bluuebunny/crossref_metadata_2025 huggingface dataset:
An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors
Authors: Indarte Martin , Puentes Roisin , Maruggi Marco , Ihle Nathan T. , Grandjean Geoffrey , Scott Michael , Ahmed Zamal , Meuillet Emmanuelle J. , Zhang Shuxing , Lemos Robert , Du-Cuny Lei , Layng Fabiana I.A.L. , Correa Ricardo G. , Bankston Laurie A. , Liddington Robert C. , Kirkpatrick Lynn , Powis Garth
Published: April 2019

Cnk1 (connector enhancer of kinase suppressor of Ras 1) is a pleckstrin homology (PH) domain–containing scaffold protein that increases the efficiency of Ras signaling pathways, imparting efficiency and specificity to the response of cell proliferation, survival, and migration. Mutated KRAS (mut-KRAS) is the most common proto-oncogenic event, occurring in approximately 25% of human cancers and has no effective treatment. In this study, we show that selective inhibition of Cnk1 blocks growth and Raf/Mek/Erk, Rho and RalA/B signaling in mut-KRAS lung and colon cancer cells with little effect on wild-type (wt)-KRAS cells. Cnk1 inhibition decreased anchorage-independent mut-KRas cell growth more so than growth on plastic, without the partial "addiction" to mut-KRAS seen on plastic. The PH domain of Cnk1 bound with greater affinity to PtdIns(4,5)P2 than PtdIns(3,4,5)P3, and Cnk1 localized to areas of the plasma membranes rich in PtdIns, suggesting a role for the PH domain in the biological activity of Cnk1. Through molecular modeling and structural modification, we identified a compound PHT-7.3 that bound selectively to the PH domain of Cnk1, preventing plasma membrane colocalization with mut-KRas. PHT-7.3 inhibited mut-KRas, but not wild-type KRas cancer cell and tumor growth and signaling. Thus, the PH domain of Cnk1 is a druggable target whose inhibition selectively blocks mutant KRas activation, making Cnk1 an attractive therapeutic target in patients with mut-KRAS–driven cancer.

Significance:

These findings identify a therapeutic strategy to selectively block oncogenic KRas activity through the PH domain of Cnk1, which reduces its cell membrane binding, decreasing the efficiency of Ras signaling and tumor growth.
Contact-Dependent Killing by Cytotoxic T Lymphocytes Is Insufficient for EL4 Tumor Regression In Vivo
Authors: Beck Richard J. , Slagter Maarten , Beltman Joost B.
Published: April 2019

Immunotherapies are an emerging strategy for treatment of solid tumors. Improved understanding of the mechanisms employed by cytotoxic T lymphocytes (CTL) to control tumors will aid in the development of immunotherapies. CTLs can directly kill tumor cells in a contact-dependent manner or may exert indirect effects on tumor cells via secretion of cytokines. Here, we aim to quantify the importance of these mechanisms in murine thymoma EL4/EG7 cells. We developed an agent-based model (ABM) and an ordinary differential equation model of tumor regression after adoptive transfer of a population of CTLs. Models were parameterized based on in vivo measurements of CTL infiltration and killing rates applied to EL4/EG7 tumors and OTI T cells. We quantified whether infiltrating CTLs are capable of controlling tumors through only direct, contact-dependent killing. Both models agreed that the low measured killing rate of CTLs in vivo was insufficient to cause tumor regression. In our ABM, we also simulated CTL production of the cytokine IFNγ in order to explore how an antiproliferative effect of IFNγ might aid CTLs in tumor control. In this model, IFNγ substantially reduced tumor growth compared with direct killing alone. Collectively, these data demonstrate that contact-dependent killing is insufficient for EL4 regression in vivo and highlight the potential importance of cytokine-induced antiproliferative effects in T-cell–mediated tumor control.

Significance:

Computational modeling highlights the importance of cytokine-induced antiproliferative effects in T-cell–mediated control of tumor progression.
A Distinct Epidemiologic Pattern of Precancerous Lesions of Esophageal Squamous Cell Carcinoma in a High-risk Area of Huai'an, Jiangsu Province, China
Authors: Pan Da , Su Ming , Zhang Ting , Miao Caiyun , Fu Lingmeng , Yang Ligang , Song Guang , Raine Philip J. , Wang Shaokang , Sun Guiju
Published: April 2019

