bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ESR1 Mutations: From Bedside to Bench to Bedside
Authors: Hermida-Prado Francisco , Jeselsohn Rinath 
Published: February 2021

Abstract
The ESR1 ligand–binding mutations were unveiled a number of years ago and are the most common genetic mechanism of acquired resistance to endocrine treatment, particularly, to aromatase inhibitors. The discovery of these mutations was enabled after advancements in sequencing technologies and when metastatic tissue samples were interrogated. The ESR1 ligand–binding domain mutations are activating mutations that lead to constitutive ligand-independent activity, which explains the emergence of these mutations under the selective pressure of aromatase inhibitors. Arnesen and colleagues have generated new models of the ESR1 mutations using CRISPR technology to generate single-cell–derived clones in which the ESR1 ligand–binding mutations were “knocked-in” and expressed under the endogenous promoter of estrogen receptor. The authors have extensively characterized these models and have shed new light on the functional consequences ESR1 mutations.
See related article by Arnesen et al., p. 539
Dual‐Specificity Phosphatase 26 Protects Against Cardiac Hypertrophy Through TAK1
Authors: Zhao Jing , Jiang Xiaoli , Liu Jinhua , Ye Ping , Jiang Lang , Chen Manhua , Xia Jiahong 
Published: January 2021

Background
Heart pathological hypertrophy has been recognized as a predisposing risk factor for heart failure and arrhythmia. DUSP (dual‐specificity phosphatase) 26 is a member of the DUSP family of proteins, which has a significant effect on nonalcoholic fatty liver disease, neuroblastoma, glioma, and so on. However, the involvement of DUSP26 in cardiac hypertrophy remains unclear.

Methods and Results
Our study showed that DUSP26 expression was significantly increased in mouse hearts in response to pressure overload as well as in angiotensin II–treated cardiomyocytes. Cardiac‐specific overexpression of DUSP26 mice showed attenuated cardiac hypertrophy and fibrosis, while deficiency of DUSP26 in mouse hearts resulted in increased cardiac hypertrophy and deteriorated cardiac function. Similar effects were also observed in cellular hypertrophy induced by angiotensin II. Importantly, we showed that DUSP26 bound to transforming growth factor‐β activated kinase 1 and inhibited transforming growth factor‐β activated kinase 1 phosphorylation, which led to suppression of the mitogen‐activated protein kinase signaling pathway. In addition, transforming growth factor‐β activated kinase 1–specific inhibitor inhibited cardiomyocyte hypertrophy induced by angiotensin II and attenuated the exaggerated hypertrophic response in DUSP26 conditional knockout mice.

Conclusions
Taken together, DUSP26 was induced in cardiac hypertrophy and protected against pressure overload induced cardiac hypertrophy by modulating transforming growth factor‐β activated kinase 1–p38/ c‐Jun N‐terminal kinase–signaling axis. Therefore, DUSP26 may provide a therapeutic target for treatment of cardiac hypertrophy and heart failure.
Transcriptomic and Functional Analyses of Mitochondrial Dysfunction in Pressure Overload‐Induced Right Ventricular Failure
Authors: Hwang HyunTae V. , Sandeep Nefthi , Nair Ramesh V. , Hu Dong‐Qing , Zhao Mingming , Lan Ingrid S. , Fajardo Giovanni , Matkovich Scot J. , Bernstein Daniel , Reddy Sushma 
Published: January 2021

Background
In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading to RV hypertrophy and eventually RV failure. The mechanisms that promote the transition from stable RV hypertrophy to RV failure are unknown. We evaluated the role of mitochondrial bioenergetics in the development of RV failure.

