bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the healthcare response to domestic violence and abuse in UK primary care: interrupted time series evaluation of a system-level training and support programme
Authors: Sohal Alex Hardip , Feder Gene , Boomla Kambiz , Dowrick Anna , Hooper Richard , Howell Annie , Johnson Medina , Lewis Natalia , Robinson Clare , Eldridge Sandra , Griffiths Chris 
Published: March 2020

Abstract
Background
It is unknown whether interventions known to improve the healthcare response to domestic violence and abuse (DVA)—a global health concern—are effective outside of a trial.

Methods
An observational interrupted time series study in general practice. All registered women aged 16 and above were eligible for inclusion. In four implementation boroughs’ general practices, there was face-to-face, practice-based, clinically relevant DVA training, a prompt in the electronic medical record, reminding clinicians to consider DVA, a simple referral pathway to a named advocate, ensuring direct access for women to specialist services, overseen by a national, health-focused DVA organisation, fostering best practice. The fifth comparator borough had only a session delivered by a local DVA specialist agency at community venues conveying information to clinicians. The primary outcome was the daily number of referrals received by DVA workers per 1000 women registered in a general practice, from 205 general practices, in all five northeast London boroughs. The secondary outcome was recorded new DVA cases in the electronic medical record in two boroughs. Data was analysed using an interrupted time series with a mixed effects Poisson regression model.

Results
In the 144 general practices in the four implementation boroughs, there was a significant increase in referrals received by DVA workers—global incidence rate ratio of 30.24 (95% CI 20.55 to 44.77, p < 0.001). There was no increase in the 61 general practices in the other comparator borough (incidence rate ratio of 0.95, 95% CI 0.13 to 6.84, p = 0.959). New DVA cases recorded significantly increased with an incident rate ratio of 1.27 (95% CI 1.09 to 1.48, p < 0.002) in the implementation borough but not in the comparator borough (incidence rate ratio of 1.05, 95% CI 0.82 to 1.34, p = 0.699).

Conclusions
Implementing integrated referral routes, training and system-level support, guided by a national health-focused DVA organisation, outside of a trial setting, was effective and sustainable at scale, over four years (2012 to 2017) increasing referrals to DVA workers and new DVA cases recorded in electronic medical records.
Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram
Authors: Sun Ting , Yang Wei , Toprani Sneh M. , Guo Wei , He Lile , DeLeo Albert B. , Ferrone Soldano , Zhang Gong , Wang Enwen , Lin Zunwen , Hu Pan , Wang Xinhui 
Published: March 2020

Abstract
Background
The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.

Methods
High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24−/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).

Results
We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.

Conclusion
DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.

Graphical abstract
Instrumented assessment of motor function in dyskinetic cerebral palsy: a systematic review
Authors: Haberfehlner Helga , Goudriaan Marije , Bonouvrié Laura A. , Jansma Elise P. , Harlaar Jaap , Vermeulen R. Jeroen , van der Krogt Marjolein M. , Buizer Annemieke I. 
Published: March 2020

AbstractBackgroundIn this systematic review we investigate which instrumented measurements are available to assess motor impairments, related activity limitations and participation restrictions in children and young adults with dyskinetic cerebral palsy. We aim to classify these instrumented measurements using the categories of the international classification of functioning, disability and health for children and youth (ICF-CY) and provide an overview of the outcome parameters.MethodsA systematic literature search was performed in November 2019. We electronically searched Pubmed, Embase and Scopus databases. Search blocks included (a) cerebral palsy, (b) athetosis, dystonia and/or dyskinesia, (c) age 2–24 years and (d) instrumented measurements (using keywords such as biomechanics, sensors, smartphone, and robot).ResultsOur search yielded 4537 articles. After inspection of titles and abstracts, a full text of 245 of those articles were included and assessed for further eligibility. A total of 49 articles met our inclusion criteria. A broad spectrum of instruments and technologies are used to assess motor function in dyskinetic cerebral palsy, with the majority using 3D motion capture and surface electromyography. Only for a small number of instruments methodological quality was assessed, with only one study showing an adequate assessment of test-retest reliability. The majority of studies was at ICF-CY function and structure level and assessed control of voluntary movement (29 of 49) mainly in the upper extremity, followed by assessment of involuntary movements (15 of 49), muscle tone/motor reflex (6 of 49), gait pattern (5 of 49) and muscle power (2 of 49). At ICF-CY level of activities and participation hand and arm use (9 of 49), fine hand use (5 of 49), lifting and carrying objects (3 of 49), maintaining a body position (2 of 49), walking (1 of 49) and moving around using equipment (1 of 49) was assessed. Only a few methods are potentially suitable outside the clinical environment (e.g. inertial sensors, accelerometers).ConclusionAlthough the current review shows the potential of several instrumented methods to be used as objective outcome measures in dyskinetic cerebral palsy, their methodological quality is still unknown. Future development should focus on evaluating clinimetrics, including validating against clinical meaningfulness. New technological developments should aim for measurements that can be applied outside the laboratory.
Human papillomavirus (HPV) 16 infection is not detected in rectal carcinoma
Authors: Martins Sandra F. , Mariano Vânia , Rodrigues Mesquita , Longatto-Filho Adhemar 
Published: March 2020

