bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of patients with severe covid-19 with diabetes
Authors: Yan Yongli , Yang Yan , Wang Fen , Ren Huihui , Zhang Shujun , Shi Xiaoli , Yu Xuefeng , Dong Kun 
Published: April 2020

ObjectiveThis study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19.Research design and methodsIn this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO2/FiO2≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU).ResultsOf 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%)vs9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively.ConclusionThe mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.
Predictive value of integrated18F-FDG PET/MRI in the early response to nivolumab in patients with previously treated non-small cell lung cancer
Authors: Umeda Yukihiro , Morikawa Miwa , Anzai Masaki , Ameshima Shingo , Kadowaki Maiko , Waseda Yuko , Shigemi Hiroko , Tsujikawa Tetsuya , Kiyono Yasushi , Okazawa Hidehiko , Ishizuka Tamotsu 
Published: April 2020

BackgroundThe early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI (18F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC).MethodsTwenty-five patients with previously treated NSCLC were enrolled prospectively and underwent18F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy.ResultsThe disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADCmean(ie, negative ΔADCmean) and lower ΔTLG+ΔADCmeanthan patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADCmeanhad the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADCmeanvalue <16.5 was significantly associated with longer median progression-free survival (9.0 vs 1.8 months, p<0.00001) and overall survival (23.6 vs 4.7 months, p=0.0001) compared with ΔTLG+ΔADCmeanvalue ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADCmeanwas an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29).ConclusionsA combination of ΔTLG and ΔADCmeanmeasured by integrated18F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy.Trial registration numberUMIN 000020707.
The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a
Authors: Peluso Marisa O , Adam Ammar , Armet Caroline M , Zhang Li , O’Connor Rachel W , Lee Benjamin H , Lake Andrew C , Normant Emmanuel , Chappel Scott C , Hill Jonathan A , Palombella Vito J , Holland Pamela M , Paterson Alison M 
Published: April 2020

BackgroundCD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction with the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily expressed on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and immune cell homeostasis). CD47/SIRPα antagonists, commonly referred to as ‘macrophage checkpoint’ inhibitors, are being developed as cancer interventions. SRF231 is an investigational fully human IgG4anti-CD47 antibody that is currently under evaluation in a phase 1 clinical trial. The development and preclinical characterization of SRF231 are reported here.MethodsSRF231 was characterized in assays designed to probe CD47/SIRPα blocking potential and effects on red blood cell (RBC) phagocytosis and agglutination. Additionally, SRF231-mediated phagocytosis and cell death were assessed in macrophage:tumor cell in vitro coculture systems. Further mechanistic studies were conducted within these coculture systems to ascertain the dependency of SRF231-mediated antitumor activity on Fc receptor engagement vs CD47/SIRPα blockade. In vivo, SRF231 was evaluated in a variety of hematologic xenograft models, and the mechanism of antitumor activity was assessed using cytokine and macrophage infiltration analyses following SRF231 treatment.ResultsSRF231 binds CD47 and disrupts the CD47/SIRPα interaction without causing hemagglutination or RBC phagocytosis. SRF231 exerts antitumor activity in vitro through both phagocytosis and cell death in a manner dependent on the activating Fc-gamma receptor (FcγR), CD32a. Through its Fc domain, SRF231 engagement with macrophage-derived CD32a serves dual purposes by eliciting FcγR-mediated phagocytosis of cancer cells and acting as a scaffold to drive CD47-mediated death signaling into tumor cells. Robust antitumor activity occurs across multiple hematologic xenograft models either as a single agent or in combination with rituximab. In tumor-bearing mice, SRF231 increases tumor macrophage infiltration and induction of the macrophage cytokines, mouse chemoattractant protein 1 and macrophage inflammatory protein 1 alpha. Macrophage depletion results in diminished SRF231 antitumor activity, underscoring a mechanistic role for macrophage engagement by SRF231.ConclusionSRF231 elicits antitumor activity via apoptosis and phagocytosis involving macrophage engagement in a manner dependent on the FcγR, CD32a.
Effects of high-intensity intervals and moderate-intensity exercise on baroreceptor sensitivity and heart rate variability during recovery
Authors: Burma Joel S. , Copeland Paige V. , Macaulay Alannah , Khatra Omeet , Smirl Jonathan D. 
Published: April 2020

