bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of allogeneic and autologous membrane-bound IL-21–expanded NK cells for chronic lymphocytic leukemia therapy
Authors: Yano Max , Sharpe Chia , Lance J. Rachel , Ravikrishnan Janani , Zapolnik Kevan , Mo Xiaokui , Woyach Jennifer A. , Sampath Deepa , Kittai Adam S. , Vasu Sumithira , Bhat Seema , Rogers Kerry A. , Lee Dean A. , Muthusamy Natarajan , Byrd John C. 
Published: April 2022

AbstractSuccesses with anti-CD20 antibodies in chronic lymphocytic leukemia (CLL) and enhanced activity of Fc-engineered vs unmodified antibody therapy suggest a potentially impactful role for natural killer (NK) cells and other innate immune cells in controlling this disease. Stimulated NK cells have shown promise as a cellular therapy, but their application has been constrained by limited expansion capacity and low cytotoxic activity against CLL cells. Here, we demonstrate that both healthy donor-derived and CLL patient-derived NK cells expand rapidly when stimulated with feeder cells expressing membrane-bound interleukin-21 (mbIL-21) and have potent cytotoxic activity against allogeneic or autologous CLL cells. Combination with anti-CD20 antibodies significantly enhances NK recognition and killing of CLL targets. As any CLL immune therapy would likely be given in combination, we assess commonly used treatments and demonstrate that ibrutinib has mixed suppressive and protective effects on expanded NK cells, whereas expanded NKs are highly resistant to venetoclax. We demonstrate efficacy in vivo in 2 xenograft mouse models of human CLL that support building upon a regimen of venetoclax and obinutuzumab with mbIL-21–expanded NK cells. Collectively, these data support development of mbIL-21–expanded NKs combined with the CD20 antibody obinutuzumab and venetoclax in the treatment of CLL.
Platelets upregulate tumor cell programmed death ligand 1 in an epidermal growth factor receptor-dependent manner in vitro
Authors: Guo Qiuchen , Malloy Michael W. , Roweth Harvey G. , McAllister Sandra S. , Italiano Joseph E. , Battinelli Elisabeth M. 
Published: April 2022

AbstractProgrammed death ligand 1 (PD-L1) is an immune checkpoint protein that suppresses cytotoxic T lymphocytes and is often overexpressed in cancers. Due to favorable clinical trial results, immune checkpoint inhibition (ICI) is part of Food and Drug Administration approved immuno-oncology therapies; however, not all patients benefit from ICI therapy. High blood platelet-to-lymphocyte ratio has been associated with failure of ICI treatment, but whether platelets have a role in hindering ICI response is unclear. Here, we report that coculturing platelets with cancer cell lines increased protein and gene expression of tumor cell PD-L1, which was reduced by antiplatelet agents, such as aspirin and ticagrelor. Platelet cytokine arrays revealed that the well-established cytokines, including interferon-γ, were not the main regulators of platelet-mediated PD-L1 upregulation. Instead, the high molecular weight epidermal growth factor (EGF) is abundant in platelets, which caused an upregulation of tumor cell PD-L1. Both an EGF-neutralizing antibody and cetuximab (EGF receptor [EGFR] monoclonal antibody) inhibited platelet-induced increases in tumor cell PD-L1, suggesting that platelets induce tumor cell PD-L1 in an EGFR-dependent manner. Our data reveal a novel mechanism for platelets in tumor immune escape and warrant further investigation to determine if targeting platelets improves ICI therapeutic responses.
Dexmedetomidine attenuates oxygen-glucose deprivation/ reperfusion-induced inflammation through the miR-17-5p/ TLR4/ NF-κB axis
Authors: Suo Liangyuan , Wang Mingyu 
Published: April 2022

Abstract
Background
Dexmedetomidine (DEX) is a selective agonist of α2-adrenergic receptors with anesthetic activity and neuroprotective benefits. However, its mechanism of action at the molecular level remains poorly defined. In this study, we investigated the protective effects of DEX on oxygen-glucose deprivation/ reperfusion (OGD/R)-induced neuronal apoptosis in PC12 cells, and evaluated its underlying mechanism(s) of neuroprotection and anti-inflammation.

