bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists
Authors: Correll Christoph U. , Brevig Thomas , Brain Cecilia
Published: November 2019

Background

Minimal/non-response to antipsychotic treatment, and persistent positive symptoms despite treatment, are common among patients with schizophrenia. The aim of this study was to characterize a US treatment-resistant schizophrenia (TRS) population in terms of patient demographics, burden of symptoms, treatment history, and factors influencing therapeutic choice.

Methods

In an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia (‘non-TRS’).

Results

Respondents reported that 29.5% of their schizophrenia caseload had TRS. Selected TRS (n = 408) vs non-TRS (n = 204) patients were more likely to be unemployed (74.5% vs 45.1%, p < 0.001), hospitalized at least once (93.4% vs 74.0%, p < 0.001), and to have physical/psychiatric comorbidities including obesity (40.2% vs 23.5%, p < 0.001) and depression (38.7% vs 25.0%, p = 0.001). Psychiatric symptoms were more frequent and severe in TRS, and interfered more with social and functioning domains. Of positive symptoms, eliminating delusions and hallucinations was considered most important to improve a patient’s long-term prognosis. In TRS, clozapine monotherapy was the most common treatment (15.9%), though ranked fifth of ten options to treat TRS. Psychiatrists typically increased the antipsychotic dose or added a second antipsychotic before initiating clozapine or switching antipsychotics. Antipsychotic switches were most commonly due to lack of efficacy (TRS = 71.4% vs non-TRS = 54.3%, p < 0.001) and intolerability (34.4% vs 38.4%, p = 0.22) with the prior antipsychotic. Persistent hallucinatory behavior was the top symptom leading to treatment switches in TRS (63.9% vs 37.1%, p < 0.001).

Conclusions

According to psychiatrists, symptoms have a greater clinical burden on patients with TRS than non-TRS. TRS is commonly managed by antipsychotic dose increases/combinations, with clozapine the fifth preference despite being the only approved TRS medication. New treatments are needed for patients who do not respond to available antipsychotics.
Feasibility of peer support services among people with severe mental illness in China
Authors: Fan Yunge , Ma Ning , Ma Liang , Zhang Wufang , Xu Wei , Shi Ruina , Chen Hanyan , Lamberti J. Steven , Caine Eric D.
Published: November 2019

Background

Peer-delivered services potentially provide broad, multifaceted benefits for persons suffering severe mental illness. Most studies to date have been conducted in countries with well-developed outpatient mental health systems. The objective of this study was to examine the feasibility for developing a community-based peer service in China.

Methods

Thirteen peer service providers and 54 consumers were recruited from four communities in Beijing. We initiated the program in two communities, followed by another two in order to verify and add to our understanding of potential scalable feasibility. Semi-structured face-to-face interviews were conducted 12 month after initiation at each site to measure satisfaction and perceived benefits from perspectives of peer service providers, and consumers and their caregivers.

Results

Key stakeholders reported that peer support services were satisfying and beneficial. Eleven of 13 peer service providers were willing to continue in their roles. Ten, 8, and 7 of them perceived improvements in working skills, social communication skills, and mood, respectively. Among consumers, 39 of 54 were satisfied with peer services. Improvements in mood, social communication skills, illness knowledge, and illness stability were detected among 23, 18, 13, and 13 consumers, respectively. For caregivers, 31 of 32 expressed a positive view regarding peer services. Caregivers reported improvement in their own mood, confidence in recovery of their family members, and reduction in caretaker burdens.

Conclusions

The findings highlight that peer-delivered services have promise in China for benefiting persons with severe mental illness and their family caregivers, as well as the peer service providers themselves.
Innovation diffusion: how homogenous networks influence the uptake of community-based injectable contraceptives
Authors: Akinyemi Oluwaseun , Harris Bronwyn , Kawonga Mary
Published: November 2019

Background

Studies have shown that social networks influence health behaviors, including the adoption of health innovations. This study explored the potential for early adopters of community health worker-delivered injectable contraceptives (CHWDIC) to influence the uptake of this innovation by women in their social networks.

Methods

This Social Network Analysis (SNA) study was conducted in Gombe, Nigeria. Twenty women who were early adopters of the CHWDIC were recruited. Each participant (ego) listed ten women of reproductive age (alters) with whom they related. An interviewer-administered questionnaire was used to collect from each ego, data about the nature of her relationship with each alter (ego-alter relationship), whether she talked about CHWDIC with each alter, and whether her listed alters talked to each other about CHWDIC (alter-alter relationship). Data were also collected on age, marital status and education level for each ego and alter. Data were analyzed with UCINET social network analysis software. Variables of interest include homophilia (similarity), density (number of ties as a proportion of possible ties), degree (popularity) and betweeness (frequency of connecting actor pairs who otherwise might not communicate).