Better understanding of esophageal precancerous lesions (EPL) can inform prevention strategies for esophageal squamous cell carcinoma (ESCC). Here, a cross-sectional epidemiologic study based on the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 2011 to 2017 was performed to fully investigate and characterize the epidemiology of EPL in rural Huai'an District. Data of 11,518 participants ages 35–75 years were collected through face-to-face interviews by questionnaire. Participants underwent a routine endoscopy examination, tissues were biopsied, and diagnosed according to the histologic criteria of dysplasia. Unconditional univariate and multivariate logistic regression analyses were performed to obtain crude and adjusted odds ratios and corresponding 95% confidence intervals, respectively. A total of 667 subjects were diagnosed with EPL. Factors associated with an increased risk of EPL included: drinking shallow well water and surface water, irregular diet, excessive smoking, exposure to secondhand smoke, consumption of corn, corn flour, pickled food, fried food, and hot food, and having a history of digestive system diseases. In addition, liquor use, but not other alcohol types, contributed to risk of EPL. Consumption of deep well water and vegetables, fruits, and animal livers were associated with lower EPL risk. This study suggested a completely distinct pattern that alcohol use plays only a minor role in EPL and excessive tobacco use shows a significant association in rural Huai'an District, while eating habits and environmental exposure may be the dominant factors. This work may be promising to provide scientific evidence to support primary prevention of ESCC in this region.
Cardiac Magnetic Resonance Imaging in Patients with Acute Ischemic Stroke and Elevated Troponin: A TRoponin ELevation in Acute Ischemic Stroke (TRELAS) Sub-Study
Authors: Haeusler Karl Georg , Jensen Christoph , Scheitz Jan F. , Krause Thomas , Wollboldt Christian , Witzenbichler Bernhard , Audebert Heinrich J. , Landmesser Ulf , Fiebach Jochen B. , Nolte Christian H. , Endres Matthias , Mochmann Hans-Christian
Published: April 2019

Background: Elevated high-sensitive cardiac troponin (hs-cTn) can be found in more than 50% of the patients with acute ischemic stroke. The observational TRoponin ELevation in Acute ischemic Stroke (TRELAS) study revealed that about 25% of all stroke patients with elevated troponin had a coronary angiography-detected culprit lesion affording immediate intervention, and about 50% of all patients did not have any obstructive coronary artery disease. Given the risk of procedure-related complications, the identification of stroke patients in urgent need of invasive coronary angiography is desirable. Methods: TRELAS patients were prospectively enrolled into this sub-study. In addition to conventional coronary angiography, a cardiac magnetic resonance imaging (MRI) at 3T was performed during the in-hospital stay after acute ischemic stroke to compare the diagnostic value of both imaging modalities. Results:Nine stroke patients (median age 73 years [range 58–87]; four females; median NIH Stroke Severity score on admission 4 [range 0–6] with elevated hs-cTnT [median 74 ng/L, interquartile range 41–247] on admission) completed cardiac MRI and underwent coronary angiography. The absence of MRI-detected wall motion abnormalities and/or late gadolinium enhancement in 5 stroke patients corresponded with the exclusion of culprit lesions or significant coronary artery disease by coronary angiography. Four patients had abnormal MRI findings, whereof 2 showed evidence of myocardial infarction and in whom coronary angiography demonstrated a >70% stenosis of a coronary artery. Conclusions: The TRELAS sub-study indicates that noninvasive cardiac MRI may provide helpful information to identify stroke patients with or without acute coronary syndrome. Our findings might help to select stroke patients in urgent need of coronary angiography.
Passive Monitoring at Home: A Pilot Study in Parkinson Disease
Authors: Kabelac Zachary , Tarolli Christopher G. , Snyder Christopher , Feldman Blake , Glidden Alistair , Hsu Chen-Yu , Hristov Rumen , Dorsey E. Ray , Katabi Dina
Published: April 2019

We conducted a pilot study using a passive radio-wave-based home monitor in individuals with Parkinson disease (PD) with a focus on gait, home activity, and time in bed. We enrolled 7 ambulatory individuals to have the device installed in the bedroom of their homes over 8 weeks and performed standard PD assessments at baseline. We evaluated the ability of the device to objectively measure gait and time in bed and to generate novel visualizations of home activity. We captured 353 days of monitoring. Mean gait speed (0.39–0.78 m/s), time in bed per day (4.4–12.1 h), and number (1.4–5.9) and duration (15.0–49.8 min) of nightly awakenings varied substantially across and within individuals. Derived gait speed correlated well with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale total (r = –0.88, p = 0.009) and motor sub-score (r = –0.95, p = 0.001). Six of the seven participants agreed that their activity was typical and indicated a willingness to continue monitoring. This technology provided promising new insights into the home activities of those with PD and may be broadly applicable to other chronic conditions.
Fluid Dynamics Analysis by CT Imaging Technique of New Sorbent Cartridges for Extracorporeal Therapies
Authors: Lorenzin Anna , Neri Mauro , de Cal Massimo , Pajarin Giordano , Mansi Montenegro Giuseppe , Savastano Sergio , Alghisi Alberta , Ronco Claudio
Published: April 2019

