bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21–39 Years
Authors: Silver Michelle I. , Gage Julia C. , Schiffman Mark , Fetterman Barbara , Poitras Nancy E. , Lorey Thomas , Cheung Li C. , Katki Hormuzd A. , Locke Alexander , Kinney Walter K. , Castle Philip E. 
Published: February 2018

Abstract
Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2+. Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2+ might not be necessary after a negative cotest.
Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more severe diagnoses. More research is needed to determine whether such prolonged management might be unnecessary following a negative cotest for those women with an initial CIN2 but otherwise only low-grade findings. Cancer Prev Res; 11(3); 165–70. ©2018 AACR.
Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAFV600E-Mutant Colorectal Cancer
Authors: Corcoran Ryan B. , André Thierry , Atreya Chloe E. , Schellens Jan H.M. , Yoshino Takayuki , Bendell Johanna C. , Hollebecque Antoine , McRee Autumn J. , Siena Salvatore , Middleton Gary , Muro Kei , Gordon Michael S. , Tabernero Josep , Yaeger Rona , O'Dwyer Peter J. , Humblet Yves , De Vos Filip , Jung A. Scott , Brase Jan C. , Jaeger Savina , Bettinger Severine , Mookerjee Bijoyesh , Rangwala Fatima , Van Cutsem Eric 
Published: February 2018

Abstract
Although BRAF inhibitor monotherapy yields response rates &gt;50% in BRAFV600-mutant melanoma, only approximately 5% of patients with BRAFV600E colorectal cancer respond. Preclinical studies suggest that the lack of efficacy in BRAFV600E colorectal cancer is due to adaptive feedback reactivation of MAPK signaling, often mediated by EGFR. This clinical trial evaluated BRAF and EGFR inhibition with dabrafenib (D) + panitumumab (P) ± MEK inhibition with trametinib (T) to achieve greater MAPK suppression and improved efficacy in 142 patients with BRAFV600E colorectal cancer. Confirmed response rates for D+P, D+T+P, and T+P were 10%, 21%, and 0%, respectively. Pharmacodynamic analysis of paired pretreatment and on-treatment biopsies found that efficacy of D+T+P correlated with increased MAPK suppression. Serial cell-free DNA analysis revealed additional correlates of response and emergence of KRAS and NRAS mutations on disease progression. Thus, targeting adaptive feedback pathways in BRAFV600E colorectal cancer can improve efficacy, but MAPK reactivation remains an important primary and acquired resistance mechanism.
Significance: This trial demonstrates that combined BRAF + EGFR + MEK inhibition is tolerable, with promising activity in patients with BRAFV600E colorectal cancer. Our findings highlight the MAPK pathway as a critical target in BRAFV600E colorectal cancer and the need to optimize strategies inhibiting this pathway to overcome both primary and acquired resistance. Cancer Discov; 8(4); 428–43. ©2018 AACR.
See related commentary by Janku, p. 389.
See related article by Hazar-Rethinam et al., p. 417.
This article is highlighted in the In This Issue feature, p. 371
ПОШИРЕНІСТЬ СИНДРОМУ ЕМОЦІЙНОГО ВИГОРАННЯ У МЕДИЧНОГО ПЕРСОНАЛУ І ФАКТОРИ, ЯКІ СПРИчинЯЮТЬ ЙОГО РОЗВИТОК
Authors: Golovenko H. V. , Sopel O. M. 
Published: February 2018

У статті проаналізовано поширеність синдрому професійного вигорання в Україні та за її межами, а також фактори, що спричиняють виникнення даного захворювання.
Mouse Platelet Ral GTPases Control P-Selectin Surface Expression, Regulating Platelet–Leukocyte Interaction
Authors: Wersäll Andreas , Williams Chris M. , Brown Edward , Iannitti Tommaso , Williams Neil , Poole Alastair W. 
Published: February 2018

Objective—
RalA and RalB GTPases are important regulators of cell growth, cancer metastasis, and granule secretion. The purpose of this study was to determine the role of Ral GTPases in platelets with the use of platelet-specific gene-knockout mouse models.

Approach and Results—
This study shows that platelets from double knockout mice, in which both GTPases have been deleted, show markedly diminished (≈85% reduction) P-selectin translocation to the surface membrane, suggesting a critical role in α-granule secretion. Surprisingly, however, there were only minor effects on stimulated release of soluble α- and δ-granule content, with no alteration in granule count, morphology, or content. In addition, their expression was not essential for platelet aggregation or thrombus formation. However, absence of surface P-selectin caused a marked reduction (≈70%) in platelet–leukocyte interactions in blood from RalAB double knockout mice, suggesting a role for platelet Rals in platelet-mediated inflammation.

