicians and 66 patients randomized either to the IDeA (HealthDecision) or usual care (clinician discretion) during a clinical encounter when stroke prevention treatment options were discussed. The primary outcome was patient knowledge of personalized stroke risk. Exploratory outcomes included decisional conflict, values concordance, trust, the presence of a shared decision-making process, and patient knowledge related to time spent using the IDeA. Additionally, we conducted semistructured interviews with clinicians and patients who used the IDeA were conducted to assess acceptability and predictions of future use.

Results:

The IDeA significantly increased patients’ knowledge of their stroke risk (odds ratio, 3.88 [95% CI, 1.39–10.78];
P
<0.01]). Patients had less uncertainty about their final decision (
P
=0.04). There were no significant differences in values concordance, trust in clinician or shared decision-making. Despite training, each clinician used the IDeA differently. Qualitative analysis revealed patients prefer using the IDeA earlier in their diagnosis. Clinicians were satisfied with the IDeA, yet varied in the contexts in which they planned to use it in the future.

Conclusions:
Using an Integrated Decision Aid, or IDeA, increases patient knowledge and lessens uncertainty for decision-making around stroke prevention in atrial fibrillation. Qualitative data provide insight into potential implementation strategies in real-world practice.
Muslim Family in Northern Mozambique: Sharīʿa, Matriliny and the Official Legislation in Paquitequete
Authors: Bonate Liazzat J. K. 
Published: June 2021

Abstract
Although Islam has a long history in coastal northern Mozambique, the question of how Muslims manage family life there is little understood. Based on the analysis of historical, ethnographic and legal records, and a case study of a bairro (Port., ward) called Paquitequete in the contemporary coastal city of Pemba in Cabo Delgado province, this article focuses on Muslim family and gender relations in northern Mozambique. It argues that Muslims of this region maintain concurrent legal identities as Muslims, matrilineal Africans and citizens of the modern state. While women benefitted from matriliny by accessing the land and support from their maternal side, upon widowhood and divorce they lost access to their husband’s or common assets because the husbands’ matriclan claimed them. The perseverance of matriliny made local Muslims seem to abide less by Islamic norms, but historically they have combined the Shāfiʿī madhhab (Islamic legal school) with matrilineal custom. In contemporary Pemba, family and gender relations are regulated not only by Sharīʿa or by African ‘traditions’, but by a blend of elements from these two alongside modern legislations. Moreover, it could be said that this arrangement is endorsed by a kind of popular consensus, which is particularly salient in the Community Courts.
The origin of the Indo-European simple thematic presents
Authors: Villanueva Svensson Miguel 
Published: June 2021

Abstract
It is now generally agreed upon that the Indo-European simple thematic presents are a post-Anatolian innovation. The origin of this formation, however, remains unclear. In this paper it is argued that the initial core of simple thematic presents was of denominative origin. They go back to an early Core PIE class of denominatives derived from e-grade thematic adjectives through conversion, e.g., adj. *léu̯k-o- ‘clear’ (Gk. λευκός ‘white’) → vb. *léu̯k-e/o- ‘be/make clear’ (Ved. rócate ‘shines’, TB lyuśtär ‘will light up’). This derivational pattern became obsolete already within Core PIE and a number of original denominatives like *léu̯k-e/o- were reinterpreted as primary present stems.
Association of Sleep With Risk of Alzheimer’s Disease Mortality: NIH-AARP Diet and Health Study
Authors: Schneider Aaron C. , Moon Chooza , Whitaker Kara , Zhang Dong , Carr Lucas J. , Bao Wei , Xiao Qian 
Published: June 2021

Objectives: Alzheimer’s disease (AD) and related dementias contribute to one in three senior deaths. Lifestyle factors, including sleep, may contribute to AD risk and mortality; however, current evidence on sleep and AD mortality is mixed. Methods: We used data from the NIH-AARP Diet and Health Study. Sleep duration and napping were self-reported and AD death were ascertained via linkage to the National Death Index. Results: Long sleep and napping were both associated with increased AD mortality. Specifically, 9+ hr of sleep was associated with 50% increase (hazard ratio = 1.50, 95% CI = [1.17, 1.92]) in AD mortality when compared 7 to 8 hr, while napping for 1+ hr was associated with 29% increase (1.29 [1.08, 1.55]) when compared with no napping. Results appeared to be stronger in men and remained after removing AD deaths within first 5 years after baseline. Discussion: Long sleep and napping may predict higher AD mortality in the older population.
Evaluation of a Multimodal Heparin Laboratory Monitoring Protocol in Adult Extracorporeal Membrane Oxygenation Patients
Authors: Northam Kalynn A. , Nguyen Bobbie , Chen Sheh-Li , Sredzienski Edward , Charles Anthony 
Published: June 2021

Background: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. Objective: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. Methods: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. Results: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). Conclusion: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration.
Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist for Abortive Migraine Treatment
Authors: Nedd Madell , Garland Scott , Falk Nathan , Wilk Ashley 
Published: June 2021

Objective To review the pharmacology, efficacy, and safety of ubrogepant as an abortive migraine treatment. Data Sources A literature search of MEDLINE and PubMed was performed (January 2006 through May 2021) using the following search terms: ubrogepant, calcitonin gene related peptide, and abortive migraine therapy. Study Selection and Data Extraction Relevant studies evaluating ubrogepant’s pharmacology, efficacy, and safety in humans for the treatment of migraine were considered Data Synthesis Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved by the Food and Drug Administration for the acute treatment of migraine via data from ACHIEVE I and II. From ACHIEVE I, ubrogepant demonstrated superiority to placebo in freedom from migraine pain at 2 hours postdose (50-mg dose: odds ratio [OR] = 1.83, 95% CI = 1.25-2.66; 100-mg dose: OR = 2.04, 95% CI = 1.41-2.95) and freedom from most bothersome symptom (MBS; 50-mg dose: OR = 1.70, 95% CI = 1.27-2.28; 100-mg dose: OR = 1.63, 95% CI = 1.22-2.17). ACHIEVE II trial demonstrated efficacy of ubrogepant 50 mg compared with placebo (2-hour pain freedom: OR = 1.62, 95% CI = 1.14-2.29; 2-hour MBS freedom: OR = 1.65, 95% CI = 1.25-2.20). Relevance to Patient Care and Clinical Practice Ubrogepant is a viable option for patients who are unable to tolerate nonsteroidal anti-inflammatory drug or triptan therapy because of ineffective relief or contraindications that limit use. Conclusions Ubrogepant is a well-tolerated effective abortive migraine treatment that bridges a gap in therapy for many patients who previously could not tolerate other first-line treatments.
The Impact of Coronal Plane Deformity on Ankle Arthrodesis and Arthroplasty
Authors: Johnson Michael D. , Shofer Jane B. , Hansen Sigvard T. , Ledoux William R. , Sangeorzan Bruce J. 
Published: June 2021

Background: Ankle coronal plane deformity represents a complex 3-dimensional problem, and comparative data are lacking to guide treatment recommendations for optimal treatment of end-stage ankle arthritis with concomitant coronal plane deformity. Methods: In total, 224 patients treated for end-stage ankle arthritis were enrolled in an observational trial. Of 112 patients followed more than 2 years, 48 patients (19 arthrodesis, 29 arthroplasty) had coronal plane deformity and were compared to 64 patients without coronal plane deformity (18 arthrodesis, 46 arthroplasty) defined as greater than 10 degrees of varus or valgus. The arthroplasty implants used had different internal constraints to intracomponent coronal plane tilting. Patients completed Musculoskeletal Functional Assessment (MFA) and SF-36 preoperatively and at 3, 6, 12, 24, and 36 months postoperatively. Measures included change in SF-36 and MFA, as well as compared reoperation rates and pain scales. Results: For the groups with coronal plane ankle deformity, the median for the arthrodesis group was 19.0 degrees and the median for the arthroplasty group was 16.9 degrees. In the deformity cohort during the follow-up period, we had 7 major reoperations: 2 in the arthrodesis group and 5 in the arthroplasty group, all with the less constrained implant design. MFA, vitality, and social function of the SF-36 improved for all groups. Patients without preoperative deformities had greater improvement with fusion or replacement at both 2 and 3 years. There was no difference in improvement between those patients with coronal deformity who received arthroplasty vs arthrodesis. Conclusion: Patients with and without coronal plane deformity may benefit from ankle arthroplasty and arthrodesis, although greater improvements may be expected in those without preoperative deformity. In this study, at final follow-up of 3 years, overall we found no meaningful difference in patient-reported outcomes between the patients with preoperative coronal plane deformities whether they had a fusion or a replacement as treatment for end-stage ankle arthritis. Level of Evidence: Level II, comparative study.