bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world effect of antidepressants for depressive disorder in primary care: protocol of a population-based cohort study
Authors: De Crescenzo Franco , Garriga Cesar , Tomlinson Anneka , Coupland Carol , Efthimiou Orestis , Fazel Seena , Hippisley-Cox Julia , Cipriani Andrea 
Published: June 2020

IntroductionClinical guidelines recommend antidepressants as the first line of treatment for adults with moderate-to-severe depression. Randomised trials provide the best evidence on the comparative effectiveness of antidepressants for depression, but are limited by a short follow-up and a highly selected population. We aim to conduct a cohort study on a large database to assess acceptability, efficacy, safety and tolerability of antidepressant monotherapy in people with depressive disorder in primary care.Methods and analysisThis is a protocol for a cohort study using data from the QResearch primary care research database, which is the largest general practice research database in the UK. We will include patients registered for at least 1 year from 1 January 1998, diagnosed with a new episode of depression and on antidepressant and a comparison group not on antidepressant. The exposure of interest will be treatment with antidepressant medications. Our outcomes will be acceptability (treatment discontinuation due to any cause), efficacy (clinical response and remission); safety (adverse events (AEs) and all-cause mortality); and tolerability (dropouts due to any AE) measured at 2 months, 6 months and 1 year. For each outcome, we will estimate the absolute risks for all antidepressants, and relative effects between antidepressants using Cox’s proportion hazards models. We will calculate HRs and 99.9% CIs for each outcome of interest.DiscussionThe main limitation is the observational nature of our study, while the major strengths include the large representative population contained in QResearch and the possibly high generalisability.
Transitioning to distance learning and virtual conferencing
Authors: Arquilla John , Guzdial Mark 
Published: June 2020

The
Communications
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Communications
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John Arquilla considers responses to the Coronavirus pandemic, while Mark Guzdial ponders the impacts of competitive enrollment.
How Tumor Cell Dedifferentiation Drives Immune Evasion and Resistance to Immunotherapy
Authors: Li Jinyang , Stanger Ben Z. 
Published: June 2020

Abstract
Immunotherapy has revolutionized cancer treatment, yet most patients do not respond. While tumor antigens are needed for effective immunotherapy, a favorable tumor immune microenvironment is also critical. In this review, we discuss emerging evidence that tumor cells exploit cellular plasticity and dedifferentiation programs to avoid immune surveillance, which in turn drives metastatic dissemination and resistance to immunotherapy. A deeper understanding of these programs may provide novel opportunities to enhance the efficacy of existing immunotherapies.
Anti–PD-1 Induces M1 Polarization in the Glioma Microenvironment and Exerts Therapeutic Efficacy in the Absence of CD8 Cytotoxic T Cells
Authors: Rao Ganesh , Latha Khatri , Ott Martina , Sabbagh Aria , Marisetty Anantha , Ling Xiaoyang , Zamler Daniel , Doucette Tiffany A. , Yang Yuhui , Kong Ling-Yuan , Wei Jun , Fuller Gregory N. , Benavides Fernando , Sonabend Adam M. , Long James , Li Shulin , Curran Michael , Heimberger Amy B. 
Published: June 2020

Abstract

Purpose:
Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated inconsistent therapeutic results in patients with glioblastoma (GBM) including those with profound impairments in CD8 T-cell effector responses.

Experimental Design:
We ablated the CD8α gene in BL6 mice and intercrossed them with Ntv-a mice to determine how CD8 T cells affect malignant progression in forming endogenous gliomas. Tumor-bearing mice were treated with PD-1 to determine the efficacy of this treatment in the absence of T cells. The tumor microenvironment of treated and control mice was analyzed by IHC and FACS.

Results:
We observed a survival benefit in immunocompetent mice with endogenously arising intracranial glioblastomas after intravenous administration of anti–PD-1. The therapeutic effect of PD-1 administration persisted in mice even after genetic ablation of the CD8 gene (CD8−/−). CD11b+ and Iba1+ monocytes and macrophages were enriched in the glioma microenvironment of the CD8−/− mice. The macrophages and microglia assumed a proinflammatory M1 response signature in the setting of anti–PD-1 blockade through the elimination of PD-1–expressing macrophages and microglia in the tumor microenvironment. Anti–PD-1 can inhibit the proliferation of and induce apoptosis of microglia through antibody-dependent cellular cytotoxicity, as fluorescently labeled anti–PD-1 was shown to gain direct access to the glioma microenvironment.

