bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental health of postgraduate trainees in primary care: a cross-sectional study
Authors: Bugaj Till J. , Krug Katja , Rentschler Annalena , Nikendei Christoph , Szecsenyi Joachim , Schwill Simon 
Published: June 2020

Abstract
Background
General Practitioners (GPs) are increasingly affected by stress-related complaints and burnout. Although many studies have addressed this issue, little is known about the stress burden and burnout rates of postgraduate trainees specialising in General Practice (GP). This cross-sectional study was performed to explore the prevalence and risk of depression, stress and burnout in a large cohort of GP trainees.

Methods
All GP trainees enrolled in the postgraduate training programme KWBW Verbundweiterbildungplus© in southwest Germany were invited to participate. A paper-based survey for the purpose of psychosocial screening was used: Prevalence of depression, perceived stress and burnout were measured with the depression module of the Patient Health Questionnaire (PHQ-9), Perceived Stress Questionnaire (PSQ-20) and Maslach Burnout Inventory (MBI). Additionally, linear regression models were used to analyse the association between sociodemographic characteristics and mental health scales.

Results
N = 211 GP trainees participated in this study (response rate 95%). 75.3% (n = 159) of the participants were female and median age was 34 (IQR 32; 39). GP trainees had a mean PHQ-9 sum score of 5.4 (SD 3.4). Almost 11% (n = 23) reported symptoms of a moderate or moderately severe depression. PSQ-20 revealed moderate level of distress, whereas 20.8% (n = 42) showed a high level of perceived stress with a sum-score higher than .59. GP trainees showed moderate rates of burnout and only 2.5% (n = 5) scored high in all three dimensions of the MBI score. GP trainees showed increased levels of depression, perceived stress and burnout when compared with age-matched general population. Being a woman led to a higher PHQ-9 sum score (p < .05). Higher age was associated with less depersonalisation in the MBI (p < .05).

Conclusions
The results of our study suggest that GP trainees considerably suffer from stress. Some GP trainees were even affected by depression or burnout. To detect and support colleagues at risk, trainees should be supported by early preventive measures such as anti-stress or resilience trainings and mentoring during their training. Prospective longitudinal studies are needed to understand the character and the course of the stress burden among GP trainees.
Prediction of deep vein thrombosis by ultrasonography and D-dimer in Asian patients with ischemic stroke
Authors: Ha Sang Hee , Kim Yeon-Jung , Heo Sung Hyuk , Chang Dae-il , Kim Bum Joon 
Published: June 2020

Abstract
Background
Deep vein thrombosis (DVT) is an important complication of ischemic stroke, although the incidence of DVT is regarded as being lower in Asian than in non-Asian patients. Here, we investigated the incidence and factors associated with DVT in Asian patients with ischemic stroke.

Methods
Acute ischemic stroke patients received lower extremity ultrasonography (LEUS) to diagnose the presence of DVT. Clinical characteristics and laboratory results, including D-dimer level, were compared between patients with and without DVT. Independent risk factors for DVT were investigated using multivariable analysis. Similar analysis was performed to identify factors associated with elevated D-dimer level (> 0.5 mg/dl) in acute ischemic stroke patients.

Results
During the study period, 289 patients were enrolled, and 38 (13.1%) showed DVT. Female sex (OR = 2.579, 95% CI = 1.224–5.432; p = 0.013) and a high National Institutes of Health Stroke Scale (NIHSS) score (OR = 1.191 95% CI = 1.095–1.294; p = 0.005) were independently associated with the presence of DVT, although D-dimer level was not. Stroke mechanism, especially cardioembolic stroke (OR = 3.777, 95% CI = 1.532–9.313; p = 0.004; reference: large artery atherosclerosis), NIHSS score (OR = 1.087, 95% CI = 1.002–1.179; p = 0.001) and thrombolysis (OR = 12.360, 95% CI 2.456–62.213; p = 0.002) were independently associated with elevated abnormal D-dimer levels.