Results

There were 20 egos and 200 alters. Between two thirds (alters) and three quarters (egos) of the women were 30 years or older. All of the egos and 196 (98%) of alters were married. Most of the networks had similar (homophilic) actors according to certain sociodemographic characteristics - ethnicity, age, education and type of marriage. More than 90% of the networks had density greater than 50%, suggesting high cohesion in most networks. The majority of actors in these networks used injectable contraceptives. In some of the networks, few actors with the highest prominence (betweeness centrality) were not users of injectable contraceptives.

Conclusion

The study illustrates the application and feasibility of ego SNA in identifying champions and opinion leaders among women of reproductive age group. It also shows the influence of social networks on the diffusion of community-based injectable contraceptives, and how homophilic and dense networks may have positive health externality. The interrelatedness of network members’ decision to adopt a health innovation was also demonstrated by the findings of this study.
Acute exacerbations of fibrosing interstitial lung disease associated with connective tissue diseases: a population-based study
Authors: Cao Mengshu , Sheng Jian , Qiu Xiaohua , Wang Dandan , Wang Dongmei , Wang Yang , Xiao Yonglong , Cai Hourong
Published: November 2019

Background

Acute exacerbation (AE) is the major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis (IPF). AEs also occur in other forms of fibrosing interstitial lung disease (fILD). The clinical features and prognosis of AE patients with connective tissue diseases (CTDs) associated-ILD has not been fully described.

Methods

We retrospectively reviewed 177 patients with either IPF or a characterized CTD-ILD admitted to Nanjing Drum Tower Hospital with an AE from January 2010 to December 2016.

Results

The study cohort included 107 subjects with AE-IPF and 70 cases with AE-CTD-ILD. Female gender, prior use of corticosteroid and immunosupressants, lower serum albumin, higher D-dimer level, TLC% pred, survival, and treatment with immunosupressants and caspofungin were more common in the CTD-ILD group (all p<0.05). The incidences of AE-CTD-ILD and AE-IPF were similar in our single center (p = 0.526). TLC% pred was the risk factor for AE after ILD diagnosis for 1 year in CTD patients (p = 0.018). Log-rank tests showed patients with CTD-ILD had a significantly lower mortality rate compared with IPF patients after AEs (p = 0.029). No significant difference in survival was noted among CTD subgroups (p = 0.353). The survival was negatively correlated with WBC count, LDH and CT score, (p = 0.006, p = 0.013 and p = 0.035, respectively), and positively correlated with PaO2/FiO2 ratio (p<0.001) in the CTD-ILD group. WBC count and PO2/FiO2 ratio were the independent predictors for survival in AE-CTD-ILD after adjusting for other clinical variates in Cox regression Models (p = 0.038 and p < 0.001, respectively).

Conclusions

The clinical characteristics of patients with AE-CTD-ILD differed from those with AE-IPF, while AE incidences were similar between the two groups. Subjects with AE-CTD-fILD tended to have a better prognosis, and WBC count and PO2/FiO2 ratio were the independent survival predictors for these patients.
Musculoskeletal symptoms among radiologists in Saudi Arabia: a multi-center cross-sectional study
Authors: Al Shammari Malak , Hassan Ali , Al Dandan Omran , Al Gadeeb Mohammed , Bubshait Dalal
Published: November 2019

Background

Musculoskeletal symptoms account for the majority of work-related illnesses resulting in a significant economic burden on society. Computer users are subject to unique repetitive strains that predispose them to musculoskeletal symptoms. In the digitalized field of radiology, radiologists spend long hours interpreting medical images on computers. This study aimed to determine the prevalence of musculoskeletal symptoms among radiologists in Saudi Arabia and their contributing factors.

Methods

An online survey was sent to radiologists in all hospitals (academic, public and private) in the major cities of the Eastern Province of Saudi Arabia covering demographic characteristics, workload (e.g. the time spent at a computer workstation), and workstation environments including the number of monitors as well as the adjustability of the height of the workstation and the viewing distance. This survey of 263 radiologists was conducted in April 2019. It included an evaluation of musculoskeletal symptoms using the Nordic Musculoskeletal Questionnaire. The study outcome was the presence of disabling musculoskeletal symptoms in any body region, which restricted the performance of normal activities in the last 12 months. Results were analyzed descriptively using a Chi-square test and logistic regression analysis to estimate the odd ratio of experiencing disabling musculoskeletal symptoms in the last 12 months.

Results

The survey was completed by 198 participants (111 men and 87 women) with a response rate of 75.3%. Most participants (71.2%) were aged below 40 years. A multivariate logistic regression analysis revealed being a female radiologist (OR = 2.7; 95% CI: 1.2–6.5), aged 30–39 years (OR = 4.1; 95% CI: 1.1–15.3), and predominantly reviewing computed tomography (CT) images (OR = 4.1; 95% CI: 1.4–12.3) or ultrasound scans (OR = 5.9; 95% CI: 1.4–25.3) were associated with higher prevalence of disabling musculoskeletal symptoms, compared to those aged below 30 years and those who reviewed various imaging modalities, respectively.

