bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activin-A impedes the establishment of CD4+ T cell exhaustion and enhances anti-tumor immunity in the lung
Authors: Morianos Ioannis , Tsitsopoulou Aikaterini , Potaris Konstantinos , Valakos Dimitrios , Fari Ourania , Vatsellas Giannis , Bostantzoglou Clementine , Photiades Andreas , Gaga Mina , Xanthou Georgina , Semitekolou Maria 
Published: September 2021

Abstract
Background
Although tumor-infiltrating T cells represent a favorable prognostic marker for cancer patients, the majority of these cells are rendered with an exhausted phenotype. Hence, there is an unmet need to identify factors which can reverse this dysfunctional profile and restore their anti-tumorigenic potential. Activin-A is a pleiotropic cytokine, exerting a broad range of pro- or anti-inflammatory functions in different disease contexts, including allergic and autoimmune disorders and cancer. Given that activin-A exhibits a profound effect on CD4+ T cells in the airways and is elevated in lung cancer patients, we hypothesized that activin-A can effectively regulate anti-tumor immunity in lung cancer.

Methods
To evaluate the effects of activin-A in the context of lung cancer, we utilized the OVA-expressing Lewis Lung Carcinoma mouse model as well as the B16F10 melanoma model of pulmonary metastases. The therapeutic potential of activin-A-treated lung tumor-infiltrating CD4+ T cells was evaluated in adoptive transfer experiments, using CD4−/−-tumor bearing mice as recipients. In a reverse approach, we disrupted activin-A signaling on CD4+ T cells using an inducible model of CD4+ T cell-specific knockout of activin-A type I receptor. RNA-Sequencing analysis was performed to assess the transcriptional signature of these cells and the molecular mechanisms which mediate activin-A’s function. In a translational approach, we validated activin-A’s anti-tumorigenic properties using primary human tumor-infiltrating CD4+ T cells from lung cancer patients.

Results
Administration of activin-A in lung tumor-bearing mice attenuated disease progression, an effect associated with heightened ratio of infiltrating effector to regulatory CD4+ T cells. Therapeutic transfer of lung tumor-infiltrating activin-A-treated CD4+ T cells, delayed tumor progression in CD4−/− recipients and enhanced T cell-mediated immunity. CD4+ T cells genetically unresponsive to activin-A, failed to elicit effective anti-tumor properties and displayed an exhausted molecular signature governed by the transcription factors Tox and Tox2. Of translational importance, treatment of activin-A on tumor-infiltrating CD4+ T cells from lung cancer patients augmented their immunostimulatory capacity towards autologous CD4+ and CD8+ T cells.

Conclusions
In this study, we introduce activin-A as a novel immunomodulatory factor in the lung tumor microenvironment, which bestows exhausted CD4+ T cells with effector properties.
Network security situation prediction based on feature separation and dual attention mechanism
Authors: Li Zhijian , Zhao Dongmei , Li Xinghua , Zhang Hongbin 
Published: September 2021

AbstractWith the development of smart cities, network security has become more and more important. In order to improve the safety of smart cities, a situation prediction method based on feature separation and dual attention mechanism is presented in this paper. Firstly, according to the fact that the intrusion activity is a time series event, recurrent neural network (RNN) or RNN variant is used to stack the model. Then, we propose a feature separation method, which can alleviate the overfitting problem and reduce cost of model training by keeping the dimension unchanged. Finally, limited attention is proposed according to global attention. We sum the outputs of the two attention modules to form a dual attention mechanism, which can improve feature representation. Experiments have proved that compared with other existing prediction algorithms, the method has higher accuracy in network security situation prediction. In other words, the technology can help smart cities predict network attacks more accurately.
Supplementation of non-fermented and fermented goji berry (Lycium barbarum) improves hepatic function and corresponding lipid metabolism via their anti-inflammatory and antioxidant properties in high fat-fed rats
Authors: Lee Sunhye , Jeong Soyeon , Park Yeongju , Seo Hyunji , You Cheongbin , Hwang Unsik , Park Hoon , Suh Hee-jae 
Published: September 2021

