bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI
Authors: Schultze-Florey Christian R. , Kuhlmann Leonie , Raha Solaiman , Barros-Martins Joana , Odak Ivan , Tan Likai , Xiao Yankai , Ravens Sarina , Hambach Lothar , Venturini Letizia , Stadler Michael , Eder Matthias , Thol Felicitas , Heuser Michael , Förster Reinhold , Ganser Arnold , Prinz Immo , Koenecke Christian 
Published: September 2021

Abstract
Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells. Therefore, we analyzed the dynamics of CD8+ αβ T-cell clones in patients with DLI. In this prospective clinical study of 29 patients, we performed deep T-cell receptor β (TRB ) sequencing of sorted CD8+ αβ T cells to track patients’ repertoire changes in response to DLI. Upon first occurrence of GVL, longitudinal analyses revealed a preferential expansion of distinct CD8+TRB clones (n = 14). This did not occur in samples of patients without signs of GVL (n = 11). Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36-month study follow-up. Furthermore, absence of clonal outgrowth of the CD8+TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11.2 months ahead of actual diagnosis. Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+TRB diversity at day 15 after DLI (n = 13) had a lower relapse incidence (P = .0040) compared with patients without clonal expansion (n = 6). In conclusion, CD8+TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.
Circular RNA-0007059 protects cell viability and reduces inflammation in a nephritis cell model by inhibiting microRNA-1278/SHP-1/STAT3 signaling
Authors: Guo Peng-Wei , Huang Hai-Ting , Ma Jing , Zuo Yao , Huang Dan , He Lin-Lin , Wan Zi-Ming , Chen Cheng , Yang Fa-Fen , You Yan-Wu 
Published: September 2021

Abstract
Background
Increasing evidence has indicated that circular RNAs (circRNAs) play a role in various diseases. However, the influence of circRNAs in nephritis remains unknown.

Methods
Microarray analysis and RT-qPCR were used to detect the expression of circRNA. Type I IFN were administrated to RMC and HEK293 cells to establish a nephritis cell model. CCK-8, MTT assay, and flow cytometry were used to assess cell proliferation, viability, and apoptosis of cells. Bioinformatics analysis and dual luciferase reporter assay detect the interaction of circ_0007059, miRNA-1278, and SHP-1. Glomerulonephritis was performed in a mouse model by administration of IFNα-expressing adenovirus. IHC staining showed the pathogenic changes.

Results
In the present study, the expression of circ_0007059 in type I interferon (IFN)-treated renal mesangial cells (RMCs), lupus nephritis (LN) specimens, and HEK293 cells was downregulated compared with that in normal healthy samples and untreated cells. Circ_0007059 overexpression resulted in increased cell proliferation, cell viability, apoptosis, and inflammation-associated factors (CXCL10, IFIT1, ISG15, and MX1) in RMCs and HEK293 cells. In addition, circ_0007059 overexpression significantly restored cell proliferation and viability and inhibited IFN-induced apoptosis. Further, the increased expression resulted in reduced inflammation and the downregulation of CXCL10, IFIT1, ISG15, and MX1 in RMCs and HEK293 cells. Circ_0007059 serves as a sponge for miR-1278 so that the latter can target the 3′-untranslated region of SHP-1. Overexpressed circ_0007059 inhibited miR-1278 expression and elevated SHP-1 expression, subsequently reducing STAT3 phosphorylation. Meanwhile, miR-1278 was upregulated and SHP-1 was downregulated in LN samples and IFN-treated cells. The restoration of miR-1278 counteracted the effect of circ_0007059 on viability, apoptosis, and inflammation as well as on SHP-1/STAT3 signaling in RMCs and HEK293 cells. We also investigated the role of SHP-1 overexpression in IFN-treated RMCs and HEK293 cells; SHP-1 overexpression resulted in a similar phenotype as that observed with circ_0007059 expression.