Abstract
Introduction
Persistence of human papillomavirus (HPV) infections is associated with squamous cell carcinomas of different human anatomic sites. Several studies have suggested a potential role for HPV infection, particularly HPV16 genotype, in rectal cancer carcinogenesis.. The aim of this study was to assess the frequency of oncogenic HPV 16 viral DNA sequences in rectal carcinomas cases retrieved from the pathology archive of Braga Hospital, North Portuga.

Methods
TaqMan-based type-specific real-time PCR for HPV 16 was performed using primers and probe targeting HPV16 E7 region.

Results
Most of the rectal cancer patients (88.5%, n = 206 patients), were symptomatic at diagnosis. The majority of the lesions (55.3%, n = 129) presented malignancies of polypoid/vegetant phenotype. 26.8% (n = 63) had synchronic metastasis at diagnosis. 26.2% (n = 61) patients had clinical indication for neoadjuvant therapy. Most patients with rectal cancer were stage IV (19.7% patients), followed by stage IIA (19.3%) and stage I (18.5%). All cases of the present series tested negative for HPV16.

Conclusion
The total of negative tests for HPV 16 infection is a robust argument to support the assumption that HPV 16 infection, despite of previous evidences, is not involved in rectal cancer carcinogenesis and progression.
Sociodemographic factors, health seeking behaviors, reproductive history, and knowledge of cervical screening among women in Swaziland
Authors: Aina Ibironke O. , Raul Smruti M. , Padilla Luz A. , Mthethwa-Hleta Simangele , Preko Peter O. , Jolly Pauline E. 
Published: March 2020

Abstract
Background
Cervical cancer is the leading cause of cancer among women in Swaziland; however, a low rate of cervical screening in this population has led to high rates of morbidity and mortality from cervical cancer.

Objective
To identify factors associated with lack of cervical screening among women in Swaziland.

Methods
A cross-sectional study was conducted among 300 women aged 18–69 years attending clinics in three regions of Swaziland from May to August of 2014. An investigator-administered questionnaire was used to collect data on socioeconomic factors, health-seeking behaviors, reproductive history, and cervical screening history and knowledge from the women.

Results
Adjusted multivariable logistic regression analysis revealed that women < 30 years of age were less likely to receive a cervical exam compared to women ≥30 years of age (Odds Ratio 0.06, 95% Confidence Interval 0.01–0.67). Women who had a tertiary education were almost 6 times more likely to receive a cervical screening (OR 5.83, 95% CI 1.11–30.50). Women who said that they did not know when to receive cervical screening were 73% less likely to have a cervical exam (OR 0.27, 95% CI 0.01–0.74).

Conclusions
Younger age, lower educational level, and lack of knowledge about when to receive a cervical screening affected whether women obtained a cervical screening. This indicates the need for educating women, particularly younger women, about the importance of cervical examinations. Addressing these barriers to screening should lead to a decrease in cervical lesions and cancer, especially in this high HIV-positive population.
Development and characterization of a Nannochloropsis mutant with simultaneously enhanced growth and lipid production
Authors: Ryu Ae Jin , Kang Nam Kyu , Jeon Seungjib , Hur Dong Hoon , Lee Eun Mi , Lee Do Yup , Jeong Byeong-ryool , Chang Yong Keun , Jeong Ki Jun 
Published: March 2020

Abstract
Background
The necessity to develop high lipid-producing microalgae is emphasized for the commercialization of microalgal biomass, which is environmentally friendly and sustainable. Nannochloropsis are one of the best industrial microalgae and have been widely studied for their lipids, including high-value polyunsaturated fatty acids (PUFAs). Many reports on the genetic and biological engineering of Nannochloropsis to improve their growth and lipid contents have been published.