Conclusion
The severity of ischemic stroke, but not the D-dimer level, was associated with the presence of DVT in Asian ischemic stroke patients. D-dimer level was influenced by the stroke mechanism. LEUS in patients with severe neurological deficit, rather than screening with D-dimer, may be more beneficial for diagnosing DVT in Asian patients with acute ischemic stroke.
Patient-specific instrument-assisted minimally invasive internal fixation of calcaneal fracture for rapid and accurate execution of a preoperative plan: A retrospective study
Authors: Wang Chenggong , Xu Can , Li Mingqing , Li Hui , Xiao Han , Zhong Da , Liu Hua 
Published: June 2020

Abstract
Background
Traditional methods for minimally invasive internal fixation (MIIF) of calcaneal fractures require extensive intraoperative fluoroscopy, and fracture recovery is usually not ideal. We developed a new surgical procedure using digital surgical simulation and constructed a patient-specific instrument (PSI) for calcaneal fracture that we used during the operation. This study investigated whether PSI-assisted MIIF of calcaneal fracture enables rapid and accurate execution of the preoperative plan.

Methods
We retrospectively analyzed patients with Sanders type III or IV fresh calcaneal fractures who had undergone PSI-assisted MIIF at our hospital from January 2016 to December 2018. We analyzed perioperative data including intraoperative fluoroscopy time, concurrence of internal fixation actual usage (IFAU) with the preoperative plan, surgery time, and complications. We also compared pre- and postoperative actual measurements from X-ray radiographs and computed tomography images including Böhler, Gissane, and calcaneus valgus angles; subtalar joint width; and calcaneal volume overlap ratio with the preoperative design. All patients had been followed up and their American Orthopedic Foot and Ankle Score (AOFAS) score was available.

Results
Mean intraoperative fluoroscopy time was 3.95 ± 1.78 h; IFAU in 16 patients (16 ft) was the same as the preoperative plan; mean surgery time was 28.16 ± 10.70 min; and none of the patients developed complications. Böhler, Gissane, and calcaneus valgus angles and subtalar joint width did not differ between pre- and postoperative plans; however, the actual preoperative values of each of these parameters differed significantly from those measured postoperatively. The calcaneal volume overlap ratio with the preoperative design was 91.2% ± 2.3%. AOFAS scores increased with time, with significant differences in the score at each time point.

Conclusions
The newly developed PSI-assisted calcaneal fracture MIIF method can rapidly and accurately execute the preoperative plan.
Patterns of recurrence in adenocarcinoma of the esophagogastric junction: a retrospective study
Authors: Xu Haitao , Zhang Lianguo , Miao Jing , Liu Shuai , Liu Hongjian , Jia Teng , Zhang Qingguang 
Published: June 2020

Abstract
Background
The prognosis of adenocarcinoma of the esophagogastric junction (AEG) is poor. Understanding the postoperative recurrence pattern of AEG is helpful to verify the effectiveness of treatment and optimize subsequent treatment, so as to improve prognosis.

Methods
This single-center retrospective study included patients with stage III AEG who underwent surgical treatment between January 2009 and December 2016. According to the different postoperative treatment arm, patients were divided into surgery and surgery plus chemotherapy groups. Recurrence-free survival was used as the outcome to compare the recurrence site and pattern between the groups.

Results
In total, were 306 patients enrolled, 123 in the surgery group and 183 in the surgery plus chemotherapy group. During follow-up (median 17.1 months) of 24 months after surgery, 62.0% of patients had tumor recurrence. The overall recurrence rates in the surgery and surgery plus chemotherapy groups were 86.9% and 77.0%, respectively. The recurrence patterns of both groups were mainly distant metastasis. Postoperative chemotherapy reduced the incidence of hematogenous dissemination from 51.2 to 42.0%. Multivariate Cox analysis showed that the pN stage increased the risk of recurrence, while surgery plus chemotherapy reduced the risk.

Conclusions
Patients with AEG have a risk of hematogenous dissemination after surgery. Postoperative treatment arm and pN stage were independent risk factors in patients with AEG. Surgery plus chemotherapy can improve recurrence-free survival and reduce distant metastasis, but they do not have a beneficial role in controlling local recurrence.
The importance of social factors in the association between physical activity and depression in children
Authors: Conley May I. , Hindley Isabella , Baskin-Sommers Arielle , Gee Dylan G. , Casey B. J. , Rosenberg Monica D. 
Published: June 2020

