bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic cell-mediated cross presentation of tumor-derived peptides is biased against plasma membrane proteins
Authors: Fessenden Tim B , Stopfer Lauren E , Chatterjee Fiona , Zulueta Julian , Mesfin Josh , Cordero Dumit Therese , Reijers Irene , Hoefsmit Esmee P , Blank Christian , White Forest , Spranger Stefani 
Published: July 2022

BackgroundFor effective tumor elimination, cytotoxic CD8+T cells must recognize tumor-derived antigens presented on class I major histocompatibility complex (MHC-I). Despite a general association between the expression of immunogenic antigens, typically neoantigens, and response to immunotherapy, the majority of patients lack strong endogenous responses to most putative neoantigens due to mechanisms that are not well understood. Cytotoxic CD8+T-cell responses are induced by dendritic cells (DCs) cross-presenting tumor-derived peptides on MHC-I. We hypothesized that cross presentation may form an unappreciated source of bias in the induction of cytotoxic T-cell responses.MethodsWe used stable isotope labeling of amino acids combined with immunopeptidomics to distinguish cross-presented from endogenous MHC-I peptides on DCs. To test impacts on T-cell activation, we targeted the model antigen SIINFEKL to specific subcellular compartments in tumor cells, which were used as sources for cross presentation to T cells. In vitro observations were validated using DNA and RNA sequencing data from two cohorts of patients with melanoma undergoing checkpoint blockade therapy. We used a novel quantitative mass spectrometry approach to measure the levels of model antigen on cross-presenting DCs following various means of tumor cell death.ResultsDCs exhibited a strong bias for cross-presenting peptides derived from cytoplasmic proteins and against those from plasma membrane proteins, which was confirmed using the model antigen SIINFEKL. In patients with melanoma, the proportion of membrane-derived neoantigens was correlated with reduced survival and failure to respond to therapy. Quantification of cross-presented SIINFEKL revealed that the mode of cell death could overcome DCs’ bias against plasma membrane proteins.ConclusionsCross presentation of cellular antigens by DCs may impose constraints on the range of peptides available to activate CD8+T cells that have previously gone unappreciated. The share of neoantigens arising from membrane-derived sources may render some tumors less immunogenic due to inefficient cross presentation. These observations carry important implications for the encounter and intracellular processing of cellular antigens by DCs and merit further clinical studies for their therapeutic potential in stratifying patient populations and design of vaccine-based therapies.
Biomechanical Comparison of a Horizontal Mattress, Cross Suture and Vertical Mattress for Repair of a Tendon Weave in a Porcine Model
Authors: SENJU Takahiro , TAKEUCHI Naohide , KOZONO Naoya , HIGAKI Hidehiko , SHIMOTO Takeshi , NAKASHIMA Yasuharu 
Published: July 2022

Background: An effective suture method enables early active motion exercises and optimal post-surgical outcomes. The aim of this study is to evaluate the tensile strength of three suture configurations – horizontal mattress (HM), vertical mattress (VM) and a cross suture for repair of a tendon weave. We hypothesised that the direction of mattress sutures relative to the tendon fibres would affect the tensile strength of tendon repair. Methods: Using porcine flexor tendons and the same number of surgical sutures, three tendon weave constructs differing in the method of suture were compared: HM suture configuration (conventional technique), cross-stitch (CS) configuration (conventional technique) and VM suture configuration (novel technique). Ten pairs of each group were mounted in a material testing machine and subjected to a simple tensile test and a cyclic loading test for their biomechanical comparison. Results: The VM group and CS group had significantly higher ultimate failure load, linear stiffness and fatigue strength as compared to the HM group. The failure mode was suture breakage or tendon rupture for the VM and the CS group, while the suture pullout of the tendon only occurred in the HM group. Conclusion: Among the three techniques used for repair of a tendon weave, the VM suture technique was demonstrated to have the greatest tensile strength and least associated with suture pull-out. The direction of the mattress suture in relation the direction of tendon fibres affects the strength of repair.
DeResolver: A Decentralized Conflict Resolution Framework with Autonomous Negotiation for Smart City Services
Authors: Yuan Yukun , Ma Meiyi , Han Songyang , Zhang Desheng , Miao Fei , Stankovic John A. , Lin Shan 
Published: July 2022

