bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genome-Wide Pooled shRNA Screen Identifies PPP2R2A as a Predictive Biomarker for the Response to ATR and CHK1 Inhibitors
Authors: Qiu Zhaojun , Fa Pengyan , Liu Tao , Prasad Chandra B. , Ma Shanhuai , Hong Zhipeng , Chan Ernest R. , Wang Hongbing , Li Zaibo , He Kai , Wang Qi-En , Williams Terence M. , Yan Chunhong , Sizemore Steven T. , Narla Goutham , Zhang Junran 
Published: June 2020

AbstractThere is currently a lack of precise predictive biomarkers for patient selection in clinical trials of inhibitors targeting replication stress (RS) response proteins ATR and CHK1. The objective of this study was to identify novel predictive biomarkers for the response to these agents in treating non–small cell lung cancer (NSCLC). A genome-wide loss-of-function screen revealed that tumor suppressor PPP2R2A, a B regulatory subunit of protein phosphatase 2 (PP2A), determines sensitivity to CHK1 inhibition. A synthetic lethal interaction between PPP2R2A deficiency and ATR or CHK1 inhibition was observed in NSCLC in vitro and in vivo and was independent of p53 status. ATR and CHK1 inhibition resulted in significantly increased levels of RS and altered replication dynamics, particularly in PPP2R2A-deficient NSCLC cells. Mechanistically, PPP2R2A negatively regulated translation of oncogene c-Myc protein. c-Myc activity was required for PPP2R2A deficiency-induced alterations of replication initiation/RS and sensitivity to ATR/CHK1 inhibitors. We conclude that PPP2R2A deficiency elevates RS by upregulating c-Myc activity, rendering cells reliant on the ATR/CHK1 axis for survival. Our studies show a novel synthetic lethal interaction and identify PPP2R2A as a potential new predictive biomarker for patient stratification in the clinical use of ATR and CHK1 inhibitors.Significance:This study reveals new approaches to specifically target PPP2R2A-deficient lung cancer cells and provides a novel biomarker that will significantly improve treatment outcome with ATR and CHK1 inhibitors.
Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer
Authors: Lischka Annette , Doberstein Natalie , Freitag-Wolf Sandra , Koçak Ayla , Gemoll Timo , Heselmeyer-Haddad Kerstin , Ried Thomas , Auer Gert , Habermann Jens K. 
Published: June 2020

AbstractPurpose:The choice of therapy for patients with breast cancer is often based on clinicopathologic parameters, hormone receptor status, and HER2 amplification. To improve individual prognostication and tailored treatment decisions, we combined clinicopathologic prognostic data with genome instabilty profiles established by quantitative measurements of the DNA content.Experimental Design:We retrospectively assessed clinical data of 4,003 patients with breast cancer with a minimum postoperative follow-up period of 10 years. For the entire cohort, we established genome instability profiles. We applied statistical methods, including correlation matrices, Kaplan–Meier curves, and multivariable Cox proportional hazard models, to ascertain the potential of standard clinicopathologic data and genome instability profiles as independent predictors of disease-specific survival in distinct subgroups, defined clinically or with respect to treatment.Results:In Cox regression analyses, two parameters of the genome instability profiles, the S-phase fraction and the stemline scatter index, emerged as independent predictors in premenopausal women, outperforming all clinicopathologic parameters. In postmenopausal women, age and hormone receptor status were the predominant prognostic factors. However, by including S-phase fraction and 2.5c exceeding rate, we could improve disease outcome prediction in pT1 tumors irrespective of the lymph node status. In pT3-pT4 tumors, a higher S-phase fraction led to poorer prognosis. In patients who received adjuvant endocrine therapy, chemotherapy or radiotherapy, or a combination, the ploidy profiles improved prognostication.Conclusions:Genome instability profiles predict disease outcome in patients with breast cancer independent of clinicopathologic parameters. This applies especially to premenopausal patients. In patients receiving adjuvant therapy, the profiles improve identification of high-risk patients.
Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers
Authors: Lee Soo-Chin , Shimasaki Noriko , Lim Joline S.J. , Wong Andrea , Yadav Kritika , Yong Wei Peng , Tan Lip Kun , Koh Liang Piu , Poon Michelle L.M. , Tan Sing Huang , Ow Samuel G.W. , Bharwani Lavina , Yap Yoon Sim , Foo Mabel Z.Q. , Coustan-Smith Elaine , Sundar Raghav , Tan Hon Lyn , Chong Wan Qin , Kumarakulasinghe Nesaretnam Barr , Lieow Jedidah L.M. , Koe Priscillia J.X. , Goh Boon Cher , Campana Dario 
Published: June 2020

Abstract

Purpose:
Natural killer (NK) cells exert antibody-dependent cell cytotoxicity (ADCC). We infused expanded, activated autologous NK cells to potentiate trastuzumab-mediated ADCC in patients with HER2-positive malignancies.

Patients and Methods:
In a phase I trial, patients with treatment-refractory HER2-positive solid tumors received trastuzumab, with or without bevacizumab, and autologous NK cells expanded by 10-day coculture with K562-mb15-41BBL cells. Primary objectives included safety and recommended phase II dose determination; secondary objectives included monitoring NK-cell activity and RECIST antitumor efficacy.

Results:
In 60 cultures with cells from 31 subjects, median NK-cell expansion from peripheral blood was 340-fold (range, 91–603). NK cells expressed high levels of CD16, the mediator of ADCC, and exerted powerful killing of trastuzumab-targeted cells. In the 22 subjects enrolled in phase I dose escalation, trastuzumab plus NK cells were well tolerated; MTD was not reached. Phase IB (n = 9) included multiple cycles of NK cells (1 × 107/kg) and addition of bevacizumab. Although no objective response was observed, 6 of 19 subjects who received at least 1 × 107/kg NK cells at cycle 1 had stable disease for ≥6 months (median, 8.8 months; range 6.0–12.0). One patient, the only one with the high-affinity F158V CD16 variant, had a partial response. Peripheral blood NK cells progressively downregulated CD16 postinfusion; paired tumor biopsies showed increased NK cells, lymphocytic infiltrates, and apoptosis posttreatment.

Conclusions:
NK-cell therapy in combination with trastuzumab was well tolerated, with target engagement and preliminary antitumor activity, supporting continued assessment of this approach in phase II trials.
Optimal Use of Vasodilators for Diagnosis of Microvascular Angina in the Cardiac Catheterization Laboratory
Authors: Rahman Haseeb , Demir Ozan M. , Ryan Matthew , McConkey Hannah , Scannell Cian , Ellis Howard , Webb Andrew , Chiribiri Amedeo , Perera Divaka 
Published: June 2020

Background:
Among patients with angina and nonobstructive coronary artery disease, those with coronary microvascular dysfunction have a poor outcome. Coronary microvascular dysfunction is usually diagnosed by assessing flow reserve with an endothelium-independent vasodilator like adenosine, but the optimal diagnostic threshold is unclear. Furthermore, the incremental value of testing endothelial function has never been assessed before. We sought to determine what pharmacological thresholds correspond to exercise pathophysiology and myocardial ischemia in patients with coronary microvascular dysfunction.

Methods:
Patients with angina and nonobstructive coronary artery disease underwent simultaneous acquisition of coronary pressure and flow during rest, supine bicycle exercise, and pharmacological vasodilatation with adenosine and acetylcholine. Adenosine and acetylcholine coronary flow reserve were calculated as vasodilator/resting coronary blood flow (CFR and AchFR, respectively). Coronary wave intensity analysis was used to quantify the proportion of accelerating wave energy; a normal exercise response was defined as an increase in accelerating wave energy from rest to peak exercise. Ischemia was assessed by quantitative 3-Tesla stress perfusion cardiac magnetic resonance imaging and dichotomously defined by a hyperemic endo-epicardial gradient <1.0.

Results:
Ninety patients were enrolled (58±10 years, 77% female). Area under the curve using receiver-operating characteristic analysis demonstrated optimal CFR and AchFR thresholds for identifying exercise pathophysiology and ischemia as 2.6 and 1.5, with positive and negative predictive values of 91% and 86%, respectively. Fifty-eight percent had an abnormal CFR (of which 96% also had an abnormal AchFR). Of those with a normal CFR, 53% had an abnormal AchFR, and 47% had a normal AchFR; ischemia rates were 83%, 63%, and 14%, respectively.

Conclusions:
The optimal CFR and AchFR diagnostic thresholds are 2.6 and 1.5, with high-positive and negative predictive values, respectively. A normal CFR value should prompt the measurement of AchFR. A stepwise algorithm incorporating both vasodilators can accurately identify an ischemic cause in patients with nonobstructive coronary artery disease.
Situating Salafī Islam in Azerbaijan
Authors: Aliyev Fuad 
Published: June 2020

Abstract
Salafī daʿwa is a new phenomenon in the religious life of Azerbaijan. Entering the scene in the mid‑1990s as a result of Gulf-funded organizations and the proselytizing activities of foreign students-turned-preachers, Salafīs gradually turned into important actors of Islamic revival in the post-Communist country. Operating in a highly secularized and, moreover, Shīʿī-majority environment, the Salafī daʿwa in Azerbaijan had ex ante limitations that shaped its development patterns. A comprehensive overview of the historical development of the Salafī daʿwa shows that, over three stages, the transnational Salafī movement had become increasingly indigenized. Following these historical observations, the development patterns of the Salafī daʿwa in Azerbaijan are explored, and an attempt is made to explain them through a framework provided by social movement theory. Finally, based on its ideological variations in Azerbaijan, an attempt is undertaken to develop a refined taxonomy of the Salafī movement in this country, based on a critical reassessment of existing classifications.
An Eleventh-Century Eastern Masoretic Codex of the Pentateuch
Authors: Penkower Jordan S. 
Published: June 2020

Abstract
The Washington Pentateuch consists of an eleventh-century Pentateuch codex, and a small group of 1141 CE replacement folios. The former presents another early witness to the Masoretic Text. The text in the second hand is very close to the Aleppo Codex, but the section division exhibits several variants as compared to the Aleppo codex. The layout of the Song of the Sea and the lines before are like in the Aleppo codex, but not so the lines after the song. The 1141 CE folios are another witness to the Masoretic Text. The text is very close to the Aleppo Codex, but here, too, there are a number of section variants (which later continued in the Ashkenazi codices). The Song of Moses, though differing from the Aleppo codex, follows an alternate standard layout of 70 lines, and 6 lines before and 6 lines after the Song (later found in Sefardi manuscripts).
Hypopharyngeal Squamous Cell Carcinoma in Sisters with LMNA Associated Familial Partial Lipodystrophy: A Case Report and Review of the Literature
Authors: Youssef Stephanie J. , Macielak Robert J. , Schimmenti Lisa A. , Chatzopoulos Kyriakos , Price Daniel L. 
Published: June 2020

Objectives: LMNA-associated familial partial lipodystrophy (FPLD) is a rare autosomal dominant A-type laminopathy characterized by variable loss and redistribution of subcutaneous adipose tissue, dyslipidemia, and insulin resistance. Though A-type lamins play a key role in nuclear membrane structure and regulation of cell proliferation, an association between cancer and LMNA-associated FPLD has not been reported. Methods and Results: This report outlines the case of two biological sisters with LMNA-associated FPLD who developed hypopharyngeal squamous cell carcinoma in the absence of any other risk factors for head and neck cancer. Conclusion: These observations prompt further investigation into the potential role of A-type lamins in the development and progression of head and neck cancers.
Evolving Trust in Robots: Specification Through Sequential and Comparative Meta-Analyses
Authors: Hancock P. A. , Kessler Theresa T. , Kaplan Alexandra D. , Brill John C. , Szalma James L. 
Published: June 2020

Objective The objectives of this meta-analysis are to explore the presently available empirical findings on the antecedents of trust in robots and use this information to expand upon a previous meta-analytic review of the area. Background Human–robot interaction (HRI) represents an increasingly important dimension of our everyday existence. Currently, the most important element of these interactions is proposed to be whether the human trusts the robot or not. We have identified three overarching categories that exert effects on the expression of trust. These consist of factors associated with (a) the human, (b) the robot, and (c) the context in which any specific HRI event occurs. Method The current body of literature was examined and all qualifying articles pertaining to trust in robots were included in the meta-analysis. A previous meta-analysis on HRI trust was used as the basis for this extended, updated, and evolving analysis. Results Multiple additional factors, which have now been demonstrated to significantly influence trust, were identified. The present results, expressed as points of difference and points of commonality between the current and previous analyses, are identified, explained, and cast in the setting of the emerging wave of HRI. Conclusion The present meta-analysis expands upon previous work and validates the overarching categories of trust antecedent (human-related, robot-related, and contextual), as well as identifying the significant individual precursors to trust within each category. A new and updated model of these complex interactions is offered. Application The identified trust factors can be used in order to promote appropriate levels of trust in robots.
Trends analysis of specialized palliative care services in 51 countries of the WHO European region in the last 14 years
Authors: Arias-Casais Natalia , López-Fidalgo Jesús , Garralda Eduardo , Pons Juan José , Rhee John Y , Lukas Radbruch , de Lima Liliana , Centeno Carlos 
Published: June 2020

Background: Service provision is a key domain to assess national-level palliative care development. Three editions of the European Association for Palliative Care (EAPC) Atlas of Palliative Care monitored the changes in service provision across Europe since 2005. Aim: To study European trends of specialized service provision at home care teams, hospital support teams, and inpatient palliative care services between 2005 and 2019. Design: Secondary analysis was conducted drawing from databases on the number of specialized services in 2005, 2012, and 2019. Ratios of services per 100,000 inhabitants and increase rates on number of services for three periods were calculated. Analysis of variance (ANOVA) analyses were conducted to determine significant changes and chi-square to identify countries accounting for the variance. Income-level and sub-regional ANOVA analysis were undertaken. Setting: 51 countries. Results: Forty-two countries (82%) increased the number of specialized services between 2005 and 2019 with changes for home care teams (104% increase-rate), inpatient services (82%), and hospital support teams (48%). High-income countries showed significant increase in all types of services ( p < 0.001), while low-to-middle-income countries showed significant increase only for inpatient services. Central–Eastern European countries showed significant improvement in home care teams and inpatient services, while Western countries showed significant improvement in hospital support and home care teams. Home care was the most prominent service in Western Europe. Conclusion: Specialized service provision increased throughout Europe, yet ratios per 100,000 inhabitants fell below the EAPC recommendations. Western Europe ratios’ achieved half of the suggested services, while Central–Eastern countries achieved only a fourth. High-income countries and Western European countries account for the major increase. Central–Eastern Europe and low-to-middle-income countries reported little increase on specialized service provision.
Evaluation of distal femoral cartilage by B-mode ultrasonography and shear wave elastography in patients with knee osteoarthritis: a preliminary study
Authors: Yokuş Adem , Toprak Murat , Arslan Harun , Toprak Nurşen , Akdeniz Hüseyin , Gündüz Ali Mahir 
Published: June 2020

Background Degenerative change in articular cartilage is one of the most important factors in the development of osteoarthritis. Shear wave elastography can be used to identify pathologic cartilage. Purpose To evaluate distal femoral cartilage by shear wave elastography in patients with symptomatic knee osteoarthritis. Material and methods Twenty patients with bilateral knee osteoarthritis (study group) and 20 volunteers with the same demographic characteristics but without symptomatic knee pain (control group) were included in the study. A total of 80 knee joints of 40 individuals were evaluated. At the medial, intercondylar, and lateral condylar levels distal femoral cartilage thickness was measured by B-mode ultrasonography and stiffness was measured by shear wave elastography. Results The medial, intercondylar, and lateral cartilage thickness measurements were similar between the two groups and no statistically significant difference was observed ( P = 0.711, P = 0.766, and P = 0.575, respectively). The shear wave velocity values in the medial and intercondylar cartilage were significantly higher in the study group ( P = 0.002). Shear wave velocity values measured from lateral cartilage were higher in the study group and the difference between the groups had a borderline statistical significance ( P = 0.053). Conclusion Shear wave elastography seems to be a reliable, non-invasive, and acceptable method for the assessment of pathologic cartilage.
Examining child mealtime behavior as parents are coached to implement the Mealtime PREP intervention in the home: Findings from a pilot study
Authors: Caldwell Angela R , Skidmore Elizabeth R , Bendixen Roxanna M , Terhorst Lauren 
Published: June 2020

Introduction The purpose of this study was to examine parental use of evidence-based mealtime strategies, child mealtime behavior, and parental identification of mealtime problems over time as parents were coached to implement the Promoting Routines of Exploration and Play during Mealtime intervention as part of a pilot study. Method This repeated measures study included data collection during three phases: (a) pre-intervention; (b) intervention; (c) post-intervention. Primary outcome measures included a parental strategy use checklist (parental strategy use) and the Behavioral Pediatric Feeding Assessment (problematic child behavior and parental identification of mealtime problems). Linear mixed models were fitted to assess change over time. Results We observed significant improvements in parental strategy use ( p < .001), child mealtime behavior ( p < .001), and parental perception of mealtime problems ( p = .002) over time. Conclusions The results of these analyses signal that empowering parents to integrate evidence-based strategies into child mealtimes is a promising approach to managing child mealtime behavior. More research is needed to determine the true relationship between parental strategy use and child behavior over time.
Breast MRI Does Not Help Differentiating Radial Scar With and Without Associated Atypia or Malignancy
Authors: Alsharif Shaza , Aldis Ann , Subahi Ahmad , Khoury Mona El , Mesurolle Benoit 
Published: June 2020

Purpose: To review breast magnetic resonance imaging (MRI) features of radial scar (RS) with and without associated atypia/malignancy. Methods: Twenty-eight (mean age 56.8) patients diagnosed with 30 biopsy-proven RS (n = 25, ultrasound-guided 14-gauge, n = 5, stereotactically guided 9-gauge) subsequently underwent breast MRI followed by surgery. Magnetic resonance imaging protocol included axial T1, axial fat sat T2, and postgadolinium in axial and sagittal planes. Two radiologists reviewed the mammographic and MRI findings in consensus according to the Breast Imaging Reporting and Data System lexicon. Results: Of the 30 RSs excised surgically, 14 (14/30, 47.7%) were not associated with atypia/malignancy while atypia/malignancy was found in 16 (16/30, 53.3%) RSs. Three (3/30, 10%) RS lesions did not enhance on dynamic MR. Mean lesion size on MRI was 1.4 cm (range, 0.5-5 cm). Seventeen (17/30, 56.7%) lesions presented as nonmass enhancement and 9 (9/30, 30%) as masses. Nonmass lesions showed focal distribution (13/17, 76.5%) and heterogeneous enhancement (15/17, 88.2%). Masses showed irregular shape and margins (6/9, 67%) and heterogeneous enhancement (8/9, 89%). Multivariate analysis did not show any significant difference in MRI presentation between RS only and RS associated with atypia/malignancy. Conclusion: Breast MRI does not help differentiate between RS with or without associated atypia/malignancy.
Effects of an Individualized Active Aging Counseling Intervention on Mobility and Physical Activity: Secondary Analyses of a Randomized Controlled Trial
Authors: Siltanen Sini , Portegijs Erja , Pynnönen Katja , Hassandra Mary , Rantalainen Timo , Karavirta Laura , Saajanaho Milla J. , Rantanen Taina 
Published: June 2020

Objectives: The aim of this study was to report preplanned secondary analyses of the effects of a 12-month individualized active aging counseling intervention on six mobility and physical activity outcomes. Methods: A two-arm, single-blinded randomized controlled trial was conducted among 75- and 80-year-old community-dwelling people. The intervention group (IG, n = 101) received counseling aimed at increasing self-selected, primarily out-of-home activity. The control group (CG, n = 103) received general health information. Data were analyzed with generalized estimating equations. Results: Physical performance improved in the IG more than that in the CG (group by time p = .022), self-reported physical activity increased in both groups (time p = .012), and autonomy in outdoor mobility declined in the IG and was enhanced in the CG (group by time p = .011). No change was observed for life-space mobility, proportion of persons perceiving difficulty walking 2 km, or monitored physical activity. Discussion: Individualized counseling aiming at increasing self-selected out-of-home activity had nonsystematic effects on mobility and positively affected physical performance only.