bluuebunny/crossref_metadata_2025 huggingface dataset:
Four-Factor Prothrombin Complex Concentrate for the Reversal of Direct Oral Anticoagulants
Authors: Zada Ilanit , Wang Shan , Akerman Meredith , Hanna Adel
Published: November 2019

Background:

The prevalence of direct oral anticoagulants (DOACs) has increased with continued evidence of their efficacy and ease of use. However, the rise in their utilization also surfaced a concern regarding their reversal in patients actively bleeding and/or those requiring invasive procedures. Up until 2018, there were several reversal options available including 4-factor prothrombin complex concentrate (4-factor PCC), activated charcoal, desmopressin, and tranexamic acid. Then, in 2018, andexanet alpha, a recombinant factor Xa, was approved for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding. Nonetheless, because 4-factor PCC is more easily attainable and cost-effective, it continues to be the more favorable option for many health-care professionals.

Methods:

This retrospective chart review was conducted at NYU Winthrop Hospital in patients who received 4-factor PCC for the reversal of DOACs from January 2018 to July 2018. Patient charts were reviewed and relevant data was collected (admitting diagnosis, dose of 4-factor PCC utilized, etc).

Results:

Fifty-three patients were evaluated with 85% experiencing a positive response and complete recovery following the administration of 4-factor PCC; 8 (15%) patients died after receiving 4-factor PCC, none as a result of its administration; 3 patients died secondary to other underlying comorbidities, 4 patients died due to an intracranial hemorrhage, and 1 died due to hematoma of the tongue.

Conclusion:

Based on the results thus far, the use of 4-factor PCC may be a good treatment option in patients requiring DOAC reversal.
Blood Glucose Levels and Mortality in Patients With Sepsis: Dose–Response Analysis of Observational Studies
Authors: Wang Wen , Chen Wenwen , Liu Yanmei , Li Ling , Li Sheyu , Tan Jing , Sun Xin
Published: November 2019

Background:

We undertook a systematic review and meta-analysis to investigate the relationship between blood glucose levels and mortality in patients with sepsis.

Methods:

Medline and EMBASE were searched from inception to April 8, 2018. Cohort studies or case–control studies reported the association between blood glucose and mortality in patients with sepsis were selected. Study characteristics, baseline characteristics, definition of hyperglycemia, and outcomes of interest were extracted. We performed a dose–response meta-analysis to assess the effect of blood glucose level on mortality. We also conducted meta-analysis for patients with or without diabetes separately.

Results:

Ten cohort studies involving 26 429 patients were included, of which 5 were prospective studies and 5 retrospective studies. Dose–response analysis showed that the effect of blood glucose on mortality may differ in patients with versus without diabetes. There was a U-shaped relationship for patients with diabetes and a J-shaped relationship for patients without diabetes, with blood glucose at 145 to 155 mg/dL corresponding to lowest mortality both in patients with and without diabetes.

Conclusions:

Current evidence suggested U-shaped relationship between blood glucose and mortality in all patients irrespective of their diabetes status. Diabetic patients with blood glucose below 145 mg/dL may have poorer prognosis compared to patients without established diabetes.
Reporting Sexual Assault: Can Knowledge of How to Protect Forensic Evidence Influence Intentions to Report?
Authors: McQueen Emma J. , Kelty Sally F.
Published: November 2019

Responding to the high prevalence, low reporting, and poor conviction rates of adult sexual assault, Australian criminal jurisdictions have introduced protocols that allowed collection of medical forensic evidence from victims without police notification, since 1999. To assess the influence of reforms on potential victim behavior, this study measured lay knowledge of measures to protect forensic evidence of sexual assault, and predictors of intention to report adult sexual assault through the lens of the theory of planned behavior (TPB). An online survey was conducted with a sample of University of Canberra students and community members ( N = 204). Results indicated moderate lay knowledge of how to protect evidence of sexual assault; however, only 46.1% of the sample were aware that evidence could be collected without police notification. The TPB successfully explained 55.6% of variance in intention to report future sexual assault. Participants who had experienced previous adult sexual assault victimization were significantly less likely to intend to report future sexual assault than those who had not. Knowledge of forensic evidence of sexual assault was not related to intention to report by self-efficacy as predicted; instead, it was mediated via subjective norms. Results indicated the potential value education to improve lay awareness of how to protect and report medical forensic evidence and to foster social norms that value reporting, particularly among school and university students.
A ~1000-year 13C Suess correction model for the study of past ecosystems
Authors: Dombrosky Jonathan
Published: November 2019