Background: Recent innovations in biomaterials technology have led to the development of innovative sorbents adopted as adsorbing devices in the field of extracorporeal blood purification therapies. As removal mechanism, adsorption allows to remove specific molecules, selectively binding them to sorbent materials. In addition to the material properties, a quintessential aspect influencing device properties is blood flow distribution within the sorbent particles. Objectives: In order to adequately characterize the potential adsorbing properties for an effective blood purification therapy, an in vitro study assessing the fluid dynamics inside 3 new cartridges, HA130, HA230 and HA330 (Jafron, Zhuhai City, ­China) was conducted through CT imaging technique. ­Methods: The cartridges were placed in vertical position in the CT ­gantry. Dye solution was circulated through the cartridges at 250 mL/min, longitudinal sections, 0.5 cm thick, were recorded for 60 s. Furthermore, an in vitro test was conducted to build pressure drop profiles. Blood was circulated at a different flow rate, 100–400 mL/min, step 50 mL/min. Pre and post cartridges pressures were acquired and pressure drop calculated. Results: Sequential images demonstrated an excellent distribution of the flow inside the cartridges. Average flow velocity was 0.37 cm/s for the 3 cartridges. HA130 had a homogeneous flow profile along the entire length of the device; HA230 and HA330 showed minimal differences between central and peripheral regions. Pressure drop profiles resulted linear, increasing proportionally with blood flow rate and packing density. Conclusions: We may conclude that the structural and functional design of the studied cartridges is adequate for haemoperfusion with no channelling phenomena. This ensures maximum and optimal utilization of the sorbent contained in the devices.
Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm
Authors: Fisher Courtney L. , Demel Stacie L.
Published: April 2019

Background: Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. Summary: This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.
Sex-Specific Effects of Stress on Mood-Related Gene Expression
Authors: Barko Kelly , Paden William , Cahill Kelly M. , Seney Marianne L. , Logan Ryan W.
Published: April 2019

Women are twice as likely as men to be diagnosed with major depressive disorder (MDD). Recent studies report distinct molecular changes in depressed men and women across mesocorticolimbic brain regions. However, it is unclear which sex-related factors drive distinct MDD-associated pathology. The goal of this study was to use mouse experimental systems to investigate sex-specific mechanisms underlying the distinct molecular profiles of MDD in men and women. We used unpredictable chronic mild stress to induce an elevated anxiety-/depressive-like state and “four core genotypes” (FCG) mice to probe for sex-specific mechanisms. As predicted, based on previous implications in mood, stress impacted the expression of several dopamine-, GABA-, and glutamate-related genes. Some of these effects, specifically in the prefrontal cortex, were genetic sex-specific, with effects in XX mice but not in XY mice. Stress also impacted gene expression differently across the mesocorticolimbic circuit, with increased expression of mood-related genes in the prefrontal cortex and nucleus accumbens, but decreased expression in basolateral amygdala. Our results suggest that females are sensitive to the effects of chronic stress, partly due to their genetic sex, independent of gonadal hormones. Furthermore, these results point to the prefrontal cortex as the node in the mesocorticolimbic circuitry with the strongest female-specific effects.
Brain Connectivity in Ateles geoffroyi: Resting-State Functional Magnetic Resonance Imaging of Working Memory and Executive Control
Authors: Platas-Neri Diana , Hidalgo-Tobón Silvia , Chico-Ponce de León Fernando , Muñoz-Delgado Jairo , Phillips Kimberley A. , Téllez-Alanís Bernarda , Villanueva-Valle Javier , de Celis Alonso Benito
Published: April 2019

The objective of this research was to describe the organization and connectivity of the working memory (WM) and executive control (EC) networks in Ateles geoffroyi in resting-state conditions. Recent studies have shown that resting-state activity may underlie rudimentary brain functioning, showing that several brain regions can be tonically active at rest, maximizing the efficiency of information transfer while preserving a low physical connection cost. Whole-brain resting-state images were acquired from three healthy adult Ateles monkeys (2 females, 1 male; mean age 10.5 ± SD 2.5 years). Data were analyzed with independent component analysis, and results were grouped together using the GIFT software. The present study compared the EC and WM networks obtained with human data and with results found in the literature in other primate species. Nine resting-state networks were found, which were similar to resting networks found in healthy human adults in the prefrontal basal portion and frontopolar area. Additionally, components of the WM network were found to be extending into the hypothalamus and the olfactory areas. A key finding was the discovery of connections in the WM and EC networks to the hypothalamus, the motor cortex, and the entorhinal cortex, suggesting that information is integrated from larger brain areas. The correlated areas suggest that many elements of WM and EC may be conserved across primate species. Characterization of these networks in resting-state conditions in nonhuman primate brains is a fundamental prerequisite for understanding of the neural bases underlying the evolution and function of this cognitive system.
Measurement of Uterine and Abdominal Muscle Electromyography in Pregnant Women for Estimation of Expulsive Activities during the 2nd Stage of Labor
Authors: Qian Xueya , Li Pin , Shi Shaoqing , Garfield Robert E. , Liu Huishu
Published: April 2019

