bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Repositioning in Oncology
Authors: Serafin Marissa B. , Bottega Angelita , da Rosa Taciéli F. , Machado Catrine S. , Foletto Vitória S. , Coelho Silvana S. , da Mota Augusto D. , Hörner Rosmari 
Published: April 2019

Background:
The worldwide increase in the occurrence of cancer associated with the limitations of immunotherapy and the emergence of resistance have impaired the prognosis of cancer patients, which leads to the search for alternative treatment methods. Drug repositioning, a well-established process approved by regulatory agencies, is considered an alternative strategy for the fast identification of drugs, because it is relatively less costly and represents lower risks for patients.

Areas of Uncertainty:
We report the most relevant studies about drug repositioning in oncology, emphasizing that its implementation faces financial and regulatory obstacles, making the creation of incentives necessary to stimulate the involvement of the pharmaceutical industry.

Data Sources:
We present 63 studies in which 52 non-anticancer drugs with anticancer activity against a number of malignancies are described.

Therapeutic Innovations:
Some have already been the target of phase III studies, such as the Add-Aspirin trial for nonmetastatic solid tumors, as well as 9 other drugs (aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, and sertraline) in the CUSP9* clinical trial for the treatment of recurrent glioblastoma. Others have already been successful in repositioning such as thalidomide, zoledronic acid, celecoxib, methotrexate, and gemcitabine.

Conclusions:
Therefore, drug repositioning represents a promising alternative for the treatment of oncological disorders; however, the support from funding agencies and from the government is still needed, the latter regarding regulatory issues.
Normal and leukemic stem cell niche interactions
Authors: Oh Il-Hoan , Jeong Seon-Yeong , Kim Jin-A 
Published: April 2019

Purpose of review
Normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) interact with the stem cell niche bone marrow in different ways. Understanding the potentially unique microenvironmental regulation of LSCs is key to understanding in-vivo leukemogenic mechanisms and developing novel antileukemic therapies.

Recent findings
When leukemic cells are engrafted in the stem cell niche, the cellular nature of the niche – including mesenchymal stromal cells – is reprogramed. Altered mesenchymal cells selectively support leukemic cells and reinforce the pro-leukemic environment. As the niche plays an active role in leukemogenesis, its remodeling may significantly influence the leukemogenic pattern, and cause differences in clinical prognosis. Notably, niche cells could be stimulated to revert to a pronormal/antileukemic state, creating potential for niche-based antileukemic therapy.

Summary
Bone marrow microenvironments are under dynamic regulation for normal and leukemic cells, and there is bi-directional control of leukemic cells in the niche. Leukemic cells are both protected by stroma and able to reprogram stromal cells to transform the niche to a state, which reinforces leukemogenesis. Because of its dynamic nature, the niche could be converted to an environment with antileukemic properties, making it an attractive target for therapy.
Defining the functions of adenosine-to-inosine RNA editing through hematology
Authors: Heraud-Farlow Jacki E. , Chalk Alistair M. , Walkley Carl R. 
Published: April 2019

Purpose of review
The direct modification of RNA is now understood to be widespread, evolutionarily conserved and of consequence to cellular and organismal homeostasis. adenosine-to-inosine (A-to-I) RNA editing is one of the most common mammalian RNA modifications. Transcriptome-wide maps of the A-to-I editing exist, yet functions for the majority of editing sites remain opaque. Herein we discuss how hematology has been applied to determine physiological and malignant functions of A-to-I editing.

Recent findings
Functional studies have established that A-to-I editing and ADAR1, responsible for the majority of editing in blood cells, are essential for normal blood cell homeostasis. ADAR1 edits endogenous RNA and reshapes its secondary structure, preventing MDA5 from perceiving the cells own RNA as pathogenic. Roles for ADAR1 in human leukaemia, and most recently, cancer cell intrinsic and extrinsic functions of ADAR1 have been identified that highlight ADAR1 as a therapeutic target in cancer.