Inferences about how an ecosystem has changed through time often rely on longitudinal records of species characteristics or niche parameters, and stable isotope analysis is a common tool employed to study changes in an organism’s niche. One of the most frequently used stable isotope measures is δ13C, a ratio of 13C to 12C. However, applying δ13C to historical samples comes with some methodological hurdles. One such hurdle is correcting for the 13C Suess effect or the change in atmospheric δ13C due to increased anthropogenic CO2 emissions. The change in the amount of carbon isotopes in the atmosphere through time can confound the study of historical shifts in species characteristics. No standard way of correcting for the 13C Suess effect has been suggested despite this problem. Here, I propose a standard 13C Suess correction model for the past ~1000 years using three prehistoric/historic records of atmospheric δ13C.
Reflexive Intervention Development: Using Qualitative Research to Inform the Development of an Intervention for Women With Metastatic Breast Cancer
Authors: Wigginton Britta , Thomson Zoe O. , Sandler Carolina X. , Reeves Marina M.
Published: November 2019

There is growing consensus around the limited attention given to documenting the process of intervention development, specifically the role of qualitative research. In this article, we seek to describe a missing piece of this process: how qualitative research, and related methodologies and theories, informs intervention development. We use our research as a case study of “reflexive intervention development.” We begin by describing our interview study, consisting of 23 in-depth interviews with women diagnosed with metastatic breast cancer, and go on to detail our methodological framework and research team. We then explain how this interview study directly informed our development of the intervention materials, allowing us to attend carefully to language and its potential implications for women. We conclude by inviting researchers to reflect on the knowledge production process that is inherent in intervention development to consider not only their role in this process but also the role of qualitative research.
Promoting Healthy Marriages in Chinese Church Communities: Survey of Chinese Couples’ Marriages, Virtue-Based Training for Leaders, and Outcomes
Authors: Ripley Jennifer S. , Sells James N. , Miller Vaughn , Wang Qi , Wen Luke , Lau Christine P.T. , Worthington Everett L.
Published: November 2019

Couple research, and specifically religion and couple research, is commonly conducted in individualistic cultures. The collectivistic milieu of China makes a useful contrast to Western culture. With Chinese churches, we conducted two studies on marriage relationships. In Study 1 ( N = 810), we report a survey on marriages of parishioners. Satisfaction was high among most couples with general relationship problems such as communication reported as the highest concern. Marriage happiness was negatively correlated with couple problems. In Study 2 ( N = 241), we describe a virtue-based couple counseling program, developed collaboratively with 20 Chinese key informants. We administered an 8-hr virtue-based couple-oriented training to 241 church leaders. Training increased church leaders’ self-efficacy and hope for effective ministry. We compared responsiveness to the training by pastors and lay leaders. Lay counselors were more responsive than were pastors. This program evaluation was a field study that also included a brief follow-up interview of randomly selected recipients of the training ( n = 16). Friendship counseling was reported in the follow-up interviews as the most common way to address marriage problems.
Multimodal imaging of poppers maculopathy
Authors: Romano Francesco , Arrigo Alessandro , Sperti Andrea , Bandello Francesco , Battaglia Parodi Maurizio
Published: November 2019

Purpose:

To describe a case of poppers maculopathy by means of multimodal imaging.

Methods:

A 26-year-old male presented to our Department in April 2018 with a history of visual disturbances. He underwent a complete ophthalmologic examination, including optical coherence tomography, fundus autofluorescence, and ultra-widefield fundus photograph.

Results:

At baseline, the patient presented a visual acuity of 20/25 Snellen bilaterally, with an altered foveal reflex on funduscopic examination. Structural optical coherence tomography showed disruption of the outer retinal layers in both eyes. After 6-month observation, the status of the outer retinal layers on optical coherence tomography and his vision (20/20) appeared improved. In this occasion, we performed optical coherence tomography angiography that revealed clear and persisting choriocapillaris alterations. Upon further interrogation, he admitted the episodic use of poppers, hence leading to the diagnosis.

Conclusion:

Our findings suggest that microvascular toxicity at the level of choriocapillaris may act as primary pathogenetic insult in poppers maculopathy.
The coverage of Africa in Ghanaian newspapers: The dominant Western voice in the continent’s coverage
Authors: Serwornoo Michael Yao Wodui
Published: November 2019

A growing literature has emerged that is contesting the validity of Africa’s negative Western media representation as a myth and empirically non-existent. This article examines how four national newspapers in Ghana reported the continent. About 13,228 corpus belonging to these top four national newspapers, over a period of 2 years, were quantitatively examined for sources utilised. Based on a 2-week constructed sampling technique, 180 articles reporting Africa were further analysed for the subjects and tone of the coverage, and the dominant themes of representation. The ethnographic content analysis revealed that the coverage of the continent in these newspapers is dominated by themes of war, crime, killings, crises, terrorism and omission of progress. The African story was mostly narrated through the subject of politics and with a predominantly negative tone. I argue that the continent’s negative proxy self-coverage confirms the evasive spread of Afro-pessimism considering that Western global news organisations accounted for over 80 per cent of the reportage as sources.
Older people and placemaking in post-disaster community rebuilding: An interdisciplinary action research in Sichuan, China
Authors: Qi Hua Dong , Gu Xuebin
Published: November 2019