Conclusions—
Platelet Ral GTPases primarily control P-selectin surface expression, in turn regulating platelet–leukocyte interaction. Ral GTPases could therefore be important novel targets for the selective control of platelet-mediated immune cell recruitment and inflammatory disease.
Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function
Authors: Sarzynski Mark A. , Ruiz-Ramie Jonathan J. , Barber Jacob L. , Slentz Cris A. , Apolzan John W. , McGarrah Robert W. , Harris Melissa N. , Church Timothy S. , Borja Mark S. , He Yumin , Oda Michael N. , Martin Corby K. , Kraus William E. , Rohatgi Anand 
Published: February 2018

Objective—
Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials.

Approach and Results—

Radiolabeled and boron dipyrromethene difluoride–labeled cholesterol efflux capacity and HDL-apoA-I (apolipoprotein A-I) exchange were assessed before and after 6 months of exercise training in 2 cohorts: STRRIDE-PD (Studies of Targeted Risk Reduction Interventions through Defined Exercise, in individuals with Pre-Diabetes; n=106) and E-MECHANIC (Examination of Mechanisms of exercise-induced weight compensation; n=90). STRRIDE-PD participants completed 1 of 4 exercise interventions differing in amount and intensity. E-MECHANIC participants were randomized into 1 of 2 exercise groups (8 or 20 kcal/kg per week) or a control group. HDL-C significantly increased in the high-amount/vigorous-intensity group (3±5 mg/dL;
P
=0.02) of STRRIDE-PD, whereas no changes in HDL-C were observed in E-MECHANIC. In STRRIDE-PD, global radiolabeled efflux capacity significantly increased 6.2% (SEM, 0.06) in the high-amount/vigorous-intensity group compared with all other STRRIDE-PD groups (range, −2.4 to −8.4%; SEM, 0.06). In E-MECHANIC, non-ABCA1 (ATP-binding cassette transporter A1) radiolabeled efflux significantly increased 5.7% (95% CI, 1.2–10.2%) in the 20 kcal/kg per week group compared with the control group, with no change in the 8 kcal/kg per week group (2.6%; 95% CI, −1.4 to 6.7%). This association was attenuated when adjusting for change in HDL-C. Exercise training did not affect BODIPY-labeled cholesterol efflux capacity or HDL-apoA-I exchange in either study.

Conclusions—
Regular prolonged vigorous exercise improves some but not all measures of HDL function. Future studies are warranted to investigate whether the effects of exercise on cardiovascular disease are mediated in part by improving HDL function.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT00962962 and NCT01264406.
CSL112 (Apolipoprotein A-I [Human]) Enhances Cholesterol Efflux Similarly in Healthy Individuals and Stable Atherosclerotic Disease Patients
Authors: Gille Andreas , D’Andrea Denise , Tortorici Michael A. , Hartel Gunter , Wright Samuel D. 
Published: February 2018

Objective—
CSL112 (apolipoprotein A-I [apoA-I; human]) is a novel formulation of apoA-I in development for reduction of early recurrent cardiovascular events after acute myocardial infarction. Cholesterol efflux capacity (CEC) is a marker of high-density lipoprotein (HDL) function that is strongly correlated with incident cardiovascular disease. Impaired CEC has been observed in patients with coronary heart disease. Here, we determined whether infused apoA-I improves CEC when administered to patients with stable atherosclerotic disease versus healthy volunteers.

Approach and Results—

Measurements of apoA-I, HDL unesterified cholesterol, HDL esterified cholesterol, pre–β1-HDL, and CEC were determined in samples from patients with stable atherosclerotic disease before and after intravenous administration of CSL112. These measures were compared with 2 prior studies in healthy volunteers for differences in CEC at baseline and after CSL112 infusion. Patients with stable atherosclerotic disease exhibited significantly lower ATP-binding cassette transporter 1–mediated CEC at baseline (
P
<0.0001) despite slightly higher apoA-I levels when compared with healthy individuals (2 phase 1 studies pooled;
P
≤0.05), suggesting impaired HDL function. However, no differences were observed in apoA-I pharmacokinetics or in pre–β1-HDL (
P
=0.5) or CEC (
P
=0.1) after infusion of CSL112. Similar elevation in CEC was observed in patients with low or high baseline HDL function (based on tertiles of apoA-I–normalized CEC;
P
=0.1242). These observations were extended and confirmed using cholesterol esterification as an additional measure.

