bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking bad news: tackling cultural dilemmas
Authors: Holmes Sophie Nilusha , Illing Jan 
Published: March 2021

AbstractRequesting that serious diagnoses be concealed from patients, a widespread phenomenon in many cultures, presents a professional dilemma. Practical and sensitive communication strategies are needed.MethodologyIn this paper, we use analysis of the existing literature to develop a communication tool for practitioners facing requests for diagnostic non-disclosure. Our approach builds on existing strategies, in providing a mnemonic communication tool, permitting more than one outcome, and focusing on the need for mutual understanding and cooperation.ResultsExisting work on this dilemma highlights the need to appreciate the family's standpoint, affirm their benevolent intentions and correct misperceptions. To this end, we have developed a mnemonic tool, 'ARCHES', to be used in situations where the family has requested diagnostic non-disclosure. The model has six stages: acknowledge the request for non-disclosure, build the relationship, find common ground, honour the patient's preferences and outline the harm of non-disclosure, provide emotional support and devise a supportive solution.ConclusionFacing requests for diagnostic non-disclosure is a challenge of communication. The dilemma is particularly marked when practising across cultures. Our model gives a structure for building rapport with the family and realigning their misperceptions while upholding the patient's right to knowledge.
Dynamics of cerebral perfusion and oxygenation parameters following endovascular treatment of acute ischemic stroke
Authors: Brugnara Gianluca , Herweh Christian , Neuberger Ulf , Bo Hansen Mikkel , Ulfert Christian , Mahmutoglu Mustafa Ahmed , Foltyn Martha , Nagel Simon , Schönenberger Silvia , Heiland Sabine , Ringleb Peter Arthur , Bendszus Martin , Möhlenbruch Markus , Pfaff Johannes Alex Rolf , Vollmuth Philipp 
Published: March 2021

BackgroundWe studied the effects of endovascular treatment (EVT) and the impact of the extent of recanalization on cerebral perfusion and oxygenation parameters in patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO).MethodsForty-seven patients with anterior LVO underwent computed tomography perfusion (CTP) before and immediately after EVT. The entire ischemic region (Tmax>6 s) was segmented before intervention, and tissue perfusion (time-to-maximum (Tmax), time-to-peak (TTP), mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF)) and oxygenation (coefficient of variation (COV), capillary transit time heterogeneity (CTH), metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF)) parameters were quantified from the segmented area at baseline and the corresponding area immediately after intervention, as well as within the ischemic core and penumbra. The impact of the extent of recanalization (modified Treatment in Cerebral Infarction (mTICI)) on CTP parameters was assessed with the Wilcoxon test and Pearson’s correlation coefficients.ResultsThe Tmax, MTT, OEF and CTH values immediately after EVT were lower in patients with complete (as compared with incomplete) recanalization, whereas CBF and COV values were higher (P<0.05) and no differences were found in other parameters. The ischemic penumbra immediately after EVT was lower in patients with complete recanalization as compared with those with incomplete recanalization (P=0.002), whereas no difference was found for the ischemic core (P=0.12). Specifically, higher mTICI scores were associated with a greater reduction of ischemic penumbra volumes (R²=−0.48 (95% CI –0.67 to –0.22), P=0.001) but not of ischemic core volumes (P=0.098).ConclusionsOur study demonstrates that the ischemic penumbra is the key target of successful EVT in patients with AIS and largely determines its efficacy on a tissue level. Furthermore, we confirm the validity of the mTICI score as a surrogate parameter of interventional success on a tissue perfusion level.
The Role of OCT Angiography in the Assessment of Epiretinal Macular Membrane
Authors: Bacherini Daniela , Dragotto Francesco , Caporossi Tomaso , Lenzetti Chiara , Finocchio Lucia , Savastano Alfonso , Savastano Maria Cristina , Barca Francesco , Dragotto Martina , Vannozzi Lorenzo , Nasini Francesco , Faraldi Francesco , Rizzo Stanislao , Virgili Gianni , Giansanti Fabrizio 
Published: March 2021