It is well known that China’s population is aging, more rapidly than almost any country in recent history. In 2018, 1.67 billion or 11.9% of the population was aged 65 or older ( China Daily, 2019 ). The effect of an aging population trend is not usually represented positively—“elderly as a burden”—whether in China or elsewhere. However, our action research project of post-disaster community rebuilding in Ya’an in Sichuan Province, China challenges this mainstream discourse of elderly people. In the process, we discovered the power of the elderly who did not passively accept external assistance following the earthquake, but actively participated in rebuilding their community. They were valuable human/cultural assets and able to make a great contribution to community development. This article provides an account of interdisciplinary action research in which social workers collaborated with elderly villagers to promote sustainable community development by integrating people’s social, cultural, and economic skills into long-term reconstruction following a major disaster. Most importantly, it emphasizes the contribution of older people and challenges the dominant discourse relating to older people.
An intrusion detection system for the prevention of an active sinkhole routing attack in Internet of things
Authors: Tahir Sabeen , Bakhsh Sheikh Tahir , Alsemmeari Rayan A
Published: November 2019

Internet of things (IoT) is a complex and massive wireless network, where millions of devices are connected together. These devices gather different types of data from different systems that transform human daily lives by modernizing home appliances, business, medicine, traveling, research, and so on. Security is a critical challenge for a stable IoT network, for instance, routing attacks, especially sinkhole attack is a severe attack which has the capability to direct network data toward the intruder, and it can also disrupt and disconnect the devices from their network. The IoT needs multi-facet security solutions where network communication is protected with integrity, confidentiality, and authentication verification services. Therefore, the IoT network should be secured against intrusions and disruptions; the data exchanged throughout the network should be an encrypted form. In this article, an intrusion detection system for the prevention of an active sinkhole routing attack (PASR) in IoT is presented. The proposed PASR solves the problem of the sinkhole attack; for this purpose, the whole network is divided into the clusters of IoT. All the IoT devices are connected to their respective gateways. The gateway devices are equipped with an intrusion detection system. The intrusion detection system activates intrusion analyzer to detect anomalies in the context of ad hoc on-demand distance vector protocol. The base station is the main device that is responsible to receive data from all devices. Therefore, it detects and prevents sinkhole attacks; the base station keeps the record of all active devices and their possible links. The PASR is implemented and compared with the existing intrusion detection techniques ad hoc on-demand distance vector, and dual attack detection for black and gray hole attack. It was observed from the simulation results that the PASR outperforms in terms of data packet delivery, energy consumption, the detection rate of sinkhole attack, and routing overhead.
C-Reactive Protein to Albumin Ratio in Colorectal Cancer: A Meta-Analysis of Prognostic Value
Authors: Zhou Qiang-ping , Li Xiu-jiang
Published: November 2019

Background:

The relationship between pretreatment C-reactive protein to albumin ratio (CAR) and colorectal cancer (CRC) prognosis has been extensively studied in various tumors. However, little is known on CAR and its association with prognosis in CRC. This study aims to investigate the prognostic value of pretreatment CAR in CRC.

Methods:

We conducted a systematic search of MEDLINE, EMBASE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival and/or clinicopathology of CRC. Overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and clinicopathological features were synthesized and compared.

Results:

Nine studies including 3431 patients were analyzed in this meta-analysis. Pooled results showed that elevated pretreatment CAR was associated with poor OS (pooled hazards ratio [HR]: 2.18, 95% confidence interval [CI]: 1.70-2.78, P < .001) and DFS/RFS (pooled HR: 2.36, 95% CI: 1.40-3.98, P < .001). Moreover, elevated pretreatment CARs were correlated with male patients, large tumor diameter, late III-IV tumor node metastasis stage tumors, high serum carcinoembryonic antigen and carbohydrate antigen 19-9, and presence of lymphatic invasion and venous invasion.