Conclusions

Musculoskeletal symptoms are common among radiologists with lower back and neck pain being the most frequent complaints. Being a female radiologist, aged 30–39 years, and reviewing CT or ultrasound scans were associated with higher rates of disabling musculoskeletal symptoms.
Thoracoscopic surgical case of an ectopic mediastinal parathyroid adenoma detected by chance: a case report
Authors: Mitsuboshi Shota , Maeda Hideyuki , Aoshima Hiroe , Isaka Tamami , Matsumoto Takako , Onizuka Hiromi , Kanzaki Masato
Published: November 2019

Background

Ectopic mediastinal parathyroid tumor (EMPT) is a rare cause of primary hyperparathyroidism (PHPT); it is difficult to resect using the cervical approach. We describe a case of using video-assisted thoracic surgery (VATS) for EMPT resection.

Case presentation

A 67-year-old woman with a history of postoperative thyroid cancer had no symptoms. She was diagnosed with PHPT and underwent thyroid cancer surgery. She had serum calcium and intact parathyroid hormone (PTH) levels of 11.1 mg/dL and 206 pg/mL, respectively. Chest computed tomography showed a 10-mm nodule in the anterior mediastinum. Technetium-99 m methoxyisobutyl isonitrile scintigraphy showed an abnormal uptake lesion in the anterior mediastinum. She was diagnosed with PHPT caused by EMPT and underwent VATS. The pathological examination confirmed parathyroid adenoma. Her serum calcium and intact PTH levels were normal from 15 min after tumor resection. She has had no recurrence of EMPT.

Conclusions

The VATS approach was effective for the resection of EMPT.
Prevalence of female sexual dysfunction in allied health workers: a cross-sectional pilot study in a tertiary hospital in Singapore
Authors: Safdar Farah , Eng Chui Lee Julia , Wai Khin Lay , Tey Wan Shi , Ang Seng Bin
Published: November 2019

Background

Female sexual dysfunction (FSD) is increasingly being identified as a problem around the world. Women can have problems in various parts of the sexual cycle - desire, arousal, lubrication, orgasm or they may experience pain related to sexual activity. The only study involving Singapore with regard to sexual dysfunction in women, the Asian Global Studies of Sexual Attitudes and Behaviours in 2002, reported that Singapore had one of the lowest age-standardised sexual dysfunction rates of 32% compared with other Asian countries. This pilot study aims to evaluate the prevalence of female sexual dysfunction and to investigate the independent significant risk factors among allied health workers in a tertiary hospital in Singapore.

Methods

A cross-sectional study where an anonymous questionnaire which included 19 questions in the FSFI (Female Sexual Function Index) was distributed to all allied health workers in a tertiary hospital in Singapore aged between 18 to 70 years old.

Results

Three hundred thirty completed questionnaires were involved in analysis. 56.0% of women were found to have sexual dysfunction. A significant difference was found in the prevalence of FSD when comparing nurses to other allied health staff, where nurses had a decreased risk of developing FSD. Age was not found to be a significant risk factor in our study. Respondents below 40 years of age had significantly lower satisfaction scores than those above 40. Indians and Filipinos were found to have lower scores than the Chinese and Malay respondents in the lubrication (p = 0.02) and pain domains (p = 0.02).

Conclusion

A significant proportion our female allied health workers suffer from sexual dysfunction. In this study, we found that the overall prevalence was independent of age, race and marital status. Nurses had a lower risk of developing FSD. We will need further studies to assess the prevalence of female sexual dysfunction in the general population, to evaluate the independent significant risk factors for developing FSD, in addition to classical risk factors, as well as to assess the psychological impact of this condition and whether people would be willing to seek help for such problems.
Knowledge, attitude and practice (KAP) of health providers towards safe abortion provision in Addis Ababa health centers
Authors: Assefa Endalkachew Mekonnen
Published: November 2019

Background

Unsafe abortion remains a reality for many Ethiopian women and will remain so until safe abortion is more accessible across the country. The house of representatives of Federal Democratic Republic of Ethiopia (FDRE) revised the abortion law and Ministry of Health (MoH) of FDRE developed a revised technical and procedural guideline for safe abortion services in Ethiopia; emphasizing the need to increase knowledge and practice of health service providers on safe abortion care (SAC) and access to safe terminations of pregnancy at high standard and quality.

Methods

A facility based descriptive cross-sectional study using structured self-administered questionnaire was conducted between July and August 2015. A total of 405 mid-level providers (MLPs) including midwives, clinical nurses and health officers were included from 30 randomly selected health centers in Addis Ababa. SPSS version-21 was used for data entry, cleaning and analysis. The results were presented using frequency tables, percentages, means, Odds ratio and 95% confidence limits.