Summary
The studies reviewed have identified the key physiological function of ADAR1 and mechanistic basis for A-to-I editing in normal physiology and have now been extended to cancer. As our understanding of the biology and consequences of A-to-I editing evolve, it may be possible to target ADAR1 function advantageously in a number of settings.
A primary care pediatrician's guide to assessing problematic interactive media use
Authors: Nereim Cameron , Bickham David , Rich Michael 
Published: April 2019

Purpose of review
To review the literature and provide a guide to assessing patients with problematic interactive media use (PIMU).

Recent findings
0.3–1.0% of the world population meets criteria for internet gaming disorder (IGD). 26.8–83.3% of adolescents meeting criteria for internet addiction have comorbid attention-deficit/hyperactivity disorder. IGD is associated with increased anxiety and social anxiety/phobias. Group counseling, cognitive behavioral therapy, and sports intervention are associated with significant reductions in internet addiction.

Summary
With the Diagnostic and Statistical Manual of Mental Disorders-5 inclusion of IGD under ‘Conditions for Further Study’ and the addition of gaming disorder to International Classification of Diseases (ICD)-11, the idea that PIMU is a mental health disorder gained traction. Although certain populations may be at increased risk, all children and adolescents should be screened for PIMU given now-normal heavy media usage rates. Effective treatment of PIMU starts with identification and management of comorbid mental and behavioral health problems. Depending on their degree of functional impairment, patients may benefit from various forms of psychotherapy with coordinated outpatient management or may warrant higher level of care in one of several established residential treatment programs. Few studies have evaluated pharmacologic approaches to treating PIMU, but some medications targeting comorbid mental and behavioral health conditions improve PIMU-related behaviors.
Ovary-sparing surgery for benign pediatric ovarian masses
Authors: Lawrence Amy E. , Minneci Peter C. , Deans Katherine J. 
Published: April 2019

Purpose of review
This review highlights progress in the management of pediatric ovarian neoplasms. Recent research has identified disparities in the management of patients with benign ovarian neoplasms based on a variety of factors. However, the long-term effects of unilateral oophorectomy have prompted an emphasis on ovary-sparing surgery (OSS) for benign masses. One of the challenges still facing providers is the preoperative differentiation between benign and malignant masses.

Recent findings
Recent studies highlight the variability in practice patterns surrounding the management of benign ovarian neoplasms. Progress continues to be made in identifying reliable factors that can be used to inform preoperative risk stratification of patients who present with ovarian neoplasms. These factors include imaging characteristics, symptoms and tumor markers. In addition, the safety of OSS with regard to recurrence and upstaging in appropriate settings continues to be demonstrated.

Summary
This review highlights the importance of multidisciplinary collaboration in the treatment of ovarian neoplasms given the varied surgical approach by specialty. Multiple retrospective studies have identified factors that can be used for preoperative risk stratification and selection of patients for OSS. Prospective studies evaluating the accuracy of these factors for preoperative risk stratification are needed.
Chinese American Women's Experiences with Postpartum Depressive Symptoms and Mental Health Help-Seeking Behaviors
Authors: Ta Park Van M. , Goyal Deepika , Suen Joyce , Win Nolee , Tsoh Janice Y. 
Published: April 2019

Abstract

Purpose:
The objective of this study was to explore the perspectives of postpartum depression (PPD) and mental health help-seeking behaviors among Chinese American women.

Study Design and Methods:
Using a qualitative design, Chinese American women, who had given birth in the past year, participated in a semistructured interview (English or Mandarin). Depressive symptoms and mental health services questionnaires were also conducted.

Results:
All 15 participants were married and between 29 and 39 years of age. Content analysis revealed two main themes including culture-specific postpartum traditions and mental health help-seeking. Nine reported sadness or PPD symptoms, including three who scored above the cutoff of the Edinburgh Postnatal Depression Scale (EPDS score ≥9) for risk of PPD and others who disclosed such information during the interview. Many women shared that they experienced postpartum depressive symptoms, but some did not believe depression was applicable to Chinese women.