Background. The aim of this observational study is to assess pre- and postoperative retinochoroidal vascular changes in patients undergoing epiretinal macular membrane (ERM) surgery by using optical coherence tomography angiography (OCTA). Materials and Methods. 23 eyes affected by ERM and those which underwent phacovitrectomy associated with ERM peeling were enrolled. They were evaluated using structural OCT and OCTA before surgery and at 1, 3, and 6 months postoperatively. Results. We found a statistically significant (

p

< 0.05) increase in the superficial capillary plexus vessel density (VD) from baseline to the 6-month follow-up. We observed a large increase in both the perfusion density (PD) and the VD of the deep capillary plexus between baseline and the 6-month follow-up (

p

< 0.001). A significant decrease in the VD and PD of the choriocapillaris (CC) from baseline to the 1st month and a significant increase in CC perfusion density at the 6-month follow-up compared to the preoperative value were revealed. The FAZ area and perimeter after surgery significantly increased during the follow-up (

p

< 0.001) at baseline retinal and choroidal plexi with a lower PD or VD correlated with worse visual acuity (

p

< 0.05 for all plexi). At baseline and at the 1-month follow-up, a significant correlation was found with the FAZ area and the FAZ perimeter: a smaller FAZ area or a smaller FAZ perimeter was correlated to a lower visual acuity. Before surgery, negative correlations (

p

< 0.05) were found between the Govetto ERM stages and perfusion density of the SCP and the DCP and between the Govetto stages and vessel density of the DCP. Conclusions. In our study, OCTA detected vascular alterations induced by the presence of the ERM, allowing several correlations with functional data. In these patients, OCTA may be useful to add new potential surgical prognostic factors.
DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer
Authors: Lulli Matteo , Del Coco Laura , Mello Tommaso , Sukowati Caecilia , Madiai Stefania , Gragnani Laura , Forte Paolo , Fanizzi Francesco Paolo , Mazzocca Antonio , Rombouts Krista , Galli Andrea , Carloni Vinicio 
Published: March 2021

AbstractDefective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies.Significance:This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.
Oncometabolites in Cancer: Current Understanding and Challenges
Authors: Liu Yang , Yang Chunzhang 
Published: March 2021

Abstract
Oncometabolites are pathognomonic hallmarks in human cancers, including glioma, leukemia, neuroendocrine tumors, and renal cancer. Oncometabolites are aberrantly accumulated from disrupted Krebs cycle and affect the catalytic activity of α-ketoglutarate–dependent dioxygenases. Oncometabolites indicate distinct cancer-related patterns ranging from oncogenesis and metabolism to therapeutic resistance. Here we discuss the current understanding of oncometabolites as well as the controversies and challenges associated with oncometabolite-driven cancers. New insights into the relationship between cancer and oncometabolites will elucidate novel therapeutic avenues for improved cancer treatment.
“This Most Atrocious Crusade Against Personal Freedom” Anti-abolitionist Violence in Boston on the Eve of War
Authors: Browne Patrick T.J. 
Published: March 2021

Abstract
This essay explores increasing organization among anti-abolitionists in Boston on the eve of the Civil War and the combination of mob violence and political tactics they employed in an attempt to silence abolitionists. This opposition did not fade away on its own but was actively shut down by abolitionists who knew how to navigate politics and public opinion.
ECOWAS and the 2016 Post-Election Crisis in the Gambia: Pax Africana or What?
Authors: Basiru Adeniyi S. , Osunkoya Olusesan A. , Adebayo Tajudeen I. 
Published: March 2021

Abstract
President Yahya Jammeh’s volte face, following his earlier acceptance of the verdicts of the Gambians during the 1 December 2016 presidential poll, did not only jolt the international community but, if not for the intervention of external actors, would have set the Gambia on the path of implosion. This article, based on desk analysis, examines the mediatory role of ECOWAS in the resolution of the 2016 post-election crisis in the Gambia. It notes that unlike the previous similar case in Cote d’Ivoire, ECOWAS took the lead in resolving the political crisis and thus demonstrated that Pax Africana is at work in the sub-region. It argues and concludes that ECOWAS with or without the support from outsiders has the capacity to take charge of threats to democracy and peace in member states, by deploying mediatory diplomacy backed with threat of coercion.
The Political Economy of Institutional Corruption in Africa: The Case of the 1996–97 Tanzania Coffee Crisis
Authors: Brooks Murrell L. 
Published: March 2021

Abstract
This article argues that institutional corruption is the central governance dilemma in Africa by examining the causes, outcome, and origins of the 1996–97 Tanzania coffee crisis. It shows how the growth and crash of a coffee price bubble became a harbinger for defining corruption as historically embedded institutional tendencies and advantages, instead of acts of individual malfeasance. Institutional corruption highlights political gains from the use of public resources in the form of political influence over producer prices, concentrated market power, and centralized policymaking for the wealthy and politically connected, as opposed to personal gains.
The Impact of Assimilating ZDR Observations on Storm-Scale Ensemble Forecasts of the 31 May 2013 Oklahoma Storm Event
Authors: Putnam Bryan J. , Jung Youngsun , Yussouf Nusrat , Stratman Derek , Supinie Timothy A. , Xue Ming , Kuster Charles , Labriola Jonathan 
Published: March 2021