Conclusions
The study indicates that circ_0007059 protects RMCs against apoptosis and inflammation during nephritis by attenuating miR-1278/SHP-1/STAT3 signaling.
Boolean factor graph model for biological systems: the yeast cell-cycle network
Authors: Kotiang Stephen , Eslami Ali 
Published: September 2021

AbstractBackgroundThe desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological entities. Here, we consider the general question of the effect of perturbation on the global dynamical network behavior as well as error propagation in biological networks to incite research pertaining to intervention strategies.ResultsThis paper introduces a computational framework that combines the formulation of Boolean networks and factor graphs to explore the global dynamical features of biological systems. A message-passing algorithm is proposed for this formalism to evolve network states as messages in the graph. In addition, the mathematical formulation allows us to describe the dynamics and behavior of error propagation in gene regulatory networks by conducting a density evolution (DE) analysis. The model is applied to assess the network state progression and the impact of gene deletion in the budding yeast cell cycle. Simulation results show that our model predictions match published experimental data. Also, our findings reveal that the sample yeast cell-cycle network is not only robust but also consistent with real high-throughput expression data. Finally, our DE analysis serves as a tool to find the optimal values of network parameters for resilience against perturbations, especially in the inference of genetic graphs.ConclusionOur computational framework provides a useful graphical model and analytical tools to study biological networks. It can be a powerful tool to predict the consequences of gene deletions before conducting wet bench experiments because it proves to be a quick route to predicting biologically relevant dynamic properties without tunable kinetic parameters.
Capnometric feedback training decreases 24-h blood pressure in hypertensive postmenopausal women
Authors: Anderson David E. , Reeves Alexis N. , Mehling Wolf E. , Chesney Margaret A. 
Published: September 2021

AbstractBackgroundHigh normal resting pCO2is a risk factor for salt sensitivity of blood pressure (BP) in normotensive humans and has been associated with higher resting systolic BP in postmenopausal women. To date, however, no known studies have investigated the effects of regular practice of voluntary mild hypocapnic breathing on BP in hypertensive patients. The objective of the present research was to test the hypothesis that capnometric feedback training can decrease both resting pCO2and 24-h BP in a series of mildly hypertensive postmenopausal women.MethodsA small portable end tidal CO2(etCO2) monitor was constructed and equipped with software that determined the difference between the momentary etCO2and a pre-programmed criterion range. The monitor enabled auditory feedback for variations in CO2outside the criterion range. 16 mildly hypertensive postmenopausal women were individually trained to sustain small decreases in etCO2during six weekly sessions in the clinic and daily sessions at home. 24-h BP monitoring was conducted before and after the intervention, and in 16 prehypertensive postmenopausal women in a control group who did not engage in the capnometric training.ResultsFollowing the intervention, all 16 capnometric training participants showed decreases in resting etCO2(− 4.3 ± 0.4 mmHg;p < .01) while 15 showed decreases in 24-h systolic BP (− 7.6 ± 2.0 mmHg;p < .01). No significant changes in either measure was observed in the control group. In addition, nighttime (− 9.5 ± 2.6;p < .01) and daytime (− 6.7 ± 0.2 mmHg) systolic BP were both decreased following capnometric training, while no significant changes in nighttime (− 2.8 ± 2.2 mmHg;p = .11) or daytime (− 0.7 ± 1.0 mmHg;p ≤ .247) systolic BP were observed in the control group.ConclusionsThese findings support the hypothesis that regular practice of mild hypocapnic breathing that decreases resting etCO2reliably decreases 24-h blood pressure in hypertensive postmenopausal women. The extent to which these effects persist beyond the training period or can be observed in other hypertensive subgroups remains to be investigated.
Mastery of type 2 diabetes prevention and treatment knowledge by general practitioners in Shanghai: a cross-sectional study
Authors: Li Yaling , Yan Yunyun , Dai Huimin , Cheng Yuan , Huang Qian , Shao Jie , Zhou Jianmin , Wang Haitang , Liu Pingyang , Shen Ao , Mi Yikai , Du Zhaohui 
Published: September 2021

Abstract
Background
To study the competency of general practitioners (GPs) in Shanghai, China on prevention and management of type 2 diabetes, also understand factors that may prohibit it.

Methods
A survey questionnaire with 25 questions was designed based on 2013 Chinese Type 2 Diabetes Prevention Guidelines and Chinese Type 2 Diabetes Prevention Guidelines (Grassroots Edition) and conducted among 789 GPs who work at 54 community healthcare centers (CHCs) within 16 districts at Shanghai, China. Excel 2016 and SPSS 24.0 were used for data analysis, and a difference of P < 0.05 was considered to be statistically significant.

