bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke
Authors: Schuhmann Michael K. , Stoll Guido , Bieber Michael , Vögtle Timo , Hofmann Sebastian , Klaus Vanessa , Kraft Peter , Seyhan Mert , Kollikowski Alexander M. , Papp Lena , Heuschmann Peter U. , Pham Mirko , Nieswandt Bernhard , Stegner David 
Published: July 2020

Rationale:
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Recanalization of the occluded vessel is essential but not sufficient to guarantee brain salvage. Experimental and clinical data suggest that infarcts often develop further due to a thromboinflammatory process critically involving platelets and T cells, but the underlying mechanisms are unknown.

Objective:
We aimed to determine the role of CD (cluster of differentiation)-84 in acute ischemic stroke after recanalization and to dissect the underlying molecular thromboinflammatory mechanisms.

Methods and Results:

Here, we show that mice lacking CD84—a homophilic immunoreceptor of the SLAM (signaling lymphocyte activation molecule) family—on either platelets or T cells displayed reduced cerebral CD4
+
T-cell infiltration and thrombotic activity following experimental stroke resulting in reduced neurological damage. In vitro, platelet-derived soluble CD84 enhanced motility of wild-type but not of
Cd84
−/−
CD4
+
T cells suggesting homophilic CD84 interactions to drive this process. Clinically, human arterial blood directly sampled from the ischemic cerebral circulation indicated local shedding of platelet CD84. Moreover, high platelet CD84 expression levels were associated with poor outcome in patients with stroke.

Conclusions:
These results establish CD84 as a critical pathogenic effector and thus a potential pharmacological target in ischemic stroke.
Atrial Myocyte NLRP3/CaMKII Nexus Forms a Substrate for Postoperative Atrial Fibrillation
Authors: Heijman Jordi , Muna Azinwi Phina , Veleva Tina , Molina Cristina E. , Sutanto Henry , Tekook Marcel , Wang Qiongling , Abu-Taha Issam H. , Gorka Marcel , Künzel Stephan , El-Armouche Ali , Reichenspurner Hermann , Kamler Markus , Nikolaev Viacheslav , Ravens Ursula , Li Na , Nattel Stanley , Wehrens Xander H.T. , Dobrev Dobromir 
Published: July 2020

Rationale:
Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

Objective:
To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

Methods and Results:

Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca
2+
]
i
-recordings in atrial cardiomyocytes, along with protein-expression levels in tissue homogenates or cardiomyocytes, were assessed in 265 atrial samples from patients without or with POAF. No indices of electrical, profibrotic, or connexin remodeling were noted in POAF, but Ca
2+
-transient amplitude was smaller, although spontaneous sarcoplasmic reticulum (SR) Ca
2+
-release events and L-type Ca
2+
-current alternans occurred more frequently. CaMKII (Ca
2+
/calmodulin-dependent protein kinase-II) protein-expression, CaMKII-dependent phosphorylation of the cardiac RyR2 (ryanodine-receptor channel type-2), and RyR2 single-channel open-probability were significantly increased in POAF. SR Ca
2+
-content was unchanged in POAF despite greater SR Ca
2+
-leak, with a trend towards increased SR Ca
2+
-ATPase activity. Patients with POAF also showed stronger expression of activated components of the NLRP3 (NACHT, LRR, and PYD domains-containing protein-3)-inflammasome system in atrial whole-tissue homogenates and cardiomyocytes. Acute application of interleukin-1β caused NLRP3-signaling activation and CaMKII-dependent RyR2/phospholamban hyperphosphorylation in an immortalized mouse atrial cardiomyocyte cell-line (HL-1-cardiomyocytes) and enhanced spontaneous SR Ca
2+
-release events in both POAF cardiomyocytes and HL-1-cardiomyocytes. Computational modeling showed that RyR2 dysfunction and increased SR Ca
2+
-uptake are sufficient to reproduce the Ca
2+
-handling phenotype and indicated an increased risk of proarrhythmic delayed afterdepolarizations in POAF subjects in response to interleukin-1β.

Conclusions:

Preexisting Ca
2+
-handling abnormalities and activation of NLRP3-inflammasome/CaMKII signaling are evident in atrial cardiomyocytes from patients who subsequently develop POAF. These molecular substrates sensitize cardiomyocytes to spontaneous Ca
2+
-releases and arrhythmogenic afterdepolarizations, particularly upon exposure to inflammatory mediators. Our data reveal a potential cellular and molecular substrate for this important clinical problem.
Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture
Authors: Vaisar Tomáš , Hu Jie H. , Airhart Nathan , Fox Kate , Heinecke Jay , Nicosia Roberto F. , Kohler Ted , Potter Zachary E. , Simon Gabriel M. , Dix Melissa M. , Cravatt Benjamin F. , Gharib Sina A. , Dichek David A. 
Published: July 2020

Rationale:
Plaque rupture is the proximate cause of most myocardial infarctions and many strokes. However, the molecular mechanisms that precipitate plaque rupture are unknown.