Methods
An OGD/R model in PC12 cells was established. PC12 cells were cultured and divided into control, OGD/R, and OGD/R + DEX (1 μM, 10 μM, 50 μM) groups. Cell apoptosis was analyzed by flow cytometry and expression profiles were determined by qRT-PCR, western blot analysis, and enzyme linked immunosorbent assays (ELISA). The interaction between miRNA and its downstream targets was evaluated through luciferase reporter assays.

Results
DEX significantly decreased apoptosis rates and inhibited interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) release (P < 0.05). While expression of the pro-apoptotic proteins Bax and Caspase-3 was down-regulated, expression of Bcl-2 was upregulated in a dose-dependent manner (P < 0.05). Interestingly, miR-17-5p expression was down-regulated in the OGD/R group (compared to controls). Toll-like receptor 4 (TLR4), a key regulator of nuclear factor kappa-B (NF-κB) signaling, was identified as a novel target of miR-17-5p in PC12 cells. miR-17-5p expression was upregulated in the OGD/R + DEX group, suppressing TLR4 expression and reducing the secretion of proinflammatory cytokines.

Conclusion
DEX inhibits OGD/R-induced inflammation and apoptosis in PC12 cells by increasing miR-17-5p expression, downregulating TLR4, and inhibiting NF-κB signaling.
National trend in heart failure hospitalization and outcome under public health insurance system in Thailand 2008–2013
Authors: Janwanishstaporn Satit , Karaketklang Khemajira , Krittayaphong Rungroj 
Published: April 2022

Abstract
Background
There are limited data on the burden, characteristics, and outcomes of hospitalized heart failure (HF) patients in Thailand. The aim of this study was to investigate national trend in HF hospitalization rate, in-hospital and 1-year mortality rate, and rehospitalization rate in Thailand.

Methods
We analyzed the claims data of hospitalized patients obtained from the three major Thailand public health reimbursement systems between 2008 and 2013. Patients aged ≥ 18 years with a principal diagnosis of HF by the International Classification of Diseases, Tenth Revision, Thai modification were included. Comorbidities were identified by secondary diagnosis codes. The annual rate of HF hospitalization was calculated per 100,000 beneficiaries. Records of subsequent hospitalization of discharged patients were retrieved. For 1-year mortality rate, vital status of each patient was obtained from Thai Civil Registration of Death database. All outcomes were tested for linear trends across calendar years.

Results
Between 2008 and 2013, 434,933 HF hospitalizations were identified. The mean age was 65.3 years (SD 14.6), and 58.1% were female. The HF hospitalization rate increased from 138 in 2008 to 168 per 100,000 beneficiaries in 2013 (P for trend < 0.001). Nearly half (47.4%) had had a prior HF admission within 1 year. A small proportion of patients (7.4%) received echocardiography during hospitalization. The median length of hospital stay was 3 days. In-hospital mortality declined from 4.4 to 3.8% (P for trend < 0.001). The overall 30-day and 1-year rehospitalization rates were 34 and 73%, respectively, without significant trends over the study period. Most common cause of 30-day rehospitalization was HF (42%). One-year mortality decreased from 31.8% in 2008 to 28.5% in 2012 (P for trend < 0.001).

Conclusion
Between 2008 and 2013, HF hospitalization rate in Thailand increased. The in-hospital and 1-year mortality rates decreased slightly. However, the rehospitalization rate remained high mainly due to recurrent HF hospitalization.
Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database
Authors: Chomistek Andrea K. , Liang Caihua , Doherty Michael C. , Clifford C. Robin , Ogilvie Rachel P. , Gately Robert V. , Song Jennifer N. , Enger Cheryl , Lin Nancy D. , Wang Florence T. , Seeger John D. 
Published: April 2022

Abstract
Background
There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S. population. The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19.

