bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking the BKCa channel induces NF-κB nuclear translocation by increasing nuclear calcium concentration
Authors: Kent Lindsey N , Li Youe , Wakle-Prabagaran Monali , Naqvi Mashal Z , Weil Sophia G , England Sarah K 
Published: November 2021

AbstractNuclear factor kappa B (NF-κB) transcriptionally regulates several genes involved in initiating uterine contractions. A key factor controlling NF-κB activity is its translocation to the nucleus. In myometrial smooth muscle cells (MSMCs), this translocation can be stimulated by the inflammatory molecule lipopolysaccharide (LPS) or by blocking the potassium calcium-activated channel subfamily M alpha 1 (KCNMA1 or BKCa) with paxilline (PAX). Here, we sought to determine the mechanism by which blocking BKCa causes NF-κB-p65 translocation to the nucleus in MSMCs. We show that LPS- and PAX-induced NF-κB-p65 translocation are similar in that neither depends on several mitogen-activated protein kinase pathways, but both require increased intracellular calcium (Ca2+). However, the nuclear transport inhibitor wheat germ agglutinin prevented NF-κB-p65 nuclear translocation in response to LPS but not in response to PAX. Blocking BKCa located on the plasma membrane resulted in a transient NF-κB-p65 nuclear translocation that was not sufficient to induce expression of its transcriptional target, suggesting a role for intracellular BKCa. We report that BKCa also localizes to the nucleus and that blocking nuclear BKCa results in an increase in nuclear Ca2+ in MSMCs. Together, these data suggest that BKCa localized on the nuclear membrane plays a key role in regulating nuclear Ca2+ and NF-κB-p65 nuclear translocation in MSMCs.
Role of autocrine bone morphogenetic protein signaling in trophoblast stem cells
Authors: Au Jennie , Requena Daniela F , Rishik Hannah , Kallol Sampada , Tekkatte Chandana , Farah Omar A , Kittle Ryan , Meads Morgan , Wakeland Anna , Soncin Francesca 
Published: November 2021

Abstract
The Bone Morphogenetic Protein (BMP) pathway is involved in numerous developmental processes, including cell growth, apoptosis, and differentiation. In mouse embryogenesis, BMP signaling is a well-known morphogen for both mesoderm induction and germ cell development. Recent evidence points to a potential role in development of the extraembryonic compartment, including trophectoderm-derived tissues. In this study, we investigated the effect of BMP signaling in both mouse and human trophoblast stem cells (TSC) in vitro, evaluating the expression and activation of the BMP signaling response machinery, and the effect of BMP signaling manipulation during TSC maintenance and differentiation. Both mouse trophoblast stem cells (mTSC) and human trophoblast stem cells (hTSC) expressed various BMP ligands and the receptors BMPR1A and BMPR2, necessary for BMP response, and displayed maximal active BMP signaling when undifferentiated. We also observed a conserved modulatory role of BMP signaling during trophoblast differentiation, whereby maintenance of active BMP signaling blunted differentiation of TSC in both species. Conversely, the effect of BMP signaling on the undifferentiated state of TSC appeared to be species-specific, with SMAD-independent signaling important in maintenance of mTSC, and a more subtle role for both SMAD-dependent and -independent BMP signaling in hTSC. Altogether, these data establish an autocrine role for the BMP pathway in the trophoblast compartment. As specification and correct differentiation of the extraembryonic compartment are fundamental for implantation and early placental development, insights on the role of the BMP signaling in early development might prove useful in the setting of in vitro fertilization as well as targeting trophoblast-associated placental dysfunction.
Phthalates and alternative plasticizers differentially affect phenotypic parameters in gonadal somatic and germ cell lines
Authors: Rajkumar Abishankari , Luu Trang , Beal Marc A , Barton-Maclaren Tara S , Hales Barbara F , Robaire Bernard 
Published: November 2021

