bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded Low Allele Frequency RAS and BRAF V600E Testing in Metastatic Colorectal Cancer as Predictive Biomarkers for Cetuximab in the Randomized CO.17 Trial
Authors: Loree Jonathan M. , Dowers Anthony , Tu Dongsheng , Jonker Derek J. , Edelstein Daniel L. , Quinn Hannah , Holtrup Frank , Price Timothy , Zalcberg John R. , Moore Malcolm J. , Karapetis Christos S. , O'Callaghan Chris J. , Waring Paul , Kennecke Hagen F. , Hamilton Stanley R. , Kopetz Scott 
Published: October 2020

Abstract

Purpose:
Expanded RAS/BRAF mutations have not been assessed as predictive for single-agent cetuximab in metastatic colorectal cancer (mCRC), and low mutant allele frequency (MAF) mutations are of unclear significance. We aimed to establish cetuximab efficacy in optimally selected patients using highly sensitive beads, emulsion, amplification, and magnetics (BEAMing) analysis, capable of detecting alterations below standard clinical assays.

Patients and Methods:
CO.17 trial compared cetuximab versus best supportive care (BSC) in RAS/BRAF-unselected mCRC. We performed RAS/BRAF analysis on microdissected tissue of 242 patients in CO.17 trial using BEAMing for KRAS/NRAS (codons 12/13/59/61/117/146) and BRAF V600E. Patients without BEAMing but with previous Sanger sequencing–detected mutations were included.

Results:
KRAS, NRAS, and BRAF mutations were present in 53%, 4%, and 3% of tumors, respectively. Cetuximab improved overall survival [OS; HR, 0.51; 95% confidence interval (CI), 0.32–0.81; P = 0.004] and progression-free survival (PFS; HR, 0.25; 95% CI, 0.15–0.41; P &lt; 0.0001) compared with BSC in RAS/BRAF wild-type patients. Cetuximab did not improve OS/PFS for KRAS-, NRAS-, or BRAF-mutated tumors, and tests of interaction confirmed expanded KRAS (P = 0.0002) and NRAS (P = 0.006) as predictive, while BRAF mutations were not (P = 0.089). BEAMing identified 14% more tumors as RAS mutant than Sanger sequencing, and cetuximab lacked activity in these patients. Mutations at MAF &lt; 5% were noted in 6 of 242 patients (2%). One patient with a KRAS A59T mutation (MAF = 2%) responded to cetuximab. More NRAS than KRAS mutations were low MAF (OR, 20.50; 95% CI, 3.88—96.85; P = 0.0038).

Conclusions:
We establish single-agent cetuximab efficacy in optimally selected patients and show that subclonal RAS/BRAF alterations are uncommon and remain of indeterminate significance.
ASR490, a Small Molecule, Overrides Aberrant Expression ofNotch1in Colorectal Cancer
Authors: Tyagi Ashish , Chandrasekaran Balaji , Kolluru Venkatesh , Baby Becca V. , Sripathi Cibi A. , Ankem Murali K. , Ramisetti Srinivasa R. , Chirasani Venkat R. , Dokholyan Nikolay V. , Sharma Arun K. , Damodaran Chendil 
Published: October 2020

AbstractNotch1 activation triggers significant oncogenic signaling that manifests as enhanced metastatic potential and tumorigenesis in colorectal cancer. Novel small-molecule inhibitors, mainly plant-derived analogs, have low toxicity profiles and higher bioavailability. In this study, we have developed a small molecule, ASR490, by modifying structure of naturally occurring compound Withaferin A. ASR490 showed a growth-inhibitory potential by downregulating Notch1 signaling in HCT116 and SW620 cell lines. Docking studies and thermal shift assays confirmed that ASR490 binds to Notch1, whereas no changes in Notch2 and Notch3 expression were seen in colorectal cancer cells. Notch1 governs epithelial-to-mesenchymal transition signaling and is responsible for metastasis, which was abolished by ASR490 treatment. To further confirm the therapeutic potential of ASR490, we stably overexpressed Notch1 in HCT-116 cells and determined its inhibitory potential in transfected colorectal cancer (Notch1/HCT116) cells. ASR490 effectively prevented cell growth in both the vector (P = 0.005) and Notch1 (P = 0.05) transfectants. The downregulation of Notch1 signaling was evident, which corresponded with downregulation of mesenchymal markers, including N-cadherin and β-catenin and induction of E-cadherin in HCT-116 transfectants. Intraperitoneal administration of a 1% MTD dose of ASR490 (5 mg/kg) effectively suppressed the tumor growth in control (pCMV/HCT116) and Notch1/HCT116 in xenotransplanted mice. In addition, downregulation of Notch1 and survival signaling in ASR-treated tumors confirmed the in vitro results. In conclusion, ASR490 appears to be a potent agent that can inhibit Notch1 signaling in colorectal cancer.
‘Instruments of Justice:’ Biblical Contributions to a Public Theology of Engagement in Eastern European Context
Authors: Constantineanu Corneliu 
Published: October 2020