Conclusions—
CSL112 shows comparable, strong, and immediate effects on CEC despite underlying cardiovascular disease. CSL112 is, therefore, a promising novel therapy for lowering the burden of atherosclerosis and reducing the risk of recurrent cardiovascular events.
Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors
Authors: Liu Hanhan , Dienel Ari , Schöller Karsten , Schwarzmaier Susanne M. , Nehrkorn Kathrin , Plesnila Nikolaus , Terpolilli Nicole A. 
Published: February 2018

Background and Purpose—

Perturbations in cerebral microcirculation (eg, microvasospasms) and reduced neurovascular communication determine outcome after subarachnoid hemorrhage (SAH). ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH; however, their role in the development of microvascular dysfunction is currently unknown. Here, we investigated whether inhibiting ET
A
(endothelin A) receptors can reduce microvasospasms after experimentally induced SAH.

Methods—

SAH was induced in male C57BL/6 mice by filament perforation of the middle cerebral artery. Three hours after SAH, a cranial window was prepared and the pial and parenchymal cerebral microcirculation was measured in vivo using two-photon microscopy before, during, and after administration of the ET
A
receptor inhibitor clazosentan. In separate experiments, the effect of clazosentan treatment on neurological outcome was measured 3 days after SAH.

Results—
Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome.

Conclusions—

Our results indicate that ET
A
receptors, which mediate large artery spasms after SAH, do not seem to play a role in the development of microarterial spasms, suggesting that posthemorrhagic spasms are mediated by distinct mechanisms in large and small cerebral vessels. Given that cerebral microvessel dysfunction is a key factor for outcome after SAH, further research into the mechanisms that underlie posthemorrhagic microvasospasms is urgently needed.
Helping adolescents to better support their peers with a mental health problem: A cluster-randomised crossover trial of teen Mental Health First Aid
Authors: Hart Laura M , Morgan Amy J , Rossetto Alyssia , Kelly Claire M , Mackinnon Andrew , Jorm Anthony F 
Published: February 2018

Background: teen Mental Health First Aid (tMHFA) is a classroom-based training programme for students aged 15–18 years to improve supportive behaviours towards peers, increase mental health literacy and reduce stigma. This research evaluated tMHFA by comparing it to a matched emergency Physical First Aid (PFA) training programme. Methods: A cluster-randomised crossover trial matched four public schools in two pairs and then randomised each to first receive tMHFA or PFA for all Year 10 students. In the subsequent calendar year, the new Year 10 cohort received the opposite intervention, giving eight cohorts. Online surveys were administered at baseline and 1 week post-training, measuring quality of first aid intentions, mental health literacy, problem recognition and stigmatising beliefs, towards fictional adolescents with depression and suicidality (John) and social anxiety (Jeanie). Results: A total of 1942 students were randomised (979 received tMHFA, 948 received PFA), 1605 (84%) analysed for the John vignette at baseline and 1116 (69% of baseline) provided post-training data. The primary outcomes, ‘helpful first aid intentions’ towards John/Jeanie, showed significant group-by-time interactions with medium effect sizes favouring tMHFA ( ds = 0.50–0.58). Compared to PFA, tMHFA students also reported significantly greater improvements in confidence supporting a peer ( ds = 0.22–0.37) and number of adults rated as helpful ( ds = 0.45–0.46) and greater reductions in stigmatising beliefs ( ds = 0.12–0.40) and ‘harmful first aid intentions’ towards John/Jeanie ( ds = 0.15–0.41). Conclusions: tMHFA is an effective and feasible programme for increasing supportive first aid intentions and mental health literacy in adolescents in the short term. tMHFA could be widely disseminated to positively impact on help seeking for adolescent mental illness.
Approaching the Integration of the Social Sciences and Biblical Theology
Authors: Berry C. Markham 
Published: February 2018

Professionals who work in the social and physical sciences and who have a serious commitment to the Bible have, in a sense, two data bases. To integrate them is a difficult task. We are pressed to bring them both into focus by the holistic thrust of the Bible as well as by the penchant of our minds to synthesize. To do this effectively we need simple but not simplistic models. Our integration must further be comprehensive, not partial, basic, not peripheral. This article describes a method of doing this kind of integrative work. Initially, four fundamental criteria are presented. In the second section the basic methodology is worked out, and in the third, some primary themes are described and illustrated around which this particular integrative system works.
The “Marital Conventionalization” Argument; Implications for the Study of Religiosity and Marital Satisfaction
Authors: Schumm Walter R. , Bollman Stephan R. , Jurich Anthony P. 
Published: February 2018