Results

Among 405 MLPs 71.9% knew the definition of abortion in the in Ethiopia context, 81.5% participants were familiar with the revised abortion law. 53.1% of respondents had adequate knowledge on safe abortion care and working for 3–5 years (AOR 3.1 with CI 1.6, 5.7) and midwives (AOR = 2.9 with CI 1.8, 4.7) had better knowledge on abortion. Only eighty-three (20.5%) of MLPs were trained on safe abortion and among them sixty-eight (81.9%) were practising/used to practice safe abortion services. Half of respondents gave post abortion family planning methods. 54.1% respondents had positive attitude towards safe abortion. MLPs’ who had adequate knowledge on safe abortion care (AOR 2.02, 95% CI 1.3–3.1) and male providers (AOR 1.6, 95% CI 1.04–2.4) were more likely to have positive attitude towards safe abortion. MLPs who had adequate knowledge on abortion 3.4 times (CI of 95% =1.1–10.6) were more likely to practise safe abortion care.

Conclusion

The majority claimed to know the current abortion law; however, many failed to understand the specific provisions of the law. Type of profession and years of experiences were important in explaining providers’ knowledge related to abortion. Being male and having the knowledge significantly influenced providers’ attitude toward safe abortion. Knowledge related to abortion also influenced the practice of SAC. Efforts to improve mid-level as well as other health care providers’ knowledge on abortion are necessary, for example, through pre−/on-service training.
Prevalence and determinants of test anxiety among medical students in Addis Ababa Ethiopia
Authors: Tsegay Light , Shumet Shegaye , Damene Woynabeba , Gebreegziabhier Gebrselassie , Ayano Getinet
Published: November 2019

Background

Worldwide, problematic test anxiety is a common health problem among medical students. The magnitude of problematic test anxiety ranges from 25 to 40% in undergraduate medical students and has a detrimental effect on academic achievement and success of students. However, data on the prevalence of test anxiety among medical students is limited. Thus, the study aimed to assess the prevalence and associated factors of test anxiety among medical students.

Methods

In this cross-sectional study, a stratified random sampling technique was used to select the participants. The level of test anxiety was determined by the Westside Test Anxiety Inventory (WTAI). We utilized logistic regression to explore the association between test anxiety and the potential sociodemographic/student-related characteristics among medical students.

Results

The study included 423 medical students. Our study resulted the prevalence of problematic test anxiety among medical students to be 52.30% (95% CI 47.40–57.30). The prevalence of test anxiety was remarkably higher in women (79.75%) than in men (33.62%) students. Female sex [AOR = 3.25, 95% CI: (1.54, 6.89)], having low grade [AOR = 0.11,95% CI: (0.044,0.288)], being first year [AOR = 10.55,95% CI: (1.4,76.7)], excessive course load [AOR = 6.128,95% CI: (2.675,14.039)], and taking oral examination [AOR = 2.89,95% CI: (1.42,5.84)] were determined as some of the predicting factors of test anxiety among medical students. Additionally, lack of systemic study plan [AOR = 2.4, 95% CI: (1.25, 4.59)], poor social support [AOR = 3.6, 95% CI: (1.56, 8.29)], moderate social support [AOR = 3.39, 95% CI: (1.56, 7.4)], psychologically distressed [AOR = 2.68, 95% CI: (1.37, 5.27)] independently predicts test anxiety among medical students.

Conclusion

Findings suggest that a substantial percentage of medical students had problematic test anxiety in Ethiopia (52.30%). This study also showed a significant association between test anxiety and female sex, having poor grade point average, being the first year, excessive course load, oral examination, lack of study plan, poor social support, moderate social support, and having psychological distress. Problematic test anxiety, which is found to be common among medical students, deserves more attention.
How to tackle the conundrum of quality appraisal in systematic reviews of normative literature/information? Analysing the problems of three possible strategies (translation of a German paper)
Authors: Mertz Marcel
Published: November 2019

Background

In the last years, there has been an increase in publication of systematic reviews of normative (“argument-based”) literature or of normative information (such as ethical issues) in bioethics. The aim of a systematic review is to search, select, analyse and synthesise literature in a transparent and systematic way in order to provide a comprehensive and unbiased overview of the information sought, predominantly as a basis for informed decision-making in health care. Traditionally, one part of the procedure when conducting a systematic review is an appraisal of the quality of the literature that could be included.

Main text

However, while there are established methods and standards for appraising e.g. clinical studies or other empirical research, quality appraisal of normative literature (or normative information) in the context of a systematic review is still rather a conundrum – not only is it unclear how it could or should be done, but also the question whether it necessarily must be done is not settled yet. Based on a pragmatic definition of “normative literature” as well as on a typology of different types of systematic reviews of normative literature/information, this paper identifies and critically discusses three possible strategies of conducting quality appraisal.