Abstract
The context of Eastern Europe, where faith was hidden and restricted to the private life of believers for so many decades, requires a rediscovery of the public dimension of faith. This article explores the issue of justice in Paul’s letter to the Romans and shows how this could represent an important resource for thinking afresh about justice in the context of Eastern Europe. There is also an important and necessary discussion on the righteousness, justification, justice, terminology in Paul. Paul has a particular understanding of justice as an integral part of the gospel, and that the believers in Christ are empowered to act as ‘instruments of justice.’
‘Assisted’ Migration and the Marshall Plan: the Italian Case
Authors: Strangio Donatella 
Published: October 2020

Abstract
Italy, as a country of arrival for many migrants from outside the European Union, is currently receiving much international media attention because of the ongoing so-called ‘migration crisis’. Historically, however, Italy has been a country of outward migration. This article analyses the history of Italian migration during the post-Second World War years. This crucial period in Italian history was characterised by economic reconstruction and recovery led by international institutions and the Marshall Plan. The Marshall Plan’s provisions on migration have received little scholarly attention, and this neglect is particularly pronounced in the case of Italy. This historical research draws mainly from documents retrieved from the Marshall Plan’s collections at the archives of the Bank of Italy, originally produced in the aftermath of the Second World War. The article is divided into four parts. The first section outlines the problem and embeds it within the existing literature on the history of migration policy in Italy. The second part examines the induced aid and migration policies of post-war Italy. The third part considers the architecture of the migration policy of that time, e.g. funding allocations and requests submitted to the United States for destination countries, such as Canada, or continents such as Latin America and Africa. Finally, the last section provides more in-depth analysis of the erp itself and its impact on Italian out-migration. The article concludes that cooperating and joint programming is a necessity for states in the management of migration.
The Interconnected Legacy of Migration, Drought, and Development in Santarém do Pará
Authors: Vilgiate Timothy 
Published: October 2020

Abstract
During major droughts in 1951–1953 and 1958, families from the rural Northeast of Brazil migrated to Santarém do Pará, a port city on the Lower Amazon. Over time, migrants and their descendants developed a significant presence in commerce and local politics, while retaining a multifaceted and complicated identity rooted in the Northeast. This article considers the formation of North-eastern identity in Santarém through an intergenerational lens, examining the stories about migration told by migrants and their descendants, as well as locals. In the city, narratives about migration from the Northeast and North-eastern identities are shaped in response to local conversations about development, national discourses about regional identity, and by intrafamilial and personal responses to the memory and trauma of drought. For the most part, North-eastern migrants in Santarém have embraced their role in bringing development to the city, seeing their triumph over the circumstances of drought and their economic success in the city as a triumph over the prejudices and disadvantages faced by their ancestors.
Sniffin’ Sticks to Measure Olfactory Function and Recovery Following Bilateral Superior Turbinate Resection as Part of Endoscopic Transsphenoidal Approach
Authors: Gong Shaina W. , Ahmadi Sorour , Blackburn Spiros L. , Ulin Lindsey , Citardi Martin J. , Luong Amber , Yao William C. 
Published: October 2020