Methods
This was a cohort study using data from Optum’s longitudinal COVID-19 electronic health record database derived from a network of healthcare provider organizations across the US. The study included patients with confirmed COVID-19 (presence of ICD-10-CM code U07.1 and/or positive SARS-CoV-2 test) between January 2020 and November 2020. Patient characteristics and clinical variables at start of hospitalization were evaluated for their association with subsequent serious outcomes (critical care, mechanical ventilation, and death) using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, adjusted for demographic variables.

Results
Among 56,996 hospitalized COVID-19 patients (49.5% male and 72.4% ≥ 50 years), 11,967 received critical care, 9136 received mechanical ventilation, and 8526 died. The median duration of hospitalization was 6 days (IQR: 4, 11), and this was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Dyspnea and hypoxemia were the most prevalent symptoms and both were associated with serious outcomes in adjusted models. Additionally, temperature, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and oxygen saturation measured during hospitalization were predictors of serious outcomes as were several in-hospital diagnoses. The strongest associations were observed for acute respiratory failure (critical care: OR, 6.30; 95% CI, 5.99–6.63; ventilation: OR, 8.55; 95% CI, 8.02–9.11; death: OR, 3.36; 95% CI, 3.17–3.55) and sepsis (critical care: OR, 4.59; 95% CI, 4.39–4.81; ventilation: OR, 5.26; 95% CI, 5.00–5.53; death: OR, 4.14; 95% CI, 3.92–4.38). Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during hospitalization were inversely associated with death (OR, 0.57; 95% CI, 0.54–0.61).

Conclusions
We identified several clinical characteristics associated with receipt of critical care, mechanical ventilation, and death among COVID-19 patients. Future studies into the mechanisms that lead to severe COVID-19 disease are warranted.
Adapting MultiPLe behavior Interventions that eFfectively Improve (AMPLIFI) cancer survivor health: program project protocols for remote lifestyle intervention and assessment in 3 inter-related randomized controlled trials among survivors of obesity-related cancers
Authors: Pekmezi Dori , Fontaine Kevin , Rogers Laura Q. , Pisu Maria , Martin Michelle Y. , Schoenberger-Godwin Yu-Mei , Oster Robert A. , Kenzik Kelly , Ivankova Nataliya V. , Demark-Wahnefried Wendy 
Published: April 2022

Abstract
Background
Scalable, multiple behavior change interventions are needed to address poor diet, inactivity, and excess adiposity among the rising number of cancer survivors. Efficacy-tested diet (RENEW) and exercise (BEAT Cancer) programs were adapted for web delivery among middle-aged and older cancer survivors for the AMPLIFI study, a National Cancer Institute-funded, multi-site, program project.

Methods
Throughout the continental U.S., survivors of several obesity-related cancers are being recruited for three interconnected randomized controlled trials (RCTs). Projects 1 and 2 test 6-month diet or exercise interventions versus a wait-list control condition. Upon completion of the 6-month study period, the intervention participants receive the next behavior change sequence (i.e., diet receives exercise, exercise receives diet) and the wait-list control arm initiates a 12-month combined diet and exercise intervention. Project 3 tests the efficacy of the sequential versus simultaneous interventions. Assessments occur at baseline and semi-annually for up to 2-years and include: body mass index, health behaviors (diet quality, accelerometry-assessed physical activity/sleep), waist circumference, D3 creatine-assessed muscle mass, physical performance, potential mediators/moderators of treatment efficacy, biomarkers of inflammation and metabolic regulation, health care utilization, cost, and overall health. Four shared resources support AMPLIFI RCTs: 1) Administrative; 2) Adaptation, Dissemination and Implementation; 3) Recruitment and Retention; and 4) Assessment and Analysis.

Discussion
Representing a new generation of RCTs, AMPLIFI will exclusively use remote technologies to recruit, intervene and assess the efficacy of the newly-adapted, web-based diet and exercise interventions and determine whether sequential or combined delivery works best for at-risk (older, rural, racial minority) cancer survivors.