Numerous studies have examined heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) variables during recovery both acutely (under 3 h) and long-term (24, 48, and 72 h) postexercise. However, there is little literature examining HRV and BRS measures between these timepoints. Spontaneous short-term HRV and cardiac BRS measures were collected in 9 participants before and at zero, 1, 2, 4, 6, and 8 h after 3 separate conditions: moderate-intensity continuous exercise (MICE; 45 min at 50% heart rate reserve), high-intensity interval exercise (HIIE; 25 min including ten 1-min intervals at 85% heart rate reserve), and control (30 min quiet rest). HRV measures in the time domain were only affected immediately following HIIE and MICE at hour zero (all p < 0.043), whereas frequency-domain metrics were unaltered (all p > 0.102). These measures were highly consistent across the control day (all p > 0.420). Cardiac BRS was assessed via low-frequency (LF) gain, and revealed reductions following HIIE at hour zero (p < 0.012). Cardiac BRS LF gain remained consistent following MICE and control interventions (all p > 0.280). The common practice of waiting 12 to 24 h is overly conservative as the current findings demonstrate measures return to baseline at ∼60 min after exercise. Moreover, these metrics demonstrated high levels of within- and between-day reliability. Novelty Previously a 12-h minimum restriction from exercise was required before participation in HRV/BRS studies. Recovery from moderate-intensity exercise for HRV and BRS metrics was <60 min; whereas, high-intensity intervals led to alterations for approximately 60 min. Spontaneous HRV and cardiac BRS demonstrated high levels of within-day reproducibility.
Long baseline neutrino oscillation experiments with accelerators in Japan
Authors: Nakaya Tsuyoshi , Nishikawa Koichiro 
Published: April 2020

AbstractThe development of long baseline neutrino oscillation experiments with accelerators in Japan is reviewed. Accelerator experiments can optimize experimental conditions, such as the beam and the detector, as needed. The evidence of neutrino oscillations observed in atmospheric neutrinos was confirmed by the K2K experiment. The T2K experiment discovered the oscillation channel from a muon neutrino to an electron neutrino with the squared mass difference $$\varDelta m^2 \sim 2.5 \times 10^{-3}~\mathrm{eV}^2$$Δm2∼2.5×10-3eV2, and presents a full analysis with all three flavor states of both neutrinos and anti-neutrinos. The three mixing angles, which quantify the mixing of the three neutrino states, have been measured. They are large compared to those of quarks, especially the mixing of the second and third generation which is nearly maximal. The T2K experiment has an ongoing program producing new results, and recently has shown a hint of CP violation in neutrinos. Future generation long baseline neutrino experiments beyond T2K are expected to clarify the relationship between flavor and mass, as well as measure possible CP violation in neutrino oscillations.
BTK Inhibitors in Cancer Patients with COVID-19: “The Winner Will be the One Who Controls That Chaos” (Napoleon Bonaparte)
Authors: Chong Elise A. , Roeker Lindsey E. , Shadman Mazyar , Davids Matthew S. , Schuster Stephen J. , Mato Anthony R. 
Published: April 2020

Abstract

As the SARS-CoV-2 (COVID-19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID-19-affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID-19. In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections and impaired humoral immunity. We hypothesize that the potential benefit of blunting a hyperinflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. On the basis of this, we suggest continuing BTKi in patients with COVID-19.
miR-106a Regulates Cell Proliferation and Autophagy by Targeting LKB1 in HPV-16–Associated Cervical Cancer
Authors: Cui Xiujie , Wang Xiao , Zhou Xiaoqing , Jia Jihui , Chen Hanxiang , Zhao Weiming 
Published: April 2020