Conclusions

The paper will argue that none of the three strategies is able to provide a general and satisfying solution to the problems associated with quality appraisal of normative literature/information. Still, the discussion of the three strategies allows outlining minimal conditions that elaborated strategies have to meet in future, and facilitates sketching a theoretically and practically promising strategy.
Impact of the Medicare hospital readmissions reduction program on vulnerable populations
Authors: Gai Yunwei , Pachamanova Dessislava
Published: November 2019

Background

The Hospital Readmissions Reduction Program (HRRP) was established by the 2010 Patient Protection and Affordable Care Act (ACA) in an effort to reduce excess hospital readmissions, lower health care costs, and improve patient safety and outcomes. Although studies have examined the policy’s overall impacts and differences by hospital types, research is limited on its effects for different types of vulnerable populations. The aim of this study was to analyze the impact of the HRRP on readmissions for three targeted conditions (acute myocardial infarction, heart failure, and pneumonia) among four types of vulnerable populations, including low-income patients, patients served by hospitals that serve a high percentage of low-income or Medicaid patients, and high-risk patients at the highest quartile of the Elixhauser comorbidity index score.

Methods

Data on patient and hospital information came from the Nationwide Readmission Database (NRD), which contained all discharges from community hospitals in 27 states during 2010–2014. Using difference-in-difference (DD) models, linear probability regressions were conducted for the entire sample and sub-samples of patients and hospitals in order to isolate the effect of the HRRP on vulnerable populations. Multiple combinations of treatment and control groups and triple difference (DDD) methods were used for testing the robustness of the results. All models controlled for the patient and hospital characteristics.

Results

There have been statistically significant reductions in readmission rates overall as well as for vulnerable populations, especially for acute myocardial infarction patients in hospitals serving the largest percentage of low-income patients and high-risk patients. There is also evidence of spillover effects for non-targeted conditions among Medicare patients compared to privately insured patients.

Conclusions

The HRRP appears to have created the right incentives for reducing readmissions not only overall but also for vulnerable populations, accruing societal benefits in addition to previously found reductions in costs. As the reduction in the rate of readmissions is not consistent across patient and hospital groups, there could be benefits to adjusting the policy according to the socioeconomic status of a hospital’s patients and neighborhood.
Health professionals’ experiences of providing care for women survivors of sexual violence in psychiatric inpatient units
Authors: O’Dwyer Carol , Tarzia Laura , Fernbacher Sabin , Hegarty Kelsey
Published: November 2019

Background

Survivors of sexual violence, who are predominantly women, commonly access mental health services. Psychiatric inpatient units in Australia are predominately mixed gender and may further retraumatise these women. Sexual violence is under-recognised by mental health professionals and there is a lack of adequate policy or direction for mental health service services. To date, only a small amount of research has focused on health professionals’ experiences of providing trauma-informed care to women in psychiatric settings, with most studies focused on specific practices or interventions. Qualitative data is particularly lacking on this topic. This is a critical gap in the knowledge given that health professionals are key to detecting and addressing victimisation. The aim of this study was to gain an in-depth understanding of healthcare professionals’ experiences and perceptions in providing care to women who are survivors of sexual violence in psychiatric inpatient units.

Methods

This qualitative study utilised semi-structured interviews with 40 health professionals recruited from four psychiatric inpatient units within a large Australian public mental health organisation. Data were examined using thematic analysis.

Results

Three main typologies were developed to describe participants’ experiences of the care provided to women; 1) Dismissing and denying; 2) Acknowledging but unprepared; 3) Empathising but despairing.

Discussion

Gender, professional training, adherence to the biomedical model, and level of experience influenced health professionals’ experiences.

Conclusions

Health professionals in this study held varying attitudes towards female consumers and responses to sexual violence. Our findings suggest the need to address individual staff perception and promote trauma-informed and gender-sensitive care across all disciplines, genders, and levels of experience.
MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB
Authors: Li Yangyang , Xu Jia , Zhang Jiale , Zhang Jie , Zhang Jian , Lu Xiaoming
Published: November 2019

Background

Glioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors.

Methods

Lentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells.

Results

The expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346.

Conclusion

miR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma.
circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling
Authors: Hu Xueting , Wu Duoguang , He Xiaotian , Zhao Huiying , He Zhanghai , Lin Jiatong , Wang Kefeng , Wang Wenjian , Pan Zihao , Lin Huayue , Wang Minghui
Published: November 2019

Background

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC.

Methods

Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3β) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3β, and the detection rates of plasma circGSK3β for ESCC were investigated.

Results

We demonstrated that upregulated expression of circGSK3β was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3β promoted ESCC cell migration and invasion via direct interaction with GSK3β and inhibiting GSK3β activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3β expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively.