Trial registration
ClinicalTrials.gov, NCT04000880. Registered 27 June 2019.
Comparison of music and vapocoolant spray in reducing the pain of venous cannulation in children age 6-12: a randomized clinical trial
Authors: Ghasemi Masoomeh , Hoseinialiabadi Poria , Yazdanpanah Fatemeh , Mahani Maryam Askaryzadeh , Malekyan Leila , Najafi Kazem , Arab Mohammadreza , Arab Mansour , Ranjbar Hadi 
Published: April 2022

Abstract
Background
Venous cannulation is among the most stressful and painful experiences of children hospitalization. Children with thalassemia need regular blood transfusion which needs venous access each time. The quality of care and quality of life of children will be improved if appropriate methods are used to reduce pain. This study aimed to compare vapocoolant spray and music in the reduction of pain of Venous cannulation in children with thalassemia.

Methods
The study was a randomized controlled clinical trial with a cross-over design. Thirty-six children with thalassemia from Thalassemia Patients of Pasteur Hospital in Bam from October to December 2020 and were recruited and randomly allocated to two arms. The pain of venous cannulation (no treatment) was measured in the first blood transfusion session as control. In the second and third sessions, two arms received music and vapocoolant spray before the venous cannulation with a cross-over design. The intensity of pain was measured by a Visual Analogue Scale (VAS). The change in pain scores was tested by ANOVA and Tukey post-hoc test between three measurements.

Results
During and after the cannulation, the pain was significantly lower in the vapocoolant measurement than in control and music (p < 0.05). There was a significant effect of vapocoolant spray during the procedure F (2, 90) = 25.604, p = 0.001. Also, there was a significant effect of vapocoolant spray after the procedure F (2, 90) = 10.087, p = 0.004). Music did not reduce the pain during cannulation (p = 0.413) and after that (p = 0.807) significantly when compared with control.

Conclusions
Vapocoolant was an effective method of pain reduction in the reduction of venous cannulation pain. Music was not effective in the reduction of venous cannulation pain when we compared it with controls. The pain of venous cannulation is rated as high and it can have negative effects on the children. There is a need to do more research on the methods of pain reduction of venous cannulation.

Trial registration
The trial is registered: IRCT20111019007844N13, 13/03/2020. Available at: https://en.irct.ir/trial/42904.
Maternal stress, child behavior and the promotive role of older siblings
Authors: Amici Federica , Röder Stefan , Kiess Wieland , Borte Michael , Zenclussen Ana C. , Widdig Anja , Herberth Gunda 
Published: April 2022

AbstractBackgroundIn the first years of their lives, children develop the cognitive, social and emotional skills that will provide the foundations for their lifelong health and achievements. To increase their life prospects and reduce the long-term effects of early aversive conditions, it is therefore crucial to understand the risk factors that negatively affect child development and the factors that are instead beneficial. In this study, we tested (i) the effects of different social and environmental stressors on maternal stress levels, (ii) the dynamic relationship between maternal stress and child behavior problems during development, and (iii) the potential promotive (i.e. main) or protective (i.e. buffering) effect of siblings on child behavior problems during development.MethodsWe used longitudinal data from 373 mother–child pairs (188 daughters, 185 sons) from pregnancy until 10 years of age. We assessed maternal stress and child behavior problems (internalizing and externalizing) with validated questionnaires, and then used linear mixed models, generalized linear mixed models and longitudinal cross-lagged models to analyze the data.ResultsOur results showed that higher maternal stress levels were predicted by socio-environmental stressors (i.e. the lack of sufficient social areas in the neighborhood). Moreover, prenatal maternal stress reliably predicted the occurrence of behavior problems during childhood. Finally, the presence of older siblings had a promotive function, by reducing the likelihood that children developed externalizing problems.ConclusionsOverall, our results confirm the negative effects that maternal stress during pregnancy may have on the offspring, and suggest an important main effect of older siblings in promoting a positive child development.
Impact of anxiety and depression on the prognosis of copd exacerbations
Authors: Martínez-Gestoso Sandra , García-Sanz María-Teresa , Carreira José-Martín , Salgado Francisco-Javier , Calvo-Álvarez Uxío , Doval-Oubiña Liliana , Camba-Matos Sandra , Peleteiro-Pedraza Lorena , González-Pérez Miguel-Angel , Penela-Penela Pedro , Vilas-Iglesias Andrés , González-Barcala Francisco-Javier 
Published: April 2022