The “marital conventionalization” argument set forth by Edmonds, Withers, and Dibatista (1972) claims that empirical relationships observed between measures of religiosity and marital satisfaction are spurious artifacts of the common contamination of such measures with social desirability/acquiescence response bias, identified by Edmonds (1967) as “marital conventionalization” and measured through the Marital Conventionalization Scale (MCS). More recently, Glenn and Weaver (1978) have adopted the “marital conventionalization” argument to discount the importance of the substantial, positive associations they observed between a religious variable and a measure of marital happiness. Data from two Kansas samples of husbands and wives were analyzed to evaluate the validity of the “marital conventionalization” argument. Results indicate that religiosity is an important predictor of marital satisfaction, at least in some samples, even among subjects who do not respond in a “conventionalizing” way to an abbreviated version of the MCS. Therefore, the limitations of the “marital conventionalization” argument should be considered prior to discounting empirical relationships found between religiosity and marital satisfaction as mere artifacts of social desirability or acquiescence response biases, as measured by the MCS.
The Church and Community Mental Health; Unrealized Potential
Authors: Bufford Rodger K. , Johnston Trudi Bratten 
Published: February 2018

During the past two decades the community mental health approach has enjoyed rapid growth and broad acceptance. Widespread human need, limited professional resources, and the high cost of professional services are major factors which contributed to these developments. Economic considerations, however, have proven to be a major factor limiting implementation of the community mental health approach. The church has great potential to promote community mental health through primary prevention and can contribute to a lesser degree through tertiary prevention. The church offers meaning and purpose to life, and a setting which can foster commitment to mutual caring and concern. Religious involvement can lead to an increased sense of personal well-being. Finally, the church has available a large pool of dedicated volunteers, thus circumventing the financial limitations which have hampered implementation of community mental health goals. So far, however, the community mental health movement has only given limited attention to the role of the church. A conceptual model which suggests the role of the church and professionals in fostering positive mental health professionals is presented; examples of current approaches consistent with the model are discussed.
Adults who Report Childhood Ritualistic Abuse
Authors: Shaffer Ruth E. , Cozolino Louis J. 
Published: February 2018

Therapists are finding an increasing number of patients uncovering memories of ritualistic forms of abuse from childhood. To gain a fuller understanding of this phenomenon, twenty outpatients reporting memories of ritualistic abuse were interviewed. Questions focused on the nature of the abuse and its perceived impact on interpersonal, occupational, and spiritual development. Reasons for entering psychotherapy as well as the nature and course of treatment were also discussed. Subjects entered therapy with similar psychological complaints. Reported psychiatric sequelae included dissociative, affective, somatization, and eating disorders. Abuse experiences were reported to have affected every aspect of their adult functioning. Subjects began therapy with little or no knowledge of the phenomenon of ritualistic abuse, and only one patient reported vague memories of ritualistic abuse before entering therapy. Reports from this sample reflect striking convergence among subjects and with data from previous research and clinical reports. A composite clinical case study is presented based on these data.
Ritual Abuse, Multiplicity, and Mind-Control
Authors: Gould Catherine , Cozolino Louis 
Published: February 2018

As a result of the psychologically intolerable nature of their early childhood experiences, victims of ritual abuse frequently develop multiple personality disorder (MPD). Therapists who treat these victims often assume that all MPD stems from a system of spontaneously created defenses against overwhelming trauma. As a result, these therapists tend to focus on treating the post-traumatic stress elements of the disorder and on integrating alter personalities. Recent experience with victims of ritual abuse suggests the presence of “cult-created” multiplicity, in which the cult deliberately creates alter personalities to serve its purposes, often outside of the awareness of the victim's host personality. Each cult-created alter is programmed to serve a particular cult function such as maintaining contact with the cult, reporting information to the cult, self-injuring if cult injunctions are broken, and disrupting the therapeutic process that could lead to the individual breaking free of the cult. A majority of ritual abuse victims in psychotherapy may maintain cult contact unbeknownst to either the host personality or the treating therapist.
Identifying characteristics and practices of multidisciplinary team reviews for patients with severe mental illness: a systematic review
Authors: Woody Charlotte A , Baxter Amanda J , Harris Meredith G , Siskind Dan J , Whiteford Harvey A 
Published: February 2018

Objectives: Multidisciplinary teams in mental health receive limited guidance, leading to inconsistent practices. We undertook a systematic review of the characteristics and practices of multidisciplinary team reviews for patients with severe mental illness or in relevant mental health service settings. Methods: Sources published since 2000 were located via academic database and web searches. Results were synthesised narratively. Results: A total of 14 sources were analysed. Important characteristics and practices identified included routine monitoring and evaluation, good communication, equality between team members, and clear documentation practices. Success factors included defined leadership and clear team goals. Four sources described considerations for patients with complex clinical needs, including allocating sufficient time for discussion, maintaining connections with community providers, and ensuring culturally sensitive practices. Conclusions: No single best practice model was found, due to variations in team caseload, casemix, and resourcing levels. However, key ingredients for success were proposed. Sources were mostly descriptive; there remains a lack of evidence-based guidance regarding multidisciplinary team review characteristics and practices.