Background: Extended endoscopic transsphenoidal (EET) approaches can include complete resection of both superior turbinate (ST) for wider exposure. Moreover, ST resection has been associated with postoperative olfactory impairment. Objective: We sought to determine the impact of bilateral ST resection on olfaction during a transsphenoidal approach. Method: A prospective observational study was conducted on 29 patients undergoing endoscopic skull base surgery sparing the olfactory tracts at a tertiary academic center. Olfactory function was measured with Sniffin’ Sticks at the preoperative visit, 2-weeks and 6 to 8 weeks postoperatively. All components: odor threshold (OT), odor discrimination (OD), odor identification (OI) and composite scores (TDI = OT+OD+OI) were evaluated. Result: Study was completed in 15 patients with 14 excluded due to a variety of reasons. At 2 weeks, a significant decrease was noted in composite scores (32.3 ± 5.4 vs. 23.8 ± 5.8, P < .05) and OT (7.7 vs. 3.2, P < .05). There was a significant increase in olfactory scores between post-op weeks 2 and 6 to 8 weeks in TDI (23.8 vs. 31.4, P < .05) as well as in OT (3.2 vs. 7.6, P < .05), OD (9.4 vs. 11.1, P < .05), and OI (11.1 vs. 12.7, P < .05). No significant difference was found between TDI (32.3 ± 5.4 vs. 31.4 ± 5.1), OT (7.7 vs. 7.6), OD (11.4 vs. 11.1) and OI (13.2 vs. 12.7) from preoperative and 6-8 weeks postoperative visits. Conclusion: Patients undergoing bilateral ST resection during EET procedures experience transient hyposmia postoperatively. However, the olfactory function normalizes to preoperative levels at 6 to 8 weeks. The resection of the bilateral superior turbinate does not appear to decrease olfactory function.
Kinesio taping does not improve ankle functional or performance in people with or without ankle injuries: Systematic review and meta-analysis
Authors: Nunes Guilherme S , Feldkircher Jonatan M , Tessarin Bruna Mariana , Bender Paula Urio , da Luz Clarissa Medeiros , de Noronha Marcos 
Published: October 2020

Objective: To investigate whether Kinesio taping technique, applied to ankles of healthy people as a preventive intervention and people with ankle injuries, is superior to sham or alternative interventions on ankle function. Data Sources: Medline, Embase, Amed, CINAHL, SPORTDiscus, Cochrane Library and Web of Science, from inception to August 2020. Review methods: The terms “ankle” and “kinesio taping” were used in the search strategy. Included studies were randomized controlled trials (including crossover design) investigating Kinesio taping effects on ankle functional performance compared to any alternative or control/sham technique. Results: From 5,572 studies, 84 met the eligibility criteria which evaluated 2,684 people. Fifty-eight meta-analyses from 44 studies were performed (participants in meta-analyses ranging from 27 to 179). Fifty-one meta-analyses reported ineffectiveness of Kinesio taping: moderate evidence for star excursion balance test (anterior direction), jump distance, dorsiflexion range of motion, and plantar flexion torque for healthy people (effect size = 0.08–0.13); low to very-low evidence for balance, jump performance, range of motion, proprioception, muscle capacity and EMG for healthy people; balance for older people; and balance and jump performance for people with chronic instability. Seven meta-analyses reported results favoring Kinesio taping (effect size[95% CI]): low to very-low evidence for balance (stabilometry, ranging from 0.42[0.07–0.77] to 0.65[0.29–1.02]) and ankle inversion (0.84[0.28–1.40]) for healthy people; balance for older people (COP velocity, 0.90[0.01–1.78]); and balance for people with chronic instability (errors, 0.55[0.06–1.04]). Conclusions: Current evidence does not support or encourage the use of Kinesio taping applied to the ankle for improvements in functional performance, regardless the population.
Association entre la fréquence de consultation des médias d’information et la détresse psychologique chez les femmes enceintes durant la pandémie de COVID-19: Association between news media consulting frequency and psychological distress in pregnant women during the COVID-19 pandemic
Authors: Lemieux Roxanne , Garon-Bissonnette Julia , Loiselle Mathilde , Martel Élodie , Drouin-Maziade Christine , Berthelot Nicolas 
Published: October 2020