Results
The GPs did poorly on three aspect of diabetes prevention and treatment: (1) treatment goals in elderly patients, (2) screening methods for high-risk population, and (3) aspirin contraindications. The statistical analysis data showed that GPs who finished standardized training had correct answer on 13.58 ± 3.31 questions out of total 25, with mean accuracy rate of 54.32%. Except the questions for high-risk population screening method and the diagnostic criteria for type 2 diabetes, there was no difference in the accuracy of other questions between GPs with or without standardized training (P < 0.05). However, sex, educational level, and subspecialty experience are affective factors on their competency in type 2 diabetes prevention and treatment knowledge.

Conclusion
The results indicated that communities should strengthen the training of GPs in diabetes management and bidirectional referral. Frequent continuing education and skills training should be provided among GPs at CHCs to ensure their competency of type 2 diabetes prevention and treatment knowledge after obtaining their GP license disregard of their standardized training. In addition, attention should be paid to GPs who had lower education background or non-clinical subspecialty experience to strengthen their clinical knowledge of type 2 diabetes.
What about the others: differential diagnosis of COVID-19 in a German emergency department
Authors: Fistera David , Härtl Annalena , Pabst Dirk , Manegold Randi , Holzner Carola , Taube Christian , Dolff Sebastian , Schaarschmidt Benedikt Michael , Umutlu Lale , Kill Clemens , Risse Joachim 
Published: September 2021

Abstract
Background
The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging.

Method
We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs.

Results
Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014).

Conclusion
For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections.
Trial registration: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.
Acute ischemic stroke with cervical internal carotid artery steno-occlusive lesion: multicenter analysis of endovascular approaches
Authors: Cirillo Luigi , Romano Daniele Giuseppe , Vornetti Gianfranco , Frauenfelder Giulia , Tamburrano Chiara , Taglialatela Francesco , Isceri Salvatore , Saponiero Renato , Napoletano Rosa , Gentile Mauro , Romoli Michele , Princiotta Ciro , Simonetti Luigi , Zini Andrea 
Published: September 2021

AbstractBackgroundOcclusion of the internal carotid artery (ICA), whether isolated or in the setting of a tandem lesion (TL) have a poor response to treatment with intravenous thrombolysis. Previous studies ​​have demonstrated the superiority of mechanical thrombectomy in the treatment of acute ischemic stroke (AIS) following large vessel occlusion, compared to standard intravenous fibrinolysis. The aim of our study was to describe endovascular treatment (EVT) in AIS due to isolated ICA occlusion or TL.MethodsWe assessed the association between 90-day outcome and clinical, demographic, imaging, and procedure data in 51 consecutive patients with acute isolated ICA occlusion or TL who underwent EVT. We evaluated baseline NIHSS and mRS, ASPECTS, type of occlusion, stent placement, use of stent retrievers and/or thromboaspiration, duration of the procedure, mTICI, postprocedural therapy and complications.ResultsA favorable 90-day outcome (mRS 0–2) was achieved in 34 patients (67 %) and was significantly associated with the use of dual antiplatelet therapy after the procedure (p = 0.008), shorter procedure duration (p = 0.031), TICI 2b-3 (p < 0.001) and lack of post-procedural hemorrhagic transformation (p = 0.001). Four patients did not survive, resulting in a mortality rate of 8 %.ConclusionsOur study has shown that EVT in the treatment of AIS due to ICA occlusion is safe, and effective in determining a good functional outcome. ICA stenting led to good angiographic results and therapy with a glycoprotein IIb / IIIa inhibitor immediately after stent release did not result in a greater risk of hemorrhage. The use of post-procedural dual antiplatelet therapy was associated with favorable outcome, without a significant increase in hemorrhagic transformation.
Acute relaxation during pregnancy leads to a reduction in maternal electrodermal activity and self-reported stress levels
Authors: Bauer Ilena , Hartkopf Julia , Wikström Anna-Karin , Schaal Nora K. , Preissl Hubert , Derntl Birgit , Schleger Franziska 
Published: September 2021

Abstract
Background
Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women.

Methods
In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels.

Results
All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, ηp2 = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, ηp2 = .128.

Conclusion
Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxation after the intervention than women later in gestation. Hence, gestational age may influence perceived stress levels and should be considered when evaluating relaxation or stress management interventions during pregnancy.