AbstractBackgroundPhysical activity is associated with reduced depression in youth and adults. However, our understanding of how different aspects of youth activities—specifically, the degree to which they are social, team-oriented, and physical—relate to mental health in children is less clear.MethodsHere we use a data-driven approach to characterize the degree to which physical and non-physical youth activities are social and team-oriented. We then examine the relationship between depressive symptoms and participation in different clusters of youth activities using mixed effect models and causal mediation analyses in 11,875 children from the Adolescent Brain Cognitive Development (ABCD) Study. We test our hypotheses in an original sample (n = 4520, NDA release 1.1) and replication sample of participants (n = 7355, NDA release 2.0.1).ResultsWe show and replicate that social–physical activities are associated with lower depressive symptoms. Next, we demonstrate that social connections, measured by number of close friends, partially mediate the association between social–physical activities and lower depressive symptoms.ConclusionsOur results provide a rubric for using data-driven techniques to investigate different aspects of youth activities and highlight the social dynamics of physical activities as a possible protective factor against depression in childhood.
Antithyroid drugs and birth defects
Authors: Andersen Stine Linding , Andersen Stig 
Published: June 2020

AbstractAntithyroid drugs (ATDs) are preferred for the treatment of hyperthyroidism caused by Graves’ disease in pregnant women. The drugs have been a recognized treatment for decades, and a general risk of side effects is known. For the use of ATDs in pregnancy, a concern about teratogenic side effects has been brought forward since the 1970s. In more recent years, a number of large observational studies have added new evidence and quantified the risk of birth defects associated with different types of ATDs. The findings that both Methimazole (MMI) and Propylthiouracil (PTU) are associated with birth defects have challenged the clinical recommendations on the treatment of hyperthyroidism in pregnancy, and certain aspects remain unclarified. In this review, the current evidence on the risk of birth defects associated with the use of ATDs in early pregnancy is described, and determinants of causality are discussed. This includes the current evidence of a biological gradient and the role of maternal thyroid function per se. Finally, clinical aspects of the timing and type of treatment is discussed, and future perspectives are addressed. Current evidence corroborates a risk of birth defects associated with MMI while more evidence is needed to determine the teratogenic potential of PTU. Detailed assessment of type and timing of exposure in large cohorts are needed. Moreover, studies investigating alternative or new treatments are warranted.
Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer
Authors: Langdon Ryan , Richmond Rebecca , Elliott Hannah R. , Dudding Tom , Kazmi Nabila , Penfold Chris , Ingarfield Kate , Ho Karen , Bretherick Andrew , Haley Chris , Zeng Yanni , Walker Rosie M. , Pawlita Michael , Waterboer Tim , Gaunt Tom , Smith George Davey , Suderman Matthew , Thomas Steve , Ness Andy , Relton Caroline 
Published: June 2020

AbstractBackgroundSmoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conducted single-site and differentially methylated region (DMR) epigenome-wide association studies (EWAS) of these factors, in addition to ∼ 3-year survival, using Illumina Methylation EPIC DNA methylation profiles from whole blood in 409 individuals as part of the Head and Neck 5000 (HN5000) study. Overlapping sites between each factor and survival were then assessed using two-step Mendelian randomization to assess whether methylation at these positions causally affected survival.ResultsUsing the MethylationEPIC array in an OPC dataset, we found novel CpG associations with smoking, alcohol consumption and ~ 3-year survival. We found no CpG associations below our multiple testing threshold associated with HPV16 E6 serological response (used as a proxy for HPV infection). CpG site associations below our multiple-testing threshold (PBonferroni< 0.05) for both a prognostic factor and survival were observed at four gene regions:SPEG(smoking),GFI1(smoking),PPT2(smoking) andKHDC3L(alcohol consumption). Evidence for a causal effect of DNA methylation on survival was only observed in theSPEGgene region (HR per SD increase in methylation score 1.28, 95% CI 1.14 to 1.43,P2.12 × 10−05).ConclusionsPart of the effect of smoking on survival in those with oropharyngeal cancer may be mediated by methylation at theSPEGgene locus. Replication in data from independent datasets and data from HN5000 with longer follow-up times is needed to confirm these findings.
Bone up on spinal osseous lesions: a case review series
Authors: Nguyen Trinh T. , Thelen Jarett C. , Bhatt Alok A. 
Published: June 2020