Methods and Results

We created a murine model of RV pressure overload by pulmonary artery banding and compared with sham‐operated controls. Gene expression by RNA‐sequencing, oxidative stress, mitochondrial respiration, dynamics, and structure were assessed in pressure overload‐induced RV failure. RV failure was characterized by decreased expression of electron transport chain genes and mitochondrial antioxidant genes (aldehyde dehydrogenase 2 and superoxide dismutase 2) and increased expression of oxidant stress markers (heme oxygenase, 4‐hydroxynonenal). The activities of all electron transport chain complexes decreased with RV hypertrophy and further with RV failure (oxidative phosphorylation: sham 552.3±43.07 versus RV hypertrophy 334.3±30.65 versus RV failure 165.4±36.72 pmol/(s×mL),
P
<0.0001). Mitochondrial fission protein DRP1 (dynamin 1‐like) trended toward an increase, while MFF (mitochondrial fission factor) decreased and fusion protein OPA1 (mitochondrial dynamin like GTPase) decreased. In contrast, transcription of electron transport chain genes increased in the left ventricle of RV failure.

Conclusions
Pressure overload‐induced RV failure is characterized by decreased transcription and activity of electron transport chain complexes and increased oxidative stress which are associated with decreased energy generation. An improved understanding of the complex processes of energy generation could aid in developing novel therapies to mitigate mitochondrial dysfunction and delay the onset of RV failure.
Incidence of Ventricular Arrhythmias and 1‐Year Predictors of Mortality in Patients Treated With Implantable Cardioverter‐Defibrillator Undergoing Generator Replacement
Authors: Demarchi Andrea , Cornara Stefano , Sanzo Antonio , Savastano Simone , Petracci Barbara , Vicentini Alessandro , Pontillo Lorenzo , Baldi Enrico , Frigerio Laura , Astuti Matteo , Leonardi Sergio , Ghio Stefano , Oltrona Visconti Luigi , Rordorf Roberto 
Published: January 2021

BackgroundWhen implantable cardioverter defibrillator (ICD) battery is depleted most patients undergo generator replacement (GR) even in the absence of persistent ICD indication. The aim of this study was to assess the incidence of ventricular arrhythmias and the overall prognosis of patients with and without persistent ICD indication undergoing GR. Predictors of 1‐year mortality were also analyzed.Methods and ResultsPatients with structural heart disease implanted with primary prevention ICD undergoing GR were included. Patients were stratified based on the presence/absence of persistent ICD indication (left ventricular ejection fraction ≤35% at the time of GR and/or history of appropriate ICD therapies during the first generator's life). The study included 371 patients (82% male, 40% with ischemic heart disease). One third of patients (n=121) no longer met ICD indication at the time of GR. During a median follow‐up of 34 months after GR patients without persistent ICD indication showed a significantly lower incidence of appropriate ICD shocks (1.9% versus 16.2%,P<0.001) and ICD therapies. 1‐year mortality was also significantly lower in patients without persistent ICD indication (1% versus 8.3%,P=0.009). At multivariable analysis permanent atrial fibrillation, chronic advanced renal impairment, age >80, and persistent ICD indication were found to be significant predictors of 1‐year mortality.ConclusionsPatients without persistent ICD indication at the time of GR show a low incidence of appropriate ICD therapies after GR. Persistent ICD indication, atrial fibrillation, advanced chronic renal disease, and age >80 are significant predictors of 1‐year mortality. Our findings enlighten the need of performing a comprehensive clinical reevaluation of ICD patients at the time of GR.
Learning Slavery at Home
Authors: Livesey Andrea 
Published: January 2021

Abstract
Since Stephanie Camp wrote of the “rival” geography that enslaved people created on slave labor plantations, few studies outside the field of architectural history have used the built environment as a source to understand the lives of enslaved people and the mindsets of enslavers in the United States. This article takes adolescent outbuildings in Louisiana (garçonnières) as a starting point to understand how white parents taught and reinforced ideas of dominance over both the environment and enslaved people and simultaneously rooted young white sons to a slave labor plantation “home.” Using architectural evidence, alongside testimony left behind by both enslavers and the enslaved, this article argues that by moving young male enslavers out of the main plantation house and into a separate building, white enslaving parents created a “risk space” for sexual violence within the sexualized geography of the slave labor plantation. The garçonnière, with its privacy and age-and gender-specificity, constituted just one space of increased risk for enslaved women on Louisiana slave labor plantations from a violence that was manipulated within the built environment.
“Known To Be Equal to the Management”
Authors: Sandy Laura , Phillips Gervase 
Published: January 2021