Conclusions

CircGSK3β exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3β have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.
Circulating microRNAs as minimal residual disease biomarkers in childhood acute lymphoblastic leukemia
Authors: Rzepiel Andrea , Kutszegi Nóra , Gézsi András , Sági Judit C. , Egyed Bálint , Péter György , Butz Henriett , Nyírő Gábor , Müller Judit , Kovács Gábor T. , Szalai Csaba , Semsei Ágnes F. , Erdélyi Dániel J.
Published: November 2019

Background

Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other RNA classes. We examined the role of circulating miRs as putative less invasive MRD biomarkers.

Methods

In an exploratory experiment, expression of 46 preselected miRs was studied in platelet-free blood plasma samples of 15 de novo, 5 relapsed ALL patients and 10 controls by Custom TaqMan Array Advanced MicroRNA Card. Based on their high expression in ALL compared to controls, and on the reduction observed along the induction therapy, four miRs were selected for further analyses: miR-128-3p, -181a-5p, -181b-5p and 222-3p. Their expression was measured by qPCR at 4 time points in 27 de novo ALL patients treated in the ALL IC-BFM 2009 study.

Results

The expression of all 4 miRs significantly decreased over the first week of therapy (miR-128-3p: log2 fold change − 2.86; adjusted p 3.6 × 10−7; miR-181b-5p: log2 fold change − 1.75; adjusted p 1.48 × 10−2; miR-181a-5p: log2 fold change -1.33; adjusted p 3.12 × 10−2; miR-222-3p: log2 fold change − 1.25; adjusted p 1.66 × 10−2). However, no significant further reduction in miR expression was found after the 8th day of therapy. Measured drop in expression of 2 miRs at day 8 strongly correlated with day 15 bone marrow flow cytometry MRD results (miR-128-3p: Pearson’s r = 0.88, adjusted p = 2.71 × 10−4; miR-222-3p: r = 0.81, adjusted p = 2.99 × 10−3).

Conclusion

In conclusion, these circulating miRs might act as biomarkers of residual leukemia. MiR-128-3p and miR-222-3p in blood predict day 15 flow cytometry MRD results 7 days earlier. Although, their sensitivity falls behind that of bone marrow flow cytometry MRD at day 15.
Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial
Authors: Jacot William , Cottu Paul , Berger Frederique , Dubot Coraline , Venat-Bouvet Laurence , Lortholary Alain , Bourgeois Hugues , Bollet Marc , Servent Veronique , Luporsi Elisabeth , Espié Marc , Guiu Severine , D’Hondt Veronique , Dieras Veronique , Sablin Marie-Paule , Brain Etienne , Neffati Souhir , Pierga Jean-Yves , Bidard Francois-Clement
Published: November 2019

Background

In this prospective phase 2 trial, we assessed the efficacy of trastuzumab-emtansine (T-DM1) in HER2-negative metastatic breast cancer (MBC) patients with HER2-positive CTC.

Methods

Main inclusion criteria for screening were as follows: women with HER2-negative MBC treated with ≥ 2 prior lines of chemotherapy and measurable disease. CTC with aHER2/CEP17 ratio of ≥ 2.2 by fluorescent in situ hybridization (CellSearch) were considered to beHER2-amplified (HER2amp). Patients with ≥ 1HER2ampCTC were eligible for the treatment phase (T-DM1 monotherapy). The primary endpoint was the overall response rate.

Results

In 154 screened patients, ≥ 1 and ≥ 5 CTC/7.5 ml of blood were detected inN = 118 (78.7%) andN = 86 (57.3%) patients, respectively. ≥1HER2ampCTC was found in 14 patients (9.1% of patients with ≥ 1 CTC/7.5 ml). Among 11 patients treated with T-DM1, one achieved a confirmed partial response. Four patients had a stable disease as best response. Median PFS was 4.8 months while median OS was 9.5 months.

Conclusions

CTC withHER2amplification can be detected in a limited subset of HER2-negative MBC patients. Treatment with T-DM1 achieved a partial response in only one patient.

Trial registration

NCT01975142, Registered 03 November 2013
Associations of race and ethnicity with risk of developing invasive breast cancer after lobular carcinoma in situ
Authors: Dania Vanessa , Liu Ying , Ademuyiwa Foluso , Weber Jason D. , Colditz Graham A.
Published: November 2019

Background

Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS.

Methods

We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer.

Results

During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, 8.2% for Hispanics, 9.3% for whites, and 11.2% for blacks (P = 0.046). Compared to white women, black women had significantly elevated risks of subsequent invasive breast cancer (HR 1.33; 95% CI 1.11, 1.59), and invasive cancer in the ipsilateral breast (HR 1.37; 95% CI 1.08, 1.72) and in the contralateral breast (HR 1.33; 95% CI 1.00, 1.76). Black women had significantly higher risks of invasive subtypes negative for both estrogen receptor and progesterone receptor (HR 1.86; 95% CI 1.14, 3.03) and invasive subtypes positive for one or both of receptors (HR 1.30; 95% CI 1.07, 1.59). The risk of subsequent invasive breast cancer was comparable in Asian women and Hispanic women compared with white women.