Clinical Implications:
Healthcare professionals working with Chinese American women must be aware of culture-specific childbearing traditions to promote maternal–infant well-being outcomes.
Bifocal treatment for peri-articular femoral nonunions
Authors: Grewal Ishvinder S. , Giotakis Nikos , Narayan Badri , Nayagam Selvadurai 
Published: April 2019

Abstract

Aim:
This is a retrospective review of complex periarticular femoral nonunions where bone loss from comminution at original fracture, subsequent infection or lysis was identified and treated by radical excision, internal fixation, and concurrent femoral lengthening from a different level.

Material and Method:
Sixteen patients with a mean age of 41 years were treated. There were 6 infected nonunions. Ten nonunions were located in the distal femur and the remaining proximal. Case notes and radiograph review were used to determine fracture union, lengthening achieved, and complications. Patient outcome was assessed using the SF-12, Tegner–Lysholm Knee Score, and Oxford Hip Score.

Results:
Fracture union was achieved in all patients. The mean lengthening performed was 51 mm (range 30–80) with a fixator time averaging 39 weeks (range 17–80). The bone healing index was 1.9 months/cm. All but 2 patients were restored to within 5 mm of opposite leg length; 1 patient subsequently underwent contralateral limb shortening. The SF-12 had a mean Physical Health Composite Score of 40.0 (22.4–52.9) and a mean Mental Health Composite Score of 49 (30.7–62.0). The Oxford Hip Score was scored at a mean of 39 (21–47) and the Tegner–Lysholm score had a mean of 71 (36–94). There were 3 cases of fracture/deformity from the lengthened bone column (regenerate) and 2 patients required a quadricepsplasty for knee stiffness that was present prior to the treatment for the nonunion.

Conclusion:
Bifocal treatment of complex periarticular femoral nonunions offers a single solution for dealing with bone loss, nonunion, and instability. The method is safe and reliable but has, as with all methods involving distraction osteogenesis, a significant complication rate. Despite this caution, the patients’ outcomes were satisfactory.
Heterosexual Men Anticipate Risk Compensatory Behaviors With Future Preexposure Prophylaxis Initiation: Findings From an Exploratory Cross-Sectional Study
Authors: Roth Alexis M. , Tran Nguyen , Felsher Marisa , Szep Zsofia , Krakower Douglas 
Published: April 2019

Abstract
Among 146 urban heterosexuals screening negative for human immunodeficiency virus, one third anticipated increased sexual risk taking with human immunodeficiency virus preexposure prophylaxis. Men (vs. women) and black (vs. white) participants had increased odds for anticipating decreased condom use. Men and persons reporting transactional sex expected to increase sexual partnerships. Risk compensation could affect reproductive health and disease control.
Biomarkers of Cerebral Damage in Fatal Hypothermia
Authors: Morleo Bastien , Teresinski Gregor , Rousseau Guillaume , Tse Rexson , Tettamanti Camilla , Augsburger Marc , Palmiere Cristian 
Published: April 2019

Abstract
The identification of hypothermia as the cause of death remains challenging in forensic pathology because of unspecific radiological, morphological, and biochemical results. Hyperemia, edema, and petechial hemorrhages within the cerebral parenchyma were described in cases of death by hypothermia. On the other hand, the effect of low temperatures in the brain has been speculated to cause local injuries on a cellular level with potential occurrences of necrosis and inflammation. In the study herein described, endocan, alkaline phosphatase, neuron-specific enolase, S100 protein subunit B, glial fibrillary acidic protein, and C-reactive protein were measured in postmortem serum from femoral blood and cerebrospinal fluid in a series of hypothermia fatalities and control cases. The combination of data collected failed to identify a specific biochemical profile for death by hypothermia in postmortem serum and/or the cerebrospinal fluid, thus suggesting that an alternative panel of brain damage biomarkers indicative of diffuse hypoxic brain injury needs to be defined in hypothermia fatalities.
The Inadequate Oxygen Delivery Index and Low Cardiac Output Syndrome Score As Predictors of Adverse Events Associated With Low Cardiac Output Syndrome Early After Cardiac Bypass*
Authors: Rogers Libby , Ray Samiran , Johnson Mae , Feinstein Yael , Dominguez Troy E. , Peters Mark J. , Hoskote Aparna , Brown Katherine L. 
Published: April 2019