Abstract

miR-106a is aberrantly regulated in various tumors and plays an important role in carcinogenesis. However, the biological role and molecular mechanism by which miR-106a contributes to cervical squamous cell carcinoma (CSCC) remains elusive. In this study, we verified that miR-106a was elevated in both human papilloma virus (HPV) 16-positive CSCC tissues and cell lines. ROC curve analysis showed that miR-106a could well distinguish HPV-16–positive CSCC tissues from normal cervical squamous epithelium tissues. High expression of miR-106a was associated with malignant clinicopathologic parameters in CSCC tissues. Exogenous expression of miR-106a greatly promoted cervical cancer cell proliferation while attenuated autophagy. Furthermore, a novel target of miR-106a, liver kinase B1 (LKB1), a proven tumor suppressor in cervical cancer was verified. Here we confirmed LKB1 was negatively correlated with malignant clinicopathologic parameters in CSCC tissues. Overexpression of LKB1 neutralized the effect of miR-106a on proliferation and autophagy in cervical cancer cell lines. In addition, the role of miR-106a in cell proliferation and autophagy was via LKB1 and its downstream pathway AMP-activated protein kinase-mammalian target of rapamycin. Of note, miR-106a was upregulated by HPV-16 E7 protein. The function of HPV-16 E7 to cell proliferation was suppressed when knockdown miR-106a in HPV-16 E7–expressing cells.

Implications:
Our study highlights the tumorigenic role and regulatory mechanism of miR-106a in CSCC. miR-106a may be a potential therapeutic target in HPV-associated cervical cancer.
Genetically Determined Birthweight Associates With Atrial Fibrillation
Authors: Kember Rachel L. , Levin Michael G. , Cousminer Diana L. , Tsao Noah , Judy Renae , Schur Gayatri M. , Lubitz Steven A. , Ellinor Patrick T. , McCormack Shana E. , Grant Struan F.A. ,   Regeneron Genetics Center, Rader Daniel J. , Voight Benjamin F. , Damrauer Scott M. 
Published: April 2020

Background:
Atrial fibrillation is a common cardiovascular disorder, characterized by irregular electrical activity in the upper chambers of the heart. Both chronic cardiometabolic risk factors and genetics have been shown to contribute to the development of atrial fibrillation. Birthweight has also been associated with risk of atrial fibrillation.

Methods:
In the current study, we utilized a genetic approach to study the effect of birthweight on atrial fibrillation. We used 2-sample Mendelian randomization to consider the impact of birthweight on incident atrial fibrillation using summary data from the Early Growth Genetics Consortium GWAS of birthweight and a large biobank-based GWAS of atrial fibrillation.

Results:

Using the framework of 2-sample Mendelian randomization, we found that a 1-SD genetic elevation of birthweight was associated with increased risk of atrial fibrillation (odds ratio, 1.27 [95% CI, 1.14–1.41];
P
=1×10
−5
) with sensitivity analyses demonstrating robustness of this result.

Conclusions:
Our findings clarify the directionality of the relationship between birthweight and atrial fibrillation, supporting the growing body of evidence that intrauterine growth has a lifelong impact on cardiovascular health.
COVID‐19 Anosmia Reporting Tool: Initial Findings
Authors: Kaye Rachel , Chang C. W. David , Kazahaya Ken , Brereton Jean , Denneny James C. 
Published: April 2020

There is accumulating anecdotal evidence that anosmia and dysgeusia are associated with the COVID‐19 pandemic. To investigate their relationship to SARS‐CoV2 infection, the American Academy of Otolaryngology–Head and Neck Surgery developed the COVID‐19 Anosmia Reporting Tool for Clinicians for the basis of this pilot study. This tool allows health care providers to confidentially submit cases of anosmia and dysgeusia related to COVID‐19. We analyzed the first 237 entries, which revealed that anosmia was noted in 73% of patients prior to COVID‐19 diagnosis and was the initial symptom in 26.6%. Some improvement was noted in 27% of patients, with a mean time to improvement of 7.2 days in this group (85% of this group improved within 10 days). Our findings suggest that anomia can be a presenting symptom of COVID‐19, consistent with other emerging international reports. Anosmia may be critical in timely identification of individuals infected with SARS‐CoV2 who may be unwittingly transmitting the virus.
Disappointing long-term outcome of THA with carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) as acetabular insert liner: a prospective study with a mean follow-up of 14.3 years
Authors: Heijnens Luc JM , Schotanus Martijn GM , Verburg Aart D , van Haaren Emil H 
Published: April 2020