AbstractAssimilation of dual-polarization (dual-pol) observations provides more accurate storm-scale analyses to initialize forecasts of severe convective thunderstorms. This study investigates the impact assimilating experimental sector-scan dual-pol observations has on storm-scale ensemble forecasts and how this impact changes over different data assimilation (DA) windows using the ensemble Kalman filter (EnKF). Ensemble forecasts are initialized after 30, 45, and 60 minutes of DA for two sets of experiments that assimilate either reflectivity and radial velocity only (EXPZ) or reflectivity and radial velocity plus differential reflectivity (EXPZZDR). This study uses the 31 May 2013 Oklahoma event which included multiple storms that produced tornadoes and severe hail, with focus placed on two storms that impacted El Reno and Stillwater during the event.The earliest initialized forecast of EXPZZDR better predicts the evolution of the El Reno storm than EXPZ, but the two sets of experiments become similar at subsequent forecast times. However, the later EXPZZDR forecasts of the Stillwater storm, which organized towards the end of the DA window, produce improved results compared to EXPZ, in which the storm is less intense and weakens. Evaluation of forecast products for supercell mesocyclones (updraft helicity [UH]) and hail show similar results with earlier EXPZZDR forecasts better predicting the UH swaths of the El Reno storm and later forecasts producing improved UH and hail swaths for the Stillwater storm. The results indicate that the assimilation of ZDR over fewer DA cycles can produce improved forecasts when DA windows sufficiently cover storms during their initial development and organization.
Sclerotherapy for Benign Cystic Lesions of the Head and Neck: Systematic Review of 474 Cases
Authors: Talmor Guy , Nguyen Brandon , Mir Ghayoour , Badash Ido , Kaye Rachel , Caloway Christen 
Published: March 2021

ObjectiveThe role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck.Data SourcesPubMed/MEDLINE, Cochrane Library, and Embase.Review MethodsThe PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta‐analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty‐two studies met criteria for inclusion.ResultsA total of 474 cases of sclerotherapy were reviewed. Agents comprised OK‐432, ethanol, doxycycline, tetracycline, and bleomycin. Lesions in the analysis were ranula, thyroglossal duct cyst, branchial cleft cyst, benign lymphoepithelial cyst, parotid cyst, thoracic duct cyst, and unspecified lateral neck cyst. A total of 287 patients (60.5%) had a complete response; 132 (27.9%) had a partial response; and 55 (11.6%) had no response. OK‐432 was the most widely utilized agent, with a higher rate of complete response than that of ethanol (62.0% vs 39.4%, P =. 015). Fifty‐three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively.ConclusionSclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.
Lurasidone for Adolescents With Complex Mental Disorders: A Case Series
Authors: Mole Tom B. , Furlong Yulia , Clarke Richard J. , Rao Pradeep , Moore Julia K. , Pace Giulia , Van Odyck Hugo , Chen Wai 
Published: March 2021

Objectives: Lurasidone is a new second generation (atypical) antipsychotic agent with unique receptor affinity and side-effect profiles, but limited literature is available on its use in adolescent populations. Contrasting with research treatment trials which typically recruit patients by stringent selection criteria, this case series examined the effects and tolerability of using lurasidone in adolescents within real-life clinical settings in treating complex cases who had not responded to other therapy options. Methods: We conducted a retrospective case-note audit of 6 adolescents aged 14 to 17 years old attending community child and adolescent mental health services (CAMHS) who were prescribed lurasidone. Results: Lurasidone had been prescribed for a range of “hard-to-manage” conditions with complex comorbidities, in adolescents in relation to specific use of lurasidone on the basis of clinical and pharmacological indications after exhausting more conventional treatment options. Case-note review suggested response to lurasidone was clinically positive in 3 cases, equivocal/marginal in 2 cases, and ineffective in 1 case. There were no cases of poor tolerance or adverse effects. Notably, positive responses for depressive and irritable mood symptoms were specifically recorded by prescribing clinicians, indicative of benefits on symptom improvement. No lurasidone attributed weight gain, galactorrhoea, metabolic abnormalities, sexual dysfunction or intolerance were reported. Pro-cognitive effects were not detected; but our findings were constrained by the non-systematic and incomplete information ascertainment, typical in retrospective case-note review. Conclusion: This case series provides preliminary data supporting lurasidone’s potential use in adolescents of complex clinical needs (but without a clinical diagnosis of bipolar disorder) within real-life clinical settings. Lurasidone appears to show a weight-sparing effect, in addition to improving mood symptoms in some cases. Lurasidone deserves further study for its use in the adolescent population (outside the remit of FDA) given its potential more favorable risk-benefit profile in young people. The favorable tolerability appear to be borne out by the pharmacodynamic predictions in our complex patients who would be excluded in formal clinical trial studies.
Intravitreal dexamethasone insert in diabetic macular edema super-refractory to anti-vascular endothelial growth factor therapy
Authors: Wilkins Carl S , Sobol Ethan K , Lema Gareth MC , Lee Jessica G , Rosen Richard B , Deobhakta Avnish 
Published: March 2021