As various smart services are increasingly deployed in modern cities, many unexpected conflicts arise due to various physical world couplings. Existing solutions for conflict resolution often rely on centralized control to enforce predetermined and fixed priorities of different services, which is challenging due to the inconsistent and private objectives of the services. Also, the centralized solutions miss opportunities to more effectively resolve conflicts according to their spatiotemporal locality of the conflicts. To address this issue, we design a decentralized negotiation and conflict resolution framework named DeResolver, which allows services to resolve conflicts by communicating and negotiating with each other to reach a Pareto-optimal agreement autonomously and efficiently. Our design features a two-step self-supervised learning-based algorithm to predict acceptable proposals and their rankings of each opponent through the negotiation. Our design is evaluated with a smart city case study of three services: intelligent traffic light control, pedestrian service, and environmental control. In this case study, a data-driven evaluation is conducted using a large dataset consisting of the GPS locations of 246 surveillance cameras and an automatic traffic monitoring system with more than 3 million records per day to extract real-world vehicle routes. The evaluation results show that our solution achieves much more balanced results, i.e., only increasing the average waiting time of vehicles, the measurement metric of intelligent traffic light control service, by 6.8% while reducing the weighted sum of air pollutant emission, measured for environment control service, by 12.1%, and the pedestrian waiting time, the measurement metric of pedestrian service, by 33.1%, compared to priority-based solution.
Systematic Scalability Modeling of QoS-aware Dynamic Service Composition
Authors: Duboc Leticia , Bahsoon Rami , Alrebeish Faisal , Mera-Gómez Carlos , Nallur Vivek , Kazman Rick , Bianco Philip , Babar Ali , Buyya Rajkumar 
Published: July 2022

In Dynamic Service Composition (DSC), an application can be dynamically composed using web services to achieve its functional and Quality of Services (QoS) goals. DSC is a relatively mature area of research that crosscuts autonomous and services computing. Complex autonomous and self-adaptive computing paradigms (e.g., multi-tenant cloud services, mobile/smart services, services discovery and composition in intelligent environments such as smart cities) have been leveraging DSC to dynamically and adaptively maintain the desired QoS, cost and to stabilize long-lived software systems. While DSC is fundamentally known to be an NP-hard problem, systematic attempts to analyze its scalability have been limited, if not absent, though such analysis is of a paramount importance for their effective, efficient, and stable operations.This article reports on a new application of goal-modeling, providing a systematic technique that can support DSC designers and architects in identifying DSC-relevant characteristics and metrics that can potentially affect the scalability goals of a system. The article then applies the technique to two different approaches for QoS-aware dynamic services composition, where the article describes two detailed exemplars that exemplify its application. The exemplars hope to provide researchers and practitioners with guidance and transferable knowledge in situations where the scalability analysis may not be straightforward. The contributions provide architects and designers for QoS-aware dynamic service composition with the fundamentals for assessing the scalability of their own solutions, along with goal models and a list of application domain characteristics and metrics that might be relevant to other solutions. Our experience has shown that the technique was able to identify in both exemplars application domain characteristics and metrics that had been overlooked in previous scalability analyses of these DSC, some of which indeed limited their scalability. It has also shown that the experiences and knowledge can be transferable: The first exemplar was used as an example to inform and ease the work of applying the technique in the second one, reducing the time to create the model, even for a non-expert.
Human Colon Cancer–Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice
Authors: Drewes Julia L. , Chen Jie , Markham Nicholas O. , Knippel Reece J. , Domingue Jada C. , Tam Ada J. , Chan June L. , Kim Lana , McMann Madison , Stevens Courtney , Dejea Christine M. , Tomkovich Sarah , Michel John , White James R. , Mohammad Fuad , Campodónico Victoria L. , Heiser Cody N. , Wu Xinqun , Wu Shaoguang , Ding Hua , Simner Patricia , Carroll Karen , Shrubsole Martha J. , Anders Robert A. , Walk Seth T. , Jobin Christian , Wan Fengyi , Coffey Robert J. , Housseau Franck , Lau Ken S. , Sears Cynthia L. 
Published: July 2022

Abstract

Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient–derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients.

Significance:
Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis.
See related commentary by Jain and Dudeja, p. 1838.
This article is highlighted in the In This Issue feature, p. 1825
Impact of a Population Genomic Screening Program on Health Behaviors Related to Familial Hypercholesterolemia Risk Reduction
Authors: Jones Laney K. , Chen Nan , Hassen Dina A. , Betts Megan N. , Klinger Tracey , Hartzel Dustin N. , Veenstra David L. , Spencer Scott J. , Snyder Susan R. , Peterson Josh F. , Schlieder Victoria , Sturm Amy C. , Gidding Samuel S. , Williams Marc S. , Hao Jing 
Published: July 2022

Background:
Limited information is available regarding clinician and participant behaviors after disclosure of genomic risk variants for familial hypercholesterolemia (FH) from a population genomic screening program.

Methods:
We conducted a retrospective cohort study of MyCode participants with an FH risk variant beginning 2 years before disclosure until January 16, 2019. We analyzed lipid-lowering prescriptions (clinician behavior), medication adherence (participant behavior), and LDL (low-density lipoprotein) cholesterol levels (health outcome impact) pre- and post-disclosure. Data were collected from electronic health records and claims.