AbstractDevelopment of obesity is associated with excessive fat accumulation and oxidative stress along with chronic inflammation. Goji berries (Lycium barbarum) are high in polyphenolic compounds and have anti-inflammatory, anti-oxidant, and hypolipidemic properties that may alleviate the pathogenesis of obesity and related metabolic complications. Thus, the aim of this study was to investigate potential metabolic benefits of GB supplementation against high fat (HF) diet-induced obesity and its comorbidities in HF diet-fed rats (male Sprague–Dawley, n  =  8/group, 6 weeks old). We also sought to examine the potential metabolic benefits of fermented GB (FGB) with L. plantarum CB3 and possible distinctions in the degree and/or mechanism of action compared to GB. GB and FGB supplementation suppressed the gene expression of inflammation indices at the local (adipose tissues) and systemic (liver) levels. In addition, GB and FGB supplementation upregulated the gene expression of antioxidant enzymes compared to the HF and/or even low fat (LF) group with more remarkable antioxidant effects by GB supplementation. Also, GB and FGB supplementation protected from HF-induced damages of the liver and dyslipidemia. In conclusion, we demonstrated that GB and FGB supplementation protected from HF-induced metabolic complications primarily by improving hepatic function and corresponding lipid metabolism via their anti-inflammatory and antioxidant properties. To our knowledge, this is the first in vivo study confirming metabolic benefits of GB in a fermented form. Thus, these findings support the potential application of both GB and FGB to ameliorate obesity-associated metabolic abnormalities.
Perceptions from pharmaceutical stakeholders on how the pharmaceutical budget is allocated in South Africa
Authors: Moodley Lirosha , Suleman Fatima , Perumal-Pillay Velisha Ann 
Published: September 2021

Abstract
Background
South Africa faces a heavy burden of disease, which impacts resource allocation. The needs of South Africa require efficient translation into pharmaceutical expenditure for medicine provision, to ensure availability of medicines. Given that South Africa faces various challenges with medicine provision accompanied by rising pharmaceutical expenditure, this study aimed to report on the considerations and methods used to determine the healthcare budget for South Africa, and how it is translated into pharmaceutical expenditure for medicines provision on the Standard Treatment Guidelines and Essential Medicines List and non-essential medicines in the public sector.

Method
Qualitative, semi-structured interviews guided by a discussion guide were conducted with seven pharmaceutical officials involved in the budget and resource allocation process, between October 2019 and March 2020. Interviews were recorded and transcribed verbatim. Once the interviews were coded by the first author they were verified by the other authors. Data were thematically analysed.

Results
This study depicted the knowledge and participation of pharmaceutical services in the budget process. The National and Provincial Department of Health have improved pharmaceutical budgeting by making strides towards a collaborative, informed, and more evidence-based approach. Pharmaceutical services have roles in advising on requirements; commenting where necessary, constantly monitor and taking accountability for their budget. The main considerations that determined the budget included population size and growth, historical expenditure, the extra heavy burden of disease and incidence rate, demand data and forecasting. The local and provincial pharmacy and therapeutics committee play a vital role in monitoring the budget and expenditure; ensuring adherence to guidelines; controlling the extent to which non-Essential Medicine List items are used and advising accordingly.

Conclusion
This was the first study to report on the decision and thought processes of the healthcare budget and its translation into pharmaceutical expenditure for medicine provision in South Africa. Many factors were considered to inform the budget, with the Standard Treatment Guideline and Essential Medicines List being the principal guide for medicine provision. This process was well-controlled and monitored by the pharmaceutical therapeutics committee. Documenting the South African experience can assist other countries in their budget decisions for medicines.
Short-term follow-up HRCT Chest of COVID-19 survivors and association with persistent dyspnea
Authors: Kumar Ishan , Prakash Adity , Ranjan Manoj , Chakrabarti Sankha Shubhra , Shukla Ram C. , Verma Ashish 
Published: September 2021

Abstract
Background
There is an increasing concern that a proportion of the survivors of COVID 19 might develop fibrotic and/or other non-reversible lung changes. The aim of this retrospective study was to review the imaging findings of HRCT of lungs in a cohort of COVID 19 survivors, coming for short-term clinical follow-up and to assess the relation of the observed HRCT changes with the presence of dyspnea.

Results
In total, 40 patients with residual CT findings were included in this study with a mean age of 44.3 years and male: female ratio of 3:2. The presence of residual ground-glass opacities (85%) and reticular opacities (80%) was the most common findings. 25% of the cases had cystic changes in their lung. The presence of dyspnea was significantly associated with male sex and a history of smoking. On HRCT, the presence of cystic changes, involvement of > 10 lung segments, and an HRCT severity score > 7 were significantly associated with dyspnea.

Conclusion
Survivors of COVID 19 demonstrate persistent changes in the lung on HRCT. We recommend that a follow-up HRCT should be performed in these patients to identify those with post-COVID sequelae.
Impact of smoking behavior on cognitive functioning in persons at risk for psychosis and healthy controls: A longitudinal study
Authors: van der Heijden Heleen S. , Schirmbeck Frederike , Kempton Matthew J. , van der Gaag Mark , Allott Kelly , Nelson Barnaby , Ruhrmann Stephan , de Haan Lieuwe , Vermeulen Jentien M ,   Eu-Gei High Risk Study
Published: September 2021

Abstract

Background
The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking.

Method
A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene–environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables.

Results
At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR.