AbstractSpinal osseous neoplasms are frequently encountered and can be challenging when present as solitary lesions. Familiarity with the range of benign and malignant spinal pathology can help the radiologist formulate a comprehensive differential diagnosis. This article focuses on the spectrum of extradural spinal tumors, accounting for the majority of primary spinal tumors, by comparing the epidemiology, pathophysiology, clinical presentation, and characteristic imaging appearance of these lesions. The discussion includes the commonly encountered benign lesions, such as vertebral venous vascular malformation and enostosis, as well as malignant lesions including metastases and lymphoma. The article also includes other less-encountered primary spinal tumors such as plasmacytoma, osteoid osteoma, osteoblastoma, giant cell tumor, eosinophilic granuloma, chordoma, chondrosarcoma, osteosarcoma, Ewing’s sarcoma, and angiosarcoma. Familiarity with the characteristic imaging features can help the radiologist reach an accurate diagnosis and obviate the need for unnecessary invasive procedures such as biopsy and surgery.
Unfractionated heparin displaces sFlt-1 from the placental extracellular matrix
Authors: Moore Kyle H. , Chapman Heather , George Eric M. 
Published: June 2020

AbstractSoluble vascular endothelial growth factor receptor-1 (sFlt-1) is an anti-angiogenic protein which is secreted by numerous cell types and acts as a decoy receptor for the angiogenic protein vascular endothelial growth factor (VEGF). Despite its physiologic importance in maintaining angiogenic balance, excess sFlt-1 levels are associated with the pathogenesis of many diseases, especially those with angiogenic imbalance, endothelial dysfunction, and hypertension. Although sFlt-1 is a soluble protein, it contains a binding site for the extracellular matrix component heparan sulfate. This allows cells to retain and localize sFlt-1 in order to prevent excessive VEGF signaling. During pregnancy, placental syncytiotrophoblasts develop a large extracellular matrix which contains significant amounts of heparan sulfate. Consequently, the placenta becomes a potential storage site for large amounts of sFlt-1 bound to extracellular heparan sulfate. Additionally, it should be noted that sFlt-1 can bind to the anticoagulant unfractionated heparin due to its molecular mimicry to heparan sulfate. However, it remains unknown whether unfractionated heparin can compete with heparan sulfate for binding of localized sFlt-1. In this study, we hypothesized that administration of unfractionated heparin would displace and solubilize placental extracellular matrix(ECM)-bound sFlt-1. If unfractionated heparin can displace this large reservoir of sFlt-1 in the placenta and mobilized it into the maternal circulation, we should be able to observe its effects on maternal angiogenic balance and blood pressure. To test this hypothesis, we utilized in vitro, ex vivo, and in vivo methods. Using the BeWo placental trophoblast cell line, we observed increased sFlt-1 in the media of cells treated with unfractionated heparin compared to controls. The increase in media sFlt-1 was found in conjunction with decreased localized cellular Flt (sFlt-1 and Flt-1) as measured by total cell fluorescence. Similar results were observed using ex vivo placental villous explants treated with unfractionated heparin. Real-time quantitative PCR of the explants showed no change in sFlt-1 or heparanase-1 mRNA expression, eliminating increased production and enzymatic cleavage of heparan sulfate as causes for sFlt-1 media increase. Timed-pregnant rats given a continuous infusion of unfractionated heparin exhibited an increased mean arterial pressure as well as decreased bioavailable VEGF compared to vehicle-treated animals. These data demonstrate that chronic unfractionated heparin treatment is able to displace matrix-bound sFlt-1 into the maternal circulation to such a degree that mean arterial pressure is significantly affected. Here we have shown that the placental ECM is a storage site for large quantities of sFlt-1, and that it should be carefully considered in future studies concerning angiogenic balance in pregnancy.
Emergency department utilization by people living with HIV released from jail in the US South
Authors: Puing Alfredo G. , Li Xilong , Rich Josiah , Nijhawan Ank E. 
Published: June 2020

Abstract
Background
Incarceration is disruptive to HIV care, often resulting in poor retention in care for people living with HIV (PLWH) after jail release. This gap in HIV care might result in potentially preventable emergency department (ED) utilization. We analyzed demographic, incarceration, socioeconomic and clinical data for PLWH released from the Dallas County Jail to the community (1450 incarcerations, 1155 unique individuals) between January 2011 and November 2013.

Results
The study population consisted of predominantly men (77%), with a mean age of 39 years, 67% were black and 14% were Hispanic; half of the releasees visited the ED at least once during the first-year post-jail. In adjusted analyses, female gender, family awareness of HIV status, serious mental illness, and late engagement to HIV care were significantly associated with higher ED utilization. Compared to the general Dallas population, PLWH released from jail had a 5-fold higher proportion of ED visits classified as related to substance use or mental health.