Background: The progression of labor and delivery of the fetus is dependent upon uterine contractions and the voluntary effort of abdominal muscle contractions. A good monitor of uterine contractions and pushing is necessary for obstetrical care. Electromyography (EMG) is the underlying basis for contractility of muscle including the myometrium. Objectives: The aim of this study was to determine the relationship between EMG activity of uterine and abdominal muscles and the duration of the 2nd stage of labor in pregnant women. Methods: EMG of both uterine and abdominal muscles was simultaneously recorded from electrodes placed on the abdominal surface of 45 active 2nd stage-laboring nulliparous patients. EMG was recorded using filters to separate uterine and abdominal EMG signals, and various EMG signal parameters were analyzed. The duration of the 2nd stage of labor and other maternal and fetal characteristics were also recorded. Results: Uterine EMG bursts precede abdominal bursts and are accompanied by feelings of “urge to push” by the patients. Abdominal root mean square (RMS) and power, but not uterine EMG parameters, are reduced (p< 0.005) in patients with longer labors and linear regression analysis demonstrated a negative correlation to the duration of 2nd stage of labor (p < 0.001). Multivariate linear regression analysis of clinical characteristics (fetal weight, body mass index, placental location, etc.) and parameters of EMG showed that only abdominal RMS is negatively correlated with the duration of labor. Conclusions: (1) Uterine and abdominal EMG activities reflect the expulsive involuntary (uterine) and voluntary (abdominal) muscular activities during the 2nd stage of labor. (2) RMS and power of abdominal EMG diminish with longer labor when uterine EMG intensities are similar. (3) Recording of uterine and abdominal muscle activity provides objective evaluation of the muscle activity during the 2nd stage of labor and may aid in the evaluation of any interventions.
Unusual Course of an Aggressive Pituitary Prolactinoma: Case Report and Review of the Literature
Authors: Pérez Pinzón Juliana , González-Devia Deyanira , Kattah Calderón William , López Panqueva Rocío del Pilar , Jiménez Hakim Enrique
Published: April 2019

Pituitary carcinomas are rare tumors with heterogeneous behaviors. Their carcinogenesis is still unknown. Consequently, treatment is multimodal and not standardized. Dopamine (DA) agonists are used as first-line treatments, while radiotherapy and surgery may be used for local control of invasive tumors. We describe the case of a 35-year-old male who presented with an invasive prolactinoma, managed initially with a transsphenoidal resection, postsurgical radiotherapy and DA agonists. The patient posteriorly presented a sole metastatic lesion to the lumbar spine that was later managed with local radiotherapy. Due to pituitary recurrence of the lesion, multiple surgical resections were needed until further treatment was declined. The clinical course in this patient was unusual. He lived for 13 years after initial diagnosis, with a very invasive tumor without systemic chemotherapy. Radiotherapy is used in pituitary tumors in which surgery fails; we hypothesize that it contributed to the malignant transformation and the late resistance to DA agonists in our patient. Several biomarkers in tumoral tissue have been evaluated regarding their association with malignancy and aggressive behaviors, although more studies are still needed. Therapeutic strategies are limited, without evidence on the impact on overall survival and prognosis. Risk factors associated with early malignancy in pituitary prolactinomas include recurrent behavior, increase in prolactin levels with a stable sellar mass, and secondary development of DA agonist resistance. However, there are still no conclusive answers as to whether physicians should rigorously follow up these patients or provide direct therapy with aggressive approaches.
Decision-Making Measured by the Iowa Gambling Task in Patients with Alcohol Use Disorders Choosing Harm Reduction versus Relapse Prevention Program
Authors: Brière Marie , Tocanier Laure , Allain Phillippe , Le Gal Dewi , Allet Guillaume , Gorwood Phillip , Gohier Bénédicte
Published: April 2019

Aims: Two main therapeutic programs were offered to patients suffering from alcohol use disorders (AUDs): avoid the alcohol by abstinence or controlling their consumption. After information and motivational sessions, the patient chooses his own therapeutic plan. However, patients with AUD exhibit poor decision-making. The purpose of this study was to investigate the decision-making in AUD by comparing patients who chose to reduce and control their consumption to those who chose abstinence program. Methods: Sixty-seven subjects with alcohol use disorder were included (AUD group) for treatment, choosing either a relapse prevention program (RPP) or a harm reduction program (HRP). Patients were compared to a healthy control group (n = 31). Cognitive skills were assessed through the Montreal Cognitive Assessment test, the National Adult Reading Test, the Trail Making Test and the Iowa Gambling Task (IGT). Results: Thirty-seven patients with AUD chose the RPP while 30 followed a HRP. The AUD group performed worse than controls on the IGT. The RPP group had significantly lower performance than both HRP and control groups (these later groups being not statistically different). No correlation was observed between the available clinical, cognitive and intellectual measures. Conclusion: This study confirms that the decision-making process of patients with an alcohol use disorder is impaired. However, the 2 groups differ on the IGT scores, despite comparable clinical and cognitive profiles. The patients’ decision-making abilities could be a useful guide when developing therapeutic programs.
Merkel Cell Carcinoma of the Head in a Young African Albino Woman with HIV/HTLV-1 Coinfection Associated with Multiple Squamous Cell Carcinomas
Authors: Tenea Daniela , Dinkel Jurgen , Becker Jurgen C. , van der Walt Elisabeth
Published: April 2019

Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm of presumed neuroendocrine origin, with aggressive behavior and poor prognosis, that tends to have an increased incidence among elderly Caucasians and immunosuppressed individuals. MCC is either associated with a clonal integration of the Merkel cell polyoma virus into the host genome or with genomic alterations caused by chronic UV exposure. Tumors of either carcinogenesis show epithelial, neuroendocrine, and B-lymphoid lineage markers. HIV-infected African albinos have a higher risk of developing skin cancers, including MCC, in comparison with the general population. We report a case of MCC of the head in a young albino woman with a HIV/HTLV-1 coinfection. The patient also suffered from multiple squamous cell carcinomas of the scalp, face, lip, and ears, suggesting an UV carcinogenesis of MCC. The purpose of this case report is to emphasize the relationship between immunosuppression (HIV/HTLV-1 coinfection, chronic sun exposure, ocular-cutaneous albinism, pregnancy) and MCC. It highlights the importance of early diagnosis, dermatological screening with a risk-stratified surveillance, particularly in immunosuppressed albino patients in sub-Saharan Africa, and multidisciplinary management of this biologically unique cutaneous cancer.
Solitary Fibrous Tumor of the Urinary Bladder Associated with Hypoglycemia: An Unusual Case of Doege-Potter Syndrome
Authors: Urbina-Lima Ángel Daniel , Román-Martín Ana Ángeles , Crespo-Santos Antonia , Martínez-Rodríguez Amado , Cienfuegos-Belmonte Irene Rita , Olmo-Ruiz María , Esteban-Artiaga Ricardo , Molina-Suarez Juan Luis
Published: April 2019

Solitary fibrous tumors (SFT) are rare mesenchymal tumors, mostly benign. Less than 30 cases have been described for the urinary bladder, 2 of them malignant. These lesions show infrequent clinical and radiological usual features, making the diagnosis difficult. Therefore, an immunohistochemical and morphological comprehensive study, which will provide the main prognostic factors, is necessary for histological diagnosis. The hypoinsulinemic hypoglycemia, as a paraneoplastic syndrome associated with SFTs – also known as the Doege-Potter Syndrome – is an infrequent finding, and quite incidental when located in the bladder. In order to obtain a fair oncological result, the recommended procedure for this type of tumors is surgical exeresis with negative margins, including non-standardized chemotherapy/radiotherapy as an alternative treatment.
What Have We Learned about the Use of Cytosorb Adsorption Columns?
Authors: Ankawi Ghada , Xie Yun , Yang Bo , Xie Yuanyuan , Xie Pan , Ronco Claudio
Published: April 2019

Extracorporeal blood purification techniques have emerged and evolved in the recent years as a potential therapy for the purpose of immunomodulation in acute conditions like sepsis. Understanding the extent of immune system dysregulation involved in the pathophysiology of these conditions, resulted in the development of such treatment strategies aiming at restoring a balanced inflammatory response. Beyond conventional continuous renal replacement therapy, high volume hemofiltration, high cut-off membranes, adsorption alone and coupled plasma filtration adsorption are well-described techniques in the literature. The evidence to support their routine use, however, is conflicting and insufficient at this stage. Despite the low-quality level of evidence in favor of utilizing these techniques, studies to further explore their effectiveness, safety, and potential novel applications, continue to evolve. Our review aims at focusing on adsorption therapy, particularly using the adsorption columns Cystosorb.
Polyarticular Ochronotic Arthritis: A Case Report
Authors: Di Marco Marco , De Martinis Silvia Elena , Truzzi Marcello , Viganò Roberto
Published: April 2019

Alkaptonuria is an inherited disease due to the lack of homogentisic acid oxidase enzyme. The most common clinical presentations are a brownish-grey color of the sclera, dark skin, kidney stones, aortic calcifications, and ochronotic arthropathy. Ochronotic arthropathy is characterized by the accumulation of homogentisic acid in the connective tissue determining severe joint degeneration. We present the case of a woman affected by ochronosis since the age of 30 years. The patient showed a severe degeneration of the hip and knee joints bilaterally, associated with an important and painful functional limitation. Conservative care did not achieve good results. We performed bilateral cementless total knee arthroplasty and bilateral cementless total hip arthroplasty. We report satisfactory outcomes in terms of range of motion and pain control in a 6-year follow-up. Our approach to this pathology is the same we adopt with rheumatoid arthritis after our decennial experience. We suggest that prosthetic replacement represents a definitive way to treat ochronotic arthropathy.
“Three Long Rows of Empty Shelves” to Fill
Authors: Schröder Peter
Published: April 2019