Abstract
The developmental and reproductive toxicity associated with exposure to phthalates has motivated a search for alternatives. However, there is limited knowledge regarding the adverse effects of some of these chemicals. We used high-content imaging to compare the effects of mono (2-ethylhexyl) phthalate (MEHP) with six alternative plasticizers: di-2-ethylhexyl terephthalate (DEHTP); diisononyl-phthalate (DINP); di-isononylcyclohexane-1,2-dicarboxylate (DINCH); 2-ethylhexyl adipate (DEHA); 2,2,4-trimethyl 1,3-pentanediol diisobutyrate (TXIB) and di-iso-decyl-adipate (DIDA). A male germ spermatogonial cell line (C18–4), a Sertoli cell line (TM4) and two steroidogenic cell lines (MA-10 Leydig and KGN granulosa) were exposed for 48 h to each chemical (0.001–100 μM). Cell images were analyzed to assess cytotoxicity and effects on phenotypic endpoints. Only MEHP (100 μM) was cytotoxic and only in C18–4 cells. However, several plasticizers had distinct phenotypic effects in all four cell lines. DINP increased Calcein intensity in C18–4 cells, whereas DIDA induced oxidative stress. In TM4 cells, MEHP, and DINCH affected lipid droplet numbers, while DEHTP and DINCH increased oxidative stress. In MA-10 cells, MEHP increased lipid droplet areas and oxidative stress; DINP decreased the number of lysosomes, while DINP, DEHA, and DIDA altered mitochondrial activity. In KGN cells, MEHP, DINP and DINCH increased the number of lipid droplets, whereas DINP decreased the number of lysosomes, increased oxidative stress and affected mitochondria. The Toxicological Priority Index (ToxPi) provided a visual illustration of the cell line specificity of the effects on phenotypic parameters. The lowest administered equivalent doses were observed for MEHP. We propose that this approach may assist in screening alternative plasticizers.
Movement-related EEG signatures associated with freezing of gait in Parkinson’s disease: an integrative analysis
Authors: Karimi Fatemeh , Niu Jiansheng , Gouweleeuw Kim , Almeida Quincy , Jiang Ning 
Published: November 2021

Abstract
Freezing of gait is the most severe gait deficit associated with Parkinson’s disease and significantly affects patients’ independence and consequently their quality of life. The lack of a clear understanding of its underlying neurophysiological mechanism has resulted in limited effectiveness of the current treatment options. In this study, we investigated EEG features over (pre-)supplementary motor area and primary motor cortex during a simple cue-based ankle dorsiflexion movement. These features include movement-related cortical potentials (0.05–5 Hz) and brain oscillations (1–50 Hz). Electromyogram signal from the tibialis anterior muscle of the dominant foot was used to determine the movement onset. The EEG features before, during and following the onset of the movement were compared among three groups of participants: patients with freezing (N = 14, 11 males), patients without freezing (N = 14, 13 males) and healthy age-matched controls (N = 13, 10 males) with 15 recorded trials for each individual. Additionally, Parkinson’s disease patients with freezing of gait were separated into mild (N = 7) and severe cases (N = 5), so that EEG features associated with freezing severity could be investigated. The results indicated significant differences between patients with severe freezing of gait compared to healthy controls and patients without freezing of gait. In addition, patients with mild and severe freezing represented cortical activity differences. For patients with freezing, the initial component of movement-related cortical potential is significantly lower than that of the healthy controls (P = 0.002) and is affected by the severity of freezing. Furthermore, a striking absence of beta frequency band (12–35 Hz) desynchronization was observed in patients with freezing, especially low-beta frequency band over Cz, before the movement, which was also associated with the severity of the freezing of gait. Low-beta (13–20 Hz) and high-beta (21–35 Hz) frequency band activities represented unique features for each group. Beta event-related desynchronization over Cz present in healthy controls prior to movement onset, was partially replaced by the theta band (4–8 Hz) synchrony in patients with freezing. Patients with severe freezing also represented some level of theta band synchronization over contralateral supplementary motor area. This suggests the involvement of cognitive processing over the motor cortex in controlling cue-based voluntary movement as a compensatory mechanism associated with freezing of gait. The EEG features identified in this study are indicative of important freezing of gait clinical characteristics such as severity and contribute to a better understanding of the underlying neurophysiology of the mysterious phenomenon of freezing of gait.
Frontal cortical functional connectivity is impacted by anaesthesia in macaques
Authors: Giacometti Camille , Dureux Audrey , Autran-Clavagnier Delphine , Wilson Charles R E , Sallet Jérôme , Dirheimer Manon , Procyk Emmanuel , Hadj-Bouziane Fadila , Amiez Céline 
Published: November 2021