Objectives:
To evaluate the effectiveness of two scoring systems, the inadequate oxygen delivery index, a risk analytics algorithm (Etiometry, Boston, MA) and the Low Cardiac Output Syndrome Score, in predicting adverse events recognized as indicative of low cardiac output syndrome within 72 hours of surgery.

Design:
A retrospective observational pair-matched study.

Setting:
Tertiary pediatric cardiac ICU.

Patients:
Children undergoing cardiac bypass for congenital heart defects. Cases experienced an adverse event linked to low cardiac output syndrome in the 72 hours following surgery (extracorporeal membrane oxygenation, renal replacement therapy, cardiopulmonary resuscitation, and necrotizing enterocolitis) and were matched with a control patient on criteria of procedure, diagnosis, and age who experienced no such event.

Interventions:
None.

Measurements and Main Results:
Of a total 536 bypass operations in the study period, 38 patients experienced one of the defined events. Twenty-eight cases were included in the study after removing patients who suffered an event after 72 hours or who had insufficient data. Clinical and laboratory data were collected to derive scores for the first 12 hours after surgery. The inadequate oxygen delivery index was calculated by Etiometry using vital signs and laboratory data. A modified Low Cardiac Output Syndrome Score was calculated from clinical and therapeutic markers. The mean inadequate oxygen delivery and modified Low Cardiac Output Syndrome Score were compared within each matched pair using the Wilcoxon signed-rank test. Inadequate oxygen delivery correctly differentiated adverse events in 13 of 28 matched pairs, with no evidence of inadequate oxygen delivery being higher in cases (p = 0.71). Modified Low Cardiac Output Syndrome Score correctly differentiated adverse events in 23 of 28 matched pairs, with strong evidence of a raised score in low cardiac output syndrome cases (p < 0.01).

Conclusions:
Although inadequate oxygen delivery is an Food and Drug Administration approved indicator of risk for low mixed venous oxygen saturation, early postoperative average values were not linked with medium-term adverse events. The indicators included in the modified Low Cardiac Output Syndrome Score had a much stronger association with the specified adverse events.
Is It Possible to Develop a Prediction Model for Lymphovascular Space Invasion in Endometrioid Endometrial Cancer?
Authors: Meydanli Mehmet M. , Aslan Koray , Öz Murat , Muftuoglu Kamil H. , Yalcin Ibrahim , Engin-Ustun Yaprak 
Published: April 2019

Objective
The purpose of this retrospective study was to define a risk index that would serve as a surrogate marker of lymphovascular space invasion (LVSI) in women with endometrioid endometrial cancer (EC).

Materials and Methods
Final pathology reports of 498 women who underwent surgery with curative intent for endometrioid EC between January 2008 and June 2018 were retrospectively reviewed. Logistic regression was used to investigate clinicopathologic factors associated with positive LVSI status. Independent risk factors for LVSI were used to build a risk model and “risk of LVSI index” was defined as “tumor grade×primary tumor diameter×percentage of myometrium involved.” The scores used in the “risk of LVSI index” were weighted according to the odds ratios assigned for each variable. The risk of LVSI index was noted for each patient. The diagnostic performance of the model was expressed as sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio.

Results
According to the “risk of LVSI index,” presence of LVSI was correctly estimated in 89 of 104 LVSI-positive women at a cutoff of 161.0 (sensitivity 85.5%, specificity 79.4%, negative predictive value 95.4%, positive predictive value 52.3%, positive likelihood ratio 4.15, negative likelihood ratio 0.18). The area under curve of the receiver-operating characteristics was 0.90 (95% confidence interval, 0.87–0.93) at this cutoff.