Objective:
By applying proteomic and bioinformatic approaches in mouse models of protease-induced plaque rupture and in ruptured human plaques, we aimed to illuminate biochemical pathways through which proteolysis causes plaque rupture and identify substrates that are cleaved in ruptured plaques.

Methods and Results:

We performed shotgun proteomics analyses of aortas of transgenic mice with macrophage-specific overexpression of urokinase (SR-uPA
+/0
mice) and of SR-uPA
+/0
bone marrow transplant recipients, and we used bioinformatic tools to evaluate protein abundance and functional category enrichment in these aortas. In parallel, we performed shotgun proteomics and bioinformatics studies on extracts of ruptured and stable areas of freshly harvested human carotid plaques. We also applied a separate protein-analysis method (protein topography and migration analysis platform) to attempt to identify substrates and proteolytic fragments in mouse and human plaque extracts. Approximately 10% of extracted aortic proteins were reproducibly altered in SR-uPA
+/0
aortas. Proteases, inflammatory signaling molecules, as well as proteins involved with cell adhesion, the cytoskeleton, and apoptosis, were increased. ECM (Extracellular matrix) proteins, including basement-membrane proteins, were decreased. Approximately 40% of proteins were altered in ruptured versus stable areas of human carotid plaques, including many of the same functional categories that were altered in SR-uPA
+/0
aortas. Collagens were minimally altered in SR-uPA
+/0
aortas and ruptured human plaques; however, several basement-membrane proteins were reduced in both SR-uPA
+/0
aortas and ruptured human plaques. Protein topography and migration analysis platform did not detect robust increases in proteolytic fragments of ECM proteins in either setting.

Conclusions:

Parallel studies of SR-uPA
+/0
mouse aortas and human plaques identify mechanisms that connect proteolysis with plaque rupture, including inflammation, basement-membrane protein loss, and apoptosis. Basement-membrane protein loss is a prominent feature of ruptured human plaques, suggesting a major role for basement-membrane proteins in maintaining plaque stability.
Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome
Authors: Kharraziha Isabella , Axelsson Jonas , Ricci Fabrizio , Di Martino Giuseppe , Persson Margaretha , Sutton Richard , Fedorowski Artur , Hamrefors Viktor 
Published: July 2020

Background
Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein–coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell‐based assay.

Methods and Results

Forty‐eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10‐item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein–coupled receptor: adrenergic α
1
receptor, adrenergic β
2
receptor, cholinergic muscarinic type 2 receptor, and opioid receptor‐like 1 were treated with sera from all patients. Receptor response was analyzed using a β‐arrestin–linked transcription factor driving transgenic β‐lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein–coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (
P
<0.01 for all). The area under the curve was 0.88 (0.80–0.97,
P
<0.001) combining all 4 receptors. Adrenergic α
1
receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity,
P
=0.009) and with reduced tolerability for prolonged standing (
P
=0.037) and walking for short (
P
=0.042) or long (
P
=0.001) periods. All 4 receptors were associated with vision problems (
P
<0.05 for all).

Conclusions

Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum‐mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α
1
receptor is associated with orthostatic symptoms severity in patients with POTS.
Post-traumatic embitterment symptoms among woman victims of February 28th post-modern coup of Turkey after two decades: A comparative cross-sectional study
Authors: Görmez Aynur , Yeni Elbay Rümeysa , Karatepe Hasan Turan 
Published: July 2020

Background: Post-traumatic embitterment disorder (PTED) is characterized by embitterment reaction to stressful life events, which are seen as unjust and as a violation of basic beliefs. On 28 February 1997, a so-called post-modern coup took place in Turkey, declaring a ban on hijab which had a significant impact on women’s lives by eliminating them from public sphere if they were to wear hijab. Aim: The aim of this study was to assess the frequency of PTED symptoms among woman victims of the coup after two decades, and to investigate its correlations. Embitterment reaction was also examined in woman victims of 1999 earthquakes of Turkey, and the findings were compared. Method: We used PTED, Beck Anxiety Inventory, Beck Depression Inventory and Brief Resilience Scale, and a purpose-designed socio-demographic form. Results: Out of eligible 101 hijab ban victims responded, substantial proportion of them (48%) were suffering from chronic embitterment as well as experiencing symptoms of anxiety (37.6%) and depression (26.8%) of moderate-to-severe intensity. There was no difference in the levels of anxiety, depression and resilience between the victims of the coup and earthquake ( N = 20), but hijab ban victims were significantly more likely to present with PTED symptoms ( p < .05). Women who had family support were more resilient with less likelihood of PTED ( p < .05). Conclusion: This study provides some important insights into psychopathology of PTED as well as suggesting that it is more likely to manifest in people whose suffering is brought upon by fellow human beings.
Melioidosis: distinctive clinico-epidemiological characteristics in southern India
Authors: Basheer Aneesh , Iqbal Nayyar , C Sheeladevi , Kanungo Reba , Kandasamy Ravichandran 
Published: July 2020