Conclusions:
Our results show that the therapeutic effect of anti–PD-1 blockade in GBM may be mediated by the innate immune system, rather than by CD8 T cells. Anti–PD-1 immunologically modulates innate immunity in the glioma microenvironment—likely a key mode of activity.
Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity
Authors: Singh Kavisha , Chandra Alvin , Sperry Thomas , Joshi Parag H. , Khera Amit , Virani Salim S. , Ballantyne Christie M. , Otvos James D. , Dullaart Robin P.F. , Gruppen Eke G. , Connelly Margery A. , Ayers Colby R. , Rohatgi Anand 
Published: June 2020

Background:
High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C.

Methods:
We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke.

Results:

In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52–0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61–0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35–0.69]; for Blacks, 1.22 [95% CI, 0.76–1.98];
P
interaction
=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36–0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08–2.83];
P
interaction
<0.0001).

Conclusions:
Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.
A Review of the Work Accomplished by the Blind Relief Commission of Hamilton County, Ohio
Authors: Stricker Louis 
Published: June 2020

Editor's Note. — The pensions for the blind of Ohio are dispensed by unpaid county commissioners. Each of the eighty-eight commissions is composed of three persons. The care with which some of these boards are beginning their work is admirably shown by the following paper. At the same time that these “Pension Commissions” were created a State Commission for the Blind was established. The County Commissions have the single problem of the State Commission that of finding employment and of ameliorating, in any way possible, the condition of the blind. Dr. Stricker clearly portrays the condition of the blind who have had no friendly organization to which to turn for advice, help, or work. Professor Van Cleve explains what the State School is doing for the juvenile blind. Mr. Charles F. F. Campbell presented a paper at the Ohio Conference of Charities and Correction to the same audience addressed by Dr. Stricker and Professor Van Cleve to show what is possible for the blind along industrial lines. Space does not permit us to print his paper, but our readers can find full information regarding the workshops for the blind in the United States at the end of the July, 1908, Vol. II, No. 2. In connection with the movement in behalf of the blind which is now developing in Ohio, it is interesting to consider the results of the systematic “field work” conducted by the Massachusetts Commission for the Blind, which is ably set forth in Miss Lucy Wright's paper. It is clear to every one that the aggregation of the indigent blind throughout the country is a result of the lack of attention in the past. The Ohio pension is an attempt to relieve the needs of this accumulated group of neglected people. One of the chief purposes of the schools, workshops, societies, and state commissions for the blind is to prevent such accumulations in the future.
Prevocational Evaluation Examined
Authors: Acker Martin H. , Dauterman William L. , Macdonald Wallace R. 
Published: June 2020

On the basis of these findings it would appear that there is an urgent need for continuing study of prevocational evaluation units. If there is a conceptual framework within which we are to operate, what is it and where is it when we attempt to define our everyday procedures? What methodology is existent in our limited staffs and physical plants which permits us to carry out forty-five more or less different functions? On what validation studies does our confidence in our procedures and findings rest? Do we really mean to suggest, as is indicated by some of the terminology, that such units have three valid functions? Or does the term “evaluation” have so little significance that it often includes the functions of “treatment” and “training”? This is not the time to attempt to unify our theories and methods; but surely it must be the time for continuing agency soul searching. The justification of this expensive service in the future will have to be based on more than a sincere desire to do something for our clients, and piecemeal evidence that it is a “worthwhile service” in the opinion of vocational rehabilitation personnel.
Association of whole-grain and dietary fiber intake with cardiometabolic risk in children and adolescents
Authors: Fulgoni Victor L , Brauchla Mary , Fleige Lisa , Chu YiFang 
Published: June 2020

Background: Diet is known to affect many risk factors of cardiovascular disease (CVD), a leading cause of mortality and morbidity. Aim: The objective of this study was to explore the potential association between whole grain and dietary fiber with CVD risk factors, including metabolic syndrome (MetS) in children and adolescents using National Health and Nutrition Examination Survey (NHANES) 2003–2014. Methods: Two days of 24-hour recall data from 16,507 children and adolescents age 2–18 years were used to estimate dietary intakes. Continuous MetS scores (cMetS) were computed by aggregating age/sex regressed z-scores of waist circumference, mean arterial blood pressure, high-density lipoprotein-cholesterol, triglycerides, and glucose. Regression analyses were used to assess association of fiber and whole grain intake with cardiometabolic markers including MetS after adjusting for demographic factors. Results: Increasing tertiles of fiber intake were significantly associated with 3% lowered risk MetS in adolescents age 13–18 years. Additionally, increasing intake tertiles of fiber were associated with reduced risk elevated cholesterol (5–11% reduction), elevated diastolic blood pressure (10–23% reduction) in adolescents age 13–18 years, and risk of obesity (3–5% reduction) in children and adolescent age 2–18 years. Increasing tertiles of whole grain intake were only associated with reduced risk of elevated triglycerides (52% risk reduction) in adolescents age 13–18 years. Conclusion: The results suggest that intake of dietary fiber was inversely associated with several markers of cardiovascular disease risk including MetS.
Comparison of Patellofemoral Kinematics and Stability After Medial Patellofemoral Ligament and Medial Quadriceps Tendon–Femoral Ligament Reconstruction
Authors: Spang Robert , Egan Jonathan , Hanna Philip , Lechtig Aron , Haber Daniel , DeAngelis Joseph P. , Nazarian Ara , Ramappa Arun J. 
Published: June 2020