Abstract
Enslaved overseers have largely been neglected in the extant historiography of plantation slavery. At best they have been pushed to the margins of the literature, their numbers and their significance downplayed. Yet, as large plantations diversified over the latter years of the eighteenth century, and as relations between established planters and independently minded and aspirational white overseers became prone to mistrust and friction, many prominent modernizing planters, including both Washington and Jefferson, began to experiment with unfree managers. They often proved to be skilled, dependable and, even under the pressure of the Revolutionary War, resilient. Yet their presence raised serious questions within plantation society too; they challenged white racial hegemony, and their ‘loyalty’ was a conditional and contingent quality. They occupy a unique place in the story of plantation management, one that challenges orthodox conceptions of race and power in the slave South.
Holding the Whip-Hand
Authors: Zacek Natalie 
Published: January 2021

Abstract
This article examines two female slaveholders, one real and one fictional, to explore the relationship between gender and slave management in both history and popular culture. Annie Palmer, the “White Witch of Rose Hall” plantation in Jamaica, although the creation of folklore and journalistic exaggeration, has functioned for a century and a half as a symbol not only of the evils of slavery but of the idea that female slaveholders’ cruelty threatened the system of slavery in a way in which that practiced by males did not. In New Orleans, Delphine Lalaurie, an elite woman renowned for her elegance and piety, became a figure of monstrosity after a house fire of 1834 revealed that her French Quarter mansion held a chamber of horrors for the enslaved, and offered a similar example of the dangers of female power in slave societies. Examining these women’s continuing presence both as historical figures and as characters in novels, television shows, and other creative productions, this article illuminates the strange career of the slaveholding woman, a figure execrated in her own era and misunderstood or ignored in contemporary historiography, yet simultaneously the subject over centuries of prurient cultural fascination.
Populism and the Rule of Recognition
Authors: Adamidis Vasileios 
Published: January 2021

Abstract
By reference to legal positivism and Hart’s Concept of Law, the paper argues that populism targets and aims to reconstruct the democratic rule of recognition. In particular, populism exploits the ambiguities in the nature of this social rule, by advocating the extension of the group whose consensus determines the criteria of legal validity from the restricted sphere of judges and officials, to the people at large. Populism instrumentalises the functions of the rule of recognition, aiming to provoke uncertainty in the system in order to accomplish a shift and, thus, alter the content of the rule. Infiltrating concepts with meanings that suit its ends and reordering the criteria of legal validity, populism prioritises an absolute form of popular sovereignty over a thin, dubious version of the rule of law. Nevertheless, the latter’s ambiguity allows populism to claim that the rule of law still forms part of its rule of recognition.
Perspectives of Students Labeled Intellectually Disabled at College: Using Disability Studies in Education as a Lens to Contemplate Inclusive Postsecondary Education
Authors: Bacon Jessica , Baglieri Susan 
Published: January 2021

Abstract
This study reports on the experiences of students with intellectual disability labels who participated in inclusive postsecondary education (ipse) at a public university. A disability studies framework is employed to discern and critique the aims of ipse programs and forefront the perspectives of persons who are identified as intellectually disabled. Qualitative participant-observation data was gathered and analyzed to describe how participants narrate ways they understand and value reciprocal relationships and working towards in(ter)dependence as productive and key aspects of their experience at a college. Implications of attending to student voice to guide our program development is discussed along with broader implications for the field.
Review of Intravenous Acetaminophen for Analgesia in the Postoperative Setting
Authors: Tompkins Danielle M. , DiPasquale Arielle , Segovia Michelle , Cohn Stephen M. 
Published: January 2021