Results
We performed insertional mutagenesis in Nannochloropsis salina, and screened mutants with high lipid contents using fluorescence-activated cell sorting (FACS). We isolated a mutant, Mut68, which showed improved growth and a concomitant increase in lipid contents. Mut68 exhibited 53% faster growth rate and 34% higher fatty acid methyl ester (FAME) contents after incubation for 8 days, resulting in a 75% increase in FAME productivity compared to that in the wild type (WT). By sequencing the whole genome, we identified the disrupted gene in Mut68 that encoded trehalose-6-phosphate (T6P) synthase (TPS). TPS is composed of two domains: TPS domain and T6P phosphatase (TPP) domain, which catalyze the initial formation of T6P and dephosphorylation to trehalose, respectively. Mut68 was disrupted at the TPP domain in the C-terminal half, which was confirmed by metabolic analyses revealing a great reduction in the trehalose content in Mut68. Consistent with the unaffected N-terminal TPS domain, Mut68 showed moderate increase in T6P that is known for regulation of sugar metabolism, growth, and lipid biosynthesis. Interestingly, the metabolic analyses also revealed a significant increase in stress-related amino acids, including proline and glutamine, which may further contribute to the Mut68 phenotypes.

Conclusion
We have successfully isolated an insertional mutant showing improved growth and lipid production. Moreover, we identified the disrupted gene encoding TPS. Consistent with the disrupted TPP domain, metabolic analyses revealed a moderate increase in T6P and greatly reduced trehalose. Herein, we provide an excellent proof of concept that the selection of insertional mutations via FACS can be employed for the isolation of mutants with improved growth and lipid production. In addition, trehalose and genes encoding TPS will provide novel targets for chemical and genetic engineering, in other microalgae and organisms as well as Nannochloropsis.
Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: a study in Chinese patients with very small nodules
Authors: Chen Chen , Huang Xiaojie , Yin Wei , Peng Muyun , Wu Fang , Wu Xia , Tang Jingqun , Chen Mingjiu , Wang Xiang , Hulbert Alicia , Brock Malcolm V. , Liu Wenliang , Herman James G. , Yu Fenglei 
Published: March 2020

Abstract
Purpose
We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples.

Experimental design
Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP.

Results
Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41–69% and 49–82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84–0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm.

Conclusions
Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage.

Graphical Abstract
SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells
Authors: Jiang Yu , Liu Lei , Xiang Qin , He Xiaoqian , Wang Yan , Zhou Dishu , Zou Can , Chen Qian , Peng Mingyu , He Jin , Jiang Xianyao , Xiang Tingxiu , Yang Yucheng 
Published: March 2020

AbstractBackgroundNasopharyngeal carcinoma tends to present at an advanced stage because the primary anatomic site is located in a less visible area and its clinical symptoms are nonspecific. Prognosis of advanced nasopharyngeal carcinoma cases remains disappointing. SEPT9 is a methylation-based biomarker approved by the US Food and Drug Administration for colorectal cancer screening and diagnosis. Interestingly, downregulation of SEPT9, especially SEPT9_v2, mediated by promoter hypermethylation has been also detected in head and neck squamous cell carcinoma than in head and neck squamous epithelium, while other SEPT9 variants did not. These reasons above indicate a crucial role of SEPT9_v2 in cancer progression. Therefore, we address the methylation status of SEPT9_v2 in nasopharyngeal carcinoma and explore the role of SEPT9_v2 in nasopharyngeal carcinoma proliferation and cancer progression.ResultsSEPT9_v2 expression was found to be downregulated via promoter methylation in nasopharyngeal carcinoma cell lines and tissues. Ectopic expression of SEPT9_v2 induced G0/G1 cell cycle arrest and apoptosis, which exerted an inhibitory effect in cell proliferation and colony formation. Additionally, nasopharyngeal carcinoma cell migration and invasion were shown to be inhibited by SEPT9_v2. Furthermore, our data suggested that SEPT9_v2 inhibits proliferation and migration of nasopharyngeal carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10.ConclusionsThis study delineates SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells and, hence, SEPT9_v2 may be a promising therapeutic target and biomarker for nasopharyngeal carcinoma.
Characterization of the immunomodulatory properties of alveolar bone-derived mesenchymal stem cells
Authors: Cao Chen , Tarlé Susan , Kaigler Darnell 
Published: March 2020