Background: Some patients with diabetic macular edema (DME) fail to completely respond to anti-vascular endothelial growth factor (VEGF) therapy. These patients have a high treatment burden in the absence of significant improvement. We investigate the role of intravitreal dexamethasone insert (IDI) in eyes with super-refractory DME. Methods: A non-randomized interventional study was performed among eyes with super-refractory DME refractory to anti-VEGF therapy. Eyes were treated with IDI after failing clinical response to anti-VEGF, with a minimum of 15 prior. Failure to respond was defined as failure of vision to improve at least one line on Snellen Acuity chart, central subfield thickness (CST) greater than 320 μm, or failure of CST to improve by 10% or more. Eyes with glaucoma or prior uncontrolled steroid-responsive ocular hypertension were excluded. Patient outcomes were analyzed at weeks 6, 12, 24, and year 1. Results: Six eyes of four patients were identified. All patients had failed aflibercept. The mean number of prior anti-VEGF injections was 34.5. Eyes received an average of 2.92 dexamethasone injections per person-year (PY) and required breakthrough anti-VEGF injection at 1.95/PY. Mean pre-treatment visual acuity was 0.475 LogMAR, improving to 0.342 at week 6, and 0.375 at 1 year. Mean CST pre-injection was 386.5 mm, improving to 315 mm at 1 year. No glaucoma developed. Conclusions: Intravitreal dexamethasone insert appears effective in eyes with super-refractory DME. IDI resulted in excellent anatomic improvement on SD-OCT as well as modest visual improvement. Injection burden was reduced in those who may otherwise receive years of monthly treatments.
Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS
Authors: Oh Jiwon , Suthiphosuwan Suradech , Sati Pascal , Absinta Martina , Dewey Blake , Guenette Melanie , Selchen Daniel , Bharatha Aditya , Donaldson Emily , Reich Daniel S , Feinstein Anthony 
Published: March 2021

Objective: The central vein sign (CVS) and “paramagnetic rim lesions” (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS). Methods: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures. Results: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory( β =-0.024, p = 0.03) while PRL predicted performance on verbal memory ( β = -0.040, p = 0.04) and processing speed ( β = -0.039, p = 0.03). Conclusions: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.
Prolonged response to treatment based on cell-free DNA analysis and molecular profiling in three patients with metastatic cancer: a case series
Authors: Naqvi Mohammad Faraz , Vo Henry Hiep , Vining David , Tsimberidou Apostolia-Maria 
Published: March 2021

Background: Patients with advanced and/or metastatic solid tumors have limited treatment options. Mutations that serve as biomarkers of carcinogenesis can be found in cell-free DNA of patients’ plasma. Analysis of circulating tumor DNA (ctDNA) was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is not technically feasible or it is associated with high risk for complications. The role of ctDNA in precision oncology is promising but its clinical significance across tumor types remains to be validated. We report a case series of three heavily pretreated patients with advanced solid tumors who received matched targeted therapy based on ctDNA analysis and/or tumor molecular profiling. Case presentation: Three patients with advanced, metastatic cancer and the following characteristics are presented: a 71-year-old woman with ovarian cancer and BRCA2 mutation identified in ctDNA and tumor tissue was treated with a PARP inhibitor and achieved partial response by RECIST (Response Evaluation Criteria in Solid Tumors) for 22.6+ months; a 40-year-old woman with adenoid cystic carcinoma of the parotid gland was treated with a MEK/RAF pathway inhibitor on the basis of RAF1 amplification on ctDNA analysis and had stable disease for 20.2 months; and a 56-year-old woman with breast cancer and a BRCA1 mutation identified by ctDNA analysis was treated with a PARP inhibitor and achieved stable disease for 9.1 months. All three patients are alive at the time of this report. Conclusions: These results suggest that ctDNA analysis can contribute to selection of targeted therapy in patients with advanced, metastatic cancer. Prospective clinical trials to evaluate and optimize ctDNA biomarkers, as well as the integration of novel and/or alternative targeted therapies, are warranted to fully assess the role of ctDNA analysis in cancer therapy. Trial registration: www.clinicaltrials.gov (NCT02152254). Registered May 28, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02152254 . MD Anderson protocol # PA12-1161 (approval ID IRB1 FWA00000121) and # PA11-0377 (approval ID IRB4 FWA00005015).