Conclusion:

Elevated pretreatment CAR could be an adverse prognostic indicator in patients with CRC.
Experimental investigation on the correlation of pressure pulsation and vibration of axial flow pump
Authors: Duan Xiaohui , Tang Fangping , Duan Wenyong , Zhou Wei , Shi Lijian
Published: November 2019

Pressure and vibration displacement value are relatively measured by 14 pressure sensors and 2 vibration sensors distributing inside the tank-type model axial flow pump device under different flow rates. By comparison, it is found that the pressure pulsation on the inlet of the impeller is the main cause of hydraulic induced vibration of the pump device, and it is found to have similar amplitude trend with the vertical vibration as the flow rates increases and large correlation coefficient with the horizontal vibration under high flow rates through time-domain analysis. By frequency-domain analysis, it is found that the main frequency of pressure pulsation is three multiplies of the shaft frequency, but it is one multiplies of vertical vibration, and it changes from one multiplies to three multiplies of horizontal vibration. Combining with the analysis of phase-flow rates characteristics of both pressure pulsation and vibration, it is concluded that, for the horizontal vibration, the frequency ingredient of one multiplies ranging from low to high flow rates and three multiplies removing from unstable and high flow rates zone are possibly induced by pressure pulsation on the inlet of impeller, while for the vertical vibration, the frequency ingredient of one multiplies under design flow rates and high flow rates are possibly induced by pressure pulsation on the inlet of impeller. Both the horizontal and vertical vibrations with frequency of two multiplies have little relationship with the pressure pulsation on the inlet of impeller.
Robust improvement solution to perspective-n-point problem
Authors: Youyang Feng , Qing Wang , Yuan Yang , Chao Yan
Published: November 2019

Perspective-n-point is a classical computer vision problem that uses three-dimensional points and image pixels to estimate camera pose. The visual robot often loses its position when the camera moves too fast or the environment changes. Perspective-n-point is used to relocate robot position, but the distribution of three-dimensional points in the world frame and different choices of coordinates affect the perspective-n-point performance and make perspective-n-point results less robust and inaccurate. In this study, we review the previous perspective-n-point algorithms and provide their disadvantages when facing three-dimensional points with large variances. According to the drawbacks of previous perspective-n-point methods, we propose a normalization method inspired by the homogeneous matrix calculation process to increase perspective-n-point algorithm accuracy and robustness. The experimental results demonstrate that the proposed perspective-n-point method is robust to different choices of coordinates and is thus better than other state-of-art perspective-n-point methods. Considering that the true camera pose is difficult to obtain, the former perspective-n-point solution validation experiment is mostly based on simulated image data. In this study, we design a new experiment based on total station and chessboard to verify the robustness and accuracy of the perspective-n-point algorithm.
A new cumulative damage model for time-dependent reliability analysis of deteriorating structures
Authors: Li Junxiang , Chen Jianqiao , Chen Zhiqiang
Published: November 2019

Performance and reliability of structures will deteriorate with the effects of loads, environment, and interior factors of materials. In this article, a novel cumulative damage model is developed for time-dependent reliability analysis of deteriorating structures. The deterioration is a combination of three stochastic processes: the gradual deterioration posed by aging effects, the sudden deterioration caused by transient loads, and the additional deterioration introduced by sustained loads. The aging effect is modeled as a gamma process, while the transient load is described by a Poisson process. The sustained load is modeled by a stationary binomial process and a Poisson square wave process, respectively. The load threshold for three different scenarios are all considered and applied to not only the transient loads but also the sustained loads. The time-dependent reliability of deteriorating structures is then evaluated based on this model via semi-analytical methods or numerical simulation methods. Three numerical examples and an example involving a natural gas pipeline are used to validate the effectiveness of the proposed model for computing the time-dependent reliability.
Relevance of Ebola virus VP35 homo-dimerization on the type I interferon cascade inhibition
Authors: Di Palma Francesco , Daino Gian Luca , Ramaswamy Venkata Krishnan , Corona Angela , Frau Aldo , Fanunza Elisa , Vargiu Attilio V , Tramontano Enzo , Ruggerone Paolo
Published: November 2019

Ebola virus high lethality relies on its ability to efficiently bypass the host innate antiviral response, which senses the viral dsRNA through the RIG-I receptor and induces type I interferon α/β production. In the bypassing action, the Ebola virus protein VP35 plays a pivotal role at multiple levels of the RIG-I cascade, masking the viral 5′-triphosphorylated dsRNA from RIG-I, and interacting with other cascade components. The VP35 type I interferon inhibition is exerted by the C-terminal domain, while the N-terminal domain, containing a coiled-coil region, is primarily required for oligomerization. However, mutations at key VP35 residues L90/93/107A (VP35-3m) in the coiled-coil region were reported to affect oligomerization and reduce type I interferon antagonism, indicating a possible but unclear role of homo-oligomerization on VP35 interaction with the RIG-I pathway components. In this work, we investigated the VP35 dimerization thermodynamics and its contribution to type I interferon antagonism by computational and biological methods. Focusing on the coiled-coil region, we combined coarse-grained and all-atom simulations on wild type VP35 and VP35-3m homo-dimerization. According to our results, wild type VP35 coiled-coil is able to self-assemble into dimers, while VP35-3m coiled-coil shows poor propensity to even dimerize. Free-energy calculations confirmed the key role of L90, L93 and L107 in stabilizing the coiled-coil homo-dimeric structure. In vitro type I interferon antagonism studies, using full-length wild type VP35 and VP35-3m, revealed that VP35 homo-dimerization is an essential preliminary step for dsRNA binding, which appears to be the main factor of the VP35 RIG-I cascade inhibition, while it is not essential to block the other steps.
Making it count: Learning from a knowledge exchange with voluntary sector workers and software providers, and data from auto/biographical reflection as an activist academic
Authors: Mann Sally
Published: November 2019