In 1928-29 and 1930, the German-Brazilian anthropologist Curt Nimuendajú was contracted twice by German ethnological institutions (above all, museums) for organizing ethnographic collections and carrying out anthropological research among indigenous peoples; principally Jê-speaking peoples in various regions of today’s Maranhão and Tocantins states in Brazil. This is not only a lesser-known part of Nimuendajú’s biography, but also an example of a kind of academic cooperation difficult to imagine nowadays. The collections, partly destroyed during World War II, are still stored in the ethnological museums of Hamburg, Leipzig, and Dresden, along with a great number of mostly unpublished letters and other documents linked to them. The history of these expeditions offers an opportunity for reflections about the implicit theories involved in contemporary collecting, fieldwork methods, and the style of anthropology practiced. The research reveals influences from German ethnology on the academic environment in Brazil, which later became increasingly independent from this input.
Análise do relatório de guidance em empresas investigadas pela Polícia Federal: exame sob a perspectiva do gerenciamento de impressões
Authors: Arantes Vagner Alves , Gusmão Ivonaldo Brandani , Costa Mayla Cristina
Published: April 2019

Analisamos se as investigações de fraudes feitas pela Polícia Federal em três operações recentes geraram algum efeito na divulgação de informações prospectivas das empresas denunciadas. As operações Carne Fraca, Lava Jato e Zelotes poderiam alterar o gerenciamento de impressões nas informações prospectivas reportadas pelas empresas. Ponderamos o conteúdo dos chamados relatórios de guidance das empresas investigadas nessas operações entre 2010 a 2017, incluindo informações financeiras, operacionais e de investimentos. O período de análise coincide com o início da divulgação do relatório anual de guidance em 2010 pelas empresas listadas na Brasil Bolsa Balcão (B3). Os resultados mostram que o padrão de divulgação (tom mais positivo ou mais negativo) varia entre as empresas investigadas, indo desde uma rápida retomada do otimismo, até a descontinuidade do relatório.
Does Small Vessel Disease Burden Impact Collateral Circulation in Ischemic Stroke Treated by Mechanical Thrombectomy?
Authors: Eker Omer Faruk , Rascle Lucie , Cho Tae-Hee , Mechtouff Laura , Derex Laurent , Ong Elodie , Berthezene Yves , Nighoghossian Norbert
Published: April 2019

Background and Purpose—

The development of leptomeningeal collateral artery network might be adversely affected by small vessel wall alteration. We sought to determine whether small vessel disease (SVD) burden may impact collateral development in patients treated by mechanical thrombectomy for anterior circulation acute ischemic stroke.

Methods—

The patients admitted in our center for anterior circulation acute ischemic stroke and (1) treated by mechanical thrombectomy with or without thrombolysis and (2) who underwent a baseline magnetic resonance imaging were included in the study. The SVD burden and the pial collaterality were assessed through the cerebral SVD score (severe when ≥1) and the Higashida score (favorable when ≥ 3) on magnetic resonance imaging and digital subtraction angiography, respectively. Any association between the cerebral SVD score and the collaterality were assessed through comparative and regression analyses.

Results—

Between January 2013 and March 2018, 240 patients met the inclusion criteria (68.7±16.1 years old; 49.2 % female). The cerebral SVD scores were of 0 in 125 (52.1%), 1 in 74 (30.8%), 2 in 30 (12.5%), and 3 in 11 (4.6%) patients. Hundred and thirty-six patients (58.1%) presented a favorable collaterality score. The favorable collaterality subgroup presented a significantly higher proportion of female (79%), lower baseline National Institutes of Health Stroke Scale (
P
<0.001), and higher Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores (
P
<0.001). The regression analyses showed no impact of the cerebral SVD score on the collaterality pattern (odds ratio, 1.11, 95% CI, 0.82–1.50;
P
=0.51).

Conclusions—

In patients with anterior circulation acute ischemic stroke, collateral flow status does not seem to be influenced by SVD burden.
Working Memory Load-related Theta Power Decreases in Dorsolateral Prefrontal Cortex Predict Individual Differences in Performance
Authors: Brzezicka Aneta , Kamiński Jan , Reed Chrystal M. , Chung Jeffrey M. , Mamelak Adam N. , Rutishauser Ueli
Published: April 2019

Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy who were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information.
Climate Scientists’ Wide Prediction Intervals May Be More Likely but Are Perceived to Be Less Certain
Authors: Løhre Erik , Juanchich Marie , Sirota Miroslav , Teigen Karl Halvor , Shepherd Theodore G.
Published: April 2019