Background Acetaminophen is a non-opioid analgesic commonly utilized for pain control after several types of surgical procedures. Methods This scoping primary literature review provides recommendations for intravenous (IV) acetaminophen use based on type of surgery. Results Intravenous acetaminophen has been widely studied for postoperative pain control and has been compared to other agents such as NSAIDs, opioids, oral/rectal acetaminophen, and placebo. Some of the procedures studied include abdominal, gynecologic, orthopedic, neurosurgical, cardiac, renal, and genitourinary surgeries. Results of these studies have been conflicting and largely have not shown consistent clinical benefit. Conclusion Overall, findings from this review did not support the notion that IV acetaminophen has significant efficacy for postoperative analgesia. Given the limited clinical benefit of IV acetaminophen, especially when compared to the oral or rectal formulations, use is generally not justifiable.
Surgically Treated Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck: Outcome Predictors and the Role of Adjuvant Radiation Therapy
Authors: Kampel Liyona , Dorman Alexandra , Horowitz Gilad , Fliss Dan M. , Gutfeld Orit , Muhanna Nidal 
Published: January 2021

Objectives: Advanced cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with poor outcome despite multimodality therapy. Comprehensive risk stratification may pinpoint the most suitable adjuvant treatment. This study aimed to evaluate the outcomes of surgically treated locoregional CSCCHN and to identify prognostic indicators of treatment outcomes. Methods: We retrospectively analyzed disease variables, pathologic characteristics, and management in association with treatment outcomes of all consecutive advanced CSCCHN patients who underwent surgical resection at Tel Aviv Sourasky Medical Center. Results: From 2008 to 2018, 74 patients met the inclusion criteria. Only perineural invasion (PNI) was significantly associated with worse overall survival (OS) ( P = .001). Location within the facial “mask areas” was significantly associated with pathologically negative cervical disease ( P = .001). Forty-seven patients underwent adjuvant radiation therapy (RT) which significantly improved OS and disease-free survival versus surgery alone ( P = .025 and P = 0.035, respectively). Conclusion: PNI was associated with worse OS in surgically treated advanced CSCCHN. Adjuvant RT conferred better outcomes despite high risk features.
A novel approach for scleral fixation using Carlevale lens
Authors: Fiore Tito , Messina Marco , Muzi Alessio , Lupidi Marco , Reibaldi Michele , Giansanti Fabrizio , Cagini Carlo 
Published: January 2021

Purpose: To evaluate the surgical outcomes and feasibility of a novel approach for scleral-fixation using a single-piece acrylic foldable Carlevale lens (Soleko). Methods: Eighteen eyes of 18 patients with aphakia, dislocated IOL, subluxated lens, anisometropia, perforated trauma, and retinal detachment who underwent IOL implantation with a Carlevale lens were evaluated. All the patients underwent a standard ophthalmologic examination. Anterior segment (AS)-OCT was used postoperatively to check plugs positioning and IOL tilt. Results: Mean patients age was 73 ± 19 years. Mean follow-up was 11.2 ± 4.1 months. Mean axial length was 23.7 ± 1.65 mm, white-to-white distance was 11.74 ± 0.40 mm, and axial length was 23.67 ± 1.65 mm. Refractive spherical equivalent prediction error was −0.31 ± 0.71D. Mean IOL tilt was 2.2° ± 1.6° and plugs were placed within the sclera. Five patients had aphakia, five in-the-bag IOL subluxation, three in-the-bag IOL luxation, one high residual myopia after previous verisyse implant, one Uveitis-Glaucoma-Hyphema syndrome, one perforating trauma with phacodonesis, one intraocular foreign body and retinal detachment, two lens subluxation. One eye developed cystoid macular edema which disappeared with topical steroids and FANS. No other complications were observed throughout the follow-up. Conclusion: Carlevale lens (Soleko) appears to be a viable option for both anterior and posterior segment surgeons in the management of complex cases providing less challenging maneuvers which lead to a good lens self-centration and minimal risk of haptic rupture and/or dislocation. The lens seems to offer a good compartmentalization between the anterior and posterior chamber reducing the risk of an inflammatory response.
Clinicopathological characteristics and long-term prognosis of monoclonal immunoglobulin light chain associated Fanconi syndrome
Authors: Chen Zhixin , Li Jiaying , Shi Xiaoxiao , Wang Ying , Xia Peng , Ye Wei , Ye Wenling , Qin Yan , Li Hang , Li Mingxi , Li Xuemei , Wen Yubing , Chen Limeng 
Published: January 2021