This article offers an analysis of methodological disputes between various stakeholders in welfare provision. It addresses debates of validity, efficiency and purpose. It gathers data from two sources: a knowledge exchange event which brought together voluntary sector workers, outcome software providers and academics, and auto/biographical data from my long-term participation in a grass-roots community project seeking to tackle street homelessness and food poverty in the London Borough of Newham. It pays particular attention to the tensions inherent in measuring impact and presenting ‘softer’ outcomes. It highlights the innovative approaches adopted by those working in the third sector as they seek to comply with an often overwhelming and increasingly complex set of methodological demands from funders. This article includes a discussion of the positioning of researchers seeking to offer ‘accountable knowledge’ and the types of knowledge which arise in pursuing an approach best described as ‘theorised subjectivity’. I consider the tensions inherent in my own attempt to navigate towards being a ‘partial inbetweener’ or at least a ‘trusted outsider’ to homeless people within the project I volunteer with. To this end, discussions of the use of auto/biographical data, drawn from working as a community organiser, are included.
Predictors of Failure for Nonoperative Management of Spinal Epidural Abscess
Authors: Hunter Sarah , Cussen Robert , Baker Joseph F.
Published: November 2019

Study Design:

Retrospective cohort study.

Objectives:

The aim of this study is to identify predictive factors associated with failure of nonoperative management of spinal epidural abscess (SEA).

Methods:

Between January 2007 and January 2017, there were 97 patients 18 years or older treated for SEA at a tertiary referral center. Of these, 58 were initially managed nonoperatively. Details on presenting complaint, laboratory parameters, radiographic evaluation, demographics, comorbidities, and neurologic status (Frankel grades A-E) were collected. Success of treatment was defined as eradication of infection with no requirement for further antimicrobial therapy. Diagnosis of SEA was made via evaluation of imaging and intraoperative findings. Patients with repeat presentation of SEA, children, and those who were transferred for immediate surgical decompression were excluded.

Results:

Fifty-eight patients initially treated nonoperatively were included. Of these, 21 failed nonoperative management and required surgical intervention. The mean age was 60 years, 66% male, and 19% of Maori ethnicity. Abscess location was predominantly dorsal, and in the lumbar region (53%). Multivariate analysis identified Maori ethnicity, multifocal sepsis, and elevated white cell count as predictors of failure of nonoperative management. With 1 predictor the risk of failure was 44%. In the presence of 2 predictive variables, failure rate increased to 60%, and if all 3 variables were present, patients had a 75% risk of failure.

Conclusion:

Thirty-six percent of patients treated nonoperatively failed nonoperative management—the failure rate was significantly increased in patients with multifocal sepsis, in patients with elevated white cell count, and in patients of Maori ethnicity.
Durable Engraftment and Long-Term Survival Following Fludarabine-Based Nonmyeloablative Hematopoietic Cell Transplantation (HCT) in Patients with ATG-Refractory Severe Aplastic Anemia (SAA) and Other Nonmalignant Hematological Disorders.
Authors: Chakrabarti Sakti , Takahashi Y. , Srinivasan R. , Espinoza I. , Igarashi T. , Suffredini D. , Marquesen M. , Shalabi R. A. , Bolan C. D. , Leitman S. F. , Barrett A. J. , Young N. S. , Childs R.
Published: November 2019