Conclusions
No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.
Epstein-Barr Virus Latent Membrane Protein-1 Expression in Nasopharyngeal Carcinoma
Authors: Salano Valerie E. , Mwakigonja Amos R. , Abdulshakoor Ashfaq , Kahinga Aveline A. , Richard Enica M. 
Published: September 2021

PURPOSENasopharyngeal carcinoma (NPC), a malignant neoplasm of the epithelium covering the nasopharynx, is a rare disease in most parts of the world. Epstein-Barr virus (EBV), the most potent oncogenic virus, coupled with environmental and genetic factors has been identified to play a role in the development of NPC. An array of methods for detecting the virus do exist, from serologic detection of antibodies to DNA amplification. There is paucity of local data on the status of EBV infection in relation to NPC within the region, and this study attempts to shed more light on the subject.METHODSThis was a retrospective cross-sectional laboratory-based study on histologically confirmed, archived tissues from July 2015 to June 2019. Immunohistochemistry expression of latent membrane protein-1 (LMP-1) was used to detect EBV infection in the tissues.RESULTSA total of 71 cases were enrolled in this study. The mean age was 47.87 years ± 16.84 years with a male-to-female ratio of 1.5:1. There was a unimodal distribution of EBV detection, with the peak (26.8%) at 36-45 years. About 45.1% of the 71 samples tested positive for LMP-1, all of which were nonkeratinizing carcinoma. Nonkeratinizing carcinoma was the most common histopathologic subtype (n = 67; 94.4%), with the majority (38 of 67; 56.7%) being undifferentiated and 29 of 67 (43.3%) differentiated. Keratinizing and basaloid subtypes had two cases each, representing 2.8%.CONCLUSIONA significant proportion of NPC, particularly nonkeratinizing histologic subtype, seems to show LMP-1 positivity by immunohistochemistry, which may be adopted in resource-constrained settings to detect EBV infection in these tissue biopsies.
Using blood wisely in oncology patients: An institutional analysis of the Choosing Wisely Canada restrictive transfusion strategy guidelines.
Authors: Tesch Megan Elizabeth , Alghawas Mae , Gerrie Alina S. 
Published: September 2021

10 Background: Numerous studies support the safety of single-unit red red blood cell (RBC) transfusions and restrictive pre-transfusion hemoglobin (Hg) thresholds (≤ 70-80 g/L) among diverse populations of hospitalized patients, including those with malignancies on myelosuppressive systemic therapy. Using Blood Wisely is a national Choosing Wisely Canada (CWC) initiative that challenges hospitals to benchmark themselves on evidence-informed restrictive transfusion strategies, with the aim to decrease inappropriate RBC transfusions in Canada. We assessed transfusion practices among oncology inpatients at BC Cancer Vancouver Centre as part of this initiative and performed an exploratory analysis among outpatients. Methods: BC Cancer Vancouver RBC transfusion records were obtained for the period of October 2019-September 2020. The percentage of single-unit transfusions and transfusions for Hg ≤ 80 g/L were measured, to assess adherence to CWC targets of ≥ 65% and ≥ 80%, respectively, for these metrics. Univariate analyses were used to compare treatment variables and transfusion outcomes. Results: During the 1-year audit period, 120 inpatient and 586 outpatient RBC transfusions occurred. For inpatient transfusions, 40.8% (n = 49) were single-unit and 79.2% (n = 95) were for Hg ≤ 80 g/L. For outpatient transfusions, 11.8% (n = 69) were single-unit and 65.7% (n = 304) were for Hg ≤ 80 g/L. Outpatients and patients with solid malignancies were more likely to receive multiple-unit transfusions, compared to inpatients (p < 0.001) and patients with hematological malignancies (p < 0.001), respectively. Patients with solid malignancies and those on active treatment were more likely to be transfused when Hg was > 80 g/L, compared to patients with hematological malignancies (p = 0.004) and those off treatment (p = 0.003), respectively. Multiple RBC units were more likely to transfused when the interval from pre-transfusion bloodwork to receipt of transfusion was > 3 days (p = 0.029). Conclusions: A high rate of inappropriate RBC transfusions are being ordered for oncology patients at our institution, in discordance with CWC restrictive transfusion strategy guidelines. Quality improvement interventions are planned to adopt best practices in transfusion medicine in this high-use population.[Table: see text]
Implementing a patient navigation program to improve adherence with cancer treatment for community health center patients newly diagnosed with cancer.
Authors: Percac-Lima Sanja , Irwin Kelly , Whited Emma , Benjamin Carmen , Pichardo Ausubel , Oravcova-Mejia Mira , Thompson Solomon , Morrill James , Ford Colleen , Wheeler Amy , Moy Beverly 
Published: September 2021