Objectif: Examiner l’association entre la fréquence d’utilisation des médias d’information durant la pandémie de COVID-19 et l’ampleur de la détresse psychologique chez les femmes enceintes, considérant les impacts délétères connus de cette détresse sur le développement du fœtus. Méthode: Des femmes enceintes habitant la province de Québec ( N = 1014) ont été recrutées en avril 2020 par le biais des médias sociaux, alors qu’un état d’urgence sanitaire prévalait. Les participantes ont été divisées en quatre groupes, selon la fréquence auto-rapportée de consultation des médias d’information (peu ou pas; une fois par jour; plusieurs fois par jour; constante). Elles ont rempli des mesures des symptômes dépressifs, des affects négatifs, des symptômes de stress post-traumatique et d’anxiété spécifique de la COVID-19. Les scores aux instruments se regroupaient sous un facteur unique de détresse psychologique. Résultats: Une ANCOVA contrôlant pour l’âge, l’âge gestationnel, le niveau d’éducation, le revenu familial annuel et la présence d’un trouble mental diagnostiqué au moment de la participation à l’étude montre que la fréquence d’exposition aux médias d’information est significativement associée à la sévérité de la détresse psychologique chez les femmes enceintes au moment de la pandémie de COVID-19, F(3,998) = 27,02, p < 0,001, η2 partiel = 0,08. Selon les comparaisons de moyennes a posteriori, des taux plus élevés de détresse psychologique s’observent dès que l’exposition aux médias d’information dépasse une fois par jour (tailles de l’effet entre 0,38 et 0,81). Conclusions: Plus les femmes enceintes consultent les médias d’information pendant la pandémie de COVID-19, plus elles sont sujettes à présenter de la détresse psychologique. Les résultats offrent un des premiers appuis empiriques aux recommandations de l’Organisation mondiale de la santé, du gouvernement du Canada et d’associations de psychiatres encourageant la population à limiter sa consultation des médias d’information durant la pandémie de COVID-19.
Psychographic Profiling of Adult Tobacco Users and Implications for Mediated Message Tailoring
Authors: Duarte Danielle A. , Choi Kelvin 
Published: October 2020

Purpose: To investigate variations of psychographic profiles in adult tobacco users to inform message tailoring. Design: A cross-sectional design used data from the Simmons 2015 National Consumer Study. Setting: Data were voluntarily provided by US families through a mail survey on media, products, and services, brands, and attitudes. Subjects: US adult tobacco users (N = 4,609). Measures: Participants answered questions about general opinion/attitudes and provided demographic and tobacco use information. Analysis: A factor analysis was conducted to determine the “best” latent psychographic factor structure based on model fit, factor loadings, and interpretability. A structural equation model was then applied to assess the associations between demographics, tobacco product use, and latent psychographic factors. Results: We identified 9 latent psychographic factors: (1) helplessness, (2) happiness, (3) achievements, (4) religion, (5) interest in art and culture, (6) conscience, (7) conformity, (8) family indulgence, and (9) creativity. Endorsement of these factors varied by demographics and tobacco product use. E.g. low income tobacco users showed stronger endorsement for “helplessness” (Adjusted Standardized Regression Coefficient [ASRC]: 0.42; 95% CI: 0.33, 0.51) and “religion” (ASRC: 0.24; 95% CI: 0.14, 0.33). Less educated tobacco users showed stronger endorsement for “conformity” (ASRC: 0.16; 95% CI: 0.07, 0.24). Young adults had significant positive associations for “achievements” (ASRC: 0.57; 95% CI: 0.48, 0.67). Conclusion: Psychographic profiles of tobacco users vary by demographics and product use. Tailored anti-tobacco media campaigns to specific disparity groups matching their psychographic profiles may improve message effectiveness and reduce tobacco use disparities.
Palliative Medical Management of Inoperable Malignant Bowel Obstruction With “Triple Therapy”: Dexamethasone, Octreotide, and Metoclopramide
Authors: Wey Winston , Mian Moeena , Calabrese Rebecca , Hansen Eric , Walter Michelle , Wang Chong , Miller Austin , Case Amy A. 
Published: October 2020