We evaluated the toxicity-profile, engraftment potential, and efficacy of fludarabine-based nonmyeloablative allogeneic HCT in patients with a variety of nonmalignant hematological disorders. Twenty three patients (median age 29 years; range 11–52) with nonmalignant hematological disorders including ATG refractory SAA (n=13), severe paroxysmal nocturnal hemoglobinuria (PNH: n=9), and pure red cell aplasia (PRCA; n=1) were transplanted from 5/99 – 8/2004 at the NHLBI. The majority of patients had an extensive transfusion history including 11/23 who had HLA allo-antibodies and 4/23 with allo-antibodies to RBCs. Conditioning with fludarabine (25 mg/m2 x 5 days), ATG (40mg/kg x 4 days) and cyclophosphamide (60mg/kg x 2 days) was followed by infusion of an un-manipulated G-CSF mobilized allograft from an HLA matched sibling (n=18), parent (n=2), or single antigen mismatched sibling (n=3). GVHD prophylaxis consisted of cyclosporine (CSA) either alone (n=2) or combined with mycophenolate mofetil (n=10) or mini-dose methotrexate (n=11). Despite a high prevalence of pre-transplant allo-immunization, all patients achieved sustained donor engraftment in both myeloid and T-cell lineages. Myeloid recovery (neutrophils >500cells/uL) occurred at a median 14 days post transplant (range 8–18 days). Conversion from mixed to full donor myeloid and T-cell chimerism occurred in all patients by 110 days post-transplant. CMV reactivation occurred in 11/21 patients at risk (KM probability 52%) without any cases of CMV disease. Grade II–IV and III–IV acute GVHD was the major transplant complication occurring in 13/23 (KM probability 60%) and 8/23 (KM probability 38%) patients respectively. Fourteen of 21 evaluable patients developed chronic GVHD (limited in 11 cases), which resolved completely with low-dose alternate day steroids and/or CSA in all but 1 case. One patient who received an allograft from his HLA matched father died 16 months post-transplant from complications related to chronic GVHD. With a median follow up of 25 months (range 1–64 months), 20/21 patients evaluable more than 100 days post-transplant survive in complete remission with full donor chimerism in all lymphohematopoietic lineages (KM probability of long-term survival 92.8 %-see figure ).

Conclusion: Fludarabine-based nonmyeloablative transplantation achieves excellent donor engraftment and long-term disease free survival in heavily transfused and allo-immunized patients with ATG refractory SAA and other nonmalignant hematological disorders associated with bone marrow failure.
TAZ functions as a tumor suppressor in multiple myeloma by downregulating MYC
Authors: Grieve Stacy , Wajnberg Gabriel , Lees Miranda , Chacko Simi , Weir Jackson , Crapoulet Nicolas , Reiman Tony
Published: November 2019

Key Points

Expression of Hippo component TAZ is downregulated in MM through hypermethylation. TAZ reexpression, exogenously or pharmacologically, causes apoptosis and enhances sensitivity to anti-MM therapies by downregulating MYC.
Missed diagnosis and misdiagnosis of infectious diseases in hematopoietic cell transplant recipients: an autopsy study
Authors: Multani Ashrit , Allard Libby S. , Wangjam Tamna , Sica R. Alejandro , Epstein David J. , Rezvani Andrew R. , Ho Dora Y.
Published: November 2019

Key Points

Infectious diseases are the second most common cause of death in HCT recipients, but some are first identified only by autopsy. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality.
CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy
Authors: Pillai Vinodh , Muralidharan Kavitha , Meng Wenzhao , Bagashev Asen , Oldridge Derek A. , Rosenthal Jaclyn , Van Arnam John , Melenhorst Jos J. , Mohan Diwakar , DiNofia Amanda M. , Luo Minjie , Cherian Sindhu , Fromm Jonathan R. , Wertheim Gerald , Thomas-Tikhonenko Andrei , Paessler Michele , June Carl H. , Luning Prak Eline T. , Bhoj Vijay G. , Grupp Stephan A. , Maude Shannon L. , Rheingold Susan R.
Published: November 2019

Key Points

Preinfusion dim CD19 expression and rare CD19– events in B-ALL do not affect relapses or responses to CD19-directed CAR T-cells. Prior blinatumomab treatment increases the rate of failure to achieve MRD– remission and CD19– MRD and relapse.
MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2
Authors: Xiao Haiping
Published: November 2019

Background

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Distant metastasis is thought to be one of the most important factors responsible for the failure of NSCLC therapy. MicroRNA-7-5p (miR-7-5p) has been demonstrated to be a tumor suppressor in breast cancer, hepatocarcinoma, prostate cancer and glioblastoma multiforme (GBM). However, its role in NSCLC is still not fully understood. This study evaluated the role of miR-7-5p in the progression of NSCLC and explored the underlying mechanism.

Materials & methods

The quantitative real-time PCR (qPCR), MTT, migration and invasion assays were used to evaluate the effects of miR-7-5p on the proliferation, migration and invasion of A549 and SPCA-1 cells. A tumor xenograft model was created to determine the effects of miR-7-5p on metastasis in vivo. The dual-luciferase reporter gene, neuro-oncological ventral antigen 2 (NOVA2) overexpression and western blotting assays were performed to explore the underlying mechanism.