The use of interval forecasts allows climate scientists to issue predictions with high levels of certainty even for areas fraught with uncertainty, since wide intervals are objectively more likely to capture the truth than narrow intervals. However, wide intervals are also less informative about what the outcome will be than narrow intervals, implying a lack of knowledge or subjective uncertainty in the forecaster. In six experiments, we investigate how laypeople perceive the (un)certainty associated with wide and narrow interval forecasts, and find that the preference for accuracy (seeing wide intervals as “objectively” certain) versus informativeness (seeing wide intervals as indicating “subjective” uncertainty) is influenced by contextual cues (e.g., question formulation). Most important, we find that people more commonly and intuitively associate wide intervals with uncertainty than with certainty. Our research thus challenges the wisdom of using wide intervals to construct statements of high certainty in climate change reports.
Equalization or Selection? Reassessing the “Meritocratic Power” of a College Degree in Intergenerational Income Mobility
Authors: Zhou Xiang
Published: April 2019

Intergenerational mobility is higher among college graduates than among people with lower levels of education. In light of this finding, researchers have characterized a college degree as a great equalizer leveling the playing field, and proposed that expanding higher education would promote mobility. This line of reasoning rests on the implicit assumption that the relatively high mobility observed among college graduates reflects a causal effect of college completion on intergenerational mobility, an assumption that has rarely been rigorously evaluated. This article bridges this gap. Using a novel reweighting technique, I estimate the degree of intergenerational income mobility among college graduates purged of selection processes that may drive up observed mobility in this subpopulation. Analyzing data from the National Longitudinal Survey of Youth 1979, I find that once selection processes are adjusted for, intergenerational income mobility among college graduates is very close to that among non-graduates. This finding suggests that expanding the pool of college graduates per se is unlikely to boost intergenerational income mobility in the United States. To promote mobility, public investments in higher education (e.g., federal and state student aid programs) should be targeted at low-income youth.
Development of a mass spectrometry method for 1,25-dihydroxy vitamin D3 using immunoextraction sample preparation
Authors: Ivison Fiona M , Hinchliffe Edward , Howarth Neil , Pickersgill Mandy , Tetlow Lesley
Published: April 2019

Background

1,25-Dihydroxy vitamin D3 (DHVD) is the active metabolite of vitamin D, required to maintain blood calcium concentrations. Measurement has proved challenging as it circulates in picomolar concentrations and must be differentiated from other dihydroxyvitamin D species. Clinically, it is essential to be able to determine the cause of hypercalcaemia, which may be due to DHVD excess.

Methods

The liquid chromatography-mass spectrometry (LCMS) assay which has been developed uses immunoextraction of 0.5 mL serum followed by Amplifex™ derivatization of the dried eluent, with the analysis using the SCIEX 6500+ instrument taking a run time of 11 min.

Results

The limit of quantitation was determined (15 pmol/L) and the method is linear up to at least 600 pmol/L. Repeatability ranged from 6.1% at 23 pmol/L to 2.5% at 172 pmol/L and intermediate imprecision was 15.6% at 26 pmol/L to 8.3% at 173 pmol/L. The method is unaffected by icterus, haemolysis or lipaemia. Good performance was achieved with the samples from the vitamin D external quality assessment scheme, demonstrating a negative bias compared with the all lab trimmed mean (average –13.8%) and the specific method group (average –7.75%). A negative bias was observed across the concentration range found in 78 patient samples in comparison to a commercial radioimmunoassay (mean –47.8%). This was not unexpected and is likely due to better specificity of the mass spectrometry assay and the lack of a commutable standard reference calibrator.

Conclusions

We have developed a sensitive and robust LCMS method for the analysis of DHVD in serum, utilizing immunoextraction and derivatization to provide specificity.
Association of novel biomarkers with major clinical outcomes in a cohort of patients with atherosclerotic renovascular disease
Authors: Vassallo Diana , Alderson Helen , Vuilleumier Nicolas , Ritchie James , Green Darren , Pagano Sabrina , Virzi Julien , Chrysochou Constantina , Kalra Philip A
Published: April 2019

Introduction

In this study, we investigate whether the addition of biomarkers to a model based on traditional risk factors improves risk prediction and patient selection for revascularization in atherosclerotic renovascular disease.

Methods

Patients in the Salford Renovascular Study who had the following biomarkers analysed on a baseline sample were included in this study: FGF-23, Cystatin C, kidney injury molecule-1, myeloperoxidase, neutrophil gelatinase-associated lipocalin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity Troponin T and anti-apolipoprotein A1 IgG. Cox proportional hazards models and net reclassification index were used to study the effects of either individual or a panel of biomarkers on predicting death, end-stage kidney disease and cardiovascular events.

Results

A total of 112 patients were followed up for a median 59.9 months (IQR 33.6–86.9). In total, 75 patients died, 21 reached end-stage kidney disease and 36 suffered a cardiovascular event. Only NT-proBNP maintained a statistically significant association with all end-points (death: HR 1.62 [95% CI 1.26–2.10], P < 0.0005; end-stage kidney disease: HR 1.51 [95% 1.19–1.91], P = 0.001; cardiovascular event: HR 1.56 [95% CI 1.23–1.97], P < 0.0005). Risk reclassification improved with addition of all biomarkers as a panel to the base model. Only patients with NT-proBNP concentrations above 300 ng/L gained benefit from revascularization with regard to all adverse end-points compared with medically managed patients.