Context: Malignant bowel obstruction (MBO) is a complication of advanced malignancy. For inoperable patients, symptoms are often treated using analgesics, anticholinergics, and anti-emetics. There are, however, few published guidelines for the medical management of MBO. Objective: To measure the effect of the combination of dexamethasone, octreotide, and metoclopramide (“triple therapy”) in patients with MBO, compared to patients who received none of the 3 medications (“no drug therapy”). Methods: A retrospective cohort study of patients with MBO admitted in a single-center comprehensive cancer center. Patients who received dexamethasone, octreotide, and metoclopramide during their hospitalization for treatment of inoperable MBO were selected for analysis. Patients were excluded if they received a venting gastric tube. Rate of de-obstruction as well as time to de-obstruction were measured. Results: There were 20 patients identified who received all 3 drugs of interest, and 29 patients identified who received none of the 3 medications. There was no statistically significant difference in rates of de-obstruction between the 2 groups, though there was a non-significant trend toward patients who received triple therapy were more likely to reach de-obstruction, compared to patients who had no drug therapy (95% vs. 83%, p = 0.379); there was no significant difference in adjusted analysis. Conclusion: In patients with inoperable MBO, there was no statistically significant difference in rates of de-obstruction with triple drug therapy compared to patients who received none of the 3 drugs, though the study may not have been powered to detect a difference and further investigation is warranted.
The Association of Advance Care Planning Documentation and End-of-Life Healthcare Use Among Patients With Multimorbidity
Authors: McDermott Cara L. , Engelberg Ruth A. , Khandelwal Nita , Steiner Jill M. , Feemster Laura C. , Sibley James , Lober William B. , Curtis J. Randall 
Published: October 2020

Purpose: Multimorbidity is associated with increased intensity of end-of-life healthcare. This association has been examined by number but not type of conditions. Our purpose was to understand how intensity of care is influenced by multimorbidity within specific chronic conditions to provide guidance for interventions to improve end-of-life care for these patients. Methods: We identified adults cared for in a multihospital healthcare system who died between 2010–2017. We categorized patients by 4 primary chronic conditions: heart failure, pulmonary disease, renal disease, or dementia. Within each condition, we examined the effect of multimorbidity (presence of 4 or more chronic conditions) on hospital and ICU admission in the last 30 days of life, in-hospital death, and advance care planning (ACP) documentation >30 days before death. We performed logistic regression to estimate associations between multimorbidity and end-of-life care utilization, stratified by the presence or absence of ACP documentation. Results: ACP documentation >30 days before death was associated with lower odds of in-hospital death for all 4 conditions both in patients with and without multimorbidity. With the exception of patients with renal disease without multimorbidity, we observed lower odds of hospitalization and ICU admission for all patients with ACP >30 days before death. Conclusions: Patients with dementia and multimorbidity had the highest odds of high-intensity end-of-life care. For patients with dementia, heart failure, or pulmonary disease, ACP documentation >30 days before death was associated with lower likelihood of in-hospital death, hospitalization, and ICU use at end-of-life, regardless of multimorbidity.
Severe and prolonged hypocalcemia after a single dose of denosumab for metastatic breast cancer with diffuse bone involvement without prior calcium/vitamin D supplementations
Authors: Uhm So Jung , Hall James A , Herrington Jon D 
Published: October 2020

Introduction Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia. Case report A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia. Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk. Discussion Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors’ knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.
Complete bilateral ophthalmoplegia in malignant intracranial hypertension in a child
Authors: Interlandi Emanuela , Pellegrini Francesco , De Luca Marco , Cerullo Giovanni , De Falco Arturo , De Marco Rocco , Tortori Achille , Lee Andrew G. 
Published: October 2020

Purpose: To describe a case of fulminant idiopathic intracranial hypertension (IIH) in a child with “malignant” presentation. Case report: A 16-year-old, previously healthy, girl presented with bilateral visual loss and bilateral global limitation of eye movements in the absence of headache. Extensive laboratory evaluation for infectious, inflammatory, autoimmune, and neoplastic conditions was negative. Magnetic resonance imaging (MRI) of the brain and lumbar puncture findings were consistent with a diagnosis of IIH. Extraocular motility improved in the next few days as well as optic disc edema but visual acuity remained poor. Conclusion: The authors believe that the acute, severe, and fulminant (“malignant”) presentation with markedly elevated intracranial pressure may produce the unique presentation of severe vision loss and bilateral complete ophthalmoplegia. Interestingly, there was no headache. To our knowledge this is the first such case to be reported in the English language ophthalmic literature.