103 Background: Community health centers’ (CHCs) patients newly diagnosed with cancer often experience barriers to accessing timely treatment. Patient navigation decreases barriers to cancer screening and diagnostic care, but the exact impact on cancer treatment is unclear. We implemented patient navigation to provide underserved patients with support to access and adhere to cancer treatment. The goal of our study is to determine the effect of patient navigation on missed appointment rates, treatment adherence, and health outcomes among an underserved patient population. Here, we present preliminary data about program implementation. Methods: Utilizing a population health registry, TopCare, and referrals from CHCs physician champions, newly diagnosed cancer patients from Massachusetts General Hospital CHCs were referred to the Cancer Center, identified and verbally consented to participate in the study’s intervention. Patients are randomized either to receive in-person patient navigation or enhanced usual care, which consists of two reminder phone calls prior to each oncology appointment. Adherence to treatment, healthcare utilization, patient satisfaction with cancer care and patient navigation, patient engagement, financial burden, symptom burden, health-related quality of life, and psychosocial care are longitudinally assessed. Our primary outcome is missed appointment rate to oncology appointments. Results: The trial started in November 2017 and as of April 2021, we have identified 349 eligible patients and enrolled 261 (82% consent rate for reached patients). Of 261 enrolled patients, 50% were women, 38% identified as non-White, 25% identified as Hispanic or Latino, and 28% did not speak English. The most frequent cancer types enrolled include genitourinary (n=67), thoracic (n=47), gastrointestinal (n=47), and breast (n=46). Patients had 6257 visits and 195 were missed (3.1%). Navigators performed 4553 interventions. There were 152 emergency department visits and 127 unplanned hospital admissions. Of 120 referrals to supportive care, 54 were to social work, 38 to palliative care and 28 to Psychiatric Oncology or behavioral health. Conclusions: Patient navigation is feasible for underserved CHC patients newly diagnosed with cancer. Our current missed appointment rate is 3.1%, including the time period of the COVID-19 pandemic. After trial completion in July 2021, we will compare the outcomes in patients who received in-person patient navigation to patients who were randomized to enhanced usual care. Clinical trial information: NCT03226405.
Biomarker testing in patients (pts) with metastatic colorectal cancer (mCRC): Survey of U.S. oncologists (ONC) in rural areas and urban clusters.
Authors: Lewis Mark Andrew , Stansfield Lindsay , Kelton John M. , Edwards Michelle L. , Lieu Christopher Hanyoung 
Published: September 2021

108 Background: In the US, rural areas have higher cancer mortality rates than urban areas. Clinical practice guidelines recommend testing for BRAF and RAS mutations, and deficient mismatch repair (dMMR)/microsatellite instability (MSI) in pts with mCRC. However, data on biomarker testing rates in rural communities are limited. We surveyed ONC in the US who practice in rural areas and urban clusters to identify biomarker testing patterns and barriers. Methods: A web-based survey was administered to board-certified ONC who spend ≥ 40% of their time providing direct care to pts in rural areas or urban clusters (US Census Bureau definition) and who treated ≥ 2 pts with stage IV mCRC in the month prior to the survey. ONC in Maine, Vermont, and West Virginia were excluded (state legislature), as were those employed by the US government, Veterans Affairs, or Kaiser Permanente. Respondents were compensated. Data were analyzed descriptively. Results: From Feb 12 to Mar 18, 2021, 99 ONC (40% medical ONC, 60% hematologists/ONC) completed the survey. Respondents spent 56% and 18% of their time (mean) practicing in urban clusters and rural areas, respectively; 33% were in the South, followed by 26%, 22%, and 18% in the Northeast, Midwest, and West, respectively. 97% of ONC had ordered biomarker tests for pts; 35% referred pts for independent genomic testing. ONC tested biomarkers most commonly for stage IV disease: 72%, 65%, 63%, 59%, and 66% for KRAS, NRAS, BRAF, PD-L1, and dMMR/MSI, respectively (Table). 41% of ONC reported performing reflex testing at their primary practice, most commonly for PD-L1 (62%), KRAS (60%), and dMMR/MSI (52%). DNA-based next-generation sequencing (NGS) was the most common testing method reported. ONC indicated they would test for an actionable biomarker if it were known to occur in ≥ 28% of pts with mCRC. The most commonly cited barriers to testing were insufficient tissue samples and lack of insurance coverage. Although > 50% of ONC agreed telehealth can improve testing rates, 81% noted barriers, including pts lacking technology equipment (56%) and pts being disengaged or unwilling to use telehealth (37%). Further data on testing-related decision making and barriers will be presented. Conclusions: Biomarker testing in rural areas and urban clusters falls short of current guideline recommendations. Further exploration of rural biomarker testing practices and strategies to improve testing are needed.[Table: see text]