AbstractBackgroundFrequent and highly prevalent as comorbidities in Chronic Obstructive Pulmonary Disease (COPD) patients, both depression and anxiety seem to have an impact on COPD prognosis. However, they are underdiagnosed and rarely treated properly.AimTo establish the prevalence of depression and anxiety in patients admitted for Acute Exacerbation of COPD (AECOPD) and determine their influence on COPD prognosis.MethodsProspective observational study conducted from October 1, 2016 to October 1, 2018 at the following centers in Galicia, Spain: Salnés County Hospital, Arquitecto Marcide, and Clinic Hospital Complex of Santiago de Compostela. Patients admitted for AECOPD who agreed to participate and completed the anxiety and depression scale (HADS) were included in the study.Results288 patients (46.8%) were included, mean age was 73.7 years (SD 10.9), 84.7% were male. 67.7% patients were diagnosed with probable depression, and depression was established in 41.7%; anxiety was probable in 68.2% and established in 35.4%. 60.4% of all patients showed symptoms of both anxiety and depression. Multivariate analysis relates established depression with a higher risk of late readmission (OR 2.06, 95% CI 1.28; 3.31) and a lower risk of mortality at 18 months (OR 0.57, 95% CI 0.37; 0.90).ConclusionThe prevalence of anxiety and depression in COPD patients is high. Depression seems to be an independent factor for AECOPD, so early detection and a multidisciplinary approach could improve the prognosis of both entities. The study was approved by the Ethical Committee of Galicia (code 2016/460).
“My life became more meaningful”: confronting one’s own end of life and its effects on well-being—a qualitative study
Authors: Kukla Helena , Herrler Angélique , Strupp Julia , Voltz Raymond 
Published: April 2022

Abstract
Background
The perception of being closer to death can be experienced due to old age or life-limiting diseases, and can pose profound existential challenges. Actively confronting death-related issues and existential questions may increase psychosocial comfort and stimulate personal growth, whereas dysfunctional coping may lead to existential distress.
To date, research on individual and (semi-)professional approaches to confronting the own end of life and the effects on one’s well-being remain scarce. Therefore, the aim of this study was to explore individual strategies and wishes in order to derive ideas for appropriate support concepts.

Methods
Twenty semi-structured interviews were conducted with people over the age of 80 (n = 11) and with a life-limiting disease (n = 10). The interviews were transcribed verbatim and independently coded by two researchers according to Braun and Clarke's thematic analysis approach.

Results
While the use of (semi-)professional approaches (e.g., therapeutic support) to confronting existential questions in the shape of one’s impending death was rare, individual coping strategies did have a positive impact on psychosocial comfort. There were hardly any significant differences between the participants aged 80 and over and those with a life-limiting disease in terms of individual coping strategies or how they approached the ends of their lives. Both groups reported that theoretical education, preparing for the ends of their lives (e.g., funerals), talking about death-related topics, reflecting on death-related topics, and contemplating death in a spiritual sense had positive effects on their assurance, self-determination and relief. The necessity of confrontation and a desire for low-threshold, accessible and flexible services to meet their existential and spiritual needs were highlighted.

Conclusions
There is both a desire and a need for the addressing of existential questions. Outside of private contexts, however, the participants possessed little awareness of support services that focused on confronting end-of-life issues, and rarely used such services. Efforts to raise awareness for psychosocial and spiritual needs should be implemented within the care system, together with low-threshold support concepts, in order to increase psychosocial well-being. More research evaluating individual approaches to confronting the own end of life are needed to better understand this determinant of well-being and its mechanisms of action.

Trial registration
www.germanctr.de, DRKS-ID: DRKS00020577.