Conclusions
It seems possible to predict the presence of LVSI in women with endometrioid EC when the “risk of LVSI index” is calculated. However, external validation of this model is warranted.
Quantifying Interpersonal Dynamics for Studying Socio-Emotional Processes and Adverse Health Behaviors
Authors: Butler Emily A. , Barnard Kobus J. 
Published: April 2019

ABSTRACT

Objective
We introduce a new statistical software R package, rties, that simplifies the use of dynamic models for investigating interpersonal emotional processes. We demonstrate the package by using it to test whether emotional dynamics in romantic couples can predict, or are predicted by, shared unhealthy behaviors (SUBs).

Methods
We use data from 74 romantic couples discussing their health behaviors. The conversations were videotaped and rated for evidence that the couples engaged in unhealthy behaviors that benefitted the relationship in some way (e.g., increasing closeness). Participants also provided video-prompted continuous recall of their emotional experience during the conversation. We use the rties package to estimate the parameters for inertia-coordination and coupled-oscillator models of the couples’ emotional experience. Those parameter estimates are then used as predictors and outcomes of the couple’s SUB.

Results
The coupled-oscillator model accounted for 17% of the variance in unhealthy behavior, with both partner’s amplification predicting higher unhealthy behavior (women: B = 0.95, SE = 0.31, t(63) = 3.06, p = .003, 95% confidence interval = 0.25–1.45; men: B = 0.9, SE = 0.29, t(63) = 3.09, p = .003, 95% confidence interval = 0.32–1.47). These results suggest that co-dysregulation, an unstable interpersonal pattern of amplified emotional oscillations is associated with more SUBs. In contrast, the dynamics assessed with inertia coordination were not associated with behavior.

Conclusions
The new rties package provides a set of relatively easy-to-use statistical models for representing and testing theories about interpersonal emotional dynamics. Our results suggest that emotional co-dysregulation may be a particularly detrimental pattern for health.
Comparison Between Intermaxillary Fixation With Screws and an Arch Bar for Mandibular Fracture
Authors: Choi Jong-Woo , Kim Hyung Bae , Jeong Woo Shik , Kim Sung Chan , Koh Kyung S. 
Published: April 2019

Purpose:
Intermaxillary fixation (IMF) using the arch bar has been the standard technique for a long time in the management of mandibular fracture. But because of several complications, intermaxillary fixation with screws has been introduced and adopted to use. This investigation compared the outcomes and complications between the traditional IMF and modified intermaxillary fixation with screws techniques in terms of the malocclusion, surgical time, root injury, and screw or arch bar failure.

Methods:
This retrospective review included 66 patients who underwent reconstruction of mandibular fractures that uses traditional arch bar or IMF screws as IMF. Preoperative and postoperative facial bone computed tomography, panoramic x-ray were used to evaluate the patients. The complaints and complications were recorded in electric medical record based on patients’ consultation during follow-up.

Results:
The total complication rate was no higher using anchoring screw as an IMF than using arch bar fixation as an IMF. Mean surgical time was significantly shorter in the anchoring screw group than arch bar fixation (111 versus 157 min; P < .05). After compensation of the number of fracture sites, there was a significant difference in operation time (linear regression model, P = .009).

Conclusion:
This investigation revealed that the IMF using IMF screw systems could be a good alternative for the management of mandibular fracture. It could minimize the whole operation time with the similar complication ratio.
Intra- and Postoperative Blood Loss and Transfusion Requirements in Children Undergoing Craniofacial Surgery
Authors: D’Amore Alexander Lindholm , Rasmussen Mads , Christensen Leif , von Oettingen Gorm , Nørholt Sven Erik , Krogh Lisbeth , Hvas Anne-Mette , Juul Niels , Fenger-Eriksen Christian 
Published: April 2019

Abstract
Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors’ institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14–33 mL/kg) and postoperatively 27 mL/kg (18–37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10–24 mL/kg) and postoperative 14 mL/kg (9–21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0–6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60–300 minutes).
Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.