Conclusions

NT-proBNP is independently associated with increased risk for all adverse events in atherosclerotic renovascular disease. Novel biomarkers may have an incremental risk predictive value when used in combination with traditional risk factors, and NT-proBNP may have value in patient selection for revascularization. Given the small size of this study, larger multicentre studies are required to validate these findings.
A new design of fractional-order dynamic matrix control with proportional–integral–derivative-type structure
Authors: Wang Dawei , Zou Hongbo , Tao Jili
Published: April 2019

Most dynamic systems in practice are of fractional order and often the models using fractional-order equations can grasp their intrinsic properties with more accuracy compared with conventional differential equations. In this paper, a fractional-order modeling-based proportional–integral–derivative-type dynamic matrix control is developed and tested on a typical industrial heating furnace system with fractional-order dynamics. The Oustaloup approximation method is first adopted to obtain the model approximation of the processes, which paves the way for the application of integer order dynamic matrix control to the fractional-order systems. Meanwhile, a set of proportional–integral–derivative-type operators are introduced in the cost function to further optimize the dynamic matrix control in terms of tracking and disturbance-rejection performance. The resulting controller bears both the merits of the dynamic matrix control and the proportional–integral–derivative, and thus improved control performance is obtained. In addition, an industrial heating furnace process system is given to test the performance of the proposed method in comparison with traditional integer order model-based dynamic matrix control, and results show that the proposed method gives improved system performance.
Educating Students with Mild Handicaps in General Classrooms: Essential Teaching Practices for General and Special Educators
Authors: Cannon Glenna S. , Idol Lorna , West J. Frederick
Published: April 2019

This study was designed to identify and validate essential teaching practices needed by both general and special educators to successfully educate students with mild handicaps in general classrooms. An interdisciplinary panel of 105 experts, evenly divided into university-based and field-based participants from 35 states, identified 96 of 125 practices in six categories as being essential for effective teaching of mainstreamed students with mild handicaps. Based on a two-round Delphi procedure, a substantial majority (82%) of these teaching practices were seen as being essential for both general and special educators across all six rated categories. Panel ratings were significantly higher for special educators than general educators on four of the six categories. No significant differences in ratings were found for university-based versus field-based panelists, or for field-based panelists who were professionals directly involved in elementary or secondary teaching roles versus administrators, supervisors, and consultants. Based on essential teaching practices validated in this study, implications for preservice teacher preparation and staff development programs for general and special educators are discussed.
In search of the skilled city: Skills and the occupational evolution of British cities
Authors: Sunley Peter , Martin Ron , Gardiner Ben , Pike Andy
Published: April 2019

Recent research has argued that human capital has become the key driver of city growth and that there is a widening divergence between high- and low-skill cities. This skilled-city view includes several stylised propositions. The first is that more skills and human capital generate stronger economic growth; the second is that already-skilled cities are becoming ever more skilled; and, the third is that larger cities tend to have stronger concentrations of, and faster growth in, high-skilled, cognitive occupations. Using a detailed data set for occupational change in 85 urban Travel to Work Areas in Britain between 1981 and 2015, this paper evaluates whether these propositions apply to British urban evolution, and how they relate to the ‘hollowing-out’ of medium-skilled jobs. The results confirm the close interactive relationship between growth and high-skilled occupations. However, some of the skilled-city propositions, such as ‘smart cities becoming smarter’, and a positive relationship between agglomeration and high-skilled employment growth, do not apply in Britain where other factors have been more important. The pattern of high-skill growth has shown a strong regional dimension, and the ‘emergence’ of newer smaller cities, particularly in southern England, has been more evident than the ‘resurgence’ of large core and industrial cities.
Evergreen: The First U.S. Veterans’ Blind Rehabilitation Center
Authors: Goodrich Gregory L. , Zampieri Tom
Published: April 2019

Evergreen was a World War I (WWI) adult, inpatient vocational rehabilitation facility for war-blind soldiers, sailors, and marines in the United States. Although Evergreen shared similarities with European war-blind rehabilitation organizations, it was novel in its philosophy and approach. It was also unlike any civilian blind rehabilitation program of its day. Although there are no comprehensive records known to us of how many troops became blind or sustained vision loss during WWI, studying published reports of the veterans served by Evergreen provides some insight into this population. As the United States’ only blind rehabilitation facility for adults, Evergreen achieved several firsts, including having a national scope, being racially integrated (at least to some degree), and innovating a residential family training program. A role model of its day, it is now largely a footnote in the history of blind rehabilitation. We argue that the story of Evergreen contains lessons that should be remembered.