Conclusions
Further efforts are needed to improve the transition from incarceration to community-based HIV care, substance use disorder treatment and mental health services, and to directly address re-engagement in HIV care for out-of-care PLWH who visit the ED.
A Phase 2, Multicenter Study of Nevanimibe for the Treatment of Congenital Adrenal Hyperplasia
Authors: El-Maouche Diala , Merke Deborah P , Vogiatzi Maria G , Chang Alice Y , Turcu Adina F , Joyal Elizabeth G , Lin Vivian H , Weintraub Lauren , Plaunt Marianne R , Mohideen Pharis , Auchus Richard J 
Published: June 2020

Abstract

Context
Patients with classic congenital adrenal hyperplasia (CAH) often require supraphysiologic glucocorticoid doses to suppress adrenocorticotropic hormone (ACTH) and control androgen excess. Nevanimibe hydrochloride (ATR-101), which selectively inhibits adrenal cortex function, might reduce androgen excess independent of ACTH and thus allow for lower glucocorticoid dosing in CAH. 17-hydroxyprogesterone (17-OHP) and androstenedione are CAH biomarkers used to monitor androgen excess.

Objective
Evaluate the efficacy and safety of nevanimibe in subjects with uncontrolled classic CAH.

Design
This was a multicenter, single-blind, dose-titration study. CAH subjects with baseline 17-OHP ≥4× the upper limit of normal (ULN) received the lowest dose of nevanimibe for 2 weeks followed by a single-blind 2-week placebo washout. Nevanimibe was gradually titrated up if the primary outcome measure (17-OHP ≤2× ULN) was not met. A total of 5 nevanimibe dose levels were possible (125, 250, 500, 750, 1000 mg twice daily).

Results
The study enrolled 10 adults: 9 completed the study, and 1 discontinued early due to a related serious adverse event. At baseline, the mean age was 30.3 ± 13.8 years, and the maintenance glucocorticoid dose, expressed as hydrocortisone equivalents, was 24.7 ± 10.4 mg/day. Two subjects met the primary endpoint, and 5 others experienced 17-OHP decreases ranging from 27% to 72% during nevanimibe treatment. The most common side effects were gastrointestinal (30%). There were no dose-related trends in adverse events.

Conclusions
Nevanimibe decreased 17-OHP levels within 2 weeks of treatment. Larger studies of longer duration are needed to further evaluate its efficacy as add-on therapy for CAH.
Disease Control and Gender Predict the Socioeconomic Effects of Acromegaly: A Nationwide Cohort Study
Authors: Dal Jakob , Nielsen Eigil H , Rasmussen Ulla-Feldt , Andersen Marianne , Feltoft Claus L , Vestergaard Peter , Stochholm Kirstine , Jørgensen Jens Otto L 
Published: June 2020

Abstract

Context
Acromegaly is an insidious disease associated with severe somatic morbidity but data on socioeconomic status are scarce.

Objective
To study the socioeconomic status in acromegaly in a population-based follow-up study.

Methods
All incident cases of acromegaly (n = 576) during the period 1977-2010 were included. For every patient, 100 persons were sampled from the general population matched for date of birth and gender (comparison cohort). Cox regression and hazard ratios (HR), conditional logistic regression and linear regression with 95% confidence intervals (CI) were used.

Outcome Measures
Retirement, social security benefit, annual income, cohabitation, separation, parenthood and educational level.

Results
The proportion of retired individuals was significantly higher in patients with acromegaly after the time of diagnosis (HR, 1.43; 95% CI, 1.26-1.62) and also during the 5-year pre-diagnostic period (HR, 1.15; 95% CI, 1.03-1.28). More individuals with acromegaly received social security benefit compared with the comparison cohort during the initial period after the time of diagnosis. Among patients who maintained a job, the annual income was similar to the comparison cohort. Compared with the background population, cohabitation was lower (HR, 0.69; 95% CI, 0.50-0.95) as was parenthood (HR, 0.56; 95% CI, 0.39-0.80), whereas neither educational level (HR, 0.61; 95% CI, 0.35-1.06) nor separation (HR, 1.13; 95% CI, 0.86-1.47) were different. Female gender and insufficient disease control were associated with a significantly worse socioeconomic status.

Conclusions
1) Socioeconomic status is impaired in patients with acromegaly even before a diagnosis of acromegaly. 2) Females and patients without disease remission have worse outcomes. 3) Early diagnosis and effective treatment of acromegaly could be important factors in mitigating the negative impact on socioeconomic factors.