Trial registration
Not applicable.
Evaluating satisfaction with the quality and provision of end-of-life care for patients from diverse ethnocultural backgrounds
Authors: Nayfeh Ayah , Yarnell Christopher J. , Dale Craig , Conn Lesley Gotlib , Hales Brigette , Gupta Tracey Das , Chakraborty Anita , Pinto Ruxandra , Taggar Ru , Fowler Robert 
Published: September 2021

Abstract
Background
Recently immigrated and ethnic minority patients in Ontario, Canada are more likely to receive aggressive life-prolonging treatment at the end of life in comparison to other patients. To explore this finding further, this survey-based observational study aimed to evaluate satisfaction with the quality of end-of-life care for patients from diverse ethnocultural backgrounds.

Methods
The End-of-Life Satisfaction Survey was used to measure satisfaction with the quality of inpatient end-of-life care from the perspective of next-of-kin of recently deceased patients at Sunnybrook Health Sciences Centre in Toronto, Ontario (between March 2012 to May 2019). The primary outcome was the global rating of satisfaction. Associations with patient ethnicity, patient religion, level of religiosity/spirituality, language/communication barriers, and location of death were assessed using univariable and multivariable modified Poisson regression. Secondary outcomes included differences in satisfaction and rates of dying in intensive care units (ICU) among patient population subgroups, and identification of high priority areas for quality-of-care improvement.

Results
There were 1,543 respondents. Patient ethnicities included Caucasian (68.2%), Mediterranean (10.5%), East Asian (7.6%), South Asian (3.5%), Southeast Asian (2.1%) and Middle Eastern (2.0%); religious affiliations included Christianity (66.6%), Judaism (12.3%) and Islam (2.1%), among others. Location of death was most commonly in ICU (38.4%), hospital wards (37.0%) or long-term care (20.0%). The mean(SD) rating of satisfaction score was 8.30(2.09) of 10. After adjusting for other covariates, satisfaction with quality of end-of-life care was higher among patients dying in ICU versus other locations (relative risk [RR] 1.51, 95%CI 1.05-2.19, p=0.028), lower among those who experienced language/communication barriers (RR 0.49 95%CI 0.23-1.06, p=0.069), and lower for Muslim patients versus other religious affiliations (RR 0.46, 95%CI 0.21-1.02, p=0.056). Survey items identified as highest priority areas for quality-of-care improvement included communication and information giving; illness management; and healthcare provider characteristics such as emotional support, doctor availability and time spent with patient/family.

Conclusion
Satisfaction with quality-of-care at the end of life was higher among patients dying in ICU and lower among Muslim patients or when there were communication barriers between families and healthcare providers. These findings highlight the importance of measuring and improving end-of-life care across the ethnocultural spectrum.
Economic burden of comorbid chronic conditions among survivors of stroke in China: 10-year longitudinal study
Authors: Zhang Ji , Song Suhang , Zhao Yang , Ma Gaoting , Jin Yinzi , Zheng Zhi-Jie 
Published: September 2021

Abstract
Background
The coexistence of chronic diseases among people with stroke is common. However, little is known about the extent of incremental healthcare expenditures associated with having physically and psychologically chronic conditions among stroke survivors.

Methods
We used the nationally representative data from the China Health and Nutrition Survey, including 36,076 participants enrolled as our analytic cohort of ten years of follow-up visits (2006, 2009, 2011, 2015). Chronic conditions include hypertension, diabetes, obesity, and impaired cognitive function. Two-part models were used to estimate the effect of comorbid chronic conditions on total annual healthcare expenditure, out-of-pocket (OOP) healthcare expenditure, and incidence of catastrophic healthcare expenditure (CHE).

Results
Among survivors of stroke during 2006 to 2015, the prevalence rates of hypertension, diabetes, obesity and impaired cognitive function were 75.5, 9.8, 12.7 and 65.1%, significantly higher than those among adults without stroke history (27.9, 2.7, 10.0 and 41.2%). Having hypertension ($794.5, p = 0.004), diabetes ($3978.5, p < 0.001) were associated with the largest incremental total healthcare expenditures. Stroke survivors with diagnosed hypertension and diabetes had additional 5.7 (p < 0.001) and 10.4 (p < 0.001) percentage point of CHE rate, respectively. Total healthcare expenditures were $2413.0 (P < 0.001) and $5151.7 (P < 0.001) higher among patients with 2, and ≥ 3 chronic conditions, respectively, than those individuals with no chronic conditions.

Conclusions
Excess expenditures associated with chronic diseases were substantial among stroke survivors. These results highlight the needs for both prevention and better management of multimorbidity among stroke survivors, which in turn may lower the financial burden of treating these concurrent comorbidities.