Results

MiR-7-5p is downregulated in NSCLC tissues and lung cancer cell lines. It suppresses proliferation, migration, invasion and EMT marker expression in vitro and in vivo. Further study showed that miR-7-5p suppresses tumor metastasis of NSCLC by targeting NOVA2. Overexpression of NOVA2 attenuates the miR-7-5p-mediated inhibitory effect on lung cancer cells.

Conclusion

MiR-7-5p suppresses NSCLC metastasis. Targeting miR-7-5p may contribute to the success of NSCLC therapy.
Transcriptomic analysis of Verbena bonariensis roots in response to cadmium stress
Authors: Wang Meng-qi , Bai Zhen-yu , Xiao Ya-fang , Li Yan , Liu Qing-lin , Zhang Lei , Pan Yuan-zhi , Jiang Bei-bei , Zhang Fan
Published: November 2019

Background

Cadmium (Cd) is a serious heavy metal (HM) soil pollutant. To alleviate or even eliminate HM pollution in soil, environmental-friendly methods are applied. One is that special plants are cultivated to absorb the HM in the contaminated soil. As an excellent economical plant with ornamental value and sound adaptability, V. bonariensis could be adapted to this very situation. In our study, the Cd tolerance in V. bonariensis was analyzed as well as an overall analysis of transcriptome.

Results

In this study, the tolerance of V. bonariensis to Cd stress was investigated in four aspects: germination, development, physiological changes, and molecular alterations. The results showed that as a non-hyperaccumulator, V. bonariensis did possess the Cd tolerance and the capability to concentration Cd. Under Cd stress, all 237, 866 transcripts and 191, 370 unigenes were constructed in the transcriptome data of V. bonariensis roots. The enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that differentially expressed genes (DEGs) under Cd stress were predominately related to cell structure, reactive oxygen species (ROS) scavenging system, chelating reaction and secondary metabolites, transpiration and photosynthesis. DEGs encoding lignin synthesis, chalcone synthase (CHS) and anthocyanidin synthase (ANS) were prominent in V. bonariensis under Cd stress. The expression patterns of 10 DEGs, validated by quantitative real-time polymerase chain reaction (qRT-PCR), were in highly accordance with the RNA-Sequence (RNA-Seq) results. The novel strategies brought by our study was not only benefit for further studies on the tolerance of Cd and functional genomics in V. bonariensis, but also for the improvement molecular breeding and phytoremediation.
Young people with attention deficit hyperactivity disorder in transition from child to adult services: a qualitative study of the experiences of general practitioners in the UK
Authors: Newlove-Delgado Tamsin , Blake Sharon , Ford Tamsin , Janssens Astrid
Published: November 2019

Background

Many young people with Attention Deficit Hyperactivity Disorder (ADHD) have impairing symptoms that persist into adulthood, yet only a minority experience continuity of care into adult life. Despite growing emphasis on the primary care role in ADHD management in NICE ADHD and transition guidance, little is known about GPs’ perspectives, which could hamper efforts to improve outcomes for young people leaving children’s services. This study aimed to understand GPs’ experiences of involvement with this group and explore their views on the roles and responsibilities of primary and secondary care in transition, to inform recommendations for policy and practice.

Method

Qualitative interview study with GPs across the UK. Semi-structured telephone interviews were carried out with 14 GPs recruited through a linked mapping study, social media, and snowballing; data were analysed using thematic analysis.

Results

In the absence of a smooth transition from child to adult services, many GPs became involved ‘by default’. GPs reacted by trying to identify suitable specialist services, and were faced with the decision of whether to continue ADHD prescribing. Such decisions were strongly influenced by perceptions that prescribing carried risks, and concerns over responsibility, particularly where specialist services were lacking. Participants described variation in service availability, and some highlighted tensions around how shared care works in practice.

Conclusion

Implementation of NICE guidance is highly variable, with implications for GPs and patients. Risk and responsibility for primary care ADHD prescribing are central concerns that need to be addressed, as is the inclusion of GPs in a planned transition process.
SIRT1 (rs3740051) role in pituitary adenoma development
Authors: Liutkeviciene Rasa , Vilkeviciute Alvita , Morkunaite Greta , Glebauskiene Brigita , Kriauciuniene Loresa
Published: November 2019

Background

Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA).

Methods

The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method.

Results

Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099–0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091–0.575; p = 0.002) were associated with lower odds of occurring an invasive PA.

Conclusions

Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.
A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis
Authors: Guo Xinjian , Zhao Fuxing , Ma Xinfu , Shen Guoshuang , Ren Dengfeng , Zheng Fangchao , Du Feng , Wang Ziyi , Ahmad Raees , Yuan Xinyue , Zhao Junhui , Zhao Jiuda
Published: November 2019

Background

Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer.

Methods

RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity.