AbstractA critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional magnetic resonance imaging (rs-fMRI) in anaesthetized nonhuman primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity organization of a well-characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques show that rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas, while more caudal seeds displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrated a similar functional connectivity (FC) organization of the cingulo-frontal cortical network in awake macaque to that previously uncovered in the human brain pointing toward a preserved FC organization from macaque to human. However, it can only be observed in awake state suggesting that this network is sensitive to anaesthesia and warranting significant caution when comparing FC patterns across species under different states.
Electrophysiological evidence for a common magnitude representation of spatiotemporal information in working memory
Authors: Cui Minghui , Peng Chunhua , Huang Mei , Chen Youguo 
Published: November 2021

Abstract
Spatiotemporal interference has attracted increasing attention because it provides a window for studying the neural representation of magnitude in the brain. We aimed to identify the neural basis of spatiotemporal interference using a Kappa effect task in which two circles were presented in sequence with two time intervals and three space distances. Participants reproduced the time intervals while ignoring the space distance when electroencephalogram signals were recorded synchronously. The behavior results showed that production time increased with time interval and space distance. Offset of the time intervals elicited typical P2 and P3b components. Larger parietal P2 and P3b amplitudes were elicited by the combination of longer time intervals and longer space distances. The parietal P2 and P3b amplitudes were positively correlated with the production time, and the corresponding neural source was located in the parietal cortex. The results suggest that the parietal P2 and P3b index updates a common representation of spatiotemporal information in working memory, which provides electrophysiological evidence for the mechanisms underlying spatiotemporal interferences. Our study supports a theory of magnitude, in which different dimensions can be integrated into a common magnitude representation in a generalized magnitude system that is localized at the parietal cortex.
Pyopneumopericarditis from a gastropericardial fistula: a case report
Authors: Lee John , Ramkumar Satish , Ha Phil , Raghunath Ajay , Dundon Benjamin 
Published: November 2021

Abstract

Background
Pyopneumopericarditis is a very rare diagnosis that requires prompt recognition and urgent treatment. It denotes the presence of pus and air in the pericardium with associated inflammation of the fibrous pericardial sac.

Case summary
A 49-year-old gentleman was admitted with pyopneumoperciarditis on a background of a previous uncomplicated Roux-en-Y gastric bypass surgery performed 7 years prior. He underwent emergency surgery for an omental patch repair of an ulcer perforation involving the diaphragm and pericardium. His inpatient stay was complicated by persistent seropurulent output from the pericardial drain, loculated pleural effusion, and deconditioning.

Discussion
Management is extrapolated from the literature regarding purulent pericarditis. This condition albeit rare, requires swift recognition as without treatment mortality approaches 100%. Colchicine is an important adjunctive therapy postoperatively to prevent constrictive physiology.
Four-dimensional echocardiography and left ventricular systolic strain measured via two-dimensional speckle-tracking for Danon disease: a case series
Authors: Changsheng Ma , Fan Jiali , Bingyuan Zhou , Jiawei Zhou , Li Wang , Lin Fan , Yuping Liao , Caiming Zhao 
Published: November 2021

Abstract

Background
Danon disease is an X-linked multisystemic disorder characterized by skeletal myopathy, cardiomyopathy, and intellectual disability.