Conclusions

Black women had a significantly higher risk of developing invasive breast cancer, including both hormone receptor-positive and hormone receptor-negative subtypes, after LCIS compared with white counterparts. It provides an opportunity to address health disparities.
Differential co-expression-based detection of conditional relationships in transcriptional data: comparative analysis and application to breast cancer
Authors: Bhuva Dharmesh D. , Cursons Joseph , Smyth Gordon K. , Davis Melissa J.
Published: November 2019

Background

Elucidation of regulatory networks, including identification of regulatory mechanisms specific to a given biological context, is a key aim in systems biology. This has motivated the move from co-expression to differential co-expression analysis and numerous methods have been developed subsequently to address this task; however, evaluation of methods and interpretation of the resulting networks has been hindered by the lack of known context-specific regulatory interactions.

Results

In this study, we develop a simulator based on dynamical systems modelling capable of simulating differential co-expression patterns. With the simulator and an evaluation framework, we benchmark and characterise the performance of inference methods. Defining three different levels of “true” networks for each simulation, we show that accurate inference of causation is difficult for all methods, compared to inference of associations. We show that az-score-based method has the best general performance. Further, analysis of simulation parameters reveals five network and simulation properties that explained the performance of methods. The evaluation framework and inference methods used in this study are available in the dcanr R/Bioconductor package.

Conclusions

Our analysis of networks inferred from simulated data show that hub nodes are more likely to be differentially regulated targets than transcription factors. Based on this observation, we propose an interpretation of the inferred differential network that can reconstruct a putative causal network.
European Network of Pregnancy Registers in Rheumatology (EuNeP)—an overview of procedures and data collection
Authors: Meissner Yvette , Strangfeld Anja , Costedoat-Chalumeau Nathalie , Förger Frauke , Goll Doreen , Molto Anna , Özdemir Rebecca , Wallenius Marianne , Fischer-Betz Rebecca
Published: November 2019

Background

The collaborative initiative of the European Network of Pregnancy Registers in Rheumatology (EuNeP) aims to combine data available in nationwide pregnancy registers to increase knowledge on pregnancy outcomes in women with inflammatory rheumatic diseases (IRD) and on drug safety during pregnancy and lactation. The objective of this study was to describe the similarities and differences of the member registers.

Methods

From all registers, information about their structure and design was collected, as well as which parameters regarding demographics, maternal outcomes, treatment, course and outcome of pregnancy, and development of the child were available in the respective datasets. Furthermore, the current recruitment status was reported.

Results

The four registers (EGR2 (France), RePreg (Switzerland), RevNatus (Norway), and Rhekiss (Germany)) collect information prospectively and nationwide. Patients can be enrolled before conception or during pregnancy. To date, more than 3500 patients in total have been included, and data on 2200 pregnancies with an outcome are available. The distribution of diagnoses in the respective registers varies considerably, and only three entities (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) are captured by all the registers. Broad consistency was found in non-disease-specific data items, but differences regarding instruments and categories as well as frequency of data collection were revealed. Disease-specific data items are less homogeneously collected.

Conclusion

Although the registers in this collaboration have similar designs, we found numerous differences in the variables collected. This survey of the status quo of current pregnancy registers is the first step towards identifying data collected uniformly across registers in order to facilitate joint analyses.

Trial registration

Not applicable.
Genotypic diversity of Streptococcus suis and the S. suis-like bacterium Streptococcus ruminantium in ruminants
Authors: Okura Masatoshi , Maruyama Fumito , Ota Atsushi , Tanaka Takeshi , Matoba Yohei , Osawa Aya , Sadaat Sayed Mushtaq , Osaki Makoto , Toyoda Atsushi , Ogura Yoshitoshi , Hayashi Tetsuya , Takamatsu Daisuke
Published: November 2019

Although Streptococcus suis has attracted public attention as a major swine and human pathogen, this bacterium has also been isolated from other animals, including ruminants. However, recent taxonomic studies revealed the existence of other species that were previously identified as S. suis, and some of these isolates were reclassified as the novel species Streptococcus ruminantium. In Japan, biochemically identified S. suis is frequently isolated from diseased ruminants; however, such isolates have not yet been identified accurately, and their aetiological importance in ruminants is unclear. Therefore, to understand the importance of S. suis and S. suis-like bacteria in ruminants, we reclassified S. suis isolates from ruminants according to the updated classification and investigated their genetic diversity. Although both S. suis and S. ruminantium were isolated from healthy and diseased ruminants, most of the isolates from diseased animals were S. ruminantium, implying that S. ruminantium is more likely to be associated with ruminant disease than S. suis. However, the ruminant S. suis and S. ruminantium isolates from diseased animals were classified into diverse genotypes rather than belonging to certain clonal groups. Genome sequence analysis of 20 S. ruminantium isolates provided information about the antibiotic resistance, potential virulence, and serological diversity of this species. We further developed an S. ruminantium-specific PCR assay to aid in the identification of this bacterium. The information obtained and the method established in this study will contribute to the accurate diagnosis of ruminant streptococcal infections.
Idiopathic facial lipoatrophy in a healthy middle-aged woman: A case report
Authors: Purcell Chad , Taylor S. Mark
Published: November 2019

