bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constructing Matched Groups in Dental Observational Health Disparity Studies for Causal Effects
Authors: Cheng J. , Gregorich S.E. , Gansky S.A. , Fisher-Owens S.A. , Kottek A.M. , White J.M. , Mertz E.A. 
Published: March 2019

Introduction: Electronic health record (EHR) systems provide investigators with rich data from which to examine actual impacts of care delivery in real-world settings. However, confounding is a major concern when comparison groups are not randomized. Objectives: This article introduced a step-by-step strategy to construct comparable matched groups in a dental study based on the EHR of the Willamette Dental Group. This strategy was employed in preparation for a longitudinal study evaluating the impact of a standardized risk-based caries prevention and management program across patients with public versus private dental insurance in Oregon. Methods: This study constructed comparable dental patient groups through a process of 1) evaluating the need for and feasibility of matching, 2) considering different matching methods, and 3) evaluating matching quality. The matched groups were then compared for their average ratio in the number of decayed, missing, and filled tooth surfaces (DMFS + dmfs) at baseline. Results: This systematic process resulted in comparably matched groups in baseline covariates but with a clear baseline disparity in caries experience between them. The weighted average ratio in our study showed that, at baseline, publicly insured patients had 1.21-times (95% CI: 1.08 to 1.32) and 1.21-times (95% CI: 1.08 to 1.37) greater number of DMFS + dmfs and number of decayed tooth surfaces (DS + ds) than privately insured patients, respectively. Conclusion: Matching is a useful tool to create comparable groups with EHR data to resemble randomized studies, as demonstrated by our study where even with similar demographics, neighborhood and clinic characteristics, publicly insured pediatric patients had greater numbers of DMFS + dmfs and DS + ds than privately insured pediatric patients. Knowledge Transfer Statement: This article provides a systematic, step-by-step strategy for investigators to follow when matching groups in a study—in this case, a study based on electronic health record data. The results from this study will provide patients, clinicians, and policy makers with information to better understand the disparities in oral health between comparable publicly and privately insured pediatric patients who have similar values in individual, clinic, and community covariates. Such understanding will help clinicians and policy makers modify oral health care and relevant policies to improve oral health and reduce disparities between publicly and privately insured patients.
Expanding Pharmacist and Student Pharmacist Access to Genetics/Genomics/Pharmacogenomics Competency Education
Authors: Kisor David F , Farrell Christopher L 
Published: March 2019

Background: As pharmacogenomics (PGx), a component of genetics/genomics and precision medicine, gains traction in the clinical setting, education of health care providers and health professions students must be made broadly available to improve accessibility of such services to patients. As medication experts with education in pharmacology, pharmacokinetics, and pharmacodynamics, pharmacists must further their education to include pharmacogenomics. Currently, few opportunities exist to gain this type of education, and therefore, these services are not yet broadly available to the public. Objective: The specific goal of this study was to evaluate pharmacists’ and student pharmacists’ self-assessed perception of competence related to genetics, genomics, and pharmacogenomics as presented via an online “pharmacogenomics certification program” (PGx program). Design: The PGx program was delivered online with the content consisting of 3 background lessons and 8 specific drug-gene lessons presented in the context of pharmacist competency statements. In addition, 11 “video modules” with competency-related PGx content were included to provide a comprehensive program. A pre- and post-course survey instrument was used to evaluate the participants’ self-assessed perception of competence related to each of 16 statements. Results: One hundred thirty-seven (137) individuals enrolled in and completed the pharmacogenomics certification program. Overall, participants reported self-perceived improved competency as evidenced by the pre-course survey as compared with the post-course survey for each of the 16 competency statements related to genetics/genomics, including pharmacogenomics. Similar results were observed for the subgroups of student pharmacists (n = 63) and pharmacists (n = 74). Future direction: This study showed that dissemination of genetics/genomics/pharmacogenomics competency statements education can be accomplished via online delivery. This delivery approach can expand genetics/genomics/pharmacogenomics content dissemination. The intent is to reach a broader population of pharmacy students, pharmacists, and other health care providers and health professions students to potentially advance the availability of such services, which can improve the safety and efficacy of medication use for patients.
Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia
Authors: Flinn Ian W. , Gribben John G. , Dyer Martin J. S. , Wierda William , Maris Michael B. , Furman Richard R. , Hillmen Peter , Rogers Kerry A. , Iyer Swaminathan Padmanabhan , Quillet-Mary Anne , Ysebaert Loic , Walter Harriet S. , Verdugo Maria , Klein Christian , Huang Huang , Jiang Yanwen , Lozanski Gerard , Pignataro Daniela Soriano , Humphrey Kathryn , Mobasher Mehrdad , Kipps Thomas J. 
Published: March 2019

Abstract
This single-arm, open-label, phase 1b study evaluated the maximum tolerated dose (MTD) of venetoclax when given with obinutuzumab and its safety and tolerability in patients with relapsed/refractory (R/R) or previously untreated (first line [1L]) chronic lymphocytic leukemia (CLL). Venetoclax dose initially was escalated (100-400 mg) in a 3 + 3 design to define MTD combined with standard-dose obinutuzumab. Patients received venetoclax (schedule A) or obinutuzumab (schedule B) first to compare safety and determine dose/schedule for expansion. Venetoclax-obinutuzumab was administered for 6 cycles, followed by venetoclax monotherapy until disease progression (R/R) or fixed duration 1-year treatment (1L). Fifty R/R and 32 1L patients were enrolled. No dose-limiting toxicities were observed. Safety, including incidence of tumor lysis syndrome (TLS), did not differ between schedules (2 laboratory TLSs per schedule). Schedule B and a 400-mg dose of venetoclax were chosen for expansion. The most common grade 3-4 adverse event was neutropenia (R/R, 58% of patients; 1L, 53%). Rates of grade 3-4 infections were 29% (R/R) and 13% (1L); no fatal infections occurred in 1L. All infusion-related reactions were grade 1-2, except for 2 grade 3 events. No clinical TLS was observed. Overall best response rate was 95% in R/R (complete response [CR]/CR with incomplete marrow recovery [CRi], 37%) and 100% in 1L (CR/CRi, 78%) patients. Rate of undetectable (&lt;10−4) minimal residual disease (uMRD) in peripheral blood for R/R and 1L patients, respectively, was 64% and 91% ≥3 months after last obinutuzumab dose. Venetoclax and obinutuzumab therapy had an acceptable safety profile and elicited durable responses and high rates of uMRD. This trial was registered at www.clinicaltrials.gov as #NCT01685892.
RECIST 1.1 for Response Evaluation Apply Not Only to Chemotherapy-Treated Patients But Also to Targeted Cancer Agents: A Pooled Database Analysis
Authors: Litière Saskia , Isaac Gaëlle , De Vries Elisabeth G.E. , Bogaerts Jan , Chen Alice , Dancey Janet , Ford Robert , Gwyther Stephen , Hoekstra Otto , Huang Erich , Lin Nancy , Liu Yan , Mandrekar Sumithra , Schwartz Lawrence H. , Shankar Lalitha , Therasse Patrick , Seymour Lesley ,   on behalf of the RECIST Working Group
Published: March 2019

PURPOSE The mode of action of targeted cancer agents (TCAs) differs from classic chemotherapy, which leads to concerns about the role of RECIST in evaluating tumor response in trials with TCAs. We investigated the performance of RECIST using a pooled database from 50 clinical trials with at least one TCA. METHODS We examined the impact of the number of target lesions (TLs) on within-patient variability of tumor response. The prognostic effect of TL response (at 12 weeks or on study on the basis of a maximum five TLs) on survival was studied through landmark and time-dependent Cox models adjusted for baseline tumor load, occurrence of new lesions, or unequivocal progression of nontarget disease. RESULTS Data were obtained from 23,259 patients with cancer (36% lung, 28% colorectal, 11% breast, and 25% other); 15,620 received TCAs, predominantly transduction or angiogenesis inhibitors, as a single agent (37%), combined with other TCAs (7%), or as chemotherapy (56%); 28% received chemotherapy only; and 5% received best supportive care or placebo. A total of 17,222 patients contributed to the analyses. Within-patient variability decreased with increasing number of TLs, similarly for TCAs (with/without chemotherapy) and chemotherapy only. Mixed responses occurred proportionally in all treatment classes. Landmark analyses showed an ordinal relationship between percentage change from baseline to 12 weeks and overall survival, and demonstrated a clear distinction between tumor shrinkage and progressive disease according to RECIST. Time-dependent analysis showed no marked improvement in the ability to predict survival on the basis of TL tumor growth compared with nontarget progression or new lesion occurrence, regardless of treatment. Similar results were seen for major tumor types and different classes of TCAs. CONCLUSION This work reinforces that RECIST version 1.1 perform well for response assessment of TCAs.
Clinicopathological Features of Young Versus Older Patients With Breast Cancer at a Single Pakistani Institution and a Comparison With a National US Database
Authors: Zeeshan Sana , Ali Basim , Ahmad Khabir , Chagpar Anees B. , Sattar Abida K. 
Published: March 2019

PURPOSE The age at which women present with breast cancer varies widely among nations, and breast cancer may behave differently in younger women. Differences in clinicopathological characteristics based on age have not been well characterized in Pakistani patients with breast cancer. METHODS We conducted a retrospective review of patients with symptoms of breast cancer presenting to Aga Khan University Hospital (AKUH), a large tertiary care center in Pakistan, between 2001 and 2010; we compared young (≤ 40 years) versus older (> 40 years) patients in terms of their clinicopathological characteristics. We also compared this Pakistani cohort with the US population using data from the National Cancer Database (NCDB). RESULTS A total of 1,334 patients with breast cancer presented to our center over the 10-year review period. The median age at diagnosis was 50 years, compared with 60 years for patients in the NCDB. In the AKUH cohort, younger patients were significantly more likely than their older counterparts to present with metastatic disease (13.1% v 10.8%; P < .01). They also were more likely to present with higher-grade tumors (grade 3: 40.1% v 28.3%; P < .001), have triple hormone receptor–negative phenotype (25.4% v 14.1%, P < .001), and have positive axillary lymph node involvement (70.9% v 57.5%; P < .001) compared with older women. Younger and older patients in the AKUH cohort tended to present with higher-stage disease ( P < .001) and were more likely to have triple hormone receptor–negative disease ( P < .001), compared with all patients in the NCDB and with those of Indo-Pakistani origin. CONCLUSION Young Pakistani women, similar to their Western counterparts, present with more advanced disease and more aggressive tumor biology than their older counterparts.
Pediatric Cancer Outcomes in an Intensive Care Unit in Pakistan
Authors: Khan Sial Gull Zareen , Khan Saadiya Javed 
Published: March 2019

PURPOSE Although cancer is uncommon, it is a significant cause of pediatric morbidity and mortality in the developing world. The need for intensive care in pediatric oncology has increased with more intense chemotherapeutic interventions. It is important to identify patients who will benefit from management in the intensive care unit (ICU), given the resource limitation in developing countries. In this review, we examine our institutional experience with pediatric patients with cancer needing ICU care. METHODS A retrospective chart review from December 2015 to June 2017 was performed with institutional review board approval for all pediatric oncology patients admitted to the ICU. Data collection included age, diagnosis, disease stage, Pediatric Risk of Mortality (PRISM III) score, and therapeutic interventions. RESULTS We reviewed 59 pediatric oncology ICU medical records. There were 36 boys (61%) and 23 girls (39%). The median age was 4 years. Average stay in the ICU was 4.6 days. Three significant reasons for ICU referral were respiratory distress, sepsis, and circulatory collapse. There were 34 ICU survivors (57.6%). Among those who survived the ICU, 20 patients (58.8%) later died of therapy-related complications. Factors related to increased ICU mortality included the need for mechanical ventilation, the need for inotropic support, the number of failing organs, and a high PRISM III score. CONCLUSION The mortality rate for pediatric oncology patients admitted to the ICU in developing countries is higher than in developed countries. Mortality was significantly related to the need for mechanical ventilation. PRISM III scoring can help identify patients who can benefit from ICU treatment, which is expensive in resource-limited low- and middle-income countries such as Pakistan.
Biguanides Exert Antitumoral Actions in Pituitary Tumor Cells Through AMPK-Dependent and -Independent Mechanisms
Authors: Vázquez-Borrego Mari C , Fuentes-Fayos Antonio C , Herrera-Martínez Aura D , L-López Fernando , Ibáñez-Costa Alejandro , Moreno-Moreno Paloma , Alhambra-Expósito María R , Barrera-Martín Ana , Blanco-Acevedo Cristóbal , Dios Elena , Venegas-Moreno Eva , Solivera Juan , Gahete Manuel D , Soto-Moreno Alfonso , Gálvez-Moreno María A , Castaño Justo P , Luque Raúl M 
Published: March 2019

Abstract

Context
Pituitary neuroendocrine tumors (PitNETs) are a commonly underestimated pathology in terms of incidence and associated morbimortality. Currently, an appreciable subset of patients are resistant or poorly responsive to the main current medical treatments [i.e., synthetic somatostatin analogs (SSAs) and dopamine agonists]. Thus, development and optimization of novel and available medical therapies is necessary. Biguanides (metformin, buformin, and phenformin) are antidiabetic drugs that exert antitumoral actions in several tumor types, but their pharmacological effects on PitNETs are poorly known.

Objective
We aimed to explore the direct effects of biguanides on key functions (cell viability, hormone release, apoptosis, and signaling pathways) in primary cell cultures from human PitNETs and cell lines. Additionally, we evaluated the effect of combined metformin with SSAs on cell viability and hormone secretion.

Design
A total of 13 corticotropinomas, 13 somatotropinomas, 13 nonfunctioning PitNETs, 3 prolactinomas, and 2 tumoral pituitary cell lines (AtT-20 and GH3) were used to evaluate the direct effects of biguanides on cell viability, hormone release, apoptosis, and signaling pathways.

Results
Biguanides reduced cell viability in all PitNETs and cell lines (with phenformin being the most effective biguanide) and increased apoptosis in somatotropinomas. Moreover, buformin and phenformin, but not metformin, reduced hormone secretion in a cell type–specific manner. Combination metformin/SSA therapy did not increase SSA monotherapy effectiveness. Effects of biguanides on PitNETs could involve the modulation of AMP-activated protein kinase–dependent ([Ca2+]i, PI3K/Akt) and independent (MAPK) mechanisms.

Conclusion
Altogether, our data unveil clear antitumoral effects of biguanides on PitNET cells, opening avenues to explore their potential as drugs to treat these pathologies.
Optimized Reaction Pair of the CysHis Tag and Ni(II)-NTA Probe for Highly Selective Chemical Labeling of Membrane Proteins
Authors: Zenmyo Naoki , Tokumaru Hiroki , Uchinomiya Shohei , Fuchida Hirokazu , Tabata Shigekazu , Hamachi Itaru , Shigemoto Ryuichi , Ojida Akio 
Published: March 2019

Abstract
Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research.
A liberdade acadêmica no direito brasileiro: fundamentos e abrangência
Authors: Rodrigues Horácio Wanderlei , Oliveira Amanda Muniz 
Published: March 2019

O objeto deste trabalho é o princípio da liberdade acadêmica, analisado no âmbito constitucional e infraconstitucional, indicando as suas possibilidades e limites frente ao direito fundamental à educação e à exigência de preservação do pluralismo de ideias, em especial aqueles decorrentes da interação entre as liberdades que a compõe (de ensinar, denominada indevidamente de liberdade de cátedra, de aprender, de pesquisar e de divulgar o conhecimento). Considerando essas questões o artigo caminha no sentido de propor a adoção do termo liberdade acadêmica como o mais adequado e representativo quando se faz referência às diversas liberdades envolvidas nos processos educativos e de produção do conhecimento. Também conclui que a Constituição Federal contém a liberdade acadêmica no âmbito do direito fundamental à educação e como instrumento de garantia do pluralismo de ideias, não como liberdade em si mesma.
Avaliação dos impactos da política pública de cotas na Índia
Authors: Lima José Wilson Ferreira , Machado Bruno Amaral 
Published: March 2019

O artigo tem por objetivo avaliar peculiaridades inerentes à adoção do sistema de cotas em contextos sociais, políticos e culturais distintos da sociedade brasileira. Pretende verifi car o impacto que a adoção desse sistema proporcionou em termos de mudanças na ordem social da Índia. Diante dos estudos fundamentados, entende-se que a experiência adquirida em torno dos modelos de cotas que outros países adotaram fornece subsídios esclarecedores e signifi cativos sobre como esses modelos podem operar transformações de acordo com as características de cada sítio de análise, cujas diferenças de organização social, política, econômica, jurídica e religiosa refl etem os aspectos peculiares de cada modelo e, por essemotivo, como podem ser determinantes quanto ao seu sucesso ou ao seu fracasso. Assim, a avaliação dos impactos das políticas públicas instituídas no ambiente internacional pode ser providência útil para o Brasil, visando ao enfrentamento de futuras consequências decorrentes do emprego dessa modalidade de ação afirmativa.
Management of acute diverticulitis
Authors: Sagar Alex J 
Published: March 2019

Acute diverticulitis is a major health-care concern. The optimal management of this common condition has been critically examined in recent years leading to a number of paradigm changes. In many areas, the debate continues. Acute uncomplicated diverticulitis may be safely managed without antibiotics. A number of randomized controlled trials have examined the role of laparoscopic lavage vs resection for purulent peritonitis. In cases where resection is indicated the traditional Hartmann's procedure is being trialled against resection with primary anastomosis. In the follow up of an acute uncomplicated episode, the value of colonoscopy is being questioned but remains in current guidelines. In the elective setting, more recent studies have led to a trend away from resection to prevent complications but towards resection to improve quality of life. This article presents an overview of the current guidance, areas of controversy and the associated evidence base.
The proactive elderly care team: dementia screening of over 20 000 patients
Authors: McCann Peter 
Published: March 2019

The proactive elderly care team was introduced at Lancashire Teaching Hospitals NHS Foundation Trust in October 2012. This article describes how the team performed over 5 years (up to the end of December 2017). The proactive elderly care team had three broad aims related to all non-elective patients over the age of 75 years who either came to accident and emergency or were admitted into the hospital, irrespective of speciality: To screen all patients over the age of 75 years for delirium and dementia To identify patients over 75 years who were the most frail, and would benefit from a comprehensive geriatric assessment and targeted interventions To reduce length of stay for patients over the age of 75 years without any increase in their readmission rate. Following the introduction of the proactive elderly care team, length of stay and the readmission rate of patients who were seen by the service fell by about 50%. Almost £10 million has been saved and for every £1 invested in the proactive elderly care team service, over £12 was saved.
Discrete Element Modeling of Soil Displacement Resulting from Hoe Openers
Authors: Murray Steven , Chen Ying 
Published: March 2019

Abstract. Soil displacement is the most important performance indicator for seed openers, as it affects the uniformity of seeding depth. In this study, a hoe opener was modeled using Particle Flow Code in 3 Dimensions (PFC3D), a discrete element modeling software program. The objective was to simulate soil displacement in terms of soil throws. To validate the model, an air drill with hoe openers was tested in a field with clay soil at a working depth of 38 mm and travel speed of 8 km h-1. Soil throw resulting from the hoe opener was measured. To calibrate the model, a virtual soil shear test was created within PFC3D, and the output soil shear torque was compared to the torque measured in the same field. The result showed that the calibrated effective modulus, a critical micro-parameter of model particles, was 5.692 × 107 Pa. With this calibrated value, the simulated soil throws agreed well with the measured throws, with a relative error of 15%. The model was used to compare different hoe opener designs: single-shoot spread, double-shoot side-band, double-shoot paired-row, and triple-shoot openers. Among all these openers, the side-band opener resulted in the least lateral soil throw, and the paired-row opener resulted in the lowest vertical soil throw but the highest lateral throw. The developed model was effective for examining the effects of opener geometry on soil displacement. Keywords: DEM, Hoe, Opener, PFC3D, Soil displacement.