Background: There is a lack of evidence regarding the optimum extensor-sided fixation method for medial patellofemoral ligament (MPFL) reconstruction. There is increased interest in avoiding patellar drilling via soft tissue–only fixation to the distal quadriceps, thus reconstructing the medial quadriceps tendon–femoral ligament (MQTFL). The biomechanical implications of differing extensor-sided fixation constructs remain unknown. Hypothesis: The null hypothesis was there would be no differences between traditional MPFL reconstruction and MQTFL reconstruction with respect to resistance to lateral translation, patellar position, or patellofemoral contact pressures. Study Design: Controlled laboratory study. Methods: Nine adult knee specimens were mounted on a jig that applied static, physiologic loads to the quadriceps tendons. Patellar position and orientation, knee flexion angle, and patellofemoral pressure were recorded at 8 different flexion angles between 0° and 110°. Additionally, a lateral patellar excursion test was conducted wherein a load was applied directly to the patella in the lateral direction with the knee at 30° of flexion and subjected to 2-N quadriceps loads. Testing was conducted under 4 conditions: intact, transected MPFL, MQTFL reconstruction, and MPFL reconstruction. For MQTFL reconstruction, the surgical technique established by Fulkerson was employed. For MPFL reconstruction, a traditional technique was utilized. Results: The patellar excursion test showed no significant difference between the MQTFL and intact states with respect to lateral translation. MPFL reconstruction led to significantly less lateral translation ( P < .05) than all other states. There were no significant differences between MPFL and MQTFL reconstructions with respect to peak patellofemoral contact pressure. MPFL and MQTFL reconstructions both resulted in increased internal rotation of the patella with the knee in full extension. Conclusion: Soft tissue-only extensor-sided fixation to the distal quadriceps (MQTFL) during patella stabilization appears to re-create native stability in this time 0 cadaver model. Fixation to the patella (MPFL) was associated with increased resistance to lateral translation. Clinical Relevance: Evolving anatomic knowledge and concern for patellar fracture has led to increased interest in MQTFL reconstruction. Both MQTFL and MPFL reconstructions restored patellofemoral stability to lateral translation without increasing contact pressures under appropriate graft tensioning, with MQTFL more closely restoring native resistance to lateral translation at the time of surgery.
First generation immigrant and native nurses enacting good care in a nursing home
Authors: Ham Anita 
Published: June 2020

Background: Several studies have investigated the experiences of first-generation immigrant nurses in new workplaces. Yet, little is known about how native nurses and newcomers collaborate in their care for aging residents in European nursing homes. Objective: To gain a deeper understanding of interactions between first-generation immigrant nurses and native nurses in their care for aging residents in a Dutch nursing home. Methods: Ethnography, including 105 h of shadowing immigrant and native nurses, 8 semi-structured interviews with 4 immigrant and 4 established nurses, and 2 focus group discussions with 8 immigrant and 6 established nurses in a Dutch nursing home. Data were analyzed by a post-positivist grounded theory coding approach. Ethical consideration: The Medical Ethical Review Committee of the Leiden University Medical Center approved this study. Results: The interactions between established staff and newcomers were influenced by norms, rules and regulations, policies and protocols. In daily practice and institutional structure, we observed both opportunities and challenges. The strict time schedules and the requisite standards of care were opportunities related to nurses’ expectations. Residents’ needs were sometimes challenging and inhibited newcomers’ active participation. However, sometimes new practices were developed where nurses created common ground, tinkered, and formed an inclusive playing field to enact good care. Conclusion/ discussion: This study shows that despite obstacles, there was room to make small changes in the rules of the game of nursing. These moments of tinkering may be sufficient to establish a stable, inclusive workforce for first-generation immigrants and give room to the evolvement of hybrid professional identities. Implications: The findings of this Dutch study are relevant for nursing ethics related to “good care” and nurses in other cultural contexts on how the integration of immigrant nurses in European countries in general could be facilitated.
Critical spinal cord lesions associate with secondary progressive motor impairment in long-standing MS: A population-based case-control study
Authors: Sechi Elia , Messina Steven , Keegan B Mark , Buciuc Marina , Pittock Sean J , Kantarci Orhun H , Weinshenker Brian G , Flanagan Eoin P 
Published: June 2020