Background

Facial lipoatrophy is a rare condition described by the disappearance of facial subcutaneous fat. The etiology of lipoatrophy can be congenital, or acquired including traumatic, iatrogenic or idiopathic. Idiopathic facial lipoatrophy has only been previously identified in three case reports, among which, the patient demographics vary considerably. Two of these case reports have identified a role for autologous fat transfer as a means of treatment. This case differs from those in the literature in patient demographics and severity of the facial lipoatrophy. The aim of the current report is to present a rare case of idiopathic facial lipoatrophy, and to assess the use of autologous fat transfer as a treatment modality.

Case presentation

We present a case of a 40-year old woman from Nova Scotia, Canada who presented with asymptomatic idiopathic facial lipoatrophy. The patient was otherwise healthy, taking no medications with no trauma or surgery in the region affected. Investigations, including a full autoimmune workup, were unremarkable. The facial lipoatrophy was considerably disfiguring and was assessed as a Grade 4 on the facial lipoatrophy scale. The patient was treated over the course of 2 years with two autologous fat transfers.

Conclusions

Achieving resolution of idiopathic lipoatrophy is important to patients because it can manifest in a disfiguring form and have negative effects on quality of life. The current study reports a treatment of idiopathic lipoatrophy that achieved results acceptable to the patient.
Mild cognitive impairment: narrative review of taxonomies and systematic review of their prediction of incident Alzheimer's disease dementia
Authors: Bradfield Nicholas I. , Ames David
Published: November 2019

Early detection of Alzheimer's disease is vital for developing novel treatments. Attempts to identify the intermediate state between normal cognition and dementia have evolved over the past 50 years. Current taxonomies of mild cognitive impairment (MCI) may be criticised for their imprecise operationalisation. With the advent of biomarkers such as amyloid-beta positron emission tomography imaging in established Alzheimer's disease, much research has focused on establishing which factors predict progression from MCI to Alzheimer's disease dementia. In this review, we discuss the historical context of MCI before reviewing the literature of MCI subtypes and their risk of progression to Alzheimer's disease dementia. Finally, we summarise the literature and discuss limitations and weaknesses of how the construct is operationalised and implemented, before offering suggestions for development of the concept of MCI. We conclude that MCI must be empirically defined for the sake of its predictive validity to identify Alzheimer's disease before dementia develops.
Competencias emocionales en la formación inicial del profesorado. El aprendizaje y servicio como estrategia para su desarrollo
Authors: Sánchez Calleja Laura Sánchez , Benítez Gavira Remedios , Quesada Serra Victoria , García García Mayka
Published: November 2019

INTRODUCCIÓN. Este trabajo presenta los resultados de una investigación financiada por la Universidad de Cádiz, que indaga el desarrollo de competencias emocionales a través del aprendizaje y servicio en la formación inicial del profesorado. En primer lugar, se presenta el marco conceptual sobre el que se sostienen los constructos clave de la investigación, para, en un segundo momento, situar el estado de la cuestión. Este arroja la relación entre competencias emocionales y aprendizaje y servicio como aspecto escasamente evidenciado en trabajos de corte empírico. MÉTODO. Basándonos en el método de encuesta, el alumnado participante de una asignatura de último curso del Grado de Educación Infantil contesta a un cuestionario con el fin de conocer en qué grado han aplicado y/o desarrollado las competencias emocionales durante un proyecto de ApS. Este cuestionario se basa en el modelo pentagonal de Bisquerra (2010). RESULTADOS. En líneas generales se ponen en práctica, en mayor o menor medida, todos los aspectos de las cinco competencias emocionales analizadas. De hecho, las medias obtenidas son relativamente altas y homogéneas, situándose entre los 7,12 y 8,83 puntos. De todas ellas, la competencia social es la que ha obtenido una mayor puntuación en cuanto al grado de aplicación. DISCUSIÓN. Las competencias emocionales son un aspecto esencial en la formación inicial del profesorado, y el aprendizaje y servicio constituye una estrategia metodológica válida para el desarrollo de estas. En concreto, favorece la toma de conciencia de la necesidad de participar en la construcción de una sociedad más humana y justa a través de la toma de conciencia que supone ponernos en relación con el otro.