As it is increasingly being reported from India, we carried out a prospective study of patients with culture-proven melioidosis from south India, examining clinical, laboratory features, epidemiological data, risk factors, treatments, outcomes at three and six months, and factors associated with mortality. Between 2014 and 2018, 31 cases were identified. Diabetes (83.9%) and alcohol abuse (58.1%) were common risk factors. Musculoskeletal, skin and soft tissue manifestations together constituted 48.4% of presentations, while 29% had pneumonia. During the intensive phase, 74.2% received one of three recommended antibiotic regimes, but 51.6% did not receive continuation treatment. Pneumonia and lack of continuation treatment were independently associated with a high mortality of 25.8%. Hot spots for melioidosis exist in India, and there is considerable diversity of presentation, including skin, soft tissue, musculoskeletal and neurological involvement. High rates of bacteraemia are shown.
Management of HER2-positive breast cancer during pregnancy: a case report
Authors: Berwart Julia , Buonomo Barbara , Peccatori Fedro A. , Marioni Anabel , Lescano Juliana , Pressel Coretto Emilia 
Published: July 2020

Introduction: Breast cancer is one of the most common malignancies diagnosed during pregnancy, with an incidence of 1:3000 pregnancies. Its rising incidence is related to the trend to postpone childbearing during the last 30 years. Breast cancer during pregnancy should not be managed differently from the nonpregnant setting. Chemotherapy is reported to be safe after the first trimester, whereas trastuzumab and tamoxifen are contraindicated regardless of the trimester. Case description: A patient diagnosed with breast cancer recurrence during pregnancy was exposed to both tamoxifen and trastuzumab during the first two trimesters of pregnancy. In addition, docetaxel was administered during the second and third trimesters, without subsequent fetal malformations or obstetric complications. Conclusions: When conception occurs inadvertently during assumption of tamoxifen or anti-HER2 agents, their effects on the fetus and on the course of pregnancy are not completely understood. Further studies are needed in this setting, highlighting the importance to share clinical experiences.
Impact of time-varying center volume on technique failure and mortality in peritoneal dialysis
Authors: Yao Yen-Hung , Chen Chyong-Mei , Chou Yiing-Jenq , Huang Nicole 
Published: July 2020

Background: Most studies on volume–outcome association used the number of patients at a particular period as the independent variable. However, peritoneal dialysis (PD) is a chronic treatment, and center volume usually changes over a patient’s treatment period. Accordingly, this study used the time-varying center volume to explore the volume–outcome association in PD. Methods: We conducted a nationwide population-based retrospective cohort study, which included patients who began chronic PD between 2001 and 2010. The risk factors of 5-year technique failure and mortality were analyzed using cause-specific and subdistribution hazard models, respectively. The annual number of patients initiating PD in each patient’s treatment center was modeled as a time-varying variable with four categories. Results: We included 9071 patients who started PD in 100 centers where the number of incident patients ranged from 1 to 107 patients per year (median, 25; interquartile range, 13–42). The estimated 5-year patient and technique survival rates were 64.7% and 66.6%, respectively. Being treated in centers in the largest volume category (the number of incident PD patients ≥43 per year) was associated with significantly lower cause-specific and cumulative hazards for technique failure. No association was found between facility volume and hazards of mortality. Conclusions: Receiving PD in high-volume facilities was associated with a lower risk in technique failure. No association was found between facility volume and mortality risk.
Effects of using standardized patients on nursing students’ moral skills
Authors: Kucukkelepce Gulhan Erkus , Dinc Leyla , Elcin Melih 
Published: July 2020

