bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust and Nonrobust Aspects of Atlantic Meridional Overturning Circulation Variability and Mechanisms in the Community Earth System Model
Authors: Danabasoglu Gokhan , Landrum Laura , Yeager Stephen G. , Gent Peter R. 
Published: August 2019

Abstract
Robust and nonrobust aspects of Atlantic meridional overturning circulation (AMOC) variability and mechanisms are analyzed in several 600-yr simulations with the Community Earth System Model. The simulations consist of a set of cases where a few loosely constrained ocean model parameter values are changed, a pair of cases where round-off level perturbations are applied to the initial atmospheric temperature field, and a millennium-scale integration. The time scales of variability differ among the cases with the dominant periods ranging from decadal to centennial. These dominant periods are not stationary in time, indicating that a robust characterization of AMOC temporal variability requires long, multimillennium-scale simulations. A robust aspect is that positive anomalies of the Labrador Sea (LS) upper-ocean density and boundary layer depth and the positive phase of the North Atlantic Oscillation lead AMOC strengthening by 2–3 years. Respective contributions of temperature and salinity to these density anomalies vary across the simulations, but in a majority of the cases temperature contributions dominate. Following an AMOC intensification, all cases show that advection of warm and salty waters into the LS region results in near-neutral density anomalies. Analysis of the LS heat budget indicates that temperature acts to increase density in all cases prior to an AMOC intensification, primarily due to losses by sensible and latent heat fluxes. The accompanying salt budget analysis reveals that the salt contribution to density anomalies varies across the cases, taking both positive and negative values.
Screening for hemodialysis graft stenosis and short-term thrombosis risk: A comparison of the available tools
Authors: Tessitore Nicola , Lipari Giovanni , Contro Alberto , Moretti Francesca , Mansueto Giancarlo , Poli Albino 
Published: August 2019

Introduction: Guidelines recommend hemodialysis graft screening to identify and repair significant (>50%) stenosis at high risk of thrombosis, but there is insufficient evidence to prefer one or other screening tool due to the lack of studies comparing all available options. Methods: Seeking an optimal screening approach, we compared the performance of all currently used tools (duplex ultrasound to detect significant stenosis (StD) and measure access blood flow (QaD), ultrasound dilution access blood flow (QaU), static venous intra-access pressure ratio (VAPR), dynamic arterial and venous pressures measurement, and monitoring) for diagnosing significant angiography-proven stenosis (StA) and predicting incipient thrombosis (occurring within 4 months) in 62 grafts. All thrombotic and symptomatic acute hypotension episodes were recorded during follow-up. Results: VAPR > 0.70 and QaU < 1600 mL/min were the best indicators to angiography for those aiming to identify the majority of StA (91% sensitivity) and QaU < 1000 mL/min or StD for those aiming to avoid unnecessary angiograms (95%–93% positive predictive value). At Cox’s analysis, the only significant thrombosis predictors were acute hypotension episodes (relative risk = 4.4 (95% confidence interval = 2.2–8.8), p < 0.0001) and QaU or QaD (14% (95% confidence interval = 8–21) or 16% (95% confidence interval = 6–25) increased risk per 100 mL/min drop in Qa, p < 0.003). Thrombosis risk (adjusted for acute hypotension) became significantly higher at QaU = 1000–700 mL/min (relative risk = 3.6 (95% confidence interval = 1.6–8.2), p < 0.001) and QaD = 1300–1000 mL/min (relative risk = 3.1 (95% confidence interval = 1.1–12.8), p = 0.031). The proportion of thromboses attributable to acute hypotension was 40% (95% confidence interval = 24–57). Conclusions: Our comparative study showed that an effective screening for graft stenosis and short-term thrombosis risk can rely on Qa surveillance alone, and suggested that avoiding acute hypotension and correcting stenosis at QaU < 1000 mL/min or QaD < 1300 mL/min can contain thrombosis risk.
Angiotensinogen and interleukin 18 in serum and urine of children with kidney cysts
Authors: Plesiński Krzysztof , Adamczyk Piotr , Świętochowska Elżbieta , Morawiec- Knysak Aurelia , Gliwińska Aleksandra , Bjanid Omar , Szczepańska Maria 
Published: August 2019