Results

Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69–0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12–1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66–0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69–0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42–1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47–1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81–1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82–1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81–0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86–1.07; P = 0.47) that among Asian patients.

Conclusions

Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.
Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 Inflammasome Signalling pathway
Authors: Ma Chongyang , Wang Xueqian , Xu Tian , Yu Xue , Zhang Shuang , Liu Shuling , Gao Yushan , Fan Shuning , Li Changxiang , Zhai Changming , Cheng Fafeng , Wang Qingguo
Published: November 2019

Background

Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Drug Administration, has been widely used in clinical practice to treat cerebral ischemia in China. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is activated in cerebral ischemia and thus, is an effective therapeutic target. AMP-activated protein kinase (AMPK) is an important regulator inhibiting NLRP3 inflammasome activation.

Methods

We investigated the potential of QKL injection to provide neuroprotection after cerebral ischemia in a rat model of middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats (210–230 g) were randomly divided into three groups which consist of sham, MCAO and 3 ml/kg QKL. Rats in the QKL group received intraperitoneal injections of 3 ml/kg QKL, while rats in other groups were given saline in the same volumes. After 90 min ischemia and 24 h reperfusion, neurological function, laser speckle imaging, brain infarction, brain water content and brain blood barrier permeability were examined and cell apoptosis at prefrontal cortex were evaluated 24 h after MCAO, and western blot and real-time quantitative polymerase chain reaction was also researched, respectively.

Results

Intraperitoneal administration of QKL alleviated neurological deficiencies, cerebral infarction, blood-brain barrier permeability, brain oedema and brain cell apoptosis after MCAO induction. QKL decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and increased anti-inflammatory cytokines, IL-4 and IL-10. Furthermore, QKL activated phosphorylated AMPK, decreased oxidative stress and decreased NLRP3 inflammasome activation.

Conclusions

QKL relieved cerebral ischemia reperfusion injury and suppressed the inflammatory response by inhibiting AMPK-mediated activation of the NLRP3 inflammasome. These results suggest that QKL might have potential in treating brain inflammatory response and attenuating the cerebral ischemia-reperfusion injury.
Examining the impact of medical legal partnerships in improving outcomes on the HIV care continuum: rationale, design and methods
Authors: Muñoz-Laboy Miguel , Martinez Omar , Davison Robin , Fernandez Isa
Published: November 2019

Background

Over the past two decades, we have seen a nationwide increase in the use of medical-legal partnerships (MLPs) to address health disparities affecting vulnerable populations. These partnerships increase medical teams’ capacity to address social and environmental threats to patients’ health, such as unsafe housing conditions, through partnership with legal professionals. Despite expansions in the use of MLP care models in health care settings, the health outcomes efficacy of MLPs has yet to be examined, particularly for complex chronic conditions such as HIV.

Methods

This on-going mixed-methods study utilizes institutional case study and intervention mapping methodologies to develop an HIV-specific medical legal partnership logic model. Up-to-date, the organizational qualitative data has been collected. The next steps of this study consists of: (1) recruitment of 100 MLP providers through a national survey of clinics, community-based organizations, and hospitals; (2) in-depth interviewing of 50 dyads of MLP service providers and clients living with HIV to gauge the potential large-scale impact of legal partnerships on addressing the unmet needs of this population; and, (3) the development of an MLP intervention model to improve HIV care continuum outcomes using intervention mapping.

Discussion

The proposed study is highly significant because it targets a vulnerable population, PLWHA, and consists of formative and developmental work to investigate the impact of MLPs on health, legal, and psychosocial outcomes within this population. MLPs offer an integrated approach to healthcare delivery that seems promising for meeting the needs of PLWHA, but has yet to be rigorously assessed within this population.
Standardizing the categorizations of models of aftercare for survivors of childhood cancer
Authors: Ryan Devonne , Moorehead Paul C , Chafe Roger
Published: November 2019

Background

With significant improvements in the survival rates for most childhood cancers, there is increased pressure to determine how follow-up or aftercare for survivors is best structured.

Main body

Previous work in this area has not been consistent in how it categorizes models of aftercare, which risks confusion between studies and evaluations of different models. The adoption of a standardized method for classifying and describing different models of aftercare is necessary in order to maximize the applicability of the available evidence. We identify some of the different ways models of aftercare have been classified in previous research. We then propose a revised taxonomy which allows for a more consistent classification and description of these models. The proposed model bases the classification of models of aftercare on who is the lead provider, and then collects data on five other key features: which other providers are involved in providing aftercare, where care is provided, how are survivors engaged, which services are provided, and who receives aftercare.

Conclusion

There is a good deal of interest in the effectiveness of different models of aftercare. Future research in this area would be assisted by the adoption of a shared taxonomy that will allow programs to be identified by their structural type.