Background: Nurses and nursing students increasingly confront ethical problems in clinical practice. Moral sensitivity, moral reasoning, and ethical decision-making are therefore important skills throughout the nursing profession. Innovative teaching methods as part of the ethics training of nursing students help them acquire these fundamental skills. Aim: This study investigated the effects and potential benefits of using standardized patients in ethics education on nursing baccalaureate students’ moral sensitivity, moral reasoning, and ethical decision-making by comparing this method with in-class case analyses. Research design: This is a quasi-experimental study. Participants and research context: The sample comprised 89 students in Hacettepe University’s Faculty of Nursing. Following lectures describing the theoretical components of ethics, students were randomly assigned to two working groups, one using standardized patients and the other using in-class case analyses. Data were collected using the Moral Sensitivity Questionnaire, Rest’s Defining Issues Test, and the Nursing Dilemma Test. All data were analysed using IBM SPSS Statistics Version 23. Ethical considerations: Ethical approval and official permission were obtained. All participating students completed informed consent forms. Findings: According to the results, the moral sensitivity of students in the standardized patient group significantly improved over time compared to those in the case analysis group, while the mean scores of students in both groups for moral reasoning and ethical decision-making were not statistically significant. Conclusion: Based on our results, we recommend the use of both standardized patients and case analysis as appropriate teaching methods in ethics education.
Ethics reflection groups for school nurses
Authors: Heggestad Anne Kari Tolo , Førde Reidun , Magelssen Morten , Arnekleiv Birgit 
Published: July 2020

Background: School nurses have great responsibilities as the connecting link between school, children/adolescents, parents, and other healthcare services. Being in this middle position, and handling complex situations and problems related to children in school, may be demanding and also lead to ethical challenges. Clinical ethics support, such as ethics reflection groups, may be of help when dealing with ethical challenges. However, there is little research on experiences with ethics reflection groups among school nurses. Aim: The aim of this research was to explore how nurses in school healthcare experience their role, and how they experience participation in ethics reflection groups, using a model for systematic ethics reflection, the Centre for Medical Ethics model. Research design: The project had a qualitative design, using focus group interviews and thematic analysis. Ethical considerations: The study was evaluated by the Data Protection Official at the Norwegian Centre for Research Data (project no. 57373). The participants were given oral and written information about the study and signed a written consent. Participants and context: Twelve participants from school healthcare were recruited to the interviews. Findings: School nurses described their role as extremely challenging. How the school nurses experienced their role also influenced how they experienced participating in ethics reflection groups. The Centre for Medical Ethics model was experienced as both challenging and comprehensive. However, they also experienced that the model helped them to clarify their role and could also help them to find better solutions. Conclusion: The role as school nurse is complex and demanding, with several ethical challenges. Ethics reflection groups may be of great help when dealing with these challenges. However, it is of great importance that the methods used are adjusted to the professionals’ needs and context.
Does the ‘halo effect’ of trauma center verification extend to severe postpartum hemorrhage? A four-year retrospective review of level 1 trauma centers in the United States
Authors: Vuong Phoenix , Dardon Arturo Torices , Chen Chun-Cheng , Stankiewicz Sarah , Skupski Daniel , Saldinger Pierre , Sample Jason 
Published: July 2020

Introduction Designated high-quality trauma services have been shown to improve outcomes of trauma patients by virtue of access to specialized personnel and resources. It remains unclear if a ‘halo effect’ extends these benefits more generally to non-trauma populations. Obstetric patients who develop severe postpartum hemorrhage often require close attention in intensive care units and utilize more resources. Given the overlapping needs between trauma and obstetric patients, we hypothesize that the ‘halo effect’ might extend to patients with severe postpartum hemorrhage. Methods The Nationwide Inpatient Sample for years 2008 to 2011 was queried. Patients with severe postpartum hemorrhage were identified as those requiring transfusion, hysterectomy, or uterine repair. After stratifying by level 1 trauma center versus non-level 1 trauma center status, unadjusted univariate comparisons were made. Adjusted odds ratio of end-organ failure and death were analyzed using multivariable logistic regression. Results A total of 11,135 patients were identified with severe postpartum hemorrhage. The majority were hospitalized at non-level 1 trauma centers rather than level 1 trauma centers (71.4% vs. 28.6%). Patients at non-level 1 trauma centers were younger, more likely to be white, admitted electively, insured, and healthier with a lower comorbidity index. There was no significant difference in rates of mortality or organ failure. However, after adjustment for differences in comorbidity index, race, and emergency admission, patients at non-level 1 trauma centers had a significantly higher risk of respiratory failure (odds ratio, 1.27; 95% confidence interval, 1.01–1.59). Conclusions These findings suggest that the outcomes of obstetric patients with severe postpartum hemorrhage admitted in level 1 trauma centers are not overall significantly different when compared to those in non-level 1 trauma centers. However, after adjusting for baseline characteristics, there was a reduced risk of respiratory failure in patients admitted to level 1 trauma centers.