Introduction: Insert liner wear of the acetabular component is one of the predictive values for survival of total hip arthroplasties (THAs). This prospective single-centre study was designed to evaluate the follow-up of carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) insert liner used as bearing in cementless THAs. Methods: 29 healthy patients with an indication for cementless THA were selected for a CFR-PEEK insert liner and followed over time. All patients received a cementless THA with a CFR-PEEK insert liner used as bearing. At different follow-up moments patients were routinely examined and were analysed using the Oxford Hip Score (OHS), the modified Merle d’Aubigne-Postel (MAP) score, and radiologically. At the follow up moments the plain radiographics where assessed for loosening, cyst formations and wear of the CFR-PEEK liners. Results: At a mean of 14.3 years follow-up 4 revisions of the acetabular component were performed, resulting in a survival rate of 86.5% (CI 95%, 72.4–96.6). A statistically significant difference in OHS and MAP scores between pre- and postoperative follow-up moments was observed. The acetabular components of the remaining patients showed no radiological abnormalities at 14.3 years follow-up. The overall CFR-PEEK wear was low, with a mean of 0.81 (0.2–1.4) mm wear at 14.3 years follow-up. Conclusions: In this series we found an aseptic loosening with unclear reasons in 4 well-positioned acetabular components, hence we do not recommend routine use of CFR-PEEK insert liners as bearing in cementless THAs. All the remaining THAs and acetabular components were in situ without abnormalities at 14.3 years follow-up.
Life and priorities before death: A narrative inquiry of uncertainty and end of life in people with heart failure and their family members
Authors: Molzahn Anita E , Sheilds Laurene , Bruce Anne , Schick-Makaroff Kara , Antonio Marcy , Clark Alexander M 
Published: April 2020

Background Most patients with advanced heart failure are ill-prepared and poorly supported during the end of life. To date, research has focused primarily on generalized patient accounts of the management or self-care phase of the syndrome. Little research has examined the end of life in depth or from the perspectives of family members. Aims The purpose of this study is to describe how people diagnosed with heart failure and their family members describe uncertainty related to impending death. Methods and results A narrative inquiry was undertaken using a social constructionist perspective. Twenty participants took part in over 60 interviews: 12 participants with heart failure (eight male and four female; mean = 67.3 years) and eight family members (mean = 61.6 years) engaged in two in-depth interviews, approximately 3–4 months apart, followed by a telephone follow-up 2–3 months later. Six key themes/storylines were identified. These included: prognosis messages received from physicians; whenever I die, I die; loss isn’t new to me but … ; carrying on amidst the fragility of life; ultimately living not knowing; and the need to prepare. Conclusion The six key storylines of death and dying with advanced heart failure were consistent for both patients and family members. There was a desire for better communication with physicians. Many participants were critical of how the prognosis of advanced heart failure was communicated to them, even if they anticipated the news. Participants wanted frank, open conversations with their healthcare providers that both acknowledged that they were at end of life but did not remove all hope.
Development and psychometric testing of the self-care scale for patients with chronic atrial fibrillation (AF-SCS-10)
Authors: Son Youn-Jung , Baek Kyoung Hwa , Won Mi Hwa , Hong Hye Chong 
Published: April 2020

Background Patients with atrial fibrillation (AF) require continuous self-care due to possible complications and side effects from treatment. However, existing tools do not capture all of the critical factors of AF self-care and have limited evidence of reliability and validity. Aims The aim of this study was to develop and evaluate a new Atrial Fibrillation Self-Care Scale-10 (AF-SCS-10) that assesses disease-specific, multidimensional, person-centered self-care for AF patients in South Korea. Methods For this cross-sectional research design, 290 individuals over 20 years of age with a diagnosis of AF for at least three months were recruited. A literature review and in-depth interviews were utilized to identify the scale items. An expert panel evaluated the validity and reliability of a preliminary scale. Exploratory factor analysis and parallel analysis was performed to extract factors; confirmatory factor analysis (CFA) was performed to evaluate fit on the factor structures. Criterion validity was supported by the correlation between AF-SCS-10 and AF quality of life. Results The internal consistency reliability coefficient was 0.87. Three factors, “self-care knowledge,” “self-care behavior,” and “self-care resources” were extracted from the exploratory factory analysis, explaining 79.30% of the total variance in the data. The three-factor model was also confirmed by parallel analysis; CFA met the fitness criteria. Conclusion There is preliminary evidence for internal consistency reliability, as well as content and construct validity, for the AF-SCS-10. Future research is needed to confirm the study results using a larger, more culturally diverse sample.