Case summary
Herein, we describe two patients affected by Danon disease from the same family, a father (Patient 1) and his daughter (Patient 2). In Patient 1, a short PR interval with pre-excitation was evident. In Patient 2, over a 24-h period 2369 atrial premature beats and rare isolated ventricular ectopics were detected. Both patients exhibited left ventricular hypertrophy with non-compaction myocardium, and the left ventricular ejection fraction was impaired in Patient 1 and normal in Patient 2. In Patient 2, the total left ventricular strain value was reduced, and layer-specific strain revealed that subepicardial strain impaired more than in other layers. Late gadolinium enhancement was detected both in left and right ventricles in Patient 2, and cardiac fibrosis was more apparent in the subepicardium of left ventricular free wall. Four-dimensional (4D) echocardiography revealed that left atrial reservoir strain and left ventricular total longitudinal strain were induced.

Discussion
Novel 4D echocardiography and left ventricular systolic strain may play important role in diagnosis and myocardial functional evaluation in Danon disease.
Immunomodulation in antiphospholipid-antibody-associated endocarditis: a case report and review of the literature
Authors: Haertel Franz , Kretzschmar Daniel , Schulze P Christian , Neumann Thomas 
Published: November 2021

Abstract

Background
Non-infectious endocarditis is a rare complication in patients with systemic lupus erythematosus or antiphospholipid syndrome (APS). The mitral valve is mainly affected, usually showing vegetations on the ventricular and atrial side of the valve.

Case summary
A 27-year-old female patient with a known APS was referred to our hospital with night sweats, weight loss, reduction in performance, and dizziness. A floating structure associated to the mitral valve was identified in a transoesophageal echocardiogram with typical changes, in accordance with a non-infectious endocarditis (Libman–Sacks). Only a trace of mitral regurgitation was present and a mass on the posterior mitral valve leaflet. Laboratory findings showed antibody and inflammatory marker measurements either negative or within normal range. The patient received therapeutic oral anticoagulation using a vitamin K antagonist and a combined immunosuppression consisting of hydroxychloroquine and prednisolone. The symptoms of the patient resolved within 3 months after starting the initial treatment. The follow-up echocardiogram showed an almost normal mitral valve function with only a slight regional thickening of the posterior mitral leaflet and no stenosis. Following a 7-year period of observation being on a medical regimen of hydroxychloroquine and a vitamin K antagonist, no evidence of clinical and/or echocardiographic recurrence was detected.

Discussion
This case report represents a successful medical management of non-infectious endocarditis using immunosuppressive and anticoagulation therapies without significant residual lesions. Although optimal management of non-bacterial endocarditis remains in the area of uncertainty, this combination therapy deems promising.
Case report of heart transplantation for giant cell myocarditis in a patient with common variable immunodeficiency
Authors: Franzon Thomas A , Kovalszki Anna , Rabah Raja , Nicklas John M 
Published: November 2021

AbstractBackgroundSolid-organ transplantation in patients with common variable immunodeficiency (CVID) is controversial due to the risk for severe and recurrent infections. Determining transplantation candidacy in CVID patients is further complicated by the presence of CVID-related non-infectious complications that can reduce overall survival and also recur in the transplanted organ. Data regarding solid organ transplantation in patients with CVID are limited, particularly in heart transplantation.Case summaryA 32-year-old female with CVID presented with new heart failure after 3 months of dyspnoea on exertion. Her echocardiogram showed severe global systolic dysfunction with an ejection fraction of approximately 10%, and her right heart catheterization revealed severe biventricular pressure overload and severely reduced cardiac output. Endomyocardial biopsy revealed giant cells and mononuclear infiltrate consistent with giant cell myocarditis (GCM). Despite medical management, she developed progressive cardiogenic shock and underwent uncomplicated orthotopic heart transplantation on hospital Day 38. After 2 years of follow-up, she has had no major infectious complications and continues to have normal graft function with no recurrence of GCM.ConclusionWe report a case of successful heart transplantation for GCM in a patient with CVID, with no major infectious complications after 2 years of follow-up. CVID should not be considered an absolute contraindication for heart transplantation.
Abiraterone-induced refractory hypokalaemia and torsades de pointes in a patient with metastatic castration-resistant prostate carcinoma: a case report
Authors: Riad Mariam , Allison Jeffery Scott , Nayyal Shahla , Hritani AbdulWahab 
Published: November 2021