Background and aims: Monoclonal immunoglobulin light chain associated Fanconi syndrome (LC-FS) is a rare disease that involves proximal tubules. As most of the reported cases came from western countries, we aimed to analyze the clinicopathological characteristics of Asian LC-FS and its treatment responses to chemotherapy. Methods: A total of 26 LC-FS patients in a single-center were retrospectively studied. Results: At diagnosis, the mean age of the 26 Asian LC-FS patients was 54.7 ± 14.7 years, with females accounting for 57.7%. They presented with different degrees of proximal tubular dysfunctions with normoglycemic glycosuria (88.0%), hyperphosphaturia (84.2%) and aminoaciduria (84.0%) as the most common features. The mean estimated glomerular filtration rate (eGFR) was (68.0 ± 26.4) ml/min per 1.73 m2. After chemotherapy, renal response was achieved in 58.3% cases, which was accompanied by hematological response, and tubular response was acquired in 66.7% cases. During 3 years of follow-up, the eGFR levels significantly decreased in the monoclonal gammopathy of renal significance patients, few of whom (21.4%) had received chemotherapy. Conclusion: Asian LC-FS patients had mild renal function disorder. The chemotherapy could improve both renal and tubular functions, which may be related to the hematological response.
“Looking for Better (Job) Opportunities”: A Qualitative Analysis of the Occupational Health of Immigrants in Southern Spain
Authors: de Diego-Cordero Rocío , Romero-Saldaña Manuel , Jigato-Calero Ana , Badanta Bárbara , Lucchetti Giancarlo , Vega-Escaño Juan 
Published: January 2021

Background: Spain hosts the fourth largest number of immigrants in Europe, resulting in a large proportion of migrant workers. To date, few studies have examined the working conditions of immigrants in Southern Spain who are known to be at risk for adverse working conditions. This study aimed to investigate the patterns of work and working conditions of immigrants living in southern Spain and to understand how these factors may affect their health. Methods: A qualitative study using semi-structured interviews was conducted throughout 2019 and included 93 immigrants. Transcription, literal reading, and theoretical categorization were performed and a narrative content analysis was carried out. Results: Three themes emerged on working conditions of this study population, including social and labor-related characteristics, working conditions, and occupational health issues. Four employment sectors were most commonly occupied by these immigrants, including caregiving and food service for women and agriculture and construction for men. Most immigrants were from Latin America, unemployed or working part-time jobs, and not hired under an employment contract. Most worked in low-qualified jobs, and were exposed to occupational hazards such as falls from heights, manual handling of materials, and psychological strain. The lack of training on occupational risk prevention and labor rights was related to a low identification of work situations having a negative impact on the health of immigrants. Conclusions/Application to Practice: These findings should be taken into account by the government and public health managers to provide better assistance to immigrant workers in Europe.
Caretaker Perceptions About Self-cutting in Institutionalised Adolescents: A Comparison Between Cutters and Non-cutters
Authors: Kumar K. Raghavendra , Rajendra K. M. , Seshadri Shekhar P. , Girimaji Satish Chandra , Srinath Shoba , Sagar John Vijay 
Published: January 2021

Background: Studies are sparse on caretaker perceptions about self-cutting (SC) in institutionalised adolescents. Methods: Five caretakers in a shelter home for adolescent girls were interviewed and the data were analysed using interpretative phenomenological analysis. Results: Nine major themes emerged: expected reactions from others led to secrecy; reasons were relational and academic difficulties; benefits were control of emotions/thoughts or to get others’ attention; learning happened by witnessing and change in thinking; challenges were systemic contagion, counselling repeaters of SC and adolescent infatuation; responses were ‘we are empathetic’ and ‘friends are helpful, but have a limit’; goals for self and reflection were helpful to stop SC; vulnerabilities were lack of skills and problems faced; and protective factors were good skills and family relations. These novel findings contribute to the existing sparse literature and are useful for gaining a deeper understanding about and better management of SC.