AbstractBackgroundRecently, mesenchymal stem cells (MSCs) have been shown to have immunomodulatory properties which hold promise for their clinical use to treat inflammatory conditions. Relative to bone marrow-derived MSCs (BMSCs), which are typically isolated from the iliac crest, we have recently demonstrated that MSCs can be predictably isolated from the alveolar bone (aBMSCs) by less invasive means. As such, the aim of this study was to characterize the immunomodulatory properties of aBMSCs relative to BMSCs.MethodsaBMSCs isolated from the human alveolar bone and BMSCs isolated from the human bone marrow of the iliac crest were cultured in the same conditions. Cytokine arrays and enzyme-linked immunosorbent assays (ELISA) of a conditioned medium were used to evaluate differences in the secretion of cytokines. In different functional assays, aBMSCs and BMSCs were cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cells (PBMCs) to evaluate their effects on important immune cell functions including proliferation, differentiation, and activation.ResultsThe protein arrays identified interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 to be the major cytokines secreted by aBMSCs and BMSCs. ELISA determined that aBMSCs secreted 268.64 ± 46.96 pg/mL of IL-6 and 196.14 ± 97.31 pg/mL of MCP-1 per microgram of DNA, while BMSCs secreted 774.86 ± 414.29 pg/mL of IL-6 and 856.37 ± 433.03 pg/mL of MCP-1 per microgram of DNA. The results of the coculture studies showed that aBMSCs exhibited immunosuppressive effects on monocyte activation and T cell activation and proliferation similar to BMSCs. Both aBMSCs and BMSCs drove macrophages into an anti-inflammatory phenotype with increased phagocytic ability. Taken together, these data suggest that aBMSCs have potent immunomodulatory properties comparable to those of BMSCs.ConclusionsThe findings of this study have important implications for the development of immunomodulatory stem cell therapies aimed to treat inflammatory conditions using aBMSCs, a more feasible tissue source of MSCs.
Autologous bone marrow stem cell transplantation via the hepatic artery for the treatment of hepatitis B virus-related cirrhosis: a PRISMA-compliant meta-analysis based on the Chinese population
Authors: Sun Ani , Gao Wenni , Xiao Ting 
Published: March 2020

Abstract
Objective
Autologous bone marrow stem cell (ABMSC) transplantation has been considered a promising option for hepatitis B virus-related cirrhosis (HBV-C). Although an analysis of the published literature has been performed, the exact effects and safety have yet to be systematically investigated.

Methods
We conducted a wide-ranging online search of electronic databases (Web of Science, PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang database) to reach systematic conclusions. Outcome measurements, including therapeutic efficacy, clinical symptoms, and adverse events, were extracted and analyzed statistically.

Results
Ultimately, a total of 10 articles including 662 HBV-C patients were included in this analysis, which indicated that ABMSC therapy could significantly improve liver function in patients with HBV-C in terms of the MELD and Child-Pugh scores, total bilirubin, serum albumin, alanine aminotransferase, aspartate aminotransferase, and coagulation function. Compared with patients receiving routine therapy (RT), those treated with ABMSC and RT combined therapy showed improved clinical symptoms, as represented by increased appetite and reduced fatigue and ascitic fluid and abdominal distension. Moreover, the fibrosis indexes indicated a reduction in liver fibrosis in patients treated with combined therapy according to the improved levels of hyaluronic acid (MD = − 70.47, CI = − 103.72–37.21, P <  0.0001), laminin (MD = − 25.11, CI = − 37.73–12.49, P <  0.0001), type III procollagen (MD = − 22.42, CI = − 34.49–10.34, P = 0.0003), and type IV collagen (MD = − 22.50, CI = − 39.92–5.08, P = 0.01). No obvious adverse events occurred during ABMSC treatment.

Conclusion
ABMSC transplantation via the hepatic artery was safe and effective in treating HBV-C without causing severe adverse events.