Abstract

Background
Abiraterone, an androgen deprivation therapy, has been used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). It has been associated with increased risks of hypokalaemia and cardiac disorders. We report a case of torsades de pointes (TdP) associated with abiraterone use and refractory hypokalaemia in a man with mCRPC.

Case summary
A 78-year-old man with mCRPC presented to the emergency room for generalized weakness. Laboratory results revealed a potassium level of 2.2 mmol/L (3.5–5.0), magnesium level of 2.4 mg/dL (1.6–2.5), and normal kidney and hepatic functions. Initial electrocardiogram showed atrial fibrillation with rapid ventricular rate of 106 b.p.m., frequent premature ventricular contractions, and a QTc of 634 ms. The patient had multiple episodes of TdP, became pulseless and underwent advanced cardiac life support, including defibrillation. Despite a total of 220 mEq of intravenous potassium chloride, his potassium level only improved to 2.8 mmol/L. He received spironolactone and amiloride to promote urinary potassium reabsorption in addition to hydrocortisone, in an effort to reduce abiraterone’s effect on increasing mineralocorticoid synthesis.

Discussion
Abiraterone has been widely used in mCRPC since its approval by the Food and Drug Adminstration in 2011. Regulatory guidelines and standardized close QTc and electrolyte monitoring in patients may help prevent fatal arrhythmias associated with abiraterone.
An m-Health intervention to improve education, self-management, and outcomes in patients admitted for acute decompensated heart failure: barriers to effective implementation
Authors: Zisis Georgios , Carrington Melinda J , Oldenburg Brian , Whitmore Kristyn , Lay Maria , Huynh Quan , Neil Christopher , Ball Jocasta , Marwick Thomas H 
Published: November 2021

Abstract

Aims
Effective and efficient education and patient engagement are fundamental to improve health outcomes in heart failure (HF). The use of artificial intelligence (AI) to enable more effective delivery of education is becoming more widespread for a range of chronic conditions. We sought to determine whether an avatar-based HF-app could improve outcomes by enhancing HF knowledge and improving patient quality of life and self-care behaviour.

Methods and results
In a randomized controlled trial of patients admitted for acute decompensated HF (ADHF), patients at high risk (≥33%) for 30-day hospital readmission and/or death were randomized to usual care or training with the HF-app. From August 2019 up until December 2020, 200 patients admitted to the hospital for ADHF were enrolled in the Risk-HF study. Of the 72 at high-risk, 36 (25 men; median age 81.5 years; 9.5 years of education; 15 in NYHA Class III at discharge) were randomized into the intervention arm and were offered education involving an HF-app. Whilst 26 (72%) could not use the HF-app, younger patients [odds ratio (OR) 0.89, 95% confidence interval (CI) 0.82–0.97; P &lt; 0.01] and those with a higher education level (OR 1.58, 95% CI 1.09–2.28; P = 0.03) were more likely to enrol. Of those enrolled, only 2 of 10 patients engaged and completed ≥70% of the program, and 6 of the remaining 8 who did not engage were readmitted.

Conclusions
Although AI-based education is promising in chronic conditions, our study provides a note of caution about the barriers to enrolment in critically ill, post-acute, and elderly patients.