Background: The most common disease associated with the presence of kidney cysts in the population is autosomal dominant polycystic kidney disease (ADPKD), which finally leads to end-stage renal disease. Method: The study evaluated serum and urinary concentration of angiotensinogen (AGT) and interleukin 18 (IL-18) in a group of 39 children with renal cysts of different aetiology. Results: Serum and urinary AGT concentration in children with renal cysts was higher compared to controls, regardless of the underlying background and gender. Serum IL-18 concentration was lower, in contrast, and the concentration of IL-18 in the urine did not differ between affected and healthy children. Negative correlation between urinary IL-18 concentration and systolic and mean arterial blood pressure was noted. Conclusions: Higher AGT levels in serum and urine in children with renal cysts may indicate the activation of the renin–angiotensin–aldosterone system, including its intrarenal part, even before the onset of hypertension. Lower serum concentration of IL-18 in children with kidney cysts may indicate the loss of the protective role of this cytokine with the occurrence of hypertension.
Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms
Authors: Serrano-Falcón Blanca , Delgado-Aros Sílvia , Mearin Fermín , Ciriza de los Ríos Constanza , Serra Jordi , Mínguez Miguel , Montoro Huguet Miguel , Perelló Antonia , Santander Cecilio , Pérez Aisa Ángeles , Bañón-Rodríguez Inmaculada , Rey Enrique 
Published: August 2019

Background: Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population. Methods: In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 μg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling ‘better’ or ‘much better’ versus the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response. Results: A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1–19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%). Conclusions: Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.
Patient Complaints: Patients’ and Physicians’ Interaction in Handling Complex Requests of Care
Authors: Ryynänen Sanna 
Published: August 2019

Objective: The study report focuses on the interaction of patients’ complaint cases and their related physicians’ responses in handling patients’ complex requests based on the dynamics of power and ideology. Method: Data consist of 3 selected patients’ complaints and 7 physicians’ responses in a specialized medical care organization in December 2016. Data of the qualitative case study were used in narrative analysis. Results: The study revealed storylines of narratives ending in physicians’ collective ideology of encounters with dissatisfied patients. Conclusion: The interaction between patients’ complaints and physicians’ responses showed emergent patterns of conflicts, which were both constraining and enabling.
Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: a randomised controlled proof-of-concept trial
Authors: Kunadian Vijay , Wilson Nina , Stocken Deborah D. , Ali Hani , McColl Elaine , Burns Graham , Howe Nicola , Fisher Andrew , De Soyza Anthony 
Published: August 2019

The APPLE COPD-ICON2 trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) without prior history of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the predefined cut-off of platelet inhibition measured using the Multiplate test in COPD patients.Eligible patients were randomised to aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only for 6 months. The primary outcome comprises inhibition (binary response) of arachidonic acid- (ASPI test, cut-off <40) and adenosine diphosphate- (ADP test, cut-off <46) induced platelet aggregation at 6 months.543 patients were screened and 120 patients were recruited with mean age of 67.5 years; 47.5% patients were male. The per-protocol ASPI test response rate to aspirin was 68.3% (95% CI 52.3–80.9%). The per-protocol ADP test response rate to ticagrelaor was 68.8% (95% CI 50.4–82.6%).Platelet response to antiplatelet therapy with aspirin and ticagrelor was not observed in nearly one-third of COPD patients without prior history of cardiovascular disease. These findings support the high pro-thrombotic milieu and the need for further research to determine the effect of antiplatelet/antithrombotic therapy on cardiovascular morbidity and mortality in COPD patients.
Rethinking self-injury recovery: a commentary and conceptual reframing
Authors: Lewis Stephen P. , Hasking Penelope A. 
Published: August 2019

SummaryA growing body of research has focused on understanding what may contribute to cessation of self-injury. Although these efforts are of value, cessation represents just one component of self-injury recovery. Exclusive or primary focus on cessation may foster unrealistic expectations for those with lived experience of non-suicidal self-injury (NSSI). Accordingly, this commentary discusses the importance of expanding the concept of NSSI recovery beyond cessation in both research and clinical domains. We conclude by presenting a person-centred and non-stigmatising conceptual reframing of recovery.
Atypical, Non-V600 BRAF Mutations as a Potential Mechanism of Resistance to EGFR Inhibition in Metastatic Colorectal Cancer
Authors: Johnson Benny , Loree Jonathan M. , Jacome Alexandre A. , Mendis Shehara , Syed Muddassir , Morris II Van K. , Parseghian Christine M. , Dasari Arvind , Pant Shubham , Raymond Victoria M. , Vilar Eduardo , Overman Michael , Kee Bryan , Eng Cathy , Raghav Kanwal , Kopetz Scott 
Published: August 2019

PURPOSE

Atypical, non-V600 BRAF (
aBRAF
) mutations represent a rare molecular subtype of metastatic colorectal cancer (mCRC). Preclinical data are used to categorize
aBRAF
mutations into class II (intermediate to high levels of kinase activity,
RAS
independent) and III (low kinase activity level,
RAS
dependent). The clinical impact of these mutations on anti-EGFR treatment efficacy is unknown.

PATIENTS AND METHODS
Data from 2,084 patients with mCRC at a single institution and from an external cohort of 5,257 circulating tumor DNA (ctDNA) samples were retrospectively analyzed. Overall survival (OS) was calculated using Kaplan-Meier and log-rank tests. Statistical tests were two-sided.

RESULTS

BRAF mutations were harbored by 257 patients, including 36 with
aBRAF
mutations: 22 class III, 10 class II, four unclassified. For patients with
aBRAF
mCRC, median OS was 36.1 months, without a difference between classes, and median OS was 21.0 months for patients with

BRAF
V600E

mCRC. In contrast to right-sided predominance of tumors with

BRAF
V600E

mutation, 53% of patients with
aBRAF
mCRC had left-sided primary tumors. Concurrent
RAS
mutations were noted in 33% of patients with
aBRAF
mCRC, and 67% of patients had microsatellite stable disease. Among patients with
aBRAF RAS
wild-type mCRC who received anti-EGFR antibodies (monotherapy, n = 1; combination therapy, n = 10), no responses to anti-EGFR therapy were reported, and six patients (four with class III
aBRAF
mutations, one with class II, and one unclassified) achieved stable disease as best response. Median time receiving therapy was 4 months (range, 1 to 16). In the ctDNA cohort, there was an increased prevalence of
aBRAF
mutations and subclonal
aBRAF
mutations (
P
< .001 for both) among predicted anti-EGFR exposed compared with nonexposed patients.

CONCLUSION

Efficacy of anti-EGFR therapy is limited in class II and III
aBRAF
mCRC. Detection of
aBRAF
mutations in ctDNA after EGFR inhibition may represent a novel mechanism of resistance.
Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures
Authors: Fankhauser Maria , Bechmann Nicole , Lauseker Michael , Goncalves Judith , Favier Judith , Klink Barbara , William Doreen , Gieldon Laura , Maurer Julian , Spöttl Gerald , Rank Petra , Knösel Thomas , Orth Michael , Ziegler Christian G , Aristizabal Prada Elke Tatjana , Rubinstein German , Fassnacht Martin , Spitzweg Christine , Grossman Ashley B , Pacak Karel , Beuschlein Felix , Bornstein Stefan R , Eisenhofer Graeme , Auernhammer Christoph J , Reincke Martin , Nölting Svenja 
Published: August 2019

Abstract
There are no officially approved therapies for metastatic pheochromocytomas apart from ultratrace 131I-metaiodbenzylguanidine therapy, which is approved only in the United States. We have, therefore, investigated the antitumor potential of molecular-targeted approaches in murine pheochromocytoma cell lines [monocyte chemoattractant protein (MPC)/monocyte chemoattractant protein/3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)], immortalized mouse chromaffin Sdhb−/− cells, three-dimensional pheochromocytoma tumor models (MPC/MTT spheroids), and human pheochromocytoma primary cultures. We identified the specific phosphatidylinositol-3-kinase α inhibitor BYL719 and the mammalian target of rapamycin inhibitor everolimus as the most effective combination in all models. Single treatment with clinically relevant doses of BYL719 and everolimus significantly decreased MPC/MTT and Sdhb−/− cell viability. A targeted combination of both inhibitors synergistically reduced MPC and Sdhb−/− cell viability and showed an additive effect on MTT cells. In MPC/MTT spheroids, treatment with clinically relevant doses of BYL719 alone or in combination with everolimus was highly effective, leading to a significant shrinkage or even a complete collapse of the spheroids. We confirmed the synergism of clinically relevant doses of BYL719 plus everolimus in human pheochromocytoma primary cultures of individual patient tumors with BYL719 attenuating everolimus-induced AKT activation. We have thus established a method to assess molecular-targeted therapies in human pheochromocytoma cultures and identified a highly effective combination therapy. Our data pave the way to customized combination therapy to target individual patient tumors.
The Indian Loom, Climate Change, and Democracy
Authors: Uzramma  
Published: August 2019

Abstract
Weaving on the handloom in India remains in the twenty-first century a large industry practiced by several million people, including, besides weavers themselves, others engaged in supporting activities. Indian hand weaving is a potentially viable ecological textile industry for the future, particularly if factors such as environmental damage and social costs are included in measuring viability. However, Indian hand weaving suffers from the perception that it is a relic of the past. Too, in the market it is undercut by cheaply made machine-produced cloth fraudulently sold as handmade. Research into the history of hand weaving revealed that there were two distinct modes of production, one in which expensive cloth was made for the elite, and another in which ordinary cloth was made for ordinary people. Since the making of expensive fabrics needed expensive raw materials, the weavers were dependent on an investor to supply these materials, creating a hierarchic dependency. The vernacular production of cloth, on the other hand, was democratic with lateral relations between the different stages of production. Malkha has simplified spinning by avoiding bale-pressing cotton lint, a technology introduced in colonial times to carry cotton long distances from the field. Malkha spinning centers are substantially smaller in size than conventional mills, closer to the small scales of Indian cotton farming and hand weaving.
Two Concepts of Conversion at Meenakshipuram
Authors: Baxter Matthew H. 
Published: August 2019

AbstractThe 1981 Dalit mass conversion to Islam at Meenakshipuram, Tamil Nadu, arguably began the Hindu Right's political rise. The conversion raises two different concepts for understanding mass conversion's relationship to democracy. Though it is commonly framed in terms of B. R. Ambedkar's thought, whereby conversion's core is an interior psychic process of changing principles to see the world differently, I suggest that Meenakshipuram's event may more appropriately be framed by E. V. Ramasami's [EVR] thought, whereby conversion's core is an exterior somatic process of changing appearances to be seen differently in the world. These concepts of conversion raise alternative engagements with issues of text, force, foreignness, time, and Marxism. The argument is prefaced by a discussion of freedom's typology (Berlin), subaltern representation (Spivak), and religious mass (Geertz/Asad), which I argue favors EVR's concept of conversion over Ambedkar's. Such issues are not unimportant in an age of rising right-wing populisms globally.
The Outside (Kharij) of Tradition in the Aftermath of the Revolution
Authors: Odabaei Milad 
Published: August 2019

AbstractAfter Iran's 1979 revolution, the energies that had animated the struggle for a modern Islamic government were partially redirected to the task of the renewal of the Islamic tradition. Paradigmatic of this effort is “the Cultural Revolution” that has sought to combat what Islamic activists perceive as the destructive effects of Western culture and to align the production of knowledge with the teachings of Shi'i Islam. The effort to produce modern Islamic knowledge, however, has paradoxically intensified the translation of European thought and invested it with the ethos of seminary education. Drawing on a long-term engagement with postrevolutionary Iranian intellectuals, including fieldwork in Tehran and Qom, this article offers a historical and anthropological exploration of the interrelated questions of tradition, transmission, and translation. It is ethnographically centered in a seminar in which seminarian-academics translate Carl Schmitt, among others, to make sense of, and intervene in, Islamic politics. It highlights how European concepts and forms of thought come to mediate the relation between seminarian-academics and the Islamic tradition, its forms of knowledge, and its modern politics and argues that the elision of the historical incommensurability of European discourses renders the enacted tradition foreign to itself.
Circulating miR-21 as a prognostic and predictive biomarker in oral squamous cell carcinoma
Authors: Mahmood Nosheen , Hanif Muhammad , Ahmed Akhtar , Jamal Qamar , Mushtaq Shamim , Khan Adnan , Saqib Muhammad 
Published: August 2019

Background & Objective: The high-throughput analysis of circulating microRNAs (miRNAs) is an active area of biomarker research. The oral cancer remains a common cancer among Pakistani males that continues to present at an advance stage, thus exhibiting poor survival. MiRNA 21 (miR-21) is the most consistently over-expressed miRNA in different types of tumor tissues. However, information regarding expression of miR-21 in plasma remains to be resolved. Therefore, present study was designed to investigate if miR-21 was expressed in plasma of patients with oral cancer, and further explore its diagnostic and prognostic potential.
Methods: Present study was conducted at Ziauddin University and Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). Histologically confirmed cases of oral squamous cell carcinoma were recruited from Oncology Department of Ziauddin Hospital between 2013 and 2017. Controls were carefully selected after considering age, gender and socioeconomic condition. MiRNA was extracted and immediately reverse transcribed to cDNA. MiR-21 expression was evaluated using probes specifically designed for Real time quantitative polymerase chain reaction.
Results: A significant over expression of miRNA 21 was observed in histologically confirmed cases as compared to controls. The increased expression of miRNA 21 was also reported to be associated with tumor size, metastasis and local invasion (p<0.05).
Conclusion: The expression of circulating miR-21 in plasma samples of oral cancer patients makes it a promising diagnostic and prognostic marker.
doi: https://doi.org/10.12669/pjms.35.5.331
How to cite this:Mahmood N, Hanif M, Ahmed A, Jamal Q, Mushtaq S, Khan A, et al. Circulating miR-21 as a prognostic and predictive biomarker in oral squamous cell carcinoma. Pak J Med Sci. 2019;35(5):1408-1412. doi: https://doi.org/10.12669/pjms.35.5.331
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.