Results:

The cohort included 96 participants of mean age 57 (22–90) years with median follow-up of 14 (range, 3–39) months. Most (90%) had a hypercholesterolemia diagnosis but no specific FH diagnosis before disclosure; 29% had an FH diagnosis post-disclosure. After disclosure, clinicians made 36 prescription changes in 38% of participants, mostly in participants who did not achieve LDL cholesterol goals pre-disclosure (81%). However, clinicians wrote prescriptions for fewer participants post-disclosure (71/96, 74.0%) compared with pre-disclosure (81/96, 84.4%); side effects were documented for most discontinued prescriptions (23/25, 92%). Among the 16 participants with claims data, medication adherence improved (proportion of days covered pre-disclosure of 70% [SD, 24.7%] to post-disclosure of 79.1% [SD, 27.3%];
P
=0.05). Among the 52 (54%) participants with LDL cholesterol values both before and after disclosure, average LDL cholesterol decreased from 147 to 132 mg/dL (
P
=0.003).

Conclusions:
Despite disclosure of an FH risk variant, nonprescribing and nonadherence to lipid-lowering therapy remained high. However, when clinicians intensified medication regimens and participants adhered to medications, lipid levels decreased.
Biological attributes of Salibro™, a novel sulfonamide nematicide. Part 3: biocompatibility with beneficial soil fungi
Authors: Thoden Tim C. , Alkader Mariam A. , Markakis Emmanouil A. , Yum Man Y. , Wiles John A. 
Published: July 2022

Summary
Over the last few years, novel synthetic nematicides, such as Salibro™ nematicide (a.s. fluazaindolizine - Reklemel™ active), Velum Prime® (a.s. fluopyram) or Nimitz® (a.s. fluensulfone), have been commercialised in various regions around the world. Whilst considerable scientific information exists on their field efficacy against plant-parasitic nematodes, very little has been published on their bio-compatibility with beneficial soil fungi. In this paper in vitro studies are presented with various nematophagous (Athrobotrys, Monacrosporium, Harposporium, Purpureocillium), entomoparasitic (Beauveria, Isaria) and disease-suppressive (Trichoderma) fungi that were exposed to these nematicides under laboratory conditions. Assessments were made on their impact on radial growth and sporulation of those fungi. Clear differences in sensitivity to the nematicides were seen between the different fungi. Intrinsically, fluopyram showed the strongest adverse effects on the tested fungi that often became already visible at a concentration of 5 ppm (a.s.). Negative effects were significant at higher concentrations of 50 ppm. Fluensulfone showed limited adverse impacts on the tested fungi at 5 ppm (a.s.) but clearly inhibited most of the fungi at 50 ppm (a.s.). Fluazaindolizine had the least impact of the novel nematicides, with no adverse effects recorded on any species at 5 ppm (a.s.), and very minor growth reductions at 50 ppm (a.s.). Even when tested at 250 ppm (a.s.) fluazaindolizine still showed no impact on Purpureocillium lilacinum, as well as only a weak impact on some Trichoderma species. Vydate (a.s. oxamyl), which was often included as a traditional carbamate nematicide in the test, also showed excellent bio-compatibility with the tested fungi at concentrations of from 5 to 50 ppm (a.s.). Overall, the studies showed that beneficial soil fungi differ in their intrinsic sensitivity to these modern nematicides. These interactions may be considered when designing integrated nematode management programmes that leverage endemic or introduced biocontrol agents. However, it should be noted that additional studies under field conditions with recommended label rates of the products are needed to confirm the trends seen in these laboratory data.
East Syriac Scribal Poetry in Paratextual Manuscript Parts
Authors: Pritula Anton 
Published: July 2022

Abstract
The present paper discusses various kinds of poetry represented in scribal paratextual parts of East Syriac manuscripts, such as introductions and colophons. In the current article, we have attempted to develop a general typology of this kind of verse pieces and to discuss the details of their transmission in diachronic scope, starting with the Mongol period and focusing on the Ottoman time, when this type of texts obtained a large popularity.
COVID-19 Diagnosis in Patients With Acute Abdominal Pain Without Respiratory Symptoms: A UK Emergency General Surgical Unit Experience
Authors: Zuberi Sharukh , Mushtaq Yusuf , Patel Krashna , Vickramarajah Saranya , Askari Alan , Rashid Farhan , Gurprashad Roy 
Published: July 2022

Background Recent evidence has emerged reporting atypical clinical symptoms of the novel coronavirus (COVID-19). There is a sparsity of existing studies examining COVID-19-related abdominal pain and the role of investigative imaging for the virus in these patients. Study aims were to determine COVID-19 incidence in those with acute abdominal pain in the absence of respiratory symptoms and to assess the diagnostic performance of CT thoracic imaging in such patients. Methods Retrospective analysis of all consecutive patients admitted to our emergency general surgical unit between 1st March 2020 and 31st May 2020 was performed. In adherence with national guidelines, all patients underwent nasal and oro-pharyngeal COVID-19 RT-PCR swabs as well as thoracic and abdominal computed tomography (CT) on admission. Results From 112 patients admitted with acute abdominal pain in the absence of respiratory symptoms, 16 (14.3%) tested positive for COVID-19 on RT-PCR swab testing. Overall, 50% (8/16) of these patients had no intra-abdominal pathology on CT. The sensitivity and specificity of CT thoracic imaging for diagnosing COVID-19 was 43.8% and 91.7%, respectively. Patients with positive COVID-19 swabs had higher C-reactive protein levels, lower potassium levels and a higher proportion of those with a low lymphocyte count. Discussion One in seven patients with abdominal pain without any respiratory symptoms tested positive for COVID-19. Half of these patients represented COVID-19 manifesting primarily as acute abdominal pain. Combined swab testing and CT imaging should be performed in all abdominal pain presentations due to the varying diagnostic performance of thoracic CT in diagnosing COVID-19.
Comparing Outcomes of Appendectomy Versus Non-operative Antibiotic Therapy for Acute Appendicitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Zagales Israel , Sauder Matthew , Selvakumar Sruthi , Spardy Jeffrey , Santos Radleigh. G. , Cruz Jozef , Bilski Tracy , Elkbuli Adel 
Published: July 2022

BackgroundAcute appendicitis is one of the most common etiologies of an acute abdomen in the emergency department and first-line standard surgical care for the condition has recently been reconsidered. We aim to evaluate the effectiveness and outcomes of surgical intervention versus non-operative antibiotic therapy in the treatment of acute appendicitis in adult and pediatric patients.MethodsA literature search was conducted using PubMed, Google Scholar, and EMBASE. The search included all studies until January 15th, 2022. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were independently extracted by the authors of the study. Meta-analysis was performed and Cohen’s Q test for heterogeneous effects was performed to determine if fixed or random-effects models were appropriate for use.ResultsTwelve randomized controlled trials investigating a total of 3703 acute appendicitis patients met inclusion criteria and were included in the meta-analysis. In the systematic review, eleven RCTs demonstrated that appendectomy had improved effectiveness compared to non-operative antibiotic management. The meta-analysis demonstrated that patients undergoing appendectomy had significantly higher treatment effectiveness compared with antibiotics-only treatment (98.4% vs. 73.3%, P < .0001). The meta-analysis did demonstrate a significant .54-day reduction in hospital length of stay for the appendectomy group compared to the non-operative antibiotic therapy group.ConclusionsSurgical intervention is associated with increased effectiveness of treatment and reduced in-hospital length of stay among patients with acute appendicitis. Guidelines established by institutions and surgical organizations should indicate appendectomy as the standard and superior treatment option for patients presenting with acute appendicitis.
Brazilian Students in the United States: A Forgotten Chapter of the Cultural Cold War during the Rebel Years
Authors: Ridenti Marcelo 
Published: July 2022

From 1962 to 1971 the Associação Universitária Interamericana (Inter-American University Association—AUI) conducted a program of internships at Harvard University for Brazilian students. The goal of these internships was for Brazilian students to gain an understanding of the American way of life. The students were mostly recruited among leftists. It was their hearts and minds that the university wanted to win over to the side of the "free world" during the Cold War. These students took advantage of the situation and used the internships for their own purposes. This had implications not only for their personal careers but also for the construction of institutional and political ideas. This process took place within a complex game that involved the interests of the United States and the entrepreneurs who helped finance the AUI. Created during the Kennedy administration, the AUI ended its activities as a result of a conservative offensive launched by the Nixon administration in the United States and the Médici dictatorship in Brazil. Desde 1962 a 1971 a Associação Universitária Interamericana (Interamerican University Association—AUI) promoveu o intercâmbio universitário de estudantes brasileiros selecionados para fazer um estágio em Harvard e conhecer o modo de vida americano. Os universitários eram recrutados em sua maioria entre simpatizantes de ideias de esquerda, cujos corações e mentes se buscava conquistar para o lado do “mundo livre” na Guerra Fria. Eles aproveitaram as circunstâncias conforme suas próprias conveniências, não apenas de carreira pessoal, mas também na construção institucional e política, num jogo de mão dupla com os interesses dos Estados Unidos e dos empresários que, juntos, financiaram a entidade. Criada durante o governo Kennedy, a AUI encerrou as atividades de intercâmbio diante da ofensiva conservadora do governo Nixon nos Estados Unidos e da ditadura no Brasil do presidente Medici.