Background: Progressive motor impairment anatomically attributable to prominent, focally atrophic lateral column spinal cord lesions (“critical lesions”) can be seen in multiple sclerosis (MS), for example, progressive hemiparetic MS. Objective: The aim of this study was to investigate whether similar spinal cord lesions are more frequent in long-standing MS patients with secondary progressive motor impairment (secondary progressive MS (SPMS)) versus those maintaining a relapsing-remitting course (relapsing-remitting MS (RRMS)). Methods: We retrospectively identified Olmsted County (MN, USA) residents on 31 December 2011 with (1) RRMS or SPMS for ⩾25 years, and (2) available brain and spine magnetic resonance imaging (MRI). A blinded neuroradiologist determined demyelinating lesion burden and presence of potential critical lesions (prominent focally atrophic spinal cord lateral column lesions). Results: In total, 32 patients were included: RRMS, 18; SPMS, 14. Median (range) disease duration (34 (27–53) vs. 39 (29–47) years) and relapse number (4 (1–10) vs. 3 (1–15)) were similar. In comparison to RRMS, SPMS patients more commonly showed potential critical spinal cord lesions (8/18 (44%) vs. 14/14 (100%)), higher spinal cord (median (range) 4 (1–7) vs. 7.5 (3–12)), and brain infratentorial (median (range) 1 (0–12) vs. 2.5 (1–13)) lesion number; p < 0.05. By multivariate analysis, only the presence of potential critical lesions independently associated with motor progression ( p = 0.02). Conclusion: Critical spinal cord lesions may be important contributors to motor progression in MS.
Factors affecting moral distress in nurses working in intensive care units: A systematic review
Authors: Atashzadeh-Shoorideh Foroozan , Tayyar-Iravanlou Faraz , Chashmi Zeynab Ahmadian , Abdi Fatemeh , Cisic Rosana Svetic 
Published: June 2020

Background Moral distress is a major issue in intensive care units that requires immediate attention since it can cause nurses to burnout. Given the special conditions of patients in intensive care units and the importance of the mental health of nurses, the present study was designed to systematically review the factors affecting moral distress in nurses working in intensive care units. Methods PubMed, EMBASE, Web of Science, Scopus, and Science Direct were systematically searched for papers published between 2009 and 2019. Original articles from quantitative and qualitative studies were reviewed. The CONSORT and STROBE checklists were used to assess the quality of the quantitative papers. The JBI checklist was applied for qualitative studies. Results Factors affecting moral distress in nurses include lack of nursing staff, nurses with inadequate experience, lack of support from organizations and colleagues, inadequate education and lack of knowledge of nurses, poor collaboration of physicians with nurses, ethical insensitivity and lack of teamwork, heavy workload, poor quality of care and moral violence and they are considered as risk factors for moral distress. Conclusion Many of the related causes are due to the nature of nurses’ work and it is necessary to manage the underlying conditions of this phenomenon so that it can be effectively prevented from spreading. Levels of moral distress require more attention of authorities in the use of prevention strategies and the reduction of effective factors in distress.
Expression of Podoplanin in Sinonasal Squamous Cell Carcinoma and Its Clinical Significance
Authors: Wang Huan , Hu Chunyan , Song Xiaole , Hu Li , Li Wanpeng , Yu Hongmeng , Sun Xicai , Wang Dehui 
Published: June 2020

Background It was recently suggested that the upregulation of podoplanin (PDPN) in cancer cells plays a significant role in tumor invasion and metastasis and that it is significantly associated with poor prognosis in oral, cutaneous, and esophageal squamous cell carcinoma. The aim of this study was to investigate the expression pattern of PDPN in sinonasal squamous cell carcinoma (SNSCC) and to evaluate its role as a prognostic factor for survival outcome. Patients and methods This study included 59 subjects with SNSCC. We retrospectively collected the clinical features of these patients from medical records and retrieved the associated formalin-fixed, paraffin-embedded tissues for PDPN immunohistochemical staining. Furthermore, PDPN expression was analyzed in relation to the patients’ clinicopathological features and prognosis. Results We observed positive staining for PDPN in both cancer cells and stromal cancer-associated fibroblasts (CAFs). Positive expression of PDPN in cancer cells of patients with SNSCC was significantly correlated with the primary tumor site (p = 0.009) and local recurrence (p = 0.024). In addition, patients with PDPN-positive cancer cells had significantly lower overall survival (OS) and disease-free survival (DFS) rates than did patients with PDPN-negative cancer cells (both p < 0.05). Multivariate analysis revealed that PDPN expression in cancer cells was an independent prognostic factor for both OS (p = 0.038) and DFS (p = 0.039). Conclusions Our findings demonstrated that PDPN overexpression may be both an independent prognostic